Gale Encyclopedia of Cancer, 3rd Ed

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The GALE

ENCYCLOPEDIA of

CANCER

A GUIDE TO CANCER AND ITS TREATMENTS

THIRD EDITION

The GALE

ENCYCLOPEDIA of

CANCER

A GUIDE TO CANCER AND ITS TREATMENTS

THIRD EDITION

JACQUELINE L. LONGE, EDITOR

Gale Encyclopedia of Cancer: A Guide To Cancer And Its Treatments Project Editors: Jacqueline L. Longe Editorial: Kristin Key Product Manager: Kate Hanley Editorial Support Services: Andrea Lopeman

ª 2010 Gale, Cengage Learning ALL RIGHTS RESERVED. No part of this work covered by the copyright herein may be reproduced, transmitted, stored, or used in any form or by any means graphic, electronic, or mechanical, including but not limited to photocopying, recording, scanning, digitizing, taping, Web distribution, information networks, or information storage and retrieval systems, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without the prior written permission of the publisher.

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While every effort has been made to ensure the reliability of the information presented in this publication, Gale, a part of Cengage Learning, does not guarantee the accuracy of the data contained herein. Gale accepts no payment for listing; and inclusion in the publication of any organization, agency, institution, publication, service, or individual does not imply endorsement of the editors or publisher. Errors brought to the attention of the publisher and verified to the satisfaction of the publisher will be corrected in future editions. Library of Congress Cataloging in Publication Data The Gale encyclopedia of cancer : a guide to cancer and its treatments. 3rd ed. / Jacqueline L. Longe, editor. p. ; cm. Other title: Encyclopedia of cancer Includes bibliographical references and index. ISBN 13: 978 1 4144 7598 1 (set) ISBN 13: 978 1 4144 7599 8 (vol. 1) ISBN 13: 978 1 4144 7600 1 (vol. 2) ISBN 10: 1 4144 7598 5 (set) [etc.] 1. Cancer Encyclopedias. 2. Oncology Encyclopedias. I. Longe, Jacqueline L. II. Title: Encyclopedia of cancer. [DNLM: 1. Neoplasms Encyclopedias English. 2. Medical Oncology Encyclopedias English. QZ 13 G151 2010] RC254.5.G353 2010 616.990 4003 dc22

2010002075

Gale 27500 Drake Rd. Farmington Hills, MI, 48331 3535

ISBN 13: 978 1 4144 7598 1 (set) ISBN 13: 978 1 4144 7599 8 (vol. 1) ISBN 13: 978 1 4144 7600 1 (vol. 2)

ISBN 10: 1 4144 7598 5 (set) ISBN 10: 1 4144 7599 3 (vol. 1) ISBN 10: 1 4144 7600 0 (vol. 2)

This title is also available as an e book. ISBN 13: 978 1 4144 7601 8 ISBN 10: 1 4144 7601 9 Contact your Gale, a part of Cengage Learning sales representative for ordering information.

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CONTENTS

List of Entries . .............................................................. vii Introduction . .................................................................. xv Foreword . ..................................................................... xvii Advisory Board . ........................................................ xxi Contributors . ............................................................. xxiii Illustrations of Body Systems . ..................... xxvii Entries A-Z . ......................................................................... 1 Appendix I: National Cancer Institute-Designated Comprehensive Cancer Centers . ................................................. 1595 Appendix II: National Support Groups . .................................................................. 1599 Appendix III: Government Agencies and Research Groups . .................................. 1605 General Index . ........................................................ 1609

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v

LIST OF ENTRIES

A Abarelix Accelerated partial breast irradiation Acoustic neuroma Acute erythroblastic leukemia Acute lymphocytic leukemia Acute myelocytic leukemia Adenocarcinoma Adenoma Adjuvant chemotherapy Adrenal fatigue Adrenal tumors Adrenocortical carcinoma Adult cancer pain Advance directives AIDS-related cancers Alcohol consumption Aldesleukin Alemtuzumab Allopurinol Alopecia Altretamine Amantadine Amenorrhea American Joint Commission on Cancer Amifostine Aminoglutethimide Amitriptyline Amputation Amsacrine Anagrelide Anal cancer

Anemia Angiogenesis inhibitors Angiography Anorexia Anoscopy Antiandrogens Antibiotics Anticancer drugs Antidiarrheal agents Antiemetics Antiestrogens Antifungal therapy Antimicrobials Antineoplastic agents Antioxidants Antiviral therapy Anxiety disorder Aromatase inhibitors Arsenic trioxide Ascites Asparaginase Astrocytoma Axillary dissection Azacitidine Azathioprine

B Bacillus Calmette Guerin Barium enema Barrett’s esophagus Basal cell carcinoma BCR-ABL inhibitors Bendamustine hydrochloride

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Benzodiazepines Bevacizumab Bexarotene Bile duct cancer Biological response modifiers Biopsy Bisphosphonates Bladder cancer Bleomycin Body image/self image Bone marrow aspiration and biopsy Bone marrow transplantation Bone pain Bone survey Bortezomib Bowen’s disease Brain and central nervous system tumors BRCA 1 and 2 Breast cancer Breast reconstruction Breast self-exam Breast ultrasound Bronchoalveolar lung cancer Bronchoscopy Burkitt’s lymphoma Buserelin Busulfan

C Calcitonin Cancer Cancer biology vii

List of Entries

Cancer cluster Cancer genetics Cancer prevention Cancer screening guidelines for men Cancer screening guidelines for women Cancer therapy, palliative Cancer of unknown primary Capecitabine Capsaicin Carbamazepine Carboplatin Carcinogenesis Carcinoid tumors, gastrointestinal Carcinoid tumors, lung Carcinoma Carcinomatous meningitis Cardiomyopathy Carmustine Cartilage CAT scan Central nervous system carcinoma Central nervous system lymphoma Cervical cancer Cetuximab Chemoembolization Chemoprevention Chemotherapy Childhood cancers Chlorambucil Chondrosarcoma Chordoma Choroid plexus tumors Chromosome rearrangements Chronic lymphocytic leukemia Chronic myelocytic leukemia Cigarettes Cisplatin Cladribine Clinical trials Coenzyme Q10 Colectomy Colon cancer Colonoscopy Colorectal surgery Colostomy viii

Colposcopy Complementary cancer therapies Computed tomography Cone biopsy Corticosteroids Craniopharyngioma Craniosynotosis Craniotomy Cryoablation Cryotherapy CT-guided biopsy Cushing’s syndrome Cutaneous T-cell lymphoma Cyclooxygenase 2 inhibitors Cyclophosphamide Cyclosporine Cystectomy Cystosarcoma phylloides Cystoscopy Cytarabine Cytogenetic analysis Cytology

D Dacarbazine Daclizumab Dactinomycin Danazol Dasatinib Daunorubicin Demeclocycline Denileukin Depression Dexamethasone Dexrazoxane Diarrhea Diazepam Diethylstilbestrol diphosphate Digital rectal examination Dilatation and curettage Diphenhydramine Disseminated intravascular coagulation DNA flow cytometry Docetaxel

Doxorubicin Drug resistance Ductogram Dutasteride

E Eaton-Lambert syndrome Edatrexate Endocrine system tumors Endometrial cancer Endorectal ultrasound Endoscopic retrograde cholangiopancreatography Enteritis Environmental factors in cancer development Ependymoma Epidermal growth factor receptor agonists Epirubicin Epstein-Barr Virus Erlotinib Erythropoietin Esophageal cancer Esophageal resection Essiac Estramustine Etoposide Everolimus Ewing’s sarcoma Exenteration Extracranial germ cell tumors Extragonadal germ cell tumors

F Familial cancer syndromes Fanconi anemia Fatigue Fecal occult blood test Fertility issues Fever Fibrocystic condition of the breast Fibrosarcoma Filgrastim G A LE EN CY C LO PE DI A O F C AN C ER 3

G Gabapentin Gallbladder cancer Gallium nitrate Gallium scan Gastrectomy Gastroduodenostomy Gastrointestinal cancers Gastrointestinal complications Gefitinib Gemcitabine Gemtuzumab Genetic testing Germ cell tumors Gestational trophoblastic tumors Giant cell tumors Glossectomy Glutamine Goserelin acetate Graft-vs.-host disease Gynecologic cancers

H Hairy cell leukemia Hand-foot syndrome Head and neck cancers Health insurance Hemolytic anemia Hemoptysis Heparin Hepatic arterial infusion Herceptin Herpes simplex Herpes zoster Histamine 2 antagonists Histiocytosis X

Hodgkin’s disease Home health services Horner’s syndrome Hospice care Human growth factors Human papilloma virus Hydroxyurea Hypercalcemia Hypercoagulation disorders Hyperthermia Hypocalcemia

I Ibritumomab Idarubicin Ifosfamide Imaging studies Imatinib mesylate Immune globulin Immune response Immunoelectrophoresis Immunohistochemistry Immunologic therapies Incontinence Infection and sepsis Intensity modulated radiation therapy Interferons Interleukin 2 Intrathecal chemotherapy Intravenous urography Investigational drugs Irinotecan Itching

K Kaposi’s sarcoma Ki67 Kidney cancer

L Laparoscopy Lapatinib

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Laryngeal cancer Laryngeal nerve palsy Laryngectomy Laryngoscopy Laxatives Leiomyosarcoma Leucovorin Leukoencephalopathy Leukotriene inhibitors Leuprolide acetate Levamisole Li-Fraumeni syndrome Limb salvage Lip cancers Liver biopsy Liver cancer Lobectomy Lomustine Lorazepam Low molecular weight heparins Lumbar puncture Lumpectomy Lung cancer, non-small cell Lung cancer, small cell Lymph node biopsy Lymph node dissection Lymphangiography Lymphocyte immune globulin Lymphoma

List of Entries

Flow cytometry Floxuridine Fludarabine Fluorouracil Fluoxymesterone Folic acid

M Magnetic resonance imaging Male breast cancer Malignant fibrous histiocytoma MALT lymphoma Mammography Mantle cell lymphoma Mastectomy Matrix metalloproteinase inhibitors Mechlorethamine Meclizine Mediastinal tumors Mediastinoscopy Medroxyprogesterone acetate ix

List of Entries

Medulloblastoma Megestrol acetate Melanoma Melphalan Memory change Meningioma Meperidine Mercaptopurine Merkel cell carcinoma Mesna Mesothelioma Metastasis Methotrexate Methylphenidate Metoclopramide Mistletoe Mitoguazone Mitomycin-C Mitotane Mitoxantrone Modified radical mastectomy Mohs’ surgery Monoclonal antibodies Mucositis Multiple endocrine neoplasia syndromes Multiple myeloma Muromonab-CD3 Myasthenia gravis Mycophenolate mofetil Mycosis fungoides Myelodysplastic syndrome Myelofibrosis Myeloma Myeloproliferative diseases Myelosuppression

N Nasal cancer Nasopharyngeal cancer Nausea and vomiting Nephrectomy Nephrostomy Neuroblastoma Neuroendocrine tumors x

Neuropathy Neurotoxicity Neutropenia Night sweats Nilotinib Non-Hodgkin’s lymphoma Nonsteroidal anti-inflammatory drugs Nuclear medicine scans

O Occupational exposures and cancer Oligodendroglioma Omega fatty acids Ommaya reservoir Oncologic emergencies Oophorectomy Opioids Oprelvekin Oral cancers Orchiectomy Oropharyngeal cancer Osteosarcoma Ovarian cancer Ovarian epithelial cancer

P Paclitaxel Paget’s disease of the breast Pain management Pancreatic cancer Pancreatic cancer, endocrine Pancreatic cancer, exocrine Panitumumab Pap test Paracentesis Paranasal sinus cancer Paraneoplastic syndromes Parathyroid cancer PC-SPES Pegaspargase Pemetrexed

Penile cancer Pentostatin Percutaneous transhepatic cholangiography Pericardial effusion Pericardiocentesis Peritoneovenous shunt Peutz-Jeghers syndrome Pharyngectomy Phenytoin Pheochromocytoma Pheresis Photodynamic therapy Pilocarpine Pineoblastoma Pituitary tumors Plerixafor Pleural biopsy Pleural effusion Pleurodesis Pleuropulmonary blastoma Plicamycin Ploidy analysis Pneumonectomy Pneumonia Polymavirus hominis type I BK virus infection Porfimer sodium Positron emission tomography Prednimustine Prednisone Pregnancy and cancer Primary site Procarbazine Prostate cancer Prostatectomy Protein electrophoresis Proteomics Pruritus Psycho-oncology

Q Quadrantectomy G A LE EN CY C LO PE DI A O F C AN C ER 3

Radiation dermatitis Radiation therapy Radical neck dissection Radiofrequency ablation Radiopharmaceuticals Raloxifene Receptor analysis Reconstructive surgery Rectal cancer Rectal resection Renal pelvis tumors Retinoblastoma Revtositumomab Rhabdomyosarcoma Richter’s syndrome Rituximab

S Salivary gland tumors Sarcoma Sargramostim Saw palmetto Scopolamine Screening test Second cancers Second-look surgery Segmentectomy Semustine Sentinel lymph node biopsy Sentinel lymph node mapping Sexual dysfunction in cancer patients Sexuality Sezary syndrome Sigmoidoscopy Sirolimus Sjogren’s syndrome Skin cancer Skin cancer, non-melanoma Small intestine cancer Smoking cessation Soft tissue sarcoma Sorafenib

T Tacrolimus Tamoxifen Taste alteration Temozolomide Temsirolimus Teniposide Testicular cancer Testicular self-exam Testolactone Testosterone Tetrahydrocannabinol Thalidomide Thioguanine Thiotepa Thoracentesis Thoracic surgery Thoracoscopy Thoracotomy Thrombocytopenia Thrombopoietin Thrush Thymic cancer Thymoma Thyroid cancer Thyroid nuclear medicine scan

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Topotecan Toremifene Tositumomab Tracheostomy Transfusion therapy Transitional care Transitional cell carcinoma Transurethral bladder resection Transvaginal ultrasound Transverse myelitis Trastuzumab Tretinoin Trichilemmal carcinoma Trimetrexate Triple negative breast cancer Triptorelin pamoate Tube enterostomy Tumor grading Tumor lysis syndrome Tumor markers Tumor necrosis factor Tumor staging

List of Entries

R

Spinal axis tumors Spinal cord compression Splenectomy Squamous cell carcinoma of the skin Stenting Stereotactic needle biopsy Stereotactic surgery Stomach cancer Stomatitis Streptozocin Substance abuse Sunitinib Sun’s soup Superior vena cava syndrome Supratentorial primitive neuroectodermal tumors Suramin Syndrome of inappropriate antidiuretic hormone

U Ultrasonography Upper gastrointestinal endoscopy Upper GI series Ureterosigmoidoscopy Ureterostomy, cutaneous Urethral cancer Urostomy

V Vaccines Vaginal cancer Valrubicin Vascular access Vinblastine Vincristine Vindesine Vinorelbine Vitamins Von Hippel-Lindau disease xi

List of Entries

Von Recklinghausen’s neurofibromatosis Vorinostat Vulvar cancer

Weight loss Whipple procedure

Z

Whole brain radiotherapy

Zoledronate

Wilms’ tumor

Zollinger-Ellison syndrome Zolpidem

W Waldenstrom’s macroglobulinemia Warfarin

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X X ray Xerostomia

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PLEASE READ—IMPORTANT INFORMATION

The Gale Encyclopedia of Cancer: A Guide To Cancer And Its Treatments is a health reference product designed to inform and educate readers about a wide variety of cancers, diseases and conditions related to cancers, nutrition and dietary practices beneficial to cancer patients, and various cancer treatments including drug treatments. Cengage Learning believes the product to be comprehensive, but not necessarily definitive. It is intended to supplement, not replace, consultation with a physician or other healthcare practitioners. While Cengage Learning has made substantial efforts to provide information that is accurate, comprehensive, and

G A LE EN CY C LO PE DI A O F C AN CE R 3

up-to-date, Cengage Learning makes no representations or warranties of any kind, including without limitation, warranties of merchantability or fitness for a particular purpose, nor does it guarantee the accuracy, comprehensiveness, or timeliness of the information contained in this product. Readers should be aware that the universe of medical knowledge is constantly growing and changing, and that differences of opinion exist among authorities. Readers are also advised to seek professional diagnosis and treatment for any medical condition, and to discuss information obtained from this book with their healthcare provider.

xiii

INTRODUCTION

The Gale Encyclopedia of Cancer: A Guide to Cancer and Its Treatments is a unique and invaluable source of information for anyone touched by cancer. This collection of over 450 entries provides in-depth coverage of specific cancer types, diagnostic procedures, treatments, cancer side effects, and cancer drugs. In addition, entries have been included to facilitate understanding of common cancer-related concepts, such as cancer biology, carcinogenesis, and cancer genetics, as well as cancer issues such as clinical trials, home health care, fertility issues, and cancer prevention. This encyclopedia minimizes medical jargon and uses language that laypersons can understand, while still providing thorough coverage that will benefit health science students as well.

Scope Entries follow a standardized format that provides information at a glance. Rubrics include: Cancer types 

Definition



Description



Demographics



Causes and symptoms



Diagnosis



Treatment team



Clincial staging, treatments, and prognosis



Coping with cancer treatment



Clinical trials



Prevention



Special concerns



Resources



Key terms Cancer drugs



Definition



Purpose

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Description



Recommended dosage



Precautions



Side effects



Interactions Drugs, herbs, vitamins



Definition



Description



Recommended dosage



Precautions



Side effects



Interactions



Caregiver concerns



‘‘Questions to ask the doctor’’



Resources



Key Terms

Inclusion criteria A preliminary list of cancers and related topics was compiled from a wide variety of sources, including professional medical guides and textbooks, as well as consumer guides and encyclopedias. The advisory board, made up of medical doctors and oncology pharmacists, evaluated the topics and made suggestions for inclusion. Final selection of topics to include was made by the advisory board in conjunction with the Gale editor.

About the contributors The essays were compiled by experienced medical writers, including physicians, pharmacists, nurses, and other health care professionals. The advisors reviewed the completed essays to ensure that they are appropriate, up-to-date, and medically accurate. xv

Introduction

How to use this book The Gale Encyclopedia of Cancer has been designed with ready reference in mind. 

Straight alphabetical arrangement of topics allows users to locate information quickly.



Bold-faced terms within entries direct the reader to related articles.



Cross-references placed throughout the encyclopedia direct readers from alternate names and related topics to entries.



A list of key terms is provided where appropriate to define unfamiliar terms or concepts.



A list of questions to ask the doctor is provided whevever appropriate to help facilitate discussion with the patient’s physician.



The Resources section for non-drug entries directs readers to additional sources of medical information on a topic.



Valuable contact information for organizations and support groups is included with each cancer type entry. Appendix II at the back of Volume 2 contains an extensive list of organizations arranged in alphabetical order.

xvi



A comprehensive general index guides readers to all topics mentioned in the text.



A note about drug entries: Drug entries are listed in alphabetical order by common generic names. However, because many oncology drugs have more than one common generic name, and because in many cases, the brand name is also often used interchangeably with a generic name, drugs can be located in one of three ways. The reader can: find the generic drug name in alphabetical order, be directed to the entry from an alternate name cross-reference, or the reader can use the index to look up a brand name, which will direct the reader to the equivalent generic name entry. If the reader would like more information about oncology drugs than these entries provide, the reader is encouraged to consult with a physician, pharmacist, or the reader may find helpful any one of a number of books about cancer drugs. Two that may be helpful are: D. Solimando’s Drug Information Handbook for Oncology, or R. Ellerby’s Quick Reference Handbook of Oncology Drugs.

Graphics The Gale Encyclopedia of Cancer is also enhanced by color photographs,illustrations, and tables.

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FOREWORD

Unfortunately, humans must suffer disease. Some diseases are totally reversible and can be effectively treated. Moreover, some diseases with proper treatment have been virtually annihilated, such as polio, rheumatic fever, smallpox, and, to some extent, tuberculosis. Other diseases seem to target one organ, such as the heart, and there has been great progress in either fixing defects, adding blood flow, or giving medications to strengthen the diseased pump. Cancer, however, continues to frustrate even the cleverest of doctors or the most fastidious of health conscious individuals. Why? By its very nature, cancer is a survivor. It has only one purpose: to proliferate. After all, that is the definition of cancer: unregulated growth of cells that fail to heed the message to stop growing. Normal cells go through a cycle of division, aging, and then selection for death. Cancer cells are able to circumvent this normal cycle, and escape recognition to be eliminated. There are many mechanisms that can contribute to this unregulated cell growth. One of these mechanisms is inheritance. Unfortunately, some individuals can be programmed for cancer due to inherited disorders in their genetic makeup. In its simplest terms, one can inherit a faulty gene or a missing gene whose role is to eliminate damaged cells or to prevent imperfect cells from growing. Without this natural braking system, the damaged cells can divide and lead to more damaged cells with the same abnormal genetic makeup as the parent cells. Given enough time, and our inability to detect them, these groups of cells can grow to a size that will cause discomfort or other symptoms. Inherited genetics are obviously not the only source of abnormalities in cells. Humans do not live in a sterile world devoid of environmental attacks or pathogens. Humans must work, and working environments can be dangerous. Danger can come in the form of radiation, chemicals, or fibers to which we may be chronically exposed with or without our knowledge. Moreover, man must eat, and if our food is contaminated with these environmental hazards, or if we prepare our food G A LE EN CY C LO PE DI A O F C AN CE R 3

in a way that may change the chemical nature of the food to hazardous molecules, then chronic exposure to these toxins could damage cells. Finally, man is social. He has found certain habits which are pleasing to him because they either relax him or release his inhibitions. Such habits, including smoking and alcohol consumption, can have a myriad of influences on the genetic makeup of cells. Why the emphasis on genes in the new century? Because they are potentially the reason as well as the answer for cancer. Genes regulate our micro- and macrosopic events by eventually coding for proteins that control our structure and function. If the abovementioned environmental events cause errors in those genes that control growth, then imperfect cells can start to take root. For the majority of cases, a whole cascade of genetic events must occur before a cell is able to outlive its normal predecessors. This cascade of events could take years to occur, in a silent, undetected manner until the telltale signs and symptoms of advanced cancer are seen, including pain, lack of appetite, cough, loss of blood, or the detection of a lump. How did these cells get to this state where they are now dictating the everyday physical, psychological, and economic events for the person afflicted? At this time, the sequence of genetic catastrophes is much too complex to comprehend or summarize because, it is only in the past year that we have even been able to map what genes we have and where they are located in our chromosomes. We have learned, however, that cancer cells are equipped with a series of self-protection mechanisms. Some of the altered genes are actually able to express themselves more than in the normal situation. These genes could then code for more growth factors for the transforming cell, or they could make proteins that could keep our own immune system from eliminating these interlopers. Finally, these cells are chameleons: if we treat them with drugs to try to kill them, they can ‘‘change their colors’’ by mutation, and then be resistant to the drugs that may have harmed them before. xvii

Foreword

Then what do we do for treatment? Man has always had a fascination with grooming, and grooming involves removal—dirt, hair, waste. The ultimate removal involves cutting away the spoiled or imperfect portion. An abnormal growth? Remove it by surgery . . . make sure the edges are clean. Unfortunately, the painful reality of cancer surgery is that it is highly effective when performed in the early stages of the disease. ‘‘Early stages of the disease’’ implies that there is no spread, or, hopefully, before there are symptoms. In the majority of cases, however, surgery cannot eradicate all the disease because the cancer is not only at the primary site of the lump, but has spread to other organs. Cancer is not just a process of growth, but also a metastasizing process that allows for invasion and spread. The growing cells need nourishment so they secrete proteins that allow for the growth of blood vessels (angiogenesis); once the blood vessels are established from other blood vessels, the tumor cells can make proteins that will dissolve the imprisoning matrix surrounding them. Once this matrix is dissolved, it is only a matter of time before thecancer cells will migrate to other places making the use of surgery fruitless. Since cancer cells have a propensity to leave home and pay a visit to other organs, therapies must be geared to treat the whole body and not just the site of origin. The problem with these chemotherapies is that they are not selective and wreak havoc on tissues that are not affected by the cancer. These therapies are not natural to the human host, and result in nausea, loss of appetite, fatigue, as well as a depletion in our cells that protect us from infection and those that carry oxygen. Doctors who prescribe such medications walk a fine line between helping the patient (causing a ‘‘response’’ in the cancer by making it smaller) or causing ‘‘toxicity’’ which, due to effects on normal organs, causes the patient problems. Although these drugs are far from perfect, we are fortunate to have them because when they work, their results can be remarkable. But that’s the problem—‘‘when they work.’’ We cannot predict who is going to benefit from our therapies, and doctors must inform the patient and his/her family about countless studies that have been done to validate the use of these potentially beneficial/potentially harmful agents. Patients must suffer the frustration that oncologists have because each individual afflicted with cancer is different, and indeed, each cancer is different. This makes it virtually impossible to personalize an individual’s treatment expectations and life expectancy. Cancer, after all, is a very impersonal disease, and does not respect sex, race, wealth, age, or any other ‘‘human’’ characteristics. xviii

Cancer treatment is in search of ‘‘smart’’ options. Like modern-day instruments of war, successful cancer treatment will necessitate the construction of therapies which can do three basic tasks: search out the enemy, recognize the enemy, and kill the enemy without causing ‘‘friendly fire.’’ The successful therapies of the future will involve the use of ‘‘living components,’’ ‘‘manufactured components,’’ or a combination of both. Living components, white blood cells, will be educated to recognize where the cancer is, and help our own immune system fight the foreign cells. These lymphocytes can be educated to recognize signals on the cancer cell which make them unique. Therapies in the future will be able to manufacture molecules with these signature, unique signals which are linked to other molecules specifically for killing the cells. Only the cancer cells are eliminated in this way, hopefully sparing the individual from toxicity. Why use these unique signals as delivery mechanisms? If they are unique and are important for growth of the cancer cell, why not target them directly? This describes the ambitious mission of gene therapy, whose goal is to supplement a deficient, necessary genetic pool or diminish the number of abnormally expressed genes fortifying the cancer cells. If a protein is not being made that slows the growth of cells, gene therapy would theoretically supply the gene for this protein to replenish it and cause the cells to slow down. If the cells can make their own growth factors that sustain them selectively over normal cells, then the goal is to block the production of this growth factor. There is no doubt that gene therapy is the wave of the future and is under intense investigation and scrutiny at present. The problem, however, is that there is no way to tell when this future promise will be fulfilled. No book can describe the medical, psychological, social, and economic burden of cancer, and if this is your first confrontation with the enemy, you may find yourself overwhelmed with its magnitude. Books are only part of the solution. Newly enlisted recruits in this war must seek proper counsel from educated physicians who will inform the family and the patient of the risks and benefits of a treatment course in a way that can be understood. Advocacy groups of dedicated volunteers, many of whom are cancer survivors, can guide and advise. The most important component, however, is an intensely personal one. The afflicted individual must realize that he/she is responsible for charting the course of his/her disease, and this requires the above described knowledge as well as great personal intuition. Cancer comes as a series of shocks: the symptoms, the diagnosis, and the treatment. These shocks can be followed by cautious optimism or G A LE EN CY C LO PE DI A O F C AN C ER 3

While cancer is still life-threatening, strides have been made in the fight against the disease. Thirty years ago, a young adult diagnosed with testicular cancer had few options for treatment that could result in cure. Now, chemotherapy for good risk Stage II and III testicular cancer can result in a complete response of the tumor in 98% of the cases and a durable response in 92%. Sixty years ago, there were no regimens that could cause a complete remission for a child diagnosed

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with leukemia; but now, using combination chemotherapy, complete remissions are possible in 96% of these cases. Progress has been made, but more progress is needed. The first real triumph in cancer care will be when cancer is no longer thought of as a life-ending disease, but as a chronic disease whose symptoms can be managed. Anyone who has been touched by cancer or who has been involved in the fight against it lives in hope that that day will arrive. Helen A. Pass, M.D., F.A.C.S. Director, Breast Care Center William Beaumont Hospital Royal Oak, Michigan

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Foreword

profound disappointment. Each one of these shocks either reinforces or chips away at one’s resolve, and how an individual reacts to these issues is as unique as the cancer that is being dealt with.

ADVISORS A number of experts in the medical community provided invaluable assistance in the formulation of this encyclopedia. Our advisory board performed a myriad of duties, from defining the scope of coverage to reviewing individual entries for accuracy and accessibility. The editor would like to express her appreciation to them.

Melinda Granger Oberleitner, R.N., D.N.S. Acting Department Head and Associate Professor Department of Nursing University of Louisiana at Lafayette Lafayette, Louisiana

William Beaumont Hospital Royal Oak, Michigan

Helen A. Pass, M.D., F.A.C.S. Director, Breast Care Center

James E. Waun, M.D., M.A., R. Ph.. Associate Clinical Professor

Marianne Vahey, M.D. Clinical Instructor in Medicine Yale University School of Medicine New Haven, Connecticut

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Department of Family Practice Faculty Center for Ethics and the Humanities Michigan State University Adjunct Assistant Professor of Clinical Pharmacy Ferris State University East Lansing, Michigan

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CONTRIBUTORS

Margaret Alic, Ph.D. Science Writer Eastsound, Washington

Patricia L. Bounds, Ph.D. Science Writer Zu¨rich, Switzerland

Lisa Andres, M.S., C.G.C. Certified Genetic Counselor and Medical Writer San Jose, California

Cheryl Branche, M.D. Retired General Practitioner Jackson, Mississippi

Racquel Baert, M.Sc. Medical Writer Winnipeg, Canada Julia R. Barrett Science Writer Madison, Wisconsin Maria Basile, PhD Neuropharmacologist Neward, New Jersey Nancy J. Beaulieu, RPh., B.C.O.P. Oncology Pharmacist New Haven, Connecticut Linda K. Bennington, C.N.S., M.S.N. Clinical Nurse Specialist Department of Nursing Old Dominion University Norfolk, Virginia Kenneth J. Berniker, M.D. Attending Physician Emergency Department Kaiser Permanente Medical Center Vallejo, California Olga Bessmertny, Pharm.D. Clinical Pharmacy Manager Pediatric Hematology/Oncology/ Bone Marrow Transplant Children’s Hospital of New York Columbia Presbyterian Medical Center New York, New York

Tamara Brown, R.N. Medical Writer Boston, Massachusetts Diane M. Calabrese Medical Sciences and Technology Writer Silver Spring, Maryland Rosalyn Carson-DeWitt, M.D. Durham, North Carolina Lata Cherath, Ph.D. Science Writer Franklin Park, New York Lisa Christenson, Ph.D. Science Writer Hamden, Connecticut Rhonda Cloos, R.N. Medical Writer Austin, Texas David Cramer, M.D. Medical Writer Chicago, Illinois

Georgetown University Washington, DC Lori DeMilto Medical Writer Sicklerville, New York Stefanie B. N. Dugan, M.S. Genetic Counselor Milwaukee, Wisconsin Janis O. Flores Medical Writer Sebastopol, California Paula Ford-Martin Medical Writer Chaplin, Minnesota Rebecca J. Frey, Ph.D. Research and Administrative Associate East Rock Institute New Haven, Connecticut Jason Fryer Medical Writer Lubbock, Texas Jill Granger, M.S. Senior Research Associate University of Michigan Ann Arbor, Michigan

Tish Davidson, A.M. Medical Writer Fremont, California

David E. Greenberg, M.D. Medicine Resident Baylor College of Medicine Houston, Texas

Dominic DeBellis, Ph.D. Medical Writer and Editor Mahopac, New York

Maureen Haggerty Medical Writer Ambler, Pennsylvania

Tiffani A. DeMarco, M.S. Genetic Counselor Cancer Control

Kevin Hwang, M.D. Medical Writer Morristown, New Jersey

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Contributors

Michelle L. Johnson, M.S., J.D. Patent Attorney and Medical Writer Portland, Oregon Paul A. Johnson, Ed.M. Medical Writer San Diego, California Cindy L. A. Jones, Ph.D. Biomedical Writer Sagescript Communications Lakewood, Colorado Crystal H. Kaczkowski, M.Sc. Medical Writer Montreal, Canada David S. Kaminstein, M.D. Medical Writer Westchester, Pennsylvania

Richard A. McCartney M.D. Fellow, American College of Surgeons Diplomat, American Board of Surgery Richland, Washington Sally C. McFarlane-Parrott Medical Writer Mason, Michigan Monica McGee, M.S. Science Writer Wilmington, North Carolina Alison McTavish, M.Sc. Medical Writer and Editor Montreal, Quebec

Beth Kapes Medical Writer Bay Village, Ohio

Molly Metzler, R.N., B.S.N. Registered Nurse and Medical Writer Seaford, Delaware

Bob Kirsch Medical Writer Ossining, New York

Beverly G. Miller MT(ASCP), Technical Writer Charlotte, North Carolina

Melissa Knopper Medical Writer Chicago, Illinois

Mark A. Mitchell, M.D. Medical Writer Seattle, Washington

Monique Laberge, Ph.D. Research Associate Department of Biochemistry and Biophysics University of Pennsylvania Philadelphia, Pennsylvania

Laura J. Ninger Medical Writer Weehawken, New Jersey

Jill S. Lasker Medical Writer Midlothian, Virginia

Teresa G. Odle Medical Writer Albuquerque, New Mexico

G. Victor Leipzig, Ph.D. Biological Consultant Huntington Beach, California Lorraine Lica, Ph.D. Medical Writer San Diego, California

Melinda Granger Oberleitner Acting Department Head and Associate Professor Department of Nursing University of Louisiana at Lafayette Lafayette, Louisiana

John T. Lohr, Ph.D. Utah State University Logan, Utah

Lee Ann Paradise Science Writer Lubbock, Texas

Warren Maltzman, Ph.D. Consultant, Molecular Pathology Demarest, New Jersey

J. Ricker Polsdorfer, M.D. Medical Writer Phoenix, Arizona

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Nancy J. Nordenson Medical Writer Minneapolis, Minnesota

Elizabeth J. Pulcini, M.S. Medical Writer Phoenix, Arizona Kulbir Rangi, D.O. Medical Doctor and Writer New York, New York Esther Csapo Rastegari, Ed.M., R.N., B.S.N. Registered Nurse, Medical Writer Holbrook, Masachusetts Toni Rizzo Medical Writer Salt Lake City, Utah Martha Floberg Robbins Medical Writer Evanston, Illinois Richard Robinson Medical Writer Tucson, Arizona Edward R. Rosick, D.O., M.P.H., M.S. University Physician, Clinical Assistant Professor Student Health Services The Pennsylvania State University University Park, Pennsylvania Nancy Ross-Flanigan Science Writer Belleville, Michigan Belinda Rowland, Ph.D. Medical Writer Voorheesville, New York Andrea Ruskin, M.D. Whittingham Cancer Center Norwalk, Connecticut Laura Ruth, Ph.D. Medical, Science, & Technology Writer Los Angeles, California Kausalya Santhanam, Ph.D. Technical Writer Branford, Connecticut Marc Scanio Doctoral Candidate in Chemistry Stanford University Stanford, California G A LE EN CY C LO PE DI A O F C AN C ER 3

Kristen Mahoney Shannon, M.S., C.G.C. Genetic Counselor Center for Cancer Risk Analysis Massachusetts General Hospital Boston, Massachusetts Judith Sims, MS Science Writer Logan, Utah Genevieve Slomski, Ph.D. Medical Writer New Britain, Connecticut Anna Rovid Spickler, D.V.M., Ph.D. Medical Writer Salisbury, Maryland Laura L. Stein, M.S. Certified Genetic Counselor Familial Cancer ProgramDepartment of Hematology/ Oncology Dartmouth Hitchcock Medical Center Lebanon, New Hampshire Phyllis M. Stein, B.S., C.C.R.P. Affiliate Coordinator

Grand Rapids Clinical Oncology Program Grand Rapids, Michigan

Ellen S. Weber, M.S.N. Medical Writer Fort Wayne, Indiana

Kurt Sternlof Science Writer New Rochelle, New York

Ken R. Wells Freelance Writer Laguna Hills, California

Deanna M. Swartout-Corbeil Registered Nurse, Freelance Writer Thompsons Station, Tennessee Jane M. Taylor-Jones, M.S. Research Associate Donald W. Reynolds Department of Geriatrics University of Arkansas for Medical Sciences Little Rock, Arkansas Carol Turkington Medical Writer Lancaster, Pennsylvania Samuel Uretsky, PharmD Medical Writer Wantagh, New York Marianne Vahey, M.D. Clinical Instructor Medicine Yale University School of Medicine New Haven, Connecticut Malini Vashishtha, Ph.D. Medical Writer Irvine, California

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Contributors

Joan Schonbeck, R.N. Medical Writer Nursing Massachusetts Department of Mental Health Marlborough, Massachusetts

Barbara Wexler, M.P.H. Medical Writer Chatsworth, California Wendy Wippel, M.Sc. Medical Writer and Adjunct Professor of Biology Northwest Community College Hernando, Mississippi Debra Wood, R.N. Medical Writer Orlando, Florida Kathleen D. Wright, R.N. Medical Writer Delmar, Delaware Jon Zonderman Medical Writer Orange, California Michael V. Zuck, Ph.D. Writer Boulder, Colorado

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ILLUSTRATIONS OF BODY SYSTEMS

HUMAN SKELETON and SKIN. Some cancers that affect the skeleton are: Osteosarcoma; Ewing’s sarcoma; Fibrosarcoma (can also be found in soft tissues like muscle, fat, connective tissues, etc.). Some cancers that affect tissue near bones: Chondrosarcoma (affects joints near bones); Rhabdomyosarcoma (formed from cells of muscles attached to bones); Malignant fibrous histiocytoma (common in soft tissues, rare in bones). SKIN CANCERS: Basal cell carcinoma; Melanoma; Merkel cell carcinoma; Squamous cell carcinoma of the skin; and Trichilemmal carcinoma. Precancerous skin condition: Bowen’s disease. Lymphomas that affect the skin: Mycosis fungoides; Se´zary syndrome. (Illustration by Argosy Publishing Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HUMAN CIRCULATORY SYSTEM. Some cancers of the blood cells are: Acute erythroblastic leukemia; Acute lymphocytic leukemia; Acute myelocytic leukemia; Chronic lymphocytic leukemia; Chronic myelocytic leukemia; Hairy cell leukemia; and Multiple myeloma. One condition associated with various cancers that affects blood is called Myelofibrosis. (Illustration by Argosy Publishing Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HUMAN NERVOUS SYSTEM. Some brain and central nervous system tumors are: Astrocytoma; Carcinomatous meningitis; Central nervous system carcinoma; Central nervous system lymphoma; Chordoma; Choroid plexus tumors; Craniopharyngioma; Ependymoma; Medulloblastoma; Meningioma; Oligodendroglioma; and Spinal axis tumors. One kind of noncancerous growth in the brain: Acoustic neuroma. (Illustration by Argosy Publishing Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HUMAN LYMPHATIC SYSTEM. The lymphatic system and lymph nodes are shown here in pale green, the thymus in deep blue, and one of the bones rich in bone marrow (the femur) is shown here in purple. Some cancers of the lymphatic system are: Burkitt’s lymphoma; Cutaneous T-cell lymphoma; Hodgkin’s disease; MALT lymphoma; Mantle cell lymphoma; Se´zary syndrome; and Waldenstro¨m’s macroglobulinemia. (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HUMAN DIGESTIVE SYSTEM. Organs and cancers of the digestive system include: Salivary glands (shown in turquoise): Salivary gland tumors. Esophagus (shown in bright yellow): Esophageal cancer. Liver (shown in bright red): Bile duct cancer; Liver cancer. Stomach (pale gray-blue): Stomach cancer. Gallbladder (bright orange against the red liver): Gallbladder cancer. Colon (green): Colon cancer. Small intestine (purple): Small intestinal cancer; can have malignant tumors associated with Zollinger-Ellison syndrome. Rectum (shown in pink, continuing the colon): Rectal cancer. Anus (dark blue): Anal cancer. (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HEAD AND NECK. The pharynx, the passage that leads from the nostrils down through the neck is shown in orange. This passage is broken into several divisions. The area posterior to (behind) the nose is the nasopharynx. The area posterior to the mouth is the oropharynx. The oropharynx leads into the laryngopharynx, which opens into the esophagus (still in orange) and the larynx (shown in the large image in medium blue). Each of these regions may be affected by cancer, and the cancers include: Nasopharyngeal cancer; Oropharyngeal cancer; Esophageal cancer; and Laryngeal cancer. Oral cancers can affect the lips, gums, and tongue (pink). Referring to the smaller, inset picture of the salivary glands, salivary gland tumors can affect the parotid glands (shown here in yellow), the submandibular glands (inset picture, turquoise), and the sublingual glands (purple). (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HUMAN ENDOCRINE SYSTEM. The glands and cancers of the endocrine system include: In the brain: the pituitary gland shown in blue (pituitary tumors), the hypothalamus in pale green, and the pineal gland in bright yellow. Throughout the rest of the body: Thyroid (shown in dark blue): Thyroid cancer. Parathyroid glands, four of them adjacent to the thyroid: Parathyroid cancer. Thymus (green): Thymic cancer; Thymoma. Pancreas (turquoise): Pancreatic cancer, endocrine; Pancreatic cancer, exocrine; Zollinger-Ellison syndrome tumors can be malignant and can be found in the pancreas. Adrenal glands (shown in apricot, above the kidneys): Neuroblastoma often originates in these glands; Pheochromocytoma tumors are often found in adrenal glands. Testes (in males, shown in yellow): Testicular cancer. Ovaries (in females, shown in dark blue in inset image): Ovarian cancer. (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HUMAN RESPIRATORY SYSTEM. Air is breathed in through nose or mouth, enters the pharynx, shown here in orange, and passes through the larynx, shown here as a green tube with a ridged texture. (The smooth green tube shown is the esophagus, which is posterior to the larynx and which is involved in digestion instead of breathing.) The air then passes into the trachea (purple), a tube that divides into two tubes called bronchi. One bronchus passes into each lung, and continues to branch within the lung. These branches are called bronchioles and each bronchiole leads to a tiny cluster of air sacs called alveoli, where the exchange of gases occurs, so that the air and gases breathed in get diffused to the blood. The lungs (deep blue) are spongy and have lobes and can be affected by Lung cancer, both the non-small cell and small-cell types. (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems HUMAN URINARY SYSTEM. Organs and cancers of the urinary system include: Kidneys (shown in purple): Kidney cancer; Renal pelvis tumors; Wilms’ tumor. Ureters are shown in green. Bladder (blue-green): Bladder cancer. The kidneys, bladder, or ureters can be affected by a cancer type called Transitional cell carcinoma. (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems FEMALE REPRODUCTIVE SYSTEM. Organs and cancers of the female reproductive system include: Uterus, shown in red with the uterine or Fallopian tubes: Endometrial cancer. Ovaries (blue): Ovarian cancer. Vagina (shown in pink with a yellow interior or lining): Vaginal cancer. Breasts: Breast cancer; Paget’s disease of the breast. Shown in detailed inset only in turquoise, Cervix: Cervical cancer. (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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Illustrations of Body Systems MALE REPRODCTIVE SYSTEM. Organs, glands, and cancers of the male reproductive system include: Penis (shown in pink): Penile cancer. Testes (shown in yellow): Testicular cancer. Prostate gland (shown in full-body illustration in a peach/ apricot color, and in the inset as the dark blue gland between the bladder and the penis): Prostate cancer. (Illustration by Argosy Publishing. Cengage Learning, Gale.)

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A 2-CdA see Cladribine 5-Azacitidine see Azacitidine 5-Fluorouracil see Fluorouracil 6-Mercaptopurine see Mercaptopurine 6-Thioguanine see Thioguanine

Abarelix Definition Abarelix is an injectable gonadotrophin-releasing hormone (GnRH) antagonist that is used to decrease the production of the male hormone testosterone.

Purpose Abarelix is used in men to treat advanced prostate cancer that has not responded to other treatments or when other treatments have been refused. The prostate gland lies under the bladder and surrounds the urethra. Its main function is to produce seminal fluid that mixes with sperm prior to ejaculation. Prostate cancer is the most common cancer in men over the age of 50. Other treatments for prostate cancer should be tried before treatment with abarelix is prescribed. Early stage prostate cancer is often treated with surgery or radiation therapy and less often with cryoablation. Advanced stage prostate cancer may be treated with other drugs that decrease the production of testosterone. Another approach to treating advanced prostate cancer is surgical removal of the testicles (castration). Some men reject this surgery, making them candidates for treatment with abarelix. Because abarelix can cause serious side effects, this drug is considered appropriate for use only in the following situations: G A LE EN CY C LO PE DI A O F C AN CE R 3



The cancer has spread (metastasized) and is close to the spinal column, so that there is a risk that pressure will cause damage to the spinal nerves.



The urethra or bladder is blocked because of malignant tissue growth making urination difficult or impossible.



Prostate cancer causes severe pain in the bones that narcotic pain medication cannot control.

Description Abarelix works by blocking gonadotropin-releasing hormone (GRH) a hormone released from the anterior pituitary gland that stimulates the production of testosterone. When this messenger hormone from the pituitary is blocked, the level of testosterone in the blood decreases. Prostate cancer cells grow best in the presence of testosterone, so by decreasing the amount available, growth of the tumor is slowed or stopped. Other drugs (leuprolide acetate [Lupron], goserelin acetate [Zoladex]) are available that also decrease testosterone production. One advantage of abarelix over these other drugs is that the other drugs used to decrease testosterone levels first stimulate the production of testosterone then decrease it. With abarelix, there is no initial increase in testosterone production and decline in production of the hormone begins immediately. However, abarelix may stop working in some men after an initial period of effectiveness. The drug does not cure prostate cancer but can relieve symptoms. Abarelix is manufactured in the United States by Praecis Pharmaceuticals and sold under the brand name Plenaxis. Generic substitutes are not available, and there is only one American manufacturer. Abarelix was approved for use by the United States Food and Drug Administration (FDA) in December 2003 with restrictions. The drug can only be administered by doctors who are registered in the Plenaxis PLUS Program 1

Abarelix

Side effects

K EY T ERM S Antagonist—A drug or chemical that works against or blocks another chemical. Cryoablation—The selective freezing of cancerous tissue in order to kill it. Osteoporosis—A condition in which mineral is dissolved out of bone and bones become weakened and easily broken. Pituitary gland—A tissue located at the base of the brain that is divided into two parts (anterior and posterior). The pituitary gland produces many different hormones that regulate body metabolism or control the production of other hormones. Testes—Male reproductive organs that produce sperm and the hormone testosterone. Urethra—The tube that drains urine from the bladder.

Abarelix can cause serious or life-threatening allergic reactions either during or after administration. Therefore, the drug can only be administered by a physician registered in the Plenaxis PLUS safety program. The likelihood of life-threatening reactions increases with each injection of abarelix. For this reason, men receiving an injection of abarelix must remain under observation in the doctor’s office for at least 30 minutes following each treatment. Symptoms of rare but life-threatening reactions include:   

More common but less serious side effects include:  

(Plenaxis User Safety Program) because of its potentially life-threatening side effects.

  

Recommended dosage Abarelix is an injectable liquid. It is supplied as powder in single dose vial to which the physician adds a small amount of saline (saltwater) before use. The resulting liquid is injected into the buttocks muscle. The treatment cycle calls for an initial injection on days 1, 15, and 29 followed by an injection every 28 days. The testosterone level of the blood should be checked after the first month and then about every eight weeks to assure that the drug is continuing to work. Liver function tests should also be done regularly, as abarelix may cause changes in the liver function. These changes are usually not permanent and go away once the drug is stopped.

Precautions Certain individuals should not use abarelix. These include women, children under age 18, and men with a rare heart condition called prolongation of the QTc interval. Men with osteoporosis, liver disease, and blood clotting disorders should identify these existing problems to their doctor before beginning treatment. Abarelix may stop working in some men and is more likely to stop working in men weighing over 225 lb (102 kg). There are no special dietary restriction when receiving abarelix therapy. 2

low blood pressure, fainting, shock swelling of the face, eyelids, tongue, or throat wheezing, asthma, tightness in the chest, difficulty breathing

     

hot flashes rapid heart beat (tachycardia) rash, hives, itching, skin redness vomiting jaundice (yellowing of the whites of the eyes or skin) stomach pain breast enlargement problems sleeping breast, back or other pain constipation changes in the electrical profile of the heart

Interactions It is important for patients to discuss with their physician all prescription medications, over-the-counter medications, and herbal or alternative remedies that the patients are taking before treatment with abarelix is begun. Although as of 2005 formal drug interaction studies have not been completed, a number of drugs may interact with abarelix. These include:          

arsenic trioxide astemizole (Hismanal) bepridil (Vascor) certain antibiotics cisapride (Propulsid) cyclobenzaprine (Flexeril) DHEA (dietary supplement) dolasetron (Anzemet) droperidol halofantrine (Halfan) G A LE EN CY C LO PE DI A O F C AN C ER 3

       

estrogen or other female hormones levomethadyl (Orlaam) medications that regulate heart rhythm medications that treat depression palonosetron (Aloxi) pentamidine (Pentam) phenothiazines (found in antihistamines) pimozide (Orap) probucol (Lorelco) Tish Davidson, A. M.

burdensome for individuals living far from their treatment center, or who have to juggle multiple obligations family and work. Because APBI is of shorter duration than traditional breast saving treatment, it may be a more viable option for many women. It also targets a smaller area for treatment, meaning that fewer healthy tissues and organs are exposed to the radiation. In 2009 the American Society for Radiation Oncology issued a consensus statement on accelerated partial breast irradiation. In it, they made recommendations based on a wide range of clinical trial outcomes. They established guidelines for which women are good candidates for APBI instead of the traditional whole breast irradiation.

Demographics

Accelerated partial breast irradiation Definition Accelerated partial breast irradiation (APBI), also referred to as high dose rate breast brachytherapy, is a shortened course of high dose radiation therapy that is given to breast cancer patients. It targets the area of the breast where the cancer is most likely to recur.

Purpose One of the purposes of APBI is to reduce the radiation treatment time from seven or eight weeks, which is generally required with conventional whole breast irradiation, to four or five days. Planning for seven or eight weeks of radiation treatment is difficult for many women, especially women who work outside the home, are single parents, and/or live in rural areas. Reducing the treatment time to one week is not only more convenient for many patients, but it also helps them with emotional closure. In other words, the sooner they are done with the treatments, the sooner they can put the cancer behind them. Another purpose of APBI is to save the breast while still preventing a recurrence of the cancer. Many women are good candidates for breast conserving therapy, in which the lump is surgically removed (lumpectomy), and then radiation or chemotherapy is used to destroy any remaining cancer cells. Although this treatment leaves the breast intact, many women still choose to have a full removal of the breast (mastectomy). There are many reasons women may make this choice, including the long treatment regimen being too difficult or costly to arrange and concerns about exposing surrounding tissue and organs to radiation. Arranging for seven or eight weeks of treatment can be especially G A LE EN CY C LO PE DI A O F C AN CE R 3

Patients over 60 years of age are considered ‘‘suitable’’ candidates for APBI. Patients from 50 to 59 years of age are considered ‘‘cautionary’’, meaning in some cases the treatment may be appropriate, and patients under age 50 are considered ‘‘unsuitable’’. Guidelines also consider which women are suitable candidates along a variety of other factors, including tumor size (less than or equal to 2 cm), cancer stage (T1) and other factors.

Precautions Accelerated partial breast irradiation is a relatively new treatment method. Long-term studies of its effectiveness and safety are, as of 2009, still being carried out. For many women it may not be as effective as traditional whole breast irradiation. Clinical trials are underway to determine its long-term effectiveness and which patient populations it is most appropriate for. Until more is known about this treatment, the American Society for Radiation Oncology recommend conservative guidelines be used.

Description High Dose Rate Breast Brachytherapy There are two ways to accomplish the administration of APBI, both of which can be done on an outpatient basis. One way, called high does rate breast brachytherapy, involves inserting multiple plastic tubes (catheters) in the breast area surrounding the lumpectomy cavity. A tiny radioactive seed, which delivers the correct amount of radiation, is inserted in the catheters. Generally, the treatment is given twice a day for five days, although some treatment regimes vary according to the individual needs of the patient. Treatment sessions usually take no longer than 3

Accelerated partial breast irradiation



Acoustic neuroma

20 minutes. At the end of the five-day treatment, the catheters are removed.

QUESTIONS TO ASK YOUR DOC TOR

Mammosite Breast Brachytherapy Another way to administer APBI is called mammosite breast brachytherapy, which is also known as balloon catheter brachytherapy. In this case, a small balloon is attached to a single catheter, which is inserted into the lumpectomy cavity. Then the balloon is inflated and a computer-controlled machine places the high dose radioactive seed inside the balloon. This therapy requires a fairly narrow range of cavity location and size, so it is not an appropriate treatment for all women.

 



  

Am I a good candidate for APBI? Are there any clinical trials going on for which I may qualify? What are the costs and benefits for me of having APBI instead of whole breast irradiation? Is this treatment covered by my insurance How often have you performed this procedure? Do many of your patients express regret over choosing APBI over external beam radiation therapy?

Preparation Preparation requirements are different depending on the type of procedure being performed, and the specifics of the patient’s breast and previous history. Making plans in advance with family and friends to help in providing transportation, caring for children, preparing meals, or doing housework can provide much needed support during treatment.

Aftercare Good nutrition, regular light exercise, and plenty of rest are important after any radiation therapy. Additional aftercare information is provided by treatment staff on a case-by-case basis.

Risks Possible side effects include discomfort due to the insertion and removal of the catheters and pain or soreness around the insertion sited. Other possible side effects include swelling around the irradiated area, soreness, changes in skin coloration, and fatigue.

Results

Miller, Kenneth, D. Choices in Breast Cancer Treatment: Medical Specialists and Cancer Survivors Tell You What You Need to Know. Baltimore: Johns Hopkins Univer sity Press, 2008. Wazer, David E. Accelerated Partial Breast Irradiation. New York: Springer, 2009. PERIODICALS

Dirbas, Frederick M. ‘‘Accelerated Partial Breast Irradia tion: Where Do We Stand? Journal of the National Comprehensive Cancer Network, (February 2009), 215 225. Smith, Benjamin D., et al. ‘‘Accelerated Partial Breast Irra diation Consensus Statement from the American Soci ety for Radiation Oncology. Journal of the American College of Surgeons, (August 2009), 269 277. ORGANIZATIONS

American Cancer Society, (800) ACS 2345, www.cancer.org. National Cancer Institute, 6116 Executive Boulevard Room 3036A, Bethesda, MD, 20892 8322, (800) 4 CANCER (800 422 6237), www.cancer.gov. Susan G. Komen Foundation, 5005 LBJ Freeway, Suite 250, Dallas, TX, 75244, (877) GO KOMEN, www.komen.org.

Lee Ann Paradise Tish Davidson, A.M.

Preliminary evidence suggests that for many women APBI is as effective as traditional whole breast irradiation. However, as of 2009, clinical trials were still underway to determine the long-term effectiveness of the treatment. Patients should ask their physician for the most up-to-date information on recommendations for treatment and outcome statistics. Resources BOOKS

Kneece, Judy C. Breast Cancer Treatment Handbook: Understanding the Disease, Treatments, Emotions, and Recovery from Breast Cancer, 7th ed. North Charleston, SC: EduCare, 2009. 4

Acoustic neuroma Definition An acoustic neuroma is a benign tumor involving cells of the myelin sheath that surrounds the vestibulocochlear nerve (eighth cranial nerve). G A LE EN CY C LO PE DI A O F C AN C ER 3

An acoustic neuroma can arise from the left vestibular nerve or the right vestibular nerve. A unilateral tumor is a tumor arising from one nerve and a bilateral tumor arises from both vestibular nerves. Unilateral acoustic neuromas usually occur spontaneously (by chance). Bilateral acoustic neuromas occur as part of a hereditary condition called Neurofibromatosis Type 2 (NF2). A person with NF2 has inherited a predisposition for developing acoustic neuromas and other tumors of the nerve cells.

False-color magnetic resonance image (MRI) scan of a coronal section of the head & brain of someone suffering from an acoustic neuroma (green circular area). (Photograph by Mehau Kulyk, Photo Researchers, Inc. Reproduced by permission.)

Description The vestibulocochlear nerve extends from the inner ear to the brain and is made up of a vestibular branch, often called the vestibular nerve, and a cochlear branch, called the cochlear nerve. The vestibular and cochlear nerves lie next to one another. They also run along side other cranial nerves. People possess two of each type of vestibulocochlear nerve, one that extends from the left ear and one that extends from the right ear. The vestibular nerve transmits information concerning balance from the inner ear to the brain and the cochlear nerve transmits information about hearing. The vestibular nerve, like many nerves, is surrounded by a cover called a myelin sheath. A tumor called a schwannoma can sometimes develop from the cells of the myelin sheath. A tumor is an abnormal growth of tissue that results from the uncontrolled growth of cells. Acoustic neuromas are often called vestibular schwannomas because they are tumors that arise from the myelin sheath that surrounds the vestibular nerve. Acoustic neuromas are considered benign (nonG A LE EN CY C LO PE DI A O F C AN CE R 3

Acoustic neuromas usually grow slowly and can take years to develop. Some acoustic neuromas remain so small that they do not cause any symptoms. As the acoustic neuroma grows, it can interfere with the functioning of the vestibular nerve and can cause vertigo and balance difficulties. If the acoustic nerve grows large enough to press against the cochlear nerve, then hearing loss and a ringing (tinnitus) in the affected ear will usually occur. If untreated and the acoustic neuroma continues to grow, it can press against other nerves in the region and cause other symptoms. This tumor can be life threatening if it becomes large enough to press against and interfere with the functioning of the brain.

Causes and symptoms Causes An acoustic neuroma is caused by a change or absence of both of the NF2 tumor suppressor genes in a nerve cell. Every person possesses a pair of NF2 genes in every cell of their body including their nerve cells. One NF2 gene is inherited from the egg cell of the mother and one NF2 gene is inherited from the sperm cell of the father. The NF2 gene is responsible for helping to prevent the formation of tumors in the nerve cells. In particular the NF2 gene helps to prevent acoustic neuromas. Only one unchanged and functioning NF2 gene is necessary to prevent the formation of an acoustic neuroma. If both NF2 genes become changed or missing in one of the myelin sheath cells of the vestibular nerve, then an acoustic neuroma will usually develop. Most unilateral acoustic neuromas result when the NF2 genes become spontaneously changed or missing. Someone with a unilateral acoustic neuroma that has developed spontaneously is not at increased risk for having children with an acoustic neuroma. Some 5

Acoustic neuroma

cancerous) tumors since they do not spread to other parts of the body. They can occur anywhere along the vestibular nerve but are most likely to occur where the vestibulocochlear nerve passes through the tiny bony canal that connects the brain and the inner ear.

Acoustic neuroma

K E Y TE R M S Benign tumor—A localized overgrowth of cells that does not spread to other parts of the body. Chromosome—A microscopic structure, made of a complex of proteins and DNA, that is found within each cell of the body. Cranial nerves—The set of twelve nerves found on each side of the head and neck that control the sensory and muscle functions of a number of organs such as the eyes, nose, tongue face and throat. Computed tomography (CT)—An examination that uses a computer to compile and analyze the images produced by x rays projected at a particular part of the body. DNA testing—Testing for a change or changes in a gene or genes. Gene— A building block of inheritance, made up of a compound called DNA (deoxyribonucleic acid) and containing the instructions for the production of a particular protein. Each gene is found on a specific location on a chromosome.

unilateral acoustic neuromas result from the hereditary condition NF2. It is also possible that some unilateral acoustic neuromas may be caused by changes in other genes responsible for preventing the formation of tumors. Bilateral acoustic neuromas result when someone is affected with the hereditary condition NF2. A person with NF2 is typically born with one unchanged and one changed or missing NF2 gene in every cell of their body. Sometimes they inherit this change from their mother or father. Sometimes the change occurs spontaneously when the egg and sperm come together to form the first cell of the baby. The children of a person with NF2 have a 50% chance of inheriting the changed or missing NF2 gene. A person with NF2 will develop an acoustic neuroma if the remaining unchanged NF2 gene becomes spontaneously changed or missing in one of the myelin sheath cells of their vestibular nerve. People with NF2 often develop acoustic neuromas at a younger age. The mean age of onset of acoustic neuroma in NF2 is 31 years of age versus 50 years of age for sporadic acoustic neuromas. Not all people with NF2, however, develop acoustic neuromas. People with NF2 are at 6

Magnetic resonance imaging (MRI)—A test which uses an external magnetic field instead of x rays to visualize different tissues of the body. Myelin sheath—The cover that surrounds many nerve cells and helps to increase the speed by which information travels along the nerve. Neurofibromatosis type 2 (NF2)—A hereditary condition associated with an increased risk of bilateral acoustic neuromas, other nerve cell tumors and cataracts. Protein—A substance produced by a gene that is involved in creating the traits of the human body such as hair and eye color or is involved in controlling the basic functions of the human body. Schwannoma—A tumor derived from the cells of the myelin sheath that surrounds many nerve cells. Tinnitus—A ringing sound or other noise in the ear. Vertigo—A feeling of spinning or whirling. Vestibulocochlear nerve (Eighth cranial nerve)— Nerve that transmits information, about hearing and balance from the ear to the brain.

increased risk for developing cataracts and tumors in other nerve cells. Most people with a unilateral acoustic neuroma are not affected with NF2. Some people with NF2, however, only develop a tumor in one of the vestibulocochlear nerves. Others may initially be diagnosed with a unilateral tumor but may develop a tumor in the other nerve a number of years later. NF2 should be considered in someone under the age of 40 who has a unilateral acoustic neuroma. Someone with a unilateral acoustic neuroma and other family members diagnosed with NF2 probably is affected with NF2. Someone with a unilateral acoustic neuroma and other symptoms of NF2 such as cataracts and other tumors may also be affected with NF2. On the other hand, someone over the age of 50 with a unilateral acoustic neuroma, no other tumors and no family history of NF2 is very unlikely to be affected with NF2. Recent studies in Europe have suggested a possible connection between the widespread use of mobile phones and an increased risk of developing acoustic neuromas. Some observers, however, question whether mobile phones have been in use long enough to be an identifiable risk factor. G A LE EN CY C LO PE DI A O F C AN C ER 3

Small acoustic neuromas usually only interfere with the functioning of the vestibulocochlear nerve. The most common first symptom of an acoustic neuroma is hearing loss, which is often accompanied by a ringing sound (tinnitis). People with acoustic neuromas sometimes report difficulties in using the phone and difficulties in perceiving the tone of a musical instrument or sound even when their hearing appears to be otherwise normal. In most cases the hearing loss is initially subtle and worsens gradually over time until deafness occurs in the affected ear. In approximately 10% of cases the hearing loss is sudden and severe. Acoustic neuromas can also affect the functioning of the vestibular branch of the vestibulocochlear nerve and van cause vertigo and dysequilibrium. Twenty percent of small tumors are associated with periodic vertigo, which is characterized by dizziness or a whirling sensation. Larger acoustic neuromas are less likely to cause vertigo but more likely to cause dysequilibrium. Dysequilibrium, which is characterized by minor clumsiness and a general feeling of instability, occurs in nearly 50% of people with an acoustic neuroma. As the tumor grows larger, it can press on the surrounding cranial nerves. Compression of the fifth cranial nerve can result in facial pain and or numbness. Compression of the seventh cranial nerve can cause spasms, weakness or paralysis of the facial muscles. Double vision is a rare symptom but can result when the sixth cranial nerve is affected. Swallowing and/or speaking difficulties can occur if the tumor presses against the ninth, tenth, or twelfth cranial nerves. If left untreated, the tumor can become large enough to press against and affect the functioning of the brain stem. The brain stem is the stalk-like portion of the brain that joins the spinal cord to the cerebrum, the thinking and reasoning part of the brain. Different parts of the brainstem have different functions such as the control of breathing and muscle coordination. Large tumors that impact the brain stem can result in headaches, walking difficulties (gait ataxia) and involuntary shaking movements of the muscles (tremors). In rare cases when an acoustic neuroma remains undiagnosed and untreated it can cause nausea, vomiting, lethargy and eventually coma, respiratory difficulties and death. In the vast majority of cases, however, the tumor is discovered and treated long before it is large enough to cause such serious manifestations.

Diagnosis Anyone with symptoms of hearing loss should undergo hearing evaluations. Pure tone and speech G A LE EN CY C LO PE DI A O F C AN CE R 3

audiometry are two screening tests that are often used to evaluate hearing. Pure tone audiometry tests to see how well someone can hear tones of different volume and pitch and speech audiometry tests to see how well someone can hear and recognize speech. An acoustic neuroma is suspected in someone with unilateral hearing loss or hearing loss that is less severe in one ear than the other ear(asymmetrical). Sometimes an auditory brainstem response (ABR, BAER) test is performed to help establish whether someone is likely to have an acoustic neuroma. During the ABR examination, a harmless electrical impulse is passed from the inner ear to the brainstem. An acoustic neuroma can interfere with the passage of this electrical impulse and this interference can, sometimes be identified through the ABR evaluation. A normal ABR examination does not rule out the possibility of an acoustic neuroma. An abnormal ABR examination increases the likelihood that an acoustic neuroma is present but other tests are necessary to confirm the presence of a tumor. If an acoustic neuroma is strongly suspected then magnetic resonance imaging (MRI) is usually performed. The MRI is a very accurate evaluation that is able to detect nearly 100% of acoustic neuromas. Computed tomography (CT scan, CAT scan) is unable to identify smaller tumors; but it can be used when an acoustic neuroma is suspected and an MRI evaluation cannot be performed. Once an acoustic neuroma is diagnosed, an evaluation by genetic specialists such as a geneticist and genetic counselor may be recommended. The purpose of this evaluation is to obtain a detailed family history and check for signs of NF2. If NF2 is strongly suspected then DNA testing may be recommended. DNA testing involves checking the blood cells obtained from a routine blood draw for the common gene changes associated with NF2.

Treatment The three treatment options for acoustic neuroma are surgery, radiation, and observation. The physician and patient should discuss the pros and cons of the different options prior to making a decision about treatment. The patient’s physical health, age, symptoms, tumor size, and tumor location should be considered. Microsurgery The surgical removal of the tumor or tumors is the most common treatment for acoustic neuroma. In most cases the entire tumor is removed during the surgery. If the tumor is large and causing significant 7

Acoustic neuroma

Symptoms

Acoustic neuroma

symptoms, yet there is a need to preserve hearing in that ear, then only part of the tumor may be removed. During the procedure the tumor is removed under microscopic guidance and general anesthetic. Monitoring of the neighboring cranial nerves is done during the procedure so that damage to these nerves can be prevented. If preservation of hearing is a possibility, then monitoring of hearing will also take place during the surgery. Most people stay in the hospital four to seven days following the surgery. Total recovery usually takes four to six weeks. Most people experience fatigue and head discomfort following the surgery. Problems with balance and head and neck stiffness are also common. The mortality rate of this type of surgery is less than 2% at most major centers. Approximately 20% of patients experience some degree of postsurgical complications. In most cases these complications can be managed successfully and do not result in long term medical problems. Surgery brings with it a risk of stroke, damage to the brain stem, infection, leakage of spinal fluid and damage to the cranial nerves. Hearing loss and/or tinnitis often result from the surgery. A follow-up MRI is recommended one to five years following the surgery because of possible regrowth of the tumor. Stereotactic radiation therapy During stereotactic radiation therapy, also called radiosurgery or radiotherapy, many small beams of radiation are aimed directly at the acoustic neuroma. The radiation is administered in a single large dose, under local anesthetic and is performed on an outpatient basis. This results in a high dose of radiation to the tumor but little radiation exposure to the surrounding area. This treatment approach is limited to small or medium tumors. The goal of the therapy is to cause tumor shrinkage or at least limit the growth of the tumor. The long-term efficacy and risks of this treatment approach are not known; however, as of the early 2000s, more and more patients with acoustic neuromas are choosing this approach over conventional surgery. Periodic MRI monitoring throughout the life of the patient is therefore recommended. Radiation therapy can cause hearing loss which can sometimes occurs even years later. Radiation therapy can also cause damage to neighboring cranial nerves, which can result in symptoms such as numbness, pain or paralysis of the facial muscles. In many cases these symptoms are temporary. Radiation treatment can also induce the formation of other benign or malignant schwannomas. This type of treatment may therefore be contraindicated in the treatment of 8

acoustic neuromas in those with NF2 who are predisposed to developing schwannomas and other tumors. Observation Acoustic neuromas are usually slow-growing; in some cases they will stop growing and even become smaller or disappear entirely. It may therefore be appropriate in some cases to hold off on treatment and to periodically monitor the tumor through MRI evaluations. Long-term observation may be appropriate for example in an elderly person with a small acoustic neuroma and few symptoms. Periodic observation may also be indicated for someone with a small and asymptomatic acoustic neuroma that was detected through an evaluation for another medical problem. Observation may also be suggested for someone with an acoustic neuroma in the only hearing ear or in the ear that has better hearing. The danger of an observational approach is that as the tumor grows larger it can become more difficult to treat.

Prognosis The prognosis for someone with a unilateral acoustic neuroma is usually quite good provided the tumor is diagnosed early and appropriate treatment is instituted. Long-term hearing loss and tinnitis in the affected ear are common, even if appropriate treatment is provided. Many patients also experience facial weakness, balance problems, and headaches. Regrowth of the tumor is also a possibility following surgery or radiation therapy and repeat treatment may be necessary. The prognosis can be poorer for those with NF2 who have an increased risk of bilateral acoustic neuromas and other tumors. Resources BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Acoustic Neuroma.’’ in The Merck Manual of Diag nosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2007. PERIODICALS

Broad, R. W. ‘‘Management of Acoustic Neuroma.’’ New England Journal of Medicine 340, no. 14 (April 8, 1999): 1119. Kondziolka, D., L. D. Lundsford, and J. C. Flickinger. ‘‘Acoustic Neuroma Radiosurgery. Origins, Contem porary Use and Future Expectations.’’ Neurochirurgie 50 (June 2004): 427 435. Kundi, M., K. Mild, L. Hardell, and M. O. Mattsson. ‘‘Mobile Telephones and Cancer A Review of Epide miological Evidence.’’ Journal of Toxicology and Environmental Health, Part B, Critical Reviews 7 (September October 2004): 351 384. G A LE EN CY C LO PE DI A O F C AN C ER 3

Acute erythroblastic leukemia

Lederman, G., E. Arbit, and J. Lowry. ‘‘Management of Acoustic Neuroma.’’ New England Journal of Medicine. 340, no. 14 (April 8, 1999): 1119 1120. O’Donoghue, G.M., T. Nikolopoulos, and J. Thomsen. ‘‘Management of Acoustic Neuroma.’’ New England Journal of Medicine 340, no.14 (April 8, 1999): 1120 1121. Ryzenman, J. M., M. L. Pensak, and J. M. Tew, Jr. ‘‘Patient Perception of Comorbid Conditions After Acoustic Neuroma Management: Survey Results from the Acoustic Neuroma Association.’’ Laryngoscope 114 (May 2004): 814 820. OTHER

National Institute of Health Consensus Statement Online Acoustic Neuroma 9(4)(11 13 December 1991). [cited June 28, 2001]. . University of California at San Francisco (UCSF) Information on Acoustic Neuromas. [cited June 28, 2001]. (18 March 1998). ORGANIZATIONS

Acoustic Neuroma Association. 600 Peachtree Pkwy, Suite 108, Cumming, GA 30041 6899. Phone:(770) 205 8211. Fax: (770) 205 0239. [email protected]. [cited June 28, 2001]. . Acoustic Neuroma Association of Canada Box 369, Edmonton, AB T5J 2J6. 1 800 561 ANAC(2622). (780)428 3384. [email protected]. [cited June 28, 2001]. http://www.anac.ca. British Acoustic Neuroma Association. Oak House, Ransom Wood Business Park, Southwell Road West, Mansfield, Nottingham, NG21 0HJ. Tel: 01623 632143. Fax: 01623 635313. [email protected]. [cited June 28, 2001].http://www.bana uk.com/. Seattle Acoustic Neuroma Group. [email protected]. [cited June 28, 2001]. .

Lisa Andres, M.S., CGC Rebecca J. Frey, PhD

Acquired Immune Deficiency syndrome see AIDS-related cancers Actinomycin D see Dactinomycin

Acute erythroblastic leukemia

Erythroblastic leukemia cells. (Copyright Richard Green, Science Source/Photo Researchers, Inc. Reproduced by permission.)

Description Acute erythroblastic leukemia, a variant of AML, originates in the blood and in the bone marrow. In this form of leukemia, a large number of abnormal, immature red blood cells are produced. The World Health Organization (WHO) classifies acute erythroid leukemia into two subtypes, erythroleukemia, which includes erythroblastic and myeloblastic components (blast cells are immature cells), and pure erythroid leukemia in which the erythroid component constitutes 80% or more of the bone marrow.

Demographics According to the American Cancer Society, approximately 12,810 people (6,920 males and 5,890 females) will be diagnosed with AML in 2009 with about 9,000 deaths predicted to occur from AML during that same time period. Acute erythroid leukemia accounts for about 3–5% of all cases of AML and constitutes 20–30% of cases of secondary leukemia. Erythroid leukemia has been reported from the newborn period through age 7, however, this subtype of AML is rare in children. Males are affected slightly more often than females. A small spike in incidence of erythroid leukemia appears in the fourth decade but the disease is more common after age 50. A larger peak in incidence occurs in the seventh decade.

Definition Acute erythroblastic leukemia, a subtype (M6) of acute myelogenous leukemia (AML), is also called erythroid leukemia, DiGuglielmo syndrome, or erythroleukemia, results from uncontrolled proliferation of immature erythrocytes (red blood cells). G A LE EN CY C LO PE DI A O F C AN CE R 3

Causes and symptoms The causes of acute erythroblastic leukemia are largely unknown. However, acute erythroblastic leukemia constitutes 10–20% of leukemias that develop secondary to previous exposures to ionizing radiation, 9

Acute erythroblastic leukemia

K EY T ERM S Anemia—A condition in which the number of red blood cells is below normal Blast cells—Immature cancer cells. Bone marrow aspiration—Common technique used to obtain a bone marrow sample from a patient. A needle is inserted into a marrow-containing bone, such as the hip (iliac crest) or sternum (breast bone) and a small amount of liquid bone marrow is removed for examination. Bone marrow biopsy—Another common technique used to obtain a bone marrow sample from a patient. Like bone marrow aspiration, it is performed with a needle, but a larger one is used and a small piece of bone is removed as well as bone marrow. Chemotherapy—The treatment of disease by means of chemicals. In cancer, the chemicals selectively destroy cancerous tissue. When cancer remission occurs, a course of maintenance chemotherapy is often prescribed so as to prevent recurrence.

and platelets, which results in insufficient amounts of oxygen being carried through the body. This condition is called anemia, and causes patients to experience severe weakness and tiredness. Patients may have less than the normal number of white blood cells as well. Other symptoms include fever, chills, loss of appetite and weight, easy bleeding or bruising (due to lower than normal platelet levels), bone or joint pain, headaches, vomiting, and confusion. In addition, patients with leukemia may have hepatosplenomegaly, an enlargement of the liver and spleen. Enlargement of these organs is noticed as a fullness or swelling in the abdomen, and can be felt by a doctor during a physical examination. The occurrence of Sweet’s syndrome, a rare skin disorder accompanied by fever, inflammation of the joints (arthritis), and the sudden onset of a rash, has also been associated with acute erythroblastic leukemia.

Diagnosis

Leukemia—Cancer of the blood-forming tissues. Myeloid blast cell—Type of cancer cell originating in the bone marrow.

Patients seeking treatment usually report a vague history of chronic general fatigue. Blood tests are used to establish the diagnosis. A sample of blood is examined under a microscope to identify abnormal red cells—which are larger than healthy cells—and to count the number of mature cells and blasts present. Cancer red cell precursors predominate, myeloid blasts may also be seen, and multinucleated red cell precursors are common. However, blasts may not be present at diagnosis in as many as half of the cases.

Platelet—A type of blood cell responsible for blood coagulation and for the repair of damaged blood vessels.

Other laboratory studies which may be done include:

Proliferation—Rapid reproduction of tissue.



blood chemistry profile, liver function tests and serum electrolytes



blood and urine cultures will be obtained in patients with fever or other signs of infection



vitamin B12 and folate levels should be measured to rule out severe pernicious anemia whose signs and symptoms mimic erythroleukemia



flow cytometry to determine myeloid markers for the disease



cytogenetics studies which assess for chromosomal abnormalities. Cytogenetics studies are important in diagnosis and prognosis of the disease. However, no specific chromosomal abnormalities have yet been identified for M6 subtype of AML.

Erythrocyte—Red blood cell.

Remission—Complete or partial disappearance of the symptoms of cancer following treatment.

previous treatment with chemotherapy agents known as alkylating agents which may have been used to treat Hodgkin disease, multiple myeloma, ovarian cancer, breast cancer and some other non-cancerous diseases and disorders, or as a result of overexposure to benzene. Inheritance There is type of inherited erythroid leukemia which is known as familial erythroleukemia. This familial disorder is rare and most typically occurs in the sixth decade of life. Patients diagnosed with erythroid leukemia have less than the normal amount of healthy red blood cells 10

Imaging studies will also be performed at the time of diagnosis. These studies include: 

echocardiogram or multiple-gated acquisition(MUGA)scan – used to evaluate the status of the cardiac system prior to chemotherapy administration. Some G A LE EN CY C LO PE DI A O F C AN C ER 3



Bone marrow examinations are also performed, either by aspiration or biopsy to examine the cell types further. These results of these examinations are critical to the accurate diagnosis of erythroleukemia. A lumbar puncture may be performed if neurologic involvement is suspected or is present and is also recommended in patients whose circulating leukemic cell counts are very elevated (higher than 50,000/mm3) and for those patients with elevated liver enzyme (LDH) levels.

Treatment Treatment for acute erythroblastic leukemia depends on the features of the cancer cells present and on the extent of the disease, as well as on the age of the patient, his symptoms, and general health condition. The treatment strategy is based on chemotherapy and in some patients, bone marrow or hemotopoietic stem cell transplantations are indicated as well. Chemotherapy is usually administered in combinations of two or more drugs. Cytarabine (Ara-C) is currently the most active chemotherapy agent used in the management of AML and in the erythroid subtype. Various regimens have been designed around the use of Ara-C. Post-remission therapy includes maintenance chemotherapy for most patients.

Prognosis Acute erythroblastic leukemia is a usually a very aggressive form of leukemia and typically does not respond well to the types of therapy used to treat acute myelocytic leukemia. The prognosis compared to the average for AML is worse for patients with this M6 subtype of AML.

Coping with cancer treatment Like all types of leukemias, patients with acute erythroblastic leukemia usually experience a number of specific complications and side effects resulting from treatment, as well as emotional concerns. They require supportive care to cope with these issues and to maintain their comfort and quality of life during treatment. As with every serious disease, psychological stress is increased and it is important for patients to G A LE EN CY C LO PE DI A O F C AN CE R 3

Q U E S T I O N S TO A S K T H E DOCTOR 





How can I obtain information on a rare cancer such as acute erythroblastic leukemia? How are my chances of recovery affected by the fact that this cancer is so rare? Are there current clinical trials in which I may enroll?

be able to discuss their needs and concerns about tests, treatments, hospital stays, and financial consequences of the illness. Family, friends, doctors, nurses, and other members of the health care team are the best sources of support, as well as social workers, counselors, and members of the clergy.

Clinical trials As of June 2009, one clinical trial to determine if standard chemotherapy given with idarubicin and Ara-C can help to control AML is available for patients ages 15 to 75 diagnosed with the M6 subtype of AML and who have less than 20% blasts. Other eligibility (inclusion) criteria apply as well. This clinical trial is sponsored by M.D. Anderson Cancer Center in Houston, Texas.

Prevention Since this form of cancer is very rare and its causes are largely unknown, no specific preventive measures can be recommended.

Special concerns Patients diagnosed with acute erythroblastic leukemia require special support in that they must deal with having a rare form of cancer about which there is very little specific information available. This creates additional anxiety and special care must be taken to explain to the patient that an uncommon cancer is not an untreatable one. See also Bone marrow aspiration and biopsy; Chronic myelocytic leukemia; Myeloproliferative diseases. Resources OTHER

Holkova, B., and K. Takeshita. ‘‘Erythroleukemia.’’ eMedicine Hematology July 18, 2006. http://emedicine. medscape.com/article/199965 print. 11

Acute erythroblastic leukemia



of the chemotherapy medications used to treat this subtype of AML may be toxic to the cardiac system. chest x ray is done to evaluate for pulumonary infections, enlargement of the heart, and other heart and lung problems. CT scan or MRI will be performed if there is suspicion of neurologic involvement.

Acute lymphocytic leukemia

ORGANIZATIONS

The Leukemia and Lymphoma Society of America. 1 800 955 4572. http://www.leukemia lymphoma.org/. National Cancer Information Center. 1 800 ACS 2345. National Cancer Institute. Public Inquiries Office, Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. (301)435 2848. http:// www.cancer.gov.

Monique Laberge, PhD Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Acute lymphocytic leukemia Definition Acute lymphocytic leukemia is a cancer of the white blood cells known as lymphocytes.

Description Leukemia is a cancer of white blood cells. In acute leukemia, the cancerous cells are immature forms called blasts that cannot properly fight infection; patients become ill in rapid fashion. The cells that make up blood are produced in the bone marrow and the lymph system. The bone marrow is the spongy tissue found in the large bones of the

KEY TERMS Antiangiogenic drugs—Drugs that block the forma tion of new blood vessels. Blasts—Immature blood cells. CBC—Complete blood count, a blood test that measures red cells, white cells and platelets. Graft versus host disease—After bone marrow transplant, the newly transplanted white blood cells can attack the patient’s own tissues. Intrathecal chemotherapy—Chemotherapeutic drugs instilled directly into the spinal fluid, either by spinal tap or through a special reservoir. Karyotype—The number and type of chromosomes found within cells. Lymphoblasts—The cancerous cells of ALL, imma ture forms of lymphocytes, white blood cells that fight infection. Ommaya reservoir—A special device surgically placed under the scalp with a direct connection to spinal fluid. Medications to treat central nervous system disease are injected into the reservoir. Petechiae—Pinpoint red spots seen on the skin with low platelet counts. Philadelphia chromosome—An abnormal chromo some found in 20% of adults and 5% of children with ALL, the presence of which indicates a some what worse prognosis. Sanctuary sites—Areas within the body which are relatively impermeable to medications such as che motherapy but which can harbor cancerous cells. Some of these sites are the central nervous system, the testicles, and the eyes. Thymus—A gland within the chest involved in the maturation of immune cells that can be invaded by T lymphocytes in T cell ALL.

False-color scanning electron micrograph (SEM) of white blood cells from a patient with acute lymphocytic leukemia. In this disease, certain types of white blood cells are overproduced, and these abnormal cells suppress the normal function of white and red cells, increasing the susceptibility to infections. (Copyright Aaron Polliack, Science Source/Photo Researchers, Inc. Reproduced by permission.)

12

body. The lymph system includes the spleen (an organ in the upper abdomen), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat). In addition, the lymph vessels (tiny tubes that branch like blood vessels into all parts of the body) and lymph nodes (pea-shaped organs that are found along the network of lymph vessels) are also part of the lymph system. The lymph is a milky fluid that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest. The main types of cells found in the blood are the red blood cells (RBCs), which carry oxygen and other G A LE EN CY C LO PE DI A O F C AN C ER 3

The granulocytes, as their name suggests, have particles (granules) inside them. These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms such as bacteria. Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens. The lymphocytes form the third type of white blood cell. The two types of lymphocytes are B cells, which make antibodies, and T cells, which make other infectionfighting substances. Lymphocytic leukemia can arise in either B or T cells. B-cell leukemia occurs more frequently than T-cell leukemia. It is the most common form of leukemia in children, but also occurs in adults. At diagnosis, leukemic cells can be found throughout the body, in the bloodstream, the lymph nodes, spleen, liver, occasionally in the central nervous system, and in T-cell ALL, the thymus gland. Cancerous lymphoblasts take over the bone marrow, reducing both the number and the effectiveness of all types of blood cells. The cancerous cells reduce the ability of healthy white cells to fight infection. Fewer red cells are produced, causing anemia, and fewer platelets increases the risk of bleeding and bruising. The presence of the cancerous white cells in the central nervous system can produce headaches, confusion and seizures.

Demographics ALL is the most common of the four major types of leukemia in children, representing one-third of all pediatric cancers. Peak incidence in children occurs between the ages of two and five years. Conversely, ALL is the least common type of the four major types of leukemia affecting adults. In 2009, the American Cancer Society estimates about 45,000 Americans will be diagnosed with leukemia. Of those cases, 5,760 of ALL will be diagnosed with 1 in 3 cases or about 1,900 new cases diagnosed in adults. Approximately 3,800 new cases of ALL will be diagnosed in children in the U.S. in 2009. About 1400 deaths from ALL will occur in the U.S. in 2009 with threefourths of the deaths, about 1,000, occurring in adults. The death rate for children with ALL has dropped nearly 60% in the last 30 years. The overall five-year survival rate for children with ALL is now 80%. The G A LE EN CY C LO PE DI A O F C AN CE R 3

average life-time risk of developing ALL is about 1 in 1000. ALL incidence in adults increases with age. In the United States, ALL is highest among Caucasians and lowest among Asian-Americans. The incidence of ALL is about 50% higher for men than for women. Death rates in leukemia patients are highest in African-Americans and Caucasians and lowest in Asians. In children, the highest leukemia rates in the US occur among those of Filipino descent; next highest are white Hispanics, then non-Hispanic whites, and the lowest incidence in children is in African-Americans. Survival is higher for Caucasians than AfricanAmericans. The survival rate for girls is slightly higher, in part due to the risk of relapse occurring in the testicles and in part because boys appear to have a slightly higher risk of bone marrow relapse.

Causes and symptoms Causes While specific causes for ALL are not known, there are some known risk factors, including ionizing radiation. Exposure to certain chemicals, particularly benzene (used in the manufacture of plastics, rubber, and some medicines), has also been associated with an increased risk of developing ALL. Infection with a rare virus, HTLV-1 (rare in the United States), can cause a rare type of ALL. The Epstein Barr virus (EBV), which causes mononucleosis, has also been linked to a form of ALL. The causes of ALL in children are also unknown. Certain inherited genetic abnormalities, such as Down syndrome, increase the risk. Some studies have shown prenatal exposure to ionizing radiation increases a child’s risk of ALL. Some contaminants of tap water, such as trihalomethanes, chloroform, zinc, cadmium, and arsenic are associated with an increased risk. A number of reports suggested an increased risk of ALL among children who lived in proximity to high voltage power lines, but several later analyses suggested that was not true. Studies continue in efforts to disprove or confirm this possible connection. ALL is more common in children who are not firstborn and among those whose mothers took antibiotics during their pregnancies. Breastfeeding has been found to be protective. Symptoms ADULTS. ALL in adults can cause any or all of the following symptoms:  

fevers, chills, sweats weakness, fatigue, shortness of breath 13

Acute lymphocytic leukemia

materials to all tissues of the body; white blood cells (WBCs), which fight infection; and the platelets, which play a part in the clotting of the blood. The white blood cells can be further subdivided into three main types: granulocytes, monocytes, and lymphocytes.

Acute lymphocytic leukemia

frequent infections  depressed appetite, weight loss  enlarged lymph nodes  easy bleeding or bruising  rash of small, flat red spots (petechiae)  bone and joint pain 

Symptoms of central nervous system involvement include: headache  nausea and vomiting  confusion  seizures 

CHILDREN. Symptoms in children are similar, but young children may be unable to communicate them. They include:

fevers  frequent infections  fatigue, irritability, decreased activity levels  easy bruising or bleeding  bone or joint pain  a limp  swollen belly  enlarged lymph nodes 

T-cell ALL can invade the thymus gland in the upper chest, which can cause compression of the windpipe, cough or shortness of breath, and superior vena cava syndrome (compression of a large vein that causes swelling of the head, neck, and arms). Central nervous system involvement in children produces: headache  nausea and vomiting  blurred vision  decline in school performance  seizures 

Spread to the testicles can cause painless swelling in them.

Diagnosis There are no screening tests for leukemia. The patient’s history and physical examination raise the physician’s suspicions, triggering orders for appropriate tests. Pallor, swollen lymph nodes, bleeding, bruising, pinpoint red rashes, and in children, a swollen abdomen, will suggest the diagnosis. Testing is similar for adults and children. 14

The first test is a complete blood count (CBC), examining red cells, platelets and white cells. In early leukemia, the total white blood cell count might be normal, but there will usually be circulating lymphoblasts, which is always abnormal. The red cell and platelet counts may be low. The abnormal CBC results trigger a referral to a hematologist/oncologist who will perform a bone marrow aspiration and biopsy, in which a small sample of marrow is removed with a hollow needle inserted in the hipbone. Although topical anesthetic will numb the skin and bone, most patients experience brief pain during this procedure. The sample will be examined microscopically for evidence of lymphoblasts. The marrow will be further studied to determine whether the lymphoblasts are of T-cell or B-cell origin and the cells tested for chromosomal abnormalities. A pathologist can examine the marrow and make the diagnosis immediately. The chromosome studies require several days to complete. The bone marrow aspirate will be repeated occasionally during treatment to confirm remission and to look for possible relapse. A lumbar puncture, or spinal tap, will be performed to rule out spread of ALL to the central nervous system. A thin needle is inserted between two vertebrae in the lower back, and spinal fluid removed. This fluid is examined microscopically for the presence of lymphoblasts. Topical anesthetics eliminate most of the discomfort of a spinal tap, although many patients experience headaches afterwards. Remaining flat for 30 minutes after a spinal tap decreases the likelihood of headache. A chest x ray will show enlargement of internal lymph nodes or the thymus gland. No preparation is necessary for most of the testing done to diagnose ALL. Younger children will often receive mild sedatives before procedures like spinal taps and bone marrow studies. Topical anesthetic cream can be applied an hour in advance of either a bone marrow test or a spinal tap. When treatment is complete, tests for minimal residual disease can be performed. These new tests detect the presence of lingering leukemic cells that would have been missed by standard testing. The presence of a certain amount of residual disease probably has an impact on prognosis and the likelihood of relapse.

Treatment team The treatment team consists of a hematologist/ oncologist who directs care, oncology nurses familiar with administering chemotherapy, and often social G A LE EN CY C LO PE DI A O F C AN C ER 3

In many hospitals, a Child Life specialist will participate in the care of children with ALL. They ensure that children with cancer are seen, first and foremost, as children, organizing play times, providing distraction during scary procedures and giving parents some much-needed respite.

Clinical staging, treatments, and prognosis Classification of ALL based on immunophenotyping has replaced the French American British (FAB) system of classifying ALL in adults. Results of cytogenetic testing, flow cytometry, and molecular genetic studies provide detailed information regarding specific subtypes of ALL provide clues to prognosis, and help to determine the best treatment options. ALL in adults is classified by the type of lymphocyte affected, either B cell or T cell, and by the level of differentiation or maturity of the leukemic cell. The two major subtypes of ALL are B-cell ALL and T-cell ALL. B-cell ALL can be further subdivided or classified into the following categories: 

  

early pre-B cell ALL – about 10% of cases; this type may also be referred to as pro-B ALL common ALL – comprises about 50% of cases pre B ALL – approximately 10% of cases mature B-cell ALL; also known as Burkitt leukemia; comprises about 4% of cases

T-cell ALL can be further subdivided or classified into the following categories:  

pre-T ALL – about 5–10% of cases mature T cell ALL – about 15–20% of cases

Conventional treatment for ALL consists of chemotherapy for disease in the bone marrow and treatment aimed at preventing central nervous system disease.

higher risk of relapse at the time of diagnosis, but younger adults (less than 50 years old) have a better prognosis. Adults whose initial white blood cell is higher than 50,000/mm3 at the time of diagnosis have a poorer prognosis. In addition, adults who achieve complete remission within 4 to 5 weeks of starting therapy, tend to have a more favorable prognosis. Generally, T-cell ALL has a more favorable prognosis than B-cell Burkett leukemia. The presence of an antigen called CD20 indicates a more favorable prognosis. ALL is also classified by karyotype, which is the number and composition of a cell’s chromosomes. Normal human cells contain 46 chromosomes. One chromosomal abnormality often seen in ALL is a translocation, in which a piece of one chromosome becomes attached to a different chromosome. Different translocations carry different prognoses. One translocation, labeled t(9;22) is also called the Philadelphia chromosome and is found in 5% of childhood ALL and 20% of adult ALL cases. The Philadelphia chromosome carries a somewhat less favorable prognosis. The number of chromosomes found in the leukemic cells, particularly in children, also impacts prognosis. The occurrence of more than 50 chromosomes in leukemic cells has a very favorable prognosis. Even the presence of one extra chromosome can be favorable. Children whose leukemic cells have fewer than 45 chromosomes are at highest risk of treatment failure. ADULTS. The first phase of treatment is remission induction. Combinations of various chemotherapeutic drugs are typically used. Drugs used to treat adult ALL include:         

The type of treatment a person receives for ALL depends on the presence of risk factors for relapse. Children are at standard risk if they are between ages 1 and 9, have a total white cell count of less than 50,000 per microliter of blood, and have B-precursor cell leukemia. Children are at high risk if they are younger than 1 or older than 9, if their white blood cell count exceeds 50,000 per microliter, or if they have T-cell leukemia. Compared to children, adults are all at G A LE EN CY C LO PE DI A O F C AN CE R 3

  

prednisone vincristine cytarabine cyclophosphamide asparaginase daunorubicin doxorubicin etoposide teniposide 6-mercaptopurine methotrexate dexamethasone

Most are given intravenously and a few are given orally. Depending on the disease, these drugs can achieve a complete remission in 60–90% of adults. The relapse rate is higher in adults than in children. A 50% 3-year survival has been noted in some 15

Acute lymphocytic leukemia

workers, who can address both insurance issues and psychological support. The patient’s regular physician should be kept informed of all cancerrelated care. Because treatment is so prolonged, most patients have long-term intravenous catheters placed by a surgeon.

Acute lymphocytic leukemia

research series, and very aggressive treatment with multiple drugs has produced up to a 70% survival rate. Adverse effects of these drugs include: bone marrow suppression  anemia, pallor, fatigue, shortness of breath, and angina in older patients  bleeding, bruising  increased risk of infection  hair loss (alopecia)  mouth sores  nausea and vomiting  menopausal symptoms  lower sperm counts  tumor lysis syndrome, in which the dead cancer cells can harm healthy organs 

Treatment that is directed at preventing central nervous system spread is called prophylactic. Because of the blood brain barrier, a physical and chemical barrier that prevents toxins from reaching the brain and spinal cord, chemotherapeutic drugs do not easily reach the central nervous system. Thus, chemotherapeutic drugs are administered directly into spinal fluid, which circulates around the brain and spinal cord. This is called intrathecal chemotherapy. The drugs are given by spinal tap or through an Ommaya reservoir, which is surgically inserted under the scalp. This reservoir empties into the spinal fluid around the brain. Some patients receive prophylactic radiation therapy to the brain, in addition to or instead of intrathecal chemotherapy. Some patients with Philadelphia chromosome positive ALL may receive the targeted therapy agents imatinib (Gleevec) or dasatinib (Sprycel) to treat their leukemia. The monoclonal antibody, rituximab (Rituxan), may be used to treat adult ALL in patients whose leukemic cells are positive for the CD20 antigen. CHILDREN. The treatment of ALL in children represents one of the great success stories of modern oncology. In contrast to adults, most children with cancer enter into research protocols, strict treatment regimens with careful follow-up that are built on the most successful aspects of earlier treatments. Childhood ALL now has an 80% long-term survival rate, due in large part to the extensive and widely disseminated research on the disease. Within the United States, research on ALL was conducted for many years under the auspices of either the Children’s Cancer Group or the Pediatric Oncology Group. In 1998,

16

recognizing the benefits of cooperation and collaboration, these two groups joined forces with the National Wilms’ Tumor Study Group and the Intergroup Rhabdomyosarcoma Study Group to form the Children’s Oncology Group. Excluding the treatment of B-cell ALL, the treatment of other types of childhood ALL includes 5 components or phases: induction, consolidation, interim maintenance, delayed intensification, and maintenance. The goal of the induction phase is to achieve remission or evidence of less than 5% blasts (immature cells) in the bone marrow. Drugs in the induction phase may include a glucocorticoid, vincristine, asparaginase and sometimes an anthracycline drug. Most patients, over 98%, achieve complete remission as a result of this therapy. The adverse effects of these drugs include bone marrow suppression, risk of infection, nausea, vomiting, hair loss, and mouth sores. Although these drugs can reduce sperm counts, most survivors of childhood ALL grow up to have normal fertility. Treatment may be intensified for some patients based on evidence of minimal residual disease. Drugs given in the consolidation phase are given in higher doses than those during induction or the patient may be given a different combination of drugs. Drugs which may be used in this phase include high-dose methotrexate, 6-mercaptopurine, etoposide, cytarabine or a combination of drugs. The goal during the interim maintenance phase is to maintain remission while allowing the bone marrow to recover. This phase, which lasts about 4 weeks, is followed by delayed intensification. Drugs given during the interim maintenance phase are administered orally. Treatment given during the delayed intensification component is given to eradicate any remaining leukemic cells which may have been resistant to the drugs administered in the other phases of therapy. The final phase, maintenance, consists of the administration of intrathecal methotrexate every three months in addition to monthly administration of vincristine, weekly methotrexate and daily 6mercaptopurine. Like adults, children also receive prophylaxis against central nervous system spread. They receive multiple doses of intrathecal chemotherapy, with the drugs delivered directly to the spinal fluid through a lumbar puncture or spinal tap. Cranial radiation as central nervous system prophylaxis for children is G A LE EN CY C LO PE DI A O F C AN C ER 3

Alternative and complementary therapies ADULTS. Individuals with leukemia often employ alternative or complementary therapies. Some of these provide pain relief and improve psychological well being. No controlled studies have yet shown that alternative treatments offer cures for ALL, although some may hold promise of benefit.

Patients with ALL sometimes use acupuncture, which offers relief from generalized pain, nausea, and vomiting. Other methods that may help with the physical and often emotional side effects of treatment include hypnosis, guided imagery, and yoga. Nutritional supplements and herbs are sometimes utilized by persons with leukemia. Coenzyme Q10 is an antioxidant, a substance that protects cells from toxic byproducts of metabolism. Early studies suggest, although it is not proven, that coenzyme Q10 can improve immune function and counteract some of the harmful effects of chemotherapy and radiation on healthy cells. Adverse effects of coenzyme Q10 include headache, rash, heartburn and diarrhea. Another supplement with potential benefit is polysaccharide K (PSK). A few studies have shown PSK to have some benefit in improving immunity. Supplements that have not been proven to be of value or are potentially dangerous to those with leukemia include camphor, sometimes called 714-X. Green tea has received much press for its reported abilities to enhance the immune system and fight cancer, but studies have had conflicting results. Some show that green tea has preventive benefits and others show no effect. A few animal studies suggest that growth of tumors might be slowed by green tea, but this has not been shown in humans yet. Hoxsey is another supplement touted as a cancer treatment, but no studies have confirmed any benefit. Some of its ingredients have serious adverse effects. Vitamin megadoses have long been advocated as beneficial in cancer, but no conclusive studies show G A LE EN CY C LO PE DI A O F C AN CE R 3

benefit, and they have significant potential for adverse effects, such as diarrhea, kidney stones, iron overload, nerve damage and liver disease. Laetrile, or amygdalin, was once touted as a cure for cancer and leukemia. No human or animal studies conducted in the decades since have shown any benefit other than relief of some pain. Laetrile can, however, cause cyanide poisoning. CHILDREN. Complementary and alternative treatments are recommended less frequently for children. Real caution must be used in administering herbal remedies to children, whose metabolisms are very different from those of adults. For example, jin bu hua, a traditional Chinese medicine, can cause heart or breathing problems. Life root and comfrey can both cause fatal liver damage in children.

While many children are too young for formal guided imagery, they can be distracted from the fears and pain associated with some treatments by toys and videotapes. Reading favorite books during scary procedures can relieve some of their fears.

ALL in remission ADULTS. Remission is achieved in many people within days of beginning treatment. Treatment does not end at that point, but rather enters into the next phases, called consolidation and maintenance. Several different approaches can be used in these. Some patients receive long term chemotherapy with drugs that might include Ara-C (cytarabine), cyclophosphamide, methotrexate, mercaptopurine, vincristine, prednisone, or doxorubicin. Other patients undergo highdose chemotherapy or combination chemotherapy and radiation therapy to ablate or wipe out their own bone marrow, and then have bone marrow or stem cell transplants. Adverse effects of bone marrow transplant include significant risk of serious infection and graftvs.-host disease (GVHD), in which the transplanted cells fail to ‘‘recognize’’ the host’s cells as self and attack the host cells. Medications to decrease this risk include those that suppress the immune system and steroids.

Central nervous system prophylaxis, as either intrathecal chemotherapy or radiation therapy or both, typically continues through at least a portion of the post-remission therapy. Adults who receive intensive chemotherapy have a 40% likelihood of long-term survival.

Recurrent ALL ADULTS. Adults who relapse after initial remission and maintenance therapy often undergo reinduction

17

Acute lymphocytic leukemia

infrequently used. Though once standard, brain radiation produced a high incidence of cognitive and learning disabilities, especially among those younger than five years old. Cranial radiation is reserved for those children felt to be at high risk of central nervous system disease, including those older than ten at the time of diagnosis, those with initial white blood cell counts of more than 50,000 per microliter, and those with T-cell leukemia. Some high-risk children who enter remission rapidly with induction chemotherapy receive intrathecal chemotherapy alone, without radiation therapy.

Acute lymphocytic leukemia

chemotherapy and are then referred for bone marrow or stem cell transplant. Some receive transplants of umbilical cord blood. Such transplants carry the risk of graft versus host disease, but also carry the possibility of graft versus leukemia, in which the transplanted cells attack the residual leukemic cells. Unlike graft versus host disease, graft versus leukemia is useful. New treatments for relapsed ALL include immunotherapies or biological response modifiers. Some reduce adverse effects of treatment and others are used to fight the leukemia. Some of these include cytokines, substances that stimulate the production of blood cells after treatment has suppressed the bone marrow, and colony-stimulating factors, which have the same effect. Other patients may be offered options of bone marrow or peripheral blood stem cell transplantation. CHILDREN. The treatment and prognosis of children who relapse depends on the timing of that relapse. Relapse that occurs within six months is often treated with bone marrow transplantation. Early relapse carries the least favorable prognosis, with only 10–20% chance of long term survival. Relapse that occurs more than a year after initial treatment is finished can be treated with another full round of chemotherapy, and bone marrow transplant or stem cell transplant reserved for those children who relapse a second time. Those with such late relapses have a 30–40% chance of long term survival.

Recurrent disease may occur in a sanctuary site, or a part of the body difficult to penetrate with chemotherapeutic drugs. The central nervous system is the most common site of such recurrences. Children who have an isolated central nervous system relapse during the first 18 months of treatment have a 45% likelihood of long-term survival. Children with central nervous system relapse after the first 18 months of treatment have up to an 80% chance of long-term survival. Treatment for relapse in the central nervous system includes intrathecal chemotherapy, and for most children, the use of radiation therapy to the brain and spinal cord. The testicles are the second most common site of relapse. Early testicular relapse (within the first 18 months of treatment) carries a 40% chance of longterm survival, and late testicular relapse carries an 85% chance of long-term survival. Another sanctuary site is the eye, but isolated relapse here is unusual.

Coping with cancer treatment The treatment of ALL can be particularly draining, not only due to adverse effects but due to its 18

prolonged time course. Although much of the treatment can be given on an outpatient basis, many protocols utilize lengthy intravenous infusions of chemotherapy and require hospitalization. ADULTS. To prevent nausea and vomiting, adults can take oral anti-nausea medication an hour or so before scheduled treatments, including intrathecal treatments. To avoid headache, they should remain flat for at least 30 to 60 minutes after intrathecal chemotherapy. Nurses can give instructions in mouth care if mouth sores occur and skin care if rashes occur after radiation treatment. Books, music, and television can provide distraction and reduce anxiety during chemotherapy infusions.

Patients scheduled for inpatient stays can bring their own pillows, pajamas and even food, with their doctor’s approval. Temporary issuance of handicapped parking stickers are often helpful. CHILDREN. The presence of parents during treatment is critical. While some hospitals exclude parents during treatments, others invite them to be present. Blood can be drawn and intravenous catheters placed while children sit in their parents’ laps. If at all possible, a parent should spend the night during any hospitalizations.

Like adults, children can take anti-nausea drugs an hour or so before scheduled treatments. Children, and some adults, can apply topical anesthetic creams to sites of bone marrow aspirates or spinal taps. Favorite stuffed animals or blankets can be present for most procedures. Play and fun are as important to children with cancer as to healthy children. Items such as board games, modeling clay, video games, dolls, and toy cars can be enjoyed even with intravenous lines in place. Play dates with friends should be encouraged, with proper screening to limit exposure to contagious illnesses. School districts are required to accommodate the special needs of children. Children with ALL might require shorter school days or the provision of a tutor at home. Children who develop learning disabilities due to treatment might require the intervention of a special education team.

Clinical trials There are numerous clinical trials looking at novel strategies for the treatment of ALL in adults and children. Most oncologists consider bone marrow transplants to be state-of-the-art in specific circumstances, and some insurance companies agree. Many G A LE EN CY C LO PE DI A O F C AN C ER 3

QUESTIONS TO ASK THE DOCTOR 



 













What type of leukemia do I or does my child have? What characteristics of my or my child’s illness are favorable? Which are unfavorable? What course of therapy do you recommend? What medications will you use and what side effects are anticipated? Will I or my child need to be hospitalized for those treatments? Should I or my child be enrolled in a clinical trial? Can I continue to work or can my child go to school? Can I stay with my child for procedures? For hospitalizations? How and what should we tell our child about this illness? What should we tell our other children?

still require extensive reviews before approving coverage for transplant. A variety of biological agents are currently under study. These include antibodies that react specifically against leukemic cells, causing their death, and chemicals that interfere with the leukemic cells’ normal DNA function or their ability to make proteins. Researchers are developing second and third generation versions of established chemotherapeutic drugs, isolating the molecular components of those drugs that seem to be most useful in ALL and amplifying them. Locating and enrolling in clinical trials has been made easier by listings on the Internet. A general search under ‘‘clinical trials and leukemia’’ will yield several listings. University-affiliated hospitals and oncologists participate in many trials and can refer patients to other sites if necessary.

Prevention There are few preventive measures to take against ALL. Those who work with chemicals should be cautious, particularly around benzene. Pregnant women should avoid exposure to ionizing radiation to reduce the risk to their unborn children. G A LE EN CY C LO PE DI A O F C AN CE R 3

Parents of children with ALL have specific concerns regarding the long-term consequences of treatment for ALL, such as learning disabilities. Organizations devoted to childhood cancer, hospital social workers, pediatric oncologists and other parents can be important resources when advocating for the educational needs of the child with ALL. When cranial radiation must be used, children have a risk of developing secondary cancers in the central nervous system years later. Some children are left infertile by the treatment. Chicken pox can be lethal in children with ALL. The introduction of the chicken pox vaccine has reduced this risk, but parents must still be vigilant. Resources BOOKS

Margolin, J.F., Steuber, C.P., Poplack, D.G. Acute Lymphoblastic Leukemia in Principles and Practice of Pediatric Oncology, 15th ed. 2006. PERIODICALS

de Labarthe, A., et al. ‘‘Imatinib Combined with Induction or Consolidation Chemotherapy with de novo Phila delphia Chromosome Positive Acute Lymphoblastic Leukemia: Results of the GRAAPH 2003 Study.’’ Blood 109, no. 4 (February 15, 2007):1408 1413. Pui, C.H. & Evans, W.E.‘‘Treatment of Acute Lympho blastic Leukemia.’’ New England Journal of Medicine. 353, no.2 (January 12, 2006):166 78. Pui, C.H., Robinson, L.L., & Look, A.T.‘‘Acute Lympho blastic Leukemia.’’ Lancet 371 no. 9617 (March 22, 2008):1030 1043. ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., Atlanta, GA, 30329. (800) ACS 2345. http://www.cancer.org. Cancer Care, Inc. 275 Seventh Ave, Floor 22 New York, NY 10001. (212) 712 8400 or (800) 813 4673. http://www. cancercare.org. Candlelighters Childhood Cancer Foundation. National Office P.O. Box 498 Kensington, MD 20895 0498. (800) 366 CCCF. http://www.candlelighters.org. The Leukemia and Lymphoma Society of America (for merly The Leukemia Society of America). 1311 Mamaroneck Ave., White Plains, NY 10605. (800) 955 4572. http://www.leukemia lymphoma.org. The National Cancer Institute. Cancer Information Service. Building 31, Room 10A31, 31 Center Dr., MSC 2580, Bethesda, MD 20892 2580. (301) 435 3848. http:// www.cancer.gov/. National Childhood Cancer Foundation. 440 E. Huntington Dr., Suite 400, Arcadia, CA 91066 3776. (800) 458 6223. http://www.curesearch.org. 19

Acute lymphocytic leukemia

Special concerns

Acute myelocytic leukemia

National Marrow Donor Program. Suite 100, 3001 Broad way St. NE, Minneapolis, MN 55413 1753. (800) MARROW 2. http://www.marrow.org/.

Marianne Vahey, M.D. Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Acute myelocytic leukemia Definition Acute myelocytic leukemia (AML) is an acute cancer that affects white blood cells, primarily those of the granulocyte or monocyte types.

Description Acute myelogenous leukemia and acute nonlymphocytic leukemia (ANLL) are other names for AML and refer to the identical disease. The cells that make up blood are produced in the bone marrow and the lymph system. The bone marrow is the spongy tissue found in the large bones of the body. The lymph system includes the spleen (an organ in the upper abdomen), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat). In addition, the lymph vessels (tiny tubes that branch like blood vessels into all parts of the body) and lymph nodes (pea-shaped organs that are found along the network of lymph vessels) are also part of the lymph system. The lymph is a milky fluid

An acute myelocytic leukemia patient with a rash, one of the symptoms of the disease. (Custom Medical Stock Photo. Reproduced by permission.)

that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest. The main types of cells found in the blood are the red blood cells (RBCs), which carry oxygen and other materials to all tissues of the body; white blood cells (WBCs), which fight infection; and the platelets, which play a part in the clotting of the blood. The white blood cells can be further subdivided into three main types: granulocytes, monocytes, and lymphocytes.

An enhanced scanning electron microscopy (SEM) image of acute myelocytic leukemia cells. (Photograph by Robert Becker, Ph.D., Custom Medical Stock Photo. Reproduced by permission.)

20

The granulocytes, as their name suggests, have particles (granules) inside them. These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms such as bacteria. Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens. The lymphocytes form the third type of white blood cell. G A LE EN CY C LO PE DI A O F C AN C ER 3

Acute leukemias are of two types: acute lymphocytic leukemia and acute myelogenous leukemia. Different types of white blood cells are involved in the two leukemias. In acute lymphocytic leukemia (ALL), it is the lymphocytes that become cancerous. AML is a cancer of the monocytes and/or granulocytes. The reason certain leukemias are now called acute is because of names received decades ago. Before the discovery of modern methods of cancer treatment, these were illnesses that progressed rapidly. In contrast, chronic leukemias were, in this period before newer methods had been invented, illnesses that progressed more slowly.

Demographics According to the American Cancer Society, approximately 13,290 people were diagnosed with AML in the Unites States in 2008. An estimated 8,820 people died of the disease during that same time period. Older persons are considerably more likely to develop AML. As the general population continues to age, it is anticipated that the number of cases of AML will continue to rise as well. AML sometimes affects children. About 500 children develop AML in the United States every year. Approximately one in five of all children who develop leukemia develop AML. The disease affects boys and girls in roughly equal numbers. Children in all ethnic groups may develop the disease. If one of two identical twins develop AML, the chances are considerable that the other twin will develop the disease as well.

Causes and symptoms AML is neither contagious nor inherited. However, people who suffer from certain genetic disorders, such as Fanconi anemia, Klinefelter syndrome, Patau syndrome, Bloom syndrome, and Down syndrome, are at greater risk of developing AML than the general population. A child with Down syndrome is roughly 14 times as likely as the average child to develop leukemia. G A LE EN CY C LO PE DI A O F C AN CE R 3

Any person who has been exposed to radiation at high doses is at heightened risk of developing AML, as are people exposed to benzene, a chemical used in the manufacture of plastics, rubber, medicines, and certain other chemicals including petrochemicals. Another group of people at increased risk for developing AML are those who have been treated for cancer previously. The number of treatment-related cases of AML is increasing particularly in survivors of childhood and adolescent cancers such as Hodgkin’s disease, lymphoma, sarcoma, testicular cancer and breast cancer. The symptoms of AML are generally vague and non-specific. A patient may experience all or some of the following symptoms:             

weakness or chronic fatigue fever of unknown origin shortness of breath weight loss that is not due to dieting or exercise frequent bacterial or viral infections headaches skin rash non-specific bone pain easy bruising bleeding from gums or nose blood in urine or stools enlarged lymph nodes and/or spleen abdominal fullness

A small minority of patients with AML have a tumor of leukemic cells at diagnosis. Such a tumor may appear in the lung, breast, brain, uterus, ovary, stomach, prostate, or certain other places in the body. Some children with AML present to their doctor with very few symptoms, while other children present with severe symptoms. Anemia is usually present. The symptoms of the anemia may include fatigue, dizziness, headache, paleness of the skin, or, infrequently, congestive heart failure. Easy bruising, bleeding gums, and nosebleeds may be present, as may fever. There may be swollen gums, bone pain or joint pain, or, rarely, an actual tumor. Some infants with AML have skin disorders.

Diagnosis Like all cancers, acute leukemias are best treated when found early. There are no screening tests available. A thorough diagnostic evaluation should be conducted. This is important because the doctor must determine more than whether or not AML is present. 21

Acute myelocytic leukemia

The bone marrow makes stem cells, which are the precursors of the different blood cells. These stem cells mature through stages into either RBCs, WBCs, or platelets. In acute leukemias, the maturation process of the white blood cells is interrupted. The immature cells (or ‘‘blasts’’) proliferate rapidly and begin to accumulate in various organs and tissues, thereby affecting their normal function. This uncontrolled proliferation of the immature cells in the bone marrow affects the production of the normal red blood cells and platelets as well.

Acute myelocytic leukemia

If it is suspected, has it affected the general health of the patient? Is the patient capable of undergoing rigorous treatment? A doctor who suspects leukemia may start by obtaining a thorough medical history. The doctor may then conduct a very thorough physical examination to look for enlarged lymph nodes in the neck, underarm, and pelvic region. Swollen gums, enlarged liver or spleen, bruises, or pinpoint red rashes all over the body are among the signs of the disease. In addition, the physician may examine the teeth and look for dental abscesses, and may explore whether back pain is present. Urine and blood tests may be ordered to check for microscopic amounts of blood in the urine and to obtain a complete differential blood count. This count will give the numbers and percentages of the different cells found in the blood. An abnormal blood test might suggest leukemia. Patients suffering from AML may have high leukocyte counts and typically have low counts of both red blood cells and platelets. Many patients with AML have low counts of all of the major components of the blood. A microscopic exploration of the blood will usually show that leukemic blast cells are present. However, the diagnosis has to be confirmed by more specific tests. The doctor may perform a bone marrow aspiration and biopsy to confirm the diagnosis of leukemia. Aspiration involves the withdrawal of a liquid sample of marrow. During the biopsy, a cylindrical piece of bone and marrow is removed. The tissue is generally taken out of the hipbone. These samples are sent to the laboratory for examination. In addition to diagnosis, the aspiration and biopsy may be repeated during the treatment phase of the disease to see if the leukemia is responding to therapy. A chest x ray is taken. Cardiac tests, including an electrocardiogram, are conducted. The patient is examined for possible infection. These diagnostic procedures often disclose bleeding in the stomach or intestines, and there may be bleeding in the lungs, brain, or eyes. Anemia is often present and may be severe. Sophisticated cytogenetic studies, which examine the number and shape of the chromosomes in the DNA of individual blast cells, should be conducted in addition to the immunophenotyping of cells of the bone marrow. This procedure involves applying various stains to the marrow cells. These stains help doctors identify some of the proteins lying on the surface of the cells. A spinal tap (lumbar puncture) is another procedure the doctor may order to diagnose leukemia. In 22

this procedure, a small needle is inserted into the spinal cavity in the lower back to withdraw some cerebrospinal fluid and to look for leukemic cells. Routine screening with lumbar puncture is not warranted in AML patients at the time of diagnosis, however. Standard imaging tests such as x rays may be used to check whether the leukemic cells have invaded other areas of the body, such as the bones, chest, kidneys, abdomen, or brain. Other tests, such as computed tomography scans (CT scans), magnetic resonance imaging (MRI), or gallium scans, are not typical for AML but may also be performed. Children with AML undergo most of the same studies used for adults.

Clinical staging, treatments, and prognosis Unlike several other cancers, AML is not staged. However, a classification system is used to separate different forms of AML. One of the most important classification systems, devised by a team of physicians, is known as the French-American-British (FAB) Classification System. A newer staging system for AML is the World Health Organization (WHO) Staging System which takes into account newer prognostic factors and the results of cytogenetic analyses such as molecular markers and chromosomal translocations. The WHO classification includes a minimum of 17 subclassifications of AML. In general, AML is distinguished from other highly myelodysplastic diseases when the percentage of blast (immature) cells in the bone marrow or in the blood exceeds 30%. The goal of AML treatment is to achieve a complete remission (CR). What is a complete remission? It is a measure that indicates that the patient’s disease has gotten markedly better in several ways. In general, it might be said that CR is achieved once the body has regained its ability to produce blood cells normally. At this point, the number of blood cells of various types should return to normal ranges, while none of the immature cells called leukemic blast cells should be present in the blood or the marrow. Chemotherapy is the use of drugs to kill cancer cells. It is usually the treatment of choice in AML and is used to relieve symptoms and achieve long-term remission of the disease. Generally, combination chemotherapy, in which multiple drugs are used, is more efficient than using a single drug for the treatment. Some drugs may be administered intravenously through a vein in the arm; others may be given by mouth in the form of pills. If the cancer cells have invaded the brain, then chemotherapeutic drugs may be put into the fluid that surrounds the brain and spinal cord. This is known as G A LE EN CY C LO PE DI A O F C AN C ER 3

Patients who are anemic or who have low platelet counts should receive transfusions. These transfusions should be sufficient to restore counts of various components of the blood to adequate levels. There are two general phases of treatment of acute leukemia in adults, the induction phase and the consolidation (post-induction or post-remission) phase. The first phase is called induction therapy. During this phase, the main aim of treatment is to reduce the number of leukemic cells as much as possible and induce a remission in the patient. Patient characteristics such as age and presence of co-morbidities, play a role significant role in determining the treatment strategies offered during the induction phase. For example, older patients (greater than age 60) may not be able to tolerate the intensity of the induction chemotherapy regimens and may be treated with supportive care or with therapy that is of a lower intensity. A variety of chemotherapy agents may be used during the induction therapy portion of AML treatment. For patients ages 60 and younger the chemotherapy agent Ara-C (cytarabine) is often used in combination with either daunorubicin or idarubicin (Idamycin). This standard regimen for AML induction therapy has not changed in 25 years. Participation in a clinical trial may be an option for older individuals with a poor cytogentic prognosis. For older AML patients with a better cytogenetic prognosis, enrollment in a clinical trial may also be an option. These individuals may also be treated with standard chemotherapy for AML. Two newer agents, decitabine and clofarabine, are being studied in large scale clinical trials at this time as options for induction therapy for older individuals diagnosed with AML. A second phase of treatment is initiated once CR is achieved. This is called post-remission or consolidation therapy. The goal of therapy now becomes killing any remaining cells and maintaining the remission for as long as possible. For patients under the age of 60, post-induction or consolidation therapy is determined by the effectiveness of the induction therapy. A bone marrow aspirate and biopsy are conducted one week to 10 days after completion of induction therapy to evaluate the effectiveness of the therapy. If the induction therapy failed to bring the patient into remission, allogeneic stem cell transplant with an HLA-matched donor may be an option. If no matched donor is available, the patient may be enrolled in a clinical trial. For G A LE EN CY C LO PE DI A O F C AN CE R 3

younger patients who are in remission post-induction, 3-4 cycles of high dose cytarabine therapy has been the standard regimen since 1994. Other options may include 1 or more cycles of high dose cytarabine followed by autologous stem cell transplant or allogeneic stem cell transplant from a sibling or unrelated donor. Transplantation therapy has been studied very thoroughly. It involves taking blood-making cells, whether from the patient or from another person, and infusing them into the patient following removal of the diseased marrow, with either high doses of chemotherapy or total body irradiation. These procedures are potentially very effective because of the remarkable ability of these cells to create a sustained replacement of the patient’s blood cells. Other treatment strategies may also be implemented. Approaches used for patients younger than 60 years of age may differ from those used for patients of older ages. Post-induction therapy for those over the age of 60 also includes an evaluation of the bone marrow 10 to 14 days after the completion of induction therapy. Patients with significant responses to induction therapy will receive standard dose cytarabine plus an anthracycline or anthracenedione agent. Some older patients may be candidates for reduced intensity stem cell transplantation as consolidation therapy. Post-remission follow-up for older patients includes undergoing a complete blood count and platelet count every one to three months for two years after the completion of consolidation therapy. After two years the CBC and platelet count will be done very 3 to 6 months for five years. Growth factor support may be considered for patients older than 60 after the conclusion of therapy. Patients over the age of 60 whose disease relapses may be treated with the drug, gemtuzumab ozogamicin. Because leukemia cells can spread to all the organs via the blood stream and the lymph vessels, surgery is not considered an option for treating leukemias. Most children diagnosed with AML undergo treatment in two phases: induction and intensification (consolidation). Often two or three medicines are used in conjunction with one another. After remission is achieved in a young patient, typically after 2 or 3 treatments, postremission therapy is started. The type of postremission therapy depends largely on the type of AML the patient has. It may involve additional chemotherapy or stem cell transplantation. Chemotherapy to the central nervous system (CNS) is given to most children, since without it, roughly one in five will develop CNS relapse. The CNS includes the brain and spinal cord. 23

Acute myelocytic leukemia

intrathecal chemotherapy. Chemotherapy should start soon after diagnosis.

Acute myelocytic leukemia

The prognosis of patients with AML varies, however, outcomes for AML, particularly for older patients, have not changed appreciably in 30 years. A number of different matters should be examined before the prognosis of any individual patient is assessed. The most important of these is whether or not the patient attains a complete remission (CR). The most important consideration in terms of whether a patient is likely to achieve CR is the patient’s age. However, it may be that chronological age is not what really matters. Rather, to a large extent, what is truly significant is the patient’s ability to survive the difficulties associated with induction therapy. For example, the patient who has some other disease in addition to AML may have a more difficult time with the rigors of the therapy. Yet, it is also true that older patients are more likely to have AML that expresses certain characteristics associated with poorer outcomes. Other factors also affect the patient’s prognosis. For example, in the tests performed during diagnosis, the chromosomes of cells are examined. Some chromosomal findings are associated with a good prognosis. Others are only mildly good, while still others indicate the patient is less likely to achieve CR. Other factors that may provide physicians with hints as to the patient’s prognosis include: how long symptoms were present before the illness was diagnosed, and how quickly immature blast cells disappear after treatment is started.

Coping with cancer treatment One of the most important aspects of treatment is guaranteeing that the patient will have the supportive care needed to come through the treatment period with physical and emotional strength intact. Part of what this means is that AML should be treated in major cancer centers, because only these centers have the medical and nursing expertise necessary to provide not only the right medicine but also the intensive supportive care reqired during treatment for AML. One way physicians help AML patients cope with treatment is to guarantee that adequate blood bank support is available. Many patients require platelet transfusions. One of the great dangers to patients during induction treatment and other steps of treatment is the threat of serious infectious disease. These patients have deficient blood components and are therefore more susceptible to infectious illness than the average person is. The leading cause of death for patients 24

Q U E S T I O N S T O A S K TH E DOC TOR 



       

What type of AML do I have? What does it mean to have this variant of the disease? How can I obtain supportive care so I come through this not only alive but with my family and emotional life intact? Do I have any infections? What are the results of the cytogenetic testing? What are the results of the immunophenotyping? What is my prognosis? Are blasts present? Are blood counts returning to normal levels? Has complete remission been achieved? What can I do to lower my risk of infection during chemotherapy?

receiving induction treatment and chemotherapy following remission is infectious illness. To help build the patient’s white cell count, doctors may prescribe growth factors. These encourage the body to produce certain types of blood cells. The types of growth factors prescribed most frequently are granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). The psychological aspects of cancer treatment are a major concern. Patients should ask their physician about local support groups and survivor networks that can help with the stresses associated with this disease.

Prevention High doses of radiation and exposure to the chemical benzene (used in the manufacture of plastics, rubber, and medicines) are strong risk factors. With the exception of people with such rare genetic conditions as Fanconi anemia, Klinefelter syndrome, Patau syndrome, Bloom syndrome, and Down syndrome, there is no known genetic predisposition to AML. Resources PERIODICALS

Applebaum, F.R., Gundacker, H, Head, D.R.‘‘Age and Acute Myeloid Leukemia.’’Blood 107 (2006): 3481 3485. Kantarjian, H., O’Brien, S., Cortes, Jl, et al. ‘‘Results of Intensive Chemotherapy in 998 Patients Age 65 Years and Older with Actue Myeloid Leukemia or High G A LE EN CY C LO PE DI A O F C AN C ER 3

OTHER

‘‘Acute Myeloid Leukemia.’’ National Comprehensive Cancer Network (NCCN) Practice Guidelines in Oncology, v.1.2009. http://www.nccn.org. ‘‘Acute Myelogenous Leukemia (AML). Emotional Aspects of Childhood Leukemia. Making Intelligent Choices About Therapy. Understanding Blood Counts.’’ Patient Aid Program. Family Support Group. Information Resource Center. The Leukemia and Lymphoma Society. (800) 955 4572. http://www.leukemia lymphoma.org. ‘‘Acute Myeloid Leukemia Treatment, Childhood. Acute Myeloid Leukemia Treatment, Adult.’’ National Cancer Institute. (800) 4 CANCER. http://www.nci.cancer.gov. ‘‘Adult Acute Leukemia.’’ American Cancer Society. (800) ACS 2345. http://www.cancer.org. ‘‘How Is Childhood Leukemia Treated.’’ American Cancer Society. (800) ACS 2345. http://www.cancer.org.

Lata Cherath, Ph.D. Bob Kirsch Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Acute myelogenous leukemia see Acute myelocytic leukemia Acute promyelocytic leukemia see Acute myelocytic leukemia Acyclovir see Antiviral therapy

Adenocarcinoma Definition Cancer that begins in the epithelial cells that line certain internal organs and have glandular (secretory) properties. Some types of adenocarcinomas include cancers of the breast, thyroid, colon, stomach, pancreas, and prostate, cervix, as well as certain types of lung cancer.

Description There are many different types of cancers. One way of classifying cancers is to group them based on the specific cell type which produced the cancer. The four G A LE EN CY C LO PE DI A O F C AN CE R 3

major categories for classifying cancers using this methodology include: carcinomas (which includes adenocarcinoma), sarcomas, lymphomas, and leukemias. Most cancers arise from one of these major cell types. Carcinomas are cancers which develop in the cells that line the inside of organs. These cells are called epithelial cells. Epithelial cells form the outer layers of skin and are found in the tissues lining the digestive tract, the bladder, the uterus, and all of the tubes and ducts which are found in virtually every body organ. Sarcomas develop from cells in the body’s connective tissues such as bone, muscle, cartilage, and fibrous tissues. Lymphomas arise from cells in the lymph system, which is a component of the immune system. Organs in the lymph system include lymph nodes, the spleen, bone marrow, and the thymus gland. Leukemias, which can be classified as acute or chronic, develop from the white blood cells circulating in the body. Leukemias also affect the bone marrow and the spleen. Carcinomas are the most common of the four major cell types that produce cancer, constituting about 85% of all cancers. Carcinomas can be further divided into sub-groups depending on which specific type of epithelial cell is responsible for originating the cancer and in which specific part of the body the cancer originated. The four major types of epithelial cells are: squamous cells, adeno cells, transitional cells, and basal cells. Squamous cells are found in the skin, the lining of the mouth and digestive tract, the trachea, and the bronchi in the lungs as well as in other parts of the body. Adeno cells line all of the glands in the body including the breasts, kidneys and in the digestive organs such as the stomach, bowel and pancreas and many other organs. Transitional cells are found only in the lining of the bladder and other parts of the urinary tract and basal cells form one of the layers of the skin. Therefore, when a cancer starts in the transitional cells in the lining of the bladder that tumor is called a transitional cell carcinoma of the bladder. If an individual develops skin cancer in the basal cells of the skin that cancer is called a basal cell carcinoma of the skin. A woman who develops a cancer of the glands in the breast would be diagnosed with adenocarcinoma of the breast. As stated earlier, adenocarcinomas can originate in many different body organs including the colon and rectum, the breast, the lung, the pancreas, the stomach, the ovary and in several other organs. Adenocarcinomas are malignant tumors that have the ability to metastasize to other parts of the 25

Adenocarcinoma

Risk Myelodysplastic Syndrome’’ Cancer 106 (2006): 1090 1098. Smith, M., Barnett, M., Bassen, R., et al.‘‘Adult Acute Myeloid Leukemia.’’ Critical Reviews in Onc/Hem. 50 (2004): 197 222. Storb, R. ‘‘Can Reduced Intensity Allogeneic Transplanta tion Cure Older Adults with AML.’’ Best Prac Res Clin Haematol. 20 (2007): 85 90.

Adenoma

body. Determining the type of cell in which the cancer originated plays an important role in determining the best treatment options for the patient. Kate Kretschmann Melinda Granger R.N.,D.N.S., A.P.R.N., C.N.S.

Adenoma Definition An adenoma is a benign (noncancerous) tumor that forms from the cells lining the inside or the surface of an organ.

Demographics Certain types of adenomas are more common in women than in men (e.g., pituitary tumors and liver adenoma), and some are more common in older adults (e.g., adenomas of the colon, pituitary). Specific demographics depend on the specific type of adenoma. Adrenal adenomas are found in less than 1% of individuals younger than 30 years, but are found in 7% of individuals 70 years or older. Adenomas of the colon are found in are found in 30–40% of individuals 60 years or older.

Description Adenomas arise from epithelial cells that are specialized for secretion. This type of epithelial cell is found in glands. Glands produce sweat, saliva, mucus, milk, digestive juices, hormones, and an array of other substances. Hormone-secreting (endocrine) glands include the thyroid, pituitary, parathyroids, adrenals, ovaries, and testes. Adenomas can arise from most gland cells in the body. Adenomas arise from excessive growth of normal epithelial cells in much the same way as malignant (cancerous) tumors. In healthy cells, cell division and growth is controlled so that new cells are created in an orderly way only when the body needs them. When cells continue to divide uncontrollably and grow beyond what the body needs, a mass or tumor is formed. Unlike malignant tumors, adenomas are not cancerous and do not spread (metastasize) to nearby tissue or other parts of the body. Some adenomas have specialized names, depending on where they are located. A gastrinoma is found in the small intestine or pancreas; a bronchial adenoma is found in the lungs; and a villous adenoma is found in the intestines. 26

The two major medical concerns related to all tumors found in glands are whether they are malignant and whether they are secreting hormones. Many adenomas affect the normal functioning of the gland in which they arise, most often by secreting a hormone. Elevated hormone levels in the blood and can cause uncomfortable symptoms and sometimes life-threatening conditions. Tumors found in some glands are more likely to be adenomas than malignant. For example, 80% of adrenal tumors are both benign and nonfunctioning, meaning that they are not cancerous and produce no hormones. Hormone-secreting adenomas of the adrenal are associated with Cushing syndrome, a disorder caused by excess levels of the hormone cortisol. Adenomas also form in the gastrointestinal system. About half of tumors that secrete the hormone gastrin (gastrinomas) that are associated with Zollinger-Ellison syndrome are benign. Other glands that tend to have a high level of adenomas include the pituitary gland and the salivary glands. In most cases, the occurrence of an adenoma does not indicate an increased risk for the later development of a carcinoma. The exceptions, however, are colon cancer and rectal cancer, which are thought to develop from adenomas. Also, one type of lung adenoma called a bronchial adenoma can potentially develop into lung cancer. Risk factors Advanced age appears the be the most common risk factor for the development of an adenoma.

Causes and symptoms The cause of most adenomas is unknown (idiopathic). Liver adenomas in women have been linked to the use of oral contraceptives, and some conditions, such as a type of adrenal adenoma know as a pheochromocytoma, and colon adenomas, can be inherited. No single set of symptoms can be applied to all adenomas. Some disorders have similar or identical symptoms whether due to an adenoma or carcinoma. Ultimately, the signs and symptoms depend on the location of the adenoma: 



Adrenal glands: an adrenocortical adenoma often shows the same symptoms of an adrenocortical carcinoma, including abdominal pain and loss of weight. A benign and malignant pheochromocytoma also has the same symptoms, including headaches, sweating, and chest pains. Breast: a marble-like benign fibroadenoma causes no symptoms and can be either too small to detect by touch or several inches across and easily detected. G A LE EN CY C LO PE DI A O F C AN C ER 3

















Colon or rectum: persistent diarrhea can indicate villous adenomas of the rectum. Blood in stool samples can indicate adenomas in the colon or rectum. Many other conditions can cause similar symptoms. Liver: a hepatic adenoma causes pain and a mass that is detectable by touch. Lung: a chronic or bloody cough, fever, chills, and shortness of breath can indicate a bronchial adenoma. Pancreas: pain in the abdomen, diarrhea, stomach pain, persistent fatigue, fainting, and weight gain can indicate one of the various types of pancreatic adenomas or pancreatic cancer. Parathyroid: weakness, fatigue, constipation, kidney stones, loss of appetite, and bone pain are signs of a condition known as hyperparathyroidism, in which excess parathyroid hormone is secreted. This condition can occur in individuals with either parathyroid adenomas or parathyroid cancer. Salivary gland: adenomas are small and usually painless but can cause swelling around the chin or jawbone, numbness of the face, and pain in the face, chin, or neck. Stomach and intestine: a gastrinoma causes a peptic ulcer in the intestines or stomach. The occurrence of many ulcers in the stomach, intestine, and pancreas that do not respond well to treatment can indicate Zollinger-Ellison syndrome. Sweat gland: adenomas may appear as many small, smooth, and firm bumps on the lower eyelids and upper parts of the cheek (syringomas), or as small bumps with bluish or dark-brown coloration on the head and neck area (hidrocystoma). Solitary adenomas (poromas) occur on the sole of the foot or palm of the hand. Thyroid: a lump in the neck region accompanied by a cough and difficulty swallowing or breathing often indicates a benign thyroid nodule; however, these are the same symptoms for thyroid cancer.

Diagnosis Most adenomas are found incidentally during an imaging procedure related to another condition or in the process of diagnosing confusing symptoms. Once found, a variety of techniques are used to determine whether the mass is an adenomas or a malignant tumor. Tests Blood and urine samples are taken to detect elevated levels of hormones or other substances associated with a specific adenoma. Tumors are located using a combination of ultrasonography, computed tomography scan (CT scan), magnetic resonance G A LE EN CY C LO PE DI A O F C AN CE R 3

Adenoma



Q U E S T I O N S TO A S K Y O U R DOCTOR 





Does the occurrence of this adenoma increase my chances of developing cancer? If I choose to have the adenoma surgically removed, what are the chances that I will develop another adenoma? Will all my symptoms disappear once the adenoma is removed?

imaging (MRI), and possibly radionuclide imaging. A biopsy may be performed to determine whether a tumor is benign or malignant.

Treatment Treatment depends on the location of the adenoma, whether it is secreting a hormone, and the symptoms it is causing, and whether it is related to an underlying condition. Surgical removal is the recommended treatment for many adenomas, especially colon and rectal adenomas, as they are associated with an increased risk for cancer. In some cases, surgery may be impractical, and symptoms of some adenomas, such as some occurring in the pituitary, can be treated with medication.

Prognosis Outcome depends on the location of the adenoma, whether it is active and is producing symptoms, the symptoms it is causing, the presence of an underlying disease, the type of treatment (surgical or drug therapy) and the response to treatment.

Prevention Adenomas cannot be prevented because their cause is unknown. ORGANIZATIONS

National Endocrine and Metabolic Diseases Information Service, 6 Information Way, Bethesda, MD, 20892 3569, (888) 828 0904; TTY (866) 569 1162, (703) 738 4929, [email protected], http:// www.endocrine.niddk.nih.gov/pubs/cushings/ cushings.htm.

Monica NcGee, M.S. Tish Davidson, A.M. 27

Adjuvant chemotherapy

Adjuvant chemotherapy

QUESTIONS TO ASK YOUR DOC TOR

Definition Adjuvant chemotherapy is cancer treatment that is administered after the primary therapy. For example, when the primary therapy to treat a cancerous tumor is surgery, chemotherapy would be an adjuvant therapy.

Purpose Even if there is no clear sign that the cancer has spread, adjuvant chemotherapy is administered to prevent the chance of a recurrence by killing any cancer cells that may have spread. The rationale behind adjuvant chemotherapy is that the chemotherapy drugs are more effective when they are given immediately after the tumor has been removed and any remaining cancer is in small amounts. For some cancers, especially breast and colorectal cancers, adjuvant chemotherapy has been shown to decrease the chance the cancer will return. In addition, cancer patients who received adjuvant chemotherapy tend to live longer than those who do not receive the treatment.

Description Patient selection Patients selected for adjuvant chemotherapy are usually considered to have a high risk of recurrence. In order to determine the chance of recurrence, physicians look at the prognostic factors, which means they study the characteristics of the tumor. Tumor size, histology, and the proliferation rates are three prognostic factors that help determine the necessity for adjuvant chemotherapy. For example, patients with small tumors (2 centimeters or less) have a better prognosis, in general, than patients with large tumors (5 centimeters or more). Histology (or histologic grade) refers tow hat the tumor cells look like under a microscope. In other words, are the cells close to normal or are they far from normal. The term used to describe them is differentiated. When a tumor is well differentiated, the prognosis is better, because the cells closely resemble normal cells. When a tumor is poorly differentiated, the prognosis is considered to be not as good because the cells look very little like normal cells. A high proliferation rate refers to the rate in which cancer cells divide to make more cells. When the cancer cells are multiplying quickly, the cancer is described as aggressive, which often means adjuvant chemotherapy is needed. 28

 



 

Will I need assistance performing my daily tasks? Are there certain food limitations associated with chemotherapy treatment? What other options do I have if this treatment doesn’t work? How soon will I be able to return to work? Are there any clinical trials I should join?

Other prognostic factors may need to be considered, depending on the cancer type. For example, the degree of lymph node involvement is an important consideration when the patient has breast cancer. During the tumor surgery, physicians often remove some of the underarm lymph nodes to see if they contain any cancerous cells. Positive lymph nodes indicate a higher risk of recurrence, because research shows if the cancer has spread to the lymph nodes, it may have spread to other parts of the body. Hormone receptor status (high levels of estrogen or progesterone that affect cell growth) may also impact the decision whether or not to treat a patient with adjuvant chemotherapy. It should be noted, however, that a panel of experts at a conference sponsored by the National Institutes of Science concluded that ‘‘adjuvant chemotherapy improves survival [of breast cancer patients] and should be offered to most women with primary breast cancers (larger than 1 centimeter in diameter) regardless of tumor involvement in the lymph nodes under the arm, menopausal status, or hormone receptor status.’’ Despite the value of analyzing prognostic factors, physicians cannot predict with 100% certainty what the outcome of adjuvant chemotherapy will be. Treatment decisions must be made on an individual basis, taking into account the patient’s general health, as well as his or her preferences. Treatment specifics In general, adjuvant chemotherapy is started as soon as possible after surgery. In the case of colorectal cancer patients, for example, physicians don’t like to wait more than six weeks after surgery to begin adjuvant chemotherapy. Chemotherapy regimes generally include more than one drug, but not always. The drug combinations are selected based on the kind of cancer being treated and individual patient considerations. Adjuvant chemotherapy treatments are usually given over a period of months in cycles, meaning a G A LE EN CY C LO PE DI A O F C AN C ER 3

Preparation Each patient should talk with his or her doctor regarding any preparations that need to be made prior to treatment. Patients who work outside the home might want to plan, if possible, to take the entire day off from work on the day the chemotherapy is given. Depending on how a patient responds to treatment, the patient may need the next day off as well. The laws vary from state to state regarding employee rights, but many states have specific laws that address what the obligations of an employer are to an employee who is seriously ill. Patients concerned that they might be treated unfairly should consult an attorney. Many patients prefer to have someone with them when they receive chemotherapy treatments, especially with regard to driving them home. Some cancer treatment centers insist that a patient have someone provide transportation. Patients who do not have friends or family available to help them can call the American Cancer Society. They manage a volunteer program that provides cancer patients with rides to and from the hospital or clinical where they will receive their treatments. For patients that live over 30 miles away from the nearest treatment center or hospital, the American Cancer Society also tries to arrange free-ofcharge hotel rooms for cancer patients. Patients with children may want to arrange to have someone stay with them while they are having chemotherapy, especially the day of or the day after the treatments. Patients should ask their physicians what local support groups exist in their area that specialize in this type of assistance. Church groups often have volunteers who will be willing to lend a hand as well. In addition, the hospital or cancer treatment center is likely to have a list of available services from a variety of sources.

Aftercare Patients can expect to have some side effects associated with chemotherapy, although the particular side effects will vary depending on the patient and the drug combinations. Most patients lose their hair during chemotherapy treatment. Patients can also expect to be more prone to infection and feel fatigued, G A LE EN CY C LO PE DI A O F C AN CE R 3

even for a period of time after the therapy is all done. For example, patients whose gums tend to bleed when they brush their teeth may be advised to brush their teeth gently and use a soft brush. Other cautions may be to avoid crowds and people who patients know are sick. Other common side effects are nausea, vomiting, diarrhea, and mouth sores. Chemotherapy doses can be adjusted and medication can be prescribed to help the patient overcome nausea. Patients should refrain from taking any medications (over-the-counter or prescription) without first talking to their oncologist (a physician who specializes in cancer treatment). In general, it is a good idea for patients to talk with all their treatment team regarding the toxic effects associated with adjuvant chemotherapy.

Risks There is some concern that woman over 70 years of age, for example, are more likely to develop severe side effects than younger women. However, in a large randomized clinical trial conducted by Muss and colleagues, which was published in the Journal of the American Medical Association, it was concluded that age alone was not a significant enough reason to avoid treating elderly women with adjuvant chemotherapy. In the study, the researchers tracked 6,487 breast cancer patients, all of whom had a high risk of recurrence, to see how they responded to high doses of chemotherapy. The study included 542 patients who were 65 years of age or older and 159 of them were 70 years of age and older. Although the researchers found that older patients did have a slightly higher risk of bad reactions to the chemotherapy, the researchers concluded that the risks did not outweigh the benefits of treatment.

Results Treatment results vary from patient to patient, depending on a variety of factors. However, research shows that the benefits of adjuvant chemotherapy often outweigh the risks, especially for patients with breast or colorectal cancers. A patient’s physician will perform various tests to determine if the treatment is working, such as blood tests and physical examinations. Some patients think that the side effects provide some indication as to how the treatment is working. The truth is, however, that the severity or lack of severity of the side effects has nothing to do with the effectiveness of the treatment. 29

Adjuvant chemotherapy

treatment is followed by a recovery period. The treatments can be administered orally, intravenously (through a vein), by injection, or by a patch on the skin. Most patients receive adjuvant chemotherapy as an outpatient in a hospital or clinic, but, in some cases, the treatments can be given at home.

Adrenal fatigue

Demographics

Resources PERIODICALS

Muss, H. B., Woolf, S., Berry, D., et al. ‘‘Adjuvant chemotherapy in older and younger women with lymph node positive breast cancer.’’ Journal of the American Medical Association 293 (2005): 1118 1120. OTHER

American Cancer Society. ‘‘Older Women Less Likely To Be Offered Adjuvant Chemotherapy.’’ American Cancer Society 9 May 2003 American Cancer Society. 24 Feb 2005 http://www.cancer.org/. National Cancer Institute ‘‘Adjuvant Therapy for Breast Cancer: Questions and Answers. National Cancer Institute 13 May 2002 National Cancer Institute. 24 Feb. 2005 http://www.cancer.gov/. Susan G. Komen Breast Cancer Foundation. ‘‘Recommen dations for Adjuvant Therapy for Breast Cancer Updated by the National Institute of Health Consensus Panel.’’ Susan G. Komen Breast Cancer Foundation 2 Jan 2001 Susan G. Komen Breast Cancer Foundation. 19 March 2005 http://www.cancer.org/. Susan G. Komen Breast Cancer Foundation. ‘‘Adjuvant Therapy Improves Survival for Women with Fast Growing Localized Breast Cancer.’’ Susan G. Komen Breast Cancer Foundation 2 Feb 2002 Susan G. Komen Breast Cancer Foundation. 19 March 2005 http:// www.cancer.org/.

Lee Ann Paradise

Because adrenal fatigue is not widely recognized as a medical condition, there are no reliable statistics about its incidence. Some proponents assert that at some point in their lives an estimated 80% of people in industrialized nations are affected by adrenal fatigue. The condition is believed to be stress-related and, by some estimations, 75–90% of visits to primary care physicians in the United States are stress-related.

Description The adrenal glands, also called the suprarenal glands, are walnut-sized organs located near the top of each kidney. The adrenals, along with the hypothalamus and pituitary gland, constitute the master control network of the endocrine system. The adrenal glands produce a large number of essential hormones including epinephrine, norepinephrine, sex hormones, and cortisol. Among its many other functions, cortisol is an important component of the body’s stress response. It is the major ‘‘fight or flight’’ hormone that helps the human body respond to danger and other stressful situations. Cortisol affects virtually every system of the body. It is responsible, in part, for regulating: 



 

Adrenal fatigue Definition Adrenal fatigue refers to suboptimal functioning of the adrenal glands, particularly the inadequate secretion of the hormone cortisol. The syndrome is characterized by a collection of generalized symptoms, especially lack of energy, fatigue, and anxiety. Adrenal fatigue is an accepted diagnosis among practitioners of alternative medicine, but is not widely recognized in conventional medicine. Adrenal fatigue is also referred to as: adrenal apathy  adrenal neurasthenia  hypoadrenalism  neurasthenia  non-Addison’s hypoadrenia  sub-clinical hypoadrenia 

30



blood sugar (glucose) levels through its control of fat, protein, and carbohydrate metabolism blood pressure and heart and blood vessel tone and contraction central nervous system activation immune system responses anti-inflammatory activity

Stress is believed to play a role in many diseases, particularly cardiovascular and gastrointestinal disorders. It also causes generalized anxiety and sleep disorders. The contribution of stress to disease is thought to be due, in part, to increased production of cortisol and other stress hormones and the resulting decrease in immune system functioning. In addition to its secretion in response to stress, cortisol is secreted in response to 24-hour circadian rhythms. Cortisol secretion by the adrenals is at its lowest level at about 4 A.M. and peaks at about 8 A.M. Adrenal insufficiency or Addison’s disease is a serious condition in which an underlying disease or disorder results in inadequate production of cortisol and possibly other adrenal hormones. Adrenal fatigue is usually defined as a mild form of adrenal insufficiency. It can occur when the adrenal glands do not respond adequately to the demands of stress or when G A LE EN CY C LO PE DI A O F C AN C ER 3

Proponents claim that adrenal fatigue can contribute to a broad spectrum of conditions including:    

    



frequent infections allergies chemical sensitivities premenstrual syndrome (PMS) and menopausal symptoms imbalances in thyroid hormones chronic anxiety mild depression chronic fatigue syndrome autoimmune diseases such as fibromyalgia and rheumatoid arthritis obesity

the ‘‘fight or flight’’ response, resulting in increased secretion of cortisol, epinephrine, and norepinephrine by the adrenal glands. These hormones increase heart rate, blood pressure, and blood sugar levels and shunt blood away from the digestive system. Proponents of adrenal fatigue argue that the adrenal glands cannot produce hormones in sufficient quantities to meet the demands of a body that is often in a ‘‘fight or flight’’ state of arousal. They further argue that chronic, frequent, or persistent stress—and the demands that it puts on the adrenals—disrupts the normal circadian release of cortisol and perhaps other hormones. These disruptive effects on the adrenal glands can continue long after the stress has passed. A wide range of stresses can stimulate the release cortisol and the catecholamine stress hormones epinephrine and norepinephrine and lead to suboptimal adrenal function. These stresses include:   

Risk factors



Some practitioners believe that adrenal fatigue appears to run in families and may be inherited. Other commonly cited risk factors include:



chronic illness recurrent infections a life crisis chronic stress caused by financial or other pressures poor diet sleep deprivation smoking substance abuse pregnancy



        

 

 



The primary symptom of adrenal fatigue is tiredness that is not relieved by sleep and a general malaise. Patients with adrenal fatigue usually: 

Causes and symptoms Adrenal insufficiency has a variety of causes including: 



 

genetic disorders such as congenital adrenal hyperplasia, in which the adrenals do not make sufficient cortisol and in which other hormones may be out of balance pituitary tumors, since the activity of the adrenal glands is controlled by the pituitary gland bleeding infections

In contrast, it is usually argued that adrenal fatigue is caused by physical, mental, and/or emotional stress that is frequent, persistent, or severe. Stress activates G A LE EN CY C LO PE DI A O F C AN CE R 3

caloric restriction poor diet sleep deprivation excessive exercise extreme weather (too hot or too cold) life-changing events various mental states injury surgery metal toxicity, such as exposure to lead, mercury, cadmium, or aluminum acute or chronic infections, especially respiratory infections such as flu, bronchitis, or pneumonia



  

wake in the morning feeling tired do not feel completely awake until after their noon meal feel low between 2 P.M. and 4 P.M. feel better after 6 P.M. are usually tired again by 9 P.M. In the most severe cases, patients may have difficulty spending more than a few hours a day out of bed. Other symptoms of adrenal fatigue may include:

     

lack of energy sleep disturbances insomnia muscle weakness body aches nervousness, anxiety, or stress 31

Adrenal fatigue

they do not function at an adequate level even when the body is at rest. This diminished adrenal function— the inability to secrete the hormones necessary for maintaining the body’s homeostasis—is said to result from over-stimulation of the adrenal glands.

Adrenal fatigue

inability to relax or exercise  depression  cravings for sweet or salty snacks  decreased sex drive  increased PMS or perimenopausal or menopausal symptoms  absentmindedness, forgetfulness  digestive problems  mild constipation alternating with diarrhea  low blood pressure  weight loss  lightheadedness, dizziness, fainting  loss of body hair  memory loss

Treatment



Diagnosis Examination A complete medical history and physical examination is conducted. The symptoms of adrenal fatigue are similar to those of Addison’s disease. The healthcare provider also must rule out conditions such as depression and fibromyalgia that can cause similar symptoms Tests Adrenal insufficiency is typically diagnosed by blood tests to measure the levels of adrenal hormones. However it is claimed that these tests are not sensitive enough to reveal the smaller hormonal deficiencies of adrenal fatigue: The most accurate measure of adrenal function may be an ACTH stimulation test, in which the adrenal steroids are measured in urine collected over a 24-hour period and then compared with a second 24-hour urine collection following an injection of ACTH to stimulate the adrenals.  Commercially available saliva tests measure cortisol in the saliva at four times during the day: 8 A.M., noon, 4 P.M., and between 11 P.M. and midnight, although sometimes only the morning cortisol level is determined. These tests can also measure sex hormone levels.  Postural hypotension, also called orthostatic hypotension—lowered blood pressure that occurs when rising from a seated or prone posture—can be determined by repeatedly measuring blood pressure as the patient is moved between horizontal and upright positions on a tilt table.  Thyroid tests are usually performed to rule out hypothyroidism. 

32

Traditional Pituitary tumors that cause cortisol deficiency can be treated with surgery or microsurgery, radiation therapy, chemotherapy, or a combination of these therapies. Drugs Adrenal hormone insufficiencies are treated with replacement hormone. Hydrocortisone (Cortef) is administered if the adrenals are not producing cortisol. Some people take these every day and others only when they are ill. Alternative Adrenal fatigue is most often treated by an alternative medical practitioner. A wide variety of botanicals, nutritional supplements, and combinations are commercially available for treating adrenal fatigue. Adaptogens are botanicals that improve the general response to stress and promote recovery from stress. The term was coined in the 1940s by the Russian physician I. I. Brekhman who defined the properties of adaptogens as follows:   



They are harmless. Their effects are generally nonspecific. They increase resistance to physical, chemical, or biological stressors. They act as general stabilizers or normalizers.

Adaptogens that are thought to act primarily on the adrenal glands include: 





Panax ginseng—Korean ginseng or its active ingredients, particularly in combination with multivitamins and minerals Eleutherococcus senticosus, also known as Acanthopanax senticosus, Ciwujia, or Siberian ginseng Withania somnifera, also called ashwagandha or Indian ginseng, which is used in Ayurvedic medicine to counteract the effects of extreme stress including changes in blood sugar, adrenal weight, and cortisol levels

Glycyrrhiza glabra (licorice) and Glycyrrhiza uralensis have been postulated to act synergistically with cortisol. Glycyrrhizin, a component of licorice which is structurally similar to cortisol, can bind to corticoid receptors, weakly mimicking the role of cortisol. Therefore it may increase the effective half-life of endogenous cortisol and reduce the demand on the adrenals for cortisol secretion. Licorice may elevate G A LE EN CY C LO PE DI A O F C AN C ER 3

The reported effects of Rhodiola rosea include:

Home remedies Many practitioners believe that adrenal fatigue can be effectively treated at home with lifestyle and dietary changes, nutritional supplements, stressreducing techniques, and possibly detoxification. Other recommendations include frequent rest periods during the day, sleeping in late whenever possible, and an early bedtime.



prevention of stress-induced depletion of adrenal catecholamines



decreased salivary cortisol



improved concentration and mental performance



decreased stress-related fatigue



improved physical fitness and coordination



improved sleep



improved motivation





greater mood stability





improved general well-being



improvement of general anxiety disorder symptoms

Various substances have been suggested to modulate the effects of cortisol and counteract stressinduced activation of the hypothalamus-pituitaryadrenal axis: 

Phosphatidylcholine may reduce the levels of cortisol and ACTH released in response to physical stress and relieve soreness and depression.



Fish oil may reduce stress-induced cortisol and epinephrine levels.



Plant sterols/sterolins may reduce the levels of physical-stress-induced cortisol.



Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, may reduce levels of cortisol and the adrenal stress marker chromogranin A.











Dietary recommendations for treating adrenal fatigue include: 

 









Foods to avoid include:  

Thiamine (vitamin B1) may protect against surgeryinduced adrenal fatigue, reducing cortisol levels before and during surgery and preventing post-surgical reduction in blood cortisol levels.



Pantetheine/pantothenic acid (vitamin B5) may enhance adrenal cortex activity and down-regulate cortisol over-secretion in response to stress.



Methylcobalamin (vitamin B12) may normalize cortisol peaks, resetting the cortisol peak to the circadian rhythm. Ascorbic acid (vitamin C) can reduce high cortisol levels. A combination of ascorbic acid and vitamins B1 and B6 may improve adrenal glucocorticoid function and normalize the rhythmic activities of glucocorticoid hormones.

G A LE EN CY C LO PE DI A O F C AN CE R 3

breakfast before 10 A.M., lunch before noon, a nutritious snack between 2 P.M. and 3 P.M., an evening meal between 5 P.M. and 6 P.M., and a small nutritious snack before bed slow, deliberate eating a combination of protein, fat, and complex carbohydrates such as whole grains at every snack and meal whole grains as the primary source of carbohydrates combinations of grains and legumes or legumes and seeds or nuts for complete protein lightly cooked or raw protein and avoidance of processed proteins 6–8 daily servings of a wide variety of vegetables variously prepared, especially brightly colored vegetables 1–2 tablespoons daily of essential oils (olive, grape seed, safflower, flax, etc.) in grains, vegetables, or meat moderate salt, except in the rare cases where adrenal fatigue is accompanied by high blood pressure





fruit in the mornings sugar and white flour products hydrogenated and partially hydrogenated oils such as vegetable shortening, margarine, and oils added to commercial peanut butters caffeine, chocolate, soft drinks, and alcohol deep-fried foods fast and junk foods

Nutritional supplements for treating adrenal fatigue include: 

    

vitamin C, 2,000–4,000 mg/day of sustained-release tablets vitamin E with mixed tocopherols, 800 IU/day vitamin B complex niacin, 125–150 mg/day as inositol hexaniacinate vitamin B6, 150 mg/day pantothenic acid, 1,200–1,500 mg/day 33

Adrenal fatigue

blood pressure and should not be used by patients with a history of hypertension or renal failure or who are using digitalis preparations such as digoxin. G. uralensis has been used in China, in combination with corticosteroids, to treat early-stage Addison’s disease.

Adrenal tumors

QUESTIONS TO ASK YOUR DOC TOR 







What tests will you use to determine whether I have adrenal fatigue? How will you rule out other conditions that may be affecting my adrenal hormones? What treatments do you recommend for adrenal fatigue? What lifestyle changes should I make to relieve adrenal fatigue?

magnesium citrate, 400–1,200 mg/day liquid trace minerals (zinc, manganese, selenium, chromium, molybdenum, copper, iodine) for their calming effects  S-adenosylmethionine (SAMe; 200 mg twice a day) and D,L-phenylalanine (DLPA; 500 mg twice a day) if depression is present  

Prognosis Alternative practitioners generally believe that adrenal fatigue can be overcome with a good diet, physical and mental rest and relaxation, and possibly nutritional and/or botanical supplementation.

‘‘SOS for Adrenal Fatigue.’’ Better Nutrition 70, no. 10 (October 2008): 30 31. OTHER

‘‘Adrenal Gland Disorders.’’ National Institute of Child Health and Human Development.http://www.nichd. nih.gov/health/topics/Adrenal_Gland_Disorders.cfm Dr. James Wilson’s www.AdrenalFatigue.org.http://www. adrenalfatigue.org. Grimes, Melanie. ‘‘A Stressful Lifestyle Can Cause Adrenal Fatigue.’’ HealthNews.http://www.healthnews.com/ blogs/melanie grimes/disease illness/a stressful life style can cause adrenal fatigue 3572.html. Nippoldt, Todd B. ‘‘Is There Such a Thing as Adrenal Fatigue?’’ MayoClinic.com.http://www.mayoclinic. com/print/adrenal fatigue/AN01583/ METHOD print. Wade, Vicki. ‘‘Adrenal Fatigue.’’ Project AWARE.http:// www.project aware.org/Resource/articlearchives/ adrenalfatigue.shtml. ORGANIZATIONS

The American Institute of Stress, 124 Park Avenue, Yonkers, NY, 10703, (914) 963 1200, (914) 965 6267, [email protected], http://www.stress.org. National Institute of Child Health and Human Develop ment (NICHD) Information Resource Center, PO Box 3006, Rockville, MD, 20847, (800) 370 2943, (866) 760 5947, [email protected]. gov, http://www.nichd.nih.gov.

Margaret Alic, PhD

Prevention Stress is usually unavoidable in daily life and can be associated with disease and mortality. However a healthy diet, adequate exercise, and stress-reducing techniques such as meditation can help prevent adrenal fatigue. Resources BOOKS

Bharadvaj, Daivati. Natural Treatments for Chronic Fatigue Syndrome. Westport, CT: Praeger, 2008. Null, Gary, and Amy McDonald. Be a Healthy Woman. New York: Seven Stories Press, 2009. Watson, James L. Adrenal Fatigue: The 21st Century Stress Syndrome. Petaluma, CA: Smart Publications, 2007. PERIODICALS

Head, Kathleen A., and Gregory S. Kelly. ‘‘Nutrients and Botanicals for Treatment of Stress: Adrenal Fatigue, Neurotransmitter Imbalance, Anxiety, and Restless Sleep.’’ Alternative Medicine Review 14, no. 2 (June 1, 2009): 114 140. Singh, Karta Purkh. ‘‘Avert Adrenal Fatigue.’’ Better Nutrition 70, no. 10 (October 2008): 28. 34

Adrenal tumors Definition Tumors that occur on one or both of the adrenal glands. Adrenal tumors are rare tumors that are characterized by overproduction of hormones produced by the adrenal glands.

Description The two small adrenal glands, one located just above each kidney, are among the many endocrine (hormone-secreting) glands in the body. All endocrine glands make and store hormones. Hormones are chemical messages that are sent from an endocrine gland and are received by an organ or a cell to trigger a specific reaction. When the body requires hormone levels to rise, endocrine glands secrete them into the bloodstream. Adrenal gland tumors often cause overproduction of one or a combination of the adrenal hormones. G A LE EN CY C LO PE DI A O F C AN C ER 3

An adrenal tumor is shown at lower left. The gallbladder is white, and the nearby liver is deep red. (Custom Medical Stock Photo. Reproduced by permission.)

Adrenal glands are comprised of two parts. The outer portion of the gland is called the cortex. The inner portion of the gland is called the medulla. Nervous system hormones are produced by the adrenal medulla. Most tumors that arise from the adrenal cortex are benign and are termed benign adenomas. Benign adenomas are usually small tumor and typically produce no symptoms. Should symptoms arise the tumors can be removed by surgically removing the adrenal gland that houses the benign tumor. Some benign adenomas can be treated with medications while others require no treatment. A malignant adrenal tumor (cancer) that arises in the adrenal cortex is called an adrenal cortical carcinoma and can produce high blood pressure, weight gain, excess body hair, weakening of the bones and diabetes. A malignant adrenal tumor (cancer) in the adrenal medulla is called a pheochromocytoma and can cause high blood pressure, headache, palpitations, and excessive perspiration. An adrenal gland has two parts, each of which secretes different hormones. The inner part is called the adrenal medulla, and the outer part is the adrenal cortex. The adrenal medulla secretes the nervous system hormones epinephrine and norepinephrine. These hormones help maintain normal blood pressure. In high-stress situations, they help prepare the body for quick action by increasing heartbeat and breathing rate, increasing the flow of blood to the heart and lungs, and increasing blood pressure.

G A LE EN CY C LO PE DI A O F C AN CE R 3

Cortisol is a steroid, an organic compound that affects metabolism. Many hormones and drugs used to relieve swelling and inflammation are steroids. Cortisol helps maintain blood pressure and is crucial in the breakdown of proteins, carbohydrates, and fats. It also raises blood sugar (glucose) when levels are too low, thus providing needed energy for the body’s activities. Cortisol also prevents inflammation and is important for the normal response to stress. The level of cortisol in the blood is carefully controlled. When the body needs cortisol, a small area of the brain called the hypothalamus releases coricotripoin-releasing hormone (CRH). The pituitary gland, located at the base of the brain, receives the message from the hypothalamus and begins secreting adrenocorticotropic hormone (ACTH). ACTH is received by the cortex of the adrenal glands, which responds by producing cortisol. When the level of cortisol meets the body’s need, the pituitary stops producing ACTH, which then stops the adrenal cortex from secreting cortisol.

Demographics About 8% of people worldwide develop benign (noncancerous) adrenal tumors. Malignant (cancerous) tumors are very rare, occurring in two out of every one million people worldwide. The exact incidence of adrenal cancers in the United States is unknown but is thought to be about 300–500 new adrenal cancers per year. This cancer is more common in women than in men. Although adrenal cancers can happen at any age, most are diagnosed in adults ages 45 to 50.

Causes and symptoms It is not known what causes adrenal gland cancer, but some cases are associated with hereditary diseases. Symptoms of adrenal cancer are related to the specific hormones produced by that tumor. An adrenocortical carcinoma typically secretes high amounts of cortisol, producing Cushing’s syndrome. This syndrome produces progressive weight gain, rounding of the face, and increased blood pressure. Women can experience menstrual cycle alterations and men can experience feminization. The symptoms for pheochromocytoma 35

Adrenal tumors

The adrenal cortex secretes aldosterone and cortisol. They also make small amounts of androgens, which affect the expression of female and male sex characteristics. Aldosterone helps maintain normal salt levels in the blood and the normal functioning of the kidneys. Cortisol (also called hydrocortisone) is the major adrenal hormone.

Adrenal tumors

QUESTIONS TO ASK YOUR DOC TOR  



Is my adrenal tumor malignant or benign? What type of tests will be required to determine what type of tumor I have? How do you anticipate that my tumor will be treated?



include hypertension, acidosis, unexplained fever and weight loss. Because of the hormones produced by this type of tumor, anxiety is often a feature also.

Diagnosis It is often difficult for a pathologist to distinguish between a benign and a malignant adrenal tumor. Several criteria are used to make a diagnosis, including the size and weight of the tumor, whether hormones are produced, and what hormones are produced. A benign tumor (adenoma) is usually less than 4–6 centimeters (1.57–2.3 inches) in diameter and likely causes changes in the blood level of only one hormone or may cause no changes at all. A malignant tumor is larger and may alter the level of several adrenal hormones. One reliable indicator for a malignant tumor is evidence that the cancer has spread (metastasis). Tests which may be used in the diagnosis of adrenal cancers include:





chest x ray  computed tomography (CT)  positron emission tomography (PET scan)  magnetic resonance imaging (MRI)  biopsy  laparoscopy  blood and urine tests 

Types of cancers Adrenal cortex A disorder caused by an adrenal cortex tumor can occur alone, but often two or more conditions occur simultaneously. These disorders include 

Cushing’s syndrome: a disorder resulting from prolonged exposure to high levels of cortisol. Most cases are the result of a pituitary gland dysfunction that causes excessive secretion of ACTH, but 20–25% are caused by a benign adrenal tumor, of which about 50% are malignant. Symptoms include obesity,

36

moon-shaped face, increased fat in neck region, skin that bruises easily, severe fatigue, weak muscles, and high blood pressure. The common treatment is surgical removal of the affected gland. The outcome for a Cushing’s syndrome patient with a benign adrenal adenoma is very good. Surgery usually results in a cure. The outcome is variable for malignant tumors. Aldosteronism: a condition resulting from an abnormally high level of the hormone aldosterone. It is usually caused by an adenoma and rarely is the result of a malignant adrenal tumor. Symptoms include headaches, weakness, fatigue, high blood salt levels, frequent urination, high blood pressure, and an irregular heartbeat. An adenoma is usually removed surgically, although medication that controls the secretion of aldosterone is an effective treatment in many cases. Virilization syndrome (also called adrenal virilism or adrenogenital syndrome): a disorder caused by an excessive secretion of androgen hormones, leading to high levels of the male hormone testosterone. Adenomas that cause virilization are rare. When the condition accompanies Cushing’s syndrome it may indicate an adrenocortical carcinoma. In males, the symptom is early onset of puberty, whereas in females symptoms include deepening of voice, a masculine build, and abnormal hairiness. The recommended treatment depends on the cause. If the condition is caused by an adenoma, use of medications that surpress ACTH secretion by the pituitary is the preferred treatment. Adrenocortical carcinoma: a rare cancer that is often not detected until it has spread to the liver or lung. The symptoms can include that of Cushing’s syndrome, aldosteronism, virilization, or a combination of each of these conditions. The preferred treatment depends on the stage of the cancer, but usually involves surgery to remove the tumor, chemotherapy, and radiation therapy. If the cancer is caught at an early stage, the long-term survival can be good. If found at a later stage, about 30% of patients will survive five years after the initial diagnosis. Adrenal medulla

Only one type of tumor is associated with the adrenal medulla: 

Pheochromocytoma: a tumor that produces and secretes epinephrine and norepinephrine. Excessive secretion of these hormones can cause life-threatening hypertension and an irregular heartbeat. About 90% of these tumors are benign. Five percent of those diagnosed with this tumor have either Von Hippel-Lindau syndrome, type 2 of the multiple G A LE EN CY C LO PE DI A O F C AN C ER 3

National Adrenal Diseases Foundation. 505 Northern Boulevard, Great Neck, NY 11021. 516 487 4992. http://www.medhelp.org/nadf.

Monica McGee, M.S. Cindy L.A. Jones, PhD Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Treatment Treatment is aimed at removing the tumor by surgery. In some cases, this can be done by laparoscopy. Surgery is sometimes followed by chemotherapy and/or radiation therapy. Because the surgery removes the source of many important hormones, hormones must be supplemented following surgery. If adrenocortical cancer recurs or has spread to other parts of the body (metastasized), additional surgery may be done followed by chemotherapy.

Prognosis The prognosis for adrenal gland cancer is variable. For localized pheochromocytomas the 5-year survival rate is 95%. This rate decreases with aggressive tumors that have metastasized. The prognosis for adrenal cortical cancer is dependent upon stage at diagnosis. Tumors diagnosed in stages I and II have a 50–60% five year survival rate while tumors diagnosed in more advanced stages (Stages III and IV) have more dismal survival rates of 20% and less than 10% respectively.

Prevention Since so little is known about the cause of adrenal gland cancer, it is not known if it can be prevented. See also Endocrine system tumors. Resources PERIODICALS

Cook, L.K. ‘‘Pheochromocytoma.’’ American Journal of Nursing109 (2009):50 53. Kissane, N.A. & Cendran, J.C. ‘‘Patients with Cushing’s Syn drome Are Care Intensive Even in the Era of Laproscopic Adrenalectomy.’’American Surgery75(2009):279 83. Miller, J.C., Blake, M.A., Boland, G.W., Copeland, P.M., Thrall, J.H., Lee, S.I. ‘‘Adrenal Masses.’’ Journal of the American College of Radiology6(2009):206 11. ORGANIZATIONS

American Association of Clinical Endocrinologists. 1000 Riverside Avenue Suite 205, Jacksonville, FL 32204. 904 353 7878. http://www.aace.com. G A LE EN CY C LO PE DI A O F C AN CE R 3

Adrenocortical carcinoma Definition Adrenocortical carcinoma is a malignant growth that originates in the cortex, or the outer portion, of one of the two adrenal glands.

Description There are two adrenal glands in the body. Each one is paired with a kidney. The adrenal gland rests atop the kidney, on the side of the kidney that is nearest to the head. An adrenal gland has two parts. The inner part (medulla) produces hormones such as epinephrine (adrenaline) that increases the heart rate. The cortex, or outer part, is made up of layers of epithelial cells, the cells that form coverings for the surfaces of the body. The cortex produces cortical hormones that are essential to well-being, or homeostasis. The hormones produced by the cortex include glucocorticoids, mineralocorticoids, and sex hormones. Among the many hormones the cortex makes, three—aldosterone, cortisol and adrenal sex hormones—are very important. Aldosterone helps regulate salt and water content in the body. Cortisol helps keep sugars, fats and proteins in balance. Adrenal sex hormones influence sex organ development and sex drive (libido). Adrenocortical carcinoma is a cancer that originates in the cortex of the adrenal gland. When a tumor grows in the adrenal cortex, it interferes with the production of hormones. Consequently, the effects of adrenocortical carcinoma can be severe and are almost always a threat to life. There are two types of adrenocortical carcinoma. In one type, a tumor functions—that is, it makes hormones. In the other type, the tumor does not function. If the tumor functions, it acts like the cells in the cortex from which it grew and thus, produces hormones. But since it grows large, it produces extra 37

Adrenocortical carcinoma

endocrine neoplasia syndromes (MEN), Von Recklinghausen’s neurofibromatosis, or another inherited disorder. Symptoms include headaches, sweating, and chest pains. Treatment involves medication to control hypertension and the surgical removal of the affected gland. Long-term survival depends on early detection of the tumor and whether the tumor is benign or malignant.

Adrenocortical carcinoma

K EY T ERM S Biopsy—Tissue sample is taken from body for examination. Carcinoma—A cancer that originates in cells that developed from epithelial tissue, a tissue found on skin and mucosal surfaces. Computed tomography (CT)—X rays are aimed at slices of the body (by rotating equipment) and results are assembled with a computer to give a three-dimensional picture of a structure. Homeostasis—Self-regulating mechanisms are working, body is in equilibrium, no uncontrolled cell growth. Hormone—A chemical released by one organ of the body that affects the activity of another organ. Inferior vena cava—The large vein that returns blood from the lower body to the heart. Lymph nodes—Part of the lymphatic system, these clusters of tissue help to protect the body from foreign substances, organisms, and cancer cells. Magnetic resonance imaging (MRI)—Magnetic fields used to provide images of the internal organs of the body. Pituitary—A gland at the base of the brain that produces hormones. Venography—Technique used for examining veins for blockage, using a dye to make the vein visible with scans similar to x ray.

Q U E S T I O N S T O A S K TH E DOC TOR  









In which stage is the carcinoma? With this type of carcinoma, what is the fiveyear survival rate for a person of my age and gender? What is the one-year survival rate? Is there a center that specializes in treating this type of cancer? Are there any clinical trials in which I might be eligible to participate? Does this health care institution have a support group for individuals with my type of carcinoma? What is your approach to relieving pain?

normal loop of feedback from the pituitary area of the brain. The pituitary is geared to send information, via a stimulating hormone, to the adrenal cortex, to prompt the tissue to manufacture adrenal sex hormone. When there is an extra amount of adrenal sex hormone in the body, the pituitary stops sending instructions to the adrenal cortex, as well as to other organs that produce the hormones responsible for male features. Thus, a man can begin to look like a woman because he does not have enough male hormones. A woman can begin to look like a man because she has too much adrenal sex hormone. When a tumor does not function

amounts of hormones and the body is thrown far out of balance in any one of a number of ways. When a tumor functions How excess hormones cause the symptoms they produce is complex because more than one hormone from the adrenal cortex can be involved in producing a single symptom. For example, both aldosterone and cortisol, when present in extra quantities, may contribute to the increase in blood pressure (hypertension) many patients experience. Extra amounts of adrenal sex hormones can cause children to begin to display the sexual characteristics (hair growth, genital maturation) of adults. And adults with extra amounts of sex hormones often begin to display the sexual characteristics of the opposite sex. A woman may grow excess facial hair. A man may begin to develop fatty tissue in his breasts. Large quantities of adrenal sex hormones coursing through the body disrupt what would be a 38

If the tumor does not function, it just grows large, and may go unnoticed for a long time. Sometimes a tumor that does not function is called dormant. Often, the tumor that does not function first gets attention when it grows large enough to push against the body wall or an organ and cause pain; or when it has spread (metastasized) to another organ. The adrenocortical carcinoma that does not function has a high likelihood of metastasizing before it is discovered. The two most common sites for metastases are the lungs and liver. Thus, even a non-functioning tumor may cause serious complications.

Demographics Adrenocortical carcinoma is rare. Fewer than two in one million people, and perhaps as few as one in four million people, are diagnosed in a year. Two age groups are most likely to be diagnosed: those between G A LE EN CY C LO PE DI A O F C AN C ER 3





Causes and symptoms Causes The cause of adrenocortical carcinoma is not known. Infection with bacteria or parasites is linked to other conditions of the adrenal glands, and there could be a connection with adrenocortical carcinoma. There is also evidence that adrenocortical carcinoma in children is caused by some chemical to which they were exposed as fetuses— possibly a chemical that the women carrying the children were exposed to in food, drink, or in the air. Many tumors of the adrenal cortex have cells with extra copies of chromosomes, the beads of genetic material or DNA. Chemicals in the environment that are known to affect cells and cause mutations are being investigated as possible causes for adrenocortical carcinoma.

  



thin, fragile skin, with a tendency toward both bruising and slow healing abnormalities in the processing of sugars (glucose), with occasional development of actual diabetes increased risk of infections irregular menstrual periods in women decreased sex drive in men and difficulty maintaining an erection abormal hair growth in women (in a male pattern, such as in the beard and mustache area), as well as loss of hair from the head (receding hair line)

Similarly, virilization syndrome, or the tendency of a child to exhibit adult sexual features, or a female adult to exhibit male features, can be caused by other conditions, such as tumors in the pituitary, or by adrenocortical carcinoma. So, too, with feminization, or the tendency of a male individual to exhibit female characteristics, such as enlarged breasts and fat deposits on the hips.

Diagnosis Symptoms Depending on whether or not the tumor interferes with the production of hormones, the tumor may or may not be linked to symptoms during its early growth. A group of Japanese surgeons led by K. Kunieda reported the case of a 52-year-old man who had a tumor weighing more than two pounds at the time it was discovered. The tumor had not been producing extra hormones, and was not producing symptoms. An adrenocortical tumor that functions produces many symptoms. Some of them are similar to those linked to other conditions, and many of these conditions have names that are based on a collection of symptoms and not on the cause. A combination of the following symptoms, known as Cushing’s syndrome, could be caused by a tumor in the pituitary area of the brain, as well as by adrenocortical carcinoma: 



   

an abnormal accumulation of fatty pads in the face (creating the distinctive ‘‘moon face’’ of Cushing’s syndrome); in the trunk (termed ‘‘truncal obesity’’); and over the upper back and the back of the neck (giving the individual what has been called a ‘‘buffalo hump’’) purple and pink stretch marks across the abdomen and flanks high blood pressure weak, thinning bones (osteoporosis) muscle atrophy (due to protein loss) low energy

G A LE EN CY C LO PE DI A O F C AN CE R 3

Symptoms usually cause a patient to talk with a physician. Blood and urine samples are examined to learn whether hormones are out of balance. Venography, a way of getting a picture of the inside of veins, is a technique that is still used to examine the adrenal glands prior to any decision about surgery. But the magnetic resonance imaging (MRI) scan has replaced venography in many facilities. Computed tomography (CT) scan is also used to examine the adrenal cortex.

Treatment team Depending on symptoms, the first specialized physician an individual consults may either be an endocrinologist (a physician who focuses on hormones) or a urologist (a physician who focuses on the study of the kidneys and nearby structures). Either one of them, or a medical oncologist (a physician who focuses on treating patients with cancer) will lead the treatment team. A surgeon will be on the team too because in almost all cases removal of the adrenocortical carcinoma to the fullest extent possible is standard procedure. Nurses will be on the team to help with administering drugs and monitoring the status of the patient. And if the patient is given chemotherapy, technicians skilled in the treatment will be part of the team.

Clinical staging, treatments, and prognosis Adrenocortical tumors are assigned to one of four stages. 39

Adrenocortical carcinoma

zero and ten years of age, and those between 40 and 50 years.

Adult cancer pain

Stage I tumors have not spread beyond the cortex of the adrenal gland and are less than two in (5 cm) in their greatest dimension.  Stage II tumors have not spread beyond the cortex of the adrenal gland and are more than two inches.  Stage III tumors have either spread into tissues around the adrenal cortex or they have spread into lymph nodes near the adrenal glands, or both.  Stage IV tumors have spread to lymph nodes and other organs near the adrenal cortex or to other organs of the body. 

A plan for treatment is based on the size and extent of the tumor. Surgical removal of the tumor, radiation and chemotherapy are all used. Method of treatment depends on how large the carcinoma is and whether it has spread to other organs. In some cases the treatment is strictly palliative (provides comfort) and is not expected to halt the course of the cancer. Palliative treatment can include surgery to reduce the size of the tumor, as well the pain a large tumor causes by pushing against other organs. Because adrenocortical carcinoma that metastasizes often moves into the renal (kidney) vein and then, the inferior vena cava, venography or MRI scan prior to surgical removal of all or part of the tumor is important. If the tumor has grown into a vein, a piece of it can be dislodged and become a dangerous object. The piece of tumor begins to move in the blood flow and it is capable of getting stuck in a small blood vessel in the heart or the brain, and causing a stroke.

Clinical trials The Cancer Information Service at the National Institutes of Health, Bethesda, Md., offers information about clinical trials that are looking for volunteers. The Service offers a toll-free number at 1-800422-6237.

Prevention No prevention is known.

Special concerns The excess production of hormones that indicate functioning tumors in adrenocortical carcinoma can also be symptoms of other conditions. A tumor in the pituitary gland can cause the pituitary to produce too much of the hormone that stimulates the adrenal cortex to make cortical hormones. The symptoms are identical to those for the adrenocortical tumor. A pituitary tumor must sometimes be ruled out when an adrenocortical carcinoma is suspected. Brain scans may be necessary. Resources PERIODICALS

Kunieda, K., et al. ‘‘Recurrence of giant adrenocortical carcinoma in the contralateral adrenal gland 6 years after surgery.’’ Surgery Today 30 (March 2000): 294 7. Wajchenber, B. L., et al. ‘‘Adrenocortical carcinoma: clinical and laboratory observations.’’ Cancer 88 (February 15, 2000):711 36.

Diane M. Calabrese

The drug mitotane gives some good results is slowing tumor growth in certain patients. But the only therapy that provides relief in most patients is the removal of the tumor. The outlook for individuals with adrenocortical carcinoma depends on the stage of the cancer. Because seven in ten individuals are diagnosed only after the cancer has reached stage III or stage IV the five-year survival rate for all stages is 40%. And for individuals with stage IV carcinoma it is much less, with most patients dying within nine months of diagnosis.

Adult cancer pain Definition Most adult cancer pain is caused by the cancer itself, although treatment and other cancer-related conditions also can cause pain. Not all cancer patients have pain and the pain varies greatly from day to day and patient to patient. Controlling cancer pain is an integral part of cancer treatment.

Alternative and complementary therapies Yoga, biofeedback, or other relaxation techniques may help manage pain.

Coping with cancer treatment Being an active member of the treatment team is important. Premier cancer centers encourage patients to play such a role. A support group can also help. 40

Demographics Many—but not all—cancer patients have pain. About 70% of cancer patients experience pain at some point during their illness. Between 30% and 40% of patients undergoing cancer treatment report pain and 70–90% of those with advanced cancer have pain. However fewer than 50% receive adequate treatment for their pain. G A LE EN CY C LO PE DI A O F C AN C ER 3









Description There are two categories of pain. Nociceptive pain is pain caused during the normal process of an outside agent (or disease) acts upon the body’s tissues and causes damage. Neuropathic pain is caused by the peripheral or central nervous system (CNS) incorrectly processing sensory input. Not all cancers cause pain and the pain can almost always be controlled and managed. The existence of cancer pain and its severity depends on:      

the location of the cancer the type of cancer the type of damage that the cancer is causing the stage or extent of the cancer treatments the patient’s pain threshold or tolerance for pain and how the patient experiences pain









There are three major types of cancer treatment pain: 

There are different types of adult cancer pain: 





Acute pain is mild to severe, comes on quickly, and lasts only a short time. Chronic pain is mild to severe and lasts longer than three months or recurs often. Breakthrough pain occurs in patients with chronic pain that is controlled by round-the-clock medication. Breakthrough pain is an intense sudden increase in pain that may occur several times in a day, but usually lasts less than one hour. It may occur as the last dose of medication begins to wear off. However it often is unpredictable.





Causes and symptoms There are various causes of cancer pain. Most cancer pain is caused by the cancer itself; however cancer treatments can also cause pain. More advanced cancer is likely to cause more pain: G A LE EN CY C LO PE DI A O F C AN CE R 3

Neuropathic pain may occur when certain types of chemotherapy or the cancer itself damages nerves. It is often a burning, shooting, or sharp pain. Peripheral neuropathy is pain in the arms, legs, hands, or feet. Phantom pain comes from a body part that has been surgically removed. It is not well understood; however it lasts longer than pain from the surgery.

Cancer pain that is not treated may cause patients to become fatigued, worried, stressed, angry, lonely, and depressed. The pain may interfere with daily activities and make it difficult to eat and sleep.

Diagnosis Examination

Risk factors The risk of cancer pain depends on a variety of factors. The major risk for pain is advanced cancer.

A tumor that is growing or spreading and pressing on surrounding tissues such as organs, bones, nerves, or the spinal cord can cause pain. Spinal cord compression occurs when a tumor spreads to the spine and presses on the spinal cord. It often begins with back and/or neck pain that is made worse by coughing, sneezing, or other movements. Cancer that has spread to the bones can cause bone pain. Medical tests and procedures that are performed to diagnose and stage cancer or to measure the effectiveness of treatment can cause pain. These include biopsies, spinal taps, and bone marrow tests. Chemotherapy and radiation can cause painful sores in the mouth and throat that make it difficult to eat and drink. Radiation therapy can also cause painful skin burns, scarring, or injury to the throat, intestines, or bladder. Surgical pain usually lasts from a few days to a few weeks. Other conditions related to cancer—such as stiffness from inactivity, muscle spasms, bedsores, and constipation—can cause pain.

The physician will take a medical history and perform physical and neurological examinations. However diagnosis of adult cancer pain usually depends on the patient’s self-report, possibly with the help of a family member or friend. The physician must have the following information from the patient:  

the location of the pain whether the pain is constant or intermittent, sharp or dull, throbbing, burning, or shooting 41

Adult cancer pain

According to the World Health Organization (WHO), in most parts of the world the majority of cancer patients are not presented for treatment until their cancers are advanced and pain relief is the only treatment possible. However in many countries cancer pain relief is limited by national drug laws. In developing countries cancer pain relief also may be limited by geographical barriers, medical infrastructure, and financial resources.

Adult cancer pain

the pain intensity  the pain duration  the time of day or activities during which the pain occurs  factors that ease and worsen the pain  whether the pain interferes with daily activities 

worker. Pain control plans are always individualized for the patient. Although cancer pain is most often treated with drugs, other treatments also may be used: 

Openly sharing details about their cancer pain helps the pain control team determine how the cancer and treatments are affecting the body and how to best control the pain. Patients may be asked to keep a pain control record that lists:



the name and dose of all pain medications  when the medications are administered  when more or less than the prescribed dose is administered  any side effects  the duration of a single dose’s effectiveness  any over-the-counter (OTC) drugs, alternative, herbal, or home remedies used  other pain relief methods  activities that ease or worsen the pain  activities that the pain interferes with  any medications taken for other health problems  allergies to any drugs





Procedures There are several procedures for determining a patient’s pain threshold and measuring the effectiveness of the pain treatment plan: The most common procedure is a numeric pain intensity scale: patients rate their pain on a scale of zero to ten, with 0 as no pain and 10 as the worst possible pain.  With a simple descriptive pain intensity scale, patients use words to describe their pain.  With a visual analog scale (VAS), patients are shown pictures of faces with a range of expressions and choose the face that best describes how they feel. 

Treatment Traditional Controlling cancer pain is an integral component of overall cancer treatment. Pain is much easier to treat and control when it first begins than after it has become more severe. Cancer pain is sometimes treated by a pain specialist, who may also be an oncologist, anesthesiologist, neurologist, surgeon, other physician, nurse, or pharmacist. Some patients have a pain control team that may include a psychologist or social 42







Radiation therapy can shrink the tumor and reduce pain. Surgery can remove part or all of a tumor that is pressing on nerves or other parts of the body. Neurosurgery can cut the nerves, usually those near the spinal cord, that transmit pain messages to the brain. Nerve blocks are local anesthetics, possibly combined with a steroid, that an anesthesiologist injects into or around a nerve or into the spine. Sometimes phenol or alcohol is injected for longer-lasting pain relief. Transcutaneous electric nerve stimulation (TENS) counteracts pain by transmitting a gentle electric current from a small power pack that patients hold or attach to themselves. Occasionally radiofrequency ablation may be used to destroy tumors in certain areas of the body to relieve pain. Drugs

There are a wide variety of medications for treating cancer pain and each patient is medicated differently, depending, in part, on the type of pain and its severity. Different pain medications are more effective for some people than for others and there is no correct dose for cancer pain. The goal is to control the pain, whatever it takes. It is important that the medications always be taken as prescribed to prevent pain from starting or becoming worse. It is harder to control pain that has already started and it is much easier to control pain when it is mild. Cancer patients who take their pain medications as prescribed rarely become addicted to them; nor do their bodies become immune to pain medication, so there is no reason to avoid or put off taking stronger medications. However tolerance to pain medication is a common problem with cancer patients and may require increasing the dose, changing medications, or adding a medication. Cancer pain is most often treated with analgesics: 

Nonopioids are used for mild to moderate pain—one to four on a scale of zero to ten—as well as for pain from fever and swelling. OTC drugs often are all that is needed. These include acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, naproxen (Aleve), and ibuprofen (Advil, G A LE EN CY C LO PE DI A O F C AN C ER 3



Pain medications are most often pills or liquids taken by mouth. However they also can be:   









placed inside the cheek or under the tongue rectal suppositories as capsules or pills skin patches that slowly release medication over two to three days injections under the skin (subcutaneous) or into a vein (intravenous, IV) epidural injections into the space around the spinal cord intrathecal injections into the fluid around the spinal cord, often with a patient-controlled analgesia (PCA) pump that enables patients to dose themselves as needed a surgical implant that injects medication directly into the spinal fluid or the space around the spine

Other types of drugs used to treat cancer pain include: 







Antidepressants such as amitriptyline, nortriptyline, and desipramine—alone or in combination with nonopioids and opioids—can relieve tingling and burning pain from nerve damage caused by cancer treatments. Anti-seizure drugs, also called anticonvulsants—such as carbamazepine, gabapentin, and phenytoin—also help control tingling and burning from nerve damage. Steroids, such as prednisone or dexamethasone, are prescribed for pain caused by swelling. Stimulants and amphetamines, such as caffeine or dextroamphetamine, can increase the pain-relieving

G A LE EN CY C LO PE DI A O F C AN CE R 3

effects of opioids and reduce the drowsiness they cause. 

Chemotherapy drugs can shrink a tumor, which may relieve pain.



Hormone therapy can be used to shrink prostate tumors to reduce pain.



Radioactive materials that settle in diseased bone and bisphosphonates that strengthen bones may be used to treat bone pain.



Antibiotic therapy can relieve pain caused by infections. Alternative

Alternative and complementary therapies for relieving pain, as well as stress and anxiety, and for helping patients cope with cancer include: 

acupuncture



hypnosis



biofeedback



massage



therapeutic touch



physical therapy



reiki



tai chi



yoga



psychological therapies to influence pain perception Home remedies

Home remedies for controlling cancer pain include: 

cold packs to numb pain or heat to relieve muscle soreness, for no more than ten minutes at a time



guided imagery



meditation



distraction to move the focus away from the pain, such as watching television, listening to music, singing, praying, talking, or engaging in other activities



exercise therapy



relaxation techniques such as visual concentration, rhythmic massage, slow rhythmic breathing, breathing and muscle tensing, progressive relaxation of body parts, relaxation CDs, music or art therapy



skin stimulation such as massage, pressure, vibration, heat, cold, or menthol



social and spiritual support to influence pain perception 43

Adult cancer pain



Motrin). Acetaminophen only treats pain. NSAIDs also treat inflammation. There are prescriptionstrength as well as OTC nonopioids. Opioids or narcotics are used to treat moderate to severe pain, often in combination with acetaminophen, aspirin, or ibuprofen. Common opioids include codeine, fentanyl, hydromorphone, levorphanol, meperidine, methadone, morphine, oxycodone, and oxymorphone. Drugs to treat chronic or persistent cancer pain are long-acting or sustained-release and are taken on a regular schedule, usually every 8–12 hours or via a skin patch. Rapid-onset opioids are used to treat breakthrough pain. Sometimes called rescue medicines, they act quickly for a short period of time. They are taken as needed immediately upon experiencing breakthrough pain or as a preventative if the breakthrough is predictable. They include fast-acting oral morphine and fentanyl in a lozenge that is sucked and absorbed through the mouth.

Advance directives

QUESTIONS TO ASK YOUR DOC TOR         





How should I take this pain medication? How much medication should I take? How often should I take pain medication? Can I take more if my pain does not go away? How much more should I take? How long does it take to work? For how long is a dose effective? What if I miss a dose? Can I drink alcohol or drive a car on this medication? Will this medication interact with my other drugs? What side effects might I experience?

McMains, Vanessa. ‘‘Study Tries to Put Pain in Perspec tive.’’ Chicago Tribune (August 16, 2009): 13. Savage, Liz. ‘‘Chemotherapy Induced Pain Puzzles Scien tists.’’ Journal of the National Cancer Institute 99, no. 14 (July 18, 2007): 1070 1071. OTHER

‘‘Global Cancer Facts & Figures 2007.’ American Cancer Society.http://www.cancer.org/downloads/STT/ Global_Facts_and_Figures_2007_rev2.pdf. ‘‘Pain.’’ StopPain.org.http://www.stoppain.org/palliative_ care/content/symptom/pain.asp. ‘‘Pain Control: A Guide for People with Cancer and Their Families.’’ American Cancer Society.http://www.cancer. org/docroot/MIT/content/MIT_7_2x_Pain_ Contro l_A_Guide_for_People_with_Cancer_ Chest x ray of patient with Hodgkin’s disease.Chest x ray of patient with Hodgkin’s disease.Custom Medical Stock Photo. Reproduced by permission.and_Their_Families.asp ‘‘Pain Control: Support for People with Cancer.’’ National Cancer Institute.http://www.cancer.gov/cancertopics/ paincontrol. ORGANIZATIONS

Prognosis All pain can be treated and most cancer pain can be relieved or controlled. Cancer pain can be reduced to the point where it is possible to pursue normal activities, work, eat and sleep well, enjoy family and friends, have sexual intimacy, avoid depression, and enjoy life. However if pain medication is avoided or delayed, the pain may become worse, may take longer to control, or may require higher doses of the medication.

Prevention

American Cancer Society, 1599 Clifton Road NE, Atlanta, GA, 30329 4251, (800) ACS 2345, http://www. cancer.org. American Pain Foundation, 201 North Charles Street, Suite 710, Baltimore, MD, 21201 4111, (888) 615 PAIN (7246), [email protected], http://www. painfoundation.org. National Cancer Institute, NCI Public Inquiries Office, 6116 Executive Boulevard, Room 3036A, Bethesda, MD, 20006, (800) 4 CANCER, http://www.cancer.gov. The Wellness Community, 919 18th St. NW, Washington, DC, 20006, (202) 659 9709, (888) 793 well, (202) 659 9703, [email protected], www.thewellnesscommunity.org.

The best means of preventing cancer pain is to treat it before it starts or becomes worse. Communicating openly about pain with the healthcare team is the best way to ensure that the pain is properly treated.

Margaret Alic, PhD

Resources BOOKS

Fisch, Michael J., and Allen W. Burton. Cancer Pain Man agement. New York: McGraw Hill, 2007. Patt, Richard B., and Susan S. Lang. The Complete Guide to Relieving Cancer Pain and Suffering. New York: Oxford University Press, 2007. Shannon, Joyce Brennfleck. Pain Sourcebook, 3rd ed. Detroit: Omnigraphics, 2008.

Advance directives Definition An advance directive is a written document in which people clearly specify how medical decisions affecting them are to be made if they are unable to make them, or to authorize a specific person to make such decisions for them.

PERIODICALS

Brawley, Otis W., Daniel E. Smith, and Rebecca A. Kirch. ‘‘Taking Action to Ease Suffering: Advancing Cancer Pain Control as a Health Care Priority.‘‘ Ca: A Cancer Journal for Clinicians 59, no. 5 (September/October 2009): 285. 44

Description Advance directives are recognized in most industrialized countries of the world. In the United States, by law, the creation of an advance directive is the right of G A LE EN CY C LO PE DI A O F C AN C ER 3

Q U E S T I O N S TO A S K T H E DOCTOR

Competent—Duly qualified; having sufficient ability or authority; possessing all the requirements of law. Dialysis—A technique used to remove waste products from the blood and excess fluid from the body as a treatment for kidney failure.

   

Hyperalimentation—The administration of a nutrient solution into a large, central vein near the heart. It is often used supplementary to eating, but can provide complete nourishment. Tube feeding—Administration of nourishment, in nutritionally complete solutions, via tube into the stomach or intestines. Tubes can be either nasogastric, or inserted through the nose into the stomach via the esophagus, or surgically implanted directly into the stomach. These are usually used to sustain life when a person is unable to eat or take fluids by mouth.



What is the prognosis for my type of cancer? What are the possible treatments? What are the side effects of these treatments? What are the laws in my state regarding living wills and durable powers of attorney for health care? How can I ensure that my wishes will be carried out regarding advance directives?

each state’s laws have differences as to whether one or all of these types of preparation of the document are legal and binding in that state. It is recommended that people speak to their attorney or physician to ensure that their wishes are carried out. Durable power of attorney for health care

all competent adults. The goal of this legislation is to empower all health care consumers to make their own judgments regarding medical decision-making, to approve of potential treatment they believe they would want, and to refuse care they do not perceive as being in their best interest. These directives are generally divided into living wills or durable powers of attorney. Federal law requires that all health care providers (health maintenance organizations, or HMOs, skilled nursing care facilities, hospices, home health care providers, and hospitals) make information regarding advance directives available to all people in their care. Many states require that two people witness such advance directives. Living wills Living wills go into effect while the individual is still living, but is unable to communicate his/her wishes regarding care. Traditionally, a living will has specified the individual’s wishes concerning procedures that would sustain life if he/she were terminally ill. Newer advance directives do not limit such preferences to terminal illness but instead go into effect whenever the individual is unable to speak for him/herself. There are several ways of preparing a living will. Sometimes a preprinted form is provided, or people may create their own form, or may simply write down their wishes. Though all 50 states and the District of Columbia recognize the validity of advance directives, G A LE EN CY C LO PE DI A O F C AN CE R 3

A durable power of attorney for health care is the second type of advance directive. This is a signed, dated, and witnessed document that authorizes a designated person (usually a family member or close friend) to act as an agent, or proxy. This empowers the proxy to make medical decisions for a person when the person is deemed unable to make these decisions him/herself. Such a power of attorney frequently includes the person’s stated preferences in regard to treatment. Several states do not allow any of the following people to act as a person’s proxy:  







the person’s physician, or other health care provider the staff of health care facilities that is providing the person’s care guardians (often called conservators) of the person’s financial affairs employees of federal agencies financially responsible for a person’s care any person that serves as agent or proxy for 10 people or more

As in the case of living wills, regulations regarding such powers of attorney vary from state to state. Some states provide printed forms, and require witnesses, while other states do not.

Causes As medical advances provide greater than ever means of extending life, it becomes increasingly important for people to evaluate which of the available 45

Advance directives

K E Y T ERM S

AIDS-related cancers

means they would wish used. If this is not done, people run the risk of having health care providers make critical decisions regarding their care. The absence of advance directive information can also create dilemmas and increased stress for loved ones. Some of the terms describing now-routine medical interventions that can maintain life under dire circumstances include: 







Who should act as the person’s proxy or agent? It is important for the person making an advance directive to actually speak with this designated person and make his/her wishes known. Though there is no formula for specificity, the AARP recommends that instructions be made as clear and specific as possible, but should not restrict the proxy from making informed decisions at the time that cannot be anticipated in advance. To ensure that an advance directive is carried out, copies of it should be given to a person’s physician, proxy, family, or any other interested party.

cardiopulmonary resuscitation (CPR), the use of chest compressions and/or mouth-to-mouth resuscitation to restart heart beat and/or respirations



ventilators or respirators that physically deliver oxygen via a tube into the windpipe when the lungs are unable to work on their own

Resources

Life-sustaining care encompasses the use of machinery or equipment that prolongs life by keeping the body functioning. Examples of life-sustaining care include hyperalimentation, tube feedings, and kidney dialysis.

In contrast, life-enhancing care, sometimes referred to as Care and Comfort Only, involves the provision of high quality, but non-heroic medical care until death occurs naturally. Important examples of life-enhancing care include administration and monitoring of medications, carrying out other measures to control pain, comfort measures such as bathing and massage, and offering food and fluids.

Special concerns Though specifics vary, all states have laws allowing people to spell out their health care wishes for a time when they might be unable to speak for themselves. But, as noted, there is a potential for disparity in how advance directives are interpreted. In most hospitals, an ethics committee is available to assist and support both patients and families faced with decisions regarding medical care. In 1995, the American Association of Retired Persons (AARP), with the help of the American Bar Association (ABA) and the American Medical Association (AMA), produced a combined living will and power of attorney for health care document that provides very specific and detailed statements of a person’s wishes. Further information regarding the laws in individual states can be obtained from the AARP, ABA, or AMA. The AARP recommends that those individuals considering making an advance directive address the following issues: 



What the person’s goals for medical treatment are: Should treatment be used to sustain life, regardless of the quality of that life?

46

ORGANIZATIONS

American Association of Retired Persons Legal Counsel for the Elderly., P.O. Box 96474, Washington, DC, 20090 6474. American Bar Association. http://www.abanet.org. American Medical Association. http://www.ama assn.org. Center for Healthy Aging. http://www.careproject.net. Choices In Dying, Inc., 200 Varick Street, New York, New York 10014 4810. (800) 989 WILL.

Joan Schonbeck, R.N.

AIDS-related cancers Definition The AIDS-related cancers are a group of cancers that occur more frequently in persons with human immunodeficiency virus (HIV) infection than in the general population. Individuals with HIV/AIDS are at high risk for developing certain cancers, particularly Kaposi’s sarcoma (KS), non-Hodgkin lymphoma (NHL), and cervical cancer. Because these cancers occur so frequently in patients diagnosed with HIV/ AIDS they are known as AIDS-defining conditions. The most common form of AIDS-related cancer, Kaposi’s sarcoma (KS), was one of the first indications of the AIDS epidemic in the early 1980s. Other types of cancers which may develop in patients diagnosed with HIV/AIDS include anal cancer, liver cancer, several different types of skin cancer, Hodgkin lymphoma, angiosarcoma, testicular cancer and colorectal cancer.

Demographics The demographic distribution of AIDS-related cancers varies somewhat depending on the type of G A LE EN CY C LO PE DI A O F C AN C ER 3

Numbers of cases of HIV/AIDS-related NHL, the second most commonly occurring AIDS-related cancer, continue to increase slightly. Approximately 4 – 10% of people with HIV/AIDS develop NHL. HIV/AIDSrelated NHL is observed in all high risk groups for the development of HIV/AIDS including intravenous drug users and in children of HIV-positive individuals Women diagnosed with HIV/AIDS are at higher risk for developing the pre-cancerous condition cervical intraepithelial neoplasia (CIN). CIN occurs in as much as 30% of women with HIV/AIDS. Women with HIV/AIDS are more likely to be diagnosed with a more aggressive form of CIN which can eventually develop into invasive cervical cancer.

Description In order to understand the causes and treatment of AIDS-related cancers, it is useful to begin with a basic description of HIV infection. AIDS, or acquired immunodeficiency syndrome, is a disease of the immune system that is caused by HIV. HIV is a retrovirus, a single-stranded virus containing ribonucleic acid (RNA) and an enzyme called reverse transcriptase. This enzyme enables the retrovirus to make its genetic material part of the DNA in the cells that it invades. HIV selectively infects and destroys certain subtypes of white blood cells called CD4 cells, which are an important part of the body’s immune system. As an infected person’s number of CD4 cells drops, he or she is at risk of developing opportunistic infections, disorders of the nervous system, or an AIDS-related cancer. HIV is transmitted through blood or blood products that enter the bloodstream—most commonly through sexual contact or contaminated hypodermic needles.

KS) is characterized by purplish or brownish lesions (areas of diseased or injured tissue) on the skin, in the mouth, or in the internal organs. The lesions may take the form of small patches or lumps (nodular lesions), large patches that grow downward under the skin (infiltrating lesions), or lumpy swellings in the lymph nodes. Unlike other cancers that typically develop in one organ or area of the body, KS often appears simultaneously in many different parts of the body. It may be the first indication that the patient has AIDS. Non-Hodgkin’s lymphoma Lymphomas are cancers of the immune system that develop when white blood cells called lymphocytes begin to grow and multiply abnormally. The increased numbers of lymphocytes cause the lymph nodes, the organs that produce these white blood cells, to swell and form large lumps that can be felt. Lymphomas are divided into two major categories: Hodgkin’s disease (HD), and non-Hodgkin’s lymphoma (NHL). HD can be differentiated from NHL by the presence of Reed-Sternberg cells in the lymphatic tissue; these cells are not found in any other type of cancer. NHL occurs more often than Hodgkin’s disease. NHL can involve the spleen, liver, bone marrow, or digestive tract as well as the lymph nodes. Most AIDS related lymphomas are categorized as aggressive B cell type tumors. Three important types AIDS-related lymphomas are: 



Kaposi’s sarcoma Kaposi’s sarcoma is the most common type of cancer related to HIV infection. There are two other major subtypes of KS—so-called classic KS and African KS—with different causes that are not yet well understood. AIDS-related KS (also called epidemic G A LE EN CY C LO PE DI A O F C AN CE R 3



Primary central nervous system lymphomas (PCNSL). This type accounts for about 20% of NHL cancers found in AIDS patients, but only 1% to 2% of NHL cancers in patients not infected by HIV. Lymphomas of this type start in the brain or the spinal cord. Symptoms include headaches, paralysis, seizures, and changes in the patient’s mental condition. Patients diagnosed with PCNSL are more likely to suffer from advanced HIV infection than patients with other types of NHL. Systemic lymphomas. These also are called peripheral lymphomas. They begin in the lymph nodes or other parts of the lymphatic system and may spread throughout the body. Burkitt’s lymphoma (BL) is a type of systemic lymphoma that is 1,000 times more common in AIDS patients than in the general population. Primary effusion lymphomas, also called body cavity-based lymphomas (BCBL). This type of NHL is relatively rare, but seems to be related to infection by human herpesvirus 8 (HHV-8) in addition to HIV. 47

AIDS-related cancers

cancer. KS has reached epidemic proportions in areas such as southern Africa due to the large numbers of people infected with AIDS in that area of the world. In Africa, KS is most likely to occur in men although incidence is increasing among African women and children. In the United States, incidence of KS is decreasing. HIV/AIDS-related KS is most commonly diagnosed in gay men and is over 20,000 times more common in individuals with AIDS than it is in individuals without AIDS.

AIDS-related cancers

Many cases of this type of HIV/AIDS-related NHL are also associated with the Epstein-Barr virus. Cervical cancer In women, cancer of the cervix (the lower end of the uterus or womb) is more likely to occur in HIVinfected individuals than in the general female population. About 60% of women with HIV infection are found to have some kind of abnormal tissue growth or cell formation in the cervix when a Pap test is performed. The human papilloma virus (HPV) is thought to be a co-factor in the development of cervical cancers. Papilloma viruses are a group of tumor-causing viruses that also cause genital warts. Cervical cancers develop more rapidly in HIV-positive than in HIVnegative women, are harder to cure, and are more likely to recur. Risk factors Risk factors associated with the development of HIV/AIDS-related cancers include: Infection with the human papillomavirus (HPV) – infection with this virus is a risk factor for the development of cervical cancer.  Infection with the human herpesvirus 8(HHV-8)associated with the development of KS and with primary effusion lymphoma  Infection with the Epstein-Barr Virus (EBV) – EBV is a herpes-related virus implicated in the development of several types of lymphomas 

Causes and symptoms The most common types of AIDS-related cancers have been linked to oncogenic (tumor-causing) viruses: Human herpesvirus 8 (HHV-8) is associated with KS and some of the less common types of AIDS-related lymphomas (ie. cancers of the lymphatic system).  Epstein-Barr virus (EBV) is associated with the more common types of AIDS-related lymphomas, particularly PCNSL and Burkitt’s lymphoma.  Human papillomavirus (HPV) is associated with anal cancer and with cervical cancer in women. 

Oncogenic viruses cause cancer by changing the genetic material inside tissue cells. When this genetic material is changed, the cells begin to grow and multiply uncontrollably. The abnormal tissue formed by this uncontrolled growth is called a tumor. A healthy human immune system has a greater ability to protect the body against oncogenic viruses and to stop or slow down tumor formation. Since the retrovirus that 48

causes AIDS weakens the immune system, persons with AIDS are at greater risk of developing cancers caused by oncogenic viruses. Some types of AIDS-related cancers, such as Burkitt’s lymphoma, have been linked to changes in human chromosomes (translocations). In a translocation, a gene or group of genes moves from one chromosome to another. Burkitt’s lymphoma is associated with exchanges of genetic material between chromosomes 8 and 14 or between chromosomes 2 and 22. Symptoms associated with AIDS-related KS include the presence of purplish or brownish lesions (areas of diseased or injured tissue) on the skin, in the mouth, or in the internal organs. The lesions may take the form of small patches or lumps (nodular lesions), large patches that grow downward under the skin (infiltrating lesions), or lumpy swellings in the lymph nodes. Unlike other cancers that typically develop in one organ or area of the body, KS often appears simultaneously in many different parts of the body. It may be the first indication that the patient has AIDS. Other symptoms of KS include lymphedema or swelling in an arm or leg, a cough that is unexplained, chest pain, pain in the stomach or intestines, bleeding from the mouth and/or rectum, as well as diarrhea and/or symptoms resulting from the gastrointestinal system being blocked by KS lesions. Symptoms of AIDS-related NHL are dependent upon the location of the cancer and can include enlarged lymph nodes, enlarged liver and spleen, unexplained fever, weight loss, and sweating and chills. Unusual periods, bleeding between periods or after menopause, pain during intercourse and increased vaginal discharge are symptoms of cervical cancer.

Diagnosis The diagnosis of an AIDS-defining condition such as KS, NHL, or cervical cancer may indicate that a person infected with the HIV virus has progressed to the development of AIDS. Procedures and tests which may be used to diagnose HIV/AIDS-related malignancies include tissue biopsy and imaging scans in addition to a variety of other tests depending on the specific type of cancer and on the location of the cancer in the body.

Treatments AIDS-related Kaposi’s sarcoma treatment KS differs from other solid tumors in that it lacks a stage or site of origin in which it can be cured. In G A LE EN CY C LO PE DI A O F C AN C ER 3

The use of systemic chemotherapy to treat AIDSrelated KS is limited. Drugs which have been used as single agent therapy or as combination therapy include bleomycin, docetaxel, doxorubicin, etoposide, paclitaxel, vinblastine, and vincristine. AIDS-related Non-Hodgkin’s lymphoma AIDS-related NHL is typically treated using chemotherapy and/or radiation therapy. The primary treatment choice is treatment with chemotherapy. The monoclonal antibody, rituximab (Rituxan), is used in combination with chemotherapy in most cases.

Q U E S T I O N S TO A S K Y O U R DOCTOR 



 



 

What type of HIV/AIDS-related cancer do I have? Does diagnosis with this cancer mean I have AIDS? How will my cancer be treated? Will I continue treatment with my anti-retroviral medication during my treatment for the cancer? How effective is the treatment for my type of cancer? How long with the treatments last? What is my prognosis?

antiretroviral therapy may increase the risk for developing non-AIDS related cancers, HIV-infected patients are more affected by risk factors for those cancers than other people and/or infection with the HIV virus or another undetected virus may increase a person’s risk for developing one of these cancers.

Prevention Cervical cancers Treatment of CIN in women diagnosed with HIV/ AIDS is more difficult than in women without HIV/ AIDS. Recurrence of CIN is high HIV/AIDS affected women after treatment. Women infected with HIV/ AIDS who progress to cervical cancer are treated with surgery initially. Disease progression after surgery may be treated with chemotherapy. HIV/AIDS infected women are also treated with anti-retroviral therapy to improve the treatment outcomes for the cervical cancer.

AIDS-related cancers develop as a result of infection with the HIV virus. Incorporating strategies to maintain a healthy immune system, including adherence to treatment with anti-retroviral drugs, is critical for patients diagnosed with HIV/AIDS to minimize the potential for development of AIDS-related cancers. See also Immunologic therapies. Resources PERIODICALS

Prognosis Treatment with anti-retroviral drugs has proven to be very effective in treating HIV/AIDS. As a result, incidence of AIDS-related cancers is decreasing overall. However, as individuals affected by HIV/AIDS live longer they are increasingly being diagnosed with cancers not typically associated with HIV/AIDS. Results of recent research reported in 2009 that analyzed data from more than 100,000 patients treated in the Veterans Administration System between 1997 and 2004, indicated HIV patients were 60% more likely to develop anal cancer, lung cancer, Hodgkin lymphoma, melanoma, or liver cancer as compared to patients without HIV infection. The researchers offer several theories to explain this increase: use of G A LE EN CY C LO PE DI A O F C AN CE R 3

Bedimo, R.J., McGinnis, K.A., Dunlap, M., Rodriguez Barradas, M.C., & Justice, A.C.‘‘Incidence of Non AIDS Defining Malignancies in HIV Infected Versus Non Infected Patients.’’ Journal of Acquired Immune Deficiency Syndromes 52(Oct. 2009):203 8. Di Lorenzo, G., Konstantinopoulos, P.A., Pantanowitz, L., et al. ‘‘Management of AIDS related Kaposi’s Sarcoma.’’ Lancet Oncology 8(2007):167 76. Graber, S., Abraham, B., Mahamat, A., et al.‘‘Differential Impact of Combination Antiretroviral Therapy in Pre venting Kaposi’s Sarcoma With and Without Visceral Involvement.’’ J Clin Oncol 24(2006):3408 14. ORGANIZATIONS

AIDS Clinical Trials Group (ACTG). c/o William Duncan, PhD, National Institutes of Health. 6003 Executive Boulevard, Room 2A07, Bethesda, MD 20892. 49

AIDS-related cancers

addition, there is no relationship between the stage of KS and its response to treatment. Currently, there is no indication that treatment of KS improves survival. Small localized lesions may be treated by surgical excision, electrode dessication, and/or by curettage cryotherapy. KS tumors typically respond well to treatment with radiation therapy which is generally reserved to treat localized lesions on the skin and in the oral cavity. Localized lesions also respond to treatment using injections of the chemotherapy drug vinblastine directly into the lesion. The topical treatment alitretinoin (Panretin) 0.1% gel may also be used to treat KS skin lesions.

Alcohol consumption

American Cancer Society (ACS). 1599 Clifton Road, NE, Atlanta, GA 30329. (404) 320 3333 or (800) ACS 2345. Fax: (404) 329 7530. http://www.cancer.org. National Cancer Institute, Office of Cancer Communica tions. 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. (800) 4 CANCER. TTY: (800) 332 8615. http://www.cancer.gov. San Francisco AIDS Foundation (SFAF). 995 Market Street, #200, San Francisco, CA 94103. (415) 487 3000 or (800) 367 AIDS. Fax: (415) 487 3009. http://www.sfaf.org.

Rebecca J. Frey, Ph.D. Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N.,C.N.S

recommended for reducing the risk of heart disease, other lifestyle factors, such as a healthy diet and exercise, reduce the risk of both heart disease and cancer. Studies have also found that moderate alcohol consumption appears to decrease the risk of developing type 2 diabetes and gallstones. Gallstones are hard masses of cholesterol and calcium that form in the gallbladder. Although the risks of alcohol consumption outweigh its potential health benefits, moderate social drinking can also provide psychological benefits. Heavy alcohol consumption has no health benefits and poses many health risks.

Description

AJCC see American Joint Commission on Cancer

Alcohol consumption Definition Alcohol consumption is the ingestion of substances containing ethyl alcohol (ethanol), including beer, wine, and distilled spirits such as gin, whiskey, or vodka.

Purpose In earlier times in subsistence agricultural societies, alcoholic beverages, usually beer or mead (fermented honey and water), provided a substantial proportion of dietary calories. Today people drink alcohol to relax and socialize, to get high, or because they are physically addicted to it. Alcohol has an effect on almost every system of the body and it can be a dangerous substance of abuse. However a large number of studies have found some health benefits from the consumption of moderate amounts of alcohol by middle-aged and older adults. Moderate alcohol consumption can reduce the risk of heart attack, sudden cardiac death, peripheral vascular disease, and stroke caused by blood clots (ischemic stroke) by 25–40%. This risk reduction occurs in both men and women and in people who have no apparent heart disease, as well as those who are at high risk of heart disease because of type 2 diabetes, high blood pressure (hypertension), angina (chest pain), or a previous heart attack. Researchers suggest that this protective effect occurs because alcohol increases the amount of high-density lipoprotein (HDL; ‘‘good’’ cholesterol) and also because alcohol affects various proteins in ways that reduce the risk of blood clots. However, although moderate alcohol consumption may be 50

Ethanol is produced by yeast fermentation of the natural sugars in plants, such as grapes (wine), hops (beer), sugar cane (rum), agave (tequila), and rice (saki). The process of fermenting plants to produce alcohol is at least 10,000 years old and developed independently in many cultures. Although alcohol sales and consumption are prohibited in some countries and by some religions, the production of alcoholic beverages is a huge industry worldwide.

Recommended dosage The federal government’s Dietary Guidelines for Americans defines moderate alcohol consumption as one drink per day for women and two drinks for men. This gender difference is because women tend to be smaller than men and their bodies contain a lower percentage of water. Therefore equivalent amounts of alcohol consumption result in a higher blood alcohol concentration in women than in men. A drink, as defined by these guidelines, contains about 14 grams of alcohol and is equivalent to approximately:   

12 fluid ounces of regular beer 5 fluid ounces of wine 1.5 fluid ounces of 80-proof distilled spirits

Heavy alcohol consumption is defined as 15 or more alcoholic drinks per week for men and 8 or more drinks per week for women. Between moderate and heavy alcohol consumption is a gray area of potentially problem drinking that includes binge drinking—heavy alcohol consumption that occurs intermittently. Bingeing is defined as 5 or more drinks in a period of about two hours for men and 4 or more drinks in the same period for women. About 60% of American men ages 18–25 binge drink. Some people should never drink any alcohol:  

children and adolescents under age 21 women who are pregnant, breastfeeding, or who could become pregnant G A LE EN CY C LO PE DI A O F C AN C ER 3





  

people who cannot control their drinking and keep it at the level of moderate consumption people who plan to drive a car, fly a plane, operate dangerous equipment, act as a lifeguard, or perform any activity that requires quick reactions, good judgment, and coordination people who are unable to control their aggression when they drink people taking certain medications people with liver or kidney damage recovering alcoholics

Precautions By far the greatest risk of frequent moderate alcohol consumption is that it can lead to heavy alcohol consumption, alcohol abuse, and alcohol dependency. Twin and family studies indicate that there is an inherited tendency for some individuals to develop alcohol abuse disorders. In women even moderate alcohol consumption is associated with a modest increase in the risk of developing breast cancer. Research has shown that women who consume only one alcoholic drink per day have a 30% higher risk of dying from breast cancer than abstainers. However, some researchers suggest that taking at least 600 micrograms (mcg) of folic acid daily will counteract this increased risk. Pediatric Alcohol interferes with brain development in fetuses, children, and adolescents. Recent research indicates that the human brain continues to undergo development until people are in their early 20s. In addition, alcohol consumption by adolescents substantially increases their risk for:     

fatal and nonfatal motor-vehicle accidents risky sexual behavior school failure suicide death by homicide

Furthermore, adolescents are particularly susceptible to alcohol poisoning, a potentially fatal condition. Children who begin drinking before age 15 are five times more likely to develop alcoholism than those who begin drinking at age 21.











Pregnant or breastfeeding There is no known safe level of alcohol consumption during pregnancy. Any level of alcohol consumption by a pregnant woman has the potential to damage the developing fetus, resulting in fetal alcohol syndrome disorders, including mental retardation or other conditions. Breastfeeding women should also abstain from alcohol, as it can pass through the breast milk to the infant. Other conditions or allergies Although approximately 34% of Americans never consume alcohol, about 7%, or more than 17 million people, are alcohol dependent or have alcoholism. Alcohol abuse is more common in men than in women and alcoholic men started drinking at an earlier age than women alcoholics. Costs related to alcohol disorders are estimated to be more than $185 billion annually. Alcohol disorders are related to increased rates of motor-vehicle deaths, homicides, suicides, and domestic violence. Heavy alcohol consumption leads to two alcohol abuse disorders that are recognized in the Diagnostic and Statistical Manual for Mental Disorders (DSMIV-TR) published by the American Psychiatric Association. Alcohol dependence is diagnosed when one or more of the following occur within a 12-month period: 



Geriatric It is generally recommended that older men and women limit their alcohol consumption to one drink per day: G A LE EN CY C LO PE DI A O F C AN CE R 3

Older adults have a lower tolerance for the effects of alcohol. Age-associated reductions in lean body mass can cause decreases in total body water, leading to higher blood alcohol concentrations in older adults than in younger people who consume the same amount of alcohol. Older adults are more likely to have medical conditions that are adversely affected by alcohol consumption. Older adults are more likely to be taking medications that interact with alcohol. Some research suggests that even moderate alcohol consumption in postmenopausal women increases their risk of breast cancer.

 

Repeated alcohol use causes failure to fulfill obligations at work, home, or school. Driving or hazardous activities such as operating machinery occurs while under the influence of alcohol. Alcohol use results in legal problems. Alcohol use continues despite causing problems in relationships. 51

Alcohol consumption



Alcohol consumption

Alcohol abuse, or alcoholism, is diagnosed when three or more of the following occur within a 12month period: 

Tolerance develops to the effects of alcohol.



Abstaining causes, or would cause, physical symptoms of withdrawal.



More alcohol is regularly consumed than is intended.



Efforts to reduce unsuccessful.



Obtaining alcohol, consuming it, and recovering from its consumption takes up a great deal of time.



Work, social, and recreational activities are replaced by drinking or recovering from drinking.



Alcohol use continues despite obvious physical and/ or psychological problems resulting from it.

alcohol

consumption







Side effects

are

Alcoholism is a chronic progressive disease that is often fatal. It is a primary disorder, although it can also be a symptom of another disease or emotional disorder. Factors such as psychology, culture, genetics, and response to physical pain influence the severity of alcoholism. The best-known treatment for alcohol abuse disorders is the 12-step program of Alcoholics Anonymous. This program uses social support, rewards, and mentoring to change behavior. For it to succeed, the alcoholic must want to recover and must be willing to work at achieving sobriety. Relapses are common. Families of alcoholics may be helped by Al-Anon and Alateen for adolescents, regardless of whether their alcoholic family member participates in Alcoholics Anonymous.

The effect of alcohol consumption on the body depends on the alcohol content of the drinks, how much is consumed, and how often it is consumed. One of the most common side effects of alcohol consumption is the altering of sleep patterns. Alcohol consumption can cause a wide range of disorders, from poisoning to malnutrition to liver disease to cancer. There is also a broad spectrum of physical and mental disorders that result from fetal alcohol exposure. Alcohol poisoning occurs when an overdose of alcohol shuts down the control of breathing and the gag reflex. Alcohol poisoning can cause a person to stop breathing and can cause irreversible brain damage. Binge drinking can result in a person continuing to drink beyond a fatal dose before losing consciousness. Signs of alcohol overdose include:   





Two other common forms of treatment for alcoholism are cognitive-behavioral therapy and interactional group psychotherapy based on a 12-step program. People with mild to moderate withdrawal symptoms are usually treated in outpatient programs through counseling and/or support groups. Alcoholics may be treated in a general or psychiatric hospital or substance-abuse rehabilitation facility if they: 

have not responded to more conservative treatments



have coexisting medical or psychiatric disorders



have a difficult home environment



are a danger to themselves or others Inpatient programs may include detoxification, physical activities, psychotherapy or cognitive-behavioral therapy, and a 12-step program.

The U.S. Food and Drug Administration (FDA) has approved three medications for the treatment of alcoholism: 52

Disulfiram (Antabuse) causes illness with alcohol consumption. Naltrexone (Depade, ReVia) acts on the brain to reduce the craving for alcohol. Acamprosate (Canpral) reduces withdrawal symptoms.



mental confusion vomiting breathing that is slow (less than eight breaths per minute) or irregular (10 seconds or more between breaths) hypothermia (low body temperature, bluish skin color, paleness) seizures unconsciousness

Alcoholics generally do not eat healthy balanced diets and they may replace food with alcohol. Alcohol can decrease eating by interfering with the body’s mechanisms for regulating food intake. Like food, alcohol contains energy in the form of calories. Alcohol contains approximately 7 calories per gram, whereas carbohydrates and protein contain about 4 calories per gram: 

 

One regular beer contains about 144 calories; light beer averages 108. One glass of wine averages about 100 calories. One shot of distilled spirits has about 96 calories plus the calories in any mixer.

Alcoholism is a major cause of malnutrition because serious nutritional deficiencies develop when at least 30% of total calories come from alcohol, which does not contain many of the nutrients required G A LE EN CY C LO PE DI A O F C AN C ER 3

    

  

protein essential amino acids carbohydrates fats B-complex vitamins, especially vitamins B1 (thiamine), B2, B6, folate, and B12 fat-soluble vitamins (A, E, and K) vitamin C minerals such as calcium and magnesium Alcoholics may have either a deficiency or an excess of vitamin A.

Alcohol can further compromise nutritional status via:    

inducing early satiation immune system suppression respiratory disorders liver, gastrointestinal, and pancreatic damage

One of the most common side effects of chronic alcohol consumption is liver disease: steatosis (fatty liver), alcoholic hepatitis, and cirrhosis—liver damage that leads to scarring and dysfunction. Alcohol abuse is responsible for 60–75% of cirrhoses and worldwide about 32% of alcoholics die of cirrhosis. Cirrhosis is also a major risk factor for the development of primary liver cancer. Alcohol consumption is an important risk factor for many types of cancer including cancer of the pharynx, larynx, mouth, breast, liver, lung, esophagus, stomach, pancreas, urinary tract, prostate, and brain. It also increases the risk for ovarian and colorectal cancer, lymphoma, and leukemia. The risk of breast and other cancers rises with increased alcohol consumption. Approximately 75% of esophageal cancers and 50% of cancers of the mouth, throat, and larynx are due to alcoholism, although wine appears to pose less of a danger than beer or hard liquor. People who consume 40–100 grams of alcohol per day have a 3–8-fold increased risk for esophageal cancer. A 2004 study reported that although moderate wine consumption might help protect against the formation of precancerous polyps in the colon, heavy alcohol consumption greatly increases the risk of developing colorectal cancer. Even moderate alcohol consumption can have detrimental effects on the health of cancer patients.

Q U E S T I O N S TO A S K Y O U R PHARMACIST   





 

immune system suppression resulting in infections, especially pneumonia

G A LE EN CY C LO PE DI A O F C AN CE R 3

Does this medication contain alcohol? Will alcohol interact with this medication? Can I consume alcohol while taking this medication?

gastrointestinal problems, especially diarrhea and hemorrhoids mental and neurological disorders, including depression, confusion, and destruction of gray matter in the brain, leading to mental disturbances and psychosis male impotence osteoporosis

Heavy drinking and alcoholism are also risk factors for:    

  

loss of judgment loss of motor skills loss of memory damage to the endrocrine, immune, and hematopoietic systems stroke and cardiovascular disease brain damage violent death

Alcoholism takes an emotional and psychological toll on relationships and families, especially children.

Interactions Alcohol is a central nervous system depressant that can interact with more than 150 different drugs. Some of these interactions can be fatal, especially those involving narcotic drugs that also depress the central nervous system. Categories of drugs that interact with alcohol include:     

narcotics sleeping pills antidepressants antianxiety medications antihistamines Alcohol consumption can also:



Other possible side effects of alcoholism include: 

Alcohol consumption

by the body. Alcohol also decreases the absorption, metabolism, and storage of nutrients from food. Alcoholics may have deficiencies in:



cause hypoglycemia (a drop in blood sugar), which is particularly dangerous for diabetics taking insulin interfere with the effectiveness of anticancer therapy and possibly cause the patient to become even sicker 53

Aldesleukin



when combined with smoking, significantly increase the risk of developing mouth, throat, pharynx, larynx, and esophageal cancers

Resources BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR), 4th ed., text rev. Arlington, VA: American Psychiatric Associ ation, 2007. Califano, Joseph A., Jr. High Society: How Substance Abuse Ravages America and What to Do About It. New York: Public Affairs Press, 2007. National Center on Addiction and Substance Abuse (CASA) at Columbia University. Women under the Influence. Baltimore: Johns Hopkins University Press, 2006. Sher, Leo. Research on the Neurobiology of Alcohol Use Disorders. New York: Nova Science Publishers, 2008. PERIODICALS

Butler, Katy. ‘‘The Grim Neurology of Teenage Drinking.’’ New York Times (July 4, 2006): F1. ‘‘Heavy Alcohol Consumption Linked to CRC.’’ Patient Care (January 2004): 8 10. Miller, J. W., et al. ‘‘Binge Drinking and Associated Health Risk Behaviors Among High School Students.’’ Pedia trics 119 (2007): 76 85. Young, Emma. ‘‘Inside the Brain of an Alcoholic.’’ New Scientist 189 (February 4 10, 2006): 18.

Recovery With Abstinence.’’ National Institute on Alcohol Abuse and Alcoholism. http://pubs.niaaa.nih. gov/publications/arh314/362 376.htm. U.S. Department of Agriculture and Department of Health and Human Services. ‘‘Alcoholic Beverages.’’ Dietary Guidelines for Americans. http://www.health.gov/ DIETARYGUIDELINES/dga2005/document/html/ chapter9.htm. ORGANIZATIONS

Al Anon/Alateen, 1600 Corporate Landing Parkway, Vir ginia Beach, VA, 23454 5617, (757) 563 1600, (757) 563 1655, wso@al anon.org, http://www.al anon. alateen.org. Alcoholics Anonymous, PO Box 459, New York, NY, 10163, (212) 870 3400, http://www.aa.org. National Clearinghouse for Alcohol and Drug Information, P.O. Box 2345, Rockville, MD, 20847 2345, (877) SAMHSA7, (240) 221 4292, http://ncadi.samhsa.gov/ default.aspx. National Council on Alcoholism and Drug Dependence, 244 East 58th Street, 4th Floor, New York, NY, 10022, (212) 269 7797, (800) NCA CALL, (212) 269 7510, [email protected], http://www.ncadd.org. National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5635 Fishers Lane, MSC 9304, Bethesda, MD, 20892 9304, (301) 443 3860, http://www.niaaa. nih.gov/.

Tish Davidson, AM Crystal Heather Kaczkowski, MS Margaret Alic, PhD

OTHER

‘‘Alcohol: Frequently Asked Questons.’’ Centers for Disease Control and Prevention. http://www.cdc.gov/alcohol/ faqs.htm. ‘‘FAQ for the General Public.’’ National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov/ FAQs/General English/default.htm. ‘‘Fetal Alcohol Spectrum Disorders.’’ National Institutes of Health. http://www.nih.gov/about/researchresultsfor thepublic/FetalAlcohol.pdf. Harvard School of Public Health. ‘‘Alcohol: Balancing Risks and Benefits.’’ The Nutrition Source. http://www. hsph.harvard.edu/nutritionsource/what should you eat/alcohol full story/index.html. Higdon, Jane. ‘‘Alcoholic Beverages.’’ Micronutrient Infor mation Center. http://lpi.oregonstate.edu/infocenter/ foods/alcohol. National Institute on Alcohol Abuse and Alcoholism. ‘‘Alcohol Calorie Counter.’’ College Drinking Changing the Culture. http://www.collegedrinkingprevention.gov/ CollegeStudents/calculator/alcoholcalc.aspx. National Institutes of Health. ‘‘Discussing Drinking: A Back to School Conversation You Need to Have.’’ NIH News in Health. http://newsinhealth.nih.gov/2006/ September/docs/01features_01.htm. Rosenbloom, Margaret J., and Adolf Pfefferbaum. ‘‘Mag netic Resonance Imaging of the Living Brain: Evidence for Brain Degeneration Among Alcoholics and 54

Aldesleukin Definition Aldesleukin is interleukin-2 (IL-2), or specific kind of biological response modifier, that is used to treat metastatic renal cell carcinoma (a form of kidney cancer) and metastatic malignant melanoma. U.S. brand names Aldesleukin is also known as interleukin-2, IL-2 and the trademarked brand name Proleukin.

Purpose When patients diagnosed with renal cell carcinoma and metastatic melanoma (cancer of the skin that arises in the pigmented cells of the skin or eyes) do not respond to other therapies, they may be candidates for treatment with aldesleukin. G A LE EN CY C LO PE DI A O F C AN C ER 3

Aldesleukin is a biological response modifier (BMR). It promotes the development of T cells, or the cells in the lymphatic system that can fight cancer cells in cell-to-cell interaction. The human body produces aldesleukin naturally. For use in therapy, aldesleukin is manufactured in a laboratory setting, using biotechnology methods, or methods that combine biological mechanisms and tools from technology. In the instance of aldesleukin, the compound is made in large quantities by using recombinant DNA technology. The DNA, or hereditary material, that provides instructions for making aldesleukin, is put in bacterial cells under laboratory confinement. The cells then produce large quantities of the human compound that are harvested, purified, and used for treatment. Treatment with aldesleukin may control the growth of tumors, but this treatment does not produce a cure. In some cases, aldesleukin is used together with an anticancer drug.

by thallium stress testing and pulmonary function testing. Patients with normal thallium stress test and pulmonary function test results but who have a history of prior cardiac or pulmonary disease and who are to be treated with aldesleukin should be treated with extreme caution. Patients treated with aldesleukin may develop capillary leak syndrome (CLS) which results in hypotension and reduced perfusion of organs which may result in death. CLS is also associated with many other serious conditions including heart attack, breathing difficulties, renal problems and mental status changes. Patients with bacterial infections or those prone to developing infection should be free of any infection prior to the start of therapy with aldesleukin. Continued administration of aldesleukin to patients who develop lethargy may result in coma. Pediatric Aldesleukin in not approved for use in children. Geriatric

Recommended dosage Standard treatment with aldesleukin is via an intravenous line. The standard dose is 0.037 milligrams per kilogram (600,000 IU/kg) of body weight every eight hours to a maximum of 14 doses. The patient then remains off of the drug for 9 days. Following the 9 day rest period, the schedule is repeated for another 14 doses (the total is a maximum of 28 doses per course of treatment) as tolerated. Treatment with aldesleukin may result in severe side effects, therefore, lowering doses, withholding doses, and interrupting doses during treatment with this drug are not uncommon occurrences. Each treatment course should be separated by a rest period of at least 7 weeks from the date of hospital discharge prior to initiation of the next course of treatment. Additional treatment is warranted only if there is evidence of decrease in tumor size since the last course and/or if there are no other contraindications to treating the patient again with aldesleukin.

Precautions Side effects from aldesleukin are generally very severe. Therefore, the drug should only be administered in a hospital setting under the supervision of clinicians (oncology nurses, oncologists, and pharmacists) who are experienced in the administration of cancer therapies. Access to an intensive care unit is required when administering this drug. Aldesleukin should only be given to patients with normal cardiac and pulmonary function as validated G A LE EN CY C LO PE DI A O F C AN CE R 3

As stated earlier, patients who may be candidates for aldesleukin therapy must have normal cardiac and pulmonary functioning. This drug is contraindicated in patients with significant renal, hepatic, and/or central nervous system impairment. Pregnant or breastfeeding At this time in 2009, there have been no studies which have determined whether aldesleukin is safe for use in pregnant woman. The drug should be given in pregnancy only if potential benefit to the mother justifies the potential risk to the fetus. It is not yet known whether aldesleukin is excreted in human breast milk. However, there is potential for serious adverse reactions in infants of breastfeeding mothers. Therefore, women who have been prescribed aldesleukin while breastfeeding should make the decision to discontinue breastfeeding or to discontinue the drug. Other conditions and allergies The effect of aldesleukin on fertility has not been studied. The manufacturer recommends this drug not be administered to fertile persons of either gender who are not using effective contraceptive methods and practices.

Side effects Aldesleukin causes changes in the ways body fluids accumulate in the body that can lead to ascites and pleural effusions. Changes in personality are common due to the influence the drug has on the central nervous 55

Aldesleukin

Description

Alemtuzumab

QUESTIONS TO ASK YOUR PHARMACI ST OR DOCTOR 

 





 

Am I an appropriate candidate for treatment with aldesleukin? Will I receive this drug in the hospital? Is there an intensive care unit facility in the hospital where I will be receiving this drug? What is the experience of the medical and nursing staffs with this drug? Am I on any other medications which could potentially interact with aldesleukin? How many doses should I expect to receive? What types of laboratory and other testing will I have to undergo prior to receiving aldesleukin?

system. Among the most severe side effects is the possibility a patient will slip into a coma, or unconscious state. Other side effects may include alterations in liver function, skin reactions, such as rash, and infections may be severe and life threatening. Less serious, and almost always transient side effects, include flu-like symptoms, such as nausea and vomiting.

Interactions Aldesleukin interacts with drugs that affect the central nervous system and it should not be taken with drugs that are used to modify moods or disposition (psychotropic agents). Many drugs, including those used to control blood pressure, heart beat and kidney function, increase the toxicity of aldesleukin and should not be taken in combination with it. Corticosteroids also interfere with the action of aldesleukin. Physicians must be informed about every drug a patient is taking so interactions can be avoided. Other drugs used to treat cancer which may interact with aldesleukin include dacarbazine, cisplatinum, tamoxifen and interferon-alfa. Some patients (approximately 11–28% of patients in one study) previously treated with IL-2 containing regimens who then underwent radiological procedures which required use of iodinated contrast media, experienced adverse reactions including fever, chills, nausea and vomiting, rash, diarrhea, hypotension and other adverse effects. Diane M. Calabrese Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S. 56

Alemtuzumab Definition Alemtuzumab is an anti-cancer chemotherapeutic drug used to treat a type of cancer of the blood and bone marrow called leukemia.

Purpose Alemtuzumab is used to treat a type of leukemia called B-cell chronic lymphocytic leukemia, also known as chronic lymphoid leukemia (CLL). Alemtuzumab is considered a first line agent for treatment of CLL, meaning that it may be a part of the first group of medicines used once a patient is diagnosed with CLL. Alemtuzumab is also used to treat CLL that has not responded to other drugs. Chronic lymphoid leukemia is cancer of a white blood cell called a lymphocyte. Lymphocytes are part of the immune defense of the body useful in fighting infections. The type of lymphocyte that creates antibodies against foreign invaders is the B cell. B cells are formed in the bone marrow, mature in lymph nodes, and travel via the blood and lymphatic system to fight infection. In CLL, the B cells are abnormal and do not fight infection. Instead the B cells present in CLL grow at an abnormally high rate, fill up the bone marrow and blood with abnormal B cells, and keep other normal immune system cells from growing. Most patients with CLL are greater than 50 years of age and male, but CLL can occur in either gender and at any age. Reports of patients with CLL less than 35 years of age are rare. Alemtuzumab is currently being investigated for possible use in other types of cancer in addition to CLL.

Description Alemtuzumab is a type of monoclonal antibody used in the treatment of leukemia. Monoclonal antibodies are produced in the laboratory as substances that can locate and bind to cancer cells to destroy them. Alemtuzumab is marketed as the drug Campath by Bayer and Berlex Labs. Studies have shown that use of alemtuzumab increases median survival time and progression-free survival compared to placebo. Median survival time is a term used to describe the time from either diagnosis or treatment at which half of the patients with a given disease are expected to still be alive. The term progression-free survival describes the length of time during and after treatment in which a patient is living with a disease that does not get worse. In a clinical trial G A LE EN CY C LO PE DI A O F C AN C ER 3

Anaphylactic shock—Acute systemic allergic reaction that can be life threatening. Aplastic anemia—Type of anemia in which the bone marrow does not produce enough new cells to replenish the blood.

joints, tendons, and the big toe causing painful arthritic attacks. Leukemia—Group of cancers of the blood or bone marrow characterized by an abnormal multiplication of white blood cells.

Autoimmune hemolytic anemia—Type of anemia in which the immune system of the body attacks its own red blood cells and destroys them in a process known as hemolysis.

Lymphocyte—White blood cells of the immune system. Monoclonal antibody—Antibodies produced by one type of B cell that are all clones of the parent cell and so are identical.

Autoimmune thrombocytopenia—Condition in which the immune system of the body attacks its own blood system, resulting in decreased number of platelets necessary for normal blood clotting. B cell—Type of white blood cell that creates antibodies to fight infection.

Multiple sclerosis—Autoimmune disease where the immune system is attacking the nervous system causing scars in the brain and spinal cord and physical and cognitive difficulty.

Bone marrow suppression—Disorder often caused by anti-cancer drugs in which the bone marrow no longer produces enough of the blood cells necessary for oxygen transport and the immune system often causing anemia and life-threatening infections. Gout—Disease caused by elevated levels of uric acid in the bloodstream that deposit as crystals in

designed to test out a cancer drug in humans, both median survival time and progression-free survival are ways to measure how effective a treatment is.

Recommended dosage Alemtuzumab therapy is dependent on a maintenance dose, the dose required to maintain a therapeutic level or range of alemtuzumab present in the bloodstream. However, the maintenance dose is often too high for patients to tolerate without working up to it gradually. Alemtuzumab therapy is begun at low doses and increased on a daily basis over a period of days or up to several weeks, to gradually bring the patient to the maintenance dose necessary for therapeutic effect. Alemtuzumab is given as an intravenous infusion over 2 hours three times per week, at a dose of 30 mg per infusion. Infusions are given on alternate days. The total duration of therapy, including initial dosage and dosage escalation, is up to 12 weeks. Single doses exceeding 30 mg or cumulative weekly doses exceeding 90 mg increase the incidence of toxicity and treatment related blood disorders. Alemtuzumab intravenous therapy is associated with severe infusion reactions, ranging from skin G A LE EN CY C LO PE DI A O F C AN CE R 3

Oral mucositis— Painful inflammation and ulceration of the lining of the mouth, usually as a side effect of chemotherapy in the treatment of cancer. Pancytopenia—Disorder in which all blood elements are deficient, red blood cells, white blood cells, and platelets. Psoriasis—Chronic autoimmune disease that affecting skin and joints that causes red scaly patches of inflammation on the skin.

inflammation and itching, to life-threatening drop in blood pressure, difficulty breathing, heart attack, collapse of the blood vessels, and shock. To help prevent infusion reactions both diphenhydramine (Benadryl) and acetaminophen (Tylenol) are given 30 minutes prior to the alemtuzumab infusion during dose escalation. The doses used are 50 mg of diphenhydramine and 500 mg to 1 g acetaminophen. Alemtuzumab depresses the immune system and makes a patient more susceptible to infections. Opportunistic infections are infections that may not normally occur in a healthy individual whose immune system is strong enough to fight them off. However, in individuals with depressed immune systems these infectious organisms are often able to get a foothold. To minimize this risk, several medications are given prophylactically when starting alemtuzumab therapy and continued for a time after therapy. The antibiotic sulfamethoxazole/trimethoprim is given in a dose of 800mg/160mg twice a day three times in a week. This antibiotic protects against an opportunistic pneumonia called Pneumocystis jiroveci. The antiviral drug famciclovir may be given in a dose of 250 mg twice a day to prevent herpes infection. These therapies are 57

Alemtuzumab

KEY TERM S

Alemtuzumab

continued for 2 months after alemtuzumab treatment or when the immune system has healthy levels of immune cells again (whichever is later).

Precautions Alemtuzumab is a pregnancy category C drug, and is used during pregnancy only when medically necessary. A pregnancy category C drug is one for which studies done in animals have shown potential harm to a fetus but there is not sufficient data in humans. If the potential benefits for the patient outweigh the potential risks to the fetus, the drug may be used during pregnancy. However, alemtuzumab may cause harm to a fetus. Alemtuzumab is contraindicated for use during breastfeeding and cannot be used within 3 months of beginning breastfeeding. The safety and effectiveness of alemtuzumab has not been established in patients less than 18 years of age. Clinical studies done on alemtuzumab did not include sufficient numbers of patients greater than 65 years of age to determine any differences in response in this age group, however no differences in geriatric patients have been reported. Patients should not have any vaccinations while taking alemtuzumab without the consent of their treating physician, and live vaccines should not be given. Patients taking alemtuzumab should also avoid being around people who have recently had the oral polio vaccine or the inhaled flu vaccine, as these are both live vaccines. Some serious and even fatal side effects have been observed with alemtuzumab therapy. Alemtuzumab may cause fatal blood cell toxicities, including autoimmune hemolytic anemia, autoimmune thrombocytopenia, and pancytopenia. Alemtuzumab therapy has caused serious bone marrow suppression and immune system suppression resulting in increased risk for dangerous opportunistic infections. Serious and fatal reactions to the infusion have occurred including respiratory arrest, heart attack, cardiac arrhythmias, loss of consciousness, severe fever, chills, nausea, and vomiting, dangerously low blood pressure, and anaphylactoid shock. Most infusion reactions occur within the first week of therapy. Several different types of monitoring tests are done during alemtuzumab therapy. Blood is monitored weekly in most patients, more frequently if initial signs of blood abnormality occur. Blood monitoring checks for disorders such as developing anemia, deficiency in any blood cells, and to check immune system cells are present in appropriate amounts. 58

QUESTIONS TO ASK YOUR PHARMACI ST OR DOCTOR 





How long will I need to take this drug before you can tell if it helps for me? Is this drug safe to take with the other drugs that I am currently taking? What side effects should I watch for? When should I call the doctor about them?

Alemtuzumab may not be suitable for patients who have a form of anemia called autoimmune hemolytic anemia or aplastic anemia, thrombocytopenia, bacterial infections, bone marrow depression, fungal Infections, HIV infection, heart disorders, depressed immune system, or viral Infections. Monitoring is done for any sign of an infusion reaction, especially in the first several weeks of therapy. Because the immune system is depressed by alemtuzumab therapy, patients are monitored for opportunistic cytomegalovirus (CMV) infection throughout therapy and for 2 months after completion of treatment. During therapy CMV testing may be done weekly, then biweekly after therapy.

Side Effects Alemtuzumab is used when the medical benefit is judged to be greater than the risk of side effects. Potential side effects include anemia, mouth sores, infusion reactions, rash, dizziness, fatigue, cough, nausea, vomiting, fever, chills, muscle stiffness, heart disorders, heart attack, difficulty breathing, sweating, headache, itchiness, wheezing, abdominal pain and cramping, diarrhea, constipation, loss of appetite, increased bacterial, viral, and fungal infections, sudden low blood pressure, high blood pressure, increased bleeding and bruising, racing heartbeat, anxiety, insomnia, and shock. Side effects involving infusion reactions are most likely to appear within the first week of treatment.

Interactions Alemtuzumab may cause multiple different potentially serious adverse effects. Use of alemtuzumab in the same time period as other drugs that cause similar medical problems may cause an additive effect. Use of alemtuzumab with the psoriasis drug alefacept, the immunosuppressant drugs azathioprine or corticosteroids, the antipsychotic drug clozapine, the antiviral drug ganciclovir, or the gout drug allopurinol G A LE EN CY C LO PE DI A O F C AN C ER 3

Resources BOOKS

Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Eleventh Edition. McGraw Hill Medical Publishing Division, 2006. Tarascon Pharmacopoeia Library Edition. Jones and Bartlett Publishers, 2009. OTHER

MedscapeAlemtuzumab. RxListAlemtuzumab. ORGANIZATIONS

National Cancer Institute. 6116 Executive Boulevard, Room 3036A, Bethesda, MD 20892 8322. (800)4 CANCER. http://www.cancer.gov. FDA U.S. Food and Drug Administration. 10903 New Hampshire Ave, Silver Spring, MD 20993. (888)INFO FDA. http://www.fda.gov.

KEY T ERMS ACE inhibitors—A group of drugs used to treat high blood pressure. These drugs work by decreasing production of a certain chemical in the kidneys that causes constriction of blood vessels. Gout—A disease, especially common in men, in which patients may have high uric acid levels in the blood and sudden attacks of severe joint pain and swelling caused by the deposits of uric acid crystals in those joints. These gout attacks most commonly affect the big toe. Kidney stone—A concretion in the kidney made of various materials, such as uric acid crystals, calcium, or lipids. These concretions, or stones, cause severe pain when they are transported from the kidney into the bladder and out of the body. Tumor lysis syndrome—A potentially life-threatening condition caused by cancer chemotherapy associated with very high blood levels uric acid, phosphate, and potassium, low calcium, and acute kidney failure. Uric acid—White, poorly soluble crystals found in the urine. Sometimes uric acid forms small solid stones or crystals that are deposited in different organs in the body, such as the kidney. High levels of uric acid can be seen in patients with gout or cancer.

Maria Basile, Ph.D.

Recommended dosage Adults

Allopurinol Definition This medication, also known as (Zyloprim), is used for the treatment and prevention of gout attacks and certain types of kidney stones. It is also used to treat elevated uric acid levels in the blood and urine, which can occur in patients receiving chemotherapy for the treatment of leukemia, lymphoma and other types of cancer. If left untreated, high uric acid levels in patients receiving cancer chemotherapy can cause kidney stones and kidney failure.

Description Allopurinol decreases uric acid levels in the blood and urine by inhibiting a certain enzyme responsible for production of uric acid. It has been used for over three decades for prevention of gouty arthritis, kidney stones, and tumor lysis syndrome in cancer patients. G A LE EN CY C LO PE DI A O F C AN CE R 3

GOUT. 200–300 mg per day for mild gout and 400–600 mg per day for severe gout. Patients greater than 65 years of age should be started at 100 mg per day. Their dose can be increased until desired uric acid levels in the blood are reached.

Children over 10 years of age and adults PREVENTION OF URIC ACID KIDNEY STONES IN CANCER PATIENTS. 600–800 mg per day divided into several

doses, usually starting 1-2 days before cancer chemotherapy and stopped two to three days after the chemotherapy is completed for that cycle. Total daily dose greater than 300 mg should be given in divided doses. Children less than 10 years of age PREVENTION OF URIC ACID KIDNEY STONES IN CANCER PATIENTS. 10 mg per kg per day of allopurinol in

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Allopurinol

may cause toxicity in the form of immunosuppression. There are many drugs with which alemtuzumab may cause additive immunosupression, and the treating physician should be made aware of all medications the patient is taking before starting therapy with alemtuzumab. Use of alemtuzumab with the multiple sclerosis drug natalizumab may increase risk of infection. Use of alemtuzumab within 24 hours before, during, or 24 hours after the oral mucositis drug palifermin may increase the severity of mouth sores.

Alopecia

two to three divided doses up to a maximum dose of 800 mg per day. Another alternative is to give 150 mg per day in three divided doses for children 6 years of age and 300 mg per day in two to three divided doses for children 6-10 years of age. Administration Allopurinol should be taken after meals to avoid stomach upset. Patients should drink plenty of fluids (at least eight glasses of water per day) while taking this medicine unless otherwise directed by a physician. Drinking a lot of water can prevent formation of kidney stones.

Precautions The use of allopurinol in pregnant women should be avoided whenever possible because its effects on the human fetus are not known. Allopurinol should be used with caution by the following populations: Patients who have had an allergic reaction to allopurinol in the past.  Patients who are taking certain medicines for high blood pressure such as diuretics (water pills) or angiotensin converting enzyme (ACE) inhibitors (captopril, lisinopril, enalapril). These people may be at higher risk of hypersensitivity with allopurinol.  Breast-feeding mothers.  Children (except those who have high uric acid levels caused by cancer, chemotherapy, or genetic diseases). 

Patients should call a doctor immediately if any of these symptoms develop:

combination with a rash. The risk of rash is higher in people with kidney disease or people taking amoxicillin or ampicillin. The use of allopurinol should be discontinued at first sign of a rash. Other side effects include nausea, vomiting, decreased kidney function and drowsiness (especially during the first few days of therapy). Because allopurinol can cause drowsiness, caution should be taken when performing tasks requiring alertness, such as cooking or driving.

Interactions Patients should consult their doctor before drinking alcoholic beverages; alcohol can decrease the effectiveness of allopurinol. People consuming large amounts of vitamin C can be at an increased risk for kidney stones. Allopurinol can prolong the effects of blood thinners such as warfarin (Coumadin) and put patients at risk for bleeding. It can also increase chances of low blood sugar with chlorpropamide (Diabinese) and nerve toxicity with vidarabine. Allopurinol can decrease breakdown of azathioprine (Imuran), mercaptopurine (6-MP), cyclosporine (Neoral, Sandimmune) and theophylline (Theo-Dur, Theolair, Theo24) by the liver, increasing blood levels and side effects. Doses of azathioprine and mercaptopurine need to be reduced when they are used together with allopurinol. Mercaptopurine can be substituted for thioguanine (6-TG) to avoid this interaction altogether. The use of amoxicillin and ampicillin should be avoided if possible in patients taking allopurinol because of increased risk of rash. Water pills such as hydrochlorthiazide (Diuril) can increase the risk of toxicity and allergic reaction when used with allopurinol.

rash, itching, swelling of lips or mouth, trouble breathing (also known as hypersensitivity reaction)  yellowing of the skin or eyes  pain when urinating or blood in the urine  unusual bleeding or bruising 

Olga Bessmertny, Pharm.D.

Patients with kidney problems may need to use lower doses of allopurinol. Patients taking allopurinol will need to see a physician before starting therapy and occasionally during therapy to do blood tests for monitoring of kidney and liver function and complete blood count.

Side effects Allopurinol is usually well tolerated by most patients. The most common side effect is skin rash, hives and itching. Loss of hair, fever, and feelings of discomfort or uneasiness can happen alone or in 60

Alopecia Definition Alopecia is the loss of hair for any reason. It can refer to thinning hair, patchy bald spots, partial or complete baldness, or hair loss confined to specific parts of the body. Androgenetic alopecia—also called adrogenic alopecia or pattern baldness or hair loss—is the thinning of scalp hair in response to androgens or male hormones, which is a natural part of aging in both men and women. G A LE EN CY C LO PE DI A O F C AN C ER 3

Up to 70% of all men and approximately onethird of women are affected by alopecia at some point in their lives. In males androgenetic alopecia begins anytime after puberty. It usually becomes noticeable during the third decade of life and almost always by the fourth decade. Androgenetic alopecia affects about 50% of Caucasian men over age 40, but is less common and often less severe in Asian, Native American, and African-American men. It has been estimated that about 13% of premenopausal and about 37% of postmenopausal women have some degree of androgenetic alopecia.

Although alopecia itself is a harmless, painless condition, it can significantly affect body image, selfesteem, and sexuality. It can cause people to limit their social activities and bring on depression. Risk factors Androgenetic alopecia has a genetic basis. A family history of androgenetic alopecia increases one’s risk of inheriting the condition. It is also associated with coronary heart disease, prostate enlargement in men, and polycystic ovary syndrome in women. Other risk factors for alopecia include:  

Description Alopecia can be a natural process, a symptom of an underlying physical or mental health condition, or the result of cancerchemotherapy or other drug treatments. Alopecia may affect only the hair and or the underlying skin as well. For example, some systemic diseases selectively affect hair growth, whereas others cause alopecia by altering the scalp skin. 

 

Alopecia areata is the loss of patches of hair due to an unknown cause. Alopecia totalis is complete baldness. Alopecia universalis is loss of hair all over the body.

The average person has 5 million hairs growing all over the body except the lips, palms, and soles of the feet. The scalp usually has about 100,000 hairs. Each hair grows out of a microscopic depression in the skin called a hair follicle. No new follicles are formed after birth. Each hair normally grows to its maximum length, stops growing, and is shed and replaced: 







About 88% of hairs are in the growing or anagen stage, which lasts for two to six years. Hair generally grows about one inch every four months. When a hair stops growing, it enters the catagen or transitional stage that lasts two to four weeks. It then enters the telogen or resting stage, which lasts for two to five months. In the exogen stage the hair falls out and a new hair begins to grow, beginning the cycle anew. Most people lose about 50–100 hairs each day. Alopecia of the scalp becomes noticeable only after about half of the hair has fallen out.

Hair follicles contain receptors for androgens circulating in the blood. Androgens binding to these receptors affect the hair-growth cycle in both makes and females. Although scalp hair grows in the absence of androgens, body hair is dependent on androgens. G A LE EN CY C LO PE DI A O F C AN CE R 3



a family history of alopecia areata various diseases including diabetes, thyroid disease, lupus erythematosus, or infection chemotherapy or other drug treatments

Causes and symptoms 











Androgenetic alopecia or pattern baldness is caused by a shortened anagen stage and the regrowth of thinner more fragile hair. With each growth cycle the hair is less firmly rooted and more easily shed. Androgenetic alopecia occurs in response to circulating androgens in the blood and is the most common cause of alopecia in both men and women. Male-pattern hair loss or hereditary baldness is considered normal in adult males. It is easily recognized by hair loss over the top and front of the head, with a receding hairline at the temples and balding on top, eventually leading to partial or complete baldness. The scalp remains healthy. Female pattern hair loss is also hereditary androgenetic alopecia, although the pattern is somewhat different than in men. It is characterized by a reduction in hair density over the crown and frontal scalp—thinning at the front, sides, or crown—but without a receding hairline. Hair loss in women is more common with advancing age and tends to be very gradual, although it accelerates during pregnancy and menopause. Hormonal changes or imbalances can cause temporary hair loss. These include pregnancy, giving birth, discontinuing birth control pills, entering menopause, or an underactive or overactive thyroid gland. Poor nutrition resulting from lack of protein or iron in the diet, fad or crash diets, or eating disorders can cause alopecia. Alopecia areata ranges from patchy hair loss to complete baldness. Most often it is characterized by a few small round smooth patches on the scalp, about the size of quarters. However it can occur anywhere on 61

Alopecia

Demographics

Alopecia

the body, including the eyelashes or beard. Rarely, alopecia areata extends to the loss of all body hair. Soreness and itching may precede the hair loss. Although the hair regrows, the condition is often cyclical with hair repeatedly falling out and regrowing. Although the cause is unknown, it is believed to be an autoimmune condition. Most people with alopecia areata are otherwise healthy and there is little or no inflammation of the scalp. 

Several systemic autoimmune diseases—conditions in which the body’s immune system attacks its own cells—cause alopecia by affecting the skin and/or hair. Lupus erythematosus causes alopecia by affecting the skin. Hyperthyroidism—excess thyroid hormone—causes the hair to become thin and fine. Hypothyroidism—thyroid hormone deficiency— thickens both the hair and skin, causing alopecia. Diabetes can also cause alopecia.



Tinea capitis, or ringworm of the scalp, is a common contagious infection caused by mold-like fungi similar to those that cause athlete’s foot. It usually causes patchy hair loss. Other scalp infections can also cause alopecia



Cicatricial (scarring) hair loss is a rare condition in which inflammation permanently damages and scars the hair follicle, preventing new hair from growing. It may be accompanied by itching or pain. Although the precise cause of the inflammation is unknown, it is associated with several conditions including lupus erythematosus and a skin disease called lichen planus.



Telogen effluvium is the sudden loss of clumps of hair that occurs when washing, combing, or simply gently tugging on the hair. Telogen effluvium usually results in thinning rather than bald patches. It occurs when the hair-growth cycle is prematurely forced into the telogen stage, often as the result of physical or emotional trauma.



Trichotillomania is a mental disorder in which people compulsively pull out their own hair, resulting in bald spots.



Traction apolecia results from hairstyles—such as tight pigtails, braids, cornrows, or tight curlers— that pull on the scalp. Hair loss usually occurs at the spots where the hair is pulled. Over-styling and excessive brushing can also cause hair loss from damage and breakage.



Harsh hair treatments, including tinting, dyeing, bleaching, straightening, or permanents, can cause alopecia. African-American women often suffer from alopecia as a result of harsh chemical treatments that damage the hair shaft and follicles.

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Complete hair loss is a common side effect of the toxic drugs used in cancer chemotherapy. Occasionally drugs for treating gout, arthritis, depression, heart problems, or high blood pressure or birth control pills can cause alopecia. Radiation therapy causes hair loss only in the area of skin being treated. In children, alopecia is usually caused by drug treatments, radiation therapy, a skin disorder, or a hormone imbalance.

In addition to killing rapidly growing cancer cells, chemotherapy drugs also kill normal body cells that are growing rapidly. These include the cells of the hair bulb at the base of each hair. The hair falls out when these cells are killed. Some drugs affect the hair bulb, causing the hair to narrow and weaken and leading to breakage during normal brushing or shampooing. Most patients undergoing chemotherapy, especially those who are being treated with more than one drug, will suffer from hair loss. Alopecia usually occurs between two and three weeks after the first cancer treatment. Hair loss is usually gradual, occurring over a three-to-four-week period. However the chemotherapy drug paclitaxel can cause all of the hair of the body to fall out within a 24-hour period. Other cancer treatments also can cause hair loss on the face, including the eyelashes and eyebrows, as well as the hair of the genitals, underarms, and other body areas. Loss of head hair usually begins on the top (crown) and sides of the head, presumably due to friction caused by pillows, bed linens, and hats. Although many chemotherapy drugs can cause alopecia, certain drugs are more likely to cause hair loss than others. The likelihood of alopecia is also affected by the way in which the drug is administered, the dose, and the treatment schedule. The rapid administration of large doses, called bolus-dosing, is more toxic to the hair bulb than the slow administration of lower doses. Chemotherapy drugs with very high potential for causing alopecia include:       

cyclophosphamide daunorubicin doxorubicin (at doses higher than 50 milligrams) etoposide ifosamide paclitaxel docetaxel (Taxotere)

Radiation treatments also kill rapidly dividing cells. However hair loss occurs only at the site receiving the radiation. A high dose of radiation (greater than 6,000 cGy) usually permanently damages the hair G A LE EN CY C LO PE DI A O F C AN C ER 3

Genetic profile Genetic factors determine the degree to which circulating androgens affect hair follicles in men. Androgens can activate genes that shorten the anagen cycle, causing the hair follicles to shrink. As the follicles shrink, the hair becomes shorter and finer and loses its pigment. Androgenic alopecia in women also appears to have a genetic component, but is not well-understood and may result from a combination of androgen-dependent and androgen-independent mechanisms. Genetic factors also influence the age at which alopecia begins, the speed that it progresses, and the pattern and extent of hair loss.

Procedures Diagnosis of more unusual diseases or conditions underlying alopecia may require a skin punch biopsy. Using a local anesthetic, a circular tool removes a tiny bit of the deeper layers of skin for microscopic examination. Skin biopsies are often used to diagnose alopecia areata or cicatricial (scarring) apolecia.

Treatment Traditional Temporary alopecia requires successful treatment of the underlying cause. This may require an effective cure of the scalp fungus, control of a systemic disease, or completion of chemotherapy. There are various surgical treatments for androgenetic alopecia or other permanent hair loss: 

Diagnosis Examination Dermatologists can often diagnosis the cause of alopecia by its appearance. Androgenetic alopecia is easily recognized by the pattern of hair loss on the top and front of the head and by the healthy condition of the scalp. Dermatologists use the Norwood scale to evaluate the extent of androgenetic alopecia in men. Female pattern hair loss is less easily recognizable. Dermatologists use the Ludwig scale or the Savin scale to evaluate female androgenetic alopecia. For other types of alopecia, a complete patient and family medical history, physical examination, and possibly a psychological evaluation may be required. Tests If the cause of the alopecia is not apparent tests may include: 

Pull testing, in which several dozen hairs are gently tugged to observe how many are removed, is used to determine the stage of shedding and diagnose or rule out telogen effluvium.



Skin scrapings remove small samples of skin and a few hairs to be examined for infection.



The fungus causing tinea capitis usually glows under ultraviolet light.



Systemic diseases underlying alopecia, such as diabetes, lupus, or thyroid disease, usually require a battery of specialized tests for diagnosis.

G A LE EN CY C LO PE DI A O F C AN CE R 3







Hair transplantation involves the surgical transplantation of thousands of individual hair follicles. Tiny plugs of skin, each containing one to several hairs, are removed from the back side of the scalp and implanted into the bald sections. Hair grafting, in which micrografts of one or two hairs are transplanted per follicle, tends to give the best results with the fewest complications. Scalp reduction involves reducing the bald area by stretching the skin, removing the hairless area of scalp, and closing the space with hair-covered scalp. Rotation flaps involve folding skin with hair over an area of bald skin. Drugs

Minoxidil (Rogaine) and finasteride (Propecia) are the only approved drugs for promoting hair growth. They are effective in a significant minority of patients, especially those with male pattern baldness or alopecia areata and they are both considered to be safe when used as directed. However any new hair growth ceases as soon as the treatment is discontinued. Minoxidil is an over-the-counter 2% liquid or foam that is rubbed into the scalp twice a day. When used continuously for long periods of time, minoxidil produces satisfactory results—regrowth and/or a slower rate of loss—in about 25% of patients with androgenic alopecia and as many as half of patients with alopecia areata, although the new hair may be shorter and is often thinner and lighter in color. It can take 12 weeks of treatment to regrow any hair. If there is no regrowth within six months, further treatment is unlikely to be effective. Minoxidil appears to increase the length of the anagen phase, enlarge the hair 63

Alopecia

follicles, preventing the hair from regrowing. If hair regrowth does occur, the hairs may be finer than before the treatment. Hair usually regrows following low doses of radiation (less than 6,000 cGy).

Alopecia

follicles, and rouse the follicles from catagen. Minoxidil can be effective for both men and women, but an over-the-counter extra-strength (5%) form of minoxidil is approved for use by men only. Minoxidil may cause scalp irritation. Finasteride is a prescription drug that is taken orally. It prevents the conversion of the male hormone testosterone to dihydrotestosterone (DHT), the hormone that shrinks hair follicles. Many men experience slowed hair loss with finasteride and occasionally some regrowth, although results may take several months. Finasteride should not be used by women of childbearing age because it adversely affects male fetuses. Pregnant women should not even handle the drug. Finasteride has not been shown to be effective in women with postmenopausal androgenetic alopecia. Other drugs that are sometimes used to treat alopecia include: hormones, which can sometimes reverse hair loss due to hormonal changes or imbalances  monthly corticosteroid injections into the scalp for alopecia areata  oral corticosteroids for extensive hair loss  corticosteroid ointments and lotions, although these are less effective  anthralin (Dritho-Scalp) cream or ointment, a psoriasis drug, which may stimulate new hair growth in alopecia areata when applied to the scalp  topical or oral antifungal medications for tinea capitis 

Alternative Patients suffering from alopecia may benefit from certain vitamins, minerals, and supplements that promote healthy hair: zinc  selenium  magnesium  iron  vitamins A, B-complex, and C  vitamin E massaged into the scalp  evening primrose oil and flaxseed oil, which are rich sources of omega-3 and omega-6 fatty acids that are important for healthy hair 

Herbalists recommend rinsing hair with sage tea or massaging the scalp with essential oil of rosemary to improve blood circulation and stimulate hair follicles. Chinese medicinal herbs that promote hair growth include 64



cornus



Chinese foxglove root



Chinese yam



lycium fruit



polygonum

Cancer patients should check with their oncologist before taking any vitamin, mineral, or herbal supplements because of the possibility that they could interfere with the effectiveness of chemotherapy. Home remedies There are a variety of hair-replacement methods, including weaving remaining hair together with hair from another person. Spray-on scalp dye treatments can help disguise hair loss by making the remaining hair appear thicker. Cancer patients are encouraged to buy a wig before they lose their hair, so it will be available when needed and match the color and texture of their normal hair. Patients with long hair can have a wig made with their own hair. A doctor’s prescription is required if the wig is covered by insurance. Some patients prefer to shave their head once hair loss begins.

Prognosis The prognosis for alopecia depends on the cause of the hair loss. It is generally much easier to lose one’s hair than to regrow it and regrown hair is often thinner and less attractive. Androgenetic alopecia is almost always permanent and there are no truly effective treatments. Generally the more extensive the hair loss, the less effective medications will be. However female androgenetic alopecia rarely results in complete baldness. Cicatricial alopecia is also permanent. Hair loss due to hormonal changes, alopecia areata, tinea capitis, and telogen effluvium is usually temporary. However with telogen effluvium it may take months for the hair to regrow. If the pulling that causes traction alopecia is discontinued before the roots are permanently damaged or the scalp is scarred, the hair usually grows back normally. Chemotherapy-induced alopecia is usually temporary. Hair typically regrows in about three to five months, although it may be of a different color or type than before treatment. Radiation-induced alopecia may be permanent. G A LE EN CY C LO PE DI A O F C AN C ER 3

QUESTIONS TO ASK YOUR DOCTOR    

What is causing my hair loss? Will it grow back? What are my treatment options? What are the side effects of treatment?

Prevention Steps for maintaining healthy hair and minimizing alopecia include:   

   

    

a nutritionally balanced diet handling hair gently avoiding tight hairstyles such as buns, pigtails, and braids avoiding twisting, rubbing, or pulling hair using a mild shampoo using hair brushes with soft bristles avoiding the use of hair dryers, hot curlers, and curling irons using the lowest setting on a hair dryer avoiding hair dyes avoiding permanent-wave solutions wearing sunscreen or a hat outdoors using satin pillowcases

Alopecia resulting from cancer treatment is unavoidable. The safety and effectiveness of various methods for preventing chemotherapy-induced alopecia are somewhat controversial. Certain medications are sometimes used. A scalp tourniquet, which puts pressure on the scalp to block blood flow, may prevent the drugs from damaging hair follicles. Scalp hypothermia uses ice or a cooling device to reduce the amount of drug taken up by the hair bulb cells. Resources BOOKS

Haber, Robert S., and Dow B. Stough. Hair Transplanta tion. Philadelphia: Elsevier Saunders, 2006. Hoffman, Candace. Breaking the Silence on Women’s Hair Loss. Orem, UT: Woodland Publishing, 2006. Levy, Janey. Alopecia Areata. New York: Rosen Publishing Group, 2007. National Cancer Institute. Hair Loss (Alopecia). Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, 2008. Sherrow, Victoria. Encyclopedia of Hair: A Cultural History. Westport, CT: Greenwood Press, 2006. G A LE EN CY C LO PE DI A O F C AN CE R 3

Harrison, S., and W. Bergfeld. ‘‘Diffuse Hair Loss: Its Trig gers and Management.’’ Cleveland Clinic Journal of Medicine 76, no. 6 (June 2009): 361 367. Rogers, N. E., and M. R. Avram. ‘‘Medical Treatments for Male and Female Pattern Hair Loss.’’ Journal of the American Academy of Dermatology 59 (2008): 547 566. Rulon, E., et al. ‘‘Clinical Inquiries: What is the Best Diag nostic Approach to Alopecia in Women?’’ Journal of Family Practice 58, no. 7 (July 2009): 378 380. ‘‘Treating Female Pattern Hair Loss. Noticeable Hair Loss Can Be Deeply Distressing. Here Are Some Medical Treatments that May Help.’’ Harvard Women’s Health Watch 16, no. 10 (June 2009): 1 3. OTHER

‘‘Alopecia Areata.’’ National Institute of Arthritis and Mus culoskeletal and Skin Diseases. http://www.niams.nih. gov/Health_Info/Alopecia_Areata/alopecia_areata_ ff.asp. ‘‘Best Rx Options for Hair Loss in Women: Dermatologists Say First Find the Cause.’’ American Academy of Dermatology. http://www.skincarephysicians.com/ agingskinnet/hair_loss_options.html. ‘‘Hair Diseases and Hair Loss.’’ MedlinePlus. http://www. nlm.nih.gov/medlineplus/hairdiseasesandhairloss.html. ‘‘Hair Loss.’’ American Cancer Society. http://www.cancer. org/docroot/MIT/content/MIT_7_2X_Hair_Loss.asp. ‘‘Is Your Hair Taking a Break? Dermatologists Can Help Women Get to the Root of Hair Loss.’’ American Academy of Dermatology. http://www.aad.org/media/ background/news/Releases/Is_Your_Hair_ Taking_a_Break_Dermatologists_Can_Hel/ ‘‘Male and Female Pattern Hair Loss Information.’’ Androgenetic Alopecia.com. http:// www.androgeneticalopecia.com Mayo Clinic Staff. ‘‘Hair Loss.’’ MayoClinic.com. http:// www.mayoclinic.com/health/hair loss/DS00278 ORGANIZATIONS

American Academy of Dermatology, PO Box 4014, Schaumburg, IL, 60168, (847) 240 1280, (866) 503 SKIN (7546), (847) 240 1859, http://www.aad.org. American Cancer Society, 1599 Clifton Road NE, Atlanta, GA, 30329 4251, (800) ACS 2345, http:// www.cancer.org. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Information Clearinghouse, National Institutes of Health, 1 AMS Circle, Bethesda, MD, 20892 3675, (301) 495 4484, (877) 22 NIAMS (226 4267), (301) 718 6366, [email protected]. gov, http://www.niams.nih.gov.

Belinda Rowland, PhD Beth A. Kapes Margaret Alic, PhD

Alternative therapies see Complementary cancer therapies 65

Alopecia

PERIODICALS

Altretamine

Altretamine Definition Altretamine, also known by the brand name Hexalen, is an anticancer agent used to treat ovarian cancer.

Purpose Altretamine is used to treat persistent or recurrent ovarian cancer, usually after treatment of the cancer with cisplatin and/or an alkylating agent fails to effectively treat the tumor.

KEY T ERMS Antiemetic—Agents used to alleviate nausea and vomiting, used during and sometimes following treatment with chemotherapy or radiotherapy. Peripheral neuropathy—Symptoms resulting from damage to the peripheral nerves, that is, nerves not found in the spinal cord or brain.

not known whether this drug is excreted in the breast milk, nursing mothers are cautioned not to breast feed while being treated with altretamine.

Description The mechanism of action of altretamine is not known. However, it is thought that it may inhibit DNA and RNA synthesis.

Recommended dosage Alretamine is administered orally. Doses for the drug may be different depending on the protocol that is used by the physician. Some example dosing regimens are: 4 to 12 mg per kg in three to four divided doses for 21 to 90 days; 240 to 320 mg per square meter of body surface area in three to four divided doses for 21 days, repeated every six weeks; 260 mg per square meter of body surface area per day for 14 to 21 days of a 28 days cycle in four divided doses; or 150 mg per square meter of body surface area in three to four divided doses for 14 days of a 28 day cycle. The dose of altretamine may be decreased if the patient has intolerable stomach side effects, low blood count of cells that fight infection (white blood cells) or cells that prevent bleeding (platelets), or if the patient has progressive toxicity affecting the nerves of the brain and body.

Precautions Caution is usually taken in prescribing altretamine to patients with decreased kidney or liver function or damage to nerves due to previous chemotherapy. Careful monitoring of nerve, kidney, and liver function is required for these patients. Pregnant women should be warned before taking this drug, as it may cause permanent harm to the fetus. Women who are of childbearing age should apply contraceptive methods to avoid pregnancy until they have discontinued drug use. Altretamine may also affect fertility. Additionally, although it is 66

Side effects Nausea and vomiting may gradually occur as patients receive continuous high dose of altretamine. In most instances, antiemetics can help control these side effects. However, some patients may experience severe nausea and vomiting that requires either reducing the dose or stopping treatment with altretamine. Other common side effects include loss of appetite (anorexia) and diarrhea. Patients may also experience nerve toxicity, which is described as numbness, tingling, and burning sensations in the fingers and toes. Patients can also have difficulty walking because of these sensation changes. Patients may also commonly experience: thrombocytopenia, a decrease of the platelet cells responsible for blood clotting; anemia, a decrease of the red blood cells responsible for oxygen transport to tissues and organs; and leukopenia, a decrease of the white blood cells responsible for fighting infections. Less common side effects include seizures, depression, dizziness, stomach cramps, liver toxicity, rash, and hair loss (alopecia).

Interactions Persons taking altretamine and monoamine oxidase inhibitors (MAO inhibitors) may experience severe hypotension (low blood pressure) when standing up. Additionally, the drug cimetidine may increase the toxicity of altretamine. Prior to starting any overthe-counter medications, herbal medications, or new medications, patients should consult with their physician, nurse, or pharmacist to ensure that there are no potential drug interactions. Michael Zuck, Ph.D. G A LE EN CY C LO PE DI A O F C AN C ER 3

Definition Amantadine is a synthetic antiviral drug, similar to rimantadine, in a class known as M2 inhibitors or M2-channel blockers. It is also considered to be an anticholinergic drug and a central nervous system stimulant and has strong anti-parkinsonian properties.

Purpose Amantadine is used to prevent and treat viral infections caused by some strains of influenza A. It inhibits the replication of influenza A subtypes H1N1, H2N2, and H3N2. It is not active against influenza B. Amantadine may be used to prevent influenza A symptoms when a flu vaccine is unavailable or contraindicated or in the period after a flu vaccination before the vaccine becomes effective. It is also used to treat early-stage uncomplicated respiratory tract infections caused by influenza A viruses. However flu viruses can develop resistance to amantadine quite rapidly, so it is not usually the drug of choice during flu season. Amantadine is also used to treat Parkinson’s disease and parkinsonism or parkinsonian symptoms that occur as side effects of antipsychotic medications for mental disorders such as schizophrenia. These side effects, called drug-induced extrapyramidal reactions, are similar to symptoms of Parkinson’s disease and include tremors, difficulties with voluntary movements such as walking, and poor muscle tone. Amantadine is also used to treat parkinsonism caused by encephalitis, nervous system damage from carbon monoxide poisoning, and cerebral arteriosclerosis. However it is less effective in treating Parkinson’s disease than other drugs such as L-dopa. Amantadine increases the level of dopamine—a central nervous system stimulant and neurotransmitter—and helps restore the chemical balance between dopamine and acetylcholine in the brain. Amantadine is sometimes used off-label to treat other conditions including Creutzfeldt-Jakob disease.

Description For flu prevention amantadine is administered in anticipation of an influenza outbreak, before or after contact with infected persons, or for two to four weeks after a flu vaccination until the vaccine can take effect. It is continued for at least 10 days following exposure to the flu. For treating influenza A the drug should be started within 24–48 hours of the appearance of signs G A LE EN CY C LO PE DI A O F C AN CE R 3

Amantadine is available in 100-milligram (mg) tablets and capsules and as a syrup containing 50 mg per teaspoon (5 milliliters). U.S. brand names Amantadine is available under the brand name Symmetrel and as a generic drug, amantadine hydrochloride. Canadian brand names   

Symmetrel Endantadine PMS-Amantadine International brand names

    

Symmetrel Amantadin Mantadix PK-Merz Viregyt-K

Recommended dosage The usual dose of amantadine for adults and children over age nine is 200 mg once a day or 100 mg twice a day. Splitting the dose may reduce central nervous system side effects. Some patients may need a total daily dose as high as 300 mg, especially patients with Parkinson’s disease who find the drug’s effectiveness decreasing after a few months of use. Patients who are taking other anti-parkinsonian drugs concomitantly may take a lower dose, such as 100 mg daily. Elderly patients and those with kidney disease or on hemodialysis must take lower doses, ranging from 100 mg daily to as little as 200 mg every seven days. The dosage for children aged one through nine is 2–4 mg per lb of body weight daily (4.4–8.8 mg/kg/ day), not to exceed 150 mg per day.

Precautions Amantadine can cause visual disturbances and affect mental alertness and coordination. Patients should not operate motor vehicles or dangerous machinery while taking amantadine if they have central nervous system effects or blurred vision from the drug. Suicide attempts and completed suicides have been reported in patients taking amantadine, often for flu prevention or treatment. 67

Amantadine

Amantadine

and symptoms and continued for 24–48 hours after their disappearance.

Amantadine

Pediatric

QUESTIONS TO ASK YOUR PHARMACIST

The safety and effectiveness of amantadine in infants under one year-of-age have not been established.

 

Geriatric



Elderly patients should take lower doses of amantadine and be carefully monitored.

 

How should I take this drug? Should I take it with food? What if I miss a dose? What side effects might I experience? When should I call my doctor about side effects?

Pregnant or breastfeeding Adequate human studies on amantadine during pregnancy have not been performed; however the drug should not be taken during pregnancy unless the potential benefits outweigh the risk to the fetus. Amantadine enters breast milk and should not be used by nursing mothers. Other conditions and allergies Because amantadine increases the levels of dopamine in the brain, patients with a history of epilepsy or other seizure disorders should be carefully monitored while taking this drug.  Patients with kidney or liver disease or a history of congestive heart failure or peripheral edema should also be closely monitored while taking amantadine. Kidney insufficiency significantly reduces clearance of the drug from the body.  Amantadine can exacerbate mental disturbance in patients with histories of psychiatric disorders or substance abuse.  Amantadine should not be discontinued abruptly in patients with Parkinson’s disease because of the risk of a severe symptomatic episode.  All patients should be carefully observed if the dose of amantadine is abruptly reduced or the drug is discontinued.  It should not be given to patients who have a hypersensitivity to amantadine or to any of the inactive ingredients in the medication. 

About 1–5% of patients taking amantadine experience some or all of the following nervous system side effects: 

irritability or agitation



depression



confusion



lack of coordination



nightmares



fatigue



headache Up to 1% of patients may experience:



hallucinations



euphoria (excitement)



extreme forgetfulness



aggressive behavior



personality changes



seizures Seizures are the most serious side effects associated with amantadine.

Amantadine can also cause gastrointestinal side effects. About 5–10% of patients experience nausea. Up to 5% of patients experience dry mouth, loss of appetite, constipation, and vomiting. In most cases these side effects can be treated symptomatically.

About 5–10% of patients taking amantadine experience some or all of the following nervous system side effects:

About 1–5% of patients taking amantadine report a bluish tinge to their skin, usually on the legs, which is associated with enlargement of the blood vessels (livedo reticularis). This side effect usually appears from one month to one year after starting the drug and subsides within weeks or months after the drug is discontinued. Patients experiencing this or other side effects from any medication should consult their physician.

dizziness or lightheadedness insomnia  nervousness or anxiety  impaired concentration

Overdoses of amantadine can result in cardiac dysfunction or respiratory, renal, or nervous system toxicity. As little as 1,000 mg of amantadine can be fatal.

Side effects

 

68

G A LE EN CY C LO PE DI A O F C AN C ER 3

Taking amantadine together with other drugs used to treat parkinsonism or parkinsonian side effects may cause increased confusion or even hallucinations. The combination of amantadine and other central nervous system stimulants, such as amphetamines or decongestants, may increase central nervous system side effects and the likelihood of seizures. Alcohol can also increase the central nervous system side effects of amantadine and should be avoided.

National Parkinson Foundation, Inc., 1501 N.W. 9th Ave nue/Bob Hope Road, Miami, FL, 33136 1494, (305) 243 6666, (800) 327 4545, (305) 243 6073, contact@ parkinson.org, http://www.parkinson.org. U.S. Food and Drug Administration, 10903 New Hamp shire Ave., Silver Spring, MD, 20993 0002, (888) INFO FDA, http://www.fda.gov.

Jack Raber, PharmD Ruth A. Wienclaw, PhD Margaret Alic, PhD

Resources BOOKS

Factor, Stewart A., and William J. Weiner. Parkinson’s Disease: Diagnosis and Clinical Management, 2nd ed. New York: Demos, 2008. PERIODICALS

Cady, Sarah D., and Mei Hong. ‘‘Amantadine Induced Conformational and Dynamical Changes of the Influ enza M2 Transmembrane Proton Channel.’’ Proceed ings of the National Academy of Sciences USA 105, no. 5 (February 5, 2008): 1483. Donfrancesco, Renato, et al. ‘‘Open Label Amantadine in Children with Attention Deficit/Hyperactivity Disor der.’’ Journal of Child and Adolescent Psychopharma cology 17, no. 5 (2007): 657 663. Stouffer, Amanda L., et al. ‘‘Amantadine Structural Basis for the Function and Inhibition of an Influenza Virus Proton Channel.’’ Nature 451 (January 31, 2008): 596 600. OTHER

‘‘Amantadine.’’ University of Maryland Medical Center. http://www.umm.edu/altmed/drugs/amantadine 003900.htm. American Society of Health System Pharmacists. ‘‘Amantadine.’’ MedlinePlus. http://www.nlm.nih.gov/ medlineplus/druginfo/meds/a682064.html. Di Minno, Mariann, and Michael J. Aminoff. ‘‘Treatment Options.’’ National Parkinson Foundation. http://www. parkinson.org/Page.aspx?&pid 227&srcid 244. National Institute of Neurological Disorders and Stroke. ‘‘Parkinson’s Disease: Hope Through Research.’’ NIH Publication No. 06 139. http://www.ninds.nih.gov/dis orders/parkinsons_disease/detail_parkinsons_disease.htm ‘‘Symmetrel (Amantadine Hydrochloride, USP) Tablets and Syrup: Package Insert.’’ Endo Pharmaceuticals. http:// www.endo.com/PDF/symmetrel_pack_insert.pdf. ORGANIZATIONS

Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30333, (888) 232 6348, (301) 563 6595, [email protected], http://www.cdc.gov. National Institute of Neurological Disorders and Stroke (NINDS), NIH Neurological Institute, PO Box 5801, Bethesda, MD, 20824, (301) 496 5751, (800) 352 9424, http://www.ninds.nih.gov/index.htm. G A LE EN CY C LO PE DI A O F C AN CE R 3

Amenorrhea Definition Amenorrhea is the absence of menstruation and is a symptom, not a diagnosis. Primary amenorrhea refers to the absence of the onset of menstruation by age 16 whether or not normal growth and secondary sexual characteristics are present, or the absence of menses after age 14 when normal growth and signs of secondary sexual characteristics are present. Secondary amenorrhea is the absence of menses for three cycles or six months in women who have previously menstruated. In terms of the relationship of amenorrhea to cancer, amenorrhea may be a symptom of a gynecologic tumor, or the pause or cessation in menstruation may develop as a side effect of cancer treatment.

Demographics The prevalence of primary amenorrhea is 0.3% and secondary amenorrhea occurs in approximately 1–3% of women. However, among college students and athletes the incidence can range from 3–5% and 5–60%, respectively. For cancer-related amenorrhea, one clinician noted that nine out of ten women under his care reported secondary amenorrhea following bone marrow transplants. Chemotherapy and abdominal-pelvic radiation therapy likewise produce similar outcomes.

Causes Normal menstrual bleeding occurs between menarche and menopause and has an average length of 28 days but varies from woman to woman. The normal menstrual cycle depends on cyclic changes in estrogen and progesterone levels, as well as the integrity of the clotting system and the ability of the spiral 69

Amenorrhea

Interactions

Amenorrhea

arterioles in the uterus to constrict. Abnormalities in any of these components may cause bleeding to stop or increase. Primary amenorrhea There are multiple causes for primary amenorrhea once pregnancy, lactation and missed abortion are ruled out. These include:

Secondary amenorrhea Once pregnancy, lactation and menopause are ruled out, the causes for secondary amenorrhea include:    



anorexia nervosa/bulimia/malnutrition



extreme obesity



hyperthyroidism/hypoglycemia





congenital heart disease





cystic fibrosis/Crohn’s disease





genetic abnormalities



obstructions: imperforate hymen/vaginal or cervical absence



ovarian, pituitary (craniopharyngioma) or adrenal tumors



polycystic ovarian disease



testicular feminization

It is rare for primary amenorrhea to be caused by tumors but it can be a cause and should always be a consideration if other factors are ruled out. Gonadal failure (a nonfunctioning sex gland) is the most common cause of primary amenorrhea, accounting for almost half the patients with this syndrome. The second most common cause is uterovaginal agenesis (absence of a uterus and/or vagina) with an incidence of about 15% of individuals with this syndrome. One of the most important, and probably most common, causes of amenorrhea in adolescent girls is anorexia nervosa, which occurs in about 1 in 1,000 white women. It is uncommon in women older than 25 and rare in women of both African and Asian descent. When women lose weight 15% below ideal body weight, amenorrhea can occur due to central nervous system-hypothalamic dysfunction. When weight loss drops below 25% ideal body weight, pituitary gonadotrophin function (follicle stimulating hormone and luteinizing hormone) can also become abnormal. Each year of athletic training before menarche (the beginning of menstrual function) delays menarche about four to five months. Amenorrhea associated with strenuous exercise is related to stress, not weight loss, and is most probably caused by an increase in central nervous system endorphins and other compounds which interfere with gonadotrophin-releasing hormone release. 70



extreme obesity prolonged or extreme exercise anxiety or emotional distress non-oral contraceptives (Norplant/Depo-Provera) D & C (dilatation and curettage)(Asherman’s syndrome) early menopause autoimmune dysfunction pituitary tumors and central nervous system lesions Cancer and secondary amenorrhea

As mentioned, not only does amenorrhea occur as a symptom of a tumor and/or lesion, but it often develops in women undergoing treatment for cancer. RADIATION. Radiation therapy is used in conjunction with chemotherapy in a number of clinical situations, including Hodgkin’s disease and childhood leukemia and lymphomas. Ovarian damage occurs under these circumstances to varying degrees, depending upon the total dosage of radiation as well as the age of the patient at the time of exposure. CHEMOTHERAPY. Premenopausal women receiving single or multi-agent chemotherapy are at risk for short-term amenorrhea, as well as ovarian damage. Even young women who resume menstruation following chemotherapy are at risk for early menopause; therefore, those treated in childhood and adolescence should be counseled regarding the chance of early menopause in order to plan ahead for childbearing. WEIGHT LOSS. Side effects of cancer as well as treatments can cause a decrease in appetite and nausea and vomiting, which, in turn, can cause severe weight loss as associated with malnutrition. Thus, menstruation may cease for the same reasons as it does in young adolescents with anorexia nervosa—hypothalamic dysfunction. STRESS. Stress has always been noted to play a large role in the cause of amenorrhea, so the actual stress of having cancer and undergoing treatments may also cause amenorrhea to occur. RETURN OF NORMAL OVARIAN FUNCTION FOLLOWING TREATMENT. Research on the recovery of normal

ovarian function with young girls and/or young women has not revealed any reliable data. There are individual success stories especially with new advances in assisted reproductive technologies (ARTs), but G A LE EN CY C LO PE DI A O F C AN C ER 3

Treatments Even with the possibility of ovarian compromise, women previously treated for cancer have successfully achieved pregnancy via ART’s. Advances in the area of ART’s include the use of donor eggs, the possibility of freezing embryos, and eventual oocyte (immature ovum) pretreatment offer more options to young women facing cancer chemotherapy.

Special concerns The need for effective contraception during and after cancer treatment is imperative. Normal menstrual cycles do not imply normal fertility and likewise, irregular menses or even amenorrhea does not imply a lack of fertility. Women with dysfunctional bleeding or amenorrhea are still capable of spontaneous ovulation and conception. The most reliable form of birth control for any population of women is injectable progestins, which suppress luteinizing hormone secretion. Depo-Provera, 150 mg injected intramuscularly, will effectively block ovulation for four months. Norplant (six rubber capsules placed under anesthesia in the upper arm) will effectively block ovulation for five years. If the treatment or the specific cancer diagnosis contraindicates the use of either of these contraceptives, other options should be considered, i.e., sterilization for the woman or her partner, an intrauterine device (IUD), or barrier methods (condoms, diaphragm or spermicides). See also Fertility and cancer. Resources BOOKS

Jarvis, Carolyn. Physical Examination and Health Assess ment. Philadelphia: W. B. Saunders Company, 2000. Trimble, E. Cancer Obstetrics and Gynecology. Philadelphia: Lippincott William & Wilkins, 1999.

Linda K. Bennington, C.N.S., M.S.N. G A LE EN CY C LO PE DI A O F C AN CE R 3

Amifostine

overall, the return of normal ovarian function seems to be age-dependent. One researcher recently reported on ovarian function in 65 women who underwent high-dose chemotherapy and bone marrow transplants for aplastic anemia. All women younger than 26 years at the time of chemotherapy recovered ovarian function, while 7 of the 18 women aged 26 to 38 years did not recover ovarian function. Thus, the risk of ovarian dysfunction appears to increase with advancing age when ovarian reserve decreases. Additionally, the risk of dysfunction increases with the dose of alkylating agents, notably cyclophosphamide.

American Joint Commission on Cancer Definition The American Joint Commission on Cancer (AJCC) is an organization dedicated to creating and promoting a universal system of classifying tumors according to their location in the body and involvement with surrounding tissues.

Description Created in 1959, the AJCC works with the International Union Against Cancer (UICC), its European counterpart, and other organizations to standardize cancer-related information and data collection. The AJCC bases its classification on the TNM staging system, a universally accepted method of describing the extent of cancer, and other clinical information. The result is a standardized method of categorizing tumors that helps physicians to predict patient prognosis and develop treatment guidelines. The AJCC periodically publishes its Cancer Staging Manual, which is used widely by health care professionals in the diagnosis and treatment of cancer patients. See also Tumor staging. Tamara Brown, R.N.

Amifostine Definition Amifostine, also known as the brand name Ethyol and as ethiofos or WR2721, is a medicine that helps protect certain tissues of the body from damage caused by chemotherapy or radiation therapy.

Purpose Amifostine is a protectant agent that is used in combination with the chemotherapy drug cisplatin or in combination with radiation therapy. Amifostine is approved by the Food and Drug Administration (FDA) to prevent kidney damage caused by repeat doses of the chemotherapy agent cisplatin in patients who have a diagnosis of ovarian cancer or non-small cell lung cancer. It is also FDA approved for patients with head and neck cancer who are receiving radiation therapy after surgery. In this group of patients, 71

Amifostine

Recommended dosage

K EY T ERM S Chemotherapy—Specific drugs used to treat cancer. Enzyme—A protein in the body that breaks down substances, such as food or medicines, into simpler substances that the body can use. Food and Drug Administration—A government agency that oversees public safety in relation to drugs and medical devices. The FDA gives approval to pharmaceutical companies for commercial marketing of their products. Intravenous—To enter the body through a vein. Radiation therapy—The use of high-energy beams focused to treat cancerous tumors.

amifostine helps decrease radiation damage to the salivary glands, which can cause dry mouth.

Description Amifostine has been on the market since the mid1990s. A clear colorless solution, it is administered into a vein before chemotherapy and has been shown to decrease kidney damage by greater than 50% in advanced ovarian cancer patients who have received multiple cycles of cisplatin. It is also used before radiation therapy to prevent damage to the salivary gland known as the parotid gland. When cisplatin is given to patients, it becomes broken down into toxic substances that destroy cancer cells and normal cells. When amifostine is administered into the body, it is broken down by an enzyme that occurs in large quantities in normal cells but not in cancerous cells. It then is converted into a substance called free thiol, which combines with the poisonous cisplatin by-products in the normal cells and makes them nontoxic. In patients who receive radiation to the mouth area, including the salivary glands, the radiation causes the release of substances called free oxygen species, which damage cells of the mouth. An enzyme in cells of the mouth breaks down amifostine into a substance called free thiol. The free thiol blocks the free oxygen substances from damaging the salivary cells and decreases the amount of dry mouth patients suffer from when they receive radiation to the head and neck area. 72

Before dosing amifostine in chemotherapy or radiation therapy patients, intravenous fluids need to be given to keep the body well flushed with fluid and to maintain a normal blood pressure. All patients will receive amifostine lying down, sometimes with the head of the body lower than the feet. Patients should also receive medication to help prevent the nausea and vomiting that occurs due to amifostine. Amifostine dosages can be determined using a mathematical calculation that measures a person’s body surface area (BSA). This number is dependent upon a patient’s height and weight. The larger the person, the greater the body surface area. Body surface area is measured in units known as square meter (m2). To determine the actual dose a patient is to receive, the body surface area is calculated and then multiplied by the drug dosage in milligrams per squared meter (mg/m2). The recommended dosage of amifostine for protection of the kidney is 910mg/m2 administered as a 15-minute infusion into a vein. This is to begin 30 minutes before chemotherapy administration. If a patient has difficulty with this dose, the dosage can be lowered to 740 mg/m2. The recommended dosage of amifostine for radiation therapy patients is 200 mg/m2 administered once a day into a vein over a three-minute time period 15 to 30 minutes before the patient receives radiation treatment.

Precautions Amifostine can cause a decrease in blood pressure when it is administered. During the 24 hours before receiving amifostine, patients need to drink a lot of liquids. When amifostine is being administered, medical personnel will be monitoring the patient’s blood pressure. If the blood pressure drops significantly, the infusion of amifostine will be stopped until blood pressure returns to normal. The doctor will decide if the patient should receive any additional amifostine. Patients who have low blood pressure to begin with or patients who are not drinking a lot of fluids—referred to as being dehydrated—should not receive amifostine. Patients with a known previous allergic reaction to aminothiol drugs should not receive amifostine. Patients who may be pregnant, thinking of becoming pregnant, or who have a history of heart problems or strokes should tell their doctor before receiving amifostine.

Side effects The most common side effect from receiving amifostine is a lowering of blood pressure, which occurs in G A LE EN CY C LO PE DI A O F C AN C ER 3

Nausea and vomiting are common side effects. They occur rapidly and can be severe. Usually, patients are given medicines before receiving amifostine that can help prevent or decrease these side effects. Other side effects include sneezing, hiccups, a warm feeling and redness of the face, sleepiness and dizziness, metallic taste, fever, rash, and chills. Rare side effects of amifostine are: a lowering of calcium levels in the blood, seizures, allergic reactions which include symptoms of fever, shaking chills, itching, low blood pressure, shortness of breath, and rashes. There have been rare reports of throat swelling, chest tightness, and heart stopping. All side effects a patient experiences should be reported to their doctor.

Interactions Amifostine causes a decrease in blood pressure and should be used with caution in patients who take blood pressure lowering medicines or other medications that may lower blood pressure. If patients are taking blood pressure medications, they may be asked to stop taking these medications for 24 hours before receiving amifostine. Patients should tell their doctors if they have a known allergic reaction to amifostine or any other medications or substances, such as foods and preservatives. Before taking any new medications, including nonprescription medications, vitamins, and herbal medications, patients should notify their doctors. Nancy J. Beaulieu, RPh., BCOP

Aminoglutethimide Definition Aminoglutethimide, also known by the brand name Cytadren, is a cancer drug which inhibits the formation of hormones like adrenal glucocorticoids, mineralocorticoids, estrogen, androgens, and aldosterone. G A LE EN CY C LO PE DI A O F C AN CE R 3

KEY T ERMS Hormone—A substance, such as cortisol or estrogen, that causes specific effects on target organs in the body. Hormones may be required for tumor growth or survival. Hormones usually travel in the bloodstream from the organ where they originate to a different organ where they have their effect.

Purpose Aminoglutethimide is used to treat Cushing’s disease, breast cancer, or prostate cancer. It blocks the conversion of cholesterol to delta-5-pregnenolone, a precursor for the formation of the corticosteroids.

Description Aminoglutethimide is used clinically to reduce the amount of the hormones that can sometimes cause tumors to grow more quickly or are necessary for the survival of the tumor. For example, estrogen is important for the growth of some breast tumors. Lowering estrogen production by the administration of aminoglutethimide might reduce tumor growth or contribute to the destruction of the tumor.

Recommended dosage Aminoglutethimide is given orally and dosages vary from patient to patient based on a number of factors, including the underlying disease process.

Precautions Because some corticosteroid is necessary for normal function, patients should receive steroid replacement in addition to aminoglutethimide. Patients may require more corticosteroid when undergoing surgery, illness, or other conditions that cause stress. Hormones that affect the balance of sodium in the body may also be affected by aminoglutethimide and might have to be replaced as a result. If they are not replaced, patients may experience constant low blood pressure or low blood pressure upon standing. Pregnant women should be warned that aminoglutethimide administration could cause fetal abnormalities. Pregnant patients should consult their physician about the current state of knowledge regarding risks and alternatives before beginning administration of aminoglutethimide. Female patients of childbearing age should attempt to avoid pregnancy 73

Aminoglutethimide

approximately 62% of patients treated at a dose of 910mg/m2. This lowering of blood pressure occurs within the first 15 minutes of administering the drug. Blood pressure is monitored throughout the infusion of amifostine. If the blood pressure drops to certain level then the drug is stopped and restarted only when blood pressure returns to normal.

Amitriptyline

while taking this drug. Mothers who are nursing should discontinue nursing while taking this drug.

Side effects Common side effects from the administration of aminoglutethimide is rash (possibly associated with fever) which usually occurs in the first two weeks of therapy. It is usually self-limiting and gets better in a about a week. If the rash continues after one week patient should contact his/her physician or nurse. Fatigue is another common side effect of the drug and usually occurs in the first week of therapy. It may take about a month before it gets better. It can be very severe in some patients and if this is the case the patient’s physician or nurse should be notified. Female patients may experience masculinization: new and excessive hair growth, a deeper voice, and irregular, abnormal, or absent menstrual periods. Thyroid function may be decreased after several weeks of therapy and the patient’s thyroid should be monitored by the physician. Mild nausea and vomiting may also occur, as well as dizziness, depression, shaking, difficulty speaking, and increased heart rate. Any of these effects, or other unusual symptoms, should be reported to the patient’s physician.

Interactions Dexamethasone, blood-thinning medications, theophylline, and digoxin doses for patients taking aminoglutethimide may need to be increased by the physician. Patients should tell their doctors if they have a known allergic reaction to aminoglutethimide medications or substances, such as foods and preservatives. Before taking any new medications, including nonprescription medications, vitamins, and herbal medications, patients should notify their doctors. Michael Zuck, Ph.D.

Purpose Amitriptyline helps relieve various forms of depression and pain. However amitriptyline and other tricyclic antidepressants are increasingly being replaced by a newer and more effective group of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs). Amitriptyline is prescribed to treat and manage pain associated with the nerves (neuropathic pain), particularly post-herpetic neuralgia—the burning and stabbing nerve pains or aches that may last for months or years after an attack of shingles— and the tingling or burning sensation that results from cancer treatment. It is sometimes prescribed to treat various types of chronic pain, as well as eating disorders, and to prevent migraine headaches. Amitriptyline is usually taken at bedtime to help patients sleep better.

Description Amitriptyline increases the levels of neurotransmitters in the brain—the chemicals that transmit nerve messages—by blocking their reabsorption by neurons. U.S. brand names Amitriptyline is available in the United States as a generic drug in the form of 10-, 25-, 50-, 70-, and 150milligram (mg) tablets that are taken by mouth. It is also available in an injectable form. It was previously available under the brand names Endep and Elavil. Amitriptyline is also available in combination with chlordiazepoxide, an antianxiety drug, as Limbitrol and Limbitrol DS, and in combination with perphenazine, an antipsychotic, as Duo-Vil 2-10 and DuoVil 2-25. Canadian brand names    

Apo-Amitriptyline Levate Novo-Triptyn PMS-Amitriptyline International brand names

Amitriptyline Definition Amitriptyline is a member of a class of drugs known as tricyclic antidepressants. It is prescribed to treat depression and pain and to prevent migraine headaches. 74

      

Adepril Amicen Amilent Amilit Amineurin Amiplin Amiprin G A LE EN CY C LO PE DI A O F C AN C ER 3

                                    

Amitrip Amyline Amyzol Anapsique Domical Elatrol Elatrolet Enafon Etravil Lantron Laroxyl Larozyl Lentizol Miketorin Novoprotect Novotriptyn Pinsanu Pinsaun Quietal Redomex Saroten Retard Saroten Sarotena Sarotex Syneudon Teperin Trepiline Tridep Tripta Triptizol Trynol Tryptal Tryptanol Tryptine Tryptizol Trytomer Uxen Vanatripp

Recommended dosage The usual adult dose of amitriptyline for pain management is 10–150 mg taken at bedtime to help the patient sleep. Patients are generally started on a low dose that is increased as needed. However side effects may make it difficult to increase the dosage in older adults. G A LE EN CY C LO PE DI A O F C AN CE R 3

For treating depression the dosage of amitriptyline is usually 75–150 mg, less for teens and older adults. It is taken at bedtime or in up to four divided doses during the day. It should be taken at the same time every day. If the nightly dose is missed, an extra dose should not be taken the next morning. Patients should check with their doctors if the daily dose is skipped. However those taking amitriptyline more than once per day should take a missed dose as soon as it is noted, unless it is almost time for the next dose, in which case the missed one should be skipped. Patients should not take two doses at one time.

Precautions Patients should not stop taking amitriptyline abruptly; rather the dose should be gradually decreased before discontinuing. Stopping the drug abruptly may cause experience headache, nausea, lack of energy, discomfort throughout the body, and a worsening of the original symptoms. Amitriptyline’s effects last for three to seven days after the medication has been discontinued. Other precautions include: 









Taking amitriptyline during waking hours can result in noticeable side effects. Patients should not drive or operate machinery or appliances while taking amitriptyline. Injectable amitriptyline should not be used long-term; patients should switch to tablets as soon as possible. Patients may need to stop this medication before surgery. It is possible that a patient’s mental health may change in unexpected ways—including becoming suicidal—with amitriptyline or another antidepressant, especially when the medication is first started or the dose is changed. Pediatric

This medication should not be given to children under 12. It is generally not given to children under age 18. Children, adolescents, and young adults up to 24 years-of-age who take amitriptyline or other antidepressants for depression or mental illness may be somewhat more likely to have suicidal thoughts or to become suicidal, compared with those who do not take antidepressants as treatment for these conditions. Geriatric Older adults usually are more prone to some side effects of amitriptyline. Taking a lower dose may help resolve these. Amitriptyline can also increase the risk of falls in older adults. 75

Amitriptyline



Amitriptyline

Pregnant or breastfeeding Taking amitriptyline during pregnancy has been associated with fetal deformities. Therefore pregnant women should carefully discuss the risks and benefits of this medication with their doctor. Women should not breastfeed while taking amitriptyline because it is secreted into the milk and could affect the baby. Other conditions and allergies

        

Amitriptyline: should not be taken by anyone with allergies to the drug  should not be taken by patients recovering from a heart attack  may increase or decrease blood sugar levels in diabetics  may increase psychiatric symptoms in patients with schizophrenia 

Amitriptyline should be administered with caution to patients with: glaucoma seizures  urinary retention  overactive thyroid  poor liver or kidney function  alcoholism  asthma  digestive disorders  enlarged prostate  heart disease  

  

Taking this medication with food may decrease digestive side effects. Patients should avoid direct sunlight, wear protective clothing, and apply sunscreen with a protective factor of 15 or higher. Less common side effects of amitriptyline include:         

Common side effects associated with amitriptyline include: dry mouth  drowsiness  constipation  dizziness or lightheadedness when standing



   



Sucking on ice cubes or sugarless hard candy can combat dry mouth. Increased fiber in the diet and additional fluids may help with constipation. Dizziness is usually caused by a drop in blood pressure when changing position. Patients should rise slowly from a sitting or lying position if they experience dizziness. Other side effects of amitriptyline may include: blurred vision  increased appetite  weight gain 

76

muscle tremors nervousness impaired sexual drive or function sweating rash itching hair loss ringing in the ears changes in blood composition Symptoms of amitriptyline overdose may include:



Side effects

weakness or fatigue unpleasant taste in the mouth nausea diarrhea vomiting heartburn nightmares headaches pain, burning, or tingling in the hands or feet irregular or fast heartbeat or palpitations raising or lowering of blood pressure skin that is more sun-sensitive

     

irregular heartbeat drowsiness difficulty concentrating agitation confusion hallucinations muscle rigidity vomiting fever lowered body temperature seizures coma Geriatric

Older adults are usually more prone to some side effects of amitriptyline, especially:   

drowsiness blurred vision dry mouth G A LE EN CY C LO PE DI A O F C AN C ER 3

QUESTIONS TO ASK YOUR PHARMACI ST 

   

Will amitriptyline interact with any of my other prescription or over-the-counter medications? What time of day should I take amitriptyline? Should I take it with food? What if I miss a dose? Can I stop amitriptyline whenever I choose?



Amitriptyline has other interactions: 





    

difficulty urinating constipation dizziness mental confusion

Interactions Patients should always tell all of their doctors and dentists that they are taking this and all other medications. Patients should always tell their doctor and pharmacist about any and all prescription and nonprescription medications, vitamins, nutritional supplements, or herbal preparations that they are taking. They should not start any dietary supplements while taking amitriptyline without first consulting their physician. Amitriptyline should not be taken in combination with any other antidepressant. It should not be taken within 14 days of taking any monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). High fever, convulsions, and death can occur if amitriptyline is taken in combination with an MAOI. It is important to inform the doctor if the patient has stopped taking the antidepressant fluoxetine (Prozac, Sarafem) within the past 5 weeks. Amitriptyline should not be taken in combination with: 

 



 

epinephrine and other adrenaline-type drugs, as this can cause severe high blood pressure methylphenidate, a central nervous system stimulant cisapride (Propulsid; not available in the United States) Tagamet (cimetidine) or Neo-Synephrine, a nasal spray, because these can increase the blood levels and side effects of amitriptyline St. John’s wort (Hypericum perforatum) belladonna (Atropa belladonna)

G A LE EN CY C LO PE DI A O F C AN CE R 3

henbane (Hyoscyamus niger) scopolia (Scopolia carniolica)



Alcohol and other central nervous system depressants can increase drowsiness induced by amitriptyline. Alcohol blocks the antidepressive action of amitriptyline. Amitriptyline may decrease the effectiveness of some drugs used to treat high blood pressure. Amitriptyline may interact with valproate, which is used to treat the manic phase of bipolar disorder and seizures and to prevent migraines. Black tea may decrease the absorption of amitriptyline. There should be at least two hours between ingesting tea and the drug.

Resources BOOKS

Hales, Robert E., Stuart C. Yudofsky, and Robert H. Chew. What Your Patients Need to Know about Psychiatric Medications. Washington, DC: American Psychiatric Publishing, 2007. Stahl, S. M. Essential Psychopharmocology: The Prescriber’s Guide: Antidepressants. New York: Cambridge Uni versity Press, 2006. PERIODICALS

Berger, A., S. Mercadante, and G. Oster. ‘‘Use of Antiepi leptics and Tricyclic Antidepressants in Cancer Patients with Neuropathic Pain.’’ European Journal of Cancer Care 15, no. 2 (May 2006): 138 145. Frese, A., and S. Evers. ‘‘Pharmacologic Treatment of Cen tral Post Stroke Pain.’’ Clinical Journal of Pain 22, no. 3 (March 2006): 252 260. Miyasaki, J. M., et al. ‘‘Practice Parameter: Evaluation and Treatment of Depression, Psychosis, and Dementia in Parkinson Disease (an Evidence Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology.’’ Neurology 66, no. 7 (April 2006): 96 1002. Sterr, Andrea, et al. ‘‘Electroencephalographic Abnormal ities Associated with Antidepressant Treatment: A Comparison of Mirtazapine, Venlafaxine, Citalopram, Reboxetine, and Amitriptyline.’’ Journal of Clinical Psychiatry 67, no. 2 (February 2006): 325 326. Veldhuijzen, D. S., et al. ‘‘Acute and Subchronic Effects of Amitriptyline on Processing Capacity in Neuropathic Pain Patients Using Visual Event Related Potentials: Preliminary Findings.’’ Psychopharmacology 183, no. 4 (2006): 462 470. Weber Hamann, B., et al. ‘‘Resistin and Adiponectin in Major Depression: The Association with Free Cortisol and Effects of Antidepressant Treatment.’’ Journal of Psychiatric Research 41, nos. 3 4 (April June 2007): 344 350. 77

Amitriptyline



Amputation

Demographics

OTHER

American Society of Health System Pharmacists. ‘‘Ami triptyline.’’ MedlinePlus Drug Information. http:// www.nlm.nih.gov/medlineplus/druginfo/meds/ a682388.html ORGANIZATIONS

American Academy of Family Physicians, 11400 Tomahawk Creek Parkway, Leawood, KS, 66211 2680, (913) 906 6000, (800) 274 6000, (913) 906 6075, http://www.aafp. org/online/en/home.html. National Alliance on Mental Health, 2107 Wilson Blvd., Suite 300, Arlington, VA, 22201 3042, (703) 524 7600, (800) 950 NAMI, (703) 524 9094, http://www. nami.org. National Institute of Mental Health, 6001 Executive Boule vard, Room 8184, MSC 9663, Bethesda, MD, 20892 9663, (301) 443 4513, (866) 615 6464, (301) 443 4279, [email protected], http://www.nimh.nih.gov. National Mental Health Information Center, PO Box 2345, Rockville, MD, 20847, (240) 221 4021, (800) 789 2647, (240) 221 4295, http://mentalhealth.samhsa.gov. U.S. Food and Drug Administration, 10903 New Hamp shire Ave., Silver Spring, MD, 20993 0002, (888) INFO FDA, http://www.fda.gov.

Mark Mitchell, MD Ruth A. Wienclaw, PhD Margaret Alic, PhD

Amphotericin B see Antifungal therapy Amphotericin B liposomal see Antifungal therapy

Arms, legs, hands, feet, fingers, toes, and ears can be amputated. Many amputations involve small body parts such as a finger, rather than an entire limb. According to the National Limb Loss Information center, about surgical 134,000 limb amputations are performed in the United States each year. About 90% of these are due to problems associated with blood supply to the body part, and almost blood-supplyrelated amputations are of the lower limb. This category of amputations is increasing because of the increase in diabetes in the United States. Trauma is the second leading cause of amputation in the United States. About 30,000 traumatic amputations occur in United States each year. Of these, about 69% are amputations of an upper limb. Four of every five traumatic amputees are male, and most of them are between the ages of 15 and 30. The rate of traumatic amputations has been decreasing since the 1970s. Amputations due to cancer also have been decreased since the 1980s. A little over one-third of cancer-related amputations are either above or below the knee limb amputations. Congenital amputations, which are not surgical procedures but are birth defects, have remained steady since the 1970s at about 26 per 100,000 live births. Upper limb defects accounted for about 58% of all congenital amputations.

Precautions Amputations cannot be performed on patients with uncontrolled diabetes mellitus, heart failure, or infection. Patients with blood clotting disorders also are not good candidates for amputation.

Amputation Definition

Description

Amputation is performed for the following reasons:

The blood supply to an extremity can be cut off because of injury to the blood vessel, hardening of the arteries, arterial embolism, impaired circulation as a complication of diabetes mellitus, repeated severe infection that leads to gangrene (tissue death), severe frostbite, Raynaud’s disease, or Buerger’s disease. Most amputations in the United States, occur because of complications of diabetes and involve the lower limbs and feet. When the blood supply is cut off, the body part must be surgically removed in order to prevent more extensive tissue death and infection.

to remove tissue that no longer has an adequate blood supply  to remove malignant tumors  because of severe trauma to the body part

Traumatic amputation most often affects limbs and appendages such as the arms, ears, feet, fingers, hands, legs, and nose. Amputations may be partial (some tissue connects the amputated part to the

Amputation is the intentional surgical removal of a limb or body part. Traumatic amputation is the accidental severing of some or all of a body part. Congenital amputations are birth defects in which the child is born without a limb or missing part of a limb.

Purpose



78

G A LE EN CY C LO PE DI A O F C AN C ER 3

Amputation

Amputation Muscle layers Muscle incision

Bone incision

Skin incision

Femur

A.

B.

Proximal stump protected by gauze

C. Femoral artery

D.

Clamp on femoral vein

End of stump

E.

Sutures

Amputation of leg. A: The muscle is cut and the main artery exposed. B: The surgeon severs the main artery and veins. C: The surgeon saws through the femur bone. D: The muscles are sutured over the bone. (Illustration by Electronic Illustrators Group. Cengage Learning, Gale.)

body) or complete (the amputated part is completely severed from the body). Traumatic amputation begins with an accidental severing of the body part. Surgical amputation may follow when repair of the body part is not possible. G A LE EN CY C LO PE DI A O F C AN CE R 3

Some of the more common causes of traumatic amputations are accidents with lawnmowers, automobiles, motorcycles, power tools, and farm equipment. Amputations may be caused by sharp objects such as knives or blades (‘‘guillotine’’ amputation) or by heavy 79

Amputation

objects or mechanisms (crushing amputation). Crushing injuries are the more common cause of traumatic amputations. Traumatic amputations are a common injury to warfighters. Amputations can be either planned or emergency procedures. Injury and arterial embolisms are the main reasons for emergency amputations. The operation is performed under regional or general anesthesia by a general or orthopedic surgeon in a hospital operating room. Details of the operation vary slightly depending on what part is to be removed. The goal of all amputations is twofold: to remove diseased tissue so that the wound will heal cleanly, and to construct a stump that will allow the attachment of a prosthesis or artificial replacement part. The surgeon makes an incision around the part to be amputated. The body part is removed, and the bone is smoothed. A flap is constructed of muscle, connective tissue, and skin to cover the raw end of the bone. The flap is closed over the bone with sutures (surgical stitches) that remain in place for about one month. Often, a rigid dressing or cast is applied that stays in place for about two weeks.

Preparation Before an amputation is performed, extensive testing is done to determine the proper level of amputation. The goal of the surgeon is to find the place where healing is most likely to be complete, while allowing the maximum amount of limb to remain for effective rehabilitation. The greater the blood flow through an area, the more likely healing is to occur. Multiple tests are done that measure blood flow through the limb. Several or all of the following tests are done to help choose the proper level of amputation. measurement of blood pressure in different parts of the limb  xenon 133 studies, which use a radiopharmaceutical to measure blood flow  oxygen tension measurements in which an oxygen electrode is used to measure oxygen pressure under the skin. If the pressure is 0, the healing will not occur. If the pressure reads higher than 40mm Hg (40 milliliters of mercury), healing of the area is likely to be satisfactory.  laser Doppler measurements of the microcirculation of the skin  skin fluorescent studies that also measure skin microcirculation 

80





skin perfusion measurements using a blood pressure cuff and photoelectric detector infrared measurements of skin temperature

No single test is highly predictive of healing, but taken together, the results give the surgeon an excellent idea of the best place to amputate.

Aftercare After amputation, medication is prescribed for pain, and patients are treated with antibiotics to discourage infection. The stump is moved often to encourage good circulation. Physical therapy and rehabilitation are started as soon as possible, usually within 48 hours. Studies have shown that there is a positive relationship between early rehabilitation and effective functioning of the stump and prosthesis. Length of stay in the hospital depends on the severity of the amputation and the general health of the amputee, but ranges from several days to two weeks. Rehabilitation is a long, arduous process, especially for above the knee amputees. Twice daily physical therapy is common. In addition, psychological counseling is an important part of rehabilitation. Many people feel a sense of loss and grief when they lose a body part. Others are bothered by phantom limb syndrome, where they feel as if the amputated part is still in place. They may even feel pain in the limb that does not exist. Many amputees benefit from joining self-help groups and meeting others who are also living with amputation. Addressing the emotional aspects of amputation often speeds the physical rehabilitation process.

Risks Amputation is major surgery. All the risks associated with the administration of anesthesia exist, along with the possibility of heavy blood loss and the development of blood clots. Infection is of special concern to amputees. Infection rates in amputations average 15%. If the stump becomes infected, it is necessary to remove the prosthesis and sometimes to amputate a second time at a higher level. Failure of the stump to heal is another major complication. Nonhealing usually is due to an inadequate blood supply. The rate of nonhealing varies from 5–30% depending on the facility and the site of amputation. Centers that specialize in amputation usually have the lowest rates of complication. Most amputees experience some degree of persistent pain in the stump or phantom limb syndrome. About 80% of all amputees over age four experience tingling, itching, numbness, or pain in the place where G A LE EN CY C LO PE DI A O F C AN C ER 3

ORGANIZATIONS    





How long will I be I the hospital? What kind of rehabilitation will I need? How long will rehabilitation take? What kind of assistive devices are available to someone having my type of amputation? Can you refer me to someone who can assess the changes that may need to be made in my house/ apartment to accommodate my limitations? can you refer me to a support group for amputees?

the amputated part used to be. About 30% of amputees experience a sensation of the amputated part ‘‘telescoping’’ or shrinking into the viable part of the limb. Phantom sensations may begin immediately after the amputation, or they may develop months or years later. They often occur after an injury to the site of the amputation. Treatment of phantom limb pain is difficult. Finally, many amputees give up on the rehabilitation process and discard their prosthesis. Better fitting prosthetics and earlier rehabilitation have decreased the incidence of this problem. Researchers and prosthetic manufacturers continue to refine the materials and methods used to try to improve the comfort and function of prosthetic devices for amputees.

Results The five-year survival rate for all lower extremity amputees is less than 50%. For diabetic amputees, the rate is less than 40%. Up to 50% of people who have one leg amputated because of diabetes will lose the other leg within five years. Amputees who walk using a prosthesis have a less stable gait. Three to five percent of these people fall and break bones because of this instability. Although the fractures can be treated, about one-half of amputees who experience them then remain wheelchair-bound. Resources BOOKS

Cristian, Adrian Lower Limb Amputation: A Guide to Living a Quality Life New York: Demos Medical Pub., 2006. OTHER

‘‘Amputees.’’ Medline Plus August 12, 2009 [September 14, 2009]. http://www.nlm.nih.gov/medlineplus/ amputees.html. G A LE EN CY C LO PE DI A O F C AN CE R 3

American Diabetes Association, 1701 North Beauregard Street, Alexandria, VA, 22311, (800) DIABETES (342 2383), http://www.diabetes.org. Amputee Coalition of America, 900 East Hill Avenue, Suite 205, Knoxville, TN, 37915 2566, (865) 524 8772; TTY: (865) 525 4512, (888) AMP KNOW (888) 267 5669) , (865) 525 7917, http://www.amputee coalition.org. National Amputation Foundation, 40 Church Street, Mal verne, NY, 11565, (516) 887 3600, (516) 887 3667, amp [email protected], http://www.nationalamputation.org.

Tish Davidson, A.M.

Amsacrine Definition Amsacrine is an antitumor agent used to treat adult acute leukemia. It is no longer commercially available in the United States, although it is available in Canada.

Purpose Amsacrine is an investigational drug used to treat refractory acute lymphocytic and nonlymphocytic leukemias, Hodgkin’s disease, and non-Hodgkin’s lymphoma. It may also have some activity against head and neck cancers.

Description Amsacrine inhibits the synthesis of DNA. It also inhibits the enzyme responsible for cutting the strands of DNA, and untwists DNA so that replication of DNA cannot occur.

Recommended dosage The dose for amsacrine may be different depending on the protocol used by the physician. The drug is given through the vein as a 30- to 90- minute infusion or as a 24-hour continuous infusion. Example doses for adults are: 60–160 mg per square meter of body surface area every three to four weeks, or 40–120 mg per square meter of body surface area for five to seven days every three to four weeks. The dose for children is 120–150 mg per square meter of body surface area per day for five days. The dose of amsacrine is usually decreased in patients with decreased kidney or liver function. 81

Amsacrine

QUESTIONS TO ASK YOUR DOCTOR

‘‘Amputation, Traumatic.’’ MedlinePlus July 29, 2008 [Sep tember 14, 2009]. http://www.nlm.nih.gov/medline plus/ency/article/000006.htm.

Anagrelide

Precautions

Purpose and description

Amsacrine is usually given with caution to patients with underlying heart disease, severe kidney or liver disease, or to patients who have received high doses of anthracycline chemotherapy drugs, such as doxorubicin.

Anagrelide reduces the platelet count in patients with blood disorders.

Although the effects of amsacrine treatment on children are currently unknown, caution is still indicated. Women of childbearing age should take precautions to prevent pregnancy while on this drug. Women should not breastfeed while taking this medication.

Adult patients taking anagrelide should receive 0.5 mg of the drug four times daily or one mg twice daily. Based on the response to therapy, the dose of anagrelide can be increased by 0.5 mg per day every seven to 14 days if necessary. The goal is to maintain platelets at a count of less than 600,000 at the lowest dose of the drug possible to keep side effects at a minimum.

Side effects Toxicity to the heart is a common side effect of amsacrine, and patients receiving this drug are usually very closely monitored by their physician. Other common side effects of amsacrine include nausea and vomiting, diarrhea, ulcerations of the mouth and the gastrointestinal tract, decreased white blood cells and platelets, and decreased liver function. Patients may notice orange-red discoloration of the urine, but should not be alarmed as this is normal. The urine will clear again once all the drugs have been eliminated from the body. Other common side effects include headache, dizziness, confusion, seizures, abnormal touch sensation such as burning and prickling, and blurred vision. As with any side effects that occur while taking any medications, patients should notify their doctor or nurse immediately.

Recommended dosage

Precautions Patients with heart disease should be given anagrelide with caution. Anagrelide should be given with caution, if at all, in patients taking drugs that affect platelet aggregations such as aspirin, clopidrogel, ticlopodine, or non-steroidal agents. Pregnant mothers should be warned that anagrelide administration may cause fetal abnormalities. Pregnant patients should consult their physician about the current state of knowledge regarding risks and alternatives before beginning administration of anagrelide. Female patients of childbearing age should attempt to avoid pregnancy while taking this drug. Mothers who are nursing should discontinue nursing while taking this drug.

Interactions To prevent any drug interactions, patients should consult their physician, nurse, or pharmacist prior to taking any over-the-counter medications, herbal medications, or new medications. Many physicians recommend bringing the containers with the names of the drugs to an appointment. Michael Zuck, Ph.D.

Side effects The most common side effects of anagrelide are palpitations, fluid gain resulting in swelling, headaches, dizziness, diarrhea, stomach discomfort, mild to moderate nausea, passing gas, weakness, shortness of breath, and decreased platelets. Less common side effects of anagrelide include increased heart rate and chest pain, malaise, rash, vomiting, and decreased appetite. As with all medications, patients should contact their physician or nurse if any of these side effects occur.

Interactions

Anagrelide Definition Anagrelide, also known by the brand name Agrylin, is used to treat patients with thrombocytosis, a condition in which patients have too many platelet cells in their blood. Platelets are a cell type formed in the bone marrow that are involved in the blood clotting process. 82

There are no proven interactions between anagrelide and other drugs. The drug sucralfate may interfere with the absorption of anagrelide. Prior to starting any over-the-counter medications, herbal medications, or new medications, patients should consult their physician, nurse, or pharmacist to prevent drug interactions. Michael Zuck, Ph.D. G A LE EN CY C LO PE DI A O F C AN C ER 3

Anal cancer



bleeding from the anus (most common presenting symptom)



pain around the anus



the sensation of anal pressure or a mass



anal itching



anal discharge



straining to pass stool (rectal tenesmus)



change in diameter of stool



swollen lymph nodes in the anal and/or groin areas



About 30% of patients complain of pain or the sensation of a rectal mass at the time of diagnosis.

Definition Anal cancer is an uncommon cancer occurring in the tissues that make up the opening through which stool passes out of the body.

Description The anus is the opening at the end of the large intestine (rectum) through which solid waste passes out of the body. The anus is a junction between two types of tissues: mucosa, which lines the intestines, and skin. Cancer located at the junction between the rectum and anus is called ‘‘anal canal cancer’’ (also known as transitional cell, squamous, epidermoid, or basal cell cancer). Cancer located near the external skin is called ‘‘anal margin cancer.’’ Anal canal cancer is more common in women, and anal margin cancer is more common in men.

Demographics Approximately 5,070 new cases of anal cancer were diagnosed in the United States in 2008. Less than 700 Americans died as a result of anal cancers in 2008. Anal cancer accounts for about 2% of the cancers of the digestive system. Although anal cancer is considered to be a rare type of cancer, incidence rates of anal cancer are rising in the United States. The average age at diagnosis is in individuals over 50 years old. Most anal cancers are squamous cell carcinomas. Women are much more likely than men to develop anal cancer. Anal cancer is more prevalent in Caucasians than other races.

Causes and symptoms Risk factors Risk factors associated with anal cancer include: 



 



Human papilloma virus (HPV) infection (presence of anal-genital warts, history of receptive anal intercourse or presence of sexually transmitted disease (STD), history or cervical, vulvar, or vaginal cancer, immunosuppression as a result of organ transplantation or human immunodeficiency virus (HIV) infection, current smoker or history of smoking

Currently, in 2009, it is believed that the association between anal cancer and persistent infection with the HPV-16 virus is the strongest association. G A LE EN CY C LO PE DI A O F C AN CE R 3

Diagnosis Examination According to the 2009 National Comprehensive Cancer Network Clinical Practice Guidelines for Anal Cancer, the clinical evaluation of patients with suspected anal canal or anal margin cancer are the same except that a positron emission scan (PET scan) is not included in the workup for anal margin cancers. To diagnose anal cancer, the physician will first examine the skin of the anus and then will perform a digital rectal examination by inserting a greased, gloved finger into the rectum to feel for lumps. He or she will look for blood on the glove. If a lump is felt, a small sample of the lump will be removed (biopsy) through a small endoscope (flexible viewing instrument) to examine the tissue under a microscope. Procedures The biopsy may be performed using local anesthesia in the physician’s office. The physician will also carefully palpate the lymph nodes in the groin area. If inguinal lymph node involvement is suspected, a biopsy by fine needle aspiration (FNA) may be performed. Another alternative procedure which may be performed is an excisional biopsy of enlarged or suspicious lymph nodes. Although the diagnosis of anal cancer can be made by the examination alone, the cancer may be further evaluated by conducting other procedures. Endoscopic examinations of the anus (anoscopy) may be performed to see the tumor. Endorectal ultrasound, in which a wand-like ultrasound probe is inserted into the anus, enables the physician to determine how deep the tumor lies and whether or not nearby organs have been affected. 83

Anal cancer

Symptoms of anal cancer may include:

Anal cancer

Tests Other possible diagnostic procedures include x ray and/or computed tomography (CT scan) to detect tumor spread (metastasis). A PET scan may be ordered even if lymph nodes appear normal-sized on the CT scan. HIV testing and measurement of CD4 levels are also recommended at the time of diagnosis. It is also recommended that women undergo a gynecologic examination at the time of diagnosis to include cervical cancer screening due to the strong association of anal cancer and HPV infection.

Treatment team The treatment team for anal cancer may include a colorectal surgeon, gastroenterologist, oncologist, radiation oncologist, nurse oncologist, psychiatrist, psychological counselor, and social worker.

Clinical staging, treatments, and prognosis Clinical staging Most anal tumors are staged based on the size of the primary tumor as noted on direct examination and then confirmed microscopically. The American Joint Committee on Cancer (AJCC) Staging System is used to stage anal cancers. Anal canal cancer is categorized into five stages (0, I, II, III, and IV) which may be further subdivided (A and B) based on the depth or spread of cancerous tissue. This staging system does not apply to anal melanomas or sarcomas. Seventyfive percent of anal cancer patients have stage I or stage II disease. The stages of anal cancer are: Stage 0. Cancer has not spread below the limiting membrane of the first layer of anal tissue.  Stage I. Cancer is 2 cm (approximately 0.75 in) or less in greatest dimension and has not spread anywhere else.  Stage II. Cancer is between 2 and 5 cm in diameter and has spread beyond the topmost layer of tissue. There is no evidence of regional lymph node metastasis or distant metastasis.  Stage IIIA. Cancer has spread to adjacent organs (e.g. vagina, bladder) or to the perirectal lymph nodes. Tumor may be of any size.  Stage IIIB. Cancer has spread to nearby lymph nodes in the abdomen or groin or has spread to both adjacent organs and perirectal lymph nodes. Tumor may be of any size.  Stage IV. Cancer has spread to distant abdominal lymph nodes or to distant organs in the body. 

84

The AJCC Staging System for skin cancer is used to stage anal margin cancers as anal margin cancers are biologically comparable to other skin cancers. Treatments The specific treatment depends on the stage of cancer, type of cancer, and the age and overall health of the patient. Anal cancer is most frequently treated with a combination of radiation therapy and chemotherapy. Current recommendations for the primary treatment of anal cancers do not involve surgical excision. Radiation therapy uses high-energy radiation from x rays and gamma rays to kill the cancer cells. Radiation given from a machine that is outside the body is called external radiation therapy. Radiation given internally is called internal radiation therapy or brachytherapy. Sometimes applicators containing radioactive compounds are placed directly into the cancerous lesion (interstitial radiation). The skin in the treated area may become red and dry and may take as long as a year to return to normal. Fatigue, upset stomach, diarrhea, and nausea are also common complaints of patients having radiation therapy. Women may develop vaginal narrowing (stenosis) caused by radiation therapy in the pelvic area, which makes intercourse painful. Radiation may injure the anal sphincter and may cause anal ulcers and anal stenosis. Chemotherapy uses anticancer drugs to kill the cancer cells. The drugs are given by mouth (orally) or intravenously. They enter the bloodstream and can travel to all parts of the body to kill cancer cells. Generally, a combination of drugs is given because it is more effective than a single drug in treating cancer. The side effects of chemotherapy are significant and include stomach upset, vomiting, appetite loss (anorexia), hair loss (alopecia), mouth sores, and fatigue. Women may experience vaginal sores, menstrual cycle changes, and premature menopause. There is also an increased chance of infections. In the past, patients with invasive anal cancers were treated surgically with abdominoperineal resection. This procedure is typically no longer recommended as a primary treatment for anal cancer because local recurrence rates were high, five year survival rates were limited and because of the physical and psychological complications associated with a permanent colostomy. Concurrent chemoradiation (chemoRT) alone is the recommended primary treatment for patients with anal canal cancer. Anal canal cancer is treated with the G A LE EN CY C LO PE DI A O F C AN C ER 3

Prognosis Prognosis of anal cancer is related to the size of the primary tumor and the presence of lymph node involvement. For most people, anal cancer is considered a curable disease. Most (60-70%) of anal tumors are in the early stages (stage 1 or II) at the time of diagnosis. Tumors that are located in the anal canal, are less than 2 cm in diameter, and are well-differentiated have a favorable prognosis with a five year survival rate of approximately 80% after treatment with chemoRT. The five year survival rate for patients with tumors larger than 5cm at the time of diagnosis is less than 50% currently. Patients with lymph node involvement of the tumor at the time of diagnosis have a five year survival rate of 10-40%. Anal cancer can spread locally and invade other pelvic organs such as the vagina, prostate gland, and bladder. Anal cancer that spreads through the bloodstream (hematogenous spread) most often metastasizes to the liver and lungs.

Alternative and complementary therapies Although alternative and complementary therapies are used by many cancer patients, very few controlled studies on the effectiveness of such therapies exist. Mind-body techniques such as prayer, biofeedback, visualization, meditation, and yoga have not demonstrated any effect in reducing cancer but can reduce stress and have been shown to lessen some of the side effects of cancer treatments.

Coping with cancer treatment The patient should consult their treatment team regarding any side effects or complications of treatment. Many of the side effects of chemotherapy can be relieved by medications. Vaginal stenosis can be prevented and treated by vaginal dilators, gentle douching, and sexual intercourse. A water-soluble lubricant may be used to make sexual intercourse more comfortable. Patients should consult a psychotherapist and/or join a support group to deal with the emotional consequences of cancer and its treatment. G A LE EN CY C LO PE DI A O F C AN CE R 3

Clinical trials As of 2009, there are about ten active clinical trials that are specifically studying anal cancer. There are other trials underway that include all types of gastrointestinal cancers, which may include anal cancer. Patients should consult with their treatment team to determine if they are candidates for any ongoing studies. The National Cancer Institute also provides information on clinical trials, and can be reached at (800) 4-CANCER or at http://www.cancer.gov/clinicaltrials/search.

Prevention There is moderately strong evidence linking anal cancer with human immunodeficiency virus (AIDS) infection, cigarette smoking, or long term use of corticosteroids. Other factors that are strongly associated with the development of anal cancer include: 









Anogenital warts. Warts in and around the genitals and anus are found in 20% of women and heterosexual men and in 50% of homosexual men with anal cancer. Sexual activity. Having more than 10 sexual partners or being the recipient of anal intercourse increases the risk of developing anal cancer. Infections. Infection by sexually transmitted microbes, such as human papilloma virus HPV, herpesvirus, Neisseria gonorrhoeae, or Chlamydia trachomatis, places one at a higher risk of developing anal cancer. Gynecologic cancer. Women with a history of vaginal, vulvar, or cervical cancer are at risk of developing anal cancer. This risk is not due to therapeutic radiation exposure for gynecologic cancer. Chronic immunosuppression. The long-term use of drugs by organ transplant recipients to suppress the immune system increases the chance of developing a squamous carcinoma, such as anal cancer.

Because anal cancer is believed to be caused by HPV, like cervical cancer, it may be a preventable disease. Practicing safe-sex methods should help to prevent anal cancer. Persons who are at a high risk of developing anal cancer may benefit from routine screening by a physician.

Special concerns The effect of pelvic radiation therapy on fertility can be a concern for both men and women. The need for a colostomy raises many issues, including those related to body image and self esteem. See also Fertility issues. 85

Anal cancer

chemotherapy drugs 5-FU and mitomycin administered concurrently with radiation therapy. Anal margin tumors can be treated with either local surgical excision or chemoRT depending on the clinical stage of the tumor. Inclusion of bilateral inguinal/pelvic lymph nodes in the radiation field is recommended in the treatment of cancers that are more advanced.

Anemia

Q U E S T I O N S T O A S K TH E DOC TOR

National Institutes of Health. National Cancer Institute. 9000 Rockville Pike, Bethesda, MD 20982. (800) 4 CANCER. http://www.cancer.gov. OTHER

  

  











  

What type of cancer do I have? What stage of cancer do I have? What is the 5 year survival rate for persons with this type and stage of cancer? Has the cancer spread? What are my treatment options? What are the risks and side effects of these treatments? What medications can I take to relieve treatment side effects? Are there any clinical studies underway that would be appropriate for me? What effective alternative or complementary treatments are available for this type of cancer? How debilitating is the treatment? Will I be able to continue working? Are there any local support groups for anal cancer patients? What is the chance that the cancer will recur? Is there anything I can do to prevent recurrence? How often will I have follow-up examinations?

Resources BOOKS

Cummings, B.J., Ajani, J.A., & Swallow, C.J. ‘‘Cancer of the Anal Region.’’ In Cancer: Principles & Practice of Oncology 8th edition, edited by DeVita, V.T., Lawrence, T.S., and Rosenberg,S.A. Philadelphia: Lippincott Williams & Wilkins, 2008. PERIODICALS

Daling, J.R., Madeleine, M.M., Godefroy, J.L, et al. ‘‘Human Papilloma Virus, Smoking, and Sexual Practices in the Etiology of Anal Cancer.’’ Cancer 101 (2004):270 289. Dezube,B.J. ‘‘HIV associated Anal Squamous Cell Cancer: An Otherwise Preventable Disease.’’ J Clin Oncol 24(2006):4516 4517. Uronis, H.E., Bendell, J.C.‘‘Anal Cancer: An Overview.’’ Oncologist 12(2007):534 534. ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta, GA 30329. (800) ACS 2345. http://www.cancer.org. Cancer Research Institute, National Headquarters. One Exchange Plaza, 55 Broadway, Suite 1802 New York, NY 10006. (800) 992 2623. http://www.cancer research.org. 86

‘‘Anal Cancer.’’National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology2009[cited June 19, 2009]. http://www.nccn.org.

Belinda Rowland, Ph.D. Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Anastrozole see Aromatase inhibitors

Anemia Description Anemia is characterized by an abnormally low number of red blood cells in the circulating blood. It frequently affects patients with cancer. In fact, in many cancer diagnoses such as multiple myeloma and acute leukemia, the presence of anemia may be what initially prompts a doctor to suspect an underlying tumor (neoplasm). Whether or not anemia develops depends on the type of cancer found, the treatment used, and the presence or absence of other underlying medical disorders. Symptoms of malignancy-associated anemia may range from weakness, paleness, and fatigue to shortness of breath and increased heart rate. Symptoms of anemia can compromise a patient’s ability to tolerate treatment, and may severely interfere with activities of daily living. Anemia may be particularly problematic in older individuals with cancer. The incidence and severity of anemia tends to increase as the cancer progresses. Blood is comprised of three major cell types: white blood cells, which help the body fight infection; platelets, which help the blood to clot when necessary; and red blood cells, which transport oxygen from the lungs to the tissues in the body, and then transport carbon dioxide from those tissues back to the lungs. This exchange is enabled by the most important component of red blood cells—the protein called hemoglobin that binds easily to oxygen and carbon dioxide. Red blood cells are produced in the bone marrow through a process called erythropoiesis. When the bone marrow functions normally, it continuously replaces red blood cells to maintain a normal level that allows for adequate oxygenation of the tissues. G A LE EN CY C LO PE DI A O F C AN C ER 3

Causes The causes of anemia are multiple, and often the factors act in conjunction with one another. Generally, anemia may result from a direct effect of a cancerous tumor, or from an indirect effect of the tumor. The cancer process may directly cause anemia through two main mechanisms: blood loss or bone marrow replacement. However, most cases of anemia in cancer patients result from the indirect effects of the cancer. Direct effects of the tumor Anemia is a frequent complication of cancers due to bleeding. Cancers of the head and neck, the gastrointestinal and genitourinary system, and the cervix are frequently associated with endogenous bleeding, or bleeding that occurs within the body. Bleeding occasionally develops within the tumor itself, particularly in sarcomas, melanomas, and ovarian and liver carcinomas. A second direct cause of anemia in cancer is bone marrow replacement, which inhibits the body’s ability to appropriately produce red blood cells. Certain cancers, such as acute leukemia, lymphoma and myeloma, directly suppress bone marrow function, thereby causing anemia. Other types of cancer, such as prostate or breast cancer, often spread to the bone marrow, inhibiting red blood cell production by actually replacing the bone marrow itself. Indirect effects of the tumor Anemia of chronic disease, also called anemia of malignancy, is the most common type of anemia seen in individuals with cancer. It is a diagnosis made only after other possible causes are ruled out and if very specific conditions are met. The presence of low levels of iron coupled with normal levels of storage iron helps distinguish anemia of chronic disease from iron deficiency anemia. Factors that cause anemia of chronic disease are not entirely clear. However, it is believed that cytokines (non-antibody proteins) produced by the tumor reduce production of and impair responsiveness to erythropoietin. Typically, this type of anemia develops slowly. Rapid development of anemia may indicate another cause. Treatments used to manage cancer have been implicated in the development of anemia in cancer G A LE EN CY C LO PE DI A O F C AN CE R 3

patients. Radiation therapy to large areas of bone marrow, as in the hip area, may suppress bone marrow function and lead to anemia. Chemotherapy can also cause bone marrow suppression, and some drugs specifically target red blood cell production. Studies have shown that 10% to 40% of patients taking cisplatin develop significant anemia. Cisplatin, a chemotherapy drug with potentially toxic effects to the kidneys, is believed to reduce the production of the hormone erythropoietin in the kidneys. Although most treatment-induced bone marrow suppression is short term, there is some evidence to support the possibility of long-term problems with blood cell production. Treatment can increase the risk of anemia in other ways. Chemotherapy, for example, causes bone marrow suppression that may reduce the immune system’s ability to fight off opportunistic infection. The resulting infections can impact the bone marrow’s functioning, possibly leading to the development of anemia. Hemolytic anemia is a type of anemia in which the red blood cell has a shortened life span (normal life span is 90-120 days). Because the bone marrow is not able to compensate by producing more red blood cells, anemia results. Abnormalities in the red blood cells may originate in the body (intrinsic) or may be caused by environmental factors such as auto-antibodies to red blood cells or damage from chemotherapy. Although one factor may have a greater influence, it is important to realize that several factors may be causing anemia. For example, approximately 70% of patients with multiple myeloma are anemic at the time of diagnosis. Anemia in these cases is caused by a combination of mechanisms including bone marrow replacement with cancer cells, bone marrow suppression from chemotherapy, and impaired production of erythropoietin.

Treatments Treatment of the anemia is directed at the underlying cause. In many cases, treating or removing the cancer corrects the red blood cell deficit. Management of autoimmune hemolytic anemia, which can be associated with chronic lymphocytic leukemia, may range from the administration of corticosteroids to the surgical removal of the spleen. More commonly, cancerrelated anemias are treated with blood transfusions and/or a drug called epoetin alfa. Blood transfusions Blood transfusions have been the principle treatment for anemia for many years. Until the 1960s, only whole blood was given. Then, methods of separating 87

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The hormone erythropoietin stimulates red blood cell production and sends a message to the bone marrow to increase production when oxygen levels in the body are low. This mechanism is often impaired in patients with cancer.

Angiogenesis inhibitors

whole blood were devised, allowing only particular components, such as platelets, red blood cells, or plasma, to be transfused. Blood transfusions are not without risk, and must be used carefully. Many patients react to the white blood cell antigens by developing a fever. This is so common that patients are routinely premedicated to prevent fever from developing. Individuals with longterm transfusion needs, such as patients with leukemia, may be given blood products with a reduced number of white blood cells to reduce the risk of sensitization to transfused blood. Cytomegalovirus (CMV) is a virus that may be present in blood products. Although it has no effect on individuals with normally functioning immune systems, cancer patients often have a diminished ability to fight infection. These patients may be at risk for CMV if they are CMV negative and receive CMVpositive blood. Transfusion-associated graft-versus-host disease (TA-GvHD) is another risk factor associated with blood transfusions in cancer patients. Although it is very rare, it is often fatal. With TA-GvHD, the patient’s immune system does not recognize the white blood cells in the donor blood as ‘‘nonself.’’ The donor white blood cells, however, recognize the patient as ‘‘nonself,’’ and an immune-mediated reaction ensues. To prevent this reaction in at-risk patients, blood may be irradiated prior to transfusion. Epoetin alfa As mentioned previously, erythropoietin is a protein produced in the kidneys that stimulates red blood cell production. Using DNA technology, this hormone has been replicated to create the drug epoetin alfa for the treatment of anemia in select cancer patients. (The drug is also called erythropoietin.) The use of this drug in the cancer setting has shown great promise, both in the treatment of cancer-related anemia, and in the reduction in the need for blood transfusion. However, epoetin alfa therapy is not advisable for everyone. This drug is not recommended for use in cancer-related anemia caused by bleeding, hemolysis, or iron deficiencies. Nor is it recommended for patients with hypertension or albumin sensitivity. Because no human studies are available to determine its effect on a fetus, women taking epoetin alfa should take measures to prevent pregnancy. Cancer patients with anemia who are undergoing chemotherapy may benefit from this drug. Studies have shown an increased hematocrit (the volume 88

percentage of red blood cells in whole blood) level and a decreased need for blood transfusions after the first month of therapy in this population. Epoetin alfa may be injected up to three times a week, and throughout therapy, blood cell counts are monitored closely. In 2004, it was reported that a form of the drug could be injected only once every two weeks in some cancer patients with the same effect, making its use more convenient. Resources BOOKS

Abeloff, M., et al., editors. ‘‘Hematopoietic Dysfunction by Hematologic Lineage.’’ In Clinical Oncology. 2nd ed. New York: Churchill Livingstone Publishers, 2000. Lee, G., and C. Bennett, editors. ‘‘Nonmetastatic Effects of Cancer: Other Systems.’’ In Cecil Textbook of Medicine. 21st ed. Philadelphia, PA: W. B. Saunders Co., 2000. Lee, G., et al., editors. Wintrobe’s Clinical Hematology. Baltimore, MD: Williams & Wilkins Publishing, 1999. PERIODICALS

‘‘Studies: Aranesp Dosed Semiweekly Is Comparable to Epoetin Alfa Once a Week.’’ Obesity, Fitness & Well ness Week July 10, 2004:59.

Tamara Brown, R.N. Teresa G. Odle

Angiogenesis inhibitors Definition Angiogenesis inhibitors are medicines that stop the formation of new blood vessels in and around cancerous tumors.

Description Angiogenesis inhibitors are a group of medicines that prevent the formation of tiny new blood vessels to the area of cancerous tumors. Angiogenesis refers to the ability of cancer cells to form new blood vessels that invade the tumor and other surrounding areas. Tumors need a blood supply to nourish the cancer cells, and as tumors grow they must constantly form new blood vessels. These blood vessels are also used by the cancer cells to metastasize or spread the cancerous cells from one area to the next. Angiogenesis inhibitors are important because the scientific theory is that if one can remove and/or prevent the formation of new blood vessels in the tumors, the cancer cells will not be able to grow any further. This could cause the tumors G A LE EN CY C LO PE DI A O F C AN C ER 3

Nancy J. Beaulieu, RPh., BCOP

Angiography

arteries and veins) in the brain; and to diagnose problems with the retina of the eye. It is also used to give surgeons an accurate ‘‘map’’ of the heart prior to openheart surgery, or of the brain prior to neurosurgery.

Precautions Patients with kidney disease or injury may suffer further kidney damage from the contrast mediums used for angiography. Patients who have blood clotting problems, have a known allergy to contrast mediums, or are allergic to iodine, a component of some contrast mediums, may also not be suitable candidates for an angiography procedure. Because x rays carry risks of ionizing radiation exposure to the fetus, pregnant women are also advised to avoid this procedure.

Definition Angiography is the x-ray study of the blood vessels. An angiogram uses a radiopaque substance, or dye, to make the blood vessels visible under x ray. Arteriography is a type of angiography that involves the study of the arteries.

Purpose Angiography is used to detect abnormalities or blockages in the blood vessels (called occlusions) throughout the circulatory system and in some organs. The procedure is commonly used to: identify atherosclerosis; diagnose heart disease; evaluate kidney function and detect kidney cysts or tumors; detect an aneurysm (an abnormal bulge of an artery that can rupture and lead to hemorrhage), tumor, blood clot, or arteriovenous malformations (abnormal tangles of

Description Angiography is usually performed at a hospital by a trained radiologist and assisting technician or nurse. It takes place in an x-ray or fluoroscopy suite, and for most types of angiograms, the patient’s vital signs will be monitored throughout the procedure. Angiography requires the injection of a contrast dye that makes the blood vessels visible to x ray. Tissues such as bones and blood vessels absorb x rays as they pass through the body. They show up with a clear, white outline when captured on film. The dye is injected through a procedure known as arterial puncture. The puncture is usually made in the groin area, inside elbow, or neck. The site is cleaned with an antiseptic agent and injected with a local anesthetic. First, a small incision is made in the skin to help the needle pass. A needle containing an inner wire called a stylet is inserted through the skin into the artery. When the radiologist has punctured the artery with the needle, the stylet is removed and replaced with another long wire called a guide wire. It is normal for blood to spout out of the needle before the guide wire is inserted. The guide wire is fed through the outer needle into the artery and to the area that requires angiographic study. A fluoroscopic screen that displays a view of the patient’s vascular system is used to pilot the wire to the correct location. Once it is in position, the needle is removed and a catheter is slid over the length of the guide wire until it to reaches the area of study. The guide wire is removed and the catheter is left in place in preparation for the injection of the contrast medium, or dye.

An angiogram of a coronary artery. (Copyright CNRI/Phototake NYC. Reproduced by permission.)

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Depending on the type of angiography procedure being performed, the contrast medium is either injected by hand with a syringe or is mechanically 89

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to stay the same size or shrink. In addition, it may be possible to prevent the tumors from spreading by cutting off their ability to invade other surrounding areas through these newly formed blood vessels. There are a few drugs today thought to work as angiogenesis inhibitors, such as thalidomide. Additional agents being studied in ongoing oncology clinical trials.

Angiography

K E Y TE R M S Arteriosclerosis—A chronic condition characterized by thickening and hardening of the arteries and the buildup of plaque on the arterial walls. Arteriosclerosis can slow or impair blood circulation. Carotid artery—An artery located in the neck.

Fluoroscopic screen—A fluorescent screen which displays moving x rays of the body. Fluoroscopy allows the radiologist to visualize the guide wire and catheter he is moving through the patient’s artery.

Catheter—A long, thin, flexible tube used in angiography to inject contrast material into the arteries. Cirrhosis—A condition characterized by the destruction of healthy liver tissue. A cirrhotic liver is scarred and cannot break down the proteins in the bloodstream. Cirrhosis is associated with portal hypertension. Computed tomography (CT)—A non-invasive diagnostic tool radiologists may use instead of x-ray angiography.

Guide wire—A wire that is inserted into an artery to guide a catheter to a certain location in the body.

Embolism—A blood clot, air bubble, or clot of foreign material that travels and blocks the flow of blood in an artery. When blood supply to a tissue or organ is blocked by an embolism, infarction, or death of the tissue the artery feeds, occurs. Without immediate and appropriate treatment, an embolism can be fatal. Femoral artery—An artery located in the groin area that is the most frequently accessed site for arterial puncture in angiography. Fluorescein dye—An orange dye used to illuminate the blood vessels of the retina in fluorescein angiography.

injected with an automatic injector connected to the catheter. An automatic injector is used frequently because it is able to propel a large volume of dye very quickly to the angiogram site. The patient is warned that the injection will start, and instructed to remain very still. The injection causes some mild to moderate discomfort. Possible side effects or reactions include headache, dizziness, irregular heartbeat, nausea, warmth, burning sensation, and chest pain, but they usually last only momentarily. To view the area of study from different angles or perspectives, the patient may be asked to change positions several times, and subsequent dye injections may be administered. During any injection, the patient or the camera may move. Throughout the dye injection procedure, x-ray pictures and/or fluoroscopic pictures (moving x rays) will be taken. Because of the high pressure of arterial blood flow, the dye will dissipate through the patient’s 90

Ischemia—A lack of normal blood supply to a organ or body part because of blockages or constriction of the blood vessels. Magnetic resonance imaging (MRI)—A non-invasive diagnostic tool radiologists may use instead of x-ray angiography. MRI scans use magnetic waves to create a picture of structures in the body. Necrosis—Cellular or tissue death; skin necrosis may be caused by multiple, consecutive doses of radiation from fluoroscopic or x-ray procedures. Plaque—Fatty material that is deposited on the inside of the arterial wall. Portal hypertension—A condition caused by cirrhosis of the liver. It is characterized by impaired or reversed blood flow from the portal vein to the liver, an enlarged spleen, and dilated veins in the esophagus and stomach. Portal vein thrombosis—The development of a blood clot in the vein that brings blood into the liver. Untreated portal vein thrombosis causes portal hypertension.

system quickly, so pictures must be taken in rapid succession. An automatic film changer is used because the manual changing of x-ray plates can eat up valuable time. Once the x rays are complete, the catheter is slowly and carefully removed from the patient. Pressure is applied to the site with a sandbag or other weight for 10 to 20 minutes in order for clotting to take place and the arterial puncture to reseal itself. A pressure bandage is then applied. Most angiograms follow the general procedures outlined above, but vary slightly depending on the area of the vascular system being studied. In addition to x rays, technological advances have allowed physicians to use other diagnostic tools for angiography, such as computed tomography (CT) scans and magnetic resonance imaging (MRI). A variety of common angiography procedures are outlined below: G A LE EN CY C LO PE DI A O F C AN C ER 3

 





Did you see any abnormalities? How long will I need to stay in the hospital? How many days until I can resume normal activities? When can I resume any medications that were stopped? What future care will I need?

Cerebral angiography Cerebral angiography is used to detect aneurysms, blood clots, and other vascular irregularities in the brain. The catheter is inserted into the femoral artery (the main artery of the thigh) or the carotid artery in the neck, and the injected contrast medium travels through the blood vessels of the brain. Patients frequently experience headache, warmth, or a burning sensation in the head or neck during the injection portion of the procedure. A cerebral angiogram takes two to four hours to complete. Coronary angiography Coronary angiography is administered by a cardiologist with training in radiology or, occasionally, by a radiologist. The arterial puncture is typically given in the femoral artery, and the cardiologist uses a guide wire and catheter to perform a contrast injection and x-ray series on the coronary arteries (arteries that supply the heart with oxygenated blood). The catheter may also be placed in the left ventricle to examine the mitral and aortic valves of the heart. If the cardiologist requires a view of the right ventricle of the heart or of the tricuspid or pulmonic valves, the catheter will be inserted through a large vein and guided into the right ventricle. The catheter also serves the purpose of monitoring blood pressures in these different locations inside the heart. The angiogram procedure takes several hours, depending on the complexity of the procedure. Some cardiologists prefer to use a compbination of CT and x-ray angiography to study the heart.

Kidney angiography Patients with chronic renal disease or injury can suffer further damage to their kidneys from the contrast medium used in a kidney angiogram, yet they often require the test to evaluate kidney function. These patients should be well-hydrated with a intravenous saline drip before the procedure, and may benefit from available medications (e.g., dopamine) that help to protect the kidney from further injury due to contrast agents. During a kidney angiogram, the guide wire and catheter are inserted into the femoral artery in the groin area and advanced through the abdominal aorta, the main artery in the abdomen, and into the renal arteries. The procedure will take approximately one hour. Fluorescein angiography Fluorescein angiography is used to diagnose retinal problems and circulatory disorders. It is typically conducted as an outpatient procedure. The patient’s pupils are dilated with eye drops and he rests his chin and forehead against a bracing apparatus to keep it still. Sodium fluorescein dye is then injected with a syringe into a vein in the patient’s arm. The dye will travel through the patient’s body and into the blood vessels of the eye. The procedure does not require x rays. Instead, a rapid series of close-up photographs of the patient’s eyes are taken, one set immediately after the dye is injected, and a second set approximately 20 minutes later once the dye has moved through the patient’s vascular system. The entire procedure takes up to one hour. Celiac and mesenteric angiography

Pulmonary angiography Pulmonary, or lung, angiography is performed to evaluate blood circulation to the lungs. It is also considered the most accurate diagnostic test for detecting a pulmonary embolism, although some physicians prefer CT or MRI scans because they are less invasive. G A LE EN CY C LO PE DI A O F C AN CE R 3

Celiac and mesenteric angiography involves x-ray exploration of the celiac and mesenteric arteries, arterial branches of the abdominal aorta that supply blood to the abdomen and digestive system. The test is commonly used to detect aneurysm, thrombosis, and signs of ischemia in the celiac and mesenteric arteries, and to 91

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QUESTIONS TO ASK THE DOCTOR

New technology has improved the accuracy of these alternative methods. The procedure differs from cerebral and coronary angiograms in that the guide wire and catheter are inserted into a vein instead of an artery, and are guided up through the chambers of the heart and into the pulmonary artery. Throughout the procedure, the patient’s vital signs are monitored to ensure that the catheter does not cause arrhythmias, or irregular heartbeats. The contrast medium is then injected into the pulmonary artery where it circulates through the lung capillaries. The test typically takes up to 90 minutes.

Angiography

locate the source of gastrointestinal bleeding. It is also used in the diagnosis of a number of conditions, including portal hypertension and cirrhosis. The procedure can take up to three hours, depending on the number of blood vessels studied. Splenoportography A splenoportograph is a variation of an angiogram that involves the injection of contrast medium directly into the spleen to view the splenic and portal veins. It is used to diagnose blockages in the splenic vein and portal vein thrombosis and to assess the strength and location of the vascular system prior to liver transplantation. Most angiography procedures are typically paid for by major medical insurance. Patients should check with their individual insurance plans to determine their coverage.

Preparation Patients undergoing an angiogram are advised to stop eating and drinking eight hours prior to the procedure. They must remove all jewelry before the procedure and change into a hospital gown. If the arterial puncture is to be made in the armpit or groin area, shaving may be required. A sedative may be administered to relax the patient for the procedure. An IV line will also be inserted into a vein in the patient’s arm before the procedure begins in case medication or blood products are required during the angiogram. Prior to the angiography procedure, patients will be briefed on the details of the test, the benefits and risks, and the possible complications involved, and asked to sign an informed consent form.

Aftercare Because life-threatening internal bleeding is a possible complication of an arterial puncture, an overnight stay in the hospital is sometimes recommended following an angiography procedure, particularly with cerebral and coronary angiograms. If the procedure is performed on an outpatient basis, the patient is typically kept under close observation for a period of six to twelve hours before being released. If the arterial puncture was performed in the femoral artery, the patient will be instructed to keep his leg straight and relatively immobile during the observation period. The patient’s blood pressure and vital signs will be monitored and the puncture site observed closely. Pain medication may be prescribed if the patient is experiencing discomfort from the puncture, and a cold pack is applied to the site to reduce swelling. It 92

is normal for the puncture site to be sore and bruised for several weeks. The patient may also develop a hematoma, a hard mass created by the blood vessels broken during the procedure. Hematomas should be watched carefully, as they may indicate continued bleeding of the arterial puncture site. Patients may be given intravenous fluids and may experience a frequent need to urinate due to the x-ray dye. Angiography patients are also advised to enjoy a few days of rest and relaxation after the procedure in order to avoid placing any undue stress on the arterial puncture. Patients who experience continued bleeding or abnormal swelling of the puncture site, sudden dizziness, chest pains, chills, nausea, headaches, or numbness in the days following an angiography procedure should seek medical attention immediately. Patients undergoing a fluorescein angiography should not drive or expose their eyes to direct sunlight for 12 hours following the procedure.

Risks Because angiography involves puncturing an artery, internal bleeding or hemorrhage are possible complications of the test. As with any invasive procedure, infection of the puncture site or bloodstream is also a risk, but this is rare. A stroke or heart attack may be triggered by an angiogram if blood clots or plaque on the inside of the arterial wall are dislodged by the catheter and form a blockage in the blood vessels or artery. The heart may also become irritated by the movement of the catheter through its chambers during pulmonary and coronary angiography procedures, and arrhythmias may develop. Patients who develop an allergic reaction to the contrast medium used in angiography may experience a variety of symptoms, including swelling, difficulty breathing, heart failure, or a sudden drop in blood pressure. If the patient is aware of the allergy before the test is administered, certain medications can be administered at that time to counteract the reaction. Angiography involves minor exposure to radiation through the x rays and fluoroscopic guidance used in the procedure. Unless the patient is pregnant, or multiple radiological or fluoroscopic studies are required, the small dose of radiation incurred during a single procedure poses little risk. However, multiple studies requiring fluoroscopic exposure that are conducted in a short time period have been known to cause skin necrosis (cell death) in some individuals. This risk can be minimized by careful monitoring and documentation of cumulative radiation doses administered to these patients. G A LE EN CY C LO PE DI A O F C AN C ER 3

The results of an angiogram or arteriogram depend on the artery or organ system being examined. Generally, test results should display a normal and unimpeded flow of blood through the vascular system. Fluorescein angiography should result in no leakage of fluorescein dye through the retinal blood vessels.

Abnormal results Abnormal results of an angiography may display a restricted blood vessel or arterial blood flow (ischemia) or an irregular placement or location of blood vessels. The results of an angiography vary widely by the type of procedure performed, and should be interpreted and explained to the patient by a trained radiologist. Resources BOOKS

Baim, Donald S., and William Grossman, editors. Gross man’s Cardiac Catheterization, Angiography and Inter vention. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2000. OTHER

Angiography Fact Sheet. Beth Israel Hospital, 2001. [cited June 22, 2001]. Angiography Overview. Northwestern Memorial Hospital, 2001. [cited June 22, 2001]. Coronary Angiography and angioplasty. Video. Timonium, MD: Milner Fenwick, 1999. Coronary Angiography Fact Sheet. American Heart Associ ation, 2001. [cited June 22, 2001].

Paula Anne Ford-Martin

Anorexia Definition Anorexia is characterized by a loss of appetite or lack of desire to eat.

Description Anorexia is common in cancer patients with reported incidence between 15% and 40%. Primary anorexia is especially prevalent in patients with advanced malignancy, and is frequently a side effect of cancer treatments. Sometimes, early symptoms may remain undiagnosed, or will be masked by a more generalized wasting of the body from chronic disease, known as cachexia. G A LE EN CY C LO PE DI A O F C AN CE R 3

KEY T ERMS Anorexia—A condition frequently observed in cancer patients characterized by a loss of appetite or desire to eat. Cancer—A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread through the bloodstream and lymphatic system to other parts of the body. Candidiasis—A yeast-like fungal infection occuring on the skin or mucous membranes, i.e. mouth. Chemotherapy—Chemotherapy kills cancer cells using drugs taken orally or by needle in a vein or muscle. It is referred to as a systemic treatment due to fact that it travels through the bloodstream and kills cancer cells outside the small intestine. Hypercalcemia— A high calcium blood concentration above 10.5 milligrams per deciliter of blood. Increased gastrointestinal tract absorption or increased intake of calcium may lead to hypercalcemia. Malignant (also malignancy)— Meaning cancerous; a tumor or growth that often destroys surrounding tissue and spreads to other parts of the body. Radiation therapy—Also called radiotherapy; uses high-energy x-rays to kill cancer cells. Satiation—A feeling of fullness or satisfaction during or after food intake. Uremia—An excess of nitrogenous substances in the blood that are toxic and usually excreted by the kidneys.

When patients experience appetite loss, decreased energy consumption will subsequently lead to weight loss. When inadequate calories are consumed, the body may become weaker and less able to tolerate cancer therapies. As body weight decreases, cachexia sets in, and a general failure to thrive may make it more difficult to fight off illness and infection. A poor response to cancer treatments, reduced quality of life, and death may result from substantial weight loss. The spiraling effect of a patient’s reluctance to eat is a source of frequent anxiety for caregivers. Weight loss due to anorexia may be temporary or may continue at a life-threatening pace if the patient continues to consume inadequate energy to sustain bodyweight.

Causes It is normal for a patient to consume less energy when not as active. It is also natural to lose interest in 93

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food when individuals are seriously ill. However, it is essential in anorexic patients to consider whether the loss of appetite is the result of a natural disinterest in eating (primary anorexia), or is due to some reversible cause (secondary anorexia). Secondary anorexia may be a result of: nausea with or without fear of vomiting after food consumption  fatigue  constipation  sores in the mouth or mouth pain  candidiasis  unappetizing food or change in food preference due to cancer-related treatments  depression  odors in the environment, or heightened sensitivity to odors as a result of cancer-related treatments  early satiation  metabolic causes such as hypercalcemia and uremia  radiation therapy or chemotherapy  drugs such as antibiotics or drugs that can cause nausea 

Special concerns In order to allow normal tissue repair following aggressive cancer therapies, patients require adequate energy and macronutrients in the form of protein, carbohydrates, and fat. Inadequate consumption of food and/or poor nutrition may impair the ability of a patient to tolerate a specific therapy. If a low tolerance to therapy necessitates a decrease in dose, the therapy’s effectiveness could be compromised. Wound healing may also be impaired with poor nutrition and inadequate energy intake. Individuals who experience pain, nausea, or diarrhea due to the side effects of radiation and chemotherapy may want to discuss treatments options with their doctor to ease these side effects.

Treatments Dietary tips for managing anorexia Serve food when the patient is hungry. A microwave oven often helps.  Have the patient eat small meals every one to two hours, or time meals corresponding to when the patient feels best (typically early in the day).  If only a little food is consumed by the patient, it should ideally be high in protein and calories. Avoid empty calories (i.e. foods without protein and nutrients). 

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Add extra calories and protein to foods with the use of butter, skim milk powder, commercially prepared protein powder, honey, or brown sugar. Try to tempt the patient with tiny portions on small plates. Serve food in an attractive manner. Food is more likely to be eaten if it is served at frequent intervals unrelated to standard meal times. Avoid strong aromas if the patient finds them bothersome. Avoid liquids with meals to decrease problems of early satiety. A small alcoholic drink of the patient’s choice may help unless contraindicated. Consider flavors, consistency and quantity of food when preparing meals. Encourage eating with friends or family members; a meal in a social setting may help the patient to eat. Stimulate appetite with light exercise. Treat any underlying cause and, if a particular drug appears to be the cause, modify drug regimen. Have the patient take medications with high-calories fluids, i.e. commercial liquid supplements unless medication necessitates an empty stomach.

Often, patients may experience difficulty with eating due to upper gastrointestinal blockage such as problems with swallowing, esophageal narrowing, tumor, stomach weakness, paralysis, or other conditions that preclude normal food intake. In those circumstances, enteral nutrition may be administered through a tube into the gastrointestinal tract via the nose, or through surgically placed tubes into the stomach or intestines. If the gastrointestinal tract is working and will not be affected by the cancer treatments, then enteral support by feeding directly into the gut is preferable. Parenteral nutrition (most often an infusion into a vein) can be used if the gut is not functioning properly or if there are other reasons that prevent enteral feeding. An appetite stimulant may be given such as megestrol acetate or dexamethasone. In clinical trials, both these medications appear to have similar and effective appetite stimulating effects with megestrol acetate having a slightly better toxicity profile. Fluoxymesterone has shown inferior efficacy and an unfavorable toxicity profile. Alternative and complementary therapies Depression may affect approximately 15–25% of cancer patients, particularly if the prognosis for recovery is poor. If anorexia is due to depression, there are antidepressant choices available through a physician. G A LE EN CY C LO PE DI A O F C AN C ER 3

Anoscopy

Counseling may be also be sought through a psychologist or psychiatrist to deal with depression.

KEY T ERMS

St. John’s Wort has been used as a herbal remedy for treatment of depression, but it and prescription antidepressants is a dangerous combination that may cause symptoms such as nausea, weakness, and may cause one to become incoherent. It is important to check with a dietitian or doctor before taking nutritional supplements or alternative therapies because they may interfere with cancer medications or treatments.

Anorectal—Pertaining to the anus and rectum. Anus—The opening of the rectum through which feces leave the body. Rectum—The portion of the large intestine where feces is stored before leaving the body.

Purpose

Resources BOOKS

Quillin, Patrick, and Noreen Quillin. Beating Cancer With Nutrition Revised. Sun Lakes, AZ: Bookworld Services, 2001. PERIODICALS

Kant, Ashima, et al. ‘‘A Prospective Study of Diet Quality and Mortality in Women.’’ JAMA 283, no. 16 (2000): 2109 2115. Loprinzi, C.L., et al. ‘‘Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia.’’ Journal of Clinical Oncology 17, no. 10 (1999): 3299 306. Singletary, Keith. ‘‘Diet, Natural Products and Cancer Chemoprevention.’’ Journal of Nutrition 130 (2000): 465S 466S. Willett, Walter C. ‘‘Diet and cancer.’’ The Oncologist 5, no. 5 (2000): 393 404. ORGANIZATIONS

American Institute for Cancer Research. 1759 R Street N.W., Washington, D.C. 20009. (800) 843 8114 or (202) 328 7744. http://www.aicr.org. The National Cancer Institute (NCI). For information con tact the Public Inquiries Office: Building, 31, Room 10A31, 31 Center Drive, MSC 2580, Betheseda, MD 20892 2580 USA. (301) 435 3848, 1 800 4 CANCER. , . National Center for Complementary and Alternative Med icine (NCCAM). 31 Center Dr., Room #5B 58, Bethesda, MD 20892 2182. (800) NIH NCAM, Fax (301) 495 4957. .

Crystal Heather Kaczkowski, MSc.

Anoscopy Definition Anoscopy is a diagnostic procedure that allows a gastroenterologist or other physician to visually examine the rectum, anus, and anal canal. G A LE EN CY C LO PE DI A O F C AN CE R 3

Doctors use anoscopy to diagnose rectal cancer and cancer of the anus. This procedure can also help the doctor: 

detect any lesions that could not be felt during a digital examination



determine whether squamous cell carcinomas involving lymph nodes in or near the groin (inguinal lymph nodes) originated in the genital area or in or near the anus or rectum



confirm the source of malignancies that have spread to the anorectal area from other parts of the body

Doctors also perform anoscopy to determine whether a patient has hemorrhoids or anal: 

growths or nodules (polyps)



ulcer-like grooves (fissures)



inflammation infection



Description After removing underwear, the patient bends forward over the examining table or lies on one side with knees drawn up to the chest. The doctor performs a digital examination to make sure no tumor or other abnormality will obstruct the passage of a slender lubricated tube (anoscope). As the doctor gently guides the anoscope a few inches into the rectum, the patient is told to bear down as though having a bowel movement, then relax. By tensing and relaxing, the patient makes it easier for the doctor to insert the anoscope, and discover growths in the lining of the rectum that could not be detected during the digital examination. Directing a light into the anoscope gives the doctor a clear view of any tears or other irregularities in the lower anus or rectum. A doctor who suspects that a patient may have cancer will remove tissue for biopsy in the course of this procedure. 95

Antiandrogens

Abnormal results

Q U E S T I O N S T O A S K TH E DOC TOR

Abnormal results of anoscopy can indicate the presence of: 

  

Why do you want me to have anoscopy? How long will this procedure take? What will the results of this test tell you?

   

Slowly withdrawing the anoscope allows the doctor to thoroughly inspect the entire anal canal. As the procedure is being performed, the doctor explains what is happening, and why the patient feels pressure. Removing tissue samples for biopsy can pinch, but anoscopy does not usually cause pain. Patients do experience the sensation of needing to have a bowel movement.

 

cancer abscesses polyps inflammation infection fissures hemorrhoids See also Anal cancer; Digital rectal examination.

Resources OTHER

Anoscopy. [cited May 14, 2001]. Diagnostic tests:anoscopy. [cited May 17, 2001].

Maureen Haggerty

Preparation The rectum should be emptied of fecal matter (stool) before the procedure is performed. The doctor may suggest using: a laxative an enema  or some other preparationto clear the rectum  

Aftercare As soon as the procedure is completed, the doctor can tell the patient whether the results are normal or abnormal, and the patient can resume normal activities.

Risks Removing tissue for biopsy may cause a little bleeding and some slight pain, but there are no significant risks associated with anoscopy.

Normal results A normal anoscopy reveals no evidence of: tumor  tissue irregularities  polyps  fissures  hemorrhoids  inflammation  infection or other abnormalities 

The size, color, and shape of the anal canal look like they should. 96

Antiandrogens Definition Antiandrogens, including flutamide (brand name Eulexin or Euflex), bicalutamide (brand name Casodex), and nilutamide (brand name Nilandron), are medicines used in the treatment of advanced prostate cancer.

Purpose Antiandrogens are approved by the Food and Drug Administration (FDA) for the treatment of prostate gland cancer that has spread to other areas of the body.

Purpose Antiandrogen therapy stops or blocks the effect androgen presence has on tumor cells of the prostate. Antiandrogens are combined with either surgery or drug therapy that shuts down male hormone production. The common drugs used with antiandrogens are known as luteinizing hormone releasing hormone (LHRH) agonists, referred to by the brand names Lupron or Zoladex. The LHRH agonists produce side effects that the antiandrogens can keep under control; thus the combination of the two types of agents has improved survival in prostate cancer patients. G A LE EN CY C LO PE DI A O F C AN C ER 3

Adrenal gland—Small organ located above the kidneys that produce hormones. Food and Drug Administration—A government agency that oversees public safety in relation to drugs and medical devices. The FDA gives approval to pharmaceutical companies for commercial marketing of their products. LHRH agonists—Luteinizing hormone-releasing hormone drugs that initially stimulate the testes to make and release testosterone. With time, as the amount of testosterone in the blood rises, it stops the production of luteinizing hormone, which results in stopping overall production of testosterone. Monotherapy—Treatment of a disease or disorder with the use of a single drug. Osteoporosis—A condition in which the loss of minerals from the bone leads to fractures after minor trauma. Osteoporosis can develop in men taking antiandrogen drugs for prostate cancer.

Newer trends in antiandrogen therapy include intermittent treatment with the drugs rather than continuous dosage; and antiandrogen monotherapy for patients whose cancer is still localized. Monotherapy means that the patient is given only the antiandrogen drugs without any LHRH agonists. As of late 2003, however, antiandrogen monotherapy is considered an investigational treatment.

Description Antiandrogens will not cure prostate cancer, but they will help improve some of the disease’s symptoms. They may also increase survival time. Androgens are made naturally in the body and include the hormone testosterone and its related compound, dihydrotestosterone. The testes produce the majority of testosterone. The adrenal glands also produce androgens in smaller amounts. Prostate cancer cells grow due to normal levels of androgens produced by the body. Some patients have prostate tumors that are extra-sensitive to androgens in the blood. The androgens attach to receptors on the tumor cells and send a signal to the tumor cells causing them to grow and multiply. Antiandrogen drugs block the receptors on the prostate cancer cell that are sensitive to the androgen hormones. By blocking these receptors, known as androgen-receptors, the cancer cells cannot G A LE EN CY C LO PE DI A O F C AN CE R 3

Recommended dosage Flutamide Flutamide is an oral capsule dosed at 250 mg three times a day in combination with the LHRH agonist or surgical removal of the testis. Bicalutamide Bicalutamide is an oral tablet dosed at 50 mg once a day in combination with the LHRH agonist. The dose may need to be decreased in patients with decreased liver function. Nilutamide Nilutamide is an oral tablet dosed at 300 mg once a day for 30 days then 150 mg once a day in combination with surgical removal of the testis.

Precautions Although antiandrogens are primarily given to men, women taking them should avoid pregnancy. Antiandrogens block the male hormone called testosterone and, as a result, can adversely affect the developing fetus. Blood counts will be monitored while on antiandrogen therapy.

Side effects The most common side effects from all antiandrogens are due to the decreased levels of hormones. These commonly include hot flashes, loss of sex drive, tiredness, and impotence (the inability of males to have sexual intercourse). Antiandrogens can also cause mild nausea, vomiting, diarrhea, loss of appetite, enlarged breasts or breast tenderness, skin reactions, muscle aches, liver problems, blood in the urine and generalized pain and decrease in blood counts. Nilutamide may cause visual disturbances, with patients having difficulty with the dark. Rarely, lung problems have occurred due to nilutamide or bicalutamide, including cough and shortness of breath. These drugs must be used with caution in patients who are receiving the blood-thinning drug Coumadin (warfarin) or the drugs phenytoin and theophylline. Combining these drugs with antiandrogen therapy may increase the effects or side effects of these agents. Another potentially troublesome side effect of antiandrogens is bone loss. Men who are taking these 97

Antiandrogens

K E Y T ERM S

be instructed to grow and multiply. Antiandrogens also cause the body to decrease production of androgens and, as a result, their effects.

Antibiotics

drugs are at increased risk of osteoporosis and consequent bone fractures. Doctors are now recommending that male patients taking these drugs should have a baseline assessment of their bone mineral density, and should be given zoledronic acid (Zometa) if there is evidence of serious bone loss.

KEY T ERMS Gram-negative—Types of bacteria that do not retain Gram stain. Gram-positive—Types of bacteria that retain Gram stain.

Interactions

Mycobacteria—Rod-shaped bacteria, some of which cause human diseases such as tuberculosis. Pneumocystis carinii pneumonia (PCP)—Serious type of pneumonia caused by the protozoan Pneumocystis carinii.

Patients should tell their doctors if they have a known allergic reaction to antiandrogens or any other medications or substances, such as foods and preservatives. Before taking any new medications, including nonprescription medications, vitamins, and herbal medications, the patients should notify their doctors.

Protozoa—Single-celled animals. Toxoplasmosis—Infection caused by the protozoan parasite Toxoplasma gondii, affecting animals and humans with suppressed immune systems.

Resources PERIODICALS

Cooperberg, M. R., E. J. Small, A. D’Amico, and P. R. Carroll. ‘‘The Evolving Role of Androgen Deprivation Therapy in the Management of Prostate Cancer.’’ Minerva Urologica e Nefrologica 55 (December 2003): 219 238. Higano, C. S. ‘‘Management of Bone Loss in Men with Prostate Cancer.’’ Journal of Urology 170, 6 pt. 2 (December 2003): S59 S63. Holzbeierlein, J. M., E. P. Castle, and J. B. Thrasher. ‘‘Complications of Androgen Deprivation Therapy for Prostate Cancer.’’ Clinical Prostate Cancer 2 (December 2003): 147 152. Morote, J., E. Martinez, E. Trilla, et al. ‘‘Osteoporosis During Continuous Androgen Deprivation: Influence of the Modality and Length of Treatment.’’ European Urology 44 (December 2003): 661 665. ORGANIZATIONS

American Urological Association (AUA). 1000 Corporate Boulevard, Linthicum, MD 21090. (866) RING AUA or (410) 689 3700. http://www.auanet.org. United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857 0001. (888) INFO FDA (463 6332). http://www.fda.gov.

Trichomoniasis—Infection caused by a protozoan of the genus Trichomonas; especially vaginitis caused by Trichomonas vaginalis.

Purpose Many treatments for cancer destroy disease-fighting white blood cells, thereby reducing the body’s ability to fight infection. For example, bladder, pulmonary, and urinary tract infections may occur with chemotherapy. Single-celled organisms called protozoa are rarely a problem for healthy individuals. However, they can cause serious infections in individuals with low white blood cell counts. Because of the dangers that infections present for cancer patients, antibiotic treatment often is initiated before the exact nature of the infection has been determined; instead, the choice of antibiotic may depend on the site of the infection and the organism that is likely to be the cause. Often, an antibiotic that kills a broad spectrum of bacteria is chosen and several antibiotics may be used together.

Nancy J. Beaulieu, RPh., BCOP Rebecca J. Frey, PhD

Description The common antibiotics that are used during cancer treatment include: 

Antibiotics Definition Antibiotics are drugs that are used to treat infections caused by bacteria and other organisms, including protozoa, parasites, and fungi. 98



Atovaquone (Mapren): antiprotozoal drug used to prevent and treat a very serious type of pneumonia called Pneumocystis carinii pneumonia (PCP), in individuals who experience serious side effects with SMZ-TMP (Sulfamethoxazole/Trimethoprim, brand name Bactrim). Aztreonam (Azactam): monobactam antibiotic used to treat gram-negative bacterial infections of the G A LE EN CY C LO PE DI A O F C AN C ER 3





















Most of these antibiotics kill bacteria by preventing them from making protein for their cell walls. Ciprofloxacin and metronidazole prevent bacteria G A LE EN CY C LO PE DI A O F C AN CE R 3

from reproducing by interfering with their ability to make new DNA. All of these drugs are approved for prescription by the U.S. Food and Drug Administration.

Recommended dosage Dosages of antibiotics depend on the individual, the infection that is being treated, and the presence of other medical conditions. For children, the dosage usually is based on body weight and is lower than the adult dosage. To be effective, an entire treatment with antibiotics must be completed, even if the symptoms of infection have disappeared. Furthermore, it is important to keep the level of antibiotic in the body at a constant level during treatment. Therefore, the drug should be taken on a regular schedule. If a dose is missed, it should be taken as soon as possible. If it is almost time for the next dose, the missed dose should be skipped. Doubling up doses is generally not recommended. Average adult dosages of common antibiotics for cancer patients are as follows: 

















Atovaquone: for PCP treatment, 750 mg oral suspension twice a day, or tablets three times per day, for 21 days; for PCP prevention, 1,500 mg oral suspension, once a day; must be taken with balanced meals. Aztreonam: 1–2 gm every 6–12 hours, injected into a vein, over a 20–60 minute-period. Cefepime: 500 mg to 2 gm, injected into a vein or muscle, every 8–12 hours for 7–10 days. Ceftazidime: 250 mg to 2 gm, injected into a vein or muscle, every 8–12 hours. Ceftriaxone: 1–2 gm, injected into a vein or muscle, every 24 hours. Ciprofloxacin: 500–750 mg of the tablet or suspension, every 12 hours, for 3–28 days, taken two hours after meals with 8 oz of water; bone and joint infections usually are treated for at least 4–6 weeks; 200– 400 mg injected every 8–12 hours. Clindamycin: 150–300 mg of capsule or solution, every six hours; 300–600 mg every six to eight hours or 900 mg every eight hours, injected into a vein or muscle. Gentamicin: dosage determined by body weight, every 8–24 hours for at least 7–10 days, injected into a vein or muscle. Metronidazole: for bacterial infections, 7.5 mg per kg (3.4 mg per lb) of body weight up to a maximum of 1 gm, every six hours for at least seven days (capsules or tablets); 15 mg per kg (6.8 mg per lb) 99

Antibiotics



urinary and lower respiratory tracts and the female organs, and infections that are present throughout the body (systemic infections or septicemia). Cefepime (Maxipime), ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime), and ceftriaxone sodium (Rocephin): members of a group of antibiotics called cephalosporins used to treat bacterial infections of the urinary and lower respiratory tracts, and infections of the skin, bones, joints, pelvis, and abdomen. Ciprofloxacin (Cipro): fluoroquinolone antibiotic used to treat certain gram-negative and gram-positive bacteria and some mycobacteria. Clindamycin phosphate (Cleocin): used to treat gram-positive and gram-negative bacterial infections and, in individuals who are allergic to sulfadiazine, toxoplasmosis caused by a parasitic protozoa. Gentamicin (gentamycin) sulfate (generic name product, Garamycin, G-Mycin, Jenamicin): aminoglycoside antibiotic used to treat serious infections by many gram-negative bacteria that cannot be treated with other medicines. Metronidazole hydrochloride (Flagyl, Metric 21, Metro I.V., Protostat): used for anaerobic bacteria and protozoa. Pentamidine (generic name product, Pentam 300): used to treat PCP if serious side effects develop with SMZ-TMP. Pyrimethamine (Daraprim): antiprotozoal medicine used together with sulfadiazine to treat toxoplasmosis; or in combination with other medicines for treating mild to moderate PCP, in individuals who cannot tolerate the standard treatment. Sulfadiazine (generic name product): sulfonamide antibiotic used with pyrimethamine to treat toxoplasmosis. Sulfamethoxazole-Trimethoprim (SMZ-TMP) (generic name product, Bactrim, Cofatrim Forte, Cotrim, Septra, Sulfatrim): the sulfonamide antibiotic, sulfamethoxazole, used in combination with trimethoprim, to prevent and treat PCP and bacterial infections, such as bronchitis and middle ear and urinary tract infections. Trimethoprim (generic name product, Proloprim, Trimpex): primarily used to prevent or treat urinary tract infections. Vancomycin hydrochloride (generic name product, Vancocin): glycopeptide antibiotic used to treat a variety of serious gram-positive bacterial infections for which other medicines are ineffective, including strains of Staphylococcus that are resistant to most oral antibiotics.

Antibiotics

for the first dose, followed by half that dosage every six hours for at least seven days (injected into a vein); for protozoal infections caused by amebas, 500–750 mg of oral medicine, three times per day for 5–10 days; for trichomoniasis, 2 gm for one day or 250 mg three times per day for seven days (oral medicine); extended-release tablets for vaginal bacterial infections, 750 mg once a day for seven days.  Pentamidine: for treating PCP, 4 mg per kg (1.8 mg per lb) of body weight, once per day for 14–21 days, injected into a vein over one to two hours, while lying down.  Pyrimethamine: for toxoplasmosis, 25–200 mg tablets, taken with other medicine, for several weeks.  Sulfadiazine: for bacterial and protozoal infections, 2–4 gm for the first dose, followed by 1 gm every four to six hours (tablets).  SMZ-TMP: 800 mg of sulfamethoxazole and 160 mg of trimethoprim, (tablet or oral suspension), every 12 hours for bacterial infections and every 24 hours for prevention of PCP; dosage based on body weight for PCP treatment; injections based on body weight, every six, eight or 12 hours for bacterial infections and every six hours for PCP treatment.  Trimethoprim: 100 mg tablet every 12 hours for 10 days; for prevention of urinary tract infections, once a day for a long period.  Vancomycin: 7.5 mg per kg (3.4 mg per lb) of body weight, or 500 mg–1 gram, injected or taken orally, every 6–12 hours.

Precautions Stomach or intestinal problems or colitis (inflammation of the colon) may affect the use of: Atovaquone Cephalosporins  Clindamycin 

 

Trimethoprim Vancomycin

Central nervous system or seizure disorders may affect the use of:   

Ciprofloxacin Metronidazole Pyrimethamine

Anemia (low red blood cell count) or other blood disorders may affect the use of:      

Metronidazole Pentamidine Pyrimethamine Sulfadiazine SMZ-TMP Trimethoprim

Ciprofloxacin may not be suitable for individuals with tendinitis or with skin sensitivities to sunlight. Gentamicin may not be suitable for people with hearing problems, myasthenia gravis, or Parkinson’s disease. Metronidazole may not be suitable for individuals with heart disease, oral or vaginal yeast infections, or a history of alcoholism. Pentamidine may not be suitable for individuals with heart disease, bleeding disorders, or low blood pressure. Pentamidine may affect blood sugar levels, making control of diabetes mellitus or hypoglycemia (low blood sugar) difficult. Vancomycin may not be appropriate for individuals with hearing problems. Many antibiotics should not be taken during pregnancy or while breast-feeding. Older individuals may be more susceptible to the side effects of sulfadiazine, SMZ-TMP, or trimethoprim.

Side effects



Kidney or liver disease may affect the use of: Aztreonam  Cefepime  Ceftazidime  Ciprofloxacin  Clindamycin  Gentamicin  Metronidazole  Pentamidine  Pyrimethamine  Sulfadiazine  SMZ-TMP 

100

Some individuals may have allergic reactions to antibiotics. If symptoms of an allergic reaction (such as rash, shortness of breath, swelling of the face and neck), severe diarrhea, or abdominal cramping occur, the antibiotic should be stopped and the individual should seek medical advice. Because antibiotics can affect bacteria that are beneficial, as well as those that are harmful, women may become susceptible to infections by fungi when taking antibiotics. Vaginal itching or discharge may be symptoms of such infections. All patients may develop oral fungal infections of the mouth, indicated by white plaques in the mouth. Injected antibiotics may result in irritation, pain, tenderness, or swelling in the vein used for injection. G A LE EN CY C LO PE DI A O F C AN C ER 3

When gentamicin is injected into a muscle, vein, or the spinal fluid, the following side effects may occur:

The more common side effects of atovaquone, aztreonam, cephalosporins, ciprofloxacin, clindamycin, gentamicin, metronidazole, and SMZ-TMP include:



  

nausea and vomiting diarrhea loss of appetite

Eating active cultured yogurt may help counteract diarrhea, but if a patient has low white blood cells, this remedy is not recommended. For mild diarrhea with cephalosporins, only diarrhea medicines containing kaolin or attapulgite should be taken. With clindamycin, diarrhea medicines containing attapulgite should be taken several hours before or after the oral antibiotic. Diarrhea following antibiotics like clindamycin may indicate a bacterial infection that needs additional therapy, and a physician should be consulted. Other side effects of atovaquone may include:     

fever skin rash cough headache insomnia



 

Side effects from gentamicin may develop up to several weeks after the medicine is stopped. More common side effects of metronidazole include:     

     

abdominal pain increase in blood tests for kidney function dizziness or light-headedness inflammation or tearing of a tendon drowsiness insomnia

Other common side effects of clindamycin include abdominal pain and fever. Side effects may occur up to several weeks after treatment with this medicine. Gentamicin and vancomycin may cause serious side effects, particularly in elderly individuals and newborn infants. These include kidney damage and damage to the auditory nerve that controls hearing. Other, more common side effects of gentamicin may include:     

changes in urination increased thirst muscle twitching or seizures headache lethargy

G A LE EN CY C LO PE DI A O F C AN CE R 3

mouth dryness unpleasant or metallic taste dizziness or light-headedness headache stomach pain

Sugarless candy or gum, bits of ice, or a saliva substitute may relieve symptoms of dry mouth. Pentamidine, pyrimethamine, sulfonamides, SMZTMP, and trimethoprim can lower the number of white blood cells, resulting in an increased risk of infection. These drugs also can lower the number of blood platelets that are important for blood clotting. Thus, there is an increased risk of bleeding or bruising while taking these drugs. Serious side effects of pentamidine may include: 

Other side effects of ciprofloxacin may include:

leg cramps skin rash fever seizures

     

heart problems low blood pressure high or low blood sugar other blood problems decrease in urination sore throat and fever sharp pain in upper abdomen

Some of these symptoms may not occur until several months after treatment with pentamidine. Pyrimethamine and trimethoprim may lower the red blood cell count, causing anemia. Leucovorin or the vitamin folic acid may be prescribed for anemia. Some individuals become more sensitive to sunlight when taking sulfonamides, SMZ-TMP, or trimethoprim. Other common side effects of sulfonamides and SMZ-TMP include:      

dizziness itching skin rash headache mouth sores or swelling of the tongue fatigue 101

Antibiotics

Antibiotics used in cancer patients may have numerous side effects, both minor and severe; however, most side effects are uncommon or rare.

Anticancer drugs

If vancomycin is injected into a vein too quickly, it can cause flushing and a rash over the neck, face, and chest, wheezing or difficulty breathing, and a dangerous decrease in blood pressure.

American Cancer Society. Infections in Individuals with Cancer. Cancer Resource Center. 30 Sep. 1999. [cited May 27, 2001]. MEDLINEplus Drug Information. U.S. National Library of Medicine. 24 Jan. 2001. [cited May 22, 2001]. http:// www.nlm.nih.gov/medlineplus/druginformation.html.

Interactions Margaret Alic, Ph.D.

Many prescription and non-prescription medicines can interact with these antibiotics. Therefore, it is important to consult a complete list of known drug interactions. Among the more common or dangerous interactions: Antibiotics that lower the number of blood platelets, with blood thinners (anticoagulants), such as warfarin  Aztreonam and metronidazole with alcohol; it is important not to consume alcohol until at least three days after treatment with these antibiotics  Ciprofloxacin with antacids, iron supplements, or caffeine  Pentamidine or pyrimethamine with previous treatments with x rays or cancer medicines (increased risk of blood cell damage)  Trimethoprim with diuretics to remove excess fluid in the elderly

Anticancer drugs



Many medicines can increase the risk of hearing or kidney damage from gentamicin. These include: cisplatin  combination pain medicine with acetaminophen and aspirin or other salicylates (taken regularly in large amounts)  cyclosporine  inflammation or pain medicine, except narcotics  lithium  methotrexate  other medicines for infection 

The following drugs may increase the risk of liver effects with sulfadiazine or SMZ-TMP: acetaminophen, long-term, high-dose (eg Tylenol) birth control pills containing estrogens  disulfiram (Antabuse)  other medicines for infection  

Resources BOOKS

American Cancer Society. Consumers Guide to Cancer Drugs. Atlanta: Jones and Bartlett, 2000. OTHER

American Cancer Society. Cancer Drugs. Cancer Resource Center. 2000. [cited May 27, 2001]. 102

Definition Anticancer drugs, also called antineoplastic drugs, are chemicals that are used to treat malignancies, or cancerous growths, either alone or in combination with other treatments such as surgery or radiation therapy. Chemotherapy drugs target rapidly growing cells, including cancer cells. Chemotherapy drugs include:       

    

alkylating agents platinium drugs antimetabolites antitumor antibiotics topoisomerase inhibitors mitotic inhibitors corticosteroids Other, newer classes of anticancer drugs include: hormone therapies immunotherapies targeted therapies differentiating agents angiogenesis inhibitors

Purpose Anticancer drugs are used to kill or control the growth of malignant cancer cells. These cells grow uncontrollably, with loss of differentiation, and commonly metastasize or spread the cancer to other tissues and organs. Anticancer drugs may destroy the cancer, prolong life, or relieve cancer symptoms for improved quality of life. The drugs used in cancer treatment depend on the type and stage of the cancer and other factors including the patient’s age and health. Two or more anticancer drugs are often used in combination. The majority of anticancer drugs are chemotherapy drugs that act by interfering with cell growth, since cancer cells grow more rapidly than other cells. Since these drugs target cells that are reproducing, they G A LE EN CY C LO PE DI A O F C AN C ER 3

Alkylating agents directly damage DNA (deoxyribonucleic acid, the genetic material in the nucleus of the cell), thereby preventing cells from reproducing. Alkylating agents are non-cycle-specific and include:

chemotherapy drugs and may be used in combination with chemotherapy. Hormone-therapy drugs counteract the effects of hormones that stimulate the growth of cancer cells. For example breast cancers are often stimulated by estrogens and may be treated with drugs that inactivate these female sex hormones. Similarly, prostate cancer may be treated with drugs that inactivate androgens, the male sex hormones. Hormone-therapy drugs include:  



nitrogen mustards





nitrosoureas





alkyl sulfonates



triazines





ethylenimines



Other classes of chemotherapy drugs have different mechanisms of action: 





Platinium drugs also damage DNA, but are less likely than alkylating agents to cause leukemia. Antimetabolites damage DNA and RNA (ribonucleic acid, used in protein synthesis) by substituting incorrect components into the DNA and RNA as they are produced. Antimetabolites are cycle-specific and are used most often to treat leukemias, breast cancer, ovarian cancer, and intestinal cancer. Antitumor antibiotics include anthracyclines, which interfere with the synthesis of enzymes needed to replicate DNA. They work at all stages of the cell cycle and are used to treat many types of cancer, but have the potential to damage the heart in high doses.



Topoisomerase inhibitors interfere with enzymes that control the replication of DNA.



Mitotic inhibitors prevent mitosis—the process by which cells divide. They are often derived from natural products.



Corticosteroids are multipurpose drugs that are related to hormones. In cancer treatment they are used to slow cell growth and prevent nausea and vomiting caused by other anticancer drugs.





Asparaginase, an enzyme, interferes with the growth of cancer cells. It is used to treat acute lymphocytic leukemia.

Immunotherapy drugs enhance or stimulate the body’s immune system. They include:  



G A LE EN CY C LO PE DI A O F C AN CE R 3

monoclonal antibodies, a passive imnmunotherapy immunostimulating drugs that non-specifically stimulate the body’s immune response immunomodulating drugs that alter the immune response Other newer anticancer drugs include:







targeted therapies that are aimed at cancer cells expressing certain genes differentiating agents that cause cancer cells to mature into normal cells angiogenesis inhibitors that interfere with the formation of blood vessels that feed tumors and contribute to tumor growth

Description The majority of anticancer drugs are administered intravenously, either by injection or by continuous infusion. Other drugs are administered orally, as a liquid, tablet, or capsule. U.S. brand names Alkylating agents include: 

Bortezomib, a proteosome inhibitor, interferes with protein synthesis.

Some new classes of anticancer drugs target characteristics of cancer cells other than their rapid growth. These drugs may have fewer side effects than

estrogens anti-estrogens progestins luteinizing hormone-releasing hormone (LHRH) agonists aromatase inhibitors anti-androgens





nitrogen mustards: mechlorethamine (nitrogen mustard, Mustargen), chlorambucil (Leukeran), cyclophosphamide (Cytoxan, Neosar), isfofamide (isophosphamide, Ifex), melphalan (Alkeran) nitrosoureas: streptozocin (Zanosar), carmustine (BCNU, Gliadel), lomustine (CeeNU) the alkyl sulfonate busulfan (Busulfex, Myleran) 103

Anticancer drugs

commonly affect not only cancer cells, but other cells that reproduce quickly, including those of hair follicles, ovaries and testes, and blood-forming organs. There are two classes of chemotherapy drugs: cyclespecific drugs act only at specific points in a cell’s duplication cycle, such as anaphase or metaphase; non-cycle-specific drugs may act at any point in the cell cycle.

Anticancer drugs

triazines: dacarbazine (DTIC-Dome), temozolomide (Temodar)  ethylenimines: thiotepa (Thioplex), altretamine or hexamethylmelamine (Hexalen)

Hormone-therapy drugs include:



Platinium drugs include: cisplatin (Platinol) carboplatin (Paraplatin, Carboplatin Novaplus)  oxaliplatin (Eloxatin)



 

 





Antimetabolites include: 5-fluorouacil (5-FU; Adrucil)  capecitabine (Xeloda)  6-mercaptopurine (6-MP; Purinethol)  methotrexate (Rheumatrex, Trexall)  gemcitabine (Gemzar)  cytarabine (Cytosar, Tarabine, Ara-C)  fludarabine (Fludara)  pemetrexed (Alimta) 

Immunotherapy drugs include: 





daunorubicin (Cerubidine)  doxorubicin (Adriamycin, Rubex)  epirubicin (Ellence)  idarubicin (Idamycin)

   

bortezomib (Velcade) imatinib (Gleevec) gefitinib (Iressa) erlotinib (Tarceva) Differentiating agents include:

Other antitumor antibiotics include: actinomycin-D or dactinomycin (Cosmegen)  bleomycin (Blenoxane)  mitomycin (Mutamycin)  mitoxantrone (Novantrone)

monoclonal antibodies: rituximab (Rituxan), alemtuzumab (Campath) immunostimulating drugs: interleukin-2 (Il-2 or aldesleukin, Proleukin); interferon alfa-2 (Intron A, Roferon-A); BCG vaccine (TheraCys, TICE BCG) immunomodulating drugs: thalidomide (Thalomid), lenalidomide (Revlimid) Targeted therapies include:

Anthracyclines include: 

anti-estrogens: tamoxifen (Nolvadex), toremifene (Fareston), fulvestrant (Faslodex) progestin: megestrol acetate (Megace) LHRH agonists: leuprolide (Lupron, Eligard, Viadur), goserelin (Zolodex) aromatase inhibitors: anastrozole (Arimidex), exemestane (Aromasin), letrozole (Femara) anti-androgens: bicalutamide (Casodex), flutamide (Eulexin), nilutamide (Nilandron)







retinoids: tretinoin (ATRA, Atralin, Vesanoid), bexarotene (Targretin) arsenic trioxide (Trisenox)

Angiogenesis inhibitors include bevacizumab (Avastin).

Topoisomerase inhibitors include: topotecan (Hycamtin)  irinotecan (Camptosar)  etoposide or VP-16 (Toposar, VePesid)  teniposide (Vumon)  mitoxantrone (Novantrone)

Canadian brand names



Mitotic inhibitors include: taxanes: paclitaxel (Taxol, Onxal), docetaxel (Taxotere) epothilones: ixabepilone (Ixempra)  vinca alkaloids: vinblastine (Velban), vincristine (Vincasar), vinorelbine (Navelbine)  estramustine (Emcyt)  

Anticancer corticosteroids include: prednisone (Prednisone Intensol, Sterapred) methylprednisolone (Medrol)  dexamethasone (Decadron)

Alkylating agents include: 



 



Platinium (carboplatin).

Asparaginase is marketed as Elspar. 104

drugs

include

Paraplatin-AQ

Antimetabolites include:

 

nitrogen mustards: Mustargen (mechlorethamine); Leukeran (chlorambucil); Cytoxan, Procytox (cyclophosphamide); Alkeran (melphalan) nitrosoureas: Zanosar (streptozocin); BiCNU (carmustine); CeeNU (lomustine) Busulfex, Myleran (busulfan) triazines: DTIC (dacarbazine); Temodal, Temodar (temozolomide) Hexalen (altretamine)

  

Adrucil (5-fluorouacil) Xeloda (capecitabine) Purinethol (6-mercaptopurine) G A LE EN CY C LO PE DI A O F C AN C ER 3

  

Methotrexate Gemzar (gemcitabine) Cytosar (cytarabine) Fludara (fludarabine)







Anthracyclines include:    



Cerubidine (daunorubicin) Adriamycin (doxorubicin) Ellence, Pharmorubicin (epirubicin) Idamycin (idarubicin)

immunostimulating drugs: Proleukin (Il-2); ImmuCyst, Oncotice, Pacis (BCG) immunomodulating drugs: Thalomid (thalidomide) Targeted therapies include: Velcade (bortezomib) Gleevec (imatinib)

Differentiating agents include the retinoids Vesanoid (tretinoin) and Targretin (bexarotene). Angiogenesis (bevacizumab).

inhibitors

include

Avastin

Other antitumor antibiotics include:    

International brand names

Cosmegen (dactinomycin) Blenoxane (bleomycin) Mutamycin (mitomycin) Novantrone (mitoxantrone)

Alkylating agents include: 

Topoisomerase inhibitors include:     



Hycamtin (topotecan) Camptosar (irinotecan) VePesid (etoposide) Vumon (teniposide) Novantrone (mitoxantrone)

 



Mitotic inhibitors include:  



taxanes: Taxol (paclitaxel); Taxotere (docetaxel) vinca alkaloids: Vincasar, PFS (vincristine); Navelbine (vinorelbine) Emcyt (estramustine)

  

Anticancer corticosteroids include:   

Apo-Prednisone, Winpred (prednisone) Medrol (methylprednisolone) Decadron, Dexasone, Diodex, (dexamethasone)

  

Maxidex

 



 





Asparaginase is marketed as Elspar and Kidrolase.



Hormone-therapy drugs include:



anti-estrogens: Apo-Tamox, Gen-Tamoxifen, Nolvadex, Novo-Tamoxifen, PMS-Tamoxifen, Tamofen (tamoxifen); Fareston (toremifene) progestin: Megestrol, Megace LHRH agonists: Viadur, Lupron (leuprolide); Zoladex (goserelin) aromatase inhibitors: Arimidex (anastrozole); Aromasin (exemestane); Femara (letrozole) anti-androgens: Casodex (bicalutamide); Flutamide, Euflex, Eulexin (flutamide); Anandron (nilutamide) Immunotherapy drugs include:



monoclonal antibodies: rituximab (Rituxan)

G A LE EN CY C LO PE DI A O F C AN CE R 3

nitrogen mustards: Mustargen, Nitromin (mechlorethamine); Leukeran (chlorambucil); Cytoxan, Procytox, Endoxan (cyclophosphamide); Alkeran (melphalan) nitrosoureas: Zanosar (streptozocin); Bicnu, Gliadel (carmustine); CeeNU (lomustine) Busulfex, Myleran, Busilvex (busulfan) triazines: Dacarbazin, Deticene, DTIC-Dome (dacarbazine); Temodal (temozolomide) ethylenimines: Thioplex, Thiotepa (thiotepa); Hexalen (altretamine) Platinium drugs include: Platinol, Platidiam, Platinex, Platosin (cisplatin) Carboplatin, Carbosin, Paraplatin (carboplatin) Eloxatin (oxaliplatin) Antimetabolites include: Xeloda (capecitabine) Puri-Nethol, Purinethol (mercaptopurine) Methotrexate Gemzar (gemcitabine) Alexan, Cytosar (cytarabine) Fludara (fludarabine) Alimta (pemetrexed) Anthracyclines include:

 





Cerubidine, Daunoblastina (daunorubicin) Adriamycin, Adriblastina, Caelyx, Doxorubicin, Myocet, Rastocin, Rubex (doxorubicin) Farmorubicina, Farmorubicin, Pharmorubicin (epirubicin) Zavedos (idarubicin) Other antitumor antibiotics include:

   

Cosmegen (dactinomycin) Blenoxane, Bleocin (bleomycin) Mitomycin C, Mutamycin (mitomycin) Novantrone, Onkotrone (mitoxantrone) 105

Anticancer drugs



Anticancer drugs

Recommended dosage

Topoisomerase inhibitors include: 

Hycamtin (topotecan)



Campto, Camptosar (irinotecan)



Etopophos, Ebewe, VePesid (etoposide)



Vumon (teniposide)



Novantrone, Onkotrone (mitoxantrone) Mitotic inhibitors include:



taxanes: Anzatax, Taxol (paclitaxel); Taxotere (docetaxel)



vinca alkaloids: Velbe (vinblastine); Oncovin, Vincristine (vincristine); Navelbine (vinorelbine)



Emcyt (estramustine)

Dosages of anticancer drugs depend on a variety of factors including the specific drug, method of administration, the type of cancer being treated, and the patient’s health. Although dosages are often calculated based on body weight, they may also be based on blood cell counts, in order to avoid anemia (red cell depletion), neutropenia (white cell deficiency), or thrombocytopenia (platelet deficiency). Children and the elderly may be dosed differently than others. Because of the frequency and severity of side effects from anticancer drugs, chemotherapy is commonly administered in cycles, allowing time for recovery from the effects before administering the next dose.

Anticancer corticosteroids include:

Precautions



Prednisone, Meticorten (prednisone)



Medrol, Metypred (methylprednisolone)



Alin, Decadron, Dexalocal, Maxidex (dexamethasone)

Individual anticancer drugs all carry their own precautions, including the risk of their causing additional cancers. General precautions include: 

Asparaginase may be marketed as Elspar, Leunase, and Kidrolase. Hormone-therapy drugs include: 

anti-estrogens: Nolvadex, Tamofen, Tamoplex, Tamoxifen, Zitazonium (tamoxifen); Fareston (toremifene); Faslodex (fulvestrant)



progestin: Megestrol



LHRH agonists: Zoladex (goserelin); Viadur, Lupron (leuprolide)



aromatase inhibitors: Arimidex (anastrozole); Aromasin, Aromasil, Aromasine (exemestane); Femara, Femar (letrozole)



anti-androgens: Casodex (bicalutamide); Eulexin, Flutamid (flutamide); Anandron (nilutamide) Immunotherapy drugs include:



monoclonal antibodies: Mabthera Mabcambath (alemtuzumab)



immunostimulating drugs: Proleukin (Il-2)



immunomodulating drugs: Thalix (thalidomide) Targeted therapies include:



Velcade (bortezomib)



Gleevec, Glivec (imatinib)



Iressa (gefitinib) Differentiating agents include:



the retinoid Targretin (bexarotene)



arsenic trioxide (Trisenox)

106

(rituximab);







Patients should be well-informed concerning the benefits and risks of their anticancer drugs and be emotionally prepared for the side effects, some of which—including possible sterility—may be permanent. When anticancer drugs are self-administered, patients must be familiar with proper use of the drugs, including dose scheduling and interactions with food or other drugs. Since many adverse effects do not appear until several days after a dose of an anticancer drug, patients must know which side effects should be reported to their physician. Chemotherapy patients are at risk for infections due to reduced white blood cell counts. Prophylactic antibiotics may be necessary and patients should follow good hygiene practices to minimize exposure to infections. Live virus immunizations—and contact with others who have recently received a live virus immunization—are contraindicated until the patient has fully recovered from the effects of chemotherapy. Geriatric

Some anticancer drugs are only used in elderly patients. Others are generally not used in the elderly, who may be more sensitive to the toxic effects. Pregnant or breastfeeding Because most anticancer drugs can harm a fetus, women of childbearing age should use two concurrent effective methods of birth control while G A LE EN CY C LO PE DI A O F C AN C ER 3

Steps to minimize side effects include: 



Other conditions and allergies The existence of any of the following conditions should be taken into consideration before administering anticancer drugs:



chickenpox or recent exposure to someone with chickenpox shingles (Herpes zoster) mouth sores current or past seizures head injury nerve or muscle disease hearing problems infection of any kind gout colitis intestinal blockage stomach ulcers kidney stones kidney disease liver disease current or past alcohol abuse immune system disease cataracts or other eye problems high cholesterol





                 

Other side effects of anticancer drugs can include:               

Because most anticancer drugs do not target specific cell types, they can have numerous side effects. Drugs that target specific cell types may have more specific side effects. Nausea and vomiting are among the most common side effects of anticancer drugs and in some cases may be severe enough to cause dose reduction or discontinuation of treatment. Other common side effects include:

 

        

      

hair loss due to effects on hair follicles menstrual cycle changes itchy skin loss of appetite anemia immune system impairment blood clotting problems due to damage to the bloodforming organs, leading to a reduction in the number of red blood cells, white blood cells, and platelets

G A LE EN CY C LO PE DI A O F C AN CE R 3

joint pain skin rash hearing problems or ringing in the ears numbness or tingling in the fingers or toes trouble walking or balance problems swelling of the feet or lower legs unusual tiredness or weakness loss of taste seizures dizziness confusion agitation headache dark urine yellow eyes or skin flushing of the face

Uncommon but serious side effects of anticancer drugs may include:



Side effects

antinausea medications to reduce nausea and vomiting maintaining fluid levels to reduce drug toxicity, particularly to the kidneys application of a scalp tourniquet to reduce blood flow to the scalp and minimize hair loss

 

black, tarry, or bloody stools blood in the urine diarrhea fever or chills cough or hoarseness wheezing or shortness of breath sores in the mouth or on the lips unusual bleeding or bruising swelling of the face red ‘‘pinpoint’’ spots on the skin redness, pain, or swelling at the point of injection pain in the side or lower back problems urinating or painful urination fast or irregular heartbeat

Interactions Anticancer drugs can interact with numerous other drugs, affecting the actions of one or both or increasing the risk of side effects. The physician should be aware of all prescription and nonprescription (overthe-counter) medicines that a patient is taking, as well 107

Anticancer drugs

they or their males partners are being treated with anticancer drugs. Breastfeeding should be avoided during treatment.

Antidiarrheal agents

ORGANIZATIONS

QUESTIONS TO ASK YOUR PHARMACIST      



What is the name of my drug? Are there other names for this drug? How should I take this drug? What side effects can I expect? How can I minimize or mitigate side effects? When should I contact my physician regarding my side effects? Are there foods or medications that I should avoid?

American Cancer Society, 1599 Clifton Road NE, Atlanta, GA, 30329 4251, (800) ACS 2345, http://www. cancer.org. National Cancer Institute, NCI Public Inquiries Office, 6116 Executive Boulevard, Room 3036A, Bethesda, MD, 20892 8322, (800) 4 CANCER, http://www.cancer.gov.

Samuel D. Uretsky, PharmD Margaret Alic, PhD

Antidiarrheal agents Definition as radiation treatments or other anticancer drugs administered in the past.

Antidiarrheal agents are prescription and nonprescription medicines that are used to treat diarrhea.

Resources BOOKS

Abeloff, M. D., et al. Abeloff’s Clinical Oncology, 4th ed. Philadelphia: Churchill Livingstone, 2008. Nathan, David G. The Cancer Treatment Revolution: How Smart Drugs and Other New Therapies are Renewing Our Hope and Changing the Face of Medicine. Hoboken, NJ: John Wiley & Sons, 2007. Thurston, David E. Chemistry and Pharmacology of Anti cancer Drugs. Boca Raton, FL: CRC Press/Taylor & Francis, 2007.

Purpose Some types of cancer may cause diarrhea. In addition, diarrhea is a common side effect of chemotherapy treatments for cancer. This is because anticancer drugs can damage the cells of the intestines. Radiation treatment for cancer directed at the abdominal region also may cause diarrhea. Diarrhea can result in dehydration and the loss of minerals such as potassium. It may prevent the elimination of waste products in the urine, as the body attempts to conserve water.

PERIODICALS

Dawood, S., and B. Leyland Jones. ‘‘Pharmacology and Pharmacogenetics of Chemotherapeutic Agents.’’ Cancer Investigation 27, no. 5 (June 2009): 482 488. OTHER

‘‘Anticancer Drugs.’’ University of Maryland Medical Cen ter. http://www.umm.edu/altmed/articles/anticancer drugs 002712.htm ‘‘Cancer Center.’’ Drugs.com. http://www.drugs.com/ cancer.html ‘‘Cancer Chemotherapy.’’ MedlinePlus. http://www. nlm.nih.gov/medlineplus/cancerchemotherapy.html. ‘‘Drug Information Summaries.’’ National Cancer Institute. http://www.cancer.gov/cancertopics/druginfo/ alphalist ‘‘Guide to Cancer Drugs.’’ American Cancer Society. http:// www.cancer.org/docroot/CDG/cdg_0.asp ‘‘What Are the Different Types of Chemotherapy Drugs?’’ American Cancer Society. http://www.cancer.org/ docroot/ETO/content/ETO_1_4X_ What_Are_The_ Different_Types_Of_Chemotherapy_Drugs. asp? sitearea ETO 108

Description The common medicines for treating diarrhea that results from cancer and cancer treatments are:    

atropine and diphenoxylate loperamide octreotide opium tincture

Atropine and diphenoxylate are prescribed as a combination medicine with the brand names:      

Lofene Logen Lomocot Lomotil Lonox Vi-Atro

The generic name product also may be available. Atropine and diphenoxylate, antiperistaltic and anticholinergic agents, relax muscles and slow down the G A LE EN CY C LO PE DI A O F C AN C ER 3

Anticholinergic agent—Drug that slows the action of the bowel by relaxing the muscles; reduces stomach acid. Antiperistaltic agent—Drug that slows the contraction and relaxation (peristalsis) of the intestines.

movements of the gastrointestinal tract. Diphenoxylate is similar to some narcotics and may be habitforming if taken in dosages higher than prescribed. Since higher doses of atropine have unpleasant effects, it is unlikely that the combination medicine will be taken in high enough doses to cause diphenoxylatedependence. Loperamide slows down the movements of the intestines. The common brand names for this medicine are:    

Imodium Kaopectate II Maalox Anti-Diarrheal Pepto Diarrhea Control

Octreotide (brand name Sandostatin) is used to treat diarrhea and other symptoms of some types of intestinal cancers. It also is used to treat insulin-producing tumors of the pancreas and diarrhea caused by chemotherapy. Opium tincture, also known as camphorated opium tincture or laudanum, is a narcotic that is used to treat severe diarrhea. Except for loperamide liquid or tablets, all of these medicines require a prescription. Dosages vary with the individual.

Recommended dosage The atropine-diphenoxylate combination is taken by mouth as a solution or a tablet. It may be taken with food to reduce stomach upset. The initial average dosage is 5 mg (2 tsp or two tablets) three to four times daily. Subsequent doses are once daily, as needed. Loperamide is taken orally, as a liquid, tablet, or capsule. The usual dosage for adults and teenagers is 4 mg (2 capsules or tablets, 4 tsp of liquid) after the first loose bowel movement, followed by 2 mg after each successive loose bowel movement. The maximum dose is 16 mg of the capsules or 8 mg of the tablets or liquid in 24 hours. Loperamide should not be taken for more than two days unless ordered by a physician. G A LE EN CY C LO PE DI A O F C AN CE R 3

Octreotide is packaged as a kit, for injection into a vein. For treating severe diarrhea from intestinal tumors, the average initial dosage of the long-acting form, for adults and teenagers, is 20 mg injected into the gluteal muscle of the buttocks, once every four weeks for two months. The dosage may then be adjusted by the physician. For the short-acting form, the average initial dose is 50 micrograms (mcg) injected under the skin, two to three times per day. The dosage may be gradually increased up to 600 mcg per day for the first two weeks. The average dosage after two weeks is 50–1500 mcg per day. For children, the usual dosage is 1–10 mcg per kg (0.45–4.5 mcg per lb) of body weight per day. Opium tincture is taken orally, as a liquid. It may be taken with food to prevent stomach upset. The average adult dose is 5–16 drops, measured from the dropper in the bottle, four times per day, until diarrhea is controlled. It may be diluted with water. After several weeks of treatment, it may be necessary to lower the dosage gradually before stopping the medicine, to lessen the risk of side effects from opium withdrawal.

Precautions Antidiarrheal agents may cause allergic reactions in some individuals. Atropine and diphenoxylate should not be given to children. Loperamide should not be given to children under six. Opium may cause breathing problems in children up to two years of age. Older adults are more sensitive to diphenoxylate and opium than younger individuals and these drugs may cause breathing problems. Diphenoxylate and loperamide may mask the symptoms of dehydration caused by diarrhea in older individuals, so it is very important to drink sufficient fluids. Atropine and diphenoxylate Other medical conditions may affect the use of atropine and diphenoxylate: 



 

alcohol or drug abuse may increase the risk of diphenoxylate addiction colitis (inflammation of the colon) may become more severe Down syndrome may cause more severe side effects dysentery may worsen 109

Antidiarrheal agents

K E Y T ERM S

Following therapy with irinotecan (Camptosar), loperamide doses of 2 mg every two hours while awake and 4 mg every four hours at night are utilized at the onset of diarrhea to prevent severe dehydration and possible hospitalization.

Antidiarrheal agents



emphysema, asthma, bronchitis, or other chronic lung diseases increase the risk of breathing problems



enlarged prostate or urinary tract blockage may cause severe problems with urination

Side effects of opium tincture may be increased or become dangerous when combined with the following medical conditions:



gall bladder disease or gallstones may worsen





glaucoma may result in severe eye pain (rare)





heart disease may worsen





hiatal hernia may worsen with atropine (rare)





high blood pressure may increase (rare)





intestinal blockage may worsen





kidney disease may cause atropine to accumulate in the body, resulting in side effects



liver disease may cause central nervous system side effects, including coma





myasthenia gravis may become worse





overactive or underactive thyroid may cause effects on breathing and heart rate



incontinence may worsen

An overdose of atropine and diphenoxylate can lead to unconsciousness and death. Symptoms of overdose include:

Opium tincture

 



Opium tincture may be habit-forming, causing mental or physical dependence that can lead to side effects of withdrawal when stopping the medicine. The use of opium tincture during pregnancy can cause dependency in the fetus and symptoms of drug withdrawal or breathing problems in the newborn infant.



severe drowsiness



breathing problems



fast heartbeat



warmth, dryness, and flushing of skin





vision problems





severe dryness of mouth, nose, and throat





nervousness or irritability

Symptoms of opium overdose include:

 

Loperamide and octreotide

 

Other medical conditions may affect the use of loperamide:

 



colitis (inflammation of the colon) may worsen



dysentery may worsen



liver disease may increase the risk of side effects

 

Loperamide should not be used in the presence of fever or blood or mucus in stools. Medical conditions that may affect the use of octreotide include:

Atropine and diphenoxylate At low doses, taken for short periods of time, side effects of atropine and diphenoxylate are rare. However, serious side effects may include:

diabetes mellitus, since octreotide may affect blood sugar levels



gallbladder disease or gallstones, since octreotide may cause gallstones



severe kidney disease that may cause octreotide to remain in the body longer



110

seizures confusion severe restlessness or nervousness severe dizziness severe drowsiness slow or irregular breathing severe weakness cold, clammy skin low blood pressure slow heartbeat contracted eye pupils

Side effects





alcohol or drug abuse colitis (inflammation of the colon) heart disease kidney disease liver disease underactive thyroid head injury or brain disease emphysema, asthma, bronchitis, or other chronic lung disease problems with urination or enlarged prostate gallbladder disease or gallstones seizures





bloating constipation loss of appetite stomach pain with nausea and vomiting G A LE EN CY C LO PE DI A O F C AN C ER 3

           

dizziness drowsiness blurred vision confusion difficult urination dry skin or mouth fever headache depression numbness in hands or feet skin rash or itching swelling of gums

Rare side effects that may occur after stopping atropine and diphenoxylate include:     

sweating trembling or chills muscle cramps nausea or vomiting stomach cramps Loperamide

Side effects are rare with low dosages of loperamide, taken for a short time. However, severe side effects may include:       

bloating constipation loss of appetite stomach pain with nausea and vomiting skin rash dry mouth dizziness or drowsiness

 

  

Symptoms of high blood sugar (hyperglycemia) from octreotide include:            

blurred vision drowsiness and fatigue dry mouth flushed, dry skin fruity breath odor increased urination ketones in urine loss of appetite increased thirst nausea or vomiting stomach ache rapid, deep breathing

Symptoms of low blood sugar (hypoglycemia) from octreotide include:            

Octreotide

swelling of feet or lower legs inflammation of the pancreas with stomach pain, nausea, or vomiting hair loss seizures unconsciousness



anxiety and nervousness confusion blurred vision cold sweats cool, pale skin drowsiness, fatigue, weakness hunger fast heartbeat headache nausea nightmares and restless sleep shakiness slurred speech

More common side effects of octreotide may include:     

irregular or slow heartbeat constipation diarrhea flatulence discomfort at the site of injection

Less common or rare side effects of octreotide may include:   

dizziness or light-headedness fever flushing or redness of the face

G A LE EN CY C LO PE DI A O F C AN CE R 3

Opium tincture Side effects of opium tincture that are more common with higher dosages may include:       

drowsiness dizziness, light-headedness, faintness nervousness weakness or fatigue painful or strained urination frequent urination decreased volume of urine 111

Antidiarrheal agents

Other, less common or rare side effects of atropine and diphenoxylate include:

Antiemetics

Lying down and rising slowly from a seated or lying position may help relieve dizziness.



Rare side effects of opium tincture include: bloating  constipation  loss of appetite  nausea or vomiting  stomach cramps  fast or slow heartbeat  sweating  rash, hives, or itching  redness or flushing of the face  depression  troubled breathing  convulsions (seizures)







Loperamide and octreotide Antibiotics may interact with loperamide and make the diarrhea worse. Narcotic pain medicines in combination with loperamide may cause severe constipation. Because octreotide may cause high or low blood sugar, it can interact with the following medicines:

The following side effects may occur after stopping treatment with opium tincture:



runny nose or sneezing  body aches  loss of appetite  diarrhea  stomach cramps  nausea or vomiting  fever  sweating  nervousness or irritability  trembling  insomnia  dilated pupils  severe weakness





Interactions

Monoamine oxidase inhibitors may cause severe side effects if taken within two weeks of diphenoxylate and atropine. Opioid antagonists (naltrexone) may cause withdrawal from diphenoxylate addiction; naltrexone will counteract the antidiarrheal effects of the medicine. Other anticholinergics to reduce stomach acid or cramps may increase the effects of atropine.



 

antidiabetic medicines, sulfonylurea diazoxide (Proglycem) glucagon insulin growth hormone Opium tincture

The following medicines may increase side effects from opium tincture:   

anticholinergics for abdominal or stomach cramps other antidiarrheal medicines tricyclic antidepressants

Naltrexone (Trexan) makes opium less effective for treating diarrhea. Alcohol, narcotics, and other central nervous system depressants, including antihistamines, sedatives, prescription pain medicines, barbiturates, seizure medicines, muscle relaxants, or anesthetics, may lead to unconsciousness or death in combination with opium tincture.

Atropine and diphenoxylate Margaret Alic, Ph.D.

Other drugs may interact with atropine and diphenoxylate: Antibiotics (cephalosporins, clindamycin, erythromycins, tetracyclines) can counteract the effects of atropine and diphenoxylate and make the diarrhea worse.  Central nervous system depressants (alcohol, antihistamines, sedatives, pain medicines or narcotics, barbiturates, seizure medicine, muscle relaxants, anesthetics) may increase effects, such as drowsiness, from both the depressant and the antidiarrheal agent. 

112

Antiemetics Definition Antiemetic drugs are drugs used to combat nausea and vomiting. G A LE EN CY C LO PE DI A O F C AN C ER 3

Depersonalization—An alteration in the perception of self. Tardive dyskinesia—A disorder brought on by antipsychotic medication use, characterized by uncontrollable muscle spasms.

Purpose Antiemetic drugs are used to prevent vomiting (emesis) in chemotherapy patients and postoperative patients. Aside from the difficulty of maintaining proper nutrition and a healthy weight, chronic vomiting can result in dehydration, which can be a medical emergency. Following are descriptions of many common antiemetic drugs in use as of 2004.

Description Promethazine Promethazine is also known as phenergan and mepergan. It is also used to treat motion sickness, reduce allergic symptoms, and for sedation. It is one of the drugs of the phenothiazine type. In addition to other qualities, it is an antihistamine. Prochlorperazine Prochlorperazine is also known as compazine. Like promethazine, it is a member of the class of phenothiazines. Unlike promethazine, however, prochlorperazine also belongs to the class of drugs known as antipsychotics, or neuroleptics. Antipsychotic drugs are used to treat psychoses and other psychiatric disorders. In addition to its use as an antiemetic and anti-psychotic drug, prochlorperazine is also used to treat non-psychotic anxiety. Serotonin receptor antagonists The serotonin receptor antagonists include granisetron (kytril), dolasetron (anzemet), and ondansetron (zofran). These drugs are used for postoperative nausea and emesis as well as nausea and vomiting associated with chemotherapy, and are often used in combination with a corticosteroid. Ondansetron is approved for nausea and vomiting associated with radiation therapy. Neurokinin receptor antagonists The Neurokinin receptor antagonists are a new class of antiemetics. Aprepitant (Emend) was G A LE EN CY C LO PE DI A O F C AN CE R 3

Dronabinol Dronabinol (marinol) is used to combat anorexia in AIDS patients, and emesis in cancer patients who haven’t responded to other antiemetics. Marinol is the synthetic or extracted form of the active ingredient found in marijuana. Other antipsychotic (neuroleptic) drugs The other neuroleptic (antipsychotic) drugs used to treat nausea and emesis are droperidol (inapsine), haloperidol (haldol), chlorpromazine (thorazine), and perphenazine (trilafon). One other antipsychotic, triethylperazine (torecan or norzine), was used as an antiemetic, but is no longer widely available. Some of the antipsychotics are also used to treat aggressive or violent behavior or incontrollable hiccups (chlorpromazine). These drugs are similar to prochlorperazine in terms of their actions and potentially severe side effects.

Dosage Promethazine Promethazine is given in doses of 12.5 to 25 mg every 4 hours if injected into the muscle or as a suppository. As a syrup, 25 mg should be given every 4 to 6 hours. Doses for children vary by age, weight, and severity of condition. Prochlorperazine Generally, the dose is 5 to 10 mg, 3 to 4 times per day. However, the effect of medication varies widely from patient to patient, so the dose should be tailored to each individual. Prochlorperazine is available as a syrup, tablet, 25 mg slow-release capsule, and in injectable form. Aprepitant One 125-mg capsule is given by mouth one hour before chemotherapy begins. An 80-mg capsule is taken each morning for two days following the chemotherapy treatment. Dronabinol The effective dose of dronabinol varies widely from patient to patient and should be monitored and 113

Antiemetics

K E Y T ERM S

approved in 2004 for use in cancer patients. It is used in combination with other antiemetics for relief of acute and delayed nausea and vomiting caused by high-dose chemotherapy, most often caused by the chemotherapy drug cisplatin.

Antiemetics

tested by the physician. The basic dose is 5mg/m2 given 4 to 6 times per day.

Precautions Promethazine Patients with cardiovascular disease or impaired liver function should either use this drug with caution or not at all. Children should also use this drug cautiously for two reasons. First, some side effects may suggest, or mask, underlying disease, such as Reye’s syndrome. Second, large doses of this drug, or any antihistamine, may cause convulsions, hallucinations, or death in children. Patients taking this medication should not drive, operate heavy machinery, or engage in any hazardous activity while under the influence of this drug. This drug has not been established as safe for use during pregnancy, or in nursing mothers. Prochlorperazine Persons allergic to any other phenothiazine (such as promethazine) should not take prochlorperazine. Patients who have heart problems, glaucoma, or bone marrow depression should take this drug with caution, or not at all, and inform their physician of their condition. People who will be around high temperatures should also avoid this drug. In addition, those who experience seizures should be aware that administration of this drug makes seizures more likely. Breast cancer patients may wish to avoid this drug because it increases levels of prolactin in the blood. Increased prolactin may help some types of breast cancer to thrive. Prochloroperazine, like promethazine, may mask symptoms of Reye’s disease in children. It may also mask symptoms of intestinal obstructions or brain disease. In addition, children who are acutely ill, under two years of age, or under 20 pounds should not be given this drug. This drug has not been established as safe for use during pregnancy and is found in the breast milk of lactating mothers. Therefore, caution should be used when administering this drug to pregnant women and extreme caution should be used when administering to nursing women. Aprepitant Patients should not drink grapefruit juice while taking aprepitant. The physician should be told if the patient is pregnant, breast feeding, or becomes pregnant while taking the drug. 114

Serotonin receptor antagonists Patients with allergies to any drug in this category should not take any other drug in this category. Also, patients with hypokalemia, hypomagnesia, or certain heart problems should avoid taking these drugs. The effect of these drugs on the children or fetuses of nursing or pregnant mothers is not known, so they should be used with caution. Dronabinol Dronabinol is inadvisable for patients with a known allergy to either sesame oil or any part of the cannabis plant. Patients taking this drug should not drive, operate heavy machinery, or engage in hazardous tasks until used to this medication. This medication also should be used cautiously, if at all, for persons with depression, mania, or schizophrenia, elderly patients, patients with cardiac disorders, and for pregnant and nursing women. It is especially inadvisable for nursing women, since marinol is concentrated in the breast milk.

Side effects Promethazine Patients taking promethazine may experience a large number of side effects, including drowsiness, ringing in the ears, a lack of coordination, problems with vision, fatigue, euphoria, nervousness, tremors, seizures, a catatonic-like state, and hysteria. These effects are usually reversible. At high doses, patients may also exhibit extrapyramidal reactions. Extrapyramidal reactions can briefly be described as agitation (jitteriness, sometimes insomnia), muscle spasms, and/ or pseudo-Parkinson’s (a group of symptoms including, but not limited to, drooling, tremors, and a shuffling gait). Patients may also experience rashes, asthma, jaundice, abnormally low production of white blood cells, and abnormalities in how fast or slow their heart beats. Patients may sometimes experience unusual side effects not known as typical for the medication they are taking. These should be reported to the physician. Prochlorperazine Prochlorperazine has many side effects, including low blood pressure, dizziness, blurred vision, skin reactions, and jaundice. Patients also may suffer jaw, neck, and back muscle spasms, slow or difficult speech, and difficulty swallowing, as well as rhythmic face, mouth, or jaw movements. However, the most severe side effects stem from damage to the brain after G A LE EN CY C LO PE DI A O F C AN C ER 3

Two other (rare) disorders, tardive dyskinesia and neuroleptic malignant syndrome (NMS), are also associated with antipsychotic drug use. Patients with NMS have high temperatures, rigid muscles, an altered mental state, and symptoms such as excessive sweating and irregular blood pressure or heart rhythm. Patients with NMS usually respond to treatment. Patients with tardive dyskinesia have involuntary movement of muscles in the chest, arms, and legs, or in the muscles in and around the face (including the tongue). Tardive dyskinesia may be irreversible. Aprepitant Side effects of aprepitant include fatigue, dizziness, stomach pain, nausea, hiccups, diarrhea, constipation, and loss of appetite. More serious, but less common, side effects have been reported, including hives, skin rash, difficulty breathing or swallowing, hoarseness, and swelling in the face, throat, tongue, lips, eyes, feet, ankles, or lower legs. If any of these more serious side effects occur, the patient should contact the treating physician immediately. Serotonin receptor antagonists Side effects include rashes, increased sweating, problems with taste or vision, flushing, agitation, sleep disorder, depersonalization, headache, fatigue, nausea, weakness, abdominal pain, constipation, diarrhea, hypertension, dizziness, chills and shivering, and dry mouth. Patients may also have abnormal liver function tests. Dronabinol Possible side effects are fatigue, weakness, abdominal pain, nausea, vomiting, heart palpitations, fast heart rate, facial flushing, amnesia, anxiety, an abnormal mental state, depersonalization, confusion, dizziness, and euphoria. There are certain additional precautions and side effects associated with each of these drugs. Patients should be sure to notify their physician of any health concerns (including pregnancy) or medications they are taking. Patients should also ask about potential side effects for each individual medication before receiving any of these drugs. G A LE EN CY C LO PE DI A O F C AN CE R 3

Interactions Promethazine Promethazine interacts with central nervous system depressants, like alcohol and barbiturates. Therefore, the physician should be alerted to any medications the patient is taking, and doses of the drugs should be adjusted accordingly. Alcohol should be avoided. It has not been proven, but promethazine may interfere with the action of epinephrine. Prochlorperazine Like promethazine, prochlorperazine should be used cautiously, or not at all, with central nervous system depressants like alcohol and barbiturates. Prochlorperazine has also been shown to interact with anticonvulsant medication, guanethidene, propanolol, thiazide diuretics, and oral anticoagulants (like warfarin and coumadin). Aprepitant A physician can check the long list of possible drug interactions, which include possible effects on the action of certain chemotherapy drugs. Aprepitant also may interact with the blood thinner warfarin (Coumadin) and other popular drugs. The treating physician or pharmacist will need a complete list of other drugs the patient is taking before prescribing this antiemetic. Serotonin receptor antagonists These drugs may have very negative effects on the patient when combined with diuretics, anti-arrhythmia drugs, or high doses of anthracycline. Dronabinol Dronabinol interacts with the antiemetic prochlorperazine synergistically. Therefore, the use of these two drugs in combination results in a greater antiemetic effect. Patients taking central nervous system depressants, such as barbiturates or alcohol should notify their physician before taking marinol, since marinol may increase their effect. Although no drugs have been shown to interact with marinol, many drugs similar to marinol do interact with a number of other drugs, including central nervous system depressants such as alcohol or barbiturates, or drugs like flouxetine or disulfiram. Again, the physician should be alerted to any medications the patient is taking before beginning a course of dronabinol. See also Corticosteroids; Lorazepam; Metoclopramide; Scopolamine. 115

Antiemetics

long-term use. These symptoms may be reversed by treating the patient with drugs effective in treatment of Parkinson’s patients (except levodopa). A reduction or elimination in the amount of the antipsychotic medication may also be necessary to eliminate these symptoms.

Antiestrogens

Resources PERIODICALS

Boothby, Lisa A., and Paul L. Doering. ‘‘New Drug Update 2003: Part 1.’’ Drug Topics (February 23, 2004): 54.

Michael Zuck, PhD

Antiestrogens Definition Antiestrogens are a group of medications that block the effect that estrogen has on the growth of a tumor.

Purpose For about 20 years, antiestrogens have been used mainly to help prevent and treat breast cancer. Since many breast cancer tumors use hormones to fuel their growth, blocking the hormones limits their ability to grow.

Description Antiestrogens refer to a group of drugs. Many breast cancer tumors grow due to normal levels of estrogen, a hormone found in the bloodstream. Some patients have tumors that are extra-sensitive to this normal estrogen level. The estrogen attaches to the area on the outside of the tumor cells and sends a signal to the cell that causes it to grow and multiply. Antiestrogens block the protein on the outside wall of the estrogen-sensitive breast cancer cell. By blocking this protein, known as the estrogen receptor, the freefloating estrogen cannot stimulate the cancer cells to grow and multiply any further. The drug tamoxifen is a common antiestrogen that has proven to have a positive effect in breast cancer patients for both treatment and prevention. The drug raloxifene is a newer antiestrogen. Early research showed that raloxifene worked against breast cancer with fewer side effects than tamoxifene. In 2003, research also showed that raloxifene may be effective in decreasing new fractures among women with low bone mineral density. However, further clinical trials on raloxifene are needed.

Precautions Use of tamoxifen has been associated with a number of side effects, including vaginal bleeding, 116

menstrual irregularities, and hypercalcemia (excess calcium in the blood). Most women also experience hot flashes while using the drug. Serious side effects include endometrial cancer and thromboembolism (blocking of a blood vessel by a particle of a blood clot at the site the blood clot formed). In late 2003, cancer experts were beginning to recommend a new group of drugs called aromatase inhibitors (Arimidex, common name anastrozole or Femara and Novartis, common name letrozole) as an alternative to tamoxifen or following tamoxifen therapy. These drugs fight breast cancer differently, but early research shows they fight it as effectively and with fewer side effects. Resources PERIODICALS

Lewis, Jilene. ‘‘Breast Cancer Guidelines Suggest Alterna tive to Standard Therapy.’’ Drug Topics August 18, 2003: 22. Pennachio, Dorothy L. ‘‘Letrozole Improves Breast Cancer Outlook.’’ Patient Care December 2003: 4. ‘‘Raloxifene Decreases New Fractures in Women with Vertebral Cracks at Baseline.’’ Women’s Health Weekly December 4, 2003: 84. ‘‘Revised Guidelines Show Changes for Breast Cancer Treatment.’’ Biotech Week December 24, 2003: 296. OTHER

Hormonal Therapy, Breast Cancer Treatment. People Living with Cancer. http://www.peoplelivingwithcancer.org.

Nancy J. Beaulieu, RPh.,BCOP Teresa G. Odle

Antifungal therapy Definition Antifungal drugs are used to treat infections caused by fungi and to prevent the development of fungal infections in patients with weakened immune systems.

Purpose Fungal infections A fungus is a living organism that can cause infection when it grows in the human body. In healthy people, fungal infections tend to be mild and treatable. For cancer patients, however, fungal infections can become severe and must be treated quickly. Cancer patients, particularly those with leukemia or G A LE EN CY C LO PE DI A O F C AN C ER 3

K E Y T ERM S Aspergillosis—A fungal infection that can be lifethreatening to patients with a weakened immune system. Candidiasis—A fungal infection that can be mild or very serious depending on what part of the body it infects. Cryptococcosis—A fungal infection that can cause meningitis. Intravenous—A treatment that is given directly into the bloodstream. Prophylactic—Referring to a drug or other treatment given to prevent disease. Topical—A treatment that is applied directly to the skin.

lymphoma, tend to have weakened immune systems as a result of chemotherapy or the disease. Once they are infected, their weak immune system allows the fungus to grow quickly. Because of this risk, some cancer patients with no obvious fungal infection are given antifungal therapy to help prevent infection from developing. This approach to treatment is called prophylaxis or prophylactic therapy. Fungal infection can occur in two ways. Some fungi, such as candida, are usually found in the bodies of healthy people and cause little or no harm. When the immune system is weak, however, these fungi begin to grow and cause infection. Other fungi, such as aspergillus and cryptococcus, are found in the air. Infection occurs when the fungus is either inhaled into the lungs or comes into contact with an operative wound. The most common fungal infections found in patients with weakened immune systems are candidiasis, aspergillosis and cryptococcosis. Diagnostic innovations in antifungal therapy in cancer patients include the increased use of nonculture-based tests to speed up the process of diagnosis. Treatment The treatment of a fungal infection depends on the type and location of infection. Superficial infections that affect the skin, hair, and nails can be treated with topical (cream or ointment) or oral antifungal drugs. Systemic infections that affect the internal organs require aggressive treatment with either oral or intravenous drugs. G A LE EN CY C LO PE DI A O F C AN CE R 3

There are three classes of drugs typically used to treat fungal infections: polyenes, azoles, and echinocandins. Polyenes Polyenes are drugs that work by attaching to the sterol component found in the fungal membrane, causing the cells to become porous and die. The two polyenes most commonly used are nystatin (Mycostatin) and amphotericin B (Fungizone). Nystatin is often used as a topical agent to treat superficial infections, or is taken orally to treat such candidal infections as oral or esophageal candidiasis. Amphotericin B was the first antifungal drug to be approved for use, and it is still the standard therapy for the most severe systemic fungal infections. Recently, several new types of amphotericin B (Abelcet, Amphotec and AmBisome) have been introduced. These drugs, called lipid formulations, cause fewer side effects than traditional amphotericin B but are more expensive. Azoles Azoles stop fungal growth by preventing fungi from making an essential part of their cell wall. Three typical azoles are ketoconazole (Nizoral), fluconazole (Diflucan), and itraconazole (Sporanox). Ketoconazole is the oldest of these three drugs, and has been used since the 1970s. It is slightly more toxic than the other azoles and does not work for aspergillosis and many candidiasis infections. Although fluconazole is effective against both superficial and systemic candidiasis, some strains of this fungus have now become resistant to the drug. Itraconazole, the newest of the azoles, is effective against a range of different fungal infections. Unlike ketoconazole or fluconazole, it can be used to treat aspergillosis. Newer azole medications include voriconazole (Vfend), approved by the FDA in the fall of 2001, and posaconazole, approved in September 2006. Echinocandins Echinocandins are a new class of antifungal drugs that work by disrupting the wall that surrounds fungal cells. Caspofungin (Cancidas) is the first of this new class of drugs to be approved. It is an effective treatment for severe systemic fungal infections, and is given to patients who do not respond to other therapies. Micafungin, another drug in this class, has been used 117

Antifungal therapy

Description

Antifungal therapy

in Japan to treat aspergillosis in leukemia patients but has not been approved by the FDA for use in the United States.

Recommended dosage Although dosages differ for the various antifungal treatments, most therapies continue even after there is no sign of infection. Polyenes Topical nystatin should be liberally applied two to three times daily. Liquid formulations of the drug are usually taken in doses of 400,000 to 600,000 units four times a day for adults and children. The dose for the oral tablets is 500,000 to 1 million units every 8 hours. Both traditional amphotericin B and the new lipid formulations of the drug are given intravenously. Dosages are adjusted according to each patient’s tolerance and the severity and location of the infection. Patients receiving amphotericin B treatment are usually hospitalized. Azoles Ketoconazole is available as a tablet and as a topical treatment. Both treatments are usually given once daily. Treatment can last for several weeks for superficial infections, or up to a year for more serious infections. Fluconazole and itraconazole are both administered either orally or intravenously. The dose depends on the type of fungal infection, the patient’s condition and the response to treatment. Echinocandins Caspofungin is given intravenously once daily, and most patients receive the same dose.

Precautions Patients who are given topical or oral antifungal therapy should make sure they use their medication regularly, and for as long as their doctor thinks is necessary. Infections that are not completely eradicated frequently recur.

Side effects Antifungal drugs that are applied topically rarely cause side effects unless the patient is allergic to the drug. Side effects are more common when drugs are taken orally or intravenously. The most common reactions from azole drugs are nausea, diarrhea and other gastrointestinal symptoms. These symptoms usually affect less than 10% of patients. Caspofungin also 118

produces few side effects. The most common side effect is a rash. Amphotericin B can be quite toxic and most patients experience side effects. These include fever, rigors, and chills. Premedication with acetaminophen, diphenhydramine, hydrocortisone, and sometimes meperidine can be given to prevent these side effects. Amphotericin B can also seriously damage the kidneys. However, patients are carefully monitored while taking this drug. If symptoms develop, the liposomal alternative is usually given. Lipid formulations of amphotericin B are far less damaging to the kidneys.

Interactions Drug interactions are significant with antifungal treatment. Patients taking amphotericin B should not take any other drug that can cause kidney damage. Potentially serious reactions can occur when patients taking azole antifungal therapies also take certain antihistamines such as astemizole (Hismanal) or the statin drug lovastatin (Mevacor). Patients on antifungal therapy who plan to take other prescribed, over the counter, or alternative medicines should always check with their doctor first. Resources BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Systemic Fungal Diseases (Systemic Mycoses).’’ In The Merck Manual of Diagnosis and Therapy. White house Station, NJ: Merck Research Laboratories, 2007. Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L. Stang. Nurse’s Drug Guide 2003. Upper Saddle River, NJ: Prentice Hall, 2003. PERIODICALS

Hubel, K., J. Chemnitz, H. G. Brochhagen, and O. A. Cornely. ‘‘Successful Treatment of Chronic Dissemi nated Candidiasis with Caspofungin and Itraconazole in a Patient with Progressive Acute Leukemia and Pro longed Neutropenia.’’ International Journal of Hema tology 79 (April 2004): 289 292. Karthaus, M., A. J. Ullmann, and O. A. Cornely. ‘‘Current Development in the Diagnostics and Therapy of Sys temic Fungal Infections in Cancer Patients.’’ [in Ger man] Wiener medizinische Wochenschrift 154 (May 2004): 199 208. Ostrosky Zeichner, L. ‘‘Novel Approaches to Antifungal Prophylaxis.’’ Expert Opinion on Investigational Drugs 13 (June 2004): 665 672. Ota, S., J. Tanaka, K. Kahata, et al. ‘‘Successful Micafungin (FK463) Treatment of Invasive Pulmonary Aspergillo sis in a Patient with Acute Lymphoblastic Leukemia in a Phase II Study.’’ International Journal of Hematology 79 (May 2004): 390 393. G A LE EN CY C LO PE DI A O F C AN C ER 3

ORGANIZATIONS

American Society of Health System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657 3000. www.ashp.org. United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857 0001. (888) INFO FDA. www.fda.gov.

Alison McTavish, M.Sc. Rebecca J. Frey, PhD

Antimicrobials

pneumonia existed. Patients with infected wounds often had to have a wounded limb removed, or face death from infection. Now, most of these infections can be easily cured with a short course of antimicrobials. However, the future effectiveness of antimicrobial therapy is somewhat in doubt. Microorganisms, especially bacteria, are becoming resistant to more and more antimicrobial agents. Bacteria found in hospitals appear to be especially resilient, and are causing increasing difficulty for the sickest patients–those in the hospital. Currently, bacterial resistance is combated by the discovery of new drugs. However, microorganisms are becoming resistant more quickly than new drugs are being found, Thus, future research in antimicrobial therapy may focus on finding how to overcome resistance to antimicrobials, or how to treat infections with alternative means. Michael Zuck, PhD

Definition Antimicrobial drugs are used to fight infections caused by bacteria, fungi, and viruses.

Description Antimicrobial drugs are drugs designed to kill, or prevent the growth of microorganisms (bacteria, fungi, and viruses). Bacteria, fungi, and viruses are responsible for almost all of the common infectious diseases found in North America from athlete’s foot, to AIDS, to ulcers. Interestingly enough, many disorders formerly thought to be caused by other factors, like stress, are now known to be caused by bacteria. For example, it has been shown that many ulcers are caused by the bacteria Helicobacter pylori, and not by stress, as many originally thought. Thus, antimicrobials represent an important part of medicine today. The history of antimicrobials begins with the observations of Pasteur and Joubert, who discovered that one type of bacteria could prevent the growth of another. They did not know at that time that the reason one bacteria failed to grow was that the other bacteria was producing an antibiotic. Technically, antibiotics are only those substances that are produced by one microorganism that kill, or prevent the growth, of another microorganism. Of course, in today’s common usage, the term antibiotic is used to refer to almost any drug that cures a bacterial infection. Antimicrobials include not just antibiotics, but synthetically formed compounds as well. The discovery of antimicrobials like penicillin and tetracycline paved the way for better health for millions around the world. Before 1941, the year penicillin was discovered, no true cure for gonorrhea, strep throat, or G A LE EN CY C LO PE DI A O F C AN CE R 3

Antineoplastic agents Definition Antineoplastic agents are a group of specialized drugs used primarily to treat cancer (the term ‘‘neoplastic’’ refers to cancer cells). Some patients and clinicians refer to antineoplastic agents as chemotherapy.

Description The first antineoplastic agents, used in the 1940s, were made from either synthetic chemicals or natural plants. Antineoplastic agents are classified by origin and by how they work to destroy cancer cells. As of 2009, there are over one hundred of these agents approved by the Food and Drug Administration (FDA) to be used in the United States. These include: methotrexate, 5-fluorouracil (fluorouracil), doxorubicin, paclitaxel, and cyclophosphamide to name a few. Antineoplastic agents can be administered to patients alone or in combination with other antineoplastic drugs. They can also be given before, during or after a patient receives surgery, radiation therapy, biological therapies and/or bone marrow or hematopoietic stem cell transplants. Antineoplastic agents can be given via many different routes including orally, intravenously, intramuscularly, intra-arterially, intra-peritoneally and topically as well as by other routes of administration. 119

Antineoplastic agents

Rubin, Z. A., and J. Somani. ‘‘New Options for the Treat ment of Invasive Fungal Infections.’’ Seminars in Oncology 31 (April 2004): 91 98.

Antioxidants

QUESTIONS TO ASK YOUR PHARMACIST 

 



 



Which antineoplastic agent(s) have I been prescribed to treat my cancer? How long can I expect to be on these drugs? Will I need to be in the hospital to receive chemotherapy or can I receive the drugs in my oncologist’s office What kinds of experience do my oncologist and oncology nurses have with administering the types of drugs I will be receiving? What kinds of side effects can I expect? How will my oncologist know if these drugs are working for me? Will there be any long-term consequences to my taking these drugs?

to cancer. For instance, they may improve the effectiveness of chemotherapy, decrease side effects of chemotherapy and radiotherapy, and prevent some types of cancer. Sufficient epidemiological studies have shown that ingesting foods high in antioxidants, such as fruits and vegetables, can decrease the risk of many types of cancer. Studies also found that cancer patients have lower levels of antioxidants in their blood. In early 2004, the National Cancer Institute (NCI) released a new fact sheet concerning cancer prevention and antioxidants. Fruits and vegetables are high in antioxidants and evidence continued to support the role of vitamins C, E, and A, as well as lycopene and beta-carotene in helping to prevent cancer. However, clinical trial results have not been consistent. The NCI reported that three large clinical trials were trying to better answer the role of antioxidants in cancer prevention.

Precautions The treatment plan is disease-specific. It is important that patients receive treatment on schedule. Antineoplastic agents travel the body and destroy cancer cells. Side effects are expected to occur when treated with these agents, and can include nausea, mouth sores, hair loss, and lowering of the blood counts. Many of the side effects associated with antineoplastic agents occur because chemotherapy treatment destroys the body’s normal cells in addition to cancerous cells. Healthcare providers should be able to assist patients in managing these side effects so that antineoplastic therapy is a tolerable treatment. Nancy J. Beaulieu, RPh., BCOP Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Antioxidants Definition Antioxidants are chemical compounds that can bind to free oxygen radicals preventing these radicals from damaging healthy cells.

Purpose Preliminary studies have suggested that antioxidants are useful in a number of ways in regards 120

Studies of antioxidant supplements to decrease the risk of cancer have not been conclusive. Most antioxidant research has centered around vitamins A (and its provitamin, beta-carotene), C, E (alpha-tocopherol), and the trace element selenium. While some studies have shown positive effects for antioxidants in preventing cancer, they have been conducted mostly in underfed populations or persons otherwise deficient in these antioxidants. The CARET studies in the early 1990s found that if smokers take beta-carotene and vitamin A supplements they actually increase their risk of developing lung cancer. Rather than isolated antioxidants found in supplements, it may be the combination of antioxidants found in foods that are responsible for decreasing the risk of cancer. The American Institute of Cancer Research warns that antioxidant supplements cannot substitute for whole foods. Individuals who may want to consider supplements include those who are underfed, have certain medical conditions, chronic dieters, some vegetarians, some seniors, and newborns. Concern has developed about potential negative interactions between high doses of antioxidants and chemotherapy. Anthracycline antitumor antibiotics used as chemotherapy act by creating free oxygen radicals to kill tumor cells through a process known as apoptosis. Although patients taking antioxidants may improve their tolerance to chemotherapy drugs, they may be decreasing the effectiveness of treatment and risking a recurrence of the tumor in the long run. This viewpoint is theoretical, however, and no clinical studies have as yet addressed it. Patients interested in G A LE EN CY C LO PE DI A O F C AN C ER 3

Apoptosis—A type of cell death. A mechanism by which one cell dies if it becomes severely mutated as a means of protecting the entire organism. Cisplatin—An anticancer drug. Doxorubicin—An anticancer antibiotic therapy. Its trade name is Adriamycin Fluorouracil—An anticancer drug. Its trade names include Adrucil, 5-FU, Efudex, and Fluoroplex. Mutation—A change in the genetic structure of the cell. Oxidative stress—A condition where the body is producing an excess of oxygen-free radicals.

using antioxidants during chemotherapy or radiotherapy should discuss this option with their physicians. High doses of vitamins and minerals can be toxic. The National Academy of Sciences has suggested safe upper intake levels for adults for some antioxidants. These limits are 2,000 milligrams of vitamin C per day from both foods and supplements combined, 1,000 milligrams of vitamin E per day, and 400 micrograms per day of selenium from both supplements and foods. It is not known how higher levels than these will affect healthy persons. Side effects of vitamin E overdose may include fatigue, intestinal cramping, breast soreness, thrombophlebitis, acne, and diarrhea, and increase in blood pressure in certain people. Blood clotting time has been shown to increase. Vitamin E is antagonistic to iron at certain levels. Patients with anemia who are taking iron supplements should not take the two supplements at the same time. Vitamin E also may interfere with vitamin K. Selenium toxicity is characterized by dermatologic lesions, brittle hair, fragile or black fingernails, metallic taste, dizziness, and nausea.

Description Free radicals are naturally produced in the body through the normal metabolism of amino acids and fats. These free radicals are unstable molecules that can freely react with and destroy healthy cells. They can bind to and alter the structure of DNA thus leading to mutations and eventually to cancer. Besides cancer, this oxidative stress on the cells can lead to heart, eye, and neurological diseases. Glutathione, lipoic acid, and CoQ10 are antioxidants formed naturally by the body but their levels G A LE EN CY C LO PE DI A O F C AN CE R 3

Although controversy will surround the topic of supplemental antioxidants for some time, there is little if any controversy that dietary levels of antioxidants are useful in preventing cancer. Because of this evidence, the American Cancer Society suggests five servings of fruits and vegetables each day. Resources BOOKS

Moss, Ralph W. Antioxidants Against Cancer. Brooklyn, NY: Equinox Press, Inc., 2000. PERIODICALS

‘‘Chocolate’s Dark Health Secret.’’ Muscle & Fitness/Hers December 2003: 22. Kelly, Kara M. ‘‘The Labriola/Livingston Article Reviewed.’’ Oncology 13, no. 7 (1999): 1008 1011. Labriola, Dan, and Robert Livingston. ‘‘Possible Interactions Between Dietary Antioxidants and Chemotherapy.’’ Oncology 13, no. 7 (1999): 1003 1008. Lamson, Davis W, and Matthew S. Brignall. ‘‘Antioxidants in Cancer Therapy: Their Actions and Interactions with Oncologic Therapies.’’Alternative Medicine Review 4, no. 5 (1999): 304 329. ‘‘‘Musical Fruit’ Rich Source of Healthy Antioxidants; Black Beans Highest.’’ Cancer Weekly December 23, 2003: 102. ‘‘Update on Antioxidants.’’ Nutrition Today January February 2004: 25 31. OTHER

http://www.medical.com.hk/english_site/pharmacy_site/ vitamins_s/selenium/selenium_m.htm. ORGANIZATIONS

American Cancer Society. http://www.cancer.org. American Institute for Cancer Research. 1759 R Street, NW, PO Box 97167, Washington, DC 20090 7167. (800)843 8114. http://www.aicr.org. National Academy of Science. http://www.nas.edu.

Cindy Jones, Ph.D. 121

Antioxidants

K E Y T ERM S

decline with age. Vitamins C and E are necessary antioxidants but not produced by the body and must be obtained from the diet. The most common antioxidants are the vitamins A, C, and E. Additional antioxidants are natrol, found in grapes and wine; selenium; and melatonin. Flavonoids consist of a large family of antioxidant compounds found in fruits and vegetables. Among the well-studied flavonoids in terms of cancer prevention are catechins from green tea, genistein from soy, curcumin from turmeric, anthocyanosides from blueberries, and quercetin from yellow vegetables. More recent studies have added clack beans to the list of foods high in antioxidants and a 2003 study in Rome reported that women who ate dark chocolate showed some antioxidant benefits.

Antiviral therapy

Antiviral therapy Definition Antiviral therapy is often used by cancer patients to treat viral infections. Commonly used antiviral medications include acyclovir, famciclovir, ganciclovir, valacyclovir, and foscarnet.

Description Viral infections occur in almost all people at some time in their lives. The common cold is the most easily recognizable example of a virus that can be unpleasant but generally does not cause serious problems. For people with cancer, however, viruses can often cause life-threatening illnesses. Viral infections in cancer patients can be much more serious and debilitating than in patients without cancer. Cancer patients will often have weakened immune systems from chemotherapy or from the cancer itself. Cancer patients who have bone marrow transplants are at especially high risk for life-threatening viral infections. Immediately after the transplant, the patient will have very few, if any, white blood cells, which are the body’s main infection fighters. Viral infections such as herpes simplex virus (HSV), herpes zoster virus (HZV), and cytomegalovirus are often seen in cancer patients, and all can cause serious, life-threatening infections. Until the development of the antiviral drug acyclovir 1974, no relatively safe and effective anti-viral medications for cancer patients were available. By the mid-1980s, acyclovir was being routinely used for cancer patients with herpes infections. Besides treating the infection itself, acyclovir can be taken on a daily basis to prevent infection from occurring. This can be especially important in people with very depressed immune systems, such as cancer patients who have undergone a bone marrow transplant. Since the introduction of acyclovir, other antiviral medications have been developed that have been very useful in the treatment of viral illnesses. For reasons that are still unknown, certain herpes infections in certain cancer patients do not respond to acyclovir. Fortunately, two other newer medications similar to acyclovir, called famciclovir and valaciclovir, are helpful in treating herpes infections, especially ones that are resistant to acyclovir. While antiviral drugs such as acyclovir have made a large difference in treating herpes infections in cancer patients, there are other viral infections that do not respond to acyclovir. Cytomegalovirus is a common 122

KEY T ERMS Herpes simplex virus—An infectious, contagious viral disease, caused by herpes simplex virus type one or two. It is characterized by fluid-filled lesions that can recur. Herpes zoster virus—An acute, infectious viral disease, characterized by painful, fluid-filled lesions. Cytomegalovirus—A viral disease caused by a herpes virus, generally rare but often seen in cancer patients. It can cause life-threatening pneumonia as well as blindness. Teratogenic—Causes abnormalities to occur in developing embryos. Gout—A condition, most often occurring in men, caused by a buildup of uric acid crystals deposited in joints, commonly the big toe.

viral infection among cancer patients, and especially common among cancer patients who have had bone marrow transplants. Some antiviral medications like acyclovir are not effective against cytomegalovirus. Fortunately, two other antiviral medications known as ganciclovir and foscarnet are both effective against cytomegalovirus.

Recommended dosage The recommended dosage for the various antiviral medications can vary considerably, depending on the health of the patient and how the medication is administered. For the treatment of herpes simplex and herpes zoster, the drugs acyclovir, famciclovir, and valacyclovir can be used. The recommended oral dosage ranges from 500 mg twice a day for valacyclovir, 500 mg three times a day for famciclovir, to 800 mg every four hours for acyclovir. There is also a formulation for the drug to be given administered though the vein. The dose for injection is different than the dose for oral therapy. For the treatment of Cytomegalovirus, ganciclovir or foscarnet can be used. Both medications are generally given intravenously, although there is an oral formulation available for ganciclovir. The dosage is 5 mg per kg of body weight every 12 hours for 14 to 21 days, followed by maintenance therapy at a dose of 5 mg per kg per day as a single daily dose. The dosage for foscarnet ranges from 40 mg per kg to 90 mg per kg, depending on the diagnosis. G A LE EN CY C LO PE DI A O F C AN C ER 3

The drugs acyclovir, famciclovir, valcyclovir, ganciclovir and foscarnet should all be used with caution by patients with kidney problems. With higher doses of these drugs, patients who do have kidney problems should have their kidney functioning monitored closely on a daily basis. The dosage is usually decreased depending on the degree of decreased kidney function. Kidney failure has been reported in patients taking high doses of foscarnet. Ganciclovir should be used with extreme caution in women who may be pregnant, since it is teratogenic (causes abnormalities), as well as toxic, to developing embryos. There are no well-controlled studies of the other antiviral agents in pregnant women and it is not known whether these agents are excreted in breast milk. Therefore, it is not recommended that these antiviral agents be given to pregnant or nursing mothers unless the benefit outweighs the risk.

Side effects Side effects common to all the antiviral medications include nausea, vomiting, diarrhea, headaches, and dizziness, rash, and decreased kidney function. Of the drugs used to treat herpes simplex, acyclovir seems to have more reported side effects than the other medications. The two drugs that are used to treat cytomegalovirus, ganciclovir and foscarnet, have very different side effect profiles. Ganciclovir’s major side effect is the lowering of white blood cells, a condition known as neutropenia. Because of this, a patient on ganciclovir should have their white blood cell count monitored closely. Foscarnet, while generally not causing a marked decrease in white blood cells, can cause sudden kidney failure. Patients who are taking foscarnet should make sure they maintain their fluid intake and have their kidney functions monitored closely.

Interactions The antiviral drugs used to treat herpes simplex and zoster should be used with caution with other drugs that cause kidney problems. Also, they all interact with probenecid, a medication commonly used to treat gout. Drug interactions with foscarnet and ganciclovir are more numerous and potentially dangerous. Both, especially foscarnet, must be used with caution with other drugs that cause kidney problems. Both must also be used with caution with other medications that lower seizure thresholds. Patients should notify their G A LE EN CY C LO PE DI A O F C AN CE R 3

physician or consult with their pharmacist prior to starting any over the counter or herbal medications due to the numerous drug interactions that can occur with these agents. Edward R. Rosick, DO, MPH, MS

Aromatase inhibitors Definition Aromatase inhibitors are a class of hormone drugs. They inhibit aromatase, an enzyme that regulates the production of estrogen.

Purpose The aromatase inhibitors decrease blood and tumor levels of estrogen in postmenopausal women. They are used in the treatment of some types of breast cancer in post-menopausal women.

Description Aromatase inhibitors lower a postmenopausal woman’s estrogen levels, thereby preventing the cancer cells that are dependent on estrogen from growing. U.S. brand names Aromatase inhibitors in the United States include Arimidex, Aromasin, and Femara. Anastrazole (trade name Arimidex) Anastrazole is a non-steroidal aromatase inhibitor that lowers blood levels of estradiol to prevent the rapid growth of cancerous cells. It is usually used in postmenopausal women as a treatment for advanced breast cancer that has not responded to other therapies, or it can be used as first-line therapy in breast cancer patients. Anastrazole is also indicated in the treatment of post-menopausal breast cancer which is hormone receptor positive early breast cancer. It is also indicated to treat advanced breast cancer in post-menopausal women whose cancer has progressed following treatment with tamoxifen. Exemestane (trade name Aromasin) Exemestane is an aromatase inhibitor that reduces the concentration of estradiol in the bloodstream. It is also called an aromatase inactivator because it inactivates aromatase irreversibly, potentially providing 123

Aromatase inhibitors

Precautions

Aromatase inhibitors

QUESTIONS TO ASK YOUR PHARMACIST 

 



Which aromatase inhibitor have I been prescribed? What side effects should I anticipate? Will this drug interact with any of the other medications I am taking? How long will I be taking this drug?

continued benefits after treatment is stopped. It is used to treat advanced breast cancers in postmenopausal women whose cancers have not responded to other antiestrogen therapies. It is also indicated in the adjuvant treatment of post-menopausal women with estrogen receptor positive (ER positive) early breast cancer who received 2-3 years of tamoxifen therapy and who are switched to exemestane theapy for a total of five consecutive years of adjuvant hormonal therapy.

drugs are generally prescribed for postmenopausal women, pregnancy is not usually an issue. Except in life-threatening conditions, anastrazole, exemestane, and letrozole are not used in pregnancy because of risks to the fetus. These drugs should be avoided by people allergic to them and by nursing mothers.

Side effects The aromatase inhibitors are generally tolerated well. Side effects are similar to the effects of decreased estrogen, such as hot flashes. People should report any side effects to the doctor. Anastrazole Rash is the most common side effect of anastrazole. Less common side effects include:    

Letrozole (trade name Femara) Letrozole is a non-steroidal aromatase inhibitor that lowers blood estrogen levels by hindering the conversion of androgens to estrogens. Letrozole therapy is prescribed as part of adjuvant treatment for post-menopausal women with hormone receptor positive early breast cancer; as extended adjuvant treatment of early breast cancer in post-menopausal women who have received five years of adjuvant therapy with tamoxifen; and for the first-line treatment of post-menopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer. It is used in postmenopausal women with advanced breast cancer that has progressed while on other antiestrogen therapy.



      

Exemestane Side effects include: 

Recommended dosage

 

Anastrazole: The adult dose is 1 mg a day by mouth  Exemestane: The adult dose is 25 mg a day by mouth, after a meal  Letrozole: The adult dose is 2.5 mg a day by mouth. Reduction in the dose of letrozole is recommended in women with cirrhosis and severe liver dysfunction. 

hot flashes headache, light-headedness, dizziness, confusion depression, insomnia, anxiety chest pain, high blood pressure, obstruction of blood vessels nausea and vomiting, diarrhea, constipation, abdominal pain dry mouth, altered taste, appetite loss vaginal bleeding, vulvar itching hair thinning bone pain, tumor pain, weakness, muscle aches cough, sinusitis abnormally low red blood cell levels (anemia) abnormally low white blood cell counts (leukopenia)

    

hot flashes headache, fatigue, insomnia depression, anxiety high blood pressure nausea, vomiting increase in appetite diarrhea, constipation, abdominal pain cough, difficulty breathing Letrozole

Precautions Pregnant or breastfeeding Aromatase inhibitors are not used in pregnant women because of the risk to the fetus. Since these 124

Common side effects include:   

headache nausea, vomiting lethargy G A LE EN CY C LO PE DI A O F C AN C ER 3



appetite loss (anorexia) rash, itching Less common side effects include:

      

drowsiness, dizziness depression, anxiety high blood pressure constipation, diarrhea, heartburn hair loss hot flashes, sweating cough, difficulty breathing

Interactions Patients who are taking any kind of prescription drug, over-the-counter drug, or herbal remedy should notify their physician before beginning any treatment with aromatase inhibitors. See also Megestrol acetate; Tamoxifen. Resources PERIODICALS

Deeks, E.D. & Scott, L.J. ‘‘Exemestane: A Review of Its Use in Postmenopausal Women with Breast Cancer.’’ Drugs 2009:889 918. Nabholtz, J.M., et al.‘‘Comparative Review of Anastrzole, Letrozole, and Exemestane in the Management of Early Breast Cancer.’’ Expert Opin Pharmacother. 2009:1435 47.

Rhonda Cloos, R.N. Teresa G. Odle Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Arsenic trioxide Definition Arsenic trioxide is an antitumor agent used in the treatment of a specific type of leukemia known as acute promyelocytic leukemia (APL).

Purpose Arsenic trioxide is used to treat acute promyelocytic leukemia in patients who have not responded to standard treatment or who have relapsed following standard treatment. The drug is indicated for those patients whose APL is characterized by the presence of a specific chromosome translocation, t(15;17), or PML/RAR-alpha gene expression as confirmed by cytogenetic testing. G A LE EN CY C LO PE DI A O F C AN CE R 3

Description U.S. brand names The brand name for arsenic trioxide in the United States is Trisenox. The exact mechanism of action of arsenic trioxide is not completely known at this time. However, the drug appears to cause damage to the fusion protein PML/RAR alpha, which is a protein present in APL. Once the gene which produces this fusion protein is corrected, the body no longer produces immature malignant myelocytic cells and normal white blood cells are again able to be produced by the body. Once this occurs, cytogenetic complete response to therapy has been achieved. Arsenic trioxide, like many other antineoplastic (antitumor) agents, acts by interfering with the growth of cells. Unfortunately, these drugs affect the growth of normal cells and tumor cells. In some patients the drug may have to be discontinued because normal cell growth is too severely affected. For example, a patient taking a large dose of arsenic trioxide might see tumor growth stop. However, the dosage might be high enough to also stop the body’s normal growth of platelet cells. The loss of platelets might cause severe internal bleeding–a consequence more immediately toxic than the tumor.

Recommended dosage Doses vary from individual to individual and depend on body weight as well as other medications the patient is taking. The dose to induce remission in acute promyelocytic leukemia for adults and children five years of age and older are up to 60 doses of 0.15 mg/kg of body weight per day until bone marrow remission occurs. Three to six weeks after induction therapy is finished, consolidation therapy with arsenic trioxide is started at a dose of 0.15 mg/kg/d for 25 doses within a period of no more than 5 weeks. This medication is administered intravenously.

Precautions Pregnant or breastfeeding women Arsenic trioxide has been shown to cause fetal abnormalities and miscarriage in animals. Women who might become pregnant should take precautions to ensure they do not become pregnant while taking this drug. Women who are nursing their infants should discontinue nursing while this medication is in their system. 125

Arsenic trioxide



Ascites

Pediatric There is limited data related to the effectiveness of arsenic trioxide in the treatment of patients under the age of 18. Children younger than five years of age should not be administered this drug as safety and effectiveness of arsenic trioxide in this age group have not been studied. Recommended blood testing for patients undergoing treatment with arsenic trioxide include monitoring of electrolyte values and complete blood count (CBC) with coagulation profile at least twice per week in the induction phase of therapy. Critically ill patients may require more frequent lab testing. During the consolidation phase of treatment lab studies should be monitored at least weekly. EKG testing should also be conducted prior to the initiation of therapy and at least once every week during active phases of treatment with arsenic trioxide. Monitoring of kidney function will also be done during therapy with this drug. Patients with bone marrow problems, heart problems, kidney problems, or low levels of magnesium or potassium in the blood should notify their physician before taking any of this medicine. Patients should notify their physician of any illnesses they may have before taking arsenic trioxide. Because persons taking arsenic trioxide may have decreased immunity, it is important for them to avoid infection. Caution should be taken to avoid unnecessary exposure to crowds and people with infections. Patients may experience unusual or excessive bruising and/or bleeding and should avoid situations in which it is likely they could cut or bruise themselves. Patients should consult their physician immediately if they have any indication of excessive bleeding or bruising, including black and tarry stools, blood in the urine or stools, unusual bleeding or bruising, pinpoint red marks on their skin, vomit containing blood or what appears to be coffee grounds (dried blood). Severe symptoms may indicate a medical emergency.

QUESTIONS TO ASK YOUR PHARMACIST 



 



Can my type of leukemia be treated with arsenic trioxide? What types of symptoms should I report to my doctor or nurse? How long can I expect to be on this medication? How will my oncologist know if this drug is working for me? Will this drug interact with any other medications I am currently taking?

Interactions Patients should tell their doctors if they have a known allergic reaction to arsenic trioxide or any other medications or substances, such as foods and preservatives. Before taking any new medications, including nonprescription medications, vitamins, and herbal medications, the patients should notify their doctors. This drug should be administered with caution in patients who are concurrently receiving medications which may cause EKG changes such as a prolonged QT interval or electrolyte abnormalities. These medications include certain antiarrhythmic drugs, the drug thioridazine, diuretic drugs and the drug amphotericin B. Michael Zuck, Ph.D. Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Arteriography, Angiogram see Angiography

Side effects Symptoms such as fever, difficulty breathing, weight gain and symptoms related to cardiac and pulmonary side effects may be experienced by some patients during treatment. These symptoms may indicate the occurrence of APL differentiation syndrome and can be fatal if not corrected. Treatment with high dose steroids should be started immediately by the physician and should be continued for at least three days. Patients should always notify their physician about any unusual symptoms they experience while on this medication. 126

Ascites Description Ascites is defined as an excessive amount of fluid built up within the peritoneal cavity. Both the abdominal organs and the abdomen itself are lined with membranes called the peritoneum. Between these two linings is a space referred to as the peritoneal cavity. In pathological conditions that result in edema, or excessive fluid accumulation in bodily tissues, fluid can build up in the peritoneal cavity. G A LE EN CY C LO PE DI A O F C AN C ER 3



rapid weight gain



abdominal discomfort and distention



shortness of breath and actual dyspnea, or difficulty breathing



swollen ankles

Severe cases of ascites can result in the retention of literally gallons (each gallon equals nearly four liters) of liquid in the peritoneal cavity. If fluid retention is sufficiently severe, the abdomen becomes swollen and even painful. Breathing can be affected as the fluid-filled peritoneal cavity presses upon the diaphragm, a very necessary component of respiration. The diaphragm is made up of a dome-shaped sheet of muscles that separates the thoracic, or chest, cavity from the abdomen. When the muscle fibers of the diaphragm contract, the space in the chest cavity is enlarged, and air enters the lungs to fill the enlarged space. When pressure on the diaphragm from fluid build-up occurs, it lessens the ability of these diaphragm muscular fibers to expand and contract, and results in impaired breathing. Ascites, in itself, is not a disease, but rather a symptom of several other pathological conditions. These include: 

Cirrhosis of the liver, which is responsible for 80% of all instances of ascites in the United States.



Pancreatic ascites develops when a cyst that has thick, fibrous walls (pseudocyst) bursts and permits pancreatic juices to enter the abdominal cavity.



Chylous ascites, which has a milky appearance caused by lymph that has leaked into the abdominal cavity. Although chylous ascites is sometimes caused by trauma, abdominal surgery, tuberculosis, or another peritoneal infection, it is usually a symptom of lymphoma or some other cancer.



Cancer causes 10% of all occurrences of ascites in the United States. It is most commonly a consequence of disease that originates in the peritoneum (peritoneal carcinomatosis) or of cancer that spreads (metastasizes) from another part of the body. Tumors especially prone to malignant ascites formation include ovarian cancer and metastatic gastrointestinal tumors.



Endocrine and renal ascites are rare disorders. Endocrine ascites, sometimes a symptom of an endocrine system disorder, also affects women who are taking fertility drugs. Renal ascites develops when blood levels of albumin dip below normal. Albumin is the

G A LE EN CY C LO PE DI A O F C AN CE R 3

major protein in blood plasma. It functions to keep fluid inside the blood vessels.

Causes The two most important factors in the production of ascites due to chronic liver disease are low levels of albumin in the blood and an increase in the pressure within the branches of the portal vein that run through liver (portal hypertension). Low levels of albumin in the blood cause a change in the pressure necessary to prevent fluid exchange (osmotic pressure). This change in pressure allows fluid to seep out of the blood vessels. The scarring that occurs in cirrhosis causes portal hypertension. Blood that cannot flow through the liver because of the increased pressure leaks into the abdomen and causes ascites. Other conditions that contribute to ascites development include:   

hepatitis heart or kidney failure inflammation and fibrous hardening of the sac that contains the heart (constrictive pericarditis)

Persons who have systemic lupus erythematosus but do not have liver disease or portal hypertension occasionally develop ascites. Depressed thyroid activity sometimes causes pronounced ascites, but inflammation of the pancreas (pancreatitis) rarely causes significant accumulations of fluid.

Treatments Reclining minimizes the amount of salt the kidneys absorb, so treatment generally starts with bed rest and a low-salt diet. Urine-producing drugs (diuretics) may be prescribed if initial treatment is ineffective. The weight and urinary output of patients using diuretics is normally carefully monitored, often on a daily basis. This scrutiny involves watching for signs of: 







Hypovolemia (massive loss of blood or fluid) that can often result in drastic drops in blood pressure. Azotemia (abnormally high blood levels of nitrogenbearing materials). Potassium imbalance that can result in cardiac arrhythmia. High sodium concentration. Sodium should be restricted from the diet as much as possible.

Because of the discomfort and respiratory difficulty moderate-to-severe accumulations of fluid can produce, fluid removal, or paracentesis, is often the treatment of choice. Paracentesis involves the extraction of fluid from the abdominal cavity via a needle 127

Ascites

Smaller abdominal fluid amounts usually do not produce symptoms. However, larger accumulations can cause:

Asparaginase

that is usually inserted into the peritoneum under local anesthesia. This is a relatively safe and painless method of relieving fluid build-up. It is considered safer than diuretic therapy, resulting in fewer complications and requiring shorter hospital stays. Large-volume paracentesis is also the preferred treatment for massive ascites. Diuretics are sometimes used to prevent new fluid accumulations, and the procedure may need to be repeated periodically. In cases of ascites that do not respond appropriately to the treatments described above, a peritoneovenous shunt may be inserted. This device is equipped with a one-way valve that allows fluid from the peritoneal cavity to pass into the venous blood circulatory system. From there the fluid is eliminated by the kidneys. In cases of malignant ascites, there is a concern that the use of such a shunt could enhance the spread of the cancer. This relatively small risk must be balanced against the positive effect the shunt can have on the individual’s quality of life as well as against his or her expected survival period. Alternative and complementary therapies Dietary alterations, focused on reducing salt intake, are an important facet of treatment. Potassium-rich foods like low-fat yogurt, mackerel, cantaloupe, and baked potatoes help balance excess sodium intake and help ensure proper heart function. Such complementary therapies should always be considered an adjunct to, not a substitute for, the conventional treatments described above. Resources

Asparaginase is used primarily as part of an induction regimen for the treatment of acute lymphocytic leukemia (ALL) in children. According to the manufacturer, asparaginase is not recommended for use during the maintenance phase of treatment.

Description U.S. brand names Asparaginase, also known as L-asparaginase, is sold under the brand name Elspar in the United States. Asparaginase is an enzyme made from the bacteria escherichia coli (E. coli). In this country, two forms of asparaginase are available: one made from E. coli, and a slightly changed version of the E.Coli form linked to polyethylene glycol (PEG) molecule. This PEG-linked asparaginase is called pegaspargase. This version was made available in 1994, is more expensive than the other form, and is used in patients who have developed an allergy to E. Coli. Asparaginase kills cancer cells by depleting a certain protein in the blood (L-asparagine) that is necessary for survival and growth of tumor cells in patients with ALL. Fortunately, normal cells are not dependent on L-asparagine for survival. Asparaginase is mainly given in combination with vincristine and steroids (either prednisone or dexamethasone) for the first three weeks of therapy.

Recommended dosage Adults and children

PERIODICALS

Bieligk, S.C., B.F. Calvo, and D.G. Coit. ‘‘Peritoneovenous Shunting for Nongynecologic Malignant Ascites.’’ Cancer 91, no. 7 (April 2001): 1247 9. ORGANIZATIONS

National Cancer Institute, National Institute of Health. 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. (800) 4 CANCER. http://www.nci.nih.gov.

Joan Schonbeck, R.N.

Asparaginase Definition Asparaginase is a medicine used to stop growth of cancer and formation of new cancer cells. 128

Purpose

INDUCTION CHEMOTHERAPY FOR ALL. Doses vary between different chemotherapy protocols. The usual dose is 6,000-10,000 units per square meter of body surface area given for 10 days. Patients should refer to individual protocol for recommended dose.

Administration This medicine can be given directly into the muscle (intramuscular) or into the vein (intravenous). Intramuscular injection of asparaginase lowers the risk of severe allergic reactions (also known as hypersensitivity or anaphylaxis). The risk of hypersensitivity reaction is higher with the second and third dose of the drug.

Precautions Pregnant or breastfeeding Breastfeeding mothers should use asparaginase with caution. It is not yet known whether this drug G A LE EN CY C LO PE DI A O F C AN C ER 3

The use of this medication should be avoided in patients with active pancreatitis (inflammation of the pancreas) or history of pancreatitis, and in patients with serious allergic reaction to asparaginase in the past. Asparaginase should only be given in a hospital. A patient’s blood pressure will need to be monitored every 15 minutes for the first hour. A small test dose may be given to check if patient is allergic to this medicine. This medication can lower the body’s ability to fight infections. Patients should avoid contact with crowds or any individual that may have an infection. Contact a doctor immediately if any of these symptoms develop:

Q U E S T I O N S TO A S K Y O U R PHARMACIST 

  





Does my child (or do I) have the type of leukemia that can be treated with asparaginase? What type of side effects should I expect? How long will treatment with this drug last? What kinds of experience do my oncologist and nurses have administering this drug? Is my child (or an I) on any medications that may interact with asparaginase? What happens if my child (or if I) has/have an allergic reaction to this drug?

Interactions Asparaginase can decrease effectiveness of methotrexate in killing cancer cells when given right before and together with methotrexate. The use of these two medicines together should be avoided.



fever, chills, sore throat



yellowing of the skin or eyes



puffy face, skin rash, trouble breathing, joint pain



drowsiness, confusion, hallucinations, convulsions



unusual bleeding or bruising

Risk of liver disease may be increased in patients receiving both asparaginase and mercaptopurine.



stomach pain with nausea, vomiting and loss of appetite

This medicine can increase blood sugar especially when given in together with steroids.

A physician will perform blood tests before starting therapy and during therapy to monitor complete blood count, blood sugar, and pancreas, kidney, and liver functions.

Side effects Asparaginase is a very potent medicine that can cause serious side effects. An allergic reaction with skin rash, itching, joint pain, puffy face, and difficulty breathing can occur very quickly after injection with his drug. This side effect is managed by having the drugs epinephrine, diphenhydramine, and steroids available near the bedside to counter the allergic reaction if it occurs. Other common side effects include nausea, vomiting, diarrhea, loss of appetite, stomach cramps, and yellowing of the eyes or skin. Less frequent side effects include high blood sugar, drowsiness, confusion, hallucinations, convulsions, decreased kidney function, increased blood clotting, mouth sores, and decreased ability to fight infections. Usually the side effects of asparaginase are more severe in adults than in children. G A LE EN CY C LO PE DI A O F C AN CE R 3

Asparaginase can decrease breakdown increase toxicity of cyclophosphamide.

and

Asparaginase should be given after vincristine instead of before or with vincristine because it can increase the risk of numbing, tingling and pain in hands and feet. Olga Bessmertny, Pharm.D. Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Astrocytoma Definition Astrocytoma is a tumor that arises from astrocytes, star-shaped cells that play a supportive role in the brain.

Demographics Astrocytoma is the most common type of brain tumor in children. Astrocytoma usually strikes within the first ten years of life, most commonly between ages 129

Astrocytoma

crosses into breast milk. Women who are pregnant or may become pregnant should avoid this drug unless the benefits to the mother outweigh the risks to the child.

Astrocytoma

pressure, resulting in headaches and possibly affecting normal brain function by compressing delicate brain tissue. Astrocytomas are a type of glioma, a tumor of glial cells (specialized cells that give physical support and electrical insulation between neurons). They are sometimes called gliomas, anaplastic astrocytomas, or glioblastoma multiforme. Oligoastrocytomas are a type of mixed glioma similar to astrocytomas. They usually contain cells that originate from oligodendrocytes as well as astrocytes, and are usually low grade (grading is an estimate of the tumor’s malignancy and aggressiveness; lower-grade tumors require less drastic therapy than high-grade tumors).

Causes and symptoms Magnetic resonance image (MRI) of the head and neck of a 15-year-old boy showing the recurrence of an astrocytoma of the spinal cord. The tumor appears about halfway down the neck. (ª Simon Fraser, Neuroradiology Dept., Newcastle General Hospital, Science Source/Photo Researchers, Inc. Reproduced by permission.)

five and nine. This type of tumor occurs slightly more often in males than in females. It is also slightly more common in Caucasians than in those of African or Asian descent. Although it affects both adults and children, children usually develop a less serious form with a better prognosis. The annual incidence of astrocytomas, is approximately 14 newly diagnosed cases out of every million children under the age of 15 years.

Description The brain acts as a computer that controls all of the functions of the body. It stores information, memories, and with the use of hormones and electrical impulses, regulates and sends instructions to the rest of the body. Because of the brain’s importance, cancers in the brain can affect many of the body’s functions. The location of a tumor within the brain determines which effects it will have. Astrocytomas may occur in the cerebrum, the site of thought and language, the cerebellum, the area responsible for movement and muscle co-ordination, or the brainstem, the location that regulates critical activities like breathing and heartbeat. Childhood astrocytomas are most commonly located in the cerebellum, while adults usually develop astrocytoma in the cerebrum. Astrocytomas rarely metastasize (spread) outside the brain to other parts of the body; however, they may grow and spread within the brain. As there is no extra room in the skull, the presence of a brain tumor causes an increase in intracranial (within the skull) 130

The cause of astrocytoma is not known. Brain cancer may occasionally be caused by previous radiation treatments; however, x rays are not believed to play a role. As of 2001, studies indicated that the moderate use of handheld cellular phones does not cause brain cancer; ongoing research will determine if long-term cellular phone use causes an increase in cancer incidence. Some studies suggest that brain tumors may occur more frequently in people who have occupational exposure to certain chemicals, including some pesticides, formaldehyde, vinyl chloride, phenols, acrylonitrile, N-nitroso compounds, polycyclic aromatic hydrocarbons, lubricating oils, and organic solvents. The greatest risk is associated with exposure before birth or during infancy. There is a slightly higher incidence of astrocytoma in the siblings and parents of people with this tumor; however, only one type of astrocytoma is known to have a genetic cause. The rare subependymal giant cell astrocytoma occurs in conjunction with tuberous sclerosis, a hereditary disorder. A wide variety of symptoms develop as a result of astrocytoma including the following:        

 

headache nausea and vomiting neck stiffness or pain dizziness seizures unsteadiness in walking or unusual gait lack of coordination, decreased muscle control visual problems such as blurring, double vision, or loss of peripheral vision weakness in arms or legs speech impairment G A LE EN CY C LO PE DI A O F C AN C ER 3



altered behavior loss of appetite

Because there are several different types of astrocytoma, not all patients will show the same symptoms. The location of the tumor within the brain will determine which symptoms a patient will experience. Because the tumor causes an increase in intracranial pressure, most people with astrocytoma will develop headaches and nausea and vomiting.

Diagnosis In the first stage of diagnosis the doctor will take a history of symptoms and perform a basic neurological exam, including an eye exam and tests of vision, balance, coordination and mental status. The doctor will then require a computerized tomography (CT) scan and magnetic resonance imaging (MRI) of the patient’s brain. During a CT scan, x rays of the patient’s brain are taken from many different directions; these are combined by a computer, producing a cross-sectional image of the brain. For an MRI, the patient relaxes in a tunnel-like instrument while the brain is subjected to changes of magnetic field. An image is produced based on the behavior of the brain’s water molecules in response to the magnetic fields. A special dye may be injected into a vein before these scans to provide contrast and make tumors easier to identify. If a tumor is found it will be necessary for a neurosurgeon to perform a biopsy on it. This simply involves the removal of a small amount of tumor tissue, which is then sent to a neuropathologist for examination and staging. The biopsy may take place before surgical removal of the tumor or the sample may be taken during surgery. Staging of the tumor sample is a method of classification that helps the doctor to determine the severity of the astrocytoma and to decide on the best treatment options. The neuropathologist stages the tumor by looking for atypical cells, the growth of new blood vessels, and for indicators of cell division called mitotic figures.

Treatment Treatment team Treatment of astrocytoma will involve a neurosurgeon to remove the tumor, a neuropathologist to examine the tumor sample, and an oncologist to monitor the patient’s health and coordinate radiation therapy and chemotherapy if necessary. Nurses and radiation therapists will also play a role. After treatment, the patient may be followed up by a neurologist to ensure that the tumor does not grow or recur. G A LE EN CY C LO PE DI A O F C AN CE R 3

There are several different systems for staging astrocytomas. The World Health Organization (WHO) system is the most common; it has four grades of increasing severity based on the appearance of the astrocytoma cells. Other methods of staging correspond fairly closely to the WHO system. Grades I and II are sometimes grouped together and referred to as low-grade astrocytomas. Over time, tumors may progress from a low-grade form with a relatively good prognosis to a higher-grade form and poorer prognosis. Additionally, tumors may recur at a higher grade. Grade I Pilocytic Astrocytoma This is also sometimes referred to as juvenile astrocytoma because it occurs more frequently in children than adults. Under a microscope, the astrocytes are thin and elongated, and known as pilocytes. They are accompanied by Rosenthal fibers. The tumor mass does not invade surrounding tissues and is sometimes enclosed in a cyst. In children, pilocytic astrocytoma often occurs in the cerebellum, but may also occur in the cerebrum. Treatment of this grade depends on the patient’s age and the location of the tumor. Surgery is the preferred treatment for this type of astrocytoma; it is performed by a procedure known as a craniotomy. An incision is made in the skin and an opening is made in the skull. After the tumor is removed, the bone is normally replaced and the incision closed. The neurosurgeon may also insert a shunt (drainage system) to relieve intracranial pressure; this involves inserting a catheter into a cavity inside the brain called a ventricle, then threading the other end under the skin to a drainage area where the fluid is absorbed. If the tumor can be completely surgically removed, the patient may not need further therapy and may be monitored only for recurrence. If the tumor cannot be completely removed, patients may be given chemotherapy as well. If the tumor is not completely resected or if it continues to grow after chemotherapy, radiation therapy may be necessary. Radiation therapy is not normally given to children under the age of three in order to prevent permanent damage to the child’s healthy brain tissue. Radiation treatment may cause swelling in the brain; steroids may be prescribed to reduce the swelling. The best indicator for prognosis is complete removal of the tumor. With complete tumor removal, 80% of patients are alive ten years later. Location of the tumor in the cerebellum also suggests a better prognosis than other locations. 131

Astrocytoma



Astrocytoma

Grade II Low-Grade Diffuse Astrocytoma These astrocytomas spread out and invade surrounding brain tissues but grow very slowly. Under the microscope, fibrous structures are present. Grade II astrocytomas may occur anywhere in the brain, in the cerebellum and brain stem, or in the cerebrum, including the optic pathways. Genetic studies indicate that mutations of the tumor suppressor gene p53 occur frequently in these tumors. Surgical removal of the tumor is the first choice for treatment, but it may not be possible due the tumor’s location. Surgery is usually followed by radiation. Patients under 35 years of age have a better prognosis than older patients; in older patients, lowgrade tumors progress to higher grades more rapidly. Overall median survival is four to five years. Pleimorphic xanthoastrocytoma, a tumor originating in cells of a mixture of glial and neuronal origin, is often considered a grade II astrocytoma. It is relatively benign and treated only with surgery. Grade III Anaplastic Astrocytoma Anaplastic astrocytoma occurs most frequently in people aged 50 to 60. The term anaplastic means that the cells are not differentiated; they have the appearance of immature cells and cannot perform their proper functions. Researchers believe this is due to a gradual accumulation of genetic alterations in these cells. These tumor cells invade surrounding healthy brain tissue. Anaplastic astrocytomas may be inoperable because of their location and their infiltration into normal tissue; in this case radiation therapy is recommended. Chemotherapy may include various combinations of alkylating agents and other drugs, including carmustine, cisplatin, lomustine, procarbazine and vincristine. These tumors tend to recur more frequently than grade I and II tumors. Following treatment, median survival is 12 to 18 months. The fiveyear survival rate for these patients is approximately 10% to 35%. Grade IV Glioblastoma Multiforme Glioblastoma Multiforme (GBM) is the most common primary brain tumor in adults. These tumors aggressively invade adjacent tissue and may even spread throughout the central nervous system. They frequently occur in the frontal lobes of the cerebrum. Tumor biopsies may show large areas of necrosis, or dead cells, surrounded by areas of rampant growth. There may also be a mixture of cell types within the biopsy. Genetic studies show that a number of different types of mutations can take place in genes for 132

tumor suppressor p53 and other proteins that play a role in controlling the normal growth of cells. Often GBM cannot be entirely surgically removed because it affects large areas of the brain. Radiation therapy will be given regardless of whether surgery is possible, except to very young children. Conventional radiation may be performed, but more specialized types, such as stereotactic radiosurgery, which uses imaging and a computer to treat the tumor very precisely, or interstitial radiation, which delivers radiation by placing radioactive material directly on the tumor, may also be used. Chemotherapy will follow radiation; it may include carmustine, lomustine, procarbazine, and vincristine. GBM is most common in patients over 50 years of age and rarely occurs in patients under 30. Increasing age is associated with a poorer prognosis. Median survival is 9 to 11 months following treatment. Fewer than 5% of patients are alive five years later. Because of the poor prognosis of GBM, it is treated more aggressively than low-grade astrocytomas; many clinical trials take place to test new treatments. Alternative and complementary therapies While no specific alternative therapies have become popular for this particular type of brain cancer, patients interested in pursuing complementary therapies should discuss the idea with their doctor. A doctor may be able to provide information about the efficacy of certain techniques and whether they may interfere with conventional treatment.

Coping with cancer treatment Patients may experience unpleasant side effects due to their treatment. Patients should discuss any side effects they experience with their doctors; occasionally an effect may be unexpected or dangerous and dosages may need to be adjusted. Doctors can help alleviate nausea with antinausea medications and may prescribe antidepressants to help the patient deal with the cancer on a psychological level. Joining support groups will also help patients deal with the psychological effects of treatment. Cancer survivors can help provide encouragement and offer advice for coping with cancer on a day-to-day basis.

Clinical trials Clinical trials are an important treatment possibility, especially for patients with tumors that are inoperable or do not respond well to treatment. Participation in clinical trials also gives patients an opportunity to make contributions to the search to find a G A LE EN CY C LO PE DI A O F C AN C ER 3

Trials for lower-grade astrocytomas focus on finding chemotherapy that causes fewer side effects. Some studies may also feature new combinations of drugs while others may attempt to treat the tumor by using lower dosages of drugs spread out over a longer period of time.

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Prevention Currently, scientists do not know what causes the majority of brain cancers. There may be a slight genetic predisposition, as family members of astrocytoma patients have a slightly increased incidence of the disease. Clinical studies show that a large number of genetic alterations take place in the higher grade astrocytomas; although this helps to explain what is going wrong in the cells, it does not explain what is causing these genetic mutations to take place. While it is known that ionizing radiation can cause brain tumors, most people are not exposed to this type of radiation unless they are being treated for cancer. Ongoing studies are examining the long-term risks of other types of radiation, but as of 2001, neither x rays, electromagnetic fields, or cellular phones appear to increase the likelihood of brain cancers. Although evidence is not yet conclusive, some studies suggest that some brain tumors may be caused by environmental exposure to certain organic chemicals. Exposure is most harmful to the developing fetus and infants, so pregnant women may wish to consider whether they have any occupational exposure to organic chemicals. Parents of infants should be aware of pesticides and any other potentially harmful chemical their child could come into contact with. Additionally there is some evidence that supplements containing vitamins A, C, E, and folate may have a protective effect when taken during pregnancy. The children of women who take these supplements during pregnancy are half as likely to develop brain tumors before age five.

Special concerns Children who develop astrocytoma should be monitored regularly by their physicians to ensure G A LE EN CY C LO PE DI A O F C AN CE R 3

Astrocytoma

cure for their cancer. A wide variety of clinical trials are available, particularly for the higher-grade astrocytomas. Trials for higher-grade astrocytomas may test new drugs, new combinations of drugs, drug implants, and higher doses of drugs, possibly in combination with different methods of radiation therapy. Some studies may examine the use of gene therapy or immune therapy, including vaccines.



Where inside my brain is the cancer located and where will it spread? What types of treatment are recommended? What are the possible side effects of this treatment? How can the side effects be minimized? Am I eligible for any clinical trials? Are there any alternatives to this treatment? What are the chances that the cancer will return? Will this cause any disabilities? How will this affect my daily life?

that the tumor does not recur. A follow-up schedule should be discussed with the doctor; the child may be examined twice a year initially, then tested annually afterwards. In addition to the possibility of recurrence, other health problems due to treatment may arise in the child. The child may have lower levels of growth hormone or thyroid hormone or delayed growth as a result of radiation. There may also be decreased intellectual capacity or learning or physical disabilities that can be detected during follow-up. Parents can then arrange for rehabilitation or special education for their child. Adults may also experience permanent negative effects as a result of their treatment. Radiation damage to healthy tissue may occasionally cause delayed effects such as decreased intellect, impaired memory, changes in personality, and confusion. These types of side effects should be reported to a health professional; the patient can be referred to rehabilitation specialists who can help with regaining abilities. See also Brain and central nervous system tumors; Childhood cancers; Tumor grading. Resources BOOKS

Abeloff, MD et al. Clinical Oncology. 3rd ed. Philadelphia: Elsevier, 2004. Behrman RE, et al. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders, 2004. Goetz, CG. Goetz’s Textbook of Clinical Neurology. 3rd ed. Philadelphia: Saunders, 2007. ORGANIZATIONS

American Brain Tumor Association. 2720 River Rd., Des Plaines, IL 60018. (800) 886 2282. http://www.abta.org. 133

Axillary dissection

The Brain Tumor Society. 124 Watertown St., Suite 3 H, Watertown, MA 02472. (800) 770 8287. http:// www.tbts.org. National Brain Tumor Foundation. 414 13th St., Suite 700, Oakland, CA 94612 2603. (800) 934 2873. http:// www.braintumor.org. OTHER

BRAINTMR T.H.E. Brain Trust. Electronic mailing list. [cited June 22, 2001]. http://www.braintrust.org.

Racquel Baert, M.S.

ATG, anti-thymocyte globulin see Lymphocyte immune globulin Atropine see Antidiarrheal agents

Demographics If axillary dissection is not performed, recurrence of cancer in the armpit is common even after breast surgery. Recent evidence suggests that persons who underwent lumpectomy alone without axillary dissection had a 10-year average recurrence rate of 28% in the axilla. Generally, recent evidence also suggests that the more nodes and tissues removed in the axilla, the lower the risk of recurrence of cancer. Research also indicates that 10-year axillary cancer recurrence rates are low (10% for node negative and 3% for node positive) for women who have mastectomy and axillary node removal. The recurrence rate for breast cancer is approximately 17% for women who did not have axillary node removal.

Description

Axillary dissection Definition Axillary dissection is a surgical procedure that incises (opens) the armpit (axilla or axillary) to identify, examine, or remove lymph nodes (small glands, part of the lymphatic system, which filters cellular fluids).

Purpose Axillary dissection is utilized to stage breast cancer in order to determine the necessity of further treatment based on cancer cell spread. Additionally, axillary dissection includes removal and pathological examination of axillary lymph nodes for persons having operable breast cancer. The anatomy of the axilla is complex and composed of several critical nerves, arteries, and muscles. Because of this complex anatomy and connection with the breast, the axilla is a common route for possible metastatic (cancer cell spread to distant areas within the body) involvement from breast cancer. The absence or presence of cancer cells in axillary lymph nodes is the most power prognostic (outcome) indicator for breast cancer. Axillary dissection is an accurate procedure for axillary node assessment (removal and pathological examination). Clinical examination of the breast (more specifically palpation, or feeling the affected area for lumps) for the axillary region is inaccurate and unreliable. The only method to identify whether or not a lymph node has cancer cells, is to surgically remove the node and perform examination with a microscope to detect abnormal cancer cells. 134

Lymph nodes (or lymph glands) are filtering centers for the lymphatic system (a system of vessels that collects fluids from cells for filtration and reentry into the blood). Additionally, there is a complex arrangement of muscles, tissues, nerves and blood vessels. Axillary dissection is surgically explained in terms of three levels. Level I axillary dissection is also called lower axillary dissection because it is the removal of all tissue below the axillary vein and extending to the side where the axillary vein crosses the tendon of a muscle called the latissimus dorsi. Level II dissection is continuous—it includes the removal of level tissues and further extensive removal of cancerous tissues. Level II dissection removes diseased tissues deeper in the middle (medial) area of another muscle called the pectoralis minor. Level III dissection is the most aggressive breast cancer axillary surgery, and it entails the removal of all nodal tissue (tissues related to the lymphatic system) from the axilla.

Diagnosis/Preparation Operable breast cancer is the primary indication for axillary dissection. Persons receiving this surgery have been diagnosed with breast cancer and are undergoing surgical removal of the breast. Diagnosis of breast cancer typically involves palpation of a lump (mass), and other tests such as mammography (special type of x ray used to visualize deep into breast tissues) and biopsy. The specific diagnosis to estimate the extent of axillary (cancerous) involvement can be made by performing a sentinel node biopsy. The sentinel node is the first lymph node that drains fluid from the primary tumor site. If there is no presence of cancerous cells in the sentinel node, the likelihood that higher echelon lymph nodes have cancer is G A LE EN CY C LO PE DI A O F C AN C ER 3

Preparation for axillary dissection is the same as that for modified radical mastectomy. This includes but is not limited to preoperative assessments (special tests and blood analysis), patient education, postoperative care, and follow-up consultations with surgeon and cancer specialist (medical hematologist/oncologist). Psychotherapy and/or community-centered support group meetings may also be beneficial to treatment.

WHO P ER FORMS THE P R O C E D U R E AN D W H E R E I S I T P E R FO R M E D? The procedure is performed in a hospital equipped to perform major surgery. A general surgeon usually performs the operation with specialized formal training in surgical oncology (the specialty of surgery that provides surgical treatment for operable cancers).

Aftercare One of the major problems that can result from axillary lymph node removal is lymphedema (fluid accumulation in the arm). Postoperative aftercare should include the use of compression garments, pneumatic compression pumps, and massage to combat fluid retention. Additionally, persons may have pain and should discuss this with the attending surgeon. Other surgical measures for aftercare should be followed similar to persons receiving a modified radical mastectomy. Skin care is important and caution should be exercised to avoid cuts, bites, and skin infections in the affected area. Further measures to control lymphedema can include arm exercises and maintenance of normal weight.

Risks There are several direct risks associated with axillary surgery. A recent study indicated that approximately 31% of persons may have numbness and tingling of the hand and 10% develop carpal tunnel syndrome. In females who have had a previous breast surgery before the axillary surgery, recurrent wound infections and progression of lymphedema can occur. Additionally, persons may also feel tightness and heaviness in the arm as a result of lymphedema.

Normal results Normal results can include limited but controlled lymphedema and adequate wound healing. Persons receiving axillary dissection due to breast cancer require several weeks of postoperative recovery to regain full strength.

Morbidity and mortality rates Sickness and/or death are not necessarily related to axillary surgery per se. Rather, breast cancer outcome is related to breast cancer staging. Staging determined by axillary surgery can yield valuable G A LE EN CY C LO PE DI A O F C AN CE R 3

Q U E S T I O N S TO A S K T H E DOCTOR    

How do I prepare for the procedure? How long does it take to know the results? What postoperative care will be needed? What are the possible risks involved in this procedure?

information concerning disease progression. Early stage (stage I) breast cancer usually has a better outcome, whereas advance stage cancer (stage 4) is correlated with a 10-year survival rate.

Alternatives Currently research does not support other therapies. Further study is required but other therapies are currently not recommended. There are no adequate alternatives to axillary surgery in breast cancer persons. The most recent evidence suggests that removal of lymph nodes and tissues in the armpit is correlated with elevated survival rates. Resources BOOKS

Hanna, L., Crosby, T., and Macbeth, F. Practical Clinical Oncology. 1st ed. Cambridge, UK: Cambridge Univer sity Press., 2008. Noble, J. Textbook of Primary Care Medicine. 3rd ed. St. Louis, MO: Mosby, Inc., 2001. Townsend, C., Beauchamp, D., Evers, B., and Mattox, K. Sabiston Textbook of Surgery. 18th ed. St. Louis: W. B. Saunders Company, 2007. PERIODICALS

Cantin, J., H. Scarth, M. Levine, and M. Hugi. ‘‘Clinical practice guidelines for the care and treatment of breast cancer.’’ Canadian Medical Association Journal 165 (July 24, 2001). 135

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very small. Conversely, if cancerous cells are detected in the sentinel node, then axillary dissection is recommended.

Azacitidine

Fiorica, James. ‘‘Prevention and Treatment of Breast Can cer.’’ Obstetrics and Gynecology Clinics 28 (December 2001). Hugi,M. R., I. A. Olivotto, and S. R. Harris. ‘‘Clinical practice guidelines for the care and treatment of breast cancer:11.Lymphedema.’’ Canadian Medical Associa tion Journal 164 (January 23,2001). ORGANIZATIONS

American Cancer Society. (800) ACS 2345. http://www. cancer.org. Y ME National Breast Cancer Organization. 212 W. Van Buren, Suite 500 Chicago, IL 60607. (312) 986 8338. Fax: (312) 294 8597. (800) 221 2141 (English). (800) 986 9505 (Espan˜ol). http://cancernet.nci.nih.gov/wyntk_pubs/ hodgkins.htm>. ‘‘Hodgkin’s Disease.’’ Cancer Resource Center. 10 Dec. 1999. American Cancer Society. [cited Mar. 27, 2005]. . ‘‘Hodgkin’s Lymphoma.’’ Diseases & Conditions. MayoClinic.com. [cited Mar. 27, 2005]. http:// www.mayohealth.org. National Cancer Society. ‘‘NCI/PDQ Patient Statement: Adult Hodgkin’s Disease.’’ Oncolink. Nov. 2000. Uni versity of Pennsylvania Cancer Center. [cited Mar. 27, 2005]. http://www.oncolink.upenn.edu/pdq_html/2/ engl/200003.html. National Cancer Society. ‘‘NCI/PDQ Patient Statement: Childhood Hodgkin’s Disease.’’ Oncolink. Feb. 2001. University of Pennsylvania Cancer Center. [cited Mar. 27, 2005]. http://www.oncolink.upenn.edu/pdq_html/ 2/engl/203043.html. ‘‘PET Scans Help Doctors Treat Hodgkin’s Disease.’’ ACS News Today. American Cancer Society. [cited Mar. 27, 2005]. . ORGANIZATIONS

American Cancer Society. (800) ACS 2345. http:// www.cancer.org. Provides information, funds for can cer research, prevention programs, and patient services, including education and support programs for patients and families, temporary accommodations for patients, and camps for children with cancer. ClinicalTrials.gov. U. S. National Library of Medicine. National Institutes of Health. 8600 Rockville Pike, Bethesda, MD 20894. . Information about clinical trials involving Hodgkin’s disease. Cure for Lymphoma Foundation. 215 Lexington Avenue, New York, NY 10016. (212) 213 9595. (800) CFL 6848. [email protected]. http://www.cfl.org/home.html. An advocacy organization that provides education and support programs, research grants, and information on clinical trials for Hodgkin’s and non Hodgkin’s lymphomas. 696

The Leukemia and Lymphoma Society. 600 Third Avenue, New York, NY 10016. (800) 955 4572. (914) 949 5213. http://www.leukemia lymphoma.org Provides infor mation, support, and guidance to patients and health care professionals. The Lymphoma Research Foundation of America, Inc. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204 7040). http://www.lymphoma.org. Supports research into treatments for lymphoma and provides educational and emotional support programs for patients and families. National Cancer Institute. Public Inquiries Office, Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. (800) 4 CANCER. http:// www.nci.nih.gov/. . Provides information on cancer and on clinical trials; conducts cancer research.

Rosalyn S. Carson-DeWitt, M.D. Margaret Alic, Ph.D.

Home health services Definition Home health services refers to those health care services provided to the patient in his or her own home.

Description Home health services can vary depending on the insurance coverage, but usually include nursing, physical therapy, occupational therapy, speech therapy, home health aides, social work, nutritional education, infusion therapy, blood drawing, and other laboratory services. Such services may also include bringing medical

A home healthcare nurses tends to a patient. (Photograph by Carl Glassman. The Image Works Reproduced by permission.)

G A LE EN CY C LO PE DI A O F C AN C ER 3

Home parenteral nutrition (HPN)—HPN provides liquid nutrition via infusion for patients who are malnourished, or who have had surgery altering the usual process of chewing, swallowing, or digesting food. Meditation—Meditation is a technique in which the individual focuses on a word or phrase to the exclusion of other thoughts. It has been shown to lower blood pressure and reduce stress. Respite care—A form of temporary home health care that allows family members some time away from patient care. Respite care is usually shortterm, ranging from a few hours to a weekend. T’ai chi—An Asian practice of breathing and slow physical movements that develops strength and reduces stress. Telehealth—The use of the telephone, Internet, and other forms of telecommunication to support longdistance health care, education of health care professionals, and public health concerns.

equipment into the home for patient use. Home health services do not provide around-the-clock care, but rely on the patient having other caregivers, such as family members, friends, or other community resources. Home care services can be provided by many different organizations, such as the Visiting Nurses Association (VNA), home health agencies (which vary in the range of services provided), hospice organizations, providers of home medical equipment, and pharmacies with delivery services. Patients requiring a range of specialized services may find more continuity of care if one agency is able to provide all, or almost all, of the services they need. Hospice care is care provided to patients who are terminally ill. Most hospices care for their clients within the home. The goal of hospice is to help the client and their family deal with the physical, emotional, and spiritual issues associated with dying. Excellent pain management is a priority. Nursing care Skilled nursing care provides the backbone for home care. Visits may include wound and ostomy care; infusion therapy such as home chemotherapy, antibiotics, or home parenteral nutrition (HPN); patient and caregiver teaching; ongoing assessment of the client’s physical and emotional condition and progress; pain control; psychological support; and G A LE EN CY C LO PE DI A O F C AN CE R 3

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What kind of home care will I need? For how long will I need the different services? What happens if my condition worsens? Will my insurance cover the services you are prescribing? What kind of care is available to help my family care for me? Are there alternative therapies that would help my condition? Are any of these therapies covered by my insurance? Are there any side effects to these therapies? Who is in charge of making sure my pain is well controlled?

supervision of home health aides. The nurse may function as a case manager and coordinate the various other services the client is receiving. The nurse assesses the home environment for safety and for appropriateness of continued home care. Physical therapy Physical therapists develop a plan for the client to restore (as much as possible) the physical condition lost following surgery or as a result of a decline due to the disease process. They also teach patients how to prevent further injury or deterioration and how to maintain gains made. Occupational therapy Occupational therapists assist patients in restoring or enhancing their ability to perform their tasks of daily living. Patients may need to learn how to use adaptive equipment such as a prosthesis. The goal is to achieve the highest level of functioning possible. Speech therapy Speech therapists work with clients who have difficulty swallowing or clearly communicating. Home health aides Home health aides function under the supervision of a registered nurse. They provide care with personal hygiene, such as bathing and dressing, feeding, and 697

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K E Y T ERM S

Home health services

ambulating. They may assist a nurse in providing patient care. They may provide homemaking services and companionship, or those tasks may be covered by a homemaker or attendant.

that prior to their illness, or may need ongoing care as their condition deteriorates due to metastatic disease. One trend that is gathering speed in the early 2000s is an increase in home health care services as opposed to nursing home care.

Social work Social workers may assist clients in accessing the services that are available to them based on their insurance, and in learning what community resources exist. They may also facilitate the referral process, and provide counseling and patient advocacy. Nutritional education Nutritionists and registered dieticians may educate clients on their nutritional needs, and on how to go about attaining them. They may also be involved if HPN is required. Infusion therapy Some patients may receive their chemotherapy or antibiotics at home, or may require infusion of liquid nutrition (HPN). While these services may be provided by a nurse, a separate agency or company may provide the equipment and products. Laboratory work Blood drawing and other laboratory services may be provided by a nurse, a phlebotomist, or a laboratory technician.

Special concerns Insurance coverage plays a major role in funding home health care. In organizing home care the patient must fully understand which services will be fully covered, covered but with a co-payment, or not covered at all. Insurance coverage may vary depending on whether the service provider is within a specified approved network. It must also be clear how often and for how long the services will be needed, and whether the insurance benefits cover the entire time period of anticipated care. The patient’s safety must always remain a priority. The patient and the caregiver(s) may suffer from isolation and depression. Primary caregivers may become overwhelmed with caring for the patient, and there may come a point at which the level of care needed may no longer be able to be provided in the home setting. The health of the primary caregiver must periodically be assessed.

Treatments Treatments provided in the home include wound and ostomy care, intravenous (IV) chemotherapy or antibiotics, HPN, and physical, occupational, and speech therapy.

Home medical equipment Following surgery or treatment in a hospital, patients may need the delivery and servicing of items such as special beds, wheelchairs, walkers, catheters, and wound care and ostomy supplies. Volunteers Volunteers may provide a range of assistance such as respite care for the primary caregiver(s), caring for the home, cooking, cleaning, emotional support, companionship, running errands, making telephone calls, child care, elder care, and providing transportation. They may come from the patient’s circle of friends or religious organization, or from such agencies as Meals on Wheels.

Causes Many individuals with conditions that do not necessitate care in a hospital setting often require short-term or long-term home care. They may need care to assist them in regaining their health similar to 698

Newer trends and future concerns One trend in home health care is greater use of the telephone and Internet for contact between home health care workers and medical professionals, and for information gathering. The U. S. Department of Health and Human Services has sponsored a new web site intended to help consumers as well as professionals make informed choices about home health care agencies. In addition, the growth of so-called telehealth systems has already had an impact on nursing education and practice in the home health care field. The field of telehealth is expected to expand dramatically in the early 2000s, as experts estimate that home health care is 10–15 years behind other fields in its use of computers. Another trend is the growing emphasis on culturally sensitive home health care. In many cases, patients from minority ethnic groups and cultures are more comfortable being cared for in their homes by caregivers who share their background or have been trained to understand it than to be sent to large urban nursing homes where they are isolated from familiar customs G A LE EN CY C LO PE DI A O F C AN C ER 3

One worrisome concern for the future is the increasing difficulty of recruiting and retaining highquality home health care workers in the United States and Canada. The aging of the general North American population coupled with the high turnover in the field of home health care poses a serious problem for policy makers. Alternative and complementary therapies Clients may contract to have home acupuncture or massage therapy. On their own they may engage in yoga, t’ai chi, meditation, guided imagery, visualization, or other stress-reducing techniques that help them better cope with their situation. They may also choose to investigate herbal supplements and medications; all supplemental medications should be approved by a physician before use.

ORGANIZATIONS

The American Cancer Society. 800 ACS 2345. http:// www.cancer.org. National Association for Home Care. 228 7th Street, S.E. Washington, D.C. 20003. 202 547 7424. http:// www.nahc.org. National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. 301 435 3848. http://www.nci.nih.gov. National Center for Complementary and Alternative Med icine. NCCAM Clearinghouse, P.O. Box 8218, Silver Spring, MD 20907 8218. 888 644 6226. . Office for the Advancement of Telehealth. 5600 Fishers Lane, Room 7C 22, Rockville, MD 20857. (301) 443 0447. Fax: (301) 443 1330. . Visiting Nurse Association of America. 11 Beacon Street, Suite 910; Boston, MA 02108. 617 523 4042. Fax: 617 227 4843. http://www.vnaa.org.

Esther Csapo Rastegari, R.N., B.S.N., Ed.M. Rebecca J. Frey, Ph.D.

Resources BOOKS

Levin, Bernard. American Cancer Society: Colorectal Can cer. New York: Villard Books, 1999. Runowicz, Carolyn D., Jeanne A. Petrek, and Ted S. Gans ler. American Cancer Society: Women and Cancer. New York: Villard Books/Random House, 1999. Teeley, Peter, and Philip Bashe. The Complete Cancer Sur vival Guide. New York: Doubleday, 2000. PERIODICALS

Applebaum, R. A., S. A. Mehdizadeh, and J. K. Straker. ‘‘The Changing World of Long Term Care: A State Perspective.’’ Journal of Aging and Social Policy 16 (January 2004): 1 19. Fermazin, M., M. O. Canady, P. R. Milmine, et al. ‘‘Home Health Compare: Web Site Offers Critical Information to Consumers, Professionals.’’ Lippincott’s Case Man agement 9 (March April 2004): 89 95. Hotson, K. E., S. M. Macdonald, and B. D. Martin. ‘‘Understanding Death and Dying in Select First Nations Communities in Northern Manitoba: Issues of Culture and Remote Service Delivery in Palliative Care.’’ International Journal of Circumpolar Health 63 (March 2004): 25 38. Lee, H., and M. Cameron. ‘‘Respite Care for People with Dementia and Their Carers.’’ Cochrane Database Sys tems Review February 2004: CD004396. Stone, R. I. ‘‘The Direct Care Worker: The Third Rail of Home Care Policy.’’ Annual Review of Public Health 25 (2004): 521 537. Williams, K. ‘‘Preparing Nurses for Telehealth: A Home Health Care Example.’’ Medinfo 2004(CD): 1908. G A LE EN CY C LO PE DI A O F C AN CE R 3

Horner’s syndrome Description William Edmonds Horner (1793–1853) first described a small muscle at the angle of the eyelid (tensor tarsi) as well as a description of an ingenious operation to correct problems with the lower lid in 1824 in the American Journal of the Medical Sciences. Since that time, his name has been associated with the syndrome of a small, regular pupil, drooping of the eyelid on the same side and occasional loss of sweat formation on the forehead of the affected eye. In appearance, it occurs on one side of the face with a sinking in of the eyeball (enophthalmos), drooping upper eyelid (ptosis), slight elevation of the lower lid, excessive contraction of the pupil of the eye (miosis), narrowing of the eyelid, and an absence of facial sweat on the affected side (anhidrosis). Other symptoms may include a variation in eye color of the iris and changes in the consistency of tears.

Causes Horner’s syndrome is caused by damage or interruption of the sympathetic nerve to the eye. There are two major divisions of the nervous system: the voluntary (conscious control) and involuntary (without conscious control). The involuntary (autonomic nervous system) has two divisions: sympathetic and parasympathetic 699

Horner’s syndrome

and language. Studies of the feasibility of home health care for Native Americans in remote locations are presently being conducted in Canada.

Horner’s syndrome

nervous systems. Under normal conditions, there is a fine balance between sympathetic and parasympathetic stimulation. If an individual is threatened by a situation, the pupils dilate, blood is shifted to the muscles and the heart beats faster as the person prepares to fight or flee. This is sympathetic stimulation. The eye has both sympathetic (responds to challenges) and parasympathetic (slows the body down) innervation. The nerve that carries the sympathetic innervation travels down the spinal cord from the brain (hypothalamus), emerges in the chest cavity, and then finds it way up the neck along with the carotid artery and jugular vein through the middle ear and into the eye. If these sympathetic impulses were blocked, the eye would have an overbalance of parasympathetic supply, which would result in a constriction of the pupil, relaxation of all the muscles around the eye and a sinking of the eye into the orbit— Horner’s syndrome. Thus, damage that occurs anywhere along the course of this nerve’s route from the brain to the eye can evoke this syndrome. If the syndrome exists from birth (congenital), it is typically noted around the age of two years with the presence of a variation in the color of the iris and the lack of a crease in the drooping eye. Since eye color is completed by the age of two, a variation in color is an uncommon finding in Horner’s syndrome acquired later in life. The common causes of acquired Horner’s syndrome include aortic dissection (a tear in the wall of the aorta to create a false channel where blood becomes trapped), carotid dissection, tuberculosis, Pancoast tumor (a tumor in the upper end of the lung), brain tumors, spinal cord injury in the neck, trauma to the cervical or thoracic portions of the spinal cord, cluster migraine headache, vertebrae destruction or collapse, compression of the spinal cord by enlarged lymph nodes, and neck or thyroid surgery. The diagnosis and localization of this disorder is made with the use of pharmacological testing by an ophthalmologist. The physician places drops of a 10% liquid cocaine into the eyes, blocking the parasympathetic nerves so the sympathetic nervous system can be evaluated. After thirty minutes, the dilation of the pupils is noted and a Horner’s pupil dilates poorly. A positive cocaine test does not, however, localize the area of the damage. After waiting for 48 hours, other medications are used to determine where the nerve interruption occurs. This solution routinely has been hydroxyamphetamine bromide. However, it has not been routinely available and in 2004, a study reported that a phenylephrine solution works as well. An individual’s urine can test positive for cocaine up to two days following the initial test. 700

Treatments Treatment for congenital cases Children who are diagnosed with Horner’s syndrome of a congenital origin may undergo surgical correction to strengthen the muscle of the eyelid and give it an appearance similar to the unaffected eye. The surgery improves the appearance of the child but does not alleviate the syndrome. For these cases a plastic surgeon may be preferred. Occasionally Horner’s syndrome may be seen in a newborn with a neuroblastoma (tumor originating from nerve cells). This is almost always a sign of a localized tumor and is associated with a relatively good prognosis. In these cases, a neurologist may be consulted for treatment since their specialty is the nervous system. Treatment for acquired cases The treatment for acquired Horner’s syndrome depends upon the cause and is focused toward eliminating the disease that produces the syndrome. Frequently, there is no treatment that improves or reverses the condition, but recognition of the signs and symptoms is extremely important for early diagnosis and treatment. Early detection of the syndrome may facilitate treatment related to those caused by tumors as they can be removed before extensive damage is done. Causes related to an interruption in nerve transmission once the nerve leaves the spinal cord are usually related to blood circulation and are easier to treat. Any numbness or paralysis on one side of the body means the problem is within the spinal cord or brain and is more difficult to treat. Some acquired Horner’s may be corrected slightly by plastic surgery for appearance changes. Alternative and complementary therapies Acupuncture may be utilized to enhance disruptions in nerve transmissions and herbs or supplements that improve circulation may benefit some cases of acquired syndrome. These herbs and supplements would include Gingko biloba and vitamin E. As with any complementary treatment, patients should notify their physician of any herbal or over-the-counter medications they are taking. Resources BOOKS

Jarvis, Carolyn. Physical Examination and Health Assess ment. Philadelphia: W.B. Saunders Company, 2000. PERIODICALS

Danesh Meyer, H.V., P. Savino, and R. Sergott. ‘‘The Corre lation of Phenylephrine 1% With Hydroxyamphetamine G A LE EN CY C LO PE DI A O F C AN C ER 3

KEY T ERMS

OTHER

Meditation—Meditation is a technique in which the individual focuses on a word or phrase to the exclusion of other thoughts. It has been shown to reduce stress and anxiety. Palliative care—Care focused on providing comfort, not cure.

Handbook of Ocular Disease Management. [cited July 6, 2005]. http://www.revoptom.com.

Linda K. Bennington, C.N.S., M.S.N. Teresa G. Odle

Respite care—A form of temporary home health care that allows family members some time away from patient care. Respite care is usually shortterm, ranging from a few hours to a weekend.

Hospice care

T’ai chi—An Asian practice of breathing and slow physical movements that develops strength and reduces stress. Telehealth—The use of the telephone, Internet, and other forms of telecommunication to support longdistance health care, education of health care professionals, and public health concerns.

Definition Hospice care is palliative care given to individuals who are terminally ill with an expected survival of six months or less. The focus of hospice care is on meeting the physical, emotional, and spiritual needs of the dying individual, while fostering the highest quality of life possible.

Description Hospice services provide palliative care to individuals with a life expectancy of six months or less. Most hospice care is provided in the home, but may take place in a hospice home or a hospice/palliative care area within a medical facility. Requesting hospice care may be the first time that individuals, or their families, acknowledge that their condition is not treatable. It may be the first time that they have to deal with their death as a reality taking place within a few months. The emotional journey to be able to deal with these issues may take a while, and therefore may delay the time when the person begins to receive hospice care. The focus of hospice is not on treatment, but on pain and symptom management, comfort measures, acknowledging that the individual will die, supporting the family, and trying to provide the best quality of life for the time remaining. Hospice functions under the philosophy that although some terminally ill patients may no longer receive treatment, they still require and deserve care. Hospice care is interdisciplinary in nature, providing the services of physicians, nurses, social workers, physical, speech, or occupational therapists, clergy or other spiritual guides, health care aides, and volunteers. Home hospice care relies on the family and friends of the patient to provide most of the daily care. Nursing and other services are provided daily or weekly, but with 24 hours, 7 days a week on-call access. Addressing the G A LE EN CY C LO PE DI A O F C AN CE R 3

spiritual needs of the hospice client is a fundamental aspect of hospice care. Some studies about hospice care have gleaned the following: 

 











When asked their preference, about two-thirds of cancer patients said they preferred to die in their own home. The majority of patients still die in the hospital. When surveyed, about 95% of families who received hospice care said that it had been helpful. Although satisfied with hospice care, caregivers report the job of caregiving as having a negative impact on their own quality of life, and felt the job was burdensome. When compared to a control group of noncaregivers, caregivers had higher levels of depression, anxiety, anger, and health problems. Caregivers had a higher rate of deteriorating health, social, and occupational functioning. Quality of life was influenced by the individual’s spiritual well-being. Hospice patients expressed feelings of conflict between a hope for living, and ‘‘living in hope,’’ being able to reconcile with others and coming to terms with death. Although hospice is focused on helping people in the last six months of their life, most hospice patients only receive about one month of hospice care prior to their death. 701

Hospice care

1% in Horner’s Syndrome.’’ British Journal of Ophthal mology April 2004: 592 594.

Hospice care



Q U E S T I O N S T O A S K TH E DOC TOR  





 



What do you think is my prognosis? What choices are there to manage my pain and other symptoms? What level of symptom management can I expect to receive? What types of care, conventional or alternative, would improve the quality of the time I have left? Will my insurance cover the care you suggest? If I choose hospice care, how will that affect my relationship with my doctors and treatment team? What kind of support is there for my family, both until I die and afterwards?





Special concerns A study looking at the communication between physicians and their dying patients found these issues to be very important:      



Only 20% of physicians’ prognoses about a patient’s survival was accurate. Sixty-three percent were overly optimistic, and 17% were overly pessimistic. The more experience the physicians had, the better their accuracy of prognosis.



 

Hospice care was first established in the United States in 1974 in Branford, Connecticut. The Branford hospice was patterned on St. Christopher’s Hospice in London, which was established by Dame Cicely Saunders in 1967. In 1969, the book On Death and Dying, by Dr. Elizabeth Kugler-Ross identified five stages that a terminally ill person goes through. In the book, Dr. Kubler-Ross addressed the importance of patients having a role in the decisions affecting the quality of their life and death. In 1972 she testified at the first U.S. Senate national hearing on dying with dignity. Deciding on hospice care is a choice made by the terminally ill individual. To be eligible, one’s physician needs to document that the individual’s survival is expected to be six months or less. Should the patient recover, and the prognosis change, the relationship with hospice is terminated, but can be reestablished when needed at a later date. Not all patients will choose hospice. If only home hospice care is available, individuals who would be eligible may decide that hospice is not a good choice for them. Reasons for not choosing home hospice include: The patient lives alone, with little or no family support available.  The patient has a need for 24-hour nursing care. 

702

Being honest and straightforward with patients. A willingness to talk about dying. Being sensitive when conveying bad news. Listening to patients. Encouraging patients to ask questions. Finding a balance between being honest without discouraging hope.

A Journal of the American Medical Association article found that patients at the end of their life expressed these issues as important: 

Causes

The patient has family, but they are unable to provide the supportive care required. The patient is concerned about being a burden to the caregiver. The patient feels more secure in a hospital environment.

   

being mentally aware not being a burden having their funeral arrangements planned helping others coming to peace with God freedom from pain talking about the meaning of death Among nine issues, dying at home was rated the least important.

Because time is limited for patients in hospice, patients and their caregivers need to act swiftly on areas of dissatisfaction, such as quality of care being provided or insufficient symptom management.

Treatments Curative treatments are not a part of hospice care. However, hospice places great importance on minimizing or alleviating pain and symptoms such as appetite loss (anorexia), fatigue, weakness, constipation, difficulty breathing, confusion, nausea, vomiting, cough, and dry or sore mouth. For many with advanced cancer, fatigue may be their worst symptom. Research has shown that a tailored exercise program can increase activity tolerance without increasing fatigue. In addition, patients reported an increase in quality of life and decreased anxiety. Patients who expressed the most fatigue showed the most decrease in fatigue with the exercise program. Many hospice G A LE EN CY C LO PE DI A O F C AN C ER 3

Alternative and complementary therapies Dealing with the issues of death may be addressed through talking with others, writing in a journal, creative expression such as painting, writing a poem, or composing music. Meditation may be beneficial to some patients. Gentle body movements such as with t’ai chi or yoga may be helpful, depending on the patient’s activity tolerance.

Recent trends A recent development in facilitating hospice care in the patient’s home is night respite service. In general, respite care refers to home health care offered by volunteers or home health caregivers that allows the patient’s family a few hours or a weekend away from direct patient care. Night respite care in a hospice setting involves trained aides who care for the patient in his or her home overnight, thus allowing other family members to catch up on necessary sleep. Studies indicate that many patients as well as family members feel that night respite care is a good option that allows patients to remain at home rather than being transferred to an inpatient hospice. One trend in hospice care that has attracted considerable interest in the early 2000s is ethnically and culturally sensitive hospice care. As of 2004, hospice services in the United States and Canada are utilized disproportionately by Caucasians. One innovative Native American hospice program that is working well is a palliative care program at the Pueblo of Zuni in New Mexico. The Zuni program combines tribalbased home health care with inpatient care at an Indian Health Service (IHS) hospital. Another significant trend in hospice care is the greater use of webcams, video phones, and other devices that have been introduced along with the computerization of hospital and hospice facilities. The rapid growth of ‘‘telehealth’’ since the mid-1990s indicates that technological innovations in telecommunications will affect hospice care as they have home health care and other outpatient settings. G A LE EN CY C LO PE DI A O F C AN CE R 3

Resources

Hospice care

patients have breakthrough pain in addition to their chronic pain. Research using an indwelling subcutaneous needle for pain control showed 88% pain control with this method when pain was not well controlled with oral medications. Chronic pain requires ongoing pain relief, such as might be handled with a pump or patch. Good pain control may mean waking the patient up at night for oral medication to prevent the pain from mounting during sleep.

BOOKS

Teeley, Peter and Philip Bashe. The Complete Cancer Survival Guide. New York: Doubleday, 2000. PERIODICALS

Finke, B., T. Bowannie, and J. Kitzes. ‘‘ Palliative Care in the Pueblo of Zuni.’’ Journal of Palliative Medicine 7 (February 2004): 135 143. Kristjanson, L. J., K. Cousins, K. White, et al. ‘‘Evaluation of a Night Respite Community Palliative Care Service.’’ International Journal of Palliative Nursing 10 (February 2004): 84 90. Lyke, J., and M. Colon. ‘‘Practical Recommendations for Ethnically and Racially Sensitive Hospice Services.’’ American Journal of Hospice and Palliative Care 21 (March April 2004): 131 133. Oliver, D. R., and G. Demiris. ‘‘An Assessment of the Readiness of Hospice Organizations to Accept Technological Innovation.’’ Journal of Telemedicine and Telecare 10 (March 2004): 170 174. Steinhauser, K. E., et al. ‘‘Factors Considered Important at the End of Life by Patients, Family, Physicians, and Other Care Providers.’’ Journal of the American Medical Association November 15, 2000: 2476 482. OTHER

Cancer Resources. 457 West 22nd Street, Suite B, New York, NY 10011. 800 401 2233. Fax: 212 243 1063. e mail: [email protected]. http:// www.cancerresouces.com. ORGANIZATIONS

American Cancer Society. 800 ACS 2345. http:// www.cancer.org. American Pain Society. 4700 W. Lake Ave., Glenview, IL 60025. 847 375 4715. . Hospice Association of America. 228 Seventh Street, SE; Washington, DC 20003. 202 546 4759. Fax: 202 547 9559. www.hospice america.org. National Association for Home Care. 228 7th Street, S.E. Washington, D.C. 20003. 202 547 7424. http:// www.nahc.org. National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. 301 435 3848. http://www.nci.nih.gov. National Center for Complementary and Alternative Med icine. NCCAM Clearinghouse, P.O. Box 8218, Silver Spring, MD 20907 8218. 888 644 6226. . Office for the Advancement of Telehealth. 5600 Fishers Lane, Room 7C 22, Rockville, MD 20857. (301) 443 0447. Fax: (301) 443 1330. .

Esther Csapo Rastegari, R.N., B.S.N., Ed.M. Rebecca J. Frey, Ph.D.

HPV see Human papilloma virus 703

Human growth factors

Human growth factors Definition Human growth factors are compounds made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory by genetic engineering and are used in biological therapy.

Description Human tumors express large amounts of growth factors and their receptors. A tumor will not grow beyond the size of a pinhead without new blood vessels to supply oxygen and nutrients. Growth factors are significant because they can induce angiogenesis, the formation of blood vessels around a tumor. These growth factors also encourage cell proliferation, differentiation, and migration on the surfaces of the endothelial cells—cells found inside the lining of blood vessels. Of the approximately 20 proteins that activate endothelial cell growth, two growth factors in particular, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are expressed by many tumors and appear important in contributing to tumor growth and promoting tumor spread throughout the body. Several compounds that block VEGF or its receptor are now in clinical trials. See also Angiogenesis inhibitors. Crystal Heather Kaczkowski, MSc.

Transmission electron micrograph of human papilloma virus, magnified 40,000 times. HPV is the cause of warts, including genital warts, and has been implicated in cervical cancer. (Custom Medical Stock Photo. Reproduced by permission.)

Human papilloma virus Definition HPV infection is a sexually transmitted disease (STD) caused by 30–40 of the 130 or so known strains of human papillomavirus, the name of a group of viruses that infect the skin and mucous membranes of humans and some animals. In humans these sexually transmitted strains can cause genital warts, precancerous changes in the tissues of the female vagina, or cervical cancer. Other strains of HPV are responsible for warts on the soles of the feet (plantar warts), common warts on the hands, and flat warts on the face or legs. 704

Large brown genital wart of a female. (Custom Medical Stock Photo. Reproduced by permission.)

G A LE EN CY C LO PE DI A O F C AN C ER 3

In recent years HPV infection has become the most common STD in the United States. Approximately 20 million Americans are infected with HPV as of 2009, and another 6.2 million people become newly infected each year. According to one study, 27 percent of women between the ages of 14 and 59 are infected with one or more types of HPV, and 35% of homosexual men. The Centers for Disease Control and Prevention (CDC) estimates that more than 80 percent of American women will contract at least one strain of genital HPV by age 50. About 75–80 percent of sexually active Americans of either sex will be infected with HPV at some point in their lifetime. As far as is known, men and women are at equal risk of being infected with HPV, as are members of all races and ethnic groups. In terms of specific illnesses associated with HPV, 11,000 women are diagnosed with cervical cancer each year in the United States and 3,900 women die of the disease. Another 5,800 women are diagnosed with cancers of the vagina and the external female genitals, while 3,300 men are diagnosed with cancer of the penis or the anal area. The risk of anal cancer is 17 to 31 times higher among gay and bisexual men than among heterosexual men.

It is possible that other viruses work together with human papilloma viruses to produce precancerous changes in tissue. Cases of tongue cancer have been reported in which HPV was found together with Epstein-Barr virus, or EBV. Smoking, the use of oral contraceptives for birth control for longer than 5 years, and suppression of the immune system are also thought to be factors that combine with HPV infection to lead to precancerous lesions in tissue. Risk factors Some people are at greater risk of sexually transmitted HPV than others:  



 



Causes and symptoms Causes

Description The family of human papilloma viruses includes a large number of genetically related viruses. Many of these cause warts, including the warts commonly found on the skin. Another group of HPV preferentially infect the mucosal surfaces of the genitals, including the penis, vagina, vulva, and cervix. These are spread among adults by sexual contact. One group of HPV that infect the genitals causes soft warts, often designated condylomata acuminata. These genital warts are quite common and rarely if ever become cancerous. The most common of these low-risk HPV types are designated HPV 6 and 11. The second group of viruses, termed high-risk HPV types, is associated with the development of cervical cancer. Individuals infected with these viruses are at higher risk for the development of precancerous lesions. Typically, infection with these viruses is common in adolescents and women in their twenties, and usually do not result in cancerous growth. The most common high-risk HPV is type 16. The appearance of abnormal cells containing high-risk HPV types is seen most frequently in women over the age of 30 who have abnormal Pap smears. G A LE EN CY C LO PE DI A O F C AN CE R 3

Gay and bisexual men. People with HIV or other diseases that weaken the immune system. Males or females below age 25. Younger people appear to be more biologically vulnerable to the HPV virus. People who have large numbers of sexual partners. People in relationships with partners who have sex with many other people. People who must take drugs that suppress the immune system.

The cause of sexually transmitted HPV infection is one or more strains of the human papillomavirus. The virus enters the body through small breaks in the skin surface or in the mucous membranes lining the genitals. In most cases the body fights off the virus within a few weeks. In some people, however, HPV remains dormant for a period ranging from a few weeks to three years in one of the lower layers of skin cells. The virus then begins to replicate (copy itself) when these cells mature and move upward to the surface of the skin. The virus affects the shape of the cells, leading to the formation of noticeable warts, precancerous changes in skin cells, or cervical cancer. About 1 percent of sexually active adults in the United States have genital warts at any one time; about 10 percent of women with high-risk HPV in the tissues of their cervix will develop long-lasting HPV infections that put them at risk for cervical cancer. The percentages of cancers caused by high-risk types of HPV are as follows:   

cervical cancer: 100% anal cancer: 90% cancer of the vulva: 40% 705

Human papilloma virus

Demographics

Human papilloma virus

vaginal cancer: 40%  oropharyngeal cancer: 12%  oral cancer: 3% 

Symptoms in adults Symptoms of sexually transmitted HPV infection may include: Genital warts. These appear as bumps or clusters of fleshy outgrowths around the anus or on the genitals. Some may grow into large cauliflower-shaped masses. Genital warts usually appear within weeks or months after sexual contact with an infected person. If left untreated, genital warts may go away, remain unchanged, or increase in size or number but will not turn into cancers. It is possible, however, for a person to be infected with a high-risk strain of HPV as well as one of the strains that cause genital warts; therefore the appearance of genital warts does not necessarily mean that the person is not at risk of cancer.  Precancerous changes in the tissues of the female cervix. These are flat growths on the cervix that cannot be seen or felt by the infected woman.  Cancer. High-risk strains of HPV can cause cancers of the mouth and throat as well as cancers of the anal area and the male and female genitals. These typically take years to develop after infection. In men, symptoms of anal cancer may include bleeding, pain, or a discharge from the anus, or changes in bowel habits. Early signs of cancer of the penis may include thickening of the skin, tissue growths, or sores. 

It is not fully understood as of 2009 why most infections with high-risk HPV are of short duration, while a small percentage persist and eventually transform cervical cells to a state of cancerous growth. Symptoms in children In addition to producing precancerous lesions in some patients, HPV infections in women are a health concern because they can be transmitted to the respiratory tract of a baby during childbirth. This type of HPV infection may lead to a rare disorder known as juvenileonset recurrent respiratory papillomatosis (JO-RRP) or laryngeal papillomatosis, in which papillomas or warts form in the child’s airway, producing hoarseness or partial blockage of the windpipe. Although laryngeal papillomatosis can occur in HPV-infected adults, 60– 80% of cases occur in children, most of them younger than three years. Laryngeal papillomatosis is usually diagnosed by laryngoscopy. Surgery, whether traditional or laser surgery, is the usual treatment for JO-RRP, but the 706

warts often recur and require additional surgery to remove them. In extreme cases, the patient may be given a tracheotomy, a procedure in which a hole is cut through the throat into the windpipe and a tube is inserted to keep the breathing hole open. A newer treatment for the disorder is photodynamic therapy or PDT. In PDT, a special light-sensitive dye is injected into the patient’s blood. The dye collects in the tumors rather than in healthy tissue. When bright light of a specific wavelength is shined on the throat, it destroys the tumors containing the dye. Cidofovir and interferon are often given as adjuvant treatments for this disease as of the early 2000s. JO-RRP is a serious illness, leading to death in a significant number of affected children. In a very few cases, respiratory papillomatosis can lead to cancer as well as breathing difficulties.

Diagnosis There is no general blood, urine, or imaging test for HPV infection. The diagnosis of genital warts is obvious based on their location and appearance. The doctor may, however, use a vinegar solution to identify HPV-infected areas on the skin of the genitals. The vinegar solution will turn white if HPV is present. Since genital warts are caused by low-risk strains of HPV, the doctor does not need to identify the specific strain of the virus that is present. Sexually active women should be screened periodically for the presence of changes in the tissues of the cervix. The most common test is the Papanikolaou test or Pap smear, invented by a Greek physician in the 1940s. To perform a Pap smear, the doctor takes a small spatula to obtain cells from the outer surface of the cervix and smears the collected cells on a slide that is then examined in a laboratory for signs of any abnormal cells. If abnormal or questionable cells are found, the doctor may order an HPV DNA test, which can identify the DNA of 13 high-risk types of HPV in cells taken from the cervix. There are no HPV screening tests for men as of 2009; however, some doctors are suggesting that anal Pap smears for men who have sex with men would be useful in early detection of anal cancer.. Tests The relationship among HPV, precancerous cellular changes, and cervical cancer have led to the suggestion that testing for the presence of HPV can be a useful addition to Pap tests. Pap tests involve microscopic analysis of cells removed from the cervix. The results of these tests are generally reported as either normal or G A LE EN CY C LO PE DI A O F C AN C ER 3

In some cases the cytologist or pathologist examining a Pap test reports a ‘‘borderline’’ result when abnormal cells are observed, but it is not possible to distinguish whether the changes seen are due to early precancerous changes or to inflammation caused by some infectious agent or irritant. In these cases, some physicians and scientists believe that testing for the presence of HPV can help to identify those women who should be closely followed for the development of early cancerous lesions, or who should undergo colposcopy, a procedure to examine the cervix for precancerous lesions. These cancer precursors, termed cervical intraepithelial neoplasia (CIN) when identified early, before they have become invasive, can almost always be completely removed by minor surgery, essentially curing the patient before the cancer has had a chance to develop. The cervical tissue removed, which includes the precancerous tissue, is examined as part of a biopsy to confirm the diagnosis, and if requested by a doctor, can be tested for the presence of high-risk HPV types.

Treatment Patients with genital warts should never use over-the counter-preparations designed to remove common or flat warts from the hands or face. Doctors can treat genital warts with various medical or surgical techniques: 







Cryotherapy. Cryotherapy uses liquid nitrogen to freeze the warts. The dead tissue in the wart falls away from the skin beneath in about a week. Imiquimod. Imiquimod (Aldara) is a topical cream that gets rid of genital warts by stimulating the body’s immune system to fight the virus that causes the warts. Podofilox. Podofilox (Condylox) is a topical medication available in liquid or gel form that destroys the wart tissue. Surgery. The doctor can remove the wart by drying it out with an electric needle and then scraping the tissue with a sharp instrument called a curette. Lasers can also be used to remove genital warts.

Low-grade precancerous changes in the tissue of the female cervix are not usually treated directly because most of them will eventually go away on their own without developing into cancer. The patient should, however, see the doctor for follow-up Pap smears to make sure that the tissues are returning to normal. High-risk G A LE EN CY C LO PE DI A O F C AN CE R 3

Q U E S T I O N S TO A S K Y O U R DOCTOR 







Do you think I should have an HPV test if my Pap smear results are abnormal? Based upon my Pap smear result and HPV testing, when should I have my next Pap smear? What can I do to decrease my risk of becoming (re)infected with HPV? What is your opinion of HPV vaccination for men?

precancerous lesions are removed, usually by surgery, cryotherapy, electrocauterization, or laser surgery. Since the incidence of latent and recurrent infections is high, the eradication of HPV is not always 100% effective. It is essential to be aware that HPV is a sexually transmitted disease and women must engage in safe sex practices to decrease the risk of spreading the virus or becoming reinfected. A vaccine effective against four of the HPV types most likely to cause genital warts or cervical cancer was approved for use in 2006; it is described more fully under Prevention below. As of 2009, researchers are working on developing vaccines that protect against additional types of the HPV virus.

Prognosis The prognosis of sexually transmitted HPV infections depends on the patient’s age, number of sexual partners, gender, and the condition of their immune system. Women are significantly more likely than men to develop cancers following HPV infection. However, most people of either sex with normally functioning immune systems who are infected with HPV will clear the infection from their bodies within two years.

Prevention Preventive measures that people can take to lower their risk of HPV infection include: 

  

Abstaining from sex, or having sex only with an uninfected partner who is faithful. Reducing the number of sexual partners. Using condoms regularly during sexual intercourse. For women, using a new vaccine called Gardasil. Approved by the Food and Drug Administration (FDA) in 2006, Gardasil is a vaccine that protects against the four types of HPV that cause most cervical cancers and genital warts. The vaccine is recommended for 11- and 12-year-old girls. It is also 707

Human papilloma virus

consistent with the presence of cancer or a precancerous condition. Patients receiving the latter diagnosis usually are treated either by excisional or ablative therapy surgery or some other means in order to remove the tumor or precancerous lesion.

Human papilloma virus

recommended for girls and women age 13 through 26 who have not yet been vaccinated or completed the vaccine series. Gardasil works best in girls who have not yet been sexually active. It is given as a series of three shots over a six-month period. A second human papillomavirus vaccine, Cervarix, was approved in Europe, Australia, and the Philippines in 2007. It is awaiting FDA approval for use in the United States as of September 2009. In addition to giving the available preventive vaccines to women, some doctors think it might be a useful preventive measure to vaccinate men as well to protect their female partners against infection. As of 2009, however, male vaccination for HPV is still under discussion rather than being put into clinical practice. Resources BOOKS

Gonzales, Lissette. Frequently Asked Questions about Human Papillomavirus. New York: Rosen, 2009. Krueger, Hans, et al. HPV and Other Infectious Agents in Cancer: Opportunities for Prevention and Public Health. New York: Oxford University Press, 2010. Marr, Lisa. Sexually Transmitted Diseases: A Physician Tells You What You Need to Know, 2nd ed. Baltimore, MD: Johns Hopkins University Press, 2007. Nardo, Don. Human Papillomavirus (HPV). Detroit, MI: Lucent Books, 2007. Rosenblatt, Alberto. Human Papillomavirus. New York: Springer, 2009. PERIODICALS

Burki, T. ‘‘Should Males Be Vaccinated against HPV?’’ Lancet Oncology 10 (September 2009): 845. Haug, C. ‘‘The Risks and Benefits of HPV Vaccination.’’ Journal of the American Medical Association 302 (August 19, 2009): 795 95. Hershey, J.H., and L.F. Velez. ‘‘Public Health Issues Related to HPV Vaccination.’’ Journal of Public Health Man agement and Practice 15 (September October 2009): 384 92. Lindsey, K., et al. ‘‘Anal Pap Smears: Should We Be Doing Them?’’ Journal of the American Academy of Nurse Practitioners 21 (August 2009): 437 43. O’Connor, M. B., and C. O’Connor. ‘‘The HPV Vaccine for Men.’’ International Journal of STD and AIDS 20 (April 2009): 290 91. Printz, C. ‘‘HPV Status Predicts Survival of Oropharyngeal Cancer Patients.’’ Cancer 115 (September 15, 2009): 4045. Samara, R. N., and S. N. Khleif. ‘‘HPV as a Model for the Development of Prophylactic and Therapeutic Cancer Vaccines.’’ Current Molecular Medicine 9 (August 2009): 766 73. Wang, Z., et al. ‘‘ Detection of Human Papilloma Virus Subtypes 16 and P16(ink4a) in Invasive Squamous Cell Carcinoma of the Fallopian Tube and Concomitant 708

Squamous Cell Carcinoma in Situ of the Cervix.’’ Journal of Obstetrics and Gynaecology Research 35 (April 2009): 385 89. OTHER

Centers for Disease Control and Prevention (CDC). Human Papillomavirus (HPV) Infection. http://www.cdc.gov/ std/hpv/default.htm. Centers for Disease Control and Prevention (CDC) Fact Sheet. HPV and Men. http://www.cdc.gov/std/hpv/ STDFact HPV and men.htm. Gearhart, Peter A., and Thomas C. Randall. ‘‘Human Pap illomavirus.’’ eMedicine, August 4, 2009. http://emedi cine.medscape.com/article/219110 overview. Mayo Clinic. HPV Infection. http://www.mayoclinic.com/ health/hpv infection/DS00906 National Cancer Institute (NCI). http://www.cancer.gov/ cancertopics/factsheet/Risk/HPV. National Institute of Allergy and Infectious Diseases (NIAID). Human Papillomavirus and Genital Warts. http://www3.niaid.nih.gov/topics/genitalWarts. National Institute on Deafness and Other Communication Disorders (NIDCD). Laryngeal Papillomatosis. http:// www.nidcd.nih.gov/health/voice/laryngeal.htm. ORGANIZATIONS

American College of Obstetricians and Gynecologists (ACOG), 409 12th St., S.W., P.O. Box 96920, Wash ington, DC, 20090 6920, (202) 638 5577, resources@ acog.org, http://www.acog.org/. American Social Health Association (ASHA), P.O. Box 13827, Research Triangle Park, NC, 27709, (919) 361 8400, (800)227 8922, (919)361 8425, http:// www.ashastd.org/index.cfm. Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA, 30333, (800)232 4636, [email protected], http://www.cdc.gov. National Cancer Institute, 6116 Executive Blvd., Room 3036A, Bethesda, MD, 20892 8322, (800) 422 6237, [email protected], www.cancer.gov. National Institute of Allergy and Infectious Diseases (NIAID), 6610 Rockledge Drive, MSC 6612, Bethesda, MD, 20892 6612, (301) 496 5717, (866) 284 4107, (301) 402 3573, http://www3.niaid.nih.gov. National Institute on Deafness and Other Communication Disorders (NIDCD), 31 Center Drive, MSC 2320, Bethesda, MD, 20892 2320, (800) 241 1044, (301) 770 8977, [email protected], http:// www.nidcd.nih.gov/index.asp.

Warren Maltzman, PhD Rebecca J. Frey, PhD

Hydrocodone see Opioids Hydrocortisone see Corticosteroids Hydromorphone see Opioids G A LE EN CY C LO PE DI A O F C AN C ER 3

Definition Hydroxyurea, also known by its trade name Hydrea, is an antineoplastic agent, meaning it is used to treat cancer. It is taken orally.

Purpose Hydroxyurea is used to treat the following conditions:  





 

Melanoma Chronic myelocytic leukemia that is resistant to other therapies Ovarian cancer that is recurrent, metastatic or inoperable. Squamous cell carcinoma of the head and neck, excluding the lip. (In this case, hydroxyurea is given with radiation therapy.) Sickle cell anemia Other: Hydroxyurea has shown promise in the management of thrombocytosis, a condition in which platelet levels are abnormally high

Description Hydroxyurea belongs to antimetabolites, a group of compounds that interfere with the production of nucleic acids. Hydroxyurea exerts its anticancer activity by inhibiting ribonucleotide reductase, an enzyme required for DNA synthesis. When used in conjunction with radiation therapy, the effectiveness of hydroxyurea increases because it also inhibits the ability of cells damaged by radiation to repair themselves.

Recommended dosage Hydroxyurea dosages are calculated based on a person’s weight as milligrams per kilogram (mg/kg). Doctors will usually use whichever value is lowest—the patient’s actual weight or the patient’s ideal weight—to calculate dosages. The drug is not given if white blood cell levels drop below 2500 mm3, or if red blood cell levels drop below 100,000 mm3. Usually, bone marrow recovery is rapid, and few doses are missed. Hydroxyurea is usually given for six weeks before its effectiveness can be adequately evaluated. Hydroxyurea is administered in a capsule form, each containing 500 mg of the drug. If a patient is unable to swallow the capsule, its contents can be dissolved in a glass of water and swallowed immediately. The drug will not completely dissolve in water. G A LE EN CY C LO PE DI A O F C AN CE R 3

KEY T ERMS Mucositis—A painful inflammation of the mucous membranes. Mutagen—An agent capable of causing DNA changes. Myelosuppression—Diminished bone marrow activity resulting in decreased red blood cells, white blood cells, and platelets. Plateletpheresis—A procedure in which platelets are removed from whole blood.

Dosages have not been established for children in part because the cancers for which hydroxyurea is useful do not normally occur in that age group. In the treatment of solid tumors, such as ovarian cancers, patients are usually given 80 mg/kg once every three days. Alternatively, a dose of 20–30 mg/kg may be given every day. In head and neck cancers also treated with radiation, 80 mg/kg of hydroxyurea is given once every three days. The drug should be started a week before radiation therapy begins, and should continue for some time after radiation therapy. When it is used to treat resistant chronic myelocytic leukemia, hydroxyurea is given in the dosage of 20–30 mg/kg once a day. In thrombocytosis, doses of 15–30 mg/kg taken once a day are usually effective. Platelet levels return to a normal level within two to six weeks of therapy. In more severe cases, doses of 1.5–3.0 grams per day have been given with plateletpheresis, a procedure that removes platelets from the blood.

Precautions This drug should not be administered to a person who has had a previous allergic reaction to it. Liver and kidney function should be evaluated prior to, and during, treatment. The drug may interfere with certain lab tests. For example, creatinine levels may be elevated. Patients taking hydroxyurea should stay well-hydrated, drinking up to 12 glasses per day of water or other fluids. Hydroxyurea is potentially mutagenic, meaning that it causes mutations in DNA. Patients taking the drug should discuss the potential effects on their future conception plans. Hydroxyurea should not be administered to pregnant women, and women taking the drug should use birth control methods to prevent pregnancy. 709

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Hydroxyurea is excreted in breast milk; therefore, women taking the drug should not breast-feed.

Hypercalcemia Description

Side effects Hydroxyurea and radiation therapy each cause adverse side effects. When they are used together, the incidence and severity of side effects may increase. Bone marrow suppression is the major side effect of hyroxyurea therapy, and may develop within two days of the first dose. Blood tests are performed routinely to monitor for changes. Usually, leukopenia (decreased white blood cells) develops first. Reduced red blood cells and platelets can also occur, but generally not as frequently. If anemia develops, it should be corrected with whole blood transfusions. Hydroxyurea causes red blood cell abnormalities that are not severe and that do not reduce the red blood cell survival time. Gastrointestinal symptoms are not as common as myelosuppression and are usually mild. These symptoms may include nausea, vomiting, diarrhea, and constipation. Usually, medications can control nausea and vomiting. Mucositis, a painful swelling of the mucous membranes, may also develop, especially if the patient is undergoing radiation treatment to the head and neck. Mucositis can be managed with medicated mouthwashes, good oral hygiene, and hydration to keep the mouth moist. Headache and dizziness may occur. With longterm use, skin changes, such as hyperpigmentation of the skin and nails, have also been reported. Hydroxyurea has also been linked to leg ulcers. Studies suggest that leg ulcers have been reported mainly in older patients who might be at an increased risk. There have also been reports of hydroxyurea causing leg ulceration when it is used in psoriasis for a prolonged period.

Interactions Patients at risk for bone marrow suppression should inform their doctor about all medications they are taking, both prescription and non-prescription. Many over-the-counter medications contain aspirin, which acts as a blood-thinner, increasing the potential for bleeding. Patients with reduced platelets should not take aspirin.

Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams per deciliter of blood. It is the most common lifethreatening metabolic disorder associated with cancer. Calcium plays an important role in the development and maintenance of bones in the body. It is also needed in tooth formation and is important in other body functions. As much as 99% of the body’s calcium is stored in bone tissue. A healthy person experiences a constant turnover of calcium as bone tissue is built and reshaped. The remaining 1% of the body’s calcium circulates in the blood and other body fluids. Calcium in the blood plays an important role in the control of many body functions, including blood clotting, transmission of nerve impulses, muscle contraction, and other metabolic activities. Cancer-caused hypercalcemia produces a disruption in the body’s ability to maintain a normal level of calcium. This abnormally high level of calcium in the blood develops because of increased bone breakdown and release of calcium from the bone. The disorder occurs in approximately 10-20% of all cancer cases. The most common cancers associated with hypercalcemia are breast, prostate, and lung cancer, as well as multiple myeloma or other tumors with extensive metastasis to the bone. It may also occur in patients with head and neck cancer, cancer of unknown primary, lymphoma, leukemia, kidney cancer, and gastrointestinal cancer. Hypercalcemia most commonly develops as a late complication of cancer, and its appearance constitutes an emergency. Several clinical symptoms are associated with cancer-related hypercalcemia. Symptoms may appear gradually and often look like signs of other cancers and diseases. The symptoms of hypercalcemia are not only related to the elevated level of calcium in the blood, but—more importantly—to how rapidly the hypercalcemia develops. The severity of the symptoms is often dependent upon factors such as previous cancer treatment, reactions to medications, or other illnesses a patient may have. Most patients do not experience all of the symptoms of hypercalcemia, and some may not have any signs at all. Rapid diagnosis of hypercalcemia may be complicated because the symptoms are often nonspecific and are easily ascribed to other factors. These symptoms include:  

Tamara Brown, R.N. 710

decreased muscle tone and muscle weakness delirium, disorientation, incoherent speech, and psychotic symptoms such as hallucinations and delusion G A LE EN CY C LO PE DI A O F C AN C ER 3

   

constipation fatigue poor appetite, nausea and/or vomiting frequency of urination and increased thirst pain

Causes The fundamental cause of cancer-related hypercalcemia is increased movement of calcium out of the bones and into the bloodstream, and secondarily, an inadequate ability of the kidneys to get rid of higher calcium levels. Normally, healthy kidneys are able to filter out large amounts of calcium from the blood, getting rid of the excess that is unneeded by the body and keeping the amount of the calcium the body does need. However, the high levels of calcium in the body caused by cancer-related hypercalcemia may cause the kidneys to become overworked, thus making them unable to excrete the excess. Another problem is that some tumors produce a substance that may cause the kidneys to get rid of too little calcium. Two types of cancer-caused hypercalcemia have been identified: osteolytic and humoral. Osteolytic occurs because of direct bone destruction by a primary or metastatic tumor. Humoral is caused by certain factors secreted by malignant cells, which ultimately cause calcium loss from the bones. Certain types of hormonal therapy may precipitate hypercalcemia and the use of some diuretics may contribute to the disorder. Because immobility causes an increase in the loss of calcium from bone, cancer patients who are weak and spend most of their time in bed are more prone to hypercalcemia. Cancer patients are often dehydrated because they take in inadequate amounts of food and fluids and often suffer from nausea and vomiting. Dehydration reduces the ability of the kidneys to remove excess calcium from the body, and therefore is another contributing factor in the development of hypercalcemia in cancer patients.

Treatments Individuals at risk for developing hypercalcemia may be the first to recognize symptoms, such as fatigue. The patient and family should be aware of the signs and symptoms so that a health care professional can be notified as early as possible should they occur. Patients can take several preventative measures like ensuring adequate fluid intake, controlling nausea and vomiting, maintaining the highest possible mobility, and avoiding drugs that affect the functioning of the kidneys. This includes avoiding those G A LE EN CY C LO PE DI A O F C AN CE R 3

medications containing calcium, vitamin D, or vitamin A. Since absorption of calcium is usually decreased in individuals with hypercalcemia, dietary calcium restriction is unnecessary. The mortality rate for untreated hypercalcemia is quite high. Early diagnosis and prompt treatment are essential. The magnitude of hypercalcemia and the severity of symptoms is usually the basis for determining what type of treatment is indicated. For those patients who have mild hypercalcemia, are experiencing no symptoms, and have cancer that is responsive to treatment, giving intravenous fluids and observing the patient may be all that is necessary to treat the condition. If the patient is experiencing symptoms or has a cancer that is expected to respond poorly to treatment, then medication to treat the hypercalcemia should be initiated. Additional treatment focuses on controlling nausea and vomiting, encouraging activity, and avoiding any medication that causes drowsiness. In treating moderate or severe hypercalcemia, replacing fluids is the first treatment intervention. Though providing fluid replacement will not restore normal calcium levels in all patients, it is still the most important initial step. Improvement in mental status and nausea and vomiting is usually apparent within 24 hours for most patients. However, rehydration is only a temporary measure. If the cancer is not treated, then drugs that will help to control the hypercalcemia are necessary. Many drugs are used to treat hypercalcemia, including calcitonin, plicamycin (formerly mithramycin), gallium nitrate, and bisphosphonates. Bisphosphonates are some of the most effective drugs for controlling hypercalcemia. Loop diuretics like furosemide are often given because they help to increase the excretion of excess serum calcium. For severe hypercalcemia that is complicated by kidney failure, dialysis is an option. Because of the large amounts of intravenous fluids given to treat hypercalcemia, the health care team will carefully observe for any signs of overhydration or other electrolyte imbalances. The severity of hypercalcemia determines the amount of treatment necessary. Severe hypercalcemia should be treated immediately and aggressively. Less severe hypercalcemia should be treated according to the symptoms. A positive response to the treatment is exhibited by the disappearance of the symptoms and a decreased level of calcium in the blood. Mild hypercalcemia does not usually need to be treated aggressively. After calcium levels return to normal, urine and blood should continue to be checked often to make certain the treatment is still working. 711

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Hypercoagulation disorders

Alternative and complementary therapies There are no known proven alternative treatments for cancer-related hypercalcemia. Some of the medications used are more effective than others, and the patient and family should discuss which ones are the most appropriate for the patient’s needs. Hypercalcemia usually develops as a late complication of cancer, and its appearance is very serious. The outlook is often quite grim. However, it is not clear if death occurs because of the hypercalcemia crisis or because of the advanced cancer. Because hypercalcemia is often a complication that occurs in the final stages of cancer, the decision to treat it depends upon the overall goals of treatment determined by the patient, family, and physician. The natural course of untreated hypercalcemia will progress to loss of consciousness and coma. Some patients may prefer this at the end of life rather than have unrelieved suffering and/or untreatable symptoms. It is therefore important for the patient and caregivers to discuss what supportive care measures are wanted. Resources BOOKS

Prucha, Edward J., editor. Cancer Sourcebook. Detroit: Omnigraphics, 2000. OTHER

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. (800) 4 CANCER. [cited July 5, 2005]. http:// www.nci.nih.gov.

Deanna Swartout-Corbeil, R.N.

Hypercoagulable states, Trousseau’s syndrome, Blood clots see Hypercoagulation disorders

Hypercoagulation disorders Description Hypercoagulation disorders (or hypercoagulable states or disorders) cause an increased tendency for clotting of the blood. In normal hemostasis (the stoppage of bleeding) clots form at the site of the blood vessel’s injury. However, in hypercoagulation disorders the clots can develop in circulating blood. This may put a patient at risk for obstruction of veins and arteries (phlebitis, thrombosis, or thrombophlebitis). The hypercoagulable state and thrombophlebitis is 712

common cases of cancer involving solid tumors such as pancreatic, breast, ovarian, and prostate cancer. Hypercoagulation disorders can cause clots throughout the body’s blood vessels, a condition known as thromboembolic disease. Thromboembolic disease can lead to infarction (death of tissue as a result of blocked blood supply to the tissue). Other serious results of hypercoagulation make this a dangerous condition. Clotting (thrombosis) in the veins and arteries leading to the lungs can prevent blood flow, causing sudden and severe loss of breath and chest pain. These clots, called pulmonary embolisms, are potentially fatal. Clots in the blood vessels of the brain can result in a stroke, and clots in the heart’s blood vessels can result in a heart attack. Symptoms of hypercoagulation disorders include swelling or discoloration of the limbs, pain or tenderness of the skin, visible obstructions in the surface veins, and ulcers of the lower parts of the legs. The diagnosis of hypercoagulation disorders is completed with a combination of physical examination, imaging studies, and blood tests. The presence of deep clots can be determined using Doppler ultrasound examination—special x-ray techniques called venography or arteriography (in which a solution is injected into the blood vessel to aid in imaging), or a specific type of blood pressure test called plethysmography. There are a number of blood tests that can determine the presence or absence of proteins, clotting factors, and platelet counts in the blood. Among the tests used to detect hypercoagulation is the Antithrombin III assay. Protein C and Protein S concentrations can be diagnosed with immunoassay or plasma antigen level tests.

Causes Hypercoagulation disorders are associated with cancer of the pancreas. About half of patients with pancreatic cancer experience incidence of thrombosis. Approximately 10% of patients with pancreatic cancer develop a specific type of hypercoagulation disorder known as migratory thrombophlebitis, or Trousseau’s syndrome. In Trousseau’s syndrome the blood vessels become inflamed and clots in the blood vessels spontaneously appear and disappear. Other types of cancer may also result in hypercoagulation disorders. In order for blood coagulation to occur, platelets (small, round fragments in the blood) help contract blood vessels to lessen blood loss and also to help plug damaged blood vessels. The conversion of platelets into actual clots is a complicated process involving proteins that are identified clotting factors. The factors are G A LE EN CY C LO PE DI A O F C AN C ER 3

Treatments The treatment for patients with hypercoagulation disorders varies depending upon the severity of the clotting and the other conditions it may have caused. Medications may include blood thinners (anticoagulants) such as heparin and warfarin, which prevent the formation of new blood clots; antiplatelet drugs such as aspirin; or thrombolytic drugs to dissolve existing clots. Pain medications and nonsteroidal anti-inflammatory medications may be given to reduce pain and swelling. Antibiotics will be prescribed if infection has occurred. Resources BOOKS

Deloughery, Thomas G. Hemostasis and Thrombosis. Georgetown, TX: Landes Bioscience, 1999. Goodnight, Scott H., and William E. Goodnight. Disorders of Hemostasis and Thrombosis. 2nd ed. New York: McGraw Hill, 2000. OTHER

American Academy of Family Physicians. Hypercoagula tion: Excessive Blood Clotting. (15 April 2001). [cited July 5, 2005]. http://familydoctor.org/handouts/ 244.html. ORGANIZATIONS

National Heart, Lung and Blood Institute. Building 31, Room 4A21, Bethesda, MD 20892. (301) 496 4236. http://www.nhlbi.nih.gov. National Hemophilia Foundation. 116 West 32nd St., 11th Floor, New York, NY 10001. 800 42 HANDI. http:// www.hemophilia.org.

Paul A. Johnson, Ed.M.

Hyperthermia Definition Hyperthermia refers to the use of heat to treat various cancers on and inside the body. It is also called hyperthermia therapy or thermotherapy. G A LE EN CY C LO PE DI A O F C AN CE R 3

Hyperthermia therapy for cancer should not be confused with heat therapy, which is a treatment that involves the application of mild heat from heating pads or warm compresses to localized areas of the body to relieve muscle and joint pain or stiffness. Hyperthermia therapy is specifically intended to kill or weaken tumors rather than to temporarily relieve discomfort caused by arthritis, sprains and strains, or similar conditions. It can be applied to a very small area (local hyperthermia), an entire limb or organ (regional hyperthermia), or the patient’s entire body (whole-body hyperthermia).

Purpose The purpose of hyperthermia is to shrink and hopefully destroy cancerous tissues without harming noncancerous cells. It can be used to treat cancer in many areas of the body, including the brain, thyroid, lung, breast, and prostate. It is thought that high temperatures, up to 106 degrees Fahrenheit, can help shrink cancerous tumors. Hyperthermia is starting to be more widely used because it does not usually have severe side effects like such other forms of cancer treatment as radiation or chemotherapy. In most instances, hyperthermia is used at the same time with other forms of cancer therapy.

Demographics Although hyperthermia treatment was considered an experimental form of cancer therapy in the 1980s, its proponents believe that the treatment has been accepted by many physicians, and that use of hyperthermia will increase as more cancer centers install the high-tech equipment necessary for regional and wholebody hyperthermia. As of 2009, cancer care centers offering whole-body treatment are limited in number; however, there are several in larger cities across the United States that offer local hyperthermia. In general, hyperthermia is used more often in Europe as an adjuvant treatment for cancer than in North America. The American Cancer Society has acknowledged that hyperthermia can make the cancer cells of some cancers more responsive to treatment, but still considers the treatment experimental, especially in wholebody form. The Cancer Treatment Centers of America (CTCA), however, lists local hyperthermia as a conventional treatment under the larger heading of radiation therapy. The National Cancer Institute (NCI) is sponsoring ongoing clinical trials of hyperthermia in cancer treatment; there are 71 such trials underway as of late 2009. The types of cancer being studied in these trials include breast, prostate, 713

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carried in the plasma, or liquid portion, of the blood. Proteins C and S are two of the clotting factors that are present in the plasma to help regulate or activate parts of the clotting process. It is believed that pancreatic tumors produce chemicals that promote clotting, or coagulation, of the blood (procoagulants), or that they activate platelet function. It is also possible that tumors interfere with the functions of proteins C and S.

Hyperthermia

bladder, cervical, uterine, head and neck, ovarian, thyroid, and liver cancers. Several studies are concerned with late-stage metastatic and soft-tissue cancers. All age groups are represented in these clinical trials, including children.

Precautions Patients who have extensive metastasis (spreading of the cancer throughout their body) are not considered the best candidates for hyperthermia, although they can receive whole-body treatment. Patients must be free of major infections and able to tolerate the high temperatures of the treatment. Caution must be used when areas of the body are heated with such external heat sources as heating pads to avoid potentially dangerous burns. Other types of patients who should be treated cautiously with hyperthermia include: Pregnant women.  People who are anemic.  People known to be sensitive to high temperatures.  Diabetics.  People with tuberculosis.  People with seizure disorders. 

Description Hyperthermia can be used on the body from very small areas of the body to the entire body itself. Local hyperthermia refers to heating just one area of body, usually where the tumor is located. The heat is applied for about an hour. Heat can be applied from outside the body using microwaves or high-frequency radio waves. Heat can be applied from inside the body or even inside the tumor itself by the use of thin heated wires, small tubes filled with hot water, implanted microwave antennae, or radiofrequency electrodes. Some cancer centers use ultrasound to produce heat within the tumor. Ultrasound is more easily focused than other energy modalities, and can be applied to tumors located on the skin surface or up to 3 inches (8 cm) inside the body. If heat is used to treat an entire organ or limb, it is referred to as regional hyperthermia. High-energy magnets or other devices that produce high energy, and thus heat, are placed over the larger areas to be heated. Magnetic fluid hyperthermia involves the injection of a fluid containing magnetic nanoparticles directly into the malignant tumor. When the nanoparticles are placed in an alternating magnetic field with frequencies similar to FM radio signals, they generate heat and destroy the tumors. Another method of regional hyperthermia is the use of perfusion. Hyperthermia perfusion is a 714

technique that uses the patient’s own blood; the blood is removed, heated outside the body, then pumped back into the area that contains the cancer. A warmed solution containing anticancer drugs may also be used as part of perfusion hyperthermia. One form of perfusion hyperthermia that is used to treat abdominal cancers is called continuous hyperthermic peritoneal perfusion or CHPP. Performed during open surgery, this procedure involves the circulation of heated anticancer drugs through the abdominal cavity to raise the temperature of the internal organs to 106–108 F (41–42 C). For treatment of cancers that have spread throughout the body, whole-body hyperthermia can be considered. Various methods are used to heat up a patient’s entire body, including warm-water or electric blankets, hot wax, or thermal chambers which are very much like incubators used to warm newborn babies, except much larger. Origins Hyperthermia has a long history; the earliest report of heat treatment to cure systemic disease is found in the writings of Hippocrates (c. 400 B.C.). A century before Hippocrates, another Greek philosopher/physician named Parmenides (520–450B.C.) thought that an artificially induced fever could cure any disease. In ancient India, practitioners of Ayurveda used regional and whole-body hyperthermia to treat various disorders. In North America in more recent times, many Native American tribes used sweat lodges for healing rituals or to purify warriors wounded in battle. The use of heat as a cancer treatment in scientific medicine dates from the nineteenth century. A German physician reported in 1866 that a patient with a neck sarcoma was cured of the tumor after surviving a high fever. In 1893, a Swedish gynecologist named Westermark experimented with fevers induced by bacterial toxins and the use of a coil filled with hot water to treat uterine tumors. No controlled studies were conducted at the time, however, and reports of successful cancer treatment using heat were considered anecdotal. Interest in heat as a possible treatment for cancer declined in the early twentieth century but rose again in the 1960s when some researchers working with cancer cells in mice thought that the malignant cells might be more sensitive to heat than normal cells. Unfortunately, later studies demonstrated that cancer cells are not necessarily more sensitive to heat by itself than normal cells. Doctors presently think that hyperthermia is effective only in combination with radiotherapy or chemotherapy. G A LE EN CY C LO PE DI A O F C AN C ER 3

Patients should be prepared for hyperthermia by an explanation of the specific technique that is to be used and what to expect during and after the procedure. In most cases the patient will be given a local anesthetic when temperature probes are inserted to monitor the heat levels in the part of the body being treated. Radiofrequency ablation or perfusion of the peritoneal cavity usually requires general anesthesia.

Aftercare Patients will usually need to rest afterward. Those who have had general anesthesia will need to be monitored during recovery. Patients who have had whole-body hyperthermia may need aftercare for nausea and vomiting. Patients who have had perfusion hyperthermia may need aftercare for tissue swelling or bleeding.

Risks The major risks of hyperthermia use are pain and external burns. Heat applied directly to the skin can cause minor discomfort to significant pain, especially when high temperatures are used. Blistering and actual burning of the skin can also occur at higher temperatures, although with careful application of the instrument or device, these side effects are very rare. As of 2009, many cancer centers use magnetic resonance imaging (MRI) not only to locate the tumor, but to guide the application of hyperthermia to the cancerous cells. Risks associated with perfusion hyperthermia include swollen tissues, blood clots, and bleeding; these side effects are usually temporary, however. Risks associated with whole-body hyperthermia include nausea, vomiting, and diarrhea. Rare side effects with whole-body hyperthermia include heart and vascular disorders.

Results Normal results The goal of hyperthermia is to control the growth and shrink hyperthermia-sensitive tumors. As stated earlier, hyperthermia can also be used to help sensitize tumors to such other cancer treatment modalities as radiation and chemotherapy. While hyperthermia is considered effective in shrinking tumors or making them more sensitive to other therapies, there is little evidence as of 2009 that it extends patients’ survival time. It does, however, improve their quality of life, as several European studies have reported. G A LE EN CY C LO PE DI A O F C AN CE R 3

Q U E S T I O N S TO A S K Y O U R DOCTOR 

  





Should I consider hyperthermia as an adjuvant therapy? What is your opinion of hyperthermia? What type of hyperthermia would you recommend? Can you recommend a cancer center with the necessary equipment and experience in this form of treatment? Should I consider participation in a clinical trial of hyperthermia as an adjunctive treatment for my type of cancer? What are the risks of hyperthermia?

Abnormal results Hyperthermia has fewer severe side effects than radiation therapy or chemotherapy. As noted above, tissue swelling and bleeding may be temporary side effects in some patients, while some experience nausea and other gastrointestinal disturbances following whole-body hyperthermia. Such side effects as pain and burning from external heat sources can be minimized with careful application of the heat.

Health care team roles Hyperthermia usually requires at least two doctors to administer, an oncologist and a radiologist. An anesthesiologist will be needed if the specific procedure requires the patient to be under general anesthesia. Nursing staff are required to monitor patients for vital signs and possible side effects during the recovery period.

Alternatives As of 2009, radiofrequency ablation (RFA) is used more frequently than perfusion or whole-body hyperthermia to deliver heat to malignant tumors. RFA makes use of a special probe inserted directly into a tumor that uses radiofrequency waves to heat the tumor above 122 F (50 C), a temperature that is high enough to kill the tumor cells. This is a higher temperature level than can be used with hyperthermia. In addition to its ability to actually kill malignant cells, RFA has the additional advantage of targeting malignant tumors precisely with minimal risk to nearby healthy tissue.

Research and general acceptance While radiofrequency ablation is a proven mainstream alternative to regional or whole-body 715

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Preparation

Hypocalcemia

hyperthermia, one type of hyperthermia therapy that is not only unproven but potentially dangerous is intracellular hyperthermia, also called 2-4-dinitrophenol or DNP therapy. DNP is an organic substance injected directly into the body to cause an artificial fever. There is no evidence that dinitrophenol is effective in treating cancer; moreover, some patients have died as a result of DNP injections.

Caregiver concerns Hyperthermia is administered in a clinic or hospital rather than at home. Caregivers should, however, monitor patients who have received whole-body hyperthermia after they return home for possible side effects.

Schildkopf, P., et al. ‘‘Hyperthermia in Combination with X irradiation Induces Inflammatory Forms of Cell Death.’’ Autoimmunity 42 (May 2009): 311 313. OTHER

American Cancer Society (ACS). Heat Therapy. http:// www.cancer.org/docroot/ETO/content/ ETO_5_3X_Heat_Therapy.asp. Cancer Treatment Centers of America (CTCA). Local Hyperthermia. [Includes 2 minute video] http:// www.cancercenter.com/conventional cancer treat ment/local hyperthermia.cfm. National Cancer Institute (NCI) Fact Sheet. Hyperthermia in Cancer Treatment: Questions and Answers. http:// www.cancer.gov/cancertopics/factsheet/Therapy/ hyperthermia. ORGANIZATIONS

Resources BOOKS

Abeloff, Martin D., et al., eds. Abeloff’s Clinical Oncology, 4th ed. Philadelphia: Churchill Livingstone/Elsevier, 2008. Ades, Terri, et al., editors. American Cancer Society Com plete Guide to Complementary and Alternative Cancer Therapies, 2nd ed. Atlanta, GA: American Cancer Society, 2009. Baronzio, Gian Franco, and E. Dieter Hager, eds. Hyper thermia in Cancer Treatment: A Primer. New York: Springer Science+Business Media, 2006. PERIODICALS

Bakshandeh Bath, A., et al. ‘‘Preclinical and Clinical Aspects of Carboplatin and Gemcitabine Combined with Whole body Hyperthermia for Pancreatic Adenocarcinoma.’’ Anticancer Research 29 (August 2009): 3069 3077. Chua, T.C., et al. ‘‘Intraoperative Hyperthermic Intraperi toneal Chemotherapy after Cytoreductive Surgery in Ovarian Cancer Peritoneal Carcinomatosis: Systematic Review of Current Results.’’ Journal of Cancer Research and Clinical Oncology 135 (December 2009): 1637 45. Corchero, J.L., and A. Villaverde. ‘‘Biomedical Applications of Distally Controlled Magnetic Nanoparticles.’’ Trends in Biotechnology 27 (August 2009): 468 76. Helm, C.W. ‘‘The Role of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer.’’ Oncolo gist 14 (July 2009): 683 94. Piso, P., et al. ‘‘Quality of Life after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies.’’ Journal of Surgical Oncology 100 (September 15, 2009): 317 20. Riley, W. ‘‘Belmont Hyperthermia Pump in the Conduct of Intra operative Heated Chemotherapy.’’ Perfusion 24 (March 2009): 115 118. Salloum, M., et al. ‘‘Enhancement in Treatment Planning for Magnetic Nanoparticle Hyperthermia: Optimization of the Heat Absorption Pattern.’’ International Journal of Hyperthermia 25 (June 2009): 309 21. 716

American Cancer Society, 250 Williams Street NW, Atlanta, GA, 30303, 800 ACS 2345 (227 2345), www.cancer.org. Cancer Treatment Centers of America (CTCA), 800 931 0599, http://www.cancercenter.com/. National Cancer Institute, 6116 Executive Blvd., Room 3036A, Bethesda, MD, 20892 8322, 800 422 6237, [email protected], www.cancer.gov. National Center for Complementary and Alternative Med icine (NCCAM), 9000 Rockville Pike, Bethesda, MD, 20892, 888 644 6226, [email protected], http:// nccam.nih.gov/. International Clinical Hyperthermia Society (ICHS), U.S. contact: Dr. James Haim I. Bicher, 12099 W. Wash ington Blvd., #304, Los AngelesCA, United States, 90066, 310 398 0013, inforequest@hyperthermia ichs. org, http://www.hyperthermia ichs.org/.

Edward R. Rosick, D.O., M.P.H. Rebecca J. Frey, PhD

Hypocalcemia Definition Hypocalcemia is a type of electrolyte disturbance in which the level of calcium in the blood is too low. It occurs when the concentration of free calcium ions in the blood falls below 4.0 mg/dL (dL = a deciliter or onetenth of a liter, about 3.4 fluid ounces). The normal concentration of free calcium ions in the blood serum is 4.0–6.0 mg/dL. Hypocalcemia can be caused by a range of conditions or disorders that either decrease the entry of calcium into the blood or increase the loss of calcium from the blood. G A LE EN CY C LO PE DI A O F C AN C ER 3

It is difficult to estimate the frequency of hypocalcemia in the general population because many people, particularly those with mild forms of the disorder, have no noticeable symptoms. Studies of hospitalized patients admitted to intensive care units have indicated that 15–50% have hypocalcemia. Hypocalcemia can affect persons of any age, depending on the disorder or condition causing the imbalance. As far as is known, both sexes and all races are equally likely to develop hypocalcemia.

Description Calcium is an important mineral for maintaining human health. It is not only a component of bones and teeth, but is also essential for normal blood clotting and necessary for normal muscle and nerve functioning. In the human body, 99% of the total calcium is in the bones and teeth, and 1% is in the blood plasma. The calcium ion (Ca2+) has two positive charges. In bone, calcium ions occur as a complex with phosphate to form crystals of calcium phosphate. In the bloodstream, calcium ions also occur in complexes, and here calcium is found combined with proteins and various nutrients. However, in the bloodstream, calcium also occurs in a free form. Normally, about 47% of the calcium in the blood plasma is free, while 53% occurs in a complexed form. Although all of the calcium in the bloodstream serves a useful purpose, only the concentration of free calcium ions has a direct influence on the functioning of our nerves and muscles. For this reason, the measurement of the concentration of free calcium is more important in the diagnosis of disease than measuring the level of total calcium or of complexed calcium. The level of total calcium in the blood serum is normally 8.5–10.5 mg/dL, while the level of free calcium is normally 4–5 mg/dl. Risk factors Risk factors for hypocalcemia include:        



history of kidney disorders history of thyroid disorders poor nutrition, especially vitamin D deficiency eating disorders alcoholism diagnosis of breast or prostate cancer being treated with chemotherapy for cancer heavy use of laxatives or other medications containing magnesium pancreatitis

G A LE EN CY C LO PE DI A O F C AN CE R 3

 

treatment for heavy metal poisoning diGeorge syndrome and other congenital disorders characterized by failure of the parathyroid gland to develop normally

Causes and symptoms Causes Hypocalcemia has several different possible causes. It can be caused by hypoparathyroidism, by failure to produce 1,25-dihydroxyvitamin D, by low levels of plasma magnesium, or by failure to get adequate amounts of calcium or vitamin D in the diet. Hypoparathyroidism involves the failure of the parathyroid gland to make parathyroid hormone. In some cases hypoparathyroidism results from surgical removal of the parathyroid gland or from genetic disorders that affect the normal development of the parathyroid gland. Parathyroid hormone controls and maintains plasma calcium levels. The hormone exerts its effect on the kidneys, where it triggers the synthesis of 1,25dihydroxyvitamin D. Thus, hypocalcemia can be independently caused by damage to the parathyroid gland or to the kidneys. 1,25-Dihydroxyvitamin D stimulates the uptake of calcium from the diet and the mobilization of calcium from the bone. Bone mobilization refers to the natural process by which the body dissolves part of the bone in the skeleton in order to maintain or raise the levels of plasma calcium ions. Low plasma magnesium levels (hypomagnesemia) can result in hypocalcemia. Hypomagnesemia can occur with alcoholism or with diseases characterized by an inability to properly absorb fat. Magnesium is required for parathyroid hormone to play its part in maintaining plasma calcium levels. For this reason, any disease that results in lowered plasma magnesium levels may also cause hypocalcemia. Hypocalcemia may also result from the consumption of toxic levels of phosphate. Phosphate is a constituent of certain enema formulas. An enema is a solution that is used to cleanse the intestines via a catheter or tube inserted into the rectum. Cases of hypocalcemia have been documented in which people swallowed enema formulas or an enema had been administered to an infant. Other causes of hypocalcemia include: 



Cancers that metastasize (spread) from other organs to the bone and destroy the bone. The most likely cancers of this type are breast cancer and prostate cancer. Certain cancer chemotherapy drugs, particularly cisplatin, leucovorin, and 5-fluorouracil. 717

Hypocalcemia

Demographics

Hypocalcemia

Severe pancreatitis (inflammation of the pancreas).  Chelation therapy. Chelation therapy involves the use of such chemicals as EDTA to treat heavy metal poisoning. The chelating agent binds to the mercury, lead, or other heavy metal and enables the body to excrete the toxic substance safely. Hypocalcemia is a side effect of chelation therapy, however.  Hungry bone syndrome. Hungry bone syndrome is a disorder that develops in some patients after surgical removal of the parathyroid gland.  Sepsis (whole-body inflammatory response to severe infection).  Toxic shock syndrome. 

The doctor may hear wheezing or rattling noises when listening to the patient’s breathing. An electrocardiogram (EKG) may indicate some irregularities in heart rhythm. The patient may complain of muscle cramps or spasms, intestinal cramping, difficulty swallowing, coughing spells, facial twitching, general aching sensations in the muscles, numbness in fingers or toes, or tingling sensations. In severe hypocalcemia, the patient may have such neurological symptoms as seizures, hallucinations, and confusion. Tests

Symptoms Symptoms of severe hypocalcemia include numbness or tingling around the mouth or in the feet and hands, as well as in muscle spasms in the face, feet, and hands. These involuntary muscle spasms are called tetany. Hypocalcemia can also result in depression, memory loss, or hallucinations. Severe hypocalcemia occurs when serum free calcium is under 3 mg/dL. Chronic and moderate hypocalcemia can result in cataracts (damage to the eyes). In this case, the term ‘‘chronic’’ means lasting one year or longer.

Diagnosis Hypocalcemia is frequently asymptomatic. When suspected, it is diagnosed by taking a careful patient history, a physical examination, and taking a sample of blood serum. The blood is tested for the concentraton of free calcium using a calcium-sensitive electrode. Hypocalcemia has several causes; hence a full diagnosis requires assessment of the parathyroid gland, kidneys, and plasma magnesium concentration. The patient should be asked about a history of eating disorders, vitamin deficiencies, treatment for alcoholism, kidney or liver problems, disorders of the pancreas or digestive tract, thyroid or parathyroid disorders, recent neck or bowel surgery, or epilepsy. Examination Physical examination of a patient with suspected hypocalcemia includes an examination of the patient’s skin, mouth, and hair. Patients with hypocalcemia often have dry skin, brittle hair and nails, teeth in bad condition, skin rashes or itching skin, and cataracts in the eye. If the patient has a disorder of the parathyroid gland, they may also be shorter than average, have a round ‘‘moon’’ face, and possibly mentally retarded. 718

The doctor will usually order blood tests to evaluate the level of calcium and other electrolytes (particularly magnesium and phosphate levels) in the blood as well as tests of liver and kidney function. The level of parathyroid hormone will be checked by means of an antibody-mediated radioimmunoassay. The doctor will also order an EKG if one was not performed in the office in order to evaluate abnormal heart rhythms. Two diagnostic tests that may be performed are the Chvostek and Trousseau tests. In the Chvostek test, the doctor taps over the facial nerve along the jawline about an inch in front of the ear. A patient with hypocalcemia will develop twitching at the corner of the mouth, the nose, the eye, and the other facial muscles. In the Trousseau test, a blood pressure cuff is placed on the patient’s arm and inflated above the level of the systolic pressure for 3 minutes. A patient with hypocalcemia will develop spasms in the hand and forearm and the wrist will flex upward.

Treatment Traditional The method chosen for treatment depends on the exact cause and on the severity of the hypocalcemia. Mild hypocalcemia may require nothing more than a thorough office examination and laboratory testing. Severe hypocalcemia requires admission to the hospital for supportive care and immediate injection of calcium ions, usually in the form of calcium gluconate. In severe cases, emergency room physicians will need to consult one or more specialists, including surgeons, neurologists, oncologists, dietitians, internists, endocrinologists, and toxicologists. Drugs Oral calcium supplements are prescribed for longterm treatment (non-emergency) of hypocalcemia. The G A LE EN CY C LO PE DI A O F C AN C ER 3

QUESTIONS TO ASK YOUR DOCTOR     

What is causing the hypocalcemia? How severe is it? Is the underlying condition treatable? Will I need to see a specialist? How often have you treated patients with hypocalcemia?

oral supplements may take the form of calcium carbonate, calcium chloride, calcium lactate, or calcium gluconate. Where hypocalcemia results from kidney failure, treatment includes injections of 1,25-dihydroxyvitamin D. Oral vitamin D supplements can increase gastrointestinal absorption of calcium. Where hypocalcemia results from hypoparathyroidism, treatment may include oral calcium, 1,25-dihydroxyvitamin D, or other drugs. Where low serum magnesium levels occur, concurrently with hypocalcemia, the magnesium deficiency must be corrected to effectively treat the hypocalcemia.

Prognosis The prognosis for hypocalcemia from simple dietary deficiencies is excellent. In most cases, however, the prognosis depends on the disorder or condition causing the hypocalcemia. Patients with alcoholism or eating disorders may need psychiatric intervention as well as medical treatment in order to recover fully. Severe symptomatic hypocalcemia can result in seizures, low blood pressure that does not respond to fluid, and irregular heart rhythms. In a few cases, cardiovascular collapse brought on by hypocalcemia has resulted in death.

Prevention The first and most obvious way to help prevent hypocalcemia is to ensure that adequate amounts of calcium and vitamin D are consumed each day, either in the diet or as supplements. Hypocalcemia that may occur with damage to the parathyroid gland or to the kidneys cannot be prevented. Hypocalcemia resulting from overuse of enemas can be prevented by reducing enema usage. Hypocalcemia resulting from magnesium deficiency tends to occur in chronic alcoholics, and this type of hypocalcemia can be prevented by reducing alcohol consumption and increasing the intake of healthful food.

G A LE EN CY C LO PE DI A O F C AN CE R 3

BOOKS

Fiebach, Nicholas H., et al, eds. Principles of Ambulatory Medicine. Philadelphia: Lippincott Williams and Wilkins, 2007. Jameson, J. Larry, ed. Harrison’s Nephrology and Acid base Disorders. New York: McGraw Hill Medical, 2010. Kleerekoper, Michael, Ethel S. Siris, and Michael McClung, eds. The Bone and Mineral Manual: A Practical Guide, 2nd ed. Burlington, MA: Elsevier Academic Press, 2005. PERIODICALS

Athappan, G., and V. K. Ariyamuthu. ‘‘Images in Clinical Medicine. Chvostek’s Sign and Carpopedal Spasm.’’ New England Journal of Medicine 360 (April 30, 2009): e24. Ferron, M., and G. Karsenty. ‘‘The Gutsy Side of Bone.’’ Cell Metabolism 10 (July 2009): 7 8. Jordan, R., et al. ‘‘An Alcoholic Presenting Fits.’’ Clinical Medicine 9 (June 2009): 291 92. Oztas, E., et al. ‘‘Oral Fleet Phospho Soda Laxative Induced Symptomatic Hypocalcemia in an Adult Patient with Celiac Disease.’’ American Journal of Gastroenterology 104 (June 2009): 1607 08. Zhou, P., and M. Markowitz. ‘‘Hypocalcemia in Infants and Children.’’ Pediatrics in Review 30 (May 2009): 190 92. OTHER

Beach, Christopher B. ‘‘Hypocalcemia.’’ eMedicine, March 9, 2009. http://emedicine.medscape.com/article/ 767260 overview. Lewis, James L., III. ‘‘Disorders of Calcium Concentration: Hypocalcemia.’’ Merck Manual of Diagnosis and Treatment. http://www.merck.com/mmpe/sec12/ ch156/ch156g.html#sec12 ch156 ch156g 837. Skugor, Mario. ‘‘Hypocalcemia.’’ Cleveland Clinic Disease Management Project. http://www.clevelandclinicme ded.com/medicalpubs/diseasemanagement/endocrinol ogy/hypocalcemia/. ORGANIZATIONS

American Association of Clinical Endocrinologists (AACE), 245 Riverside Ave., Suite 200, Jacksonville, FL, 32202, 904 353 7878, http://www.aace.com/. American College of Emergency Physicians (ACEP), 1125 Executive Circle, Irving, TX, 75038 2522, 972 550 0911, 800 798 1822, 972 580 2816, http://www.acep.org/. American Society for Nutrition (ASN), 9650 Rockville Pike, Bethesda, MD, 20814, 301 634 7050, 301 634 7892, [email protected], http://www.nutrition.org/. Food and Drug Administration (FDA), 10903 New Hamp shire Ave., Silver Spring, MD, 20993, 888 463 6332, http://www.fda.gov/. National Toxicology Program (NTP), P.O. Box 12233, MD K2 03, Research Triangle Park, NC, 27709, 919 541 0530, http://ntp.niehs.nih.gov/.

Tom Brody, PhD Rebecca J. Frey, PhD

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Hypocalcemia

Resources

I Ibritumomab Definition Ibritumomab is a radioimmunotherapy used to treat non-Hodgkin’s lymphoma (NHL).

Purpose Ibritumomab is used to treat individuals with low grade follicular NHL that has failed to respond or that has stopped responding to the drug rituximab (Rituxan). NHL is a cancer that arises in the organs of the lymph system. It is the most common type of lymphoma in the United States. The lymph system is important in creating and transporting blood cells called lymphocytes that fight infection throughout the body. The major organs of the lymph system are the spleen, thymus, tonsils, and bone marrow. These organs produce several different kinds of cells that fight infection. The major ones are called T-cells and B-cells. Ibritumomab specifically targets both mature and immature B-cells. In NHL, abnormal (cancerous) lymphocytes grow out of control. So many of these abnormal lymphocytes develop that they prevent other immune system cells and blood vessel from forming. There are several types of NHL. One form is called follicular lymphoma. In this form, the cancerous cells clump together. They may grow quickly, in which case the disease is called a high-grade lymphoma, or they may grow slowly, in which case the cancer is called lowgrade lymphoma. Standard treatments for NHL include chemotherapy, radiation therapy, stem cell therapy, and a newer form of therapy called biologic therapy. Biologic therapy uses the biopharmaceutical rituximab. Ibritumomab is used in patients with low-grade B-cell G A LE EN CY C LO PE DI A O F C AN CE R 3

NHL who have failed to respond or who have relapsed after standard treatment.

Description Ibritumomab, which is also called ibritumomab tiuxetan, is manufactured in the United States and sold under the brand name Zevalin by IDEC Pharmaceuticals. It was approved for use in February 2002 and was the first radioimmunotherapy approved by the United States Food and Drug Administration (FDA). Generic substitutes are not available, and currently there is only one American manufacturer. Radioimmunotherapy is a form of biologic therapy that combines a protein that attaches to the target cell with a small dose of radioactive material that disrupts and kills the cell. Unique proteins called antigens exist on the surface of every cell. The body monitors these proteins, and when it recognizes a cell as foreign or defective, it creates other antigen-specific proteins called antibodies to attach to the unwanted cells and disable them. With NHL, this system of protection fails and defective cancerous cells are allowed to continue growing. Ibritumomab is an antibody made of mouse (murine) protein that comes from Chinese hamster ovary cells. It binds with the a protein called CD20 that is found on the surface of both normal and malignant B-cells. Ibritumomab alone does not kill B-cells, so it is bound to a radioactive material, either Indium-111 (In-111) or Yttrium-90 (Y-90). The role of ibritumomab is to deliver the radioactive material to specific target cells and bind it there. The radioactive rays given off by IN-111 or Y-90 disrupt the cell’s functions, resulting in cell death. This therapy kills both healthy and cancerous B-cells.

Recommended dosage Ibritumomab is given only in a two-step cycle in conjunction with another non-radioactive antibody 721

Ibritumomab

K EY T ERM S Anaphylactic shock—A whole body allergic reaction that is often fatal. Malignant—Cancerous. Neutrophil—A type of blood cell important to fighting infection. Non-Hodgkin’s lymphoma—A cancer of the lymph system that causes the accumulation of large numbers of defective (cancerous) immune system cells. Platelet—A white blood cell that produces proteins that help blood clot. Radioimmunotherapy—A treatment in which a radioactive material is delivered to specific cells by using a protein that binds to the surface of the target cells.

used by pregnant women. Women should use birth control for 12 months after receiving this therapy. It has not been established whether this therapy is safe to use in breastfeeding women. A pediatric dose has not been established. Zevalin is radioactive when it is being administered, and care should be taken to minimize exposure of patients and health care providers.

Side effects Side effects are many and varied. Serious but rare side effects include: 





called rituximab. Rituximab attacks the same B-cells as ibritumomab but does not deliver a dose of radioactive material to the cell. The two-step cycle of administration of ibritumomab is intended to occur only once. The material needed for the therapeutic administration of ibritumomab is sold under the name Zevalin. The ibritumomab carrier antibody is mixed with the radioactive material by the physician shortly before use. Step 1 includes a single dose of rituximab. The dose is determined by the patient’s body size. Rituximab is infused slowly into a vein while the physician watches for hypersensitivity reactions. Within four hours following administration of rituximab, a single dose of 5.0 milliCuries (mCi) ibritumomab tiuxetan that contains the radioactive material In-111 is injected intravenously (IV) over a period of 10 minutes. Step 2 follows seven to nine days after Step 1. The patient is given another IV dose of rituximab, again based on body size. Within four hours following the rituximab, the patient is injected with a dose of radioactive ibritumomab Y-90. This dose is also based on body size up to a total maximum allowable dose of 32.0 mCi. This completes the active part of the therapy, but patients must continue to have their blood count monitored for several months, as the therapy continues to kills cells for weeks.

Precautions People who are allergic to any type of mouse (murine) protein, rituximab, yttrium chloride or indium chloride should not use this therapy. Ibritumomab can cause harm to the developing fetus and should not be 722

potentially fatal infusion hypersensitivity reactions, usually to the first dose of rituximab, that can cause low blood pressure, difficulty breathing, heart attack, and anaphylactic shock severe drop in platelet count (thrombocytopenia) or neutrophil count (neutropenia); uncontrolled bleeding development of secondary malignancies that arise from the therapy More common but less serious side effects include:

       

susceptibility to infections; fever or chills nausea, vomiting, diarrhea, black, tarry stools loss of appetite anemia joint pain dizziness increased cough or hoarseness rash, swelling, or puffiness around the face and neck

Interactions It is important to tell the physician about all prescription medications, over-the counter medications, and herbal or alternative remedies that are being taken before treatment with Zevalin is begun. No formal drug interaction studies have been completed, however, Zevalin therapy does interfere with blood clotting and should not be used while individuals are taking blood thinners such as warfarin (Coumadin) or clopidogrel bisulfate (Plavix). Individuals who have a very low platelet count may not be able to use this therapy. Individuals should not be vaccinated with a live virus vaccine prior to or soon after receiving this therapy. The interaction of live virus vaccines and this therapy has not been investigated, but it is recommended that individuals receiving ibritumomab avoid people who have recently been vaccinated with live virus oral polio vaccine. Tish Davidson, A. M. G A LE EN CY C LO PE DI A O F C AN C ER 3

Definition Idarubicin is a medication that kills cancer cells.

Purpose Idarubicin is approved to treat only one single cancer, acute myelocytic leukemia (AML) in adults. Recent research suggests that using idarubicin rather than the more traditional daunorubicin in treating AML results in higher rates of complete remission (CR) and longer survival for patients. CR is the total elimination of all diseased cells detectable following therapy. The Food and Drug Administration (FDA) has not approved idarubicin as treatment for acute lymphocytic leukemia (ALL). Much research involving idarubicin is now being conducted. Some of this has involved acute lymphocytic leukemia (ALL) as well as AML. For example, a recent study was conducted in patients with either AML or ALL who had received bone marrow transplantation and then relapsed. Patients received a combination of cytarabine, idarubicin, and etoposide, as well as a medicine called G-CSF (filgrastim). This treatment achieved a high CR rate in these patients. Another recent study looked at the use of idarubicin in children with AML. All of the children received cytarabine and etoposide. In addition, some of the children received idarubicin, while some received daunorubicin. Overall, patients in both groups fared equally well in terms of survival length. However, patients who had larger numbers of cells known as blasts (immature cells) tended to do better if they received idarubicin rather than daunorubicin. In addition, high-risk patients tended to do better with idarubicin than with daunorubicin. No subgroup of patients achieved better outcomes with daunorubicin than with idarubicin. For older patients with acute nonlymphocytic leukemia, treatment with Idarubicin is effective and has acceptable side effects. According to recent research from Italy, ‘‘There is growing interest in autologous stem cell transplantation (ASCT) for elderly patients with acute myeloid leukemia (AML). While mortality and toxicity from ASCT have been reduced, relapse rate is still high.

Description Idarubicin is an antibiotic, although doctors do not use this drug to attack infections. Its only use is to G A LE EN CY C LO PE DI A O F C AN CE R 3

KEY T ERMS Bilirubin—A pigment produced when the liver processes waste products. A high bilirubin level causes yellowing of the skin. Blasts—Immature cells Complete remission (CR)—Complete remission is the total elimination of all diseased cells detectable following therapy. Necrosis—The sum of the morphological changes indicative of cell death. It may affect groups of cells or part of a structure or an organ.

kill cancer cells. It does so by affecting how the DNA of cancer cells work.

Recommended dosage In the treatment of AML, 12 mg of idarubicin per square meter may be given over a period of two to three days every three weeks in combination with other medications. Patients with liver problems may be given lower doses than other patients receive. Idarubicin is not typically given by mouth, as an insufficient amount of the medication would be transported through the stomach wall if this were done. Rather, this medication is usually administered through an intravenous (IV) procedure. During this time, it circulates widely throughout the body. A new formulation of idarubicin has been developed. This permits idarubicin to be taken orally. However, this formulation is currently available only in France and only for older patients who are not good candidates for intensive intravenous treatment. There is little information currently available on the effectiveness of this oral formulation. The studies that have been performed suggest that it is less effective than other formulations of idarubicin.

Precautions Idarubicin may be associated with excessive toxicity in patients with congestive heart failure, liver function characterized by a high bilirubin level, or prior chest radiation to the heart.

Side effects Like daunorubicin and doxorubicin, idarubicin may adversely affect the patient’s heart. However, doctors are not certain how much of the drug it takes to cause such harm and, therefore, how to limit dosage 723

Idarubicin

Idarubicin

Ifosfamide

so that such harm is not caused. However, idarubicin appears to be less likely to cause heart damage than similar drugs such as daunorubicin and doxorubicin. Another serious side effect that limits how much of the drug is given to patients is its potential adverse effect upon the bone marrow, where blood cells are produced. Idarubicin may cause nausea and vomiting, baldness (alopecia), and stomach problems. In addition, idarubicin may cause blistering if extravasation occurs. Extravasation is when chemotherapy gets outside of the vein during infusion. If this occurs, the drug may cause severe local pain, swelling, or tissue necrosis that may require plastic surgery.

KEY T ERMS Antineoplastic—A drug that prevents the growth of a neoplasm by interfering with the maturation or proliferation of the cells of the neoplasm. Neoplasm—New abnormal growth of tissue.

   

Patients receiving idarubicin in conjunction with certain other anticancer drugs may develop a type of leukemia. However, this is extremely rare.



In the few studies that have been conducted on the oral formulation of idarubicin, the most prominent side effects seen are low blood cell counts, nausea, vomiting, diarrhea, and alopecia.



Bob Kirsch

Ifosfamide Definition Ifosfamide is an anticancer (antineoplastic) agent. It also acts as a suppressor of the immune system. It is available under the brand name IFEX.

Purpose Ifosfamide is approved by the Food and Drug Administration (FDA) to treat germ cell testicular cancer. It is generally prescribed in combination with another medicine (mesna), which is used to prevent the bladder problems that may be caused by ifosfamide alone. Ifosfamide also has activity against other cancers and is prescribed in practice for these cancer types: pancreatic cancer stomach cancer  soft-tissue sarcoma  Ewing’s sarcoma  acute and chronic lymphocytic leukemia  bladder cancer 

 



bone cancer breast cancer cervical cancer head and neck cancers lung cancer lymphomas neuroblastomas ovarian cancer Wilms’ tumor

Description Ifosfamide chemically interferes with the synthesis of the genetic material (DNA and RNA) of cancer cells by cross-linking of DNA strands, which prevents these cells from being able to reproduce and continue the growth of the cancer.

Recommended dosage Ifosfamide may only be taken as an injection into the vein. The dosage prescribed varies widely depending on the patient, the cancer being treated, and whether or not other medications are also being taken. Examples of common doses for adults are: 50 mg per kg per day, or 700–2,000 mg per square meter of body surface area for five days every three to four weeks. Another alternative regimen is 2,400 mg per square meter of body surface area for three days or 5000 mg per square meter of body surface area as a single dose every three to four weeks. Examples of common dosing regimens for children are: 1,200 to 1,800 mg per square meter of body surface area per day for three to five days every 21 to 28 days; 5,000 mg per square meter of body surface area once every 21 to 28 days; or 3,000 mg per square meter of body surface area for two days every 21 to 28 days.



724

Precautions Ifosfamide can cause an allergic reaction in some people. Patients with a prior allergic reaction to ifosfamide should not take this drug. G A LE EN CY C LO PE DI A O F C AN C ER 3



Ifosfamide can cause serious birth defects if either the man or the woman is taking this drug at the time of conception or if the woman is taking this drug during pregnancy. Contraceptive measures should be taken by both men and women while on this drug. Because ifosfamide is easily passed from mother to child through breast milk, breast feeding is not recommended during treatment.



Ifosfamide suppresses the immune system, and its excretion from the body is dependent on a normal functioning kidney and liver. For these reasons, it is important that the prescribing physician is aware of any of the following pre-existing medical conditions:



    

a current case of, or recent exposure to, chickenpox herpes zoster (shingles) all current infections kidney disease liver disease

Also, because ifosfamide is such a potent immunosuppressant, patients taking this drug must exercise extreme caution to avoid contracting any new infections.

Side effects Inflammation and irritation of the bladder, causing blood in the urine, is the most common and severe side effect of ifosfamide. However, this side effect can be prevented and controlled with the administration of the bladder protectant drug mesna and vigorous hydration with intravenous fluids before, during, and after chemotherapy. Patients should also urinate frequently (at least every 2 hours) to enhance removal of the drug from the body, and drink 2 to 3 liters of fluids a day for 2 to 3 days after discontinuation of the chemotherapy. Other common side effects of ifosfamide are:       



confusion hallucinations drowsiness dizziness temporary hair loss (alopecia) increased susceptibility to infection increased risk of bleeding (due to a decrease of the platelets involved in the clotting process) nausea and vomiting (can be prevented with prescribed antiemetics) Less common side effects include:



increased coloration (pigmentation) of the skin and fingernails

G A LE EN CY C LO PE DI A O F C AN CE R 3





loss of appetite (anorexia) diarrhea nasal stuffiness skin rash, itching, or hives

A doctor should be consulted immediately if the patient experiences any of these side effects:   

 



    

painful or difficult urination increase in frequency or feeling of urgency to urinate blood in the urine blood in the stool severe diarrhea mental status changes such as confusion, drowsiness, or hallucinations signs of infection such as cough, sore throat, fever and chills shortness of breath chest or abdominal pain pain in the lower back or sides unusual bleeding or bruising tiny red dots on the skin

Interactions Ifosfamide should not be taken in combination with any prescription drug, over-the-counter drug, or herbal remedy without prior consultation with a physician. Paul A. Johnson, Ed.M.

Imaging studies Definition Imaging studies are tests performed with a variety of techniques that produce pictures of the inside of a patient’s body. They have become indispensable tools in cancer screening and detection.

Description Imaging tests are performed using sound waves, radioactive particles, magnetic fields, or x rays that are detected and converted into images after passing through body tissues. Dyes are sometimes used as contrasting agents with x-ray tests so that organs or tissues not seen with conventional x rays can be enhanced. The operating principle of the various techniques is based on the fact that rays and particles 725

Imaging studies

Ifosfamide should always be taken with plenty of fluids.

Imaging studies

K EY T ERM S Cancer screening—A procedure designed to detect cancer even though a person has no symptoms, usually performed using an imaging technique. CT scan—An imaging technique that uses a computer to combine multiple x-ray images into a twodimensional cross-sectional image Mammography—An imaging technique producing x-ray pictures of the breast called mammograms. MRI—A special imaging technique used to image internal parts of the body, especially soft tissues. PET—A highly specialized imaging technique using radioactive substances to identify active tumors. Radionuclide imaging—An imaging technique in which a radionuclide is injected through tissue and a display is obtained from a scanner device.

to improve contrast and obtain images that are clearer than images obtained with x rays. Magnetic resonance imaging (MRI) Magnetic resonance imaging also produces crosssectional images of the body using powerful magnetic fields instead of radiation. MRI is especially useful to detect and locate cancers of the liver and the central nervous system, which occur in the brain or the spinal cord. It uses a cylinder housing a magnet which will induce the required magnetic field. The patient lies on a platform inside the scanner. The magnetic field aligns the hydrogen atoms present in the tissue being scanned in a given direction. Following a burst of radio-frequency radiation, the atoms flip back to their original orientation while emitting signals which a fed into a computer for conversion into a two- or three-dimensional image. Dyes can also be injected into patients to produce clearer images. Mammography

interact differently with various types of tissues, especially when cancerous growths are present. In this way, the interior of the body can be visualized and pictures are provided of normal structure and function as well as of abnormalities. Imaging tests differ from endoscopic tests, which are carried out with a flexible, lighted piece of tubing connected to a viewing lens or camera. Imaging studies are used to detect cancer in its early stages in a procedure called screening. Screening is performed in patients who have no obvious cancer symptoms. Imaging studies are also used to locate tumors in patients who have symptoms which the physician may wish to investigate further so as to distinguish between benign growths or cancerous tumors. They are also used to determine the extent of a cancer and indicate how a given treatment is unfolding. As such, they represent crucial tools for cancer diagnosis and management.

Major imaging techniques Computed tomography scan (CT scan) Computed tomography scans show a cross-section of a part of the body. In this technique, a thin beam is used to produce a series of exposures detected at different angles. The exposures are fed into a computer which overlaps them so as to yield a single image analogous to a slice of the organ or body part being scanned. A dye is often injected into the patient so as 726

Mammography is an x-ray examination of the breast. It is often used as a screening tool to detect breast abnormalities and cancers before they can be felt. Mammograms (the image produced) are acquired using an x-ray machine working at lower radiation levels than conventional x ray. The breast is compressed between two plates so as to allow the lowlevel x-ray radiation to produce a film. Nuclear scan Nuclear scans, also called radionuclide imaging or scintigraphy, use substances called tracers or radionuclides that release low levels of radioactivity. The test is based on the principle that the tracers will be absorbed to a different degree by different tissues, thus allowing to distinguish between normal and cancerous tissues. Common nuclear medicine scans for cancer patients to receive are bone scans; liver, spleen, and thyroid scans are also frequently performed. Position emission tomography (PET) Positron emission tomography uses a form of sugar that contains a radioactive atom which emits particles called positrons. The positrons are absorbed to a different extent by cells varying in their metabolic rate. PET scans are especially useful for brain imaging studies and are widely applied to the assessment of the spread of cancers in the lungs. PET scans are also being used experimentally in the assessment of breast, colon, rectum, and ovarian cancers. G A LE EN CY C LO PE DI A O F C AN C ER 3

X rays produce shallow images of certain specific organs or tissues. X rays are a form of high-energy radiation and tissues of the body can absorb it to varying degrees. For example, bones absorb less x rays than soft tissue. After passing through the body, the x rays are directed on a film, where the dense tissue appears as a white shadow, thus providing contrast with the soft tissue, which produces a darker impression on the film. X rays produce a single image. Chest x rays are used to detect lung and bronchial cancers, and also to evaluate a patient’s symptoms, such as shortness of breath. Other types of x rays, such as abdominal x rays, may also be ordered to assess a patient’s symptoms, but are not used as cancer screening tools as chest x rays may be used. X rays with dye studies Dye studies are usually performed by injecting the contrasting agent in the patient’s circulatory system or in the target organ. These studies are used to produce angiograms, cystograms, myelograms, lymphangiograms and fistulograms. ANGIOGRAM. An angiogram is an examination of the blood vessels using x rays. It is usually performed with intravenous injection of fluorescein dye followed by multiframe photography. The doctor inserts a small tube (catheter) into the blood vessel and then injects the dye that makes the vessels visible when the x-ray pictures are acquired. CYSTOGRAM. A cystogram is a scan of the bladder and ureters. The ureters are passages that lead from the kidneys to the bladder. A catheter is inserted into the bladder or a radioactive material, called a radioisotope, is introduced into the bladder. An oral cholecystogram (OCG) is an x-ray examination of the gallbladder, the organ that helps release bile into the small intestine for the digestion of fats. The gallbladder is not seen well on conventional x-ray pictures and special tablets are ingested by mouth to enhance contrast. MYELOGRAM. A myelogram is an x ray of the spine and spinal cord. The spinal cord is the nerve tissue enclosed in the vertebral column that goes from the bottom of the brain to halfway down the back. During a myelogram, x-ray dye is injected into the spinal fluid and mixes with it, flowing around the spinal cord which can then be seen and recorded on x-ray film. LYMPHANGIOGRAM. A lymphangiogram is an x ray of the lymphatic system, also carried out with

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dye injection for contrasting purposes. It is used to screen for lymph node involvement in cancer. FISTULOGRAM. A fistula is an abnormal passage within body tissue. For example, a fistula may connect two organs inside the body that are not normally connected. A fistula may also lead from an internal organ inside the body to the surface outside. Examples are: between the skin and the bowel (enterocutaneous fistula), between the stomach and the colon (gastrocolic fistula). A fistulogram is an x-ray examination of this abnormal passage. The contrasting agent is injected directly into the fistula so that it will show up on x-ray pictures.

Fluoroscopy Fluoroscopy is one of the oldest areas of diagnostic radiology. It is similar to x ray in that a small dose of x rays is directed through a body part but the image obtained is displayed on a monitor rather than on the conventional x-ray film. The fluoroscope provides images of internal body parts as they move, similar to a movie. A continuous x-ray beam is passed through the body part being examined, and is transmitted to an image-intensifying tube, which is a TV-like monitor so that the body part and its motion can be seen in detail. During fluoroscopy, the patient is placed between the x-ray source and the monitor. The live images generated by the x-ray source strike the image-intensifying tube and allow doctors to see the size, shape, and structure of a patient’s internal structures. Because the radiation is blocked more effectively by dense tissue, such as that of a tumor, the result is a dark shadow of the tumor on the screen, against a light background. Most fluoroscopy devices include television or video cameras attached to the image-intensifier tube. The camera output can be digitized and sent through a computer for image enhancement. In fluoroscopic studies, the radiologist can either insert an intravenous (IV) catheter (hollow tube inserted into blood vessels or into an organ) to biopsy a tumor or he can use a contrast agent to visualize the organ or area of interest. The contrast agent allows the image to be viewed more clearly. Contrast agents may be introduced into the patient’s body by injection, swallowing, or an enema. Fluoroscopic exams include the following types of tests: barium swallow, barium enema, and intravenous pyelography (also called intravenous urography). BARIUM SWALLOW. Used for GI series. The patient drinks a chalky, milkshake-like concoction containing barium, which coats the esophagus and stomach. The barium absorbs the x rays so that the lining of the upper digestive tract can be clearly seen. In barium x rays, fluoroscopy allows the physician to see the movement of the intestines as the barium moves through them.

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Imatinib mesylate

BARIUM ENEMA. In a lower GI series, the patient receives a barium enema, which coats the intestines and rectum. A gap in the image in the stomach or small intestine could indicate an ulcer and bubbles in the normally smooth large intestinal lining may be abnormal growths. INTRAVENOUS PYELOGRAPHY (IVP). Pyelography, also called urography, consists of several x rays of all the urinary system, meaning kidneys, ureter, bladder and urethra. A contrast agent is injected through a vein, to make the organs visible for the x rays.

See also Screening test; Ultrasonography. Resources BOOKS

Seeram, E. Computed Tomography: Physical Principles, Clinical Applications and Quality Control. Philadelphia: W. B. Saunders & Co., 2001. von Schulthess, G. K., editor. Clinical Positron Emission Tomography. Philadelphia: Lippincott, Williams & Wilkins, 1999. Westbrook, C. Handbook of MRI Techniques. Malden, MA: Blackwell Science, 1999. PERIODICALS

Frassica, F. J., J. A. Khanna, and E. F. McCarthy. ‘‘The role of MR imaging in soft tissue tumor evaluation:pers pective of the orthopedic oncologist and musculoskele tal pathologist.’’ Magnetic Resonance Imaging, Clin. N. Am. 8 (November 2000): 915 27. Hopper, K. D., K. Singapuri, and A. Finkel. ‘‘Body CT and oncologic imaging.’’ Radiology 215 (April 2000): 27 40. Jain, P., and A. C. Arroliga. ‘‘Spiral CT for lung cancer screening: is it ready for prime time?’’ Cleveland Clinical Journal of Medicine 68 (January 2001): 74 81. Pomper, M. G., and J. D. Port. ‘‘New techniques in MR imaging of brain tumors.’’ Magnetic Resonance Imag ing, Clin. N. Am. 8 (November 2000): 691 713. Roelcke, U., and K. L. Leenders. ‘‘PET in neuro oncology.’’ Journal of Cancer Research and Clinical Oncology 127 (January 2001): 2 8. OTHER

‘‘Imaging Information.’’ American Cancer Society. 15 October 1999. [cited July 11, 2005]. . ORGANIZATIONS

National Cancer Information Center. 1 800 ACS 2345. National Cancer Institute. Public Inquiries Office, Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. (301)435 2848. Imaging Information and data sheets. http://search.nci.nih. gov/ search97cgi/s97_cgi.

Monique Laberge, Ph.D. 728

Imatinib mesylate Definition Imatinib mesylate is an enzyme inhibitor used for cancer therapy. Imatinib mesylate is also known as STI571 and is sold under the brand name, Gleevec. It was given the name STI571 during early development. STI stands for signal transduction inhibitor.

Purpose Imatinib mesylate is approved by the U. S. Food and Drug Administration to treat a rare cancer called chronic myeloid leukemia (CML). (CML is also called chronic myelogenous leukemia or chronic myelocytic leukemia, as well.)

Description Imatinib mesylate is the first drug of its kind developed. It fights cancer by turning off an enzyme called tyrosine kinase that causes CML cells to lose their ability to die so they can multiply at an abnormal rate. Its function is different from other cancer drugs because it specifically targets an enzyme that allows the growth of CML cells. This drug has been shown to significantly reduce the number of cancer cells in the blood and bone marrow of treated patients. Patients who are diagnosed with CML in the three phases of disease can be treated with imatinib mesylate. Chronic myeloid leukemia appears to respond within one to three months following administration of this drug.

Recommended dosage A doctor experienced in the treatment of patients with CML should initiate therapy. To minimize the risk of gastrointestinal irritation, imatinib mesylate should be taken with food and a large glass of water. The recommended dosage varies according to clinical circumstances and phase of disease, but generally ranges between 300 and 600 mg per day. As long as the patient continues to benefit, treatment should be continued.

Precautions Studies have not been performed with imatinib mesylate to determine if it is a carcinogen (cancer causing); therefore it is not known whether this drug may cause mutations or may have cancer-causing effects. In addition, imatinib mesylate’s safety and G A LE EN CY C LO PE DI A O F C AN C ER 3

K E Y T ERM S CYP3A4—An enzyme that is predominately responsible for the metabolism of imatinib mesylate. Enzyme—Any protein that acts as a catalyst, increasing the rate of a chemical reaction. Kinase—An enzyme. Leukemia—A type of cancer in which the bone marrow produces an excessive number of abnormal (leukemic) white blood cells. White blood cells protect the body against infection but the abnormal cells suppress the production of normal white blood cells. Tumor—An abnormal mass of tissue that serves no purpose. Tumors may be either benign (non-cancerous) or malignant (cancerous).

Imatinib mesylate interacts with many other drugs. In some cases, side effects may be increased because imatinib mesylate might increase blood levels of certain drugs. Alternatively, imatinib mesylate may decrease blood levels of the drugs, thus reducing their effectiveness. In addition, the blood levels of imatinib mesylate may rise or fall because of other drugs. Therefore, side effects of imatinib mesylate may be increased or effectiveness may be reduced. The patient must discuss all of their medications with their doctor due to many potential drug-drug interactions. CYP3A4 is an enzyme that is predominately responsible for the metabolism of imatinib mesylate. The following drugs or families of drugs may interact with imatinib mesylate:

Tyrosine—A non-essential amino acid. Amino acids are the building blocks of protein. They are the raw materials used by the body to make protein. Tyrosine is labeled ‘‘nonessential’’ because, when the amino acids are lacking in the diet, they can be manufactured in the body.



Inhibitors of the CYP3A4 family, such as ketoconazole, itraconazole, erythromycin.



Co-medications that induce CYP3A4, such as dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or St. John’s wort). No formal studies have been conducted on these medications and imatinib mesylate together.

effectiveness has not been established in pediatric patients.



CYP3A4 substrates, such as cyclosporine or pimozide.

Fluid retention and edema. If patients experience swelling or weight gain from water retention, they should inform their doctor and should be closely monitored. Signs and symptoms of fluid retention should be closely monitored and patients should be weighed regularly. Appropriate treatment must be provided if an unexpected rapid weight gain occurs. The likelihood of edema is increased with higher doses and in those over age 65 years.



CYP3A4 metabolized drugs, such as certain HMGCoA reductase inhibitors, triazolo-benzodiazepines, and dihydropyridine calcium channel blockers.



Warfarin. Patients needing anticoagulant therapy while taking imatinib mesylate should be prescribed low-molecular weight or standard heparin.





gastrointestinal irritation



hematologic toxicity (toxicity of the blood)



hepatotoxicity (toxicity of the liver)



toxicities from long-term use

Side effects Commonly reported side effects include nausea and vomiting, muscle cramps, edema (water retention), skin rash, diarrhea, heartburn, and headache. Serious side effects occur less frequently, but if they occur may include severe edema liver toxicity, and the potential for bleeding especially in the elderly. G A LE EN CY C LO PE DI A O F C AN CE R 3

This list is not all-inclusive of all possible interactions. Patients must inform their doctors of any drugs they are taking in order to avoid drug interactions. Investigators also evaluated the effect of St. John’s wort, an herb used to treat mild to moderate depression, on the pharmacokinetics of imatinib. Studies showed that the administration of St. John’s wort along with imatinib mesylate reduced absorption and increased elimination of imatinib, reducing drug exposure by as much as 42%. Since clinical efficacy of imatinib is dependent on drug dose and concentration, the interaction with St. John’s wort could result in a loss of therapeutic effect. Therefore, the concurrent use of St. John’s wort and imatinib should be avoided. See also Low molecular weight heparins. Crystal Heather Kaczkowski, MSc. 729

Imatinib mesylate

Interactions

Immune globulin

Immune globulin Definition Immune globulin is a concentrated solution of antibodies, pooled from donated blood, which is sometimes given to cancer patients whose own immune systems are either not working or are suppressed as a side effect of treatment. Immune globulin can also be called gamma globulin; in the United States some of the brand names are Gamimune, Gammagard, Gammar-P, Iveegam, Polygam, Sandoglobulin, and Venoglobulin.

Purpose A healthy human body produces proteins called antibodies that act to destroy microorganisms (bacteria and viruses) that invade the body. Some cancer patients, due to the illness itself or side effects of treatment, become depleted of these proteins and therefore susceptible to serious infections. Immune globulin is given to these patients to restore their body’s immunity. The use of immune globulin in this way is also called passive immunization. For example, immune globulin is given to bone marrow transplant recipients to prevent the development of severe bacterial infections while their own immune systems are not functioning, and chronic lymphocytic leukemia patients (of the type whose antibody-producing cells are the malignant cells) are given immune globulin to prevent the recurrent infections these patients sometimes suffer. Use in this disorder also allows the use of aggressive chemotherapy that will destroy the patient’s own cancerous antibody-producing cells. Immune globulin is also used to treat other diseases such as Lambert-Eaton myasthenic syndrome, a rare neurological disorder that sometimes occurs in association with small cell lung cancer. Also called Eaton-Lambert syndrome, it is an autoimmune disease in which a patient’s own antibodies attack nerve cells. The use of immune globulin appears to cause the body to reduce its own production of antibody, thereby improving the neurological disorder.

Description Immune globulin primarily consists of antibody proteins of the type called IgG or gamma, although the solution may contain small amounts of other antibody types as well as sugars, proteins, and salt. It is produced by pooling donated blood from at least 1,000 people who have been tested to be free of blood-borne diseases like HIV or hepatitis. The 730

KEY T ERMS Autoimmune disease—A disease in which the body produces an immunologic reaction against itself. Epinephrine—A medication used to treat heart failure and severe allergic reactions. Immunoglobulins—An antibody of a specific type. Five main types are produced, known as IgA, IgD, IgE, Ig G, and IgM. Most antibody in the blood is IgG. Intramuscular administration—A shot usually in the hip or arm, in which medication is delivered into a muscle. Intravenous administration—Introduction of medication straight into a vein (commonly called IV). Neurologic—Involving the nervous system.

antibody proteins are then separated out of the whole blood, and the pH of the immune globulin solution is adjusted to match the normal pH of blood. The preparation is also treated to remove any contaminants, including infectious bacteria or viruses.

Recommended dosage The dose of immune globulin used varies with the specific problem that it is being used for. When immune gobulin is used in patients with EatonLambert Syndrome, the effective dose is usually about 1 g/kg of body weight/day. (One gram equals 0.035274 ounce; one kilogram equals 2.2046 pounds.) When used to counteract immunodeficiency, the dose is designed to produce an antibody level that stays at an effective threshold over a period of time. When immune globulin is given to bone marrow transplant recipients, it is usually begun at the time of the transplant and continued for 100 days thereafter, with the objective of maintaining the level of IgG in the patient’s blood above 400 mg per deciliter. (A deciliter equals 3.38 fluid ounces.) In patients with chronic lymphocytic leukemia (B-cell type) the target threshold for antibodies in the patient’s blood is usually about 600 mg/dL. Although the amount required to maintain these levels varies from patient to patient (because different patients metabolize the drug at different rates) a dose between 10 and 200 mg/kg of body weight, given every 3-4 weeks, is usually sufficient. Immune globulin is usually given intravenously, although intramuscular shots are available. G A LE EN CY C LO PE DI A O F C AN C ER 3

Some people may have experienced severe reactions, including allergy-type reactions, to other antibody preparations. Generally, these people should not be given intravenous immune globulin. Patients with deficiency of antibody IgA, specifically, should also avoid the use of immune globulin. People with a tendency to form blood clots, or those with kidney problems should also avoid the use of this product, especially if elderly. While many pregnant women have been treated with immune globulin for different problems that have occurred during their pregnancy, since the method of action and specific effects on the fetus are not completely understood, pregnant women should avoid the use of immune globlulin unless it is clearly necessary. Any patient who is given immune globulin should be watched carefully, and epinephrine should be kept available in case a severe allergic reaction is experienced. Immune globulin which was made to be given through intramuscular injection should never be administered intravenously.

Side effects Administration of intramuscular immune globulin may result in tenderness, swelling, and possibly hives at the site of the injection. Intravenous immune globulin may cause more severe reactions related to rapid introduction into the blood system. Possible side effects include headache, backache, aching muscles, fever, low blood pressure, and chest pain. More commonly, fever accompanied by chills or nausea and vomiting may be experienced. If these side effects occur, they are usually related to the immune globulin being administered too rapidly. If the rate of infusion is reduced, or if the infusion is stopped temporarily, negative effects will generally disappear. Rare, but potentially serious, side effects observed have been kidney failure and aseptic meningitis.

Interactions Use of immune globulin may reduce the effectiveness of vaccinations (for example, measles, mumps, and rubella) for a few months following the use of the immune globulin preparation. Patients who have been given immune globulin should notify their doctors before any vaccinations are given. In addition, in some situations patients may need to have antibody levels measured to determine whether or not they have had previous infection with a specific microorganism. Use of immune globulin can create the false G A LE EN CY C LO PE DI A O F C AN CE R 3

impression of prior exposure to the organism due to the donated antibodies in their blood. See also Immunologic therapies. Wendy Wippel, M.S.

Immune response Definition The ability of any given cell in the body to distinguish self from nonself is called the immune response. All cells in the body are recognized as self. Any microorganism (for example, a foreign body or tumor) that invades or attacks the cells is recognized as nonself—or foreign—requiring the immune system to mount a combat against the nonself.

Immune system The immune system is comprised of a network of immune cells that are generated in the bone marrow stem cell (a cell whose daughter cells may develop into other types of cells). From stem cells different types of immune cells originate that can handle specific immune functions. Phagocytes (cell eaters), serve as the first line of defense, engulfing dead cells, debris, virus, and bacteria. Macrophages are an important type of phagocyte, often presenting the antigen— which is usually a foreign protein—to other immune cells and thus are also called ‘‘antigen-presenting cells’’ (APC). T and B lymphocytes, important immunesystem cells, are also capable of recognizing the antigen and become activated. T lymphocytes are classified into two subtypes: killer T cells (also called cytotoxic T cells) and helper T cells. Killer T cells recognize and kill the infected or cancer cells that contain the antigen or the foreign protein. Helper T cells release cytokines (chemical messengers) upon activation that either directly destroy the tumor or stimulate other cells to kill the target (tumor). B lymphocytes produce antibodies after recognizing the antigens. The antibodies, which help protect the body from the antigen, are normally specific to that particular antigen. In cases of tumor the specific antibodies attach to tumor cells and, through various mechanisms, impair the functions of the tumor, ultimately leading to the death of the cancer cell. In addition to these lymphocytes are natural killer (NK) cells that particularly perform the task of 731

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Precautions

Immunoelectrophoresis

eliminating foreign cells. Natural killer cells differ from killer T cells in that they target tumor cells and do not have to recognize an antigen before activation. These cells have been shown to be of potential use in treating cancer.

Immune system and cancer The immune system serves as one of the primary defenses against cancer. When normal tissue becomes a tumor or cancerous tissue, new antigens develop on their surface. These antigens send a signal to immune cells such as the cytotoxic T lymphocytes, NK cells, and macrophages, which in turn directly kill the tumor cells or release substances like cytokines that may bring about tumor cell death. Thus, under normal circumstances, the immune system provides continued surveillance and eliminates cells that become cancers. However, tumors may survive by hiding or disguising their tumor antigens, or by producing substances that allow suppressor T cells (cells that block cytotoxic, or killer T cells that would normally attack the tumor) to proliferate (multiply).

Biological response modifiers in cancer therapy Researchers have been working on stimulating the immune cells during cancer with substances broadly classified as biological response modifiers. Cytokines are one such substance. These are proteins that are predominantly released by immune cells upon activation or stimulation. During the 1990s the number of cytokines identified increased enormously and the functions associated with them are of immense potential in diagnostics and immune therapy. Some of the key cytokines that have proven therapeutic value in cancer are interleukin-2 (IL-2), Interferon gamma, and interleukin-12 (IL-12). Cytokines are normally injected directly to cancer patients; however, there are other cases where a cancer patient’s own lymphocytes are modified under laboratory conditions and injected back into the patient. Examples of these are lymphokine-activated killer (LAK) cells and tumorinfiltrating lymphocytes (TILs). These modified cells are capable of devouring cancer cells.

Immunoprevention of cancer Immunotherapy is emerging as one of the management strategies for cancer. However, established tumors or large masses of tumor do not respond well to immunotherapy. There is clinical evidence, however, that suggests that patients with minimal residual cancer cells (a few cells left after other forms of cancer 732

treatment) are potential candidates for effective immunotherapy. In these cases immunotherapy often results in a prolonged tumor-free survival. Thus, immune responses can be manipulated to prevent recurrence, even though it does not destroy large tumors. Based on results of immunotherapy trials, most immune therapies are geared towards designing immunoprotective strategies such as cancer vaccines.

Cancer vaccines Cancer vaccines can be made either with whole, inactivated tumor cells, or with fragments or cell surface substances (called cell-surface antigens) present in the tumors. In addition to the whole cell or antigen vaccines, biological modifiers, like cytokines, serve as substances that boost immune response in cancer patients. Since cancer vaccines are still under clinical evaluation, caution should be exercised while choosing them as the mode of therapy. The cancer care team will provide further insight on whether or not cancer vaccine or cytokine therapy will be beneficial after they assess the patient’s stage and the various modes of treatments available. Resources PERIODICALS

‘‘Genetic Vaccines.’’ Scientific American July 1999. ‘‘Immunoprevention of Cancer: Is the Time Ripe?’’ Cancer Research 60 (May 15, 2000): 2571 2575 OTHER

‘‘Treating Cancer with Vaccine Therapy.’’ National Cancer Institute. 2000. [cited July 5, 2005]. .

Kausalya Santhanam, Ph.D.

Immunoelectrophoresis Definition Immunoelectrophoresis, also called gamma globulin electrophoresis, or immunoglobulin electrophoresis, is a method of determining the blood levels of three major immunoglobulins: immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA).

Purpose Immunoelectrophoresis is a powerful analytical technique with high resolving power as it combines G A LE EN CY C LO PE DI A O F C AN C ER 3

Antibody—A protein manufactured by the white blood cells to neutralize an antigen in the body. In some cases, excessive formation of antibodies leads to illness, allergy, or autoimmune disorders. Antigen—A substance that can cause an immune response, resulting in production of an antibody, as part of the body’s defense against infection and disease. Many antigens are foreign proteins not found naturally in the body, and include germs, toxins, and tissues from another person used in organ transplantation. Autoimmune disorder—A condition in which antibodies are formed against the body’s own tissues, for example, in some forms of arthritis.

separation of antigens by electrophoresis with immunodiffusion against an antiserum. The increased resolution is of benefit in the immunological examination of serum proteins. Immunoelectrophoresis aids in the diagnosis and evaluation of the therapeutic response in many disease states affecting the immune system. It is usually requested when a different type of electrophoresis, called a serum protein electrophoresis, has indicated a rise at the immunoglobulin level. Immunoelectrophoresis is also used frequently to diagnose multiple myeloma, a disease affecting the bone marrow.

Precautions Drugs that may cause increased immunoglobulin levels include therapeutic gamma globulin, hydralazine, isoniazid, phenytoin (Dilantin), procainamide, oral contraceptives, methadone, steroids, and tetanus toxoid and antitoxin. The laboratory should be notified if the patient has received any vaccinations or immunizations in the six months before the test. This is mainly because prior immunizations lead to the increased immunoglobulin levels resulting in false positive results. It should be noted that, because immunoelectrophoresis is not quantitative, it is being replaced by a procedure called immunofixation, which is more sensitive and easier to interpret.

Description Serum proteins separate in agar gels under the influence of an electric field into albumin, alpha 1, G A LE EN CY C LO PE DI A O F C AN CE R 3

There are five classes of antibodies: IgM, IgG, IgA, IgE, and IgD. IgM is produced upon initial exposure to an antigen. For example, when a person receives the first tetanus vaccination, antitetanus antibodies of the IgM class are produced 10 to 14 days later. IgM is abundant in the blood but is not normally present in organs or tissues. IgM is primarily responsible for ABO blood grouping and rheumatoid factor, yet is involved in the immunologic reaction to other infections, such as hepatitis. Since IgM does not cross the placenta, an elevation of this immunoglobulin in the newborn indicates intrauterine infection such as rubella, cytomegalovirus (CMV) or a sexually transmitted disease (STD). IgG is the most prevalent type of antibody, comprising approximately 75% of the serum immunoglobulins. IgG is produced upon subsequent exposure to an antigen. As an example, after receiving a second tetanus shot, or booster, a person produces IgG antibodies in five to seven days. IgG is present in both the blood and tissues, and is the only antibody to cross the placenta from the mother to the fetus. Maternal IgG protects the newborn for the first months of life, until the infant’s immune system produces its own antibodies. IgA constitutes approximately 15% of the immunoglobulins within the body. Although it is found to some degree in the blood, it is present primarily in the secretions of the respiratory and gastrointestinal tract, in saliva, colostrum (the yellowish fluid produced by the breasts during late pregnancy and the first few days after childbirth), and in tears. IgA plays an important role in defending the body against invasion of germs through the mucous membrane-lined organs. IgE is the antibody that causes acute allergic reactions; it is measured to detect allergic conditions. IgD, 733

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alpha 2, and beta and gamma globulins. Immunoelectrophoresis is performed by placing serum on a slide containing a gel designed specifically for the test. An electric current is then passed through the gel, and immunoglobulins, which contain an electric charge, migrate through the gel according to the difference in their individual electric charges. Antiserum is placed alongside the slide to identify the specific type of immunoglobulin present. The results are used to identify different disease entities, and to aid in monitoring the course of the disease and the therapeutic response of the patient with such conditions as immune deficiencies, autoimmune disease, chronic infections, chronic viral infections, intrauterine fetal infections, multiple myeloma, and monoclonal gammopathy of undetermined significance.

Immunohistochemistry

which constitutes the smallest portion of the immunoglobulins, is rarely evaluated or detected, and its function is not well understood.

Preparation This test requires a blood sample.

Aftercare Because this test is ordered when either very low or very high levels of immunoglobulins are suspected, the patient should be alert for any signs of infection after the test, including fever, chills, rash, or skin ulcers. Any bone pain or tenderness should also be immediately reported to the physician.

Risks Risks for this test are minimal, but may include slight bleeding from the blood-drawing site, fainting or feeling lightheaded after venipuncture, or bruising.

Increased levels of IgA can indicate chronic liver disease, chronic infections, or inflammatory bowel disease. Decreased levels of IgA can be found in ataxia, a condition affecting balance and gait, limb or eye movements, speech, and telangiectasia, an increase in the size and number of the small blood vessels in an area of skin, causing redness. Decreased IgA levels are also seen in conditions of low blood protein (hypoproteinemia), and drug immunosuppression. Resources BOOKS

Fischbach, Frances T. A Manual of Laboratory Diagnostic Tests. Philadelphia: Lippincott Williams & Wilkins, 1999. Pagana, Kathleen D., and Timothy J. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. St. Louis: Mosby, Inc., 1999.

Janis O. Flores

Normal results Reference ranges vary from laboratory to laboratory and depend upon the method used. For adults, normal values are usually found within the following ranges (1 mg = approximately .000035 oz. and 1 dL = approximately 0.33 fluid oz.): IgM: 60–290 mg/dL  IgG: 700–1,800 mg/dL  IgA: 70–440 mg/dL 

Abnormal results Increased IgM levels can indicate Waldenstro¨m’s macroglobulinemia, a malignancy caused by secretion of IgM at high levels by malignant lymphoplasma cells. Increased IgM levels can also indicate chronic infections, such as hepatitis or mononucleosis and autoimmune diseases, like rheumatoid arthritis. Decreased IgM levels can be indicative of AIDS, immunosuppression caused by certain drugs like steroids or dextran, or leukemia. Increased levels of IgG can indicate chronic liver disease, autoimmune diseases, hyperimmunization reactions, or certain chronic infections, such as tuberculosis or sarcoidosis. Decreased levels of IgG can indicate WiskottAldrich syndrome, a genetic deficiency caused by inadequate synthesis of IgG and other immunoglobulins. Decreased IgG can also be seen with AIDS and leukemia. 734

Immunohistochemistry Definition Immunohistochemistry is a method of analyzing and identifying cell types based on the binding of antibodies to specific components of the cell. It is sometimes referred to as immunocytochemistry.

Purpose Immunohistochemistry (IHC) is used to diagnose the type of cancer and to help determine the patient’s prognosis. In cases such as metastases or carcinoma of unknown primary origin, where it may be difficult to determine the type of cell from which the tumor originated, immunohistochemistry can identify cells by the characteristic markers on the cell surface. IHC can also help distinguish between benign and malignant tumors.

Description Immunohistochemistry requires a sample of tissue from a biopsy; usually the tissue sample is examined fresh, but frozen or chemically preserved material can be used. A blood sample or bone marrow may also be examined. The tissue sample is sliced extremely thinly, so that it is approximately one cell thick, then the sample is fixed onto a glass slide. The tumor cells in the sample have characteristic markers, or antigens, G A LE EN CY C LO PE DI A O F C AN C ER 3

Antibody—A protein formed by the immune system to react with a specific antigen. Antigen—Any protein that elicits a unique immune response. Biopsy—A sample of tissue taken from a tumor to compare with other normal tissue. Histology—The study of tissues.

Q U E S T I O N S TO A S K T H E DOCTOR      

on their cell surfaces which can be used to help identify the specific type of tumor cell. Antibodies against these characteristic antigens are added to the sample on the slide, and the antibodies bind wherever the antigens are present. Excess antibody is then washed away. The antibodies that remain bound to the cell have labels on them that either fluoresce (glow) or undergo a chemical reaction that makes them visible by microscope. The pathologist is able to see the specially labeled tumor antigens as they appear in the patient’s tissue. The pathologist will try to assess the level of maturity of the tumor cells, which will help him to determine their origin. He will be checking for cell types that are found in an inappropriate part of the body, for example prostate cells in a lymph node. He will also look for cell characteristics that will indicate if the tumor is benign or malignant. Proteins involved in the replication of genetic material and cell growth may be present in greater amounts; for example, antibodies against the antigen Ki-67 are used to evaluate malignant melanomas, breast carcinomas, and non-Hodgkin’s lymphomas. Hormone receptors may also be examined. The presence of receptors to estrogen and progesterone indicate a good prognosis for breast cancer patients. Pathologists may also look for an increase in tumor suppressor proteins. A wide variety of antibodies are available to help determine the origin of the tumor, whether it is growing rapidly, and whether it is a type of tumor that responds well to particular treatments.

Preparation The physician will choose the type of sample to be taken based on the type of tumor. If the patient has a solid tumor, a tissue sample may be biopsied; if the entire tumor is being removed a biopsy may be taken during surgery. In this case the patient should prepare for the surgery or the biopsy as the physician suggests. A routine blood sample may also be required; in most cases, no additional preparation is required. G A LE EN CY C LO PE DI A O F C AN CE R 3

Immunohistochemistry

K E Y T ERM S

What do you expect to learn from this test? What are the alternatives to this test? Are there any risks or complications? Are any special preparations required? Is hospitalization required? Is it possible that the test may give a false positive, a false negative, or unclear results?

Aftercare The only aftercare that might be required is from the sample collection process.

Risks The risks associated with IHC are the risks associated with the sample collection, either the biopsy of the tumor or the drawing of blood. The only other concern is the possibility that the test could yield unclear results.

Normal results Normal results will simply look like normal cells. The cells will have a high level of maturity and be located only in sites appropriate to their cell type. For example, analysis of lymph nodes will show only the cells that belong there, not cells that would normally be present in the breast. No specific tumor antigens will be present in increased numbers.

Abnormal results An abnormal result would consist of cells which appear immature or poorly differentiated, or that are found in an inappropriate tissue for their cell type. The pathologist may test for the presence of a particular antigen, such as Ki-67, carcinoembryonic antigen (CEA), or prostate specific antigen (PSA). In this case, there may be a numerical standard value to compare normal to abnormal results and help the physician in determining prognosis. See also Receptor analysis; Tumor markers. Resources BOOKS

Javois, Lorette C. Immunocytochemical Methods and Proto cols. Totowa, NJ:Humana Press Inc., 1999. 735

Immunologic therapies

PERIODICALS

Bendayan, Moise. ‘‘Worth Its Weight in Gold.’’ Science 291 (February 16, 2001): 1363 1365. Cote, R. J., et al. ‘‘Role of Immunohistochemical Detection of Lymph Node Metastases in Management of Breast Cancer.’’ The Lancet 354 (September 11, 1999): 896 900. Gastl, Gunther, et al. ‘‘Ep CAM Overexpression in Breast Cancer as a Predictor of Survival.’’ In The Lancet 356 (9 December 2000): 1981 1982.

carry brand names such as Alferon, Roferon or Intron A. Some of the interferons that are currently in use as drugs are Recombinant Interferon Alfa-2a, Recombinant Interferon Alfa-2b, Interferon Alfa-n1, and Interferon Alfa-n3. Alfa interferons are used to treat hairy cell leukemia, malignant melanoma, and AIDsrelated Kaposi’s sarcoma. In addition, interferons are also used for other conditions such as laryngeal papillomatosis, genital warts, and certain types of hepatitis.

Racquel Baert, M.S.

Immunologic therapies Definition Immunologic therapy is the treatment of disease using medicines that boost the body’s natural immune response. Some forms of immunologic therapy are intended to bypass the body’s weakened immune system while others are intended to repair or direct it.

Purpose Immunologic therapy is used to improve the immune system’s natural ability to fight diseases such as cancer, hepatitis and AIDS. These drugs may also be used to help the body recover from immunosuppression resulting from treatments such as chemotherapy or radiation therapy.

Description Most drugs in this category are synthetic versions of substances produced naturally in the body. In their natural forms, these substances help defend the body against disease. For example, aldesleukin (Proleukin) is an artificially made form of interleukin-2, which helps white blood cells work. Aldesleukin is administered to patients with kidney cancers and skin cancers that have spread to other parts of the body. Filgrastim (Neupogen) and sargramostim (Leukine) are versions of natural substances called colony stimulating factors, which drive the bone marrow to make new white blood cells. Another type of drug, epoetin (Epogen, Procrit), is a synthetic version of human erythropoietin that stimulates the bone marrow to make new red blood cells. Thrombopoietin stimulates the production of platelets, disk-shaped bodies in the blood that are important in clotting. Interferons are substances the body produces naturally using immune cells to fight infections and tumors. The synthetic interferons 736

Recommended dosage The recommended dosage depends on the type of immunologic therapy. For some medicines, the physician will decide the dosage for each patient, taking into account a patient’s weight and whether he/she is taking other medicines. Some drugs used in immunologic therapy are given only in a hospital, under a physician’s supervision. For those that patients may give themselves, check with the physician who prescribed the medicine or the pharmacist who filled the prescription for the correct dosage. Most of these drugs come in injectable form. These drugs are generally administered by the cancer care provider.

Precautions Aldesleukin This medicine may temporarily increase the chance of getting infections. It may also lower the number of platelets in the blood, and thus possibly interfering with the blood’s ability to clot. Taking these precautions may reduce the chance of such problems: 

Avoid people with infections, if possible.



Be alert to signs of infection, such as fever, chills, sore throat, pain in the lower back or side, cough, hoarseness, or painful or difficulty with urination. If any of these symptoms occur, get in touch with a physician immediately.



Be alert to signs of bleeding problems, such as black, tarry stools, inky red spots on the skin, blood in the urine or stools, or any other unusual bleeding or bruising.



Take care to avoid cuts or other injuries. Be especially careful when using knives, razors, nail clippers, and other sharp objects. Check with a dentist for the best ways to clean the teeth and mouth without injuring the gums. Do not have dental work done without checking with a physician. G A LE EN CY C LO PE DI A O F C AN C ER 3

AIDS—Acquired immunodeficiency syndrome. A disease caused by infection with the human immunodeficiency virus (HIV). In people with this disease, the immune system breaks down, increasing vulnerability to other infections and some types of cancer. Bone marrow—Soft tissue that fills the hollow centers of bones. Blood cells and platelets (disk-shaped bodies in the blood that are important in clotting) are produced in the bone marrow. Chemotherapy—Treatment of an illness with chemical agents. The term is usually used to describe the treatment of cancer with drugs. Clot—A hard mass that forms when blood gels. Dendritic cells—Immune system cells derived from a type of white blood cell called monocytes. Dendritic cells help to activate the B cells, helper T cells, and killer T cells in the immune system. Hepatitis—Inflammation of the liver caused by a virus, chemical, or drug. Immune response—The body’s natural, protective reaction to disease and infection.



Wash hands frequently, and avoid touching the eyes or inside of the nose unless the hands have just been washed.

Aldesleukin may make some medical conditions worse, such as chickenpox, shingles (herpes zoster), liver disease, lung disease, heart disease, underactive thyroid, psoriasis, immune system problems, and mental problems. The medicine may increase the chance of seizures (convulsions) in people who are prone to having them. Also, the drug’s effects may be greater in people with kidney disease, because their kidneys are slow to clear the medicine from their bodies.

Immune system—The system that protects the body against disease and infection through immune responses. Inflammation—Pain, redness, swelling, and heat that usually develop in response to injury or illness. Psoriasis—A skin disease that manifests itself with itchy, scaly, red patches on the skin. Seizure—A sudden attack, spasm, or convulsion. Shingles—A disease caused by an infection with the Herpes zoster virus the same virus that causes chickenpox. Symptoms of shingles include pain and blisters along one nerve, usually on the face, chest, stomach, or back. Sickle cell anemia—An inherited disorder in which red blood cells contain an abnormal form of hemoglobin, a protein that carries oxygen. The abnormal form of hemoglobin causes the red cells to become sickle-shaped. The misshapen cells may clog blood vessels, preventing oxygen from reaching tissues and leading to pain, blood clots and other problems. Sickle cell anemia is most common in people of African descent and in people from Italy, Greece, India, and the Middle East.

People who have kidney disease, liver disease, or conditions caused by inflammation or immune system problems can worsen these problems with colony stimulating factors. Those who have heart disease may be more likely to experience side effects such as water retention and heart rhythm problems while taking these drugs. Finally, patients who have lung disease might increase their chances of suffering from shortness of breath. Those who have any of these medical conditions should check with their personal physicians before using colony stimulating factors. Epoetin

Colony stimulating factors Certain drugs used in treating cancer reduce the body’s ability to fight infections. Although colony stimulating factors help restore the body’s natural defenses, the process takes time. Getting prompt treatment for infections is important, even while taking this medicine. Call the physician at the first sign of illness or infection, such as a sore throat, fever, or chills. People with certain medical conditions could have problems if they take colony stimulating factors. G A LE EN CY C LO PE DI A O F C AN CE R 3

Epoetin is a medicine that may cause seizures (convulsions), especially in people who are prone to having them. No one who takes these drugs should drive, use machines, or do anything considered dangerous in case of a seizure. Epoetin helps the body make new red blood cells, but it is not effective unless there is adequate iron in the body. The physician may recommend taking iron supplements or certain vitamins that help supply the body with iron. It is necessary to follow the physician’s 737

Immunologic therapies

KEY TERM S

Immunologic therapies

advice in this instance—recommendations for iron in this case, as with any supplements should only come from a physician. In studies of laboratory animals, epoetin taken during pregnancy caused birth defects, including damage to the bones and spine. However, the drug has not been reported to cause problems in human babies whose mothers take it. Women who are pregnant or who may become pregnant should check with their physicians for the most up-to-date information on the safety of taking this medicine during pregnancy. People with certain medical conditions may have problems if they take this medicine. For example, the chance of side effects may be greater in people with high blood pressure, heart or blood vessel disease, or a history of blood clots. Epoetin may not work properly in people who have bone problems or sickle cell anemia. Interferons Interferons can add to the effects of alcohol and other drugs that slow down the central nervous system, such as antihistamines, cold medicine, allergy medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants. They may also add to the effects of anesthetics, including those used for dental procedures. Those taking interferons should check with their physicians before taking any of the above. Some people experience dizziness, unusual fatigue, or become less alert than usual while being treated with these drugs. Because of these possible problems, anyone who takes these drugs should not drive, use machines, or do anything else considered dangerous until they have determined how the drugs affect them. Interferons often cause flu-like symptoms, including fever and chills. The physician who prescribes this medicine may recommend taking acetaminophen (Tylenol) before—and sometimes after—each dose to keep the fever from getting too high. If the physician recommends this, follow instructions carefully. Like aldesleukin, interferons may temporarily increase the chance of getting infections and lower the number of platelets in the blood, leading to clotting problems. To help prevent these problems, follow the precautions for reducing the risk of infection and bleeding listed for aldesleukin. People who have certain medical conditions may have problems if they take interferons. For example, the drugs may worsen some medical conditions, including heart disease, kidney disease, liver disease, 738

lung disease, diabetes, bleeding problems, and mental problems. In people who have overactive immune systems, these drugs can even increase the activity of the immune system. People who have shingles or chickenpox, or who have recently been exposed to chickenpox may increase their risk of developing severe problems in other parts of the body if they take interferons. People with a history of seizures or mental problems could at risk if taking interferon. In teenage women, interferons may cause changes in the menstrual cycle. Young women should discuss this possibility with their physicians. Older people may be more sensitive to the effects of interferons. This may increase the chance of side effects. These drugs are not known to cause fetal death, birth defects, or other problems in humans when taken during pregnancy. Women who are pregnant or who may become pregnant should ask their physicians for the latest information on the safety of taking these drugs during pregnancy. Women who are breastfeeding their babies may need to stop while taking this medicine. Whether interferons pass into breast milk is not known. Because of the chance of serious side effects to the baby, breastfeeding while taking interferon is discouraged. Check with a physician for advice. General precautions for all types of immunologic therapy Regular physician visits are necessary during immunologic therapy treatment. This gives the physician a chance to make sure the medicine is working and to check for unwanted side effects. Anyone who has had unusual reactions to drugs used in immunologic therapy should let the physician know before resuming the drugs. Any allergies to foods, dyes, preservatives, or other substances should also be reported.

Side effects Aldesleukin In addition to its helpful effects, this medicine may cause serious side effects. Generally, it is given only in a hospital, where medical professionals can watch for early signs of problems. Medical tests might be performed to check for unwanted effects. Anyone who has breathing problems, fever, or chills while being given aldesleukin should check with a physician immediately. G A LE EN CY C LO PE DI A O F C AN C ER 3

          

dizziness drowsiness confusion agitation depression nausea and vomiting diarrhea sores in the mouth and on the lips tingling of hands or feet decrease in urination unexplained weight gain of five or more pounds

Interferons This medicine may cause temporary hair loss (alopecia). While upsetting, it is not a sign that something is seriously wrong. The hair should grow back normally after treatment ends. As the body adjusts to the medicine many other side effects usually go away during treatment. These include flu-like symptoms, taste alteration, loss of appetite (anorexia), nausea and vomiting, skin rash, and unusual fatigue. If these problems persist, or if they interfere with normal life, check with a physician. A few more serious side effects should be brought to a physician’s attention as soon as possible: 

Some side effects are usually temporary and do not need medical attention unless they are bothersome. These include dry skin; itchy or burning skin rash or redness followed by peeling; loss of appetite; and a general feeling of illness or discomfort.

    

confusion difficulty thinking or concentrating nervousness depression sleep problems numbness or tingling in the fingers, toes and face

Colony stimulating factors As this medicine starts to work, the patient might experience mild pain in the lower back or hips. This is nothing to cause undue concern, and will usually go away within a few days. If the pain is intense or causes discomfort, the physician may prescribe a painkiller. Other possible side effects include headache, joint or muscle pain and skin rash or itching. These side effects tend to disappear as the body adjusts to the medicine, and do not need medical treatment. If they continue, or they interfere with normal activities, check with a physician. Epoetin This medicine may cause flu-like symptoms, such as muscle aches, bone pain, fever, chills, shivering, and sweating, within a few hours after it is taken. These symptoms usually go away within 12 hours. If they do not, or if they are troubling, check with a physician. Other possible side effects that do not need medical attention are diarrhea, nausea or vomiting and fatigue or weakness. Certain side effects should be brought to a physician’s attention as soon as possible. These include headache, vision problems, increased blood pressure, fast heartbeat, weight gain and swelling of the face, fingers, lower legs, ankles or feet. Anyone who has chest pain or seizures after taking epoetin should seek professional emergency medical attention immediately. G A LE EN CY C LO PE DI A O F C AN CE R 3

General caution regarding side effects for all types of immunologic therapy Other side effects are possible with any type of immunologic therapy. Anyone who has unusual symptoms during or after treatment with these drugs should should contact the physician immediately.

Interactions Anyone who has immunologic therapy should let the physician know all other medicines being taken. Some combinations of drugs may interact, that can increase or decrease the effects of one or both drugs or can increase the likelihood of side effects. Consultation with a physician is highly recommended to get the insight on whether the possible interactions can interfere with drug therapy or cause harmful effects.

Immunoprevention Considering that most of the biological modifiers such as cytokines elicit immune response that inhibit incipient tumors before they are clinically evident, immunoprevention has been proposed as a recent strategy for combating cancer. Treatment involving immune molecules (such as cytokines) prepared synthetically or that are not produced by the patients themselves is called as passive immunotherapy. Conversely, a vaccine is a form of active immune therapy because it elicits an immune response in patients. A cancer vaccine may be made of whole tumor cell or of 739

Immunologic therapies

Other side effects should be brought to a physician’s attention as soon as possible:

Incontinence, cancer-related

substances or fragments contained in the tumor called antigens. Newer types of immunologic therapy that are still considered investigational as of 2003 include cellbased therapies. Instead of using synthetic chemicals that resemble substances produced by the body, cellbased therapies use modified stem cells or dendritic cells as vaccines against cancer. Stem cells are undifferentiated cells whose daughter cells can develop into various types of specialized cells, while dendritic cells are cells that are able to initiate and modify the immune system’s responses to cancer by activating B cells and T cells. Dendritic cells appear to offer a promising new form of immunotherapy for cancer. Another investigational form of treatment is the development of cell-free tumor-specific peptide vaccines. Peptides are subunits of protein molecules that contain two or more amino acids. Peptide vaccines are intended to induce responses in the patient’s T cells that inhibit tumor growth. As of late 2003, however, peptide-based tumor vaccines have been shown to shrink cancerous tumors only in patients with limited disease.

National Cancer Institute.Treating Cancer with Vaccine therapy 2000. [cited June 29, 2005]. . Nieda, M., M. Tomiyama, and K. Egawa. ‘‘Ex vivo Enhancement of Antigen Presenting Function of Den dritic Cells and Its Application for DC Based Immu notherapy.’’ Human Cell 16 (December 2003): 199 204. Paczesny, S., H. Ueno, J. Fay, et al. ‘‘Dendritic Cells as Vectors for Immunotherapy of Cancer.’’ Seminars in Cancer Biology 13 (December 2003): 439 447. Rosenberg, S. A. ‘‘Progress in Human Tumor Immunology and Immunotherapy.’’ Nature 411, no. 6835 (2001): 380 385. Scheibenbogen, C., A. Letsch, A. Schmittel, et al. ‘‘Rational Peptide Based Tumour Vaccine Development and T Cell Monitoring.’’ Seminars in Cancer Biology 13 (December 2003): 423 429.

Rebecca J. Frey, Ph.D.

Immunotherapy see Immunologic therapies Implantable subcutaneous ports see Vascular access

Adoptive immunotherapy Adoptive immunotherapy involves stimulating T lymphocytes by exposing them to tumor antigens. These modified cells are grown in the laboratory and then injected into patients. Since the cells taken from a different individual for this purpose often results in rejection, patients serve both as donor and recipient of their own T cells. Adoptive immunotherapy is particularly effective in patients who have received massive doses of radiation and chemotherapy. In such patients, therapy results in immunosuppression (weakened immune systems), making them vulnerable to viral infections. For example, CMVspecific T cells can reduce the risk of cytomegalovirus (CMV) infection in transplant patients. Resources BOOKS

Reiger, Paula T. Biotherapy: A Comprehensive Overview. Sudbury: Jones and Bartlett, Inc. 2000. Stern, Peter L., P. C. Beverley, and M. Carroll. Cancer Vaccines and Immunotherapy. New York: Cambridge University Press, 2000. PERIODICALS

Fishman, M. N., and S. J. Antonia. ‘‘Cell Based Immune Therapy for Metastatic Renal Cancer.’’ Expert Review of Anticancer Therapy 3 (December 2003): 837 849. ‘‘Immunoprevention of Cancer: Is the time Ripe?’’ Cancer Research 60 (May 15, 2000): 2571 2575. 740

Incontinence, cancer-related Definition Cancer-related incontinence is the inability to control bladder or bowel function (or both) as a result of the direct effects of cancer on the body or the effects of various forms of cancer therapy. In some patients, cancer-related incontinence can be easily treated and controlled, but requires specialized consultation and treatment in others.

Demographics The demographics of urinary and fecal incontinence vary widely according to the type of cancer and the treatments for it. One study reported that about 35% of women treated for cancers of the female reproductive system developed urinary incontinence, while another found that 80% of women treated for cancer of the uterus with radiation therapy developed urinary incontinence. Between 50 and 80% of patients receiving irinotecan (Camptosar), a drug given to treat colon cancer, develop severe diarrhea and fecal incontinence. About 99% of patients given opioid drugs to relieve pain develop constipation, which can lead to fecal incontinence if untreated. G A LE EN CY C LO PE DI A O F C AN C ER 3

Incontinence is the loss of normal control of the bowel or bladder. Incontinence can involve the involuntary voiding of urine (urinary incontinence) or of stool and gas (fecal or bowel incontinence). There are several types of urinary incontinence. Those most frequently seen as side effects of cancer include overflow incontinence, urge incontinence, and stress incontinence. In rare cases incontinence occurs as the result of cancer, but more commonly it is a side effect of treatment. Because the subjects of bowel and bladder control are perceived as socially unacceptable, those affected with incontinence often feel ashamed or embarrassed by the problem. Instead of seeking medical attention, these individuals try to hide the problem or manage it themselves. For this reason, incontinence is sometimes referred to as ‘‘the silent affliction.’’ The psychological effects of incontinence include low self-esteem, social withdrawal and isolation, and depression. In most cases incontinence can be successfully treated, so affected individuals should discuss the problem with a doctor. Risk factors Risk factors for cancer-related incontinence include: 













 

Previous history of irritable bowel syndrome, Crohn’s disease, diabetes, or multiple sclerosis. Being diagnosed with Alzheimer’s or Parkinson’s disease in addition to the cancer. In women, previous history of childbirth by vaginal delivery. In men, diagnosis of and treatment for prostate cancer. Any cancer treatment that involves surgical removal of part of the digestive tract. Radiation therapy to the stomach or abdomen as part of cancer treatment. Cancers that arise in or spread to the brain and spinal cord. Anticancer drugs that affect the nervous system. Pain relievers that contain opium or opium derivatives. These drugs include fentanyl, morphine, codeine, oxycodone, tramadol, and dextropropoxyphene. Opioids can cause constipation that can lead in turn to fecal incontinence.

Causes and symptoms Incontinence can result from damage to the muscle, nerves, or the structure of the body parts involved in the control of voiding. Complex systems G A LE EN CY C LO PE DI A O F C AN CE R 3

of hollow organs (such as the bladder) and tubeshaped structures (such as the rectum and urethra) work together to store and release waste. Special muscles, including sphincters, are especially important in maintaining the tight seals that hold in waste. When physical damage to muscle or organ structure occurs, the system can no longer maintain these tight seals, and waste can leak out. Nerves carry messages between the brain and the bowel and bladder systems. Injury to these nerves, or the related part of the brain, interferes with the delivery of these messages, which can prevent the body from recognizing the signals telling it when to void. Without these signals and messages, an individual cannot coordinate the brain with the bowel and bladder systems, and incontinence results. Several types of cancer and its treatments are associated with incontinence. Usually, it is the treatment of cancer that causes incontinence, rather than the cancer itself. Fecal incontinence frequently results from anticancer drugs that cause either diarrhea or constipation. Anticancer drugs that can cause constipation include the vinca alkaloids, oxaliplatins, taxanes, and thalidomide. Drugs that can cause diarrhea include the fluoropyrimidines, adriamycin, cisplatin, and irinotecan; in one study, 80% of cancer patients receiving these drugs developed severe diarrhea. Prostate cancer The treatment of prostate cancer is one of the most common causes of cancer-related urinary incontinence, largely because the prostate is located so closely to the nerves, muscles, and structures involved in urine control. Surgical removal of the prostate, or prostatectomy, carries the highest risk of urinary incontinence as a side effect; the risk from radiation therapy is somewhat lower. The incontinence (typically stress or urge incontinence) is often temporary, but in a small percentage of men it may be long lasting. Prostate cancer itself seldom causes incontinence. However, this depends on the location and size of the cancer; a large cancerous prostate can interfere with the flow of urine and result in overflow incontinence. Bladder cancer Incontinence is only occasionally the direct result of bladder cancer, but it is a common side effect of some treatments. For early-stage cancer where treatment does not require the bladder to be removed, incontinence almost never occurs. But removal of the bladder and surrounding structures is often necessary to treat more advanced cancer. This requires creation 741

Incontinence, cancer-related

Description

Incontinence, cancer-related

of an artificial system for storing and releasing urine and carries a risk of long-term incontinence. Colon cancer and rectal cancer Muscles in the anal and rectal region largely control bowel evacuation, with the colon storing stool and gas. When these regions are removed or damaged during cancer treatment, or if injury to the related nerves occurs, fecal incontinence can result. Fecal incontinence is most commonly a side effect of surgery. Weakening of bowel muscles or damaging of nerves by radiation therapy can also cause incontinence, but this type is more likely to be mild and temporary, and will often improve as these areas heal. However, in some patients, radiation causes permanent and severe fecal incontinence; this condition is known as radiation enteritis. Other causes Loss of voluntary bowel and bladder control is less commonly associated with other cancers of the genital and urinary systems, mainly as a side effect of treatment. Incontinence can also result from cancer or treatment damage in the brain and spinal cord. Other cancers indirectly cause incontinence; for example, constant coughing from lung cancer can lead to stress incontinence. Incontinence can be a side effect of certain other medications.

Diagnosis The diagnosis of incontinence is usually obvious on the basis of the patient’s treatment history and reported symptoms.

Treatment Traditional The method of treatment depends on the cause and type of incontinence. Surgical treatment is usually reserved for severe or long-lasting incontinence. An artificial pouch for storing urine or stool can be placed inside the body as a substitute for a removed bladder, colon, or rectum. Placement of an artificial sphincter successfully treats other cases. For mild or temporary incontinence, treatment may include medications, dietary changes, muscle-strengthening exercises, or behavioral training, such as establishing a time pattern for voiding. A small group of patients, however, requires a permanent colostomy or urostomy. Electrical stimulation therapy, which targets involved muscles with low-current electricity, can be used to treat either urinary or fecal incontinence. 742

Biofeedback uses electronic or mechanical devices to improve bladder or bowel control by teaching an individual how to recognize and respond to certain body signals. Embarrassment may lead some people to manage the symptoms of incontinence themselves by wearing absorbent pads to prevent the soiling of their clothes. However, many treatments exist to successfully restore or improve control of bowel and bladder function, so individuals experiencing incontinence should speak to a doctor or nurse. Cancer patients who have difficulty with frequent or occasional incontinence may find the following tips helpful:  







Always use the bathroom before leaving home. Always carry a backpack or tote containing cleansing towelettes and a change of underwear. Locate public restrooms before the need to use them is urgent. If the problem is specifically fecal incontinence, try taking an oral fecal deodorant. Over-the-counter products approved by the Food and Drug Administration (FDA) include Devrom and Nullo. These products work by reducing the number of odor-causing bacteria in stool. Wear disposable undergarments or sanitary pads if an episode of incontinence seems likely. Drugs

Constipation caused by cancer therapy can be treated by one or more stimulant laxatives, stool softeners, lubricant laxatives, or agents that increase the bulk of the stools. Patients whose constipation is caused by opioid pain relievers can be given a drug called methylnaltrexone (Relistor), which will relieve the constipation without affecting the patient’s pain control. Diarrhea caused by cancer treatment can be treated by giving the patient loperamide, a drug that slows down intestinal motility. Other medications include absorbent materials like pectin or methylcellulose; these absorb excess liquid in the digestive tract. As of 2009, the most promising drug to treat diarrhea associated with cancer chemotherapy is octreotide (Sandostatin). Alternative Good results for cancer-related fecal incontinence have been reported for biofeedback training, although the subject is still being researched. In successful cases, patients regain complete control over defecation, or at G A LE EN CY C LO PE DI A O F C AN C ER 3

QUESTIONS TO ASK YOUR DOCTOR 





 

Is my incontinence caused by the cancer or by cancer therapy? Is it possible to change the dosage of my chemotherapy drug or try a different drug? Is it safe to take over-the-counter preparations for constipation or diarrhea caused by cancer treatment? What is the prognosis of my incontinence? Where can I go for advice about my specific difficulties with incontinence?

least improve their control, by learning to contract the external part of the anal sphincter whenever stools enter the rectum. Home remedies In some cases, patients with fecal incontinence related to cancer treatment may be helped by eating small, frequent meals and avoiding certain foods. The most frequent offenders include milk and dairy products, spicy foods, alcohol, caffeine-containing foods and beverages (including coffee, tea, and cola), certain fruit juices, gas-forming foods and beverages, high-fiber foods, and high-fat foods.

Prognosis Success in treating cancer-related incontinence depends on the location of the cancer and the methods used to treat it. In most cases the patient can obtain at least partial relief. When incontinence remains a problem despite medical treatment, disposable underwear and other commercial incontinence products are available to make life easier. Doctors and nurses can offer advice on coping with incontinence, and people should never be embarrassed about seeking their assistance. Counseling and information are also available from support groups.

Prevention Incontinence related to cancer or cancer treatment is difficult to prevent, in part because researchers do not understand as of 2009 why some patients become incontinent with cancer or cancer therapy and others do not.

G A LE EN CY C LO PE DI A O F C AN CE R 3

BOOKS

Airley, Rachel. Cancer Chemotherapy. Hoboken, NJ: Wiley Blackwell, 2009. DeAngelis, Lisa M., and Jerome B. Posner. Neurologic Complications of Cancer, 2nd ed. New York: Oxford University Press, 2009. Leupold, Nancy E., and James J. Scubba, eds. Meeting the Challenges of Oral and Head and Neck Cancer: A Sur vivor’s Guide. San Diego, CA: Plural Publishing, 2008. McKay, Judith, and Tamera Schacher. The Chemotherapy Survival Guide: Everything You Need to Know to Get through Treatment, 3rd ed. Oakland, CA: New Har binger Publications, 2009. Perry, Michael P., ed. The Chemotherapy Source Book. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2008. Pettit, Paul, editor in chief. Mayo Clinic on Managing Incontinence. Rochester, MN: Mayo Clinic, 2005. PERIODICALS

Bartlett, L., et al. ‘‘Impact of Fecal Incontinence on Quality of Life.’’ World Journal of Gastroenterology 15 (July 14, 2009): 3276 82. Chamlou, R., et al. ‘‘ Long term Results of Intersphincteric Resection for Low Rectal Cancer.’’ Annals of Surgery 246 (December 2007): 916 921. Govaert, B., et al. ‘‘Neuromodulation for Functional Bowel Disorders.’’ Best Practice and Research: Clinical Gas troenterology 23 (April 2009): 545 53. Keating, N. L. ‘‘Physical and Mental Health Status of Older Long term Cancer Survivors.’’ Journal of the American Geriatrics Society 53 (December 2005): 2145 52. Lange, M.M., and C. J. van de Velde. ‘‘Faecal and Urinary Incontinence after Multimodality Treatment of Rectal Cancer.’’ PLoS Medicine 5 (October 7, 2008): 202. Muehlbauer, P. M., et al. ‘‘ Putting Evidence into Practice: Evidence based Interventions to Prevent, Manage, and Treat Chemotherapy and Radiotherapy induced Diarrhea.’’ Clinical Journal of Oncology Nursing 13 (June 2009): 336 41. Parsons, B. A., et al. ‘‘Prostate Cancer and Urinary Incon tinence.’’ Maturitas 63 (August 20, 2009): 323 28. OTHER

American Cancer Society (ACS). Managing Incontinence after Prostate Cancer Treatment. http://www.cancer. org/docroot/NWS/content/NWS_2_1x_Managing_ Incontinence.asp. American Cancer Society (ACS). Managing Side Effects of Chemotherapy. http://www.cancer.org/docroot/MBC/ content/MBC_2_1x_Managing_Side_Effects_of_ Chemotherapy.asp?sitearea MBC. American Cancer Society (ACS). Radiation Therapy to the Stomach and Abdomen. http://www.cancer.org/doc root/MBC/content/MBC_2_3X_What_Side_Effects_ Occur_ With_Radiation_Therapy_to_the_ Stomach_and_Abdomen_Area.asp?sitearea MBC. 743

Incontinence, cancer-related

Resources

Infection and sepsis

American Society of Clinical Oncology (ASCO). Managing Side Effects of Cancer Treatment: Diarrhea. http:// www.cancer.net/patient/Diagnosis+and+Treatment/ Treating+Cancer/Managing+Side+Effects/ Diarrhea+ +ASCO+curriculum. American Society of Clinical Oncology (ASCO). Managing Side Effects of Cancer Treatment: Nervous System Side Effects. http://www.cancer.net/patient/Diagnosis+ and+Treatment/Treating+Cancer/Managing+ Side+Effects/Nervous+System+Side+Effects. International Foundation for Functional Gastrointestinal Disorders (IFFGD). About Incontinence. http://www. aboutincontinence.org/. Mayo Clinic. Fecal Incontinence. http://www.mayoclinic. com/health/fecal incontinence/DS00477. National Association for Continence (NAFC). Incontinence Overview. http://www.nafc.org/bladder bowel health/ what is incontinence/. National Cancer Institute (NCI). Coping with Cancer: Gas trointestinal Complications. http://www.cancer.gov/ cancertopics/pdq/supportivecare/gastrointestinalcom plications/healthprofessional/allpages. National Cancer Institute (NCI). Managing Chemotherapy Side Effects: Urination Changes. http://www.cancer. gov/cancertopics/chemo side effects/urination. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Fecal Incontinence. http://digestive. niddk. nih.gov/ddiseases/pubs/fecalincontinence/ index.htm ORGANIZATIONS

American Cancer Society, 250 Williams Street NW, Atlanta, GA, 30303, 800 ACS 2345 (227 2345), www.cancer.org. American College of Gastroenterology, P.O. Box 342260, Bethesda, MD, 20827 2260, 301 263 9000, http://www. acg.gi.org/. American Society of Clinical Oncology (ASCO), 2318 Mill Road, Suite 800, Alexandria, VA, 22314, 571 483 1300, 888 282 2552, [email protected], http://www.asco. org/ASCOv2?edition default. National Association for Continence (NAFC), P.O. Box 1019, Charleston, SC, 29402, 843 377 0900, 800 BLADDER, 843 377 0905, memberservices@nafc. org, http://www.nafc.org/. National Cancer Institute, 6116 Executive Blvd., Room 3036A, Bethesda, MD, 20892 8322, 800 422 6237, [email protected], www.cancer.gov. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Building 31. Rm 9A06, 31 Center Drive, MSC 2560, Bethesda, MD, 20892 2560, 301 496 3583, http://www2.niddk.nih.gov/Footer/Contact NIDDK.htm, http://www2.niddk.nih.gov/. International Foundation for Functional Gastrointestinal Disorders (IFFGD), P.O. Box 170864, MilwaukeeWI, United States, 53217 8076, 414 964 1799, 414 964 7176, [email protected], http://www.iffgd.org/.

Stefanie B.N. Dugan, M.S. Rebecca J. Frey, PhD 744

Infection and sepsis Definition In its most general sense, an infection represents the harmful colonization of a host by organisms of another species. The infecting organism seeks to exploit the host’s resources to multiply, usually at the expense of the host. Sepsis is a serious medical condition characterized by an inflammatory response of the entire body and the presence of a suspected or known infection. Because the term sepsis was used somewhat loosely before the 1990s, the American College of Chest Physicians and the Society of Critical Care Medicine drew up a set of definitions in 1992 to clarify the definitions of sepsis syndromes in order of severity: 





Sepsis: the presence of a systemic inflammatory response syndrome (SIRS) in the setting of an infection. Severe sepsis: infection with evidence of end-organ dysfunction as a result of hypoperfusion (inadequate blood supply to tissues and organs). Septic shock: severe sepsis with persistent low blood pressure despite fluid resuscitation and resulting tissue hypoperfusion.

Demographics According to the U.S. National Center for Health Statistics, the incidence of sepsis increased threefold between 1979 and 2000, from 83 cases to 240 cases per year per 100,000 population. Severe sepsis accounts for more than 500,000 visits to hospital emergency departments each year in Canada and the United States. There are several reasons for this increase: the growing proportion of elderly in the general population; more efficient diagnosis of severe disease; a sharp rise in the number of invasive procedures and organ transplantation; increased use of immunosuppressive agents and chemotherapy in cancer patients; increased use of indwelling lines and devices in hospitalized patients; and a rise in such chronic diseases as end-stage renal disease and HIV infection. As of 2009, African Americans—particularly males—have twice the risk of sepsis as members of other races, but this disparity is thought to reflect differences in access to treatment as well as differences in the severity of underlying conditions. Men of all races are at greater risk of severe sepsis and septic shock than women, but it is not known as of 2009 whether these data reflect more severe underlying conditions in men, a higher incidence of lung disease in G A LE EN CY C LO PE DI A O F C AN C ER 3



The incidence rate of sepsis in cancer patients in North America is estimated at 45%. Mortality rates from sepsis in cancer patients exceed 30%.







Pregnancy. History of lung disease. Using injected drugs of abuse. Abnormalities of the heart valves.

Infection and sepsis

men, or whether women have some inherent protection against the inflammation present in severe sepsis.

Causes and symptoms Description Infection is characterized by an inflammatory response to the presence of microorganisms in the body. This response may include fever, chills, redness, swelling, pus formation, and other responses. The most common cause of illness and death in patients with cancer is infection. Patients with cancer who are treated with chemotherapy, radiation therapy, and/or surgery are at increased risk of developing an infection. Mortality from infection in cancer patients decreased during the late 1900s due to the development of new types of antibiotics, the use of hematopoietic growth factors (HGFs) which activate proliferation (multiplication) and maturation of blood cell lines, and due to the prophylactic (preventive) use of antifungal and antiviral agents. Blood cell lines, markedly decreased due to chemotherapy, are required to fight infections. Most infections in cancer patients are due to bacteria; however, fungal infections are usually the cause of fatal infections. If left untreated, or if inadequately treated, infection can progress to sepsis. Several conditions indicate sepsis, including a temperature of greater than 38 degrees Celsius (100.4 Fahrenheit) or less than 36 C (96.8 F), heart rate greater than 90 beats per minutes, and respiratory rate greater than 20 breaths per minute. Risk factors Risk factors for infection and sepsis include:  



    



Weakened immune system. Hospitalization. Many infections are acquired during a hospital stay. Surgery, dental work, catheter or pacemaker insertion, placement of a prosthesis or artificial joint, or other procedures that involve cutting into or injuring tissue. Concurrent HIV infection. Treatment for cancer. Homelessness. Poor personal hygiene. Being treated for severe burns. Like cancer patients, burn patients are highly susceptible to infections. Age below 1 year or over 35 years.

G A LE EN CY C LO PE DI A O F C AN CE R 3

Causes There are many possible causes of infection in patients with cancer. For example, certain cancers interfere with the body’s immune system response, which results in increased risk of infection to the patient. These cancer types include acute leukemia, chronic lymphocytic leukemia, multiple myeloma, Hodgkin’s disease, and non-Hodgkin’s lymphoma. Certain therapies used to treat cancer, such as chemotherapy (which interrupts bone marrow production of white blood cells, red blood cells, and platelets), radiation therapy, bone marrow transplantation, and treatments using corticosteroids, can lead to infection in the patient with cancer. The protein-calorie malnutrition that some cancer patients experience can result in suppression of the immune system, which results in increased risk for infection. Many cancer patients develop infections from procedures which break the integrity of the skin, which then leads to the introduction of microorganisms into the body. These procedures include such common interventions in the care of cancer patients as venipunctures, biopsies, insertion of urinary catheters, and use of long-term central venous catheters. Infection rates associated with long-term central venous catheter use in cancer patients are estimated to be as high as 60%. If the cancer patient’s immune system is severely compromised, infection can occur from food sources, plants, and/or air the patient comes in contact with. Myelosuppression is the term used to describe the decrease in numbers of circulating white blood cells (WBC), red blood cells (RBC), and platelets. Myelosuppression is often a side effect of treatment with chemotherapy and/or radiation therapy. Blood counts usually begin to fall one to three weeks after treatment with chemotherapy, depending upon the type of chemotherapy and the lifespan of the blood cell. The counts generally begin to recover to normal levels within two to three weeks. The neutrophil, which is a component of the white blood cells, is the body’s first line of defense against infection caused by bacteria. A state of neutropenia exists when the number of neutrophils is decreased. Neutropenia is the single greatest predictor of infection in patients with cancer. Three key factors are important in predicting the potential of 745

Infection and sepsis

a patient to experience an infectious episode when myelosuppressed. These factors include: 1) the degree of neutropenia, i.e., the lower the neutrophil count the more likely the patient will become infected; 2) the duration of the neutropenia, i.e., the longer a patient is neutropenic, the greater the likelihood of infection; and 3) the rate at which neutropenia develops—the more rapidly it develops, the greater the risk of infection. Bacterial infections in cancer patients develop quickly, especially in the neutropenic patient, and account for 85–90% of the microorganisms associated with neutropenia accompanied by fever. The most serious episodes occur from infections attributed to such gram-negative organisms as Enterobacteriaceae or Pseudomonas aeruginosa. However, infections from such gram-positive organisms as Staphylococcus, Streptococcus, Corynebacteria, and Clostridia have increased in the 1990s, probably due to the increased use of implanted central venous catheters and prophylactic antibiotics (to which these organisms develop an immunity). Listeriosis, a severe bacterial infection caused by Listeria monocytogenes, is another infection on the increase in cancer patients. Listeriosis has become a common complication of bone marrow transplantation in the early 2000s as well as a frequent cause of patient death. Other organisms that cause infections in the immunocompromised cancer patient include such herpesviruses as herpes simplex virus 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Sources of secondary infections include the fungus Candida albicans. Common causes of secondary infection in severely immunosuppressed patients include CMV and the filamentous fungus Aspergillus. Aspergillosis is an increasingly common and often fatal infection in patients with hematologic (blood-related) cancers. The incidence of sepsis and septic shock increases when the patient remains neutropenic for longer than seven days. Other factors that put the cancer patient at high risk for the development of sepsis include infection with a gram-negative organism, presence of a central venous catheter, history of prior infection, malnutrition, history of frequent hospitalization, increased age of patient, and concurrent (at the same time) presence of such other diseases as diabetes, cardiovascular, gastrointestinal, hepatic, pulmonary, and/or renal disease. Sites of infection that most often lead to sepsis include infection of the lungs, invasive lines, and urinary tract. Symptoms Sepsis manifests (develops) with both local and systemic symptoms that involve the neurologic, 746

endocrine, immunologic, and cardiovascular systems. Signs of sepsis and septic shock include changes in blood pressure, heart rate and respiratory rate, among others. If left untreated, the patient can progress to septic shock which may result in death even if the shock episode is treated. Factors that appear to increase the patient’s chances of survival include rapid admission to an intensive care unit and aggressive treatment with antibiotics.

Diagnosis The diagnosis of sepsis is based on the following criteria:    



 



Temperature above 101 F or below 96 F. Heart rate above 90 beats per minute (bpm). Respiration more than 20 breaths per minute. WBC higher than 12,000/mm3 or lower than 4,000/mm3. Low blood pressure: lower than 90 mmHg or a reduction of 40 mmHg or more from the patient’s baseline blood pressure. Abnormalities in platelet count. Altered mental status: delirium, confusion, anxiety, and/or agitation. Reduced output of urine (oliguria).

A patient does not have to meet all these criteria to be diagnosed with severe sepsis or septic shock. Examination In addition to abnormalities in the patient’s vital signs, the doctor may also observe changes in mental status or the condition of the patient’s skin. In the early stages of septic shock, the patient’s skin is often warm to the touch; in later stages, the skin may become clammy and cool to the touch. It may also develop a pale, grayish, or mottled color. The doctor will listen to the patient’s breathing for evidence of fluid accumulation in the lungs. If the infection appears to be localized, the doctor will evaluate that portion of the patient’s body for redness, swelling, pain, or a discharge. Tests Standard laboratory tests for infection and suspected sepsis include a complete blood cell count (CBC) and a blood chemistry panel; measurement of hemoglobin levels; a blood culture to identify the organism causing the infection; liver function tests; urine tests; and a test of the patient’s sputum when pneumonia is suspected. G A LE EN CY C LO PE DI A O F C AN C ER 3

Procedures Patients with severe sepsis or septic shock are usually intubated to keep the airway open. Other procedures that may be performed include a lumbar puncture (spinal tap) if meningitis is suspected; placement of a urinary catheter to monitor the patient’s urine output; and surgical drainage of any abscesses.

Q U E S T I O N S TO A S K Y O U R DOCTOR  



 





What is causing the infection? What antibiotics will you prescribe? What are their possible side effects? What is the normal course of this illness? When can I expect to feel better? Can I transmit this infection to others? What complications might occur from this type of infection? Can I do anything to prevent them? Will treatment for the infection interfere with cancer therapy? Has the infection progressed to sepsis or severe sepsis?

Treatment Traditional Sepsis is a medical emergency and is usually treated in an intensive care unit (ICU). It includes maintenance of ventilation, oxygenation, fluid volume, and cardiac output as well as antibiotic treatment and nutritional support. Patients may be placed on a mechanical ventilator to assist with breathing or given supplemental oxygen if needed. Speed of treatment is essential; several studies have shown that for every hour of delay in the administration of appropriate antibiotic therapy, there is an associated 7% rise in mortality. Drugs Empiric antibiotic therapy is the mainstay of treatment for infection in the cancer patient. Empiric therapy refers to initiation of antibiotic therapy prior to the identification of the infecting organism. Broadspectrum antibiotics, antibiotics effective against both gram-negative and gram-positive organisms, are administered. Commonly used agents include aminoglycosides, fluoroquinolones, glycopeptides, and betalactams such as penicillins, cephalosporins, carbapenems, and monobactams. Empiric antifungal therapy is initiated 5–7 days after empiric antibiotic therapy has been started if the patient remains febrile (with a fever). Antiviral agents may be administered if there is evidence of a viral infection. The Infectious Diseases Society of America (IDSA) recommends a minimum of five to seven days further treatment with parenteral (introduced in other ways than intestinal absorption) antibiotic therapy after the fever resolves (returns to normal). Continued monitoring of bacterial and fungal culture results is G A LE EN CY C LO PE DI A O F C AN CE R 3

essential. This allows the use of more tailored antibiotics for the specific infectious agents. The neutropenic patient with fever can progress quickly to sepsis and septic shock if left untreated. The patient may also progress to septic shock if empiric antibiotic coverage is inadequate. The most common cause of septic shock in cancer patients is infection with gram-negative bacteria. In addition to antibiotics, patients with sepsis may also be given corticosteroids to bring down inflammation. Patients with severe sepsis or septic shock can be treated with drotrecogin alfa (Xigris; also known as activated protein C), which is an artificially produced human protein that prevents inflammation and blood clotting. It is thought to reduce the risk of death from severe sepsis and septic shock. Xigris was approved for the treatment of severe sepsis by the Food and Drug Administration (FDA) in 2001; it can be administered only in an ICU by a doctor qualified in critical care medicine, however.

Prognosis The mortality rate for severe sepsis and septic shock is frequently quoted as anywhere from 20% to 50%. The most detailed recent study gives a death rate of 30%. Other studies report that between 20% and 35% of patients with severe sepsis and 40–60% of patients with septic shock die within 30 days of hospital admission. Risk factors for mortality with infection and sepsis include delayed antibiotic treatment; male sex; older age (especially age over 50); the presence of two or more other illnesses; altered mental status; and acquiring the infection in a hospital. 747

Infection and sepsis

Imaging tests are ordered as appropriate for the location of the infection. They may include chest x rays, abdominal ultrasounds, CT or MRI imaging, or x-ray studies of the extremities when soft tissue infections are suspected. The patient will also usually be given an EKG to check for abnormal heart rhythms.

Infection and sepsis

Prevention Strategies that can be used to prevent or minimize infection in the neutropenic patient include:

Sepsis can be avoided by preventing infection in immunocompromised patients and by recognizing risk factors and altering those factors whenever possible.



Identification of patients at highest risk for infection.

Resources



Avoiding practices by health care team members that increase colonization of microorganisms.

BOOKS



Implementation of fewer invasive procedures when possible.

Cancer patients at risk for neutropenia may also benefit from treatment with two new hematopoietic growth factors, pegfilgrastim (Neulasta) and darbepoietin alfa (Aranesp). These drugs appear to be effective in reducing the risk of opportunistic infections in cancer patients as well as improving their overall quality of life. Specific interventions in the hospital setting that can be used to prevent or minimize infection include: 

scrupulous handwashing by patient, staff, and visitors.



good personal hygiene, including an oral care protocol by the patient.



ambulation (movement).



aggressive efforts to promote lung expansion.



elimination of uncooked fruits and vegetables from the diet.



removal of plants and other sources of stagnant water from the patient’s room.



screening and minimizing outside visitors to avoid those with infection

In addition, the hospitalized patient should be assessed by the staff at least every four hours and laboratory results collected and analyzed to determine risk for and presence of neutropenia. A newer method to prevent infection in the cancer patient works by decreasing the duration of neutropenia. This method decreases the period of maximum risk for infection by using hematopoietic growth factors (HGFs). These growth factors are administered daily beginning 24 hours after chemotherapy, and shorten the duration and severity of neutropenia. Therefore, the period of risk for infection is shortened. HGFs work by activating the production and maturation of RBCs, WBCs, and platelet cell lines. Specific HGFs stimulate the production and maturation of aggressive neutrophils and macrophages, which are effective in destroying pathogens (bacteria or viruses that cause infection or disease). 748

Daniels, Ron, and Tim Nutbeam, eds. ABC of Sepsis. Hoboken, NJ: BMJ Wiley Blackwell, 2010. Perrin, Kathleen Ouimet. Understanding the Essentials of Critical Care Nursing. Upper Saddle River, NJ: Pearson Prentice Hall, 2009. Rello, Jordi, and Marcos I. Restrepo, eds. Sepsis: New Strategies for Management. Berlin: Springer, 2008. PERIODICALS

Annane, D., et al. ‘‘Corticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults: A Systematic Review.’’ Journal of the American Medical Association 301 (June 10, 2009): 2362 75. Cohen, J. ‘‘Sepsis and Septic Shock: Inching Forward.’’ Clinical Medicine 9 (June 2009): 256 57. Cull, L.F., and M.B. Nolan. ‘‘Treating Neutropenic Fever in the Emergency Department: Delays May Be Deadly!’’ Journal of Emergency Nursing 35 (January 2009): 36 39. Hirasawa, H., et al. ‘‘Blood Glucose Control in Patients with Severe Sepsis and Septic Shock.’’ World Journal of Gastroenterology 15 (September 7, 2009): 4132 36. Mann, H.J., et al. ‘‘Protein C in Critical Illness.’’ American Journal of Health System Pharmacy 66 (June 15, 2009): 1089 96. Marraro, G. A. ‘‘Treatment of Septic Shock and Use of Drotrecogin Alfa (Activated) in Children.’’ Expert Review of Anti infective Therapy 7 (September 2009): 769 72. Panwar, R., et al. ‘‘Plasma Protein C Levels in Immuno compromised Septic Patients Are Significantly Lower Than Immunocompetent Septic Patients: A Prospective Cohort Study.’’ Journal of Hematology and Oncology 2 (October 19, 2009): 43. Park, H.Y., et al. ‘‘Outcome and Prognostic Factors of Patients with Acute Leukemia Admitted to the Inten sive Care Unit for Septic Shock.’’ Leukemia and Lym phoma 49 (October 2008): 1929 34. da Silva, E.D., et al. ‘‘Risk Factors for Death in Children and Adolescents with Cancer and Sepsis/Septic Shock.’’ Journal of Pediatric Hematology/Oncology 30 (July 2008): 513 18. OTHER

Filbin, Michael R. ‘‘Shock, Septic.’’ eMedicine, August 12, 2009. http://emedicine.medscape.com/article/ 786058 overview. JAMA Patient Page. ‘‘Sepsis.’’ Journal of the American Medical Association 301 (June 17, 2009): 2516. http:// jama.ama assn.org/cgi/reprint/301/23/2516.pdf. Mayo Clinic. ‘‘Blood Poisoning: What Does It Mean?’’ http://www.mayoclinic.com/health/blood poisoning/ AN00716. G A LE EN CY C LO PE DI A O F C AN C ER 3

ORGANIZATIONS

American College of Emergency Physicians (ACEP), 1125 Executive Circle, Irving, TX, 75038 2522, 972 550 0911, 800 798 1822, 972 580 2816, http://www.acep. org/. Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA, 30333, 800 232 4636, [email protected], http://www.cdc.gov. Infectious Diseases Society of America (IDSA), 1300 Wilson Boulevard, Suite 300, Arlington, VA, 22209, 703 299 0200, 703 299 0204, [email protected], http://www. idsociety.org/. National Institute of Allergy and Infectious Diseases (NIAID), 6610 Rockledge Drive, MSC 6612, Bethesda, MD, 20892 6612, 301 496 5717, 866 284 4107, 301 402 3573, http://www3.niaid.nih.gov. International Sepsis Forum (ISF), US mailing address: 7024 Palmetto Pines Lane, Land O’LakesFL, United States, 34637, 813 235 9813 (US only), 813 235 9014 (US only), [email protected], http://www.sepsis forum.org/. World Health Organization (WHO), Avenue Appia 20, 1211 Geneva 27, Switzerland, + 41 22 791 21 11, + 41 22 791 31 11, [email protected], http://www.who.int/en/.

Melinda Granger Oberleitner, R.N., D.N.S. Rebecca J. Frey, Ph.D.

Infertility see Fertility issues

Intensity modulated radiation therapy Definition Intensity modulated radiation therapy uses a computer to deliver precise, three-dimensional doses of x rays to a tumor to treat cancer.

Purpose As a new and special form of radiation therapy, intensity modulated radiation therapy (IMRT) offers special treatment options for cancer patients. When a patient has cancer, he or she may have radiation therapy to destroy the tumor or cancerous cells. The radiation therapy may be the only treatment given or a treatment prescribed along with surgery and/or chemotherapy. G A LE EN CY C LO PE DI A O F C AN CE R 3

The radiation aimed at the cancerous cells also can destroy nearby healthy cells. IMRT is an advanced treatment method that allows physicians to target the cancer so effectively that healthy tissue receives little to no radiation, even when the tumor is wrapped around a vital organ. This makes IMRT a good choice for many cancer patients, particularly those with small tumors, brain and spinal cord tumors, prostate cancer, cancer of the head and neck, many children, infants with certain muscle tumors, and some patients who have previously received radiation treatments. Research continues on expanding use of IMRT for a number of cancers; clinical trials are underway around the world.

Precautions Any time a patient is considered for radiation therapy, physicians weigh the risks and benefits of the procedure. IMRT, like any external radiation therapy procedure, introduces x rays (ionizing radiation) to the patient’s skin, tissues, and organs near the treatment area. Some patients will not be candidates for treatment. IMRT will require frequent trips to the radiation oncology facility for the prescribed treatment plan and careful following of instructions to deal with radiation side effects. On the positive side, the accuracy of IMRT means some patients who may not have been candidates for radiation therapy under older, less precise methods now can have radiation treatment. IMRT can deliver radiation to the intended target more precisely and do a better job of sparing surrounding organs and tissues. The oncology treatment team should discuss all risks and benefits of IMRT with the patient.

Description Physicians have used radiation to treat cancer for more than 100 years. The damaging effects of x rays can destroy cancerous cells in the body and help rid the patient of the pain or related spread and complications of some cancers. For some patients, radiation therapy is the first treatment physicians choose; for others the treatment is used after surgery or chemotherapy or at the same time as chemotherapy. Radiation therapy also sometimes is called ‘‘radiotherapy.’’ The goal of radiation therapy is to destroy as many cancer cells as possible, while limiting damage to nearby healthy tissue. To accomplish this, complicated dose measurements are made based on information gathered by studying the tumor before radiation treatment begins. Today, physicians can use procedures such as computed tomography (CT) to produce three-dimensional models that can better pinpoint the 749

Intensity modulated radiation therapy

Young, Lowell S. ‘‘Sepsis and Septic Shock.’’ Merck Manual of Medical Information, 2nd home edition. http://www. merck.com/mmhe/print/sec17/ch191/ch191c.html.

Intensity modulated radiation therapy

QUESTIONS TO ASK YOUR DOC TOR 







How long will my treatment last: how many times will I have to come in? How experienced are you and your staff in providing IMRT? What are some of the side effects I can expect from IMRT? Are there signs I should watch for following treatment that are abnormal and require a call to you or your nurse?

tumor. Planning radiation treatments in three dimensions allows physicians to target the radiation beams at the tumor’s height, width, and depth. This newer technique is called ‘‘3-D conformal radiation therapy.’’ IMRT is a new type of 3-D conformal radiation therapy that uses beams of varying intensities. By doing so, the beams, which can strike the tumor from three dimensions, also can deliver different doses to small areas of tissue at once. This offers more individualized targeting of the tumor than in the past, so that the radiation oncologist (a physician who specializes in using radiation to treat cancer) can plan higher doses to the tumor and lower doses to the nearby tissue. Insurance companies have found IMRT a valuable treatment for many cancers in recent years because of its effectiveness. Tomotherapy is a form of IMRT that delivers the radiation dose by rotating the beams over a small slice of tissue. Most IMRT procedures are performed at a cancer center, radiation oncology physician office or outpatient facility, or in a hospital. The radiation oncologist oversees the patient’s plan, working closely with a team of professionals. A medical physicist has special training in radiation physics and the operation and repair of radiology and radiation therapy equipment. The physicist also may help develop the patient’s treatment plan. A medical dosimetrist works under the direction of the radiation oncologist and medical physicist to calculate radiation dose. IMRT treatments normally are performed by a radiation therapist, a specially trained technologist who positions the patient and runs the equipment. A radiation oncology nurse also may help with managing care, side effects, and explaining the treatments. 750

KEY T ERMS Ionizing radiation—Energy that is strong enough to remove an electron from an atom. It is used for diagnostic x rays and for radiation therapy. Recur, recurrence—This refers to cancer that happens again after time has passed.

As the treatment begins, the patient is positioned on a treatment table in a precise location that has been set in treatment planning or simulation sessions. A special molding or other device may be applied to help keep the patient from moving during the procedure. The radiation therapist can observe the patient throughout the entire procedure through a window or closed circuit television. The therapist may reposition the patient during the procedure. A treatment session usually lasts about 15 to 30 minutes. The procedure should be painless, but if the patient is uncomfortable, the therapist can stop the machine. The number of treatments a patient must return for will depend on the type and stage of cancer. Some patients may receive treatments every day for a period of a several weeks.

Preparation Before beginning IMRT treatment, the radiation oncologist and treatment team will need to know the precise location of the tumor in the body (anatomical position). This means the patient may have to go for several imaging studies in addition to those already completed to diagnose the cancer. Computed tomography (CT), positron emission tomography (PET) scans, and magnetic resonance imaging (MRI) may be used to provide three-dimensional information for the IMRT system. These imaging visits and the resulting work of the treatment team often are called treatment simulation. The patient also may have to go to the radiation therapy facility prior to treatment for a planning session. At this session, a special device may be molded to help the patient maintain an exact treatment position. The patient also may receive a mark or tattoo with colored ink to help align and target the equipment once treatment begins.

Aftercare The radiation oncologist, radiation therapist, or radiation oncology nurse will provide instructions on IMRT aftercare. Since some effects of radiation therapy do not begin to show up until after several treatments, these instructions may vary throughout the G A LE EN CY C LO PE DI A O F C AN C ER 3

People undergoing radiation therapy who become fatigued may need to reduce their routines somewhat and not try to do too much. It is best to keep in touch with the treatment team for advice on feelings of fatigue and care for its effects. If skin becomes irritated, it also is important to follow the team’s instructions concerning washing, sun exposure, and use of skin care products.

Resources PERIODICALS

‘‘Beyond Conventional Radiation’’ RN (June 1998):34 38. ‘‘IMRT and Image guided Tumor Localization Improve Radiotherapy in Prostate Cancer.’’ Health & Medicine Week (April 5, 2004):691. ‘‘IMRT Reduces Radiation Dose to Healthy Breast Tissue.’’ Cancer Weekly (Oct. 26, 2004):30. Leaver, Dennis. ‘‘IMRT Part I.’’ Radiation Therapist (Fall 2002):106 124. ‘‘Study Finds IMRT Is Cost effective Compared to Previous Conformal Technique.’’ Medical Devices & Surgical Technology Week (October 31, 2004):291. OTHER

Risks Radiation therapy carries the risk of radiation reaching and damaging normal tissues or organs near the area being targeted. However, IMRT treatment is more precise than other external radiation therapy procedures. There also is a small risk of dose being calculated incorrectly and a patient receiving too much radiation, but equipment should be run by FDA-approved software. Facilities have many quality processes in place to ensure the correct dose is given to the precise location on the correct patient. Radiation therapy also can cause low levels of white blood cells and platelets. White blood cells help fight infection and platelets help blood clot. Radiation therapy causes other side effects and risks, depending on the area being treated, though many only last a short time. For example, radiation treatment to the head can cause hair loss (alopecia), but the hair eventually will grow back.

Normal results After completion of IMRT treatments, cancer cells should stop dividing and growing, which should slow tumor growth. Often, cancer cells completely die and a tumor shrinks or disappears. With IMRT, there should be little radiation damage to the normal, healthy tissues around the tumor and fewer resulting side effects.

Abnormal results The treatment may not always completely eliminate cancer cells. A cancer may still partially remain or recur at a later date. Physicians usually follow up with imaging studies to see how the treatment is progressing and set up a future schedule check for cancer recurrence. G A LE EN CY C LO PE DI A O F C AN CE R 3

External Radiation Therapy.Web page. American Cancer Society, 2004. http://www.cancer.org. Intensity modulated Radiation Therapy (IMRT).Web page. Radiological Society of North America, 2005. http:// www.radiologyinfo.org. ORGANIZATIONS

American Society for Therapeutic Radiology and Oncology. 12500 Fair Lakes Circle, Suite 375, Fairfax, VA 22033 3882. 800 962 7862. http://www.astro.org.

Teresa G. Odle

Interferons Definition Interferons are in a class of naturally occurring small proteins or glycoproteins called cytokines. They are produced by white blood cells called leucocytes and T lymphocytes (T cells) and by fibroblasts, as part of an immune response to infection or other biological stimuli. Interferons are synthesized or produced through genetic engineering for use as immunotherapy medications in the treatment of viral infections, cancer, and multiple sclerosis (MS).

Purpose The first interferon was discovered in 1957 as an immune-system agent that was produced in response to viral infection and interfered with the production of new viral particles—hence the name ‘‘interferon.’’ Recombinant DNA technology has since been adapted to produce interferons for research and drug treatments. Interferons attach to specific receptors on the surfaces of cell membranes, where they have a variety of effects 751

Interferons

course of treatment. Some side effects of radiation therapy occur soon after treatment begins, but others occur later. The most common side effects of external radiation therapy are fatigue and skin changes.

Interferons

on the immune system including the stimulation and inhibition of enzymes, inhibition of cell proliferation, and enhancement of macrophage and T-lymphocyte activities. There are several different classes of interferons, including alfa, beta, gamma, tau, and omega. These classes are further broken into subclasses designated with Arabic numerals and letters. Alfa and beta interferons are type I interferons that are produced by white blood cells and fibroblasts (a type of connective-tissue cell). Gamma interferon is a type II interferon produced by T cells when they are activated by infection or another stimulus. Alfa interferons are used to treat viral infections and cancer: Interferon alfacon-1 is a synthetic interferon used to treat chronic hepatitis C infection. It binds to the same receptor that binds the hepatitis C virus, thereby preventing the virus from entering and infecting host cells.  Interferons alfa-2a and alfa-2b are used to treat both cancer and viral infections.  Peginterferon is interferon alfa combined with polyethylene glycol, which keeps the interferon active longer. Peginterferon alfa-2a and alfa-2b are used to prevent further liver damage in patients with chronic hepatitis C infections, often in combination with the antiviral drug ribavirin. Peginterferon alfa2a is also used to treat chronic hepatitis B infections.  Interferon alfa-n3 is used to treat recurring or refractory genital or venereal warts. 

In cancer immunotherapy alfa interferons activate tumor-specific cytotoxic T lymphocytes that destroy tumor cells, although the molecular details of this activity remain unclear. Interferons may cause antigens on the exposed tumor surface to more readily stimulate the immune system’s T-cell response. Tumor growth may also be slowed by interferon-mediated damage to the blood cells that nourish the tumor. Alfa interferons are used to treat hairy cell leukemia, malignant melanoma, and Kaposi’s sarcoma, an AIDS-related cancer. Alfa interferons are used off-label to treat many other cancers including kidney and bladder cancers, chronic myelocytic leukemia, carcinoid tumors, non-Hodgkin’s lymphoma, ovarian cancer, and skin cancers. Alfa interferons may be combined with other chemotherapeutic drugs such as doxorubicin. Interferons beta-1a and beta-1b are used to decrease the number of symptomatic episodes or flare-ups of MS and to slow the progression of the disease in patients with relapsing-remitting MS. Interferon does not help patients with chronic progressive 752

MS in which symptoms are always present. MS is an autoimmune disease in which the body’s own immune system demyelinates the myelin sheaths enclosing nerve cells. Demyelination causes malfunctions in the transmission of impulses from nerve to nerve and from nerve to muscle. Interferon beta-1a is in a class of medications called immunomodulators, but it is not known exactly how it decreases MS flare-ups. Interferon beta-1b is a synthetic version of a human protein that is in a class of medications known as biologic response modifiers. It enhances T-cell activity while simultaneously reducing the production of inflammatory cytokines. Interferon beta-1b also retards the exposure of antigens on the surfaces of cells, thereby reducing the immune response to the antigen and slowing the appearance of lymphocytes in the central nervous system. This dampening of the immune response can reduce both symptomatic episodes of MS and damage to neurons in the brain. In 2006 the U.S. Food and Drug Administration (FDA) extended approval of interferon beta 1-b for use in patients who are at high risk of developing MS. Interferon gamma-1b is a synthetic version of a naturally occurring interferon. It is used to treat chronic granulomatous disease, an inherited immunesystem disorder.

Description There are no generic forms of interferon. Interferons are always administered by injection, usually by the patient or caregiver. They cannot be taken by mouth because they are destroyed by stomach acids. The injections can be either intramuscular (IM; into a muscle) or subcutaneous (SC). SC injections are made under the skin, between the fat layer and the muscle, often in the abdomen, thigh, buttocks, or upper arm— anywhere that there is a fat layer between the skin and muscle, except around the waist or near the navel. Each injection is at a different site than the previous one, because side effects at the injection site are common. Injections are always on the same day(s) of the week at approximately the same time of day, usually late afternoon or evening before bedtime, so that the worst of the side effects occur during sleep. U.S. brand names 

 

Infergen (interferon alfacon-1, SC injection) supplied as a 30-microgram (mcg) per milliliter (ml) solution of 0.3 or 0.5 ml Roferon-A (interferon alfa-2a, recombinant) Intron A (interferon alfa-2b, recombinant) G A LE EN CY C LO PE DI A O F C AN C ER 3













Pegasys (peginterferon alfa-2a), for SC injection, supplied in a 1.2-ml-solution vial of 180 mcg per ml or a pre-filled syringe with 180 mcg in 0.5 ml PEG-Intron (peginterferon alfa-2b), for SC injection, supplied as powder in a vial to which solution is added or as a single-dose injection pen Alferon N (interferon alfa-n3) supplied as a 1-ml 5-million-unit solution. Avonex (interferon beta-1a, IM injection) supplied as a liquid in a pre-filled syringe or as a powder in a single-use vial that is mixed into a solution Rebif (interferon beta-1a, SC injection) supplied in 22-mcg pre-filled syringes Betaseron (interferon beta-1b, SC injection) supplied with pre-filled syringes to which the medication is added; also available in an autoinjector Actimmune (interferon gamma-1b) Canadian brand names

     

Infergen (alfacon-1) Alferon N (alfa-n3) Pegasys (peginterferon alfa-2a) PEG-Intron (peginterferon alfa-2b) Avonex (beta-1a) Betaseron (beta-1b) International brand names

 

Infergen, Inferax (alfacon-1) Pegintron, ViraferonPeg (peginterferon alfa-2b)

Recommended dosage 







Interferon alfacon-1 is injected three times per week at 9 mcg per dose for 24 weeks. For patients who do not respond or have relapsed, the dosage may be increased to 15 mcg for six months. Dosages of interferons alfa-2a and -2b depend on various factors including the condition being treated, the patient’s weight, and other medications that are being administered. They are generally injected daily for 10–24 weeks during what is called the induction period. During the following maintenance period, the drug is injected once every three weeks. Treatment usually continues for at least six months. The usual adult dosage of peginterferon alfa-2a is 180 mcg (less if side effects are severe) once per week for 24 or 48 weeks, injected into the abdomen or thigh. Peginterferon alfa-2b is injected once per week at a dosage that depends on body weight. Treatment usually continues for one year.

G A LE EN CY C LO PE DI A O F C AN CE R 3









Interferon alfa-n3 (0.05 ml; 250,000 units) is injected into each wart twice weekly for a maximum of eight weeks. The treatment is not repeated for at least three months. The usual dosage of interferon beta-1a is 30–44 mcg. Avonex is injected once per week. Rebif is injected three times per week, with at least 48 hours between injections. The initial dosage of Rebif is usually 8.8 mcg, gradually increased to 44 mcg over a four-week period. Interferon beta-1b is usually injected every other day at an initial dose of 62.5 mcg, gradually increased over six weeks to 250 mcg. Interferon gamma-1b is SC injected three times per week.

Precautions Interferons can reduce the number of white blood cells in the body, causing increased susceptibility to infection. Patients on interferon should avoid contact with people who have infections and should consult their physicians immediately if they believe they are developing an infection. Patients should take care not to cut themselves, should not touch their eyes or inside of their nose with unwashed hands, and should take care when brushing their teeth so as not to cause bleeding. Patients are often advised to drink extra water to avoid low blood pressure. Patients on interferon beta should have periodic liver function tests. Pediatric Most interferon treatments have not been studied for safety in children under age 18. However beta interferon is approved for treating MS in children. Geriatric Although interferon treatment has not been studied in elderly patients, they may require lower dosages. Pregnant or breastfeeding Alpha interferons have not been shown to cause problems in fetuses. The fetal effects of beta interferons are unknown and they are not approved for use during pregnancy. Women of childbearing potential should use reliable birth control while on beta interferon. The FDA has required interferon manufacturers to develop pregnancy registers to monitor the outcomes in women who have become unintentionally pregnant while receiving beta interferon. Because it is not known whether interferons cross into breast milk, women should not breastfeed while undergoing interferon treatment. 753

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Interferons

Other conditions and allergies

QUESTIONS TO ASK YOUR PHARMACIST

The following conditions may be exacerbated by interferons: bleeding problems depression or other mental problems  convulsions  diabetes mellitus  heart disease  heart attack  liver disease  kidney disease  lung disease  an overactive immune system 







Patients who have had or are at risk for seizures, as well as those with heart disorders such as angina, congestive heart failure, or an irregular heartbeat, should be closely monitored following interferon injection. Before receiving an interferon injection patients should notify their doctors if they are allergic to immunoglobulins or egg whites.



  

  

Side effects

headache loss of appetite  nausea and vomiting  fatigue  fever  chills  sweating  muscle aches  an unusual metallic taste in the mouth  irritability

mental depression nervousness numbness or tingling of fingers, toes, and face Although uncommon, patients who are already clinically depressed may develop suicidal feelings during interferon treatment. Other side effects may include:



The side effects of interferon treatment vary from the uncomfortable to the severe. The most common side effects of interferons are general flu-like symptoms including:

How should I store this medication? How do I administer this medication? Will interferon interact with any of my other medications? What if I miss a dose? What side effects can I expect? When should I contact my doctor about side effects?

   



infection, swelling, inflammation, bruising, or necrosis (cell death) at the site of injection menstrual cycle changes in women liver and thyroid malfunction decreases in platelets and red and white blood cells a variety of other—sometimes very serious—side effects, depending on the specific interferon



These symptoms tend to diminish with time. Physicians may suggest taking acetaminophen (e.g., Tylenol) or ibuprofen (e.g., Advil) before each dosage. Interferons sometimes cause serious side effects from their actions on the central nervous system. Since most side effects are dose-dependent, severe side effects may require dosage modification. Symptoms of central nervous system side effects include:  

difficulty concentrating confusion

754

Other conditions and allergies Interferon induces an allergic reaction in some people. However the massive and sometimes fatal allergic reaction termed anaphylaxis is rare with interferons.

Interactions Interferons can interact with a variety of other medications, in some cases increasing their effects. Interferons should not be combined with any other medications except under a physician’s supervision. Most medications that interact with alfa interferons are those that affect the central nervous system including:     

antihistamines sedatives tranquilizers sleeping medications prescription pain medicines G A LE EN CY C LO PE DI A O F C AN C ER 3

  

seizure medications muscle relaxants narcotics barbiturates

Other drugs that may interact with interferons include:    

Warfarin Clozapine, an antipsychotic Theophylline Prednisone

Alfa interferons can increase the effects of alcohol. Alcohol can worsen the side effects of beta interferons. During interferon treatment alcohol should be consumed only with the physician’s consent. Alcohol should never be consumed by patients with hepatitis.

multiple sclerosis/treatments/medications/interferon beta 1a rebif/index.aspx. ORGANIZATIONS

American Cancer Society, 1599 Clifton Road NE, Atlanta, GA, 30329 4251, (800) ACS 2345, http://www.cancer.org. National Cancer Institute, NCI Public Inquiries Office, 6116 Executive Boulevard, Room 3036A, Bethesda, MD, 20892 8322, (800) 4 CANCER, http://www.cancer.gov. National Digestive Diseases Information Clearinghouse, 2 Information Way, Bethesda, MD, 20892 3570, (800) 891 5389, (703) 738 4929 , [email protected], http://www.digestive.niddk.nih.gov. National Multiple Sclerosis Society, 733 Third Avenue, New York, NY, 10017, (800) 344 4867, http://www. nationalmssociety.org. U.S. Food and Drug Administration, 10903 New Hamp shire Ave., Silver Spring, MD, 20993 0002, (888) INFO FDA, http://www.fda.gov.

Sally C. McFarlane-Parrott Brian Douglas Hoyle, PhD Margaret Alic, PhD

Resources BOOKS

Pitha, Paula M. Interferon: The 50th Anniversary. New York: Springer, 2007. Plotnikoff, Nicholas P. Cytokines: Stress and Immunity, 2nd ed. Boca Raton, FL: CRC/Taylor & Francis, 2007. Stephensen, Frank Harold. DNA: How the Biotech Revolu tion Is Changing the Way We Fight Disease. Amherst, NY: Prometheus Books, 2007. PERIODICALS

Coghlan, Andy. ‘‘Cheap Drug Dodges Big Pharma Patents.’’ New Scientist 193, no. 2585 (January 6 12, 2007): 14. Cooper, Chet. ‘‘MS in Children.’’ Ability Magazine 2007, no. 5 (2007): 56 61. Criscuolo, Domenico. ‘‘A Place for Proteins.’’ Applied Clin ical Trials (May 2009): 6 8. OTHER

‘‘Avonex (Interferon Beta 1a).’’ National Multiple Sclerosis Society. http://www.nationalmssociety.org/about multiple sclerosis/treatments/medications/interferon beta 1a avonex/index.aspx. ‘‘Betaseron (Interferon Beta 1b).’’ National Multiple Sclero sis Society. http://www.nationalmssociety.org/about multiple sclerosis/treatments/medications/interferon beta 1b/index.aspx. ‘‘Biological Therapies for Cancer: Questions and Answers.’’ National Cancer Institute. http://www.cancer.gov/cancer topics/factsheet/Therapy/biological. ‘‘Interferons alfa.’’ American Cancer Society. http://www. cancer.org/docroot/CDG/content/CDG_interferons_ alfa.asp. National Digestive Diseases Information Clearinghouse. ‘‘Chronic Hepatitis C: Current Disease Management.’’ NIH Publication No. 07 4230. http://digestive.niddk. nih.gov/ddiseases/pubs/chronichepc/. ‘‘Rebif (Interferon Beta 1a).’’ National Multiple Sclerosis Society. http://www.nationalmssociety.org/about G A LE EN CY C LO PE DI A O F C AN CE R 3

Interleukin 2 Definition Interleukin-2 (IL-2) is a protein produced naturally in the body in very small amounts. It is produced by a type of white blood cell called a T-lymphocyte and acts as part of the immune system by helping white blood cells work. Aldesleukin is a biological response modifier, a synthetic form of interleukin-2.

Purpose Interleukin-2 (IL-2) is a naturally occurring chemical, called a cytokine, produced by certain cells of the immune system. It is also manufactured and administered as a drug to augment immune responses. While it is approved by the U.S. Food and Drug Administration (FDA) only for the treatment of kidney cancer, it is also used in the treatment of HIV and AIDS. Inhaled interleukin-2 may halt disease progression in patients with kidney cancer that has spread to the lungs. Aldesleukin, a synthetic version of interleukin2, is used to treat cancer of the kidney and skin cancer that has spread to other parts of the body. Aldesleukin is approved by the United States Food and Drug Administration (FDA) for treatment of metastatic malignant melanoma (skin cancer that has spread to other parts of the body) and metastatic renal cell carcinoma (kidney cancer that has spread to 755

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Interleukin 2

K EY T ERM S Cytokine—A protein secreted by cells of the lymph system that affects the activity of other cells and is important in controlling inflammatory responses. Interleukin-2 is a cytokine. Metastatic—Spreading from one part of the body to another. Neutrophil—The most common type of white blood cell in humans, responsible for protecting the body against infection.

responded favorably to the treatment. About 15% of patients respond to treatment. It is difficult to estimate the cost of IL-2 treatment since the dose and number of treatment cycles given varies according to patients’ individual responses; however, the cost is quite high, perhaps as much as $2,000 for one cycle. A six-cycle regimen of IL-2 may cost about $14,100. Because of the high cost and low effectiveness of interleukin-2, it is often not covered by insurance plans, especially HMOs. It is covered by Medicare if given in a hospital.

Precautions

Subcutaneous—Under the skin. T-lymphocyte—A cell in the lymphatic system that contributes to immunity by directly attacking foreign bodies, such as viruses and bacteria.

other parts of the body). It has also been used in combination with other drugs in treatment of AIDS and cutaneous t-cell lymphoma.

Description The kidneys are a pair of bean-shaped organs, located on the sides of the spine. The kidneys filter the blood and eliminate waste in the urine through a complex system of filtration tubules. All of the blood in the body passes through the kidneys approximately twenty times an hour. Renal cell cancer (RCC) is an uncommon form of cancer that is most often characterized by the presence of cancer cells in the lining of the filtration tubules of the kidney. Advanced (metastatic) RCC refers to cancer that has spread outside the kidneys to other locations in the body. The only agent approved for metastatic RCC is high-dose Proleukin (interleukin-2). One site of cancer spread in metastatic RCC is the lungs, referred to as pulmonary metastasis.

IL-2 is highly toxic and usually makes patients feel generally unwell. Any side effects should be reported to a physician, but the course of medicine should continue even though the patient feels ill, unless the physician or healthcare professional tells the patient to stop. While using aldesleukin, IL-2 patients will be more susceptible to infection. They should avoid people with colds, flu, and bronchitis. They should not have any vaccinations without their IL-2 prescriber’s approval, and they should avoid anyone who has recently had an oral polio vaccine. Patients should drink several glasses of water a day to help reduce possible kidney problems. Aldesleukin should not be used by lactating mothers. It should also be avoided in patients with the following conditions:         

Recommended dosage IL-2 is usually administered by injection into a vein but can also be injected under the skin (subcutaneous injection). It can be given in a hospital or clinic setting by a healthcare professional and is sometimes given at home. The dosage depends on the height and weight of the patient. It is given as an infusion for 15 minutes every eight hours for up to five days followed by nine days without the drug and then another fiveday cycle of infusion. Up to four subsequent maintenance cycles of IL-2 can be given with four-week intervals without the drug to patients who have 756

          

acute s-t elevation myocardial infarction angina pectoris atrial fibrillation bacterial infection bradycardia capillary leak syndrome coma epilepsy fungal infections impaired cognition intestinal perforation ischemic bowel disease neoplasm metastatic to the central nervous system organ transplantation pericardial tamponade protozoal infection pulmonary disease renal failure supraventricular tachycardia toxic psychosis G A LE EN CY C LO PE DI A O F C AN C ER 3



ventricular tachycardia viral infection

According to , the drug should be avoided or used with extreme care in patients with the following:              

arthritis bone marrow depression bullous pemphigoid cerebral arteritis cholecystitis Crohn’s disease diabetes mellitus disease of liver glomerulonephritis myasthenia gravis psychotic disorder renal disease scleroderma thyroiditis untreated hypothyroidism

According to , the drug should be avoided by people who have the following conditions:            

chicken pox (including recent exposure) herpes zoster (shingles) heart disease immune system problems liver disease lung disease psoriasis underactive thyroid infection kidney disease mental problems history of seizures

Side effects When IL-2 is given by intravenous infusion, the most common side effect is called capillary leak syndrome. This condition causes weight gain, swelling, low blood pressure, and other problems. At lower doses, people taking IL-2 get flu-like symptoms, including fever and muscle aches. Because IL-2 stimulates the immune system, it can make some immune disorders get worse, including arthritis, psoriasis, and diabetes. It can also reduce the number of neutrophils, a particular type of infection-fighting cell, and can cause low levels of thyroid. G A LE EN CY C LO PE DI A O F C AN CE R 3

When IL-2 is given by subcutaneous injection, the side effects are usually milder than with intravenous infusions. There is the added side effect of irritation at the site of the injection. Side effects show up from two to six hours after injection of IL-2 and disappear quickly after the end of each cycle. IL-2 can cause mood changes, including irritability, insomnia, confusion, or depression. These can continue for several days after IL-2 is stopped. Interleukin-2 has a number of other side effects. More common ones are fever or chills, shortness of breath, agitation, confusion, diarrhea, dizziness, drowsiness, mental depression, nausea and vomiting, sores in the mouth and on the lips, tingling of hands or feet, unusual decrease in urination, unusual tiredness, a weight gain of five to ten pounds or more, anemia, heart problems, kidney problems, liver problems, low blood pressure, low platelet counts in blood, low white blood cell counts, other blood problems, under active thyroid, dry skin, loss of appetite, skin rash or redness with burning or itching followed by peeling, and an unusual feeling of general discomfort or illness. Less common problems include black and tarry stools, skin blisters, blood in the urine, bloody vomit, chest pain, cough or hoarseness, lower back or side pain, painful or difficult urination, pinpoint red spots on the skin, severe stomach pain, unusual bleeding or bruising, bloating and mild stomach pain, blurred or double vision, faintness, fast or irregular heartbeat, loss of taste, rapid breathing, redness, swelling, and soreness of the tongue, trouble in speaking, yellow eyes and skin, constipation, headache, joint pain, and muscle pain. Rare problems include changes in menstrual periods, clumsiness, coldness, convulsions, listlessness, muscle aches, pain or redness at site of injection, sudden inability to move, swelling in the front of the neck, swelling of the feet or lower legs, and weakness.

Interactions Interleukin-2 can adversely interact with the anticancer drug dacarbazine and hormones such as prednisone or cortisone. Ken R. Wells

Intimacy see Sexuality Intraocular melanoma see Melanoma 757

Interleukin 2



Intrathecal chemotherapy

Intrathecal chemotherapy Definition Intrathecal chemotherapy is a method of administration in which the chemotherapy drugs and other drugs are introduced directly into the cerebrospinal fluid.

Purpose Intrathecal chemotherapy is used primarily to treat leukemas and lymphomas. The chemotherapy drugs are injected directly into the cerebrospinal fluid (CSF), which is the fluid that surrounds the brain and the spinal cord. Intrathecal chemotherapy is used to kill cancer cells that have entered the CSF, but it is not used as a therapy if tumors have begun to grow on the spinal cord or brain. Intrathecal chemotherapy frequently is used in the treatment of leukemias.

Precautions Intrathecal chemotherapy is not appropriate for everyone. Chemotherapy drugs can cause serious side effects. Women who are pregnant or breastfeeding should discuss risks and alternatives with their doctors.

Description Intrathecal chemotherapy introduces chemotherapy drugs directly in the cerebrospinal fluid to kill cancer cells that exist there. To introduce the chemotherapy drugs into the CSF, two methods are commonly used. The first, called lumbar puncture (sometimes called a spinal tap) injects the chemotherapy drugs into the spinal column. The second

introduces the drugs directly into the fluid around the brain using a device called a Ommaya reservoir. Regular chemotherapy procedures, such as giving chemotherapy by mouth or intravenously, usually are not effective for killing cancer cells that exist in the CSF. This is because most chemotherapy drugs cannot move past the blood-brain barrier. The blood brain barrier is made up of special, very tightly packed cells that allow some small molecules, such as oxygen, through but do not allow larger molecules to pass into the CSF. This helps to protect the brain from bacteria, viruses, and other cells and molecules that may be harmful to it. Unfortunately, the blood brain barrier also restricts the passage of most chemotherapy drugs. Therefore, to get chemotherapy drugs into the CSF they must be injected directly. Lumbar Puncture The lumbar puncture procedure introduces chemotherapy drugs directly into the fluid surrounding the spinal cord. To begin the procedure, the patient usually lays face down on a table, and a small area of back above the spine is treated with local anesthetic. A small device (called a stopcock) is then inserted into the spinal column. The stopcock allows for the injection of chemotherapy drugs and the removal of CSF without repeated punctures. A small needle is inserted through the stopcock into the spinal column. Some of the CSF may be withdrawn for diagnostic tests or for use in flushing the stopcock after the injection of the chemotherapy drugs. The chemotherapy drugs are then injected through the stopcock, and the stopcock is flushed and removed. After removal of the stopcock the area around the puncture site is cleaned and bandaged. Ommaya Reservoir

A spinal tap is one method of administering intrathecal chemotherapy. (Alix/Photo Researchers, Inc. Reproduced by permission).

758

The Ommaya reservoir is used to introduce chemotherapy drugs directly into the fluid surrounding the brain. An Ommaya reservoir is a small plastic dome-shaped device that has a catheter (thin tube) attached to it. The placement of the Ommaya reservoir requires a surgical procedure. An area of hair is shaved, and then a small hole is made in the skull into which the reservoir is placed. The reservoir is very small, and it remains in place throughout the duration of chemotherapy treatment. It allows the doctor to remove fluid samples for testing or introduce chemotherapy drugs without requiring a new surgical incision in the skull each time. To perform intrathecal chemotherapy, a very small needle is inserted into the Ommaya reservoir, and the chemotherapy drugs are injected into the fluid surrounding the brain. G A LE EN CY C LO PE DI A O F C AN C ER 3

Each patient is given individual instructions on how to prepare for the intrathecal chemotherapy by his or her cancer care team. Patients may be advised not to eat any solid foods for three or more hours before the procedure. Patients may also be advised to drink plenty of clear liquids. In some cases, CSF is removed during the procedure, and good hydration can help the body replace the fluid more quickly. Some patients may be given anti-nausea drugs before the procedure. Nausea and vomiting are common side-effects of chemotherapy, and taking antinausea drugs before the procedure can help reduce the severity of these problems and in some cases prevent them altogether. Some patients may be asked to stop taking specific medications a day or more before the procedure. Anticoagulants such as warfarin (Coumadin) and aspirin may increase the risk of bleeding during and after the procedure, so patients may be instructed to stop taking the medications several days before the procedure. The cancer care team should provide an individualized set of instructions about which medications should be stopped and when they can be started again. Patients should never stop taking medication without consulting their physician.

Aftercare After the procedure the patient may be instructed to lie flat on his or her stomach for up to eight hours. This helps to reduce the side effects of the lumbar puncture, and can help the chemotherapy drugs to distribute evenly throughout the CSF. Activities may need to be limited for 24 hours after the procedure.

Risks Women who are pregnant should talk to their doctors carefully about the risks and benefits of intrathecal chemotherapy, as the chemotherapy drugs can pose a significant risk to the fetus. Women who are breastfeeding should talk to their doctors about alternatives to breastfeeding as chemotherapy drugs may pass to the nursing infant through the breast milk. The risks of intrathecal chemotherapy differ depending on the type and amount of chemotherapy drug being used. Risks include bleeding, soreness, and infection at the injection site, dizziness, nausea or vomiting, and fatigue. Headaches are a relatively common side effect of lumbar punctures. In some cases the headaches can be severe, although they usually resolve within hours after the procedure. Lying prone (flat and face-down) and drinking plenty of fluids can G A LE EN CY C LO PE DI A O F C AN CE R 3

Q U E S T I O N S TO A S K Y O U R DOCTOR 





 



Are there certain side effects for which I am especially at risk? Will I have to lie still after the procedure? For how long? How often and for how long will I need intrathecal chemotherapy? How long should I expect the procedure to take? Can I eat and drink normally before the procedure? Are there any medications I should stop taking before the procedure?

help reduce this risk. If the headache is very severe or does not resolve in a few hours patients should alert their doctors. Chemotherapy commonly causes hair-loss, dryness of the mouth and throat, and sores in the mouth. It also frequently causes intestinal problems that can cause diarrhea and upset stomach. Decreased interest in sex, hormone changes, and kidney and bladder irritation are also common side effects. Individuals undergoing chemotherapy are also at increased risk of infection because chemotherapy drugs kill many good immune system cells that are needed to combat infection as well as killing cancer cells.

Results Results of intrathecal chemotherapy vary. Each person’s body reacts to chemotherapy differently, and each type of cancer is different. Results can depend on the stage of the cancer, the type of chemotherapy drug used, any health problems the patient has in addition to cancer, and a variety of other factors. Patients should ask their physician and cancer care team about the expected results for their specific situation.

Health care team roles Intrathecal chemotherapy is administered by a hematologist (doctor who specializes in treating diseases of the blood) or an oncologist (doctor who specializes in treating cancer). The doctor may be assisted by another doctor during the procedure. One or more nurses may assist by helping to prepare the patient, administering local anesthetic, and providing other assistance. The chemotherapy drugs are mixed by a pharmacist with specialized knowledge of chemotherapy drugs. 759

Intrathecal chemotherapy

Preparation

Intravenous urography

Caregiver concerns Intrathecal chemotherapy affects different people in different ways. Some individuals may have few or no side-effects from the treatment, but many individuals will feel tired, sore, and/or nauseated after the procedure. If the intrathecal chemotherapy is being given on an out-patient basis, the patient will need someone to help him or her get home after treatment. If the car ride home is very long, the patient may need to lie as flat as possible in the car to help reduce side effects from the lumbar puncture and to help the chemotherapy drugs spread correctly. The patient may vomit on the way home; caregivers should be prepared for this. During a course of chemotherapy treatment patients often feel nauseated and foods that were once enjoyed may seem unappealing. Caregivers may want to organize friends and loved ones to help provide nutritious, high-calorie meals and snacks.

Intravenous urography Definition Intravenous urography is a test that x rays the urinary system using intravenous dye for diagnostic purposes. The kidneys excrete the dye into the urine. X rays can then create pictures of every structure (kidney, renal pelvis, ureter, bladder, urethra) through which the urine passes. The procedure has several variations and many names:    

Intravenous pyelography (IVP) Urography Excretory urography Pyelography

Helping with housework, childcare, errands, and chores can be a great way to help an individual undergoing intrathecal chemotherapy. Individuals undergoing chemotherapy are often very tired, and juggling chemotherapy with other responsibilities can be overwhelming. Resources BOOKS

Aryan, Henry E. Spinal Tumors: A Treatment Guide for Patients and Family. Sudbury, MA: Jones and Bartlett Publishers, 2010. McKay, Judith, and Tamera Schacher. The Chemotherapy Survival Guide: Everything You Need to Know to Get Through Treatment, 3rd ed. Oakland, CA: New Har binger Publications, 2009. Perry, Michael C., ed. The Chemotherapy Source Book,4th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2008. Polovich, M., White, J.M., Olsen, M. (Eds.)(2009) Chemo therapy and Biotherapy Guidelines and Recommenda tions for Practice, 3rd edition. Pittsburgh, PA: Oncology Nursing Society. ORGANIZATIONS

American Cancer Society, 1599 Clifton Rd., NE, Atlanta, GA, 30329, (404) 320 3333, (800) ACS 2345, http:// www.cancer.org. National Cancer Institute Public Inquires Office., 6116 Executive Boulevard, Room 3036A, Bethesda, MD, 20892 8322, (800) 4 CANCER. TTY (800) 332 8615, http://www.cancer.gov.

Tish Davidson, A.M. 760

Intravenous urography showing contrast in distal ureter. Ureter is the narrow tube shown at the lower right of the image, and the dye has traveled from the kidney (above) and is traveling to the bladder. (Custom Medical Stock Photo. Reproduced by permission.)

G A LE EN CY C LO PE DI A O F C AN C ER 3



Antegrade pyelography differentiates this procedure from ‘‘retrograde pyelography,’’ which injects dye into the lower end of the system, therefore flowing backward or ‘‘retrograde.’’ Retrograde pyelography is better able to define problems in the lower parts of the system and is the only way to get x rays if the kidneys are not working well.

Q U E S T I O N S TO A S K T H E DOCTOR  

Nephrotomography is somewhat different in that the x rays are taken by a moving x ray source onto a film moving in the opposite direction. By accurately coordinating the movement, all but a single plane of tissue is blurred, and that plane is seen without overlying shadows.

aneurysm clips, etc. The technique is far more versatile than CT scanning as it can not only demonstrate masses, but also look at the blood vessels. However, MRI requires special apparatus and, because of the powerful magnets needed, even a special, separate building. It is quite expensive and only occasionally is this degree of detail required.

Every method available gives good pictures of this system, and the question becomes one of choosing among many excellent alternatives. Each condition has special requirements, while each technique has distinctive benefits and drawbacks. 









Nuclear medicine scans rely on the radiation given off by certain atoms. Chemicals containing such atoms are injected into the bloodstream. They reach the kidneys, where images are constructed by measuring the radiation emitted. The radiation is no more dangerous than standard x rays. The images require considerable training to interpret, but unique information (e.g. blood flow, kidney function, etc.) is often available using this technology. Different chemicals can concentrate the radiation in different types of tissue. This technique may require several days for the chemical to concentrate at its destination. It also requires a special detector to create the image. Ultrasound is a quick, safe, simple, and inexpensive way to obtain views of internal organs. Although less detailed than other methods, it may be sufficient, especially to detect obstructions. Retrograde pyelography is better able to define problems in the lower parts of the system and is the only way to get x rays if the kidneys are not working well. Dye is usually injected through an instrument (cystoscope) passed into the bladder through the urethra. A computed tomography scan (CT or CAT scanning) uses the same kind of radiation used in x rays, but it collects information by computer in such a way that three dimensional images can be constructed, eliminating interference from nearby structures. CT scanning requires a special apparatus, but often gives better information on masses within the kidney. Magnetic resonance imaging (MRI) uses magnetic fields and radio frequency signals, instead of ionizing radiation, to create computerized images. This form of energy is entirely safe as long as the patient does not have any implanted metal such as artificial joints,

G A LE EN CY C LO PE DI A O F C AN CE R 3

What should I feel when I am being imaged? Why do you recommend intravenous urography rather than another imaging technique?

Purpose IVP will provide information concerning most diseases of the kidneys, ureters, and bladder. The procedure is comprised of two phases. First, it requires a functioning kidney to filter the dye out of the blood into the urine. The time required for the dye to appear on x rays correlates accurately with kidney function. The second phase gives detailed anatomical images of the urinary tract. Within the first few minutes the dye ‘‘lights up’’ the kidneys, a phase called the nephrogram. Subsequent pictures follow the dye down the ureters and into the bladder. A final film taken after urinating reveals how well the bladder empties. IVPs are most often done to assess structural abnormalities or obstruction to urine flow. If kidney function is at issue, more films are taken sooner to catch the earliest phase of the process. 

Stones, tumors and congenital malformations account for many of the findings.



Kidney cysts and cancers can be seen.



Displacement of a kidney or ureter suggests a spaceoccupying lesion (like a cancer of the colon, rectum, or gynecological organs) pushing it out of the way.



Bad valves where the ureters enter the bladder will often show up.



Bladder cancers and other abnormalities are often outlined by the dye in the bladder.



An enlarged prostate gland will show up as incomplete bladder emptying and a bump at the bottom of the bladder. 761

Intravenous urography



Intravenous urography

K EY T ERM S Contrast agent—Any substance that causes shadows on x rays; also known as contrast dye or medium. Intravenous—Into a vein.

agent. Therefore, the night before the IVP the patient is asked to evacuate the bowels and to drink sparingly. Preparation for infants and children depends on the age of the infant or child.

Aftercare Feeling weak, nauseous, and/or lightheaded for a short time after the procedure is a possibility.

Precautions The only serious complication of an IVP is allergy to the iodine-containing dye that is used. Such an allergy is rare, but it can be dramatic and even lethal. Emergency measures taken immediately are usually effective.

Description IVPs are usually done in the morning. In the x ray suite, the patient undresses and lies down. There are two methods of injecting the dye. An intravenous line can be established, through which the dye is consistently fed through the body during the procedure. The other method is to give the dye all at once through a needle that is immediately withdrawn. X rays are taken until the dye has reached the bladder, an interval of half an hour or less. The patient is asked to empty the bladder before one last x ray. A compression device (a wide belt containing 2 balloons that can be inflated) may be used to keep the contrast material in the kidneys. The patient needs to urinate after the compression device is removed. Another picture is taken after the bladder is emptied to see how empty the bladder is. In the past, of the many ways to obtain images of the urinary system, the intravenous injection of a contrast agent has been considered the best. Recent studies are showing, however, that while intravenous urography is a useful technique, there may be other imaging techniques, such as B mode ultrasound, Doppler ultrasound, renal scintigraphy with angiotensinconverting enzyme inhibitors, intra-venous and intraarterial catheter angiography, computed tomographic angiography, and magnetic resonance angiography, that are better or less costly.

Preparation Emptying the bowel with laxatives or enemas prevents bowel shadows from obscuring the details of the urinary system. An empty stomach prevents the complication of vomiting, a rare effect of the contrast 762

Risks Allergy to the contrast agent is the only risk. Anyone with a possible iodine allergy, a previous reaction to x ray dye, or an allergy to shellfish must be particularly careful to inform the x ray personnel. Exposure to x ray radiation should be noted. Most experts agree that the risk of exposure to low radiation is low compared to the benefits. Pregnant women and children are more sensitive to the risks of x rays.

Normal results X-ray images of the kidney and bladder structures appear normal.

Abnormal results An abnormal intravenous urography result may indicate kidney disease, birth defect, tumor, kidney stone, and/or inflammation caused by infections. Resources BOOKS

Ballinger, Philip W., and Eugene D. Frank. Merrill’s Atlas of Radiographic Positions and Radiologic Procedures. 9th ed. St. Louis: Year Book Medical Publishers, 1999. PERIODICALS

Aitchson, F., and A. Page. ‘‘Diagnostic Imaging of Renal Artery Stenosis’’ Journal of Human Hypertension Sep tember 1999: 595 603. Dalla Palma, L. ‘‘What is Left of I.V. Urography?’’ Euro pean Radiology March 2001: 931 939. Hession, P., et al.‘‘Intravenous Urography in Urinary Tract Surveillance in Carcinoma of the Bladder.’’ Clinical Radiology July 1999: 465 467. Little, M. A., et al. ‘‘The Diagnostic Yield of Intravenous Urography.’’ Nephrology Dialysis Transplantation February 2000: 200 204. ORGANIZATIONS

American Cancer Society (National Headquarters). 1599 Clifton Road, N.E., Atlanta, GA 30329. (800) 227 2345. http://www.cancer.org. G A LE EN CY C LO PE DI A O F C AN C ER 3

J. Ricker Polsdorfer, M.D. Laura Ruth, Ph.D.

Investigational drugs Definition ‘‘Investigational drugs’’ refers to drugs that have received FDA approval for human testing, including those drugs still undergoing clinical trials, but are not approved for marketing to the general public.

Description Investigational drugs represent interesting and novel new agents in the fight against cancer. These agents include chemotherapy designed to treat specific cancers, to provide palliative therapy for pain and symptoms, and to reduce invasive cancers in high-risk patients. The challenge faced by private and commercial investigators is to reduce the lag time in bringing an investigational drug to market without compromising drug quality or patient safety. The guidelines that insure the correct procedures are being followed in the process of drug development and approval fall under the direction of the Food and Drug Administration (FDA). At present, the cycle of investigational drug research and development, to clinical trials, to FDA approval can easily cover a period of 10-12 years. Under exceptional circumstances, provisions can be made for patient use of investigational drugs under the guidance of specially trained and registered oncologists. These specific investigational drugs are classified as ‘‘Group C’’ drugs, and have demonstrated a high level of reproducible activity in pre-clinical testing. There is also the route of ‘‘Accelerated FDA Approval’’ for some investigational drugs. G A LE EN CY C LO PE DI A O F C AN CE R 3

KEY T ERMS Oncologist—A physician who specializes in the diagnosis and treatment of cancer patients. Palliative—Therapy or medication designed to provide relief but does not affect a cure for the condition.

Accelerated approval relies on specific indicators that suggest that a particular investigational drug is likely to have beneficial effects before the benefits have been clinically verified. All investigational drugs that have been granted accelerated approval must undergo follow-up testing in order to receive final FDA approval. Some researchers are presently working on a format to combine traditional clinical testing of investigational drugs with a global database of drug information. This integrated system would give FDA monitoring agencies and healthcare providers access to the most comprehensive source of archived data available on investigational drugs. This combined approach is another attempt to reduce approval time for investigational drugs and make these agents available to the cancer patient for treatment. Resources PERIODICALS

Johnson, Dale E., and Grushenka H.I. Wolfgang. ‘‘Predict ing human safety: screening and computational approaches.’’Drug Discovery Today 5, no.10 (October 2000): 445 454. OTHER

Preclinical Development of Investigational Agents: The Developmental Therapeutics Program CTEP Info CTEP. [cited May 8, 2009]. http:// www.CTEP.info.nih.gov. Understanding the Approval Process for New Cancer Drugs. Understanding Trials. NCI Cancer Trials. [cited May 18, 2009]. http://www.cancertrials.nci.nih.gov.

Jane Taylor-Jones, Research Associate, M.S.

Irinotecan Definition Irinotecan is a drug used to treat certain types of cancer. Irinotecan, also known as CPT-11, is available under the trade name Camptosar, and may 763

Irinotecan

Cancer Research Institute (National Headquarters). 681 Fifth Avenue, New York, NY 10022. (800) 992 2623. http://www.cancerresearch.org. Kidney Cancer Association. 1234 Sherman Avenue, Suite 203, Evanston, IL 60202 1375. (800) 850 9132. http:// www.kidneycancerassociation.org. National Cancer Institute. 9000 Rockville Pike, Building 31, Room 10A16, Bethesda, MD 20892. (800) 422 6237. http://www.nci.nih.gov. National Kidney Cancer Association. 1234 Sherman Avenue, Suite 203, Evanston, IL 60202 1375. (800) 850 9132. National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622 9010. http://www. kidney.org.

Irinotecan

K EY T ERM S Alkaloid—A nitrogen-containing compound occurring in plants. Anorexia—Loss of appetite and the inability to eat. Apoptosis—An active process in which a cell dies due to a chemical signal. Programmed cell death. Diuretic—An agent that increases the amount of urine the body produces. Inflammation—A response to injury, irritation, or illness characterized by redness, pain, swelling, and heat. Metastatic—Spread of a disease from the organ or tissue of origin to other parts of the body.

also be referred to as irinotecan hydrochloride or camptothecin-11.

Purpose Irinotecan is an antineoplastic agent used to treat cancer. A primary use of the drug is treatment of colon or rectal cancers that have recurred or progressed while the patient was on 5-FU (fluorouracil) therapy. Irinotecan also can be given as first line therapy with 5FU and leucovorin for patients with metastatic colon or rectal cancer. Other uses for irinotecan include treatment of small cell lung cancer, nonsmall cell lung cancer, ovarian cancer, stomach cancer, breast cancer, pancreatic cancer, leukemia, lymphoma, and cervical cancer. Several studies showed some potential uses for irinotecan. One reported that a combination of irinotecan and docetaxel can help patients with esophageal cancer who have been extensively pretreated with cisplatin. Weekly use of irinotecan has shown preliminary results in treating patients with nonsmall cell lung cancer with minimal side effects. Another study reported that when used in combination with cancer drugs cisplatin and epirubicin, irinotecan might have promising broad antitumor activity. In the future, irinotecan might be used in combination therapies to treat many types of tumors.

Description Irinotecan is a synthetic derivative of the naturally occurring compound camptothecin. Camptothecin belongs to a group of chemicals called alkaloids and is extracted from plants such as camptotheca acuminata. Captothecin was initially investigated as a 764

chemotherapeutic agent due to its anti-cancer activity in laboratory studies. The chemical structure and biological action of irinotecan is similar to that of camptothecin and topotecan. Irinotecan inhibits the normal functioning of the enzyme topoisomerase I. The normal role of topoisomerase I is to aid in the replication, recombination, and repair of deoxyribonucleic acid (DNA). Higher levels of topoisomerase I have been found in certain cancer tumors compared to healthy tissue. Inhibiting topoisomerase I causes DNA damage. This damage leads to apoptosis, or programmed cell death.

Recommended dosage Patients should be carefully monitored during irinotecan treatment for toxicity. Irinotecan is given at a dose of 125 mg per square meter of body surface area per week for four weeks, followed by a two week rest period. Other dosing schedules include 100 mg per square meter of body surface area per day for three days every three weeks, or 100–115 mg per square meter of body surface area per week, or 200–350 mg per square meter of body surface area every three weeks. The drug is administered through the vein over a 90-minute period. The initial dose of irinotecan may be adjusted downward depending on patient tolerance to the toxic side effects of irinotecan. Treatment may be continued as long as intolerable side effects do not develop and patients continue to benefit from the treatment.

Precautions Irinotecan should only be used under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Special caution, especially in those 65 years and older, should be taken to monitor the toxic effects of irinotecan, particularly diarrhea, nausea, and vomiting. Because irinotecan is administered intravenously, the site of infusion should be monitored for signs of inflammation. Should inflammation occur, flushing the site with sterile water and applying ice are recommended. Irinotecan may cause nausea and vomiting, and premedication with antiemetic agents is recommended. Neither the effects of irinotecan in patients with significant liver dysfunction nor the safety of irinotecan in children have been established. Irinotecan should not be administered to pregnant women. Women of child-bearing age are advised not to become pregnant during treatment with this drug. G A LE EN CY C LO PE DI A O F C AN C ER 3

Early- or late-onset diarrhea are common side effects of irinotecan. Late-onset diarrhea, occurring more than 24 hours after irinotecan administration, can be life-threatening and should be treated promptly. Patients should immediately report diarrhea to their physician. Patients can also take the antidiarrheal drug loperamide as prescribed by their physician at the first sign of diarrhea. Suppression of bone marrow function is another serious side effect commonly observed in this treatment. Additional side effects, including nausea, vomiting, anorexia (loss of appetite), pain, fatigue, and hair loss (alopecia) may occur.

Interactions Irradiation treatment during the course of irinotecan treatment is not recommended. Patients who have received prior pelvic or abdominal irradiation treatment should notify their physician. Since irinotecan may cause diarrhea, the use of laxatives should be avoided. The use of diuretics should be closely monitored. The adverse side effects caused by irinotecan may be increased by other antineoplastic agents having similar adverse effects and should generally be avoided. Resources PERIODICALS

‘‘Cisplatin, Irinotecan, and Epirubicin Have Promising Broad Antitumor Activity.’’ Cancer Weekly October 14, 2003:12. ‘‘Irinotecan and Docetaxel Shows Some Activity in Exten sively Pretreated Patients.’’ Clinical Trials Week Octo ber 13, 2003: 25. ‘‘Weekly IrinotecanShowed Antitumoral Activity and Min imum Toxicity in NSCCLC.’’ Clinical Trials Week October 13, 2003: 25.

Marc Scanio Teresa G. Odle

Islet cell carcinoma see Pancreatic cancer, endocrine

Itching Description Itching, also called pruritus, is an unpleasant sensation of the skin that causes a person to scratch or rub the area to find relief. Itching can be confined to one spot (localized) or over the whole body G A LE EN CY C LO PE DI A O F C AN CE R 3

(generalized). Severe scratching can injure the skin causing redness, bumps, and scratches. Injured skin is prone to infection. Itching can profoundly affect quality of life. It can torment the patient and cause discomfort, stress, loss of sleep, concentration difficulty, and constant concern.

Causes The biology underlying itching is not fully understood. It is believed that itching results from the interactions of several different chemical messengers. Although itching and pain sensations were at one time thought to be sent along the same nerve pathways, researchers reported the discovery in 2003 of itchspecific nerve pathways. Nerve endings that are specifically sensitive to itching have been named pruriceptors. Research into itching has been helped by the recent invention of a mechanical device called the Matcher, which electrically stimulates the patient’s left hand. When the intensity of the stimulation equals the intensity of itching that the patient is experiencing elsewhere in the body, the patient stops the stimulation and the device automatically records the measurement. The Matcher was found to be sensitive to immediate changes in the patient’s perception of itching as well as reliable in its measurements. Itching is associated with a variety of factors including skin diseases, blood diseases, emotions, and drug reactions as well as by cancer and cancer treatments. Itching can be a symptom of cancer including Hodgkin’s disease, non-Hodgkin’s lymphoma, leukemia, Bowen’s disease, multiple myeloma, central nervous system (brain and spinal cord) tumors, germ cell tumors, and invasive squamous cell carcinoma. The buildup of toxins in the blood, caused by kidney, gallbladder, and liver disease, can cause itching. Cancer treatments that are associated with itching are: radiation therapy, chemotherapy, and biological response modifiers (drugs that improve the patient’s immune system). Skin reactions are more severe when both chemotherapy and radiation therapy are used. Patients treated with bone marrow transplantation may develop itching resulting from graft-vs.-host disease. Itching can be caused by infection. General medications that may be used by cancer patients can cause itching. Itching can be caused by drug reactions from antibiotics, corticosteroids, hormones, and pain relievers (analgesics). tive

Itching can be a sign that the patient is very sensito a particular chemotherapy drug. 765

Itching

Side effects

Itching

Chemotherapy drugs and biological response modifiers that can cause itching include: allopurinol  aminoglutethimide  bleomycin  carmustine  chlorambucil  cyclophosphamide  cytarabine  daunorubicin  doxorubicin  hydroxyurea  idarubicin  interleukin (aldesleukin)  mechlorethamine  megestrol acetate  mitomycin-C  tamoxifen  topiramate 

Itching commonly occurs during radiation therapy. Parts of the body that are particularly sensitive to radiation are the underarms, groin, abdomen, breasts, buttocks, and skin around the genitals (perineum) and anus (perianal). Itching is usually caused by skin dryness when the oil (sebaceous) glands are damaged by the radiation. Radiation also causes skin darkening, redness, and skin shedding, which can all cause itching. Itching caused by cancer usually disappears once the cancer is in remission or cured. Chemotherapyinduced itching usually disappears within 30 to 90 minutes after the drug has been administered. Itching caused by radiation therapy will resolve once the injured skin has healed.

   



  

To reduce skin injury caused by scratching the patient should keep fingernails short, wear soft cotton mittens and socks at night, and keep the hands clean. Gently rubbing the skin around the itch or applying pressure or vibration to the itchy spot may reduce itching. Using a soft infant toothbrush to gently stroke the itchy area may relieve itching. Itching may be relieved by applying a cool washcloth or ice to the itchy area. The most effective way to relieve itching is to treat the underlying disease. Sometimes, itching disappears as soon as a tumor is treated or removed. Itching may be relieved by applying any of a variety of different products to the skin. The patient may need to try several before the most effective one is found. The patient’s physician should be consulted before any anti-itch products are used. Topical treatments include: 





Treatments



There are three aspects in the treatment of itching: managing the underlying cancer, maintaining skin health, and relief of itching. Patients should avoid the particular things that cause or worsen their itching. Also, patients can take measures to maintain skin health. Suggestions include: taking short baths in warm water  using mild soaps and rinsing well  applying bath oil or moisturizing cream after bathing  avoiding use of cosmetics, perfumes, deodorants, and starch-based powders  avoiding wool and other harsh fabrics





766

using mild laundry detergents and rinsing thoroughly avoiding use of dryer anti-static sheets wearing loose-fitting cotton clothing avoiding high-friction garments such as belts, pantyhose, and bras maintaining a cool environment with a 30% to 40% humidity level using cotton sheets avoiding vigorous exercise (if sweating causes itching) avoiding skin products that are scented or contain alcohol or menthol

Corticosteroids, such as hydrocortisone, reduce inflammation and itching. Calamine lotions can cool and soothe itchy skin. These products can be drying, which may be helpful for weeping or oozing rashes. Antihistamine creams stop itching that is associated with the chemical messenger histamine. Moisturizers treat dry skin which helps to relieve itching. Moisturizers that are recommended to cancer patients include brand names Alpha Keri, Aquaphor, Eucerin, Lubriderm, Nivea, Prax, and Sarna. Moisturizers should be applied after bathing and at least two or three times daily. Gels that contain a numbing agent (e.g. lidocaine) can be used on some parts of the body.

Itching may be treated with whole-body medications. Some of these systemic treatments include:   

antihistamines tricyclic antidepressants sedatives or tranquilizers G A LE EN CY C LO PE DI A O F C AN C ER 3



 

such selective serotonin reputake inhibitors as paroxetine (Paxil) and sertraline (Zoloft) binding agents (such as cholestyramine which relieves itching associated with kidney or liver disease). aspirin cimetidine Alternative and complementary therapies

A well-balanced diet that includes carbohydrates, fats, minerals, proteins, vitamins, and liquids will help to maintain skin health. Capsules that contain eicosapentaenoic acid, which is obtained from herring, mackerel, or salmon, may help to reduce itching. Vitamin A plays an important role in skin health. Vitamin E (capsules or ointment) may reduce itching. Patients should check with their treating physician before using supplements. Homeopathy has been reported to be effective in treating systemic itching associated with hemodialysis. Baths containing oil with milk or oatmeal are effective at relieving localized itching. Evening primrose oil may soothe itching and may be as effective as corticosteroids. Calendula cream may relieve short-term itching. Other herbal treatments that have been recently reported to relieve itching include sangre de drago, a preparation made with sap from a South American tree; and a mixture of honey, olive oil, and beeswax. Distraction, music therapy, relaxation techniques, and visualization may be useful in relieving itching. Ultraviolet light therapy may relieve itching associated with conditions of the skin, kidneys, blood, and gallbladder. There are some reports of the use of acupuncture and transcutaneous electrical nerve stimulators (TENS) to relieve itching. Resources

PERIODICALS

Al Waili, N. S. ‘‘Topical Application of Natural Honey, Beeswax and Olive Oil Mixture for Atopic Dermatitis or Psoriasis: Partially Controlled, Single Blinded Study.’’ Complementary Therapies in Medicine 11 (December 2003): 226 234. Browning, J., B. Combes, and M. J. Mayo. ‘‘Long Term Efficacy of Sertraline as a Treatment for Cholestatic Pruritus in Patients with Primary Biliary Cirrhosis.’’ American Journal of Gastroenterology 98 (December 2003): 2736 2741. Cavalcanti, A. M., L. M. Rocha, R. Carillo, Jr., et al. ‘‘Effects of Homeopathic Treatment on Pruritus of Haemodialysis Patients: A Randomised Placebo Controlled Double Blind Trial.’’ Homeopathy 92 (October 2003): 177 181. Ikoma, A., R. Rukwied, S. Stander, et al. ‘‘Neurophysiology of Pruritus: Interaction of Itch and Pain.’’ Archives of Dermatology 139 (November 2003): 1475 1478. Jones. K. ‘‘Review of Sangre de Drago (Croton lechleri) A South American Tree Sap in the Treatment of Diarrhea, Inflammation, Insect Bites, Viral Infections, and Wounds: Traditional Uses to Clinical Research.’’ Jour nal of Alternative and Complementary Medicine 9 (December 2003): 877 896. Ochoa, J. G. ‘‘Pruritus, a Rare but Troublesome Adverse Reaction of Topiramate.’’ Seizure 12 (October 2003): 516 518. Stener Victorin, E., T. Lundeberg, J. Kowalski, et al. ‘‘Per ceptual Matching for Assessment of itch; Reliability and Responsiveness Analyzed by a Rank Invariant Statistical Method.’’ Journal of Investigative Dermato logy 121 (December 2003): 1301 1305. Zylicz, Z., M. Krajnik, A. A. Sorge, and M. Costantini. ‘‘Paroxetine in the Treatment of Severe Non Dermatological Pruritus: A Randomized, Controlled Trial.’’ Journal of Pain and Symptom Management 26 (December 2003): 1105 1112.

Belinda Rowland, Ph.D. Rebecca J. Frey, Ph.D.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Pruritus.’’ In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2007.

G A LE EN CY C LO PE DI A O F C AN CE R 3

Itraconazole see Antifungal therapy IVP, Excretory urography, Intravenous pyelography see Intravenous urography

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Itching



K 

Kaposi’s sarcoma Definition Kaposi’s sarcoma (KS) is a cancer of the skin, mucous membranes, and blood vessels; it is the most common form of cancer in AIDS patients. It was named for Dr. Moritz Kaposi (1837–1902), a Hungarian dermatologist who first described it in 1872. As of 2009, researchers disagree as to whether KS is a true cancer or a disorder of the skin that develops as a reaction to infection by a herpes virus.

Description The formal medical term for Kaposi’s sarcoma is multiple idiopathic hemorrhagic sarcoma. This term means that KS develops in many different sites on the patient’s skin or internal organs; that its cause is unknown; and that it is characterized by bleeding. The lesions (areas of diseased or damaged skin), which are usually round or elliptical in shape and a quarter of an inch to an inch in size, derive their characteristic purple or brownish color from blood leaking out of capillaries (small blood vessels) in the skin. In KS, the capillaries begin to grow too rapidly and irregularly, which causes them to become leaky and eventually break. The lesions themselves may become enlarged and bleed, or cause the mucous membranes of the patient’s internal organs to bleed.

KS is classified into five types: 









There are three types of KS lesions, defined by their appearance: 



Nodular. These are reddish-purple, but are sometimes surrounded by a border of yellowish or brown pigment. Nodular lesions may appear to be dark brown rather than purple in patients with dark skin. Infiltrating. Infiltrating lesions may be large or have a raised surface. They typically grow downward under the skin.

G A LE EN CY C LO PE DI A O F C AN CE R 3

Lymphatic. These lesions are found in the lymph nodes and may be confused with other causes of swollen lymph nodes. Classic KS. This form of KS is sometimes called indolent KS because it is slow to develop. Classical KS is most commonly found in males between 50 and 70 years of age, of Italian or Eastern European Jewish descent. African KS. This form of the disease appears in both an indolent and an aggressive form in native populations in equatorial Africa. It accounts for almost 10% of all cancers in central Africa. Immunosuppressive treatment-related KS. The third form of KS occurs in kidney transplant patients who have been given drugs to suppress their immune systems-usually prednisone and azathioprine. This form of KS is sometimes called iatrogenic KS, which means that it is caused unintentionally by medical treatment. Epidemic KS. Epidemic KS was first reported in 1981 as part of the AIDS epidemic. Most cases of epidemic KS in the United States have been diagnosed in homosexual or bisexual men. Non-epidemic gay-related KS. This form of KS occurs in homosexual men who do not develop HIV infection. Non-epidemic gay-related KS is an indolent form of the disease that primarily affects the patient’s skin.

Demographics The demographic distribution of KS varies considerably across its five types: 

Classic KS. Classic KS is considered a rare disease, with a male/female ratio of 10:1 or 15:1. In North America and Europe, most patients are between 50 and 70 years old. Classic KS is more common in men from Mediterranean countries and in Ashkenazic Jews. 769

Kaposi’s sarcoma

KEY TERMS Angiogenesis—The formation of blood vessels. Some complex proteins found in shark cartilage appear to prevent angiogenesis in tumor cells in laboratory tests. Cryotherapy—A form of treating KS lesions that involves freezing them with liquid nitrogen. Disseminated—Widely distributed or spread. Epi demic KS almost always develops into a dissemi nated form, in which the disease spreads throughout the patient’s body. Purple-colored (violaceous) plaques of Kaposi’s sarcoma on the heel and side of foot. (Centers for Disease Control.)

Highly active antiretroviral therapy (HAART)—A form of drug combination treatment for HIV infec tion introduced in 1998. Most HAART regimens are combinations of three or four drugs, usually nucleoside analogs and protease inhibitors. Iatrogenic—Caused unintentionally by medical treatment. Immunosuppressive treatment related KS is sometimes called iatrogenic KS. Immunosuppressive—Any form of treatment that inhibits the body’s normal immune response.

This HIV-positive patient is afflicted with Kaposi’s sarcoma inside the mouth. The tumor is toward the back of the mouth, to the right. (Custom Medical Stock Photo. Reproduced by permission.)



African KS. African KS has the same male/female ratio as classic KS, although most patients with African KS are younger. A form of African KS that attacks the lymphatic system primarily affects children, with a male/female ratio of 3:1.



Immunosuppresive treatment-related KS. This form of KS occurs mostly in kidney-transplant patients, at a rate of 150 to 200 times as often as in the general population. It represents 3% of all tumors that occur in kidney-transplant patients. The male/female ratio is 2:1.



Epidemic KS. Epidemic KS is overwhelmingly a disease of adult homosexual or bisexual males. It is 20,000 times more common in people with AIDS than in those without HIV infection. According to the National Institutes of Health (NIH), 95% of all

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Indolent—Relatively inactive or slow spreading. Classic KS is usually an indolent disease. Liposomes—Artificial sacs composed of fatty sub stances that are used to coat or encapsulate an inner core containing another drug. Some drugs used to treat epidemic KS are given in the form of liposomes. Opportunistic infections (OI)—Diseases caused by organisms that multiply to the point of produc ing symptoms only when the body’s immune sys tem is impaired.

the cases of epidemic KS in the United States have been diagnosed in homosexual or bisexual males. Epidemic KS is far more prevalent among homosexual or bisexual males with AIDS than among hemophiliacs or intravenous drug users with AIDS. Prior to 1995, about 26% of all homosexual males with AIDS had KS as their first symptom or eventually developed KS, as compared with fewer than 3% of heterosexual intravenous drug users with AIDS. This clustering of KS cases among a subpopulation of AIDS patients led to the hypothesis that a blood factor transmitted by sexual contact is a partial cause of KS. The number of new cases of AIDSrelated KS has declined in recent years, for reasons that are not yet clear. Some researchers think that the introduction of highly active antiretroviral therapy, G A LE EN CY C LO PE DI A O F C AN C ER 3

Causes and symptoms Causes GENETIC FACTORS. The role of genetic factors in KS varies across its five types. Classic KS is the only form associated with specific ethnic groups. In addition, patients with classic KS and immunosuppressive treatment-related KS have a higher incidence of a genetically determined immune factor called HLA-DR. MALE HORMONES. The fact that all forms of KS

affect men more often than women may indicate that androgens (male sex hormones) may be a factor in the development of KS. IMMUNOSUPPRESSION. In addition to organ transplant patients receiving immunosuppressive drugs, patients who are taking high-dose corticosteroids are also at increased risk of developing KS. INFECTIOUS AGENTS. Some researchers think that cytomegalovirus (CMV) and human papilloma virus (HPV) may be involved in the development of KS because fragments of these two types of virus have been found in KS tumor samples. The most likely candidate for an infectious agent, however, is human herpesvirus 8 (HHV-8), which is sometimes called KSassociated herpesvirus (KSHV). Fragments of the HHV-8 genome were first detected in 1994 by using a technique based on polymerase chain reaction (PCR) analysis. HHV-8 belongs to a group of herpesviruses called rhadinoviruses, and is the first herpesvirus of this subtype to be found in humans. HHV-8 is, however, closely related to the human herpesvirus called EpsteinBarr virus (EBV). EBV is known to cause infectious mononucleosis as well as tumors of the lymphatic system, and may be involved in other malignancies, including the African form of Burkitt’s lymphoma, Hodgkin’s disease, and nasopharyngeal cancer. HHV-8 has been found in tissue samples from patients with African KS, classic KS, and immunosuppression treatment-related KS as well as epidemic KS. HHV-8 is also associated with a rare non-cancerous disease called Castleman’s disease, which affects the lymph nodes. Some KS patients have been found to have KS and Castleman’s disease occurring together in the same lymph node. OTHER CAUSES. Some practitioners of alternative

medicine regard environmental toxins, psychological distress, and constitutional weaknesses as probable or G A LE EN CY C LO PE DI A O F C AN CE R 3

partial causes of KS. These theories are discussed in more detail under the heading of alternative treatments. Symptoms CLASSIC KS. The symptoms of classic KS include one or more reddish or purplish patches or nodules on one or both legs, often on the ankles or soles of the feet. The lesions slowly enlarge over a period of 10-15 years, with additional lesions sometimes developing. It is rare for classic KS to involve the patient’s internal organs, although bleeding from the digestive tract sometimes occurs. About 34% of patients with classic KS eventually develop non-Hodgkin’s lymphoma or another primary cancer. AFRICAN KS. The symptoms of the indolent form of African KS resemble those of classic KS. The aggressive form, however, produces tumors that may penetrate the tissue underneath the patient’s skin, and even the underlying bone. EPIDEMIC KS. Epidemic KS has more varied presentations than the four other types of KS. Its onset is usually, though not always, marked by the appearance of widespread lesions at many different points on the patient’s skin and in the mouth. Most HIV-infected patients who develop KS skin and mouth lesions feel healthy and have no systemic symptoms. On the other hand, KS may affect the patient’s lymph nodes or gastrointestinal tract prior to causing skin lesions.

Patients with epidemic KS almost always develop disseminated (widely spread) disease. The illness progesses from a few localized lesions to lymph node involvement and further spread to other organs. Disseminated KS is defined by the appearance of one or more of the following: a count of 25 or more external lesions; the appearance of 10 or more new lesions per month; and the appearance of visible lesions in the patient’s lungs or stomach lining. In some cases, disseminated KS causes painful swelling (edema) of the patient’s feet and lower legs. The lesions may also cause the surrounding skin to ulcerate or develop secondary infections. The spread of KS to the lungs, called pleuropulmonary KS, usually occurs at a late stage of the disease. KS involvement of the lungs causes bleeding, coughing, shortness of breath, and eventual respiratory failure. Most patients who die directly of KS die from its pleuropulmonary form.

Diagnosis Physical examination and patient history The diagnosis of any form of KS requires a careful examination of all areas of the patient’s skin. Even 771

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or HAART, is related to the decline in the number of cases of epidemic KS. Only about 12% of AIDS patients develop KS. Non-epidemic, gay-related KS. This small group of KS patients is entirely male.

Kaposi’s sarcoma

though the characteristic lesions of classic KS appear most frequently on the legs, all forms of KS can produce lesions on any area of the skin. An experienced doctor, who may be a dermatologist, an internist, or a primary care physician, can make a tentative diagnosis of KS on the basis of the external appearance of the skin lesions (size, shape, color, and location on the face or body), particularly when they are accompanied by evidence of lymph node involvement, internal bleeding, and other symptoms associated with disseminated KS. The doctor may touch or press on the lesions to find out whether they turn pale (blanch) ; KS plaques and nodules do not blanch under fingertip pressure. In addition, KS lesions are not painful when they first appear. Other signs of KS may appear on the soft palate or the membrane covering the eye (conjunctiva). In addition, the doctor will press on the patient’s abdomen in order to detect any masses in the liver or spleen. A thorough history is necessary in order to determine whether the patient’s ethnic background, lifestyle, or medical history places him or her in a high-risk category for KS. Biopsy A definitive diagnosis of KS requires a skin biopsy in order to rule out bacillary angiomatosis, a bacterial infection resembling cat-scratch disease. It is caused by a bacillus, Bartonella henselae. Collecting a tissue sample for a biopsy is not difficult if the patient has skin lesions, but can be complicated if the nodules are primarily internal. An endoscopy of the upper end of the digestive tract may be performed in order to obtain a tissue sample from an internal KS lesion. Under the microscope, an AIDS-related KS lesion will show an unusually large number of spindleshaped cells mixed together with small capillaries. The origin of the spindle-shaped cells is still unknown. The tumor cells in a KS lesion resemble smooth muscle cells or fibroblasts, which are cells that help to form the fibers in normal connective tissue. If the patient’s lymph nodes are enlarged, a biopsy may be done in order to rule out other causes of swollen lymph nodes.

 



Treatment team KS patients may receive treatment for skin lesions from a dermatologist or radiologist as well as treatment for lung or lymphatic involvement from internists or primary care practitioners. A surgeon may be called in to remove lesions in the digestive tract if they are bleeding or blocking the passage of food. Children with KS may be treated by pediatricians or by primary care physicians who specialize in treating AIDS patients.

Clinical staging, treatments, and prognosis Staging The NIH recommends individualized staging of patients with classic KS, due to the age of most patients, the localized nature of the lesions, the slow progression of the disease, and the low risk of spread to the internal organs. The criteria for staging epidemic KS have evolved over the past decade in response to changes in the treatment of HIV infection and to the recognition that KS does not fit well into standard categories of tumor assessment. Several different systems have been used to stage epidemic KS, but none is completely satisfactory. NYU STAGING SYSTEM. One staging system that originated at New York University divides KS patients into four groups according to the following symptom clusters: 





Other tests Other diagnostic tests may be performed if the patient appears to have disseminated KS. These tests include: 

Chest x ray. A radiograph of the patient’s lungs will show patchy areas of involved tissue.

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Gallium scan. The results will be negative in KS. Bronchoscopy. This procedure allows the doctor to examine the patient’s bronchial pathways for visible KS lesions. It is not, however, useful for obtaining tissue samples for biopsy. Endoscopy. Examination of the patient’s stomach allows the doctor to examine the mucous lining for KS lesions as well as to obtain a tissue sample.



Skin lesions that are indolent (slow-growing) and limited to relatively small areas of the body. Skin lesions limited to specific regions of the body but aggressive in growth. There may or may not be involvement of lymph nodes. General involvement of the skin and mucous membranes, with or without lymph node involvement. Involvement of the internal organs.

AIDS CLINICAL TRIALS GROUP (ACTG) STAGING SYSTEM. The ACTG Oncology Committee published a

staging system for epidemic KS in 1989. This system was reevaluated in 1995 and is undergoing continued assessment. It is based on three criteria: extent of G A LE EN CY C LO PE DI A O F C AN C ER 3







Tumor (T): Good risk (0) is a tumor limited to the skin and/or lymph nodes and/or minimal oral disease (limited to the palate). Poor risk (1) is any of the following: edema associated with the tumor; widespread KS in the mouth; KS in the digestive tract; KS in other viscera. Immune system (I): Good risk (0) is a CD4 cell count greater than 200 per cubic millmeter. Poor risk (1) is a CD4 cell count lower than 200 per cubic millimeter. Systemic illness (S): Good risk (0) is no history of opportunistic infections (OI) or thrush; no ‘‘B’’ symptoms (unexplained fever, night sweats, diarrhea lasting more than 2 weeks, weight loss greater than 10%); performance status above 70 on the Karnofsky scale. Poor risk (1) is any of the following: history of OI or thrush; presence of ‘‘B’’ symptoms; Karnofsky score lower than 70; and other HIV-related illnesses. Treatment

Treatment of KS depends on the form of the disease. CLASSIC KS. Radiation therapy is usually quite effective if the patient has small lesions or lesions limited to a small area of skin. Low-voltage photon radiation or electron beam therapy give good results. Surgical removal of small lesions is sometimes done, but the lesions are likely to recur. The best results are obtained from surgical treatment when many small lesions are removed over a period of years.

For widespread skin disease, radiation treatment with electron beam therapy is recommended. Classic KS has not often been treated with chemotherapy in the United States, but some researchers report that treatment with vinblastine or vincristine has been effective. Disease that has spread to the lymph nodes or digestive tract is treated with a combination of chemotherapy and radiation treatment. IMMUNOSUPPRESSIVE

TREATMENT-RELATED

KS.

The standard pattern of therapy for this form of KS begins with discontinuing the immunosuppressive medications if they are not essential to the patient’s care. Treatment of the KS itself may include radiation therapy if the disease is limited to the skin, or single- or multiple-drug chemotherapy. EPIDEMIC KS. As of 2001, there is no cure for epidemic KS. Treatment is aimed at reducing the size of skin lesions and alleviating the discomfort of open ulcers or swollen tissue in the legs. There are no data

G A LE EN CY C LO PE DI A O F C AN CE R 3

that indicate that treatment prolongs the survival of patients with epidemic KS. In addition to treatment of the KS itself, these patients also need ongoing retroviral therapy and treatment of any opportunistic infections that may develop. An additional complication in treating epidemic KS is that highly active antiretroviral therapy, or HAART, is not the ‘‘magic bullet’’ that some had hoped when it was introduced in 1998. HAART uses three- or four-drug combinations to treat HIV infection. Problems with HAART include severe psychiatric as well as physical side effects, in addition to the patient’s risk of developing a drugresistant form of HIV if even one dose of medication is missed. The complex dosing schedules as well as the medication side effects make it difficult to assess the effectiveness of treatments aimed at the KS by itself. Small KS lesions respond very well to radiation treatment. They can also be removed surgically or treated with cryotherapy, a technique that uses liquid nitrogen to freeze the lesion. Lesions inside the mouth (on the palate) can be treated with injections of vinblastine. In addition, the patient may be given topical alitretinoin (Panretin gel), which is applied directly to the lesions. Alitretinoin received FDA approval for treating KS in 1999. Systemic treatments for epidemic KS consist of various combinations of anti-cancer drugs, including vincristine (Oncovin), vinblastine (Velban), bleomycin (Blenoxane), doxorubicin (Adriamycin), daunorubicin (DaunoXome), interferon-alpha (Intron A, RoferonA), etoposide (VePesid), or paclitaxel (Taxol). The effectiveness of systemic treatments ranges from 50% for high-dose therapy with interferon-alpha to 80% for combinations of vincristine, vinblastine, bleomycin, doxorubicin, and etoposide. The drawbacks of systemic treatment include the toxicity of these drugs and their many side effects. Interferon-alpha can be given only to adult patients with relatively intact immune systems and no signs of lymphatic involvement. The side effects of systemic chemotherapy include hair loss (alopecia), nausea and vomiting, fatigue, diarrhea, headaches, loss of appetite (anorexia), allergic reactions, back pain, abdominal pain, and increased sweating. As of 2005, the standard for first-line treatment of epidemic KS is one of the FDA-approved anthracyclines such as liposomal doxorubicin (Doxil) or liposomal daunorubicin (DaunoXome), rather than a combination drug regimen. Liposomes are small sacs consisting of an outer layer of fatty substances used to coat an inner core of another medication. In addition to concentrating the drug’s effects on the tumor, liposomes moderate the side effects. 773

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tumor; condition of the patient’s immune system; and presence of systemic illness:

Kaposi’s sarcoma

In 1997, the FDA approved paclitaxel (Taxol) for epidemic KS resistant to treatment. Paclitaxel is a drug derived from the bark of the Pacific yew tree that prevents the growth of cancer cells by preventing the breakdown of normal cell structures called microtubules. After paclitaxel treatment, cancer cells become so clogged with microtubules that they cannot grow and divide. The drug has serious side effects, most notably suppression of the patient’s bone marrow. Experimental treatments for AIDS-related KS include retinoic acid, which is derived from vitamin A; and other drugs that inhibit the formation of new blood vessels (angiogenesis) in tumors. The reason for inhibiting angiogenesis is that new blood vessels keep a cancer supplied with oxygen and nutrients, which help the cancer grow and spread to other parts of the body. Antiangiogenic agents that have been proposed for treating KS include Fumagillin, SP-PG, and Platelet 4 factor. As of 2005, the effectiveness of these substances in humans is not yet known. Approval by the Food and Drug Administration will require several years after the test results are known. Prognosis The prognosis of KS varies depending on its form. Patients with classic KS often survive for many years after diagnosis; death is often caused by another cancer, such as non-Hodgkin’s lymphoma, rather than the KS itself. The aggressive form of African KS has the poorest prognosis, with a fatality rate of 100% within three years of diagnosis. Patients with immunosuppressive treatment-related KS have variable prognoses; in many cases, however, the KS goes into remission once the immune-suppressing drug is discontinued. The prognosis of patients with epidemic KS also varies, depending on the patient’s general level of health. As a rule, patients whose KS has spread to the lungs have the poorest prognosis. Alternative and complementary therapies SHARK CARTILAGE. The only alternative treatment

for epidemic KS that has been evaluated by the NIH is shark cartilage. Shark cartilage products are widely available in the United States as over-the-counter (OTC) preparations that do not require FDA approval. A 1995 review of alternative therapies found more than 40 brand names of shark cartilage products for sale in the United States to treat arthritis and psoriasis as well as KS. The cartilage can be taken by mouth or by injection. The use of shark cartilage to treat KS derives from a popular belief that sharks and other cartilaginous 774

fish (skates and rays) do not get cancer. This belief is countered by findings from samples of captured sharks that they do in fact develop various kinds of tumors. There are three explanations of the role of shark cartilage in preventing KS. Some researchers have proposed that it kills cancer cells directly. A second explanation is that cartilage stimulates the human immune system. The third theory, which has more evidence in its favor than the first two, is that the cartilage slows down or prevents angiogenesis. Two complex proteins in shark cartilage, identified as U995 and SCF2, have been shown to inhibit angiogenesis in laboratory studies. As of December 2000, only three studies using human subjects had been published; the results were inconclusive. The complete results of three other studies using shark cartilage in human subjects have not yet been published in complete form. Preliminary reports of NIH-sponsored clinical trials are also not yet available; however, all three studies being currently conducted have received the lowest rating (3iii) for the statistical strength of the study’s design. The side effects of treatment with shark cartilage include mild to moderate nausea, vomiting, abdominal cramps, constipation, low blood pressure, abnormally high levels of blood calcium (hypercalcemia), and general feelings of weakness. OTHER ALTERNATIVE THERAPIES. Other alternative treatments for KS are aimed almost completely at epidemic KS. Most are based on assumptions that AIDS victims have had their immune systems weakened by such environmental toxins as lead and radioactive materials, or by psychological stress generated by societal disapproval of homosexuality. Naturopaths would add such life-style stresses as the use of tobacco and alcohol, as well as poor sleep patterns and nutritional deficiencies. Homeopaths believe that AIDS is the product of hereditary predispositions to disease called miasms, specifically two miasms related to syphilis and gonorrhea respectively.

Alternative topical treatments for the skin lesions of AIDS-related KS include homeopathic preparations made from periwinkle, mistletoe, or phytolacca (poke root). Other alternative skin preparations include a selenium solution made from aloe gels, selenium, and tincture of silica; a mixture of aloe vera and dried kelp (seaweed); and a mixture of aloe vera, tea tree oil, and tincture of St. John’s wort. Alternative treatments for KS lesions on the internal organs include a mixture of warm wine and Yunnan Paiyao powder, a Chinese patent medicine made from ginseng; castor oil packs; or a three-to seven-day grape fast repeated every 120 days. G A LE EN CY C LO PE DI A O F C AN C ER 3







Naturopathic remedies: High doses of vitamin C, zinc, echinacea, or goldenseal to improve immune function; or preparations of astragalis, osha root, or licorice to suppress the HIV virus. Homeopathic remedies: These include a homeopathic preparation of cyclosporine and another made from a dilution of killed typhoid virus. Ozone therapy: There are isolated reports from Europe and the United States of AIDS-related KS going into several months of remission after treatment with ozone given via rectal insufflation.

Alternative treatments aimed at improving the quality of life for KS patients include Reiki, reflexology, meditation, and chromatherapy.

Coping with cancer treatment Studies of treatment side effects in patients with epidemic KS are complicated by the difficulty of distinguishing between side effects caused by treatment aimed at the HIV retrovirus itself and those caused by treatment for KS. Common problems related to KS treatment include damage to the bone marrow, hair loss, and nerve damage from medications. Other treatment-related problems include weight loss due to poor appetite, and swelling of body tissues due to fluid retention. Patients may be given nutritional counseling, medications to stimulate the appetite, and radiation treatment or diuretics to reduce the level of fluid in the tissues.

Clinical trials By 2009, there are 21 open and active clinical trials being conducted for treatments for KS, twelve for epidemic KS and one for unspecified KS. Some of these are comparing the relative effectiveness of doxorubicin, daunorubicin, and paclitaxel. Others are studies of other agents, including interleukin-11, interleukin-12, cidofovir, and filgrastim. One is a study of the effects of HAART on AIDS-related KS. The National Cancer Institute (NCI) reported that clinical trials of thalidomide indicated that the drug has some activity against epidemic KS. Updated information about the content of and patient participation in clinical trials can be obtained at the web site of the National Cancer Institute: http://cancertrials.nci.nih.gov.

Prevention The only known preventive strategy for reducing one’s risk for epidemic KS is abstinence from intercourse G A LE EN CY C LO PE DI A O F C AN CE R 3

or modification of sexual habits. Homosexual or bisexual males can reduce their risk of developing KS by avoiding passive anal intercourse. Women can reduce their risk by avoiding vaginal or anal intercourse with bisexual males. Kidney transplant patients who are at increased risk of developing KS as a result of taking prednisone or other immunosuppressive drugs should consult their primary physician about possible changes in dosage.

Special concerns The two special concerns most likely to arise with epidemic KS are social isolation due to the disfigurement caused by KS lesions on the patient’s face, and spiritual or psychological concerns related to the tumor’s connection to AIDS and homosexuality. There are many local and regional support groups for cancer patients that can help patients deal with concerns about appearance. With regard to religious/ spiritual issues, most major Christian and Jewish bodies in the United States and Canada have task forces or working groups dealing with AIDS-related concerns. The National Catholic AIDS Network (NCAN) maintains an information database and web site (http://www.ncan.org) and accepts call-in referrals at (707) 874-3031. Resources BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Hematology and Oncology.’’ Section 11 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004. Kubota, Marshall K., MD. ‘‘Human Immunodeficiency Virus Infection and Its Complications,’’ In Conn’s Current Therapy, edited by Robert E. Rakel, MD. Philadelphia: W. B. Saunders Company, 2000. PERIODICALS

Correspondence: Kaposi’s Sarcoma. New England Journal of Medicine 343, no. 8 (August 24, 2000). San Francisco AIDS Foundation. Bulletin of Experimental Treatments for AIDS. ORGANIZATIONS

AIDS Clinical Trials Group (ACTG). c/o William Duncan, PhD, National Institutes of Health. 6003 Executive Boulevard, Room 2A07, Bethesda, MD 20892. American Cancer Society (ACS). 1599 Clifton Road, NE, Atlanta, GA 30329. (404) 320 3333 or (800) ACS 2345. Fax: (404) 329 7530. Web site: http://www.cancer.org. National Cancer Institute, Office of Cancer Communica tions. 31 Center Drive, MSC 2580, Bethesda, MD 20892 2580. (800) 4 CANCER (1 800 422 6237). TTY: (800) 332 8615. Web site: http://www.nci.nih.gov. NIH National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P. O. Box 8218, 775

Kaposi’s sarcoma

Alternative systemic treatments for AIDS-related KS include:

Ki67

Silver Spring, MD 20907 8218. TTY/TDY: (888) 644 6226. Fax: (301) 495 4957. San Francisco AIDS Foundation (SFAF). 995 Market Street, #200, San Francisco, CA 94103. (415) 487 3000 or (800) 367 AIDS. Fax: (415) 487 3009. Web site: http://www.sfaf.org.

Rebecca J. Frey, Ph.D.

Ketoconazole see Antifungal therapy

Ki67 Definition Ki67 is a molecule that can be easily detected in growing cells in order to gain an understanding of the rate at which the cells within a tumor are growing.

Purpose Detection of Ki67 is carried out on biopsies, samples of tumor tissue. The goal of this assay is to evaluate an important characteristic of the cells within the tumor, the percentage of tumor cells that are actively dividing and giving rise to more cancer cells. The number obtained through this examination is termed the S-phase, growth, or proliferative fraction. This information can play an important part in deciding the best treatment for a cancer patient.

Precautions This test is performed on tissue or cells that have been removed during the initial surgery or diagnostic procedure used to determine the precise nature of the cancer. It usually does not require any new surgery or blood draw on the patient and, so, does not entail any additional precautions for the patient.

Description Cancer is a group of diseases characterized by abnormal, or neoplastic, cellular growth in particular tissues. In many instances this growth is abnormal because cells are growing more rapidly than is normal. This unregulated growth is how a tumor is formed. A tumor is more or less a collection of cells that grow more rapidly than the surrounding normal tissue. Most importantly, this difference in growth rate is central to how many cancer drugs, termed cytotoxic agents, work. The ability of these drugs to eliminate cancer cells depends on their ability to kill cells that are actively proliferating, but do less damage to cells that 776

KEY T ERMS Immunocytochemistry—Method for staining cells or tissues using antibodies so that the location of a target molecule can be determined Nucleus—The part of the cell containing chromosomes S phase—The part of the cell division cycle during which the genetic material, DNA, is duplicated

are not actively dividing. This makes it useful to know how actively the cells in tumor are growing compared to the surrounding tissue. The measurement of Ki67 is one of the most common ways to measure the growth fraction of tumor cells. This molecule can be detected in the nucleus of only actively growing cells. Analysis of Ki67 in tumors is accomplished by a pathologist who examines a piece of the tumor tissue using special techniques. The technique used is termed immunocytochemistry. This involves the preparation of a histologic section, a very thin piece of tumor tissue placed on a glass microscope slide. These kinds of tissue sections are used in the diagnosis of cancer. In the case of Ki67 assays, the section is incubated with antibodies that can react with the Ki67 molecule, and then treated with special reagents that cause a color to appear where antibody has bound. In this way, when the pathologist looks at the section using a microscope the fraction of growing cells, whose nuclei are stained for Ki67, can be determined for the tumor cells and compared with the normal tissue. In some instances, depending on the particular type of cancer, the pathologist might feel it more appropriate to use a different technique to assess the growth fraction for a specific tumor or leukemia.

Preparation, Aftercare, and Risks Because this test is performed on tissue or cells that had been removed during an initial biopsy or other diagnostic procedure, and because no new surgery or sample is required, no additional recommendations regarding preparation, aftercare, or risks are necessary.

Results The proliferative or growth fraction as determined by Ki67 analysis is interpreted in view of what is normal for the tissue in which the tumor has been found or from which it originated. In the case of certain types of tissue—for example, brain—there is little cellular growth in normal tissue. In other cases, G A LE EN CY C LO PE DI A O F C AN C ER 3

Kidney cancer

QUESTIONS TO ASK THE DOCTOR 





How far from normal is the Ki 67 labeling index of my tumor? To what extent is this result influencing the treatment I will receive? In your experience, does the proliferative fraction of my tumor predict a good response to chemotherapy?

such as breast or the cells that line the colon, cellular growth is a normal part of the function of that tissue. The significance of an increased proliferative fraction is interpreted in light of the experience of the oncologist as well as the knowledge and experience of other clinicians as reported in the medical literature. The Ki67 result, often termed the ‘‘Ki67 labeling index,’’ can be used in some cases as a prognostic indicator for some cancers. For example, for brain tumors, such as astrocytomas and glioblastomas, a high Ki67 labeling index is one factor that predicts a poor prognosis. For breast tumors, the clinician will consider the proliferative fraction in conjunction with other factors such as patient age, results of receptor assays, and whether or not there is evidence of spread of the disease to lymph nodes or other sites within the body. The value of Ki67 is not as firmly established for other cancers such as bladder or pituitary tumors. Resources PERIODICALS

Chassevent, A., et al. ‘‘S Phase Fraction and DNA Ploidy in 633 T1T2 Breast Cancers: A Standardized Flow Cytometric Study.’’ Clinical Cancer Research 7 (2001): 909 17.

Warren Maltzman, Ph.D.

An extracted cancerous kidney. (Photo by Robert Riedlinger. Custom Medical Stock Photo. Reproduced by permission.)

Background of illustration and to left: a pair of kidneys. One kidney is normal, while the other is cancerous. The foreground of the illustration and in color: a cutaway of the cancerous kidney. (Custom Medical Stock Photo. Reproduced by permission.)

of kidney cancer. Eighty-five percent of all kidney tumors are renal cell carcinomas. Wilms’ tumor is a rapidly developing cancer of the kidney most often found in children under four years of age.

Description

Kidney cancer Definition Kidney cancer is a disease in which the cells in certain tissues of the kidney start to grow uncontrollably and form tumors. Renal cell carcinoma, sometimes referred to as hypernephroma, occurs in the cells lining the kidneys (epithelial cells). It is the most common type G A LE EN CY C LO PE DI A O F C AN CE R 3

The kidneys are a pair of organs shaped like kidney beans that lie on either side of the spine just above the waist. Inside each kidney are tiny tubes (tubules) that filter and clean the blood, taking out the waste products and making urine. The urine that is made by the kidney passes through a tube called the ureter into the bladder. Urine is held in the bladder until it is discharged from the body. Renal cell carcinoma (RCC) generally develops in the lining of the tubules 777

Kidney cancer

K E Y TE R M S Biopsy—The surgical removal and microscopic examination of living tissue for diagnostic purposes. Bone scan—An x-ray study in which patients are given an intravenous injection of a small amount of a radioactive material that travels in the blood. When it reaches the bones, it can be detected by x ray to make a picture of their internal structure. Chemotherapy—Treatment with anticancer drugs. Computed tomography (CT) scan—A medical procedure in which a series of x-ray images are made and put together by a computer to form detailed pictures of areas inside the body. Cryoablation—A technique for removing tissue by destroying it with extreme cold. Hematuria—Blood in the urine. Immunotherapy—Treatment of cancer by stimulating the body’s immune defense system. Intravenous pyelogram (IVP)—A procedure in which a dye is injected into a vein in the arm. The

that filter and clean the blood. Cancer that develops in the central portion of the kidney (where the urine is collected and drained into the ureters) is known as transitional cell carcinoma of the renal pelvis. Transitional cell cancer is similar to bladder cancer. Wilms’ tumor is the most common type of childhood kidney cancer and is distinct from kidney cancer in adults. Background of illustration and to left: a pair of kidneys. One kidney is normal, while the other is cancerous. The foreground of the illustration and in color: a cutaway of the cancerous kidney.

dye travels through the body and concentrates in the urine to be discharged. It outlines the kidneys, ureters, and the urinary bladder. An x-ray image is then made and any abnormalities of the urinary tract are revealed. Magnetic resonance imaging (MRI)—A medical procedure used for diagnostic purposes in which pictures of areas inside the body can be created using a magnet linked to a computer. Nephrectomy—A medical procedure in which the kidney is surgically removed. Primary tumor—A cancer’s origin or initial growth. Radiation therapy—Treatment with high-energy radiation from x-ray machines, cobalt, radium, or other sources. Renal ultrasound—A painless and non-invasive procedure in which sound waves are bounced off the kidneys. These sound waves produce a pattern of echoes that are then used by the computer to create pictures of areas inside the kidney (sonograms).

Causes and symptoms The causes of kidney cancer are unknown, but there are many risk factors associated with kidney cancer. The risk factors listed from greatest to smallest include:      

Demographics Kidney cancer accounts for approximately 2–3% of all cancers. In the United States, kidney cancer is the tenth most common cancer and the incidence has increased by 43% since 1973; the death rate has increased by 16%. According to the American Cancer Society, 57,760 Americans will be diagnosed with kidney cancer in 2009, and 12,980 died from the disease. RCC accounts for 90–95% of malignant neoplasms that originate from the kidney. Kidney cancer occurs most often in men over the age of 40. The median age of diagnosis is 65. The male:female ratio is about 3:2. 778

       

von Hippel-Lindau disease (>100) chronic dialysis (32) obesity (3.6) tobacco use (2.3) first-degree relative with kidney cancer (1.6) hypertension (1.4) occupational exposure to dry cleaning solvents (1.4) diuretics(non-hypertension use) (1.3) trichloroethylene exposure (1.0) heavy phenacetin use (1.1–6.0) polycystic kidney disease (0.8–2.0) cadmium exposure (1.0–3.9) arsenic exposure (1.6) asbestos (1.1–1.8)

The most common symptom of kidney cancer is blood in the urine (hematuria). Other symptoms include painful urination, pain in the lower back or on the sides, abdominal pain, a lump or hard mass that G A LE EN CY C LO PE DI A O F C AN C ER 3

   







  



What should I expect from a biopsy test? What type of kidney cancer do I have? What is the stage of the disease? What are the treatment choices? Which do you recommend? Why? What are the risks and possible side effects of each treatment? What are the chances that the treatment will be successful? What new treatments are being studied in clinical trials? How long will treatment last? Will I have to stay in the hospital? Will treatment affect my normal activities? If so, for how long? What is the treatment likely to cost?

A kidney biopsy is used to positively confirm the diagnosis of kidney cancer. During this procedure, a small piece of tissue is removed from the tumor and examined under a microscope. The biopsy will give information about the type of tumor, the cells that are involved, and the aggressiveness of the tumor (tumor stage).

Staging, treatment, and prognosis Staging Staging guidelines for kidney cancer are as follows (2.5 cm equals approximately 1 in): 

can be felt in the kidney area, unexplained weight loss, fever, weakness, fatigue, and high blood pressure.



Diagnosis A diagnostic examination for kidney cancer includes taking a thorough medical history and making a complete physical examination in which the doctor will probe (palpate) the abdomen for lumps. Blood tests will be ordered to check for changes in blood chemistry caused by substances released by the tumor. Laboratory tests may show abnormal levels of iron in the blood. Either a low red blood cell count (anemia) or a high red blood cell count (erythrocytosis) may accompany kidney cancer. Occasionally, patients will have high calcium levels. If the doctor suspects kidney cancer, an intravenous pyelogram (also called an IVP or intravenous urography) may be ordered. An IVP is an x-ray test in which a dye is injected into a vein in the arm. The dye travels through the body, and when it is concentrated in the urine to be discharged, it outlines the kidneys, ureters, and the urinary bladder. On an x-ray image, the dye will reveal any abnormalities of the urinary tract. The IVP may miss small kidney cancers. Renal ultrasound is a diagnostic test in which sound waves are used to form an image of the kidneys. Ultrasound is a painless and non-invasive procedure that can be used to detect even very small kidney G A LE EN CY C LO PE DI A O F C AN CE R 3





Stage I: Primary tumor is 5 cm or less in greatest dimension and is limited to the kidney, with no lymph node involvement. Stage II: Primary tumor is larger than 5 cm in greatest dimension and is limited to the kidney, with no lymph node involvement. Stage III: Primary tumor may extend into major veins or invade adrenal glands or perinephric tissues, but not beyond Gerota’s fascia. There may be metastasis in a single lymph node. Stage IV: Primary tumor invades beyond Gerota’s fascia. Metastasis in more than one lymph node. Possible metastasis to distant structures in the body. Treatment

Each person’s treatment is different and depends on several factors. The location, size, and extent of the tumor have to be considered in addition to the patient’s age, general health, and medical history. In addation, much has changed in the treatment and management of kidney cancer since the 1980s, including new surgical techniques, new anticancer drugs, and the development of effective treatments for advanced disease. The primary treatment for kidney cancer that has not spread to other parts of the body, which is a Stage I, II, or III tumor, is surgical removal of the diseased kidney (nephrectomy). Because most cancers affect only one kidney, the patient can function well with the remaining one. Two types of surgical procedure are used. Radical nephrectomy removes the entire 779

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tumors. Imaging tests such as computed tomography (CT) scans and magnetic resonance imaging (MRI) can be used to evaluate the kidneys and the surrounding organs. These tests are used to check whether the tumor has spread outside the kidney to other organs in the abdomen. If the patient complains of bone pain, a special x ray called a bone scan may be ordered to rule out spread to the bones. A chest x ray may be taken to rule out spread to the lungs.

Kidney cancer

kidney and the surrounding tissue. Sometimes, the lymph nodes surrounding the kidney are also removed. Partial nephrectomy removes only part of the kidney along with the tumor. This procedure is used either when the tumor is very small or when it is not practical to remove the entire kidney. It is not practical to remove a kidney when the patient has only one kidney or when both kidneys have tumors. There is a small (5%) chance of missing some of the cancer. Nephrectomy can also be useful for Stage IV cancers, but alternative surgical procedures such as transarterial angioinfarction may be used.

the most promising systemic therapy for metastatic kidney cancer.

The rapid development and widespread use of laparoscopic techniques has made it possible for surgeons to remove small tumors while sparing the rest of the kidney. Most tumors removed by laparoscopy are 4 cm (1.6 in) in size or smaller. Laparoscopy also allows the surgeon to remove small tumors with cryoablation (destroying the tumor by freezing it) rather than cutting.

There are several healing philosophies, approaches, and therapies that may be used as supplemental or instead of traditional treatments. All of the items listed may have varying effectiveness in boosting the immune system and/or treating a tumor. The efficacy of each treatment also varies from person to person. None of the treatments, however, have demonstrated safety or effectiveness on a consistent basis. Patients should research such treatments for any potential dangers (laetrile, for example, has caused death due to cyanide poisoning) and notify their physician before taking them.

Radiation therapy, which consists of exposing the cancer cells to high-energy gamma rays from an external source, generally destroys cancer cells with minimal damage to the normal tissue. Side effects are nausea, fatigue, and stomach upsets. These symptoms disappear when the treatment is over. In kidney cancer, radiation therapy has been shown to alleviate pain and bleeding, especially when the cancer is inoperable. However, it has not proven to be of much use in destroying the kidney cancer cells. Therefore radiation therapy is not used very often as a treatment for cancer or as a routine adjuvant to nephrectomy. Radiotherapy, however, is used to manage metastatic kidney cancer. Treatment of kidney cancer with anticancer drugs (chemotherapy) has not produced good results. However, new drugs and new combinations of drugs continue to be tested in clinical trials. One new drug, semaxanib (SU5416), is reported to have good results in treating patients with kidney cancer. As of 2004, however, semaxanib is still undergoing clinical trials in the United States. Immunologic therapy (or immunotherapy), a form of treatment in which the body’s immune system is harnessed to help fight the cancer, is a new mode of therapy that is being tested for kidney cancer. Clinical trials with substances produced by the immune cells (aldesleukin and interferon) have shown some promise in destroying kidney cancer cells. These substances have been approved for use but they can be very toxic and produce severe side effects. The benefits derived from the treatment have to be weighed very carefully against the side effects in each case. Immunotherapy is 780

Prognosis Because kidney cancer is often caught early and sometimes progresses slowly, the chances of a surgical cure are good. It is also one of the few cancers for which there are well-documented cases of spontaneous remission without therapy.

Alternative and complementary therapies

          

714-X antineoplastons Cancell cartilage (bovine and shark) coenzyme Q10 Gerson Therapy Gonzalez Protocol Hydrazine sulfate immuno-augementative therapy Laetrile mistletoe

Coping with cancer treatment Side effects of treatment, as well as nutrition, emotional well-being, and other complications, are all parts of coping with cancer. There are many possible side effects for a cancer treatment that include:         

constipation delirium fatigue fever, chills, sweats nausea and vomiting mouth sores, dry mouth, bleeding gums pruritus (itching) sexuality sleep disorders G A LE EN CY C LO PE DI A O F C AN C ER 3

Clinical trials As of 2009, the National Cancer Institute (NCI) listed many clinical trials in place across the United States studying new types of radiation therapy and chemotherapy, new drugs and drug combinations, biological therapies, ways of combining various types of treatment for kidney cancer, side effect reduction, and improving quality of life. Immunostimulatory agents and gene-therapy techniques that modify tumor cells, antiangiogenesis compounds, cyclin-dependent kinase inhibitors, and differentiating agents are all being investigated as possible therapies. One may consult http:// clinicaltrials.gov and a doctor for a list of kidney cancer clinical trials.

Prevention The exact cause of kidney cancer is not known, so it is not possible to prevent all cases. However, because a strong association between kidney cancer and tobacco has been shown, avoiding tobacco is the best way to lower one’s risk of developing this cancer. Using care when working with cancer-causing agents such as asbestos and cadmium and eating a well-balanced diet may also help prevent kidney cancer. See also Renal pelvis tumors; von Hippel-Lindau syndrome. Resources BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Renal Cell Carcinoma (Hypernephroma; Adenocar cinoma of the Kidney).’’ In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2007. PERIODICALS

Brauch, H., G. Weirich, B. Klein, et al. ‘‘VHL Mutations in Renal Cell Cancer: Does Occupational Exposure to Trichloroethylene Make a Difference?’’ Toxicology Letters 151 (June 15, 2004): 301 310. Dutcher, J.P. ‘‘Immunotherapy: Are We Making a Differ ence?’’ Current Opinion in Urology September 2000: 435 9.

G A LE EN CY C LO PE DI A O F C AN CE R 3

Godley, P.A., and K.I. Ataga. ‘‘Renal Cell Carcinoma.’’ Current Opinion in Oncology May 2000: 260 4. Griffiths, T. R., and J. K. Mellon. ‘‘Evolving Immunother apeutic Strategies in Bladder and Renal Cancer.’’ Post graduate Medical Journal 80 (June 2004): 320 327. Jennens, R. R., M. A. Rosenthal, G. J. Lindeman, and M. Michael. ‘‘Complete Radiological and Metabolic Response of Metastatic Renal Cell Carcinoma to SU5416 (Semaxanib) in a Patient with Probable von Hippel Lindau Syndrome.’’ Urologic Oncology 22 (May June 2004): 193 196. Lam, J. S., O. Svarts, and A. J. Pantuck. ‘‘Changing Con cepts in the Surgical Management of Renal Cell Carci noma.’’ European Urology 45 (June 2004): 692 705. Lotan, Y., D. A. Duchene, J. A. Cadeddu, et al. ‘‘Changing Management of Organ Confined Renal Masses.’’ Journal of Endourology 18 (April 2004): 263 268. Moon, T. D., F. T. Lee, Jr., S. P. Hedican, et al. ‘‘Laparo scopic Cryoablation under Sonographic Guidance for the Treatment of Small Renal Tumors.’’ Journal of Endourology 18 (June 2004): 436 440. OTHER

American Cancer Society (ACS). Cancer Facts & Figures 2004.http://www.cancer.org/downloads/STT/ CAFF_finalPWSecured.pdf. ORGANIZATIONS

American Cancer Society (National Headquarters). 1599 Clifton Rd. NE, Atlanta, GA 30329. (800) 227 2345. http://www.cancer.org. American Foundation for Urologic Disease. E mail: [email protected]. American Urological Association. 1120 N. Charles St., Bal timore, MD 21201. (410) 727 1100. http://www.auanet. org/patient_info/find_urologist/index.cfm. Cancer Research Institute (National Headquarters). 681 Fifth Ave., New York, NY 10022. (800) 992 2623. http://www.cancerresearch.org. Kidney Cancer Association. 1234 Sherman Ave., Suite 203, Evanston, IL 60202 1375. (800) 850 9132. http:// www.kidneycancerassociation.org. National Cancer Institute (NCI). 9000 Rockville Pike, Building 31, Room 10A16, Bethesda, MD 20892. (800) 422 6237. http://www.nci.nih.gov. National Kidney Cancer Association. 1234 Sherman Ave., Suite 203, Evanston, IL 60202 1375. (800) 850 9132. National Kidney Foundation. 30 East 33rd St., New York, NY 10016. (800) 622 9010. http://www.kidney.org.

Lata Cherath, Ph.D. Laura Ruth, Ph.D. Rebecca Frey, Ph.D.

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Anxiety, depression, loss, post-traumatic stress disorder, sexuality, and substance abuse are all possible emotional side-effects. Nutrition and eating before, during, and after a treatment can also be of concern. Other complications of coping with cancer include fever and pain.

L Lactulose see Laxatives

Description LEMS is a disorder characterized by muscular weakness and fatigue caused by a disruption of electrical impulses between the nerves and muscle cells. The disruption in turn results from an autoimmune process.

Lambert-Eaton myasthenic syndrome Definition Lambert-Eaton myasthenic syndrome (LEMS), sometimes called Eaton-Lambert syndrome, is a rare disorder affecting the muscles and nerves. LEMS is known to be associated with small-cell lung cancer. It may also be associated with such cancers as lymphoma, non-Hodgkin’s lymphoma, T-cell leukemia, non-small-cell lung cancer, prostate cancer, and thymoma. LEMS was first identified in 1956 by a team of three American neurologists, Lee Eaton, Edward Lambert, and Edward Rooke.

Demographics LEMS is a rare disorder; the number of people affected by it is at best an estimate. Various figures that have been given are that 400 people in the United States have the disorder at any one time. This figure does not include patients with LEMS who do not have cancer. About half of patients diagnosed with LEMS do not have cancer; this form of LEMS is called idiopathic LEMS, which means that its origin is unknown. Another estimate is that LEMS affects 3% of patients with small-cell lung cancer (SCLC), or about 4 people in every million. Between 50% and 70% of patients diagnosed with LEMS have an identifiable cancer of some type, the vast majority having SCLC. LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder. G A LE EN CY C LO PE DI A O F C AN CE R 3

About half of all cases of LEMS are associated with cancer, particularly small-cell lung cancer (SCLC). The other half of cases have no known cause and are called idiopathic LEMS. The disorder is typically slow in onset; it usually begins with a dry mouth and some weakness or aching in the legs, progressing to difficulty swallowing or holding up the head, problems in focusing the eyes, and general fatigue. LEMS chiefly affects the patient’s quality of life and ability to carry out everyday activities; patients with cancer-associated LEMS usually die from the cancer, not the muscle syndrome. Risk factors Risk factors for LEMS include:  



 

Being diagnosed with SCLC or another type of cancer. Age. LEMS is more common in middle-aged and older adults than in children and adolescents. The average age at diagnosis is 60 years. Sex. LEMS is slightly more common in men than in women. It is most likely to be diagnosed in men over 40. Having another autoimmune disorder. Smoking. All patients with SCLC diagnosed with LEMS have been found to be heavy smokers.

Causes and symptoms Causes The symptoms of LEMS are the result of an insufficient release of a neurotransmitter called acetylcholine at the junctions between the nerves and muscle cells. Acetylcholine is a chemical that passes signals from the nerve cells to the muscles in order for the muscles to 783

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move. The decreased level of acetylcholine causes a muscle reaction to the nerve signal that is lower than normal. The underlying cause of the lower-than-normal neurotransmitter release seen in LEMS patients is believed to be related to a disorder of the immune system (an autoimmune reaction). This autoimmune reaction is caused by antibodies produced by the patient in response to small-cell lung cancer or one of the other cancers associated with LEMS. Since continued use of the muscles may lead to a buildup of acetylcholine to normal levels, symptoms of LEMS can often be lessened or alleviated by using the affected muscles. Myasthenia gravis (MG), another disorder that has symptoms similar to LEMS, is caused by a blockage of neurotransmitters by antibodies. Symptoms of myasthenia gravis do not improve with continued muscle use. The improvement in symptoms that is observable in LEMS patients often helps to differentiate LEMS from myasthenia gravis. In contrast to MG, the symptoms of LEMS tend to be worse in the morning and improve toward evening with exercise and nerve stimulation. In addition, LEMS usually does not affect the muscles that control breathing as severely as MG does. LEMS is made worse by neuromuscular blocking agents used during surgery; certain antibiotics, such as the aminoglycosides and fluoroquinolones; magnesium; calcium channel blockers; and iodinated intravenous contrast agents used in medical imaging. Symptoms The symptoms of LEMS in cancer patients typically begin 2–4 years before the cancer is diagnosed. The primary symptom is muscular weakness or paralysis that varies in intensity and location throughout the body. Other symptoms of LEMS include tingling sensations on the skin, double vision, difficulty maintaining a steady gaze, and dry mouth or difficulty in swallowing. The first signs of LEMS tend to be a dry mouth and weakness or soreness in the legs. Some patients also complain of a metallic taste in the mouth as well as dryness. Later symptoms of LEMS include: changes in vision decreased posture and muscle tone  difficulty in chewing or swallowing  difficulty in climbing stairs  difficulty in lifting simple objects  speech impairment  impotence in men  a drooping head  fatigue  

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and/or a need to use the hands to get up from a sitting or lying position

Diagnosis LEMS is often misdiagnosed as myasthenia gravis because of the similarities between the symptoms of these two disorders. The diagnosis is usually made by a combination of chest x-rays (to detect lung cancer), blood tests for antibodies to the calcium channels at the ends of nerve fibers, and electrical stimulation tests. An increased response of muscle fibers to very high frequencies of electrical stimulation indicates LEMS rather than MS. If the doctor does not find a tumor within the first two years after the onset of the patient’s symptoms, the patient probably has idiopathic LEMS. Examination The doctor may notice drooping eyelids, a dry mouth, and weakness when the patient is asked to stand up. The patient’s reflexes will be weaker than normal, and the muscles may appear smaller than usual or wasted.

Treatment Traditional The goal of treatment for LEMS patients is to improve muscle strength while also treating the cancer or other underlying disorder that is causing LEMS. When possible, patients affected with LEMS should undergo a physical therapy program that is tailored to their health status and abilities. This may include stretching and flexibility manuevers as well as light strength and cardiovascular exercises. Symptoms of LEMS tend to be aggravated by prolonged exercise, so any physical therapy undertaken should be relatively short in duration. Some LEMS patients are not able to undergo physical therapy because of their current state of health. In these cases, plasmapheresis (also called plasma exchange), a procedure in which blood plasma is removed from the patient and replaced, may be recommended. This procedure can be effective in a majority of LEMS patients. Heat appears to worsen the symptoms of LEMS; patients typically feel much worse in hot weather and when they are running a fever. The doctor will usually advise the patient to take lukewarm rather than hot showers or baths. Drugs Medications that suppress the immune response or that suppress the antibodies responsible for the G A LE EN CY C LO PE DI A O F C AN C ER 3

QUESTIONS TO ASK YOUR DOCTOR 







Should I be tested for LEMS if I have an autoimmune disorder? What are the differences between LEMS and myasthenia gravis? What are my chances of developing LEMS after I have been diagnosed with cancer? Have you ever treated anyone with LEMS?

muscle weakness have also been shown to improve LEMS symptoms in some patients. These medications include high-dose intravenous immunoglobulin, azathioprine, and steroid drugs like prednisone. Another type of drug that has been shown to be beneficial is drugs that improve the transmission of nerve impulses to the muscles. These drugs include di-amino pyridine (DAP) and pyridostigmine bromide (Mestinon). Alternative and complementary therapies Yoga and other stretching exercises may be effective treatments for alleviating the physical symptoms of LEMS patients. Some LEMS patients also report improvement of symptoms after deep body massage or hydrotherapy.

Prognosis The most important prognostic factor for LEMS patients diagnosed with cancer is the prognosis of the cancer. People with idiopathic LEMS have a better prognosis than those with cancer; however, recovery of muscle strength varies from patient to patient. In general, patients whose symptoms progress more rapidly have a worse prognosis.

Prevention There is no way to prevent LEMS as of 2009 because its underlying cause is presently unknown. Resources BOOKS

Benatar, Michael. Neuromuscular Disease: Evidence and Analysis in Clinical Neurology. Totowa, NJ: Humana Press, 2006. Kalman, Bernadette, and Thomas H. Brannagan III. Neu roimmunology in Clinical Practice. Malden, MA: Blackwell Publishing, 2008. G A LE EN CY C LO PE DI A O F C AN CE R 3

Titulaer, M. J., et al. ‘‘Screening for Small cell Lung Cancer: A Follow up Study of Patients with Lambert Eaton Myasthenic Syndrome.’’ Journal of Clinical Oncology 26 (September 10, 2008): 4276 81. Ueda, T., et al. ‘‘Dropped Head Syndrome Caused by Lambert Eaton Myasthenic Syndrome.’’ Muscle and Nerve 40 (July 2009): 134 36. Weimer, M. B., and J. Wong. ‘‘Lambert Eaton Myasthenic Syndrome.’’ Current Treatment Options in Neurology 11 (March 2009): 77 84. Wirtz, P.W., et al. ‘‘ Efficacy of 3,4 diaminopyridine and Pyridostigmine in the Treatment of Lambert Eaton Myasthenic Syndrome: A Randomized, Double blind, Placebo controlled, Crossover Study.’’ Clinical Phar macology and Therapeutics 86 (July 2009): 44 48. OTHER

Kleinschmidt, Paul. ‘‘Lambert Eaton Myasthenic Syn drome.’’ eMedicine, February 15, 2007.http://emedici ne.medscape.com/article/792803 overview Medline Plus Medical Encyclopedia. Lambert Eaton Syn drome. http://www.nlm.nih.gov/medlineplus/ency/ article/000710.htm. National Institute of Neurological Disorders and Stroke (NINDS). Lambert Eaton Myasthenic Syndrome Infor mation Page. http://www.ninds.nih.gov/disorders/ lambert_eaton/lambert_eaton.htm. Stickler, David E., and Donald B. Sanders. ‘‘Lambert Eaton Myasthenic Syndrome.’’ eMedicine, January 20, 2009. http://emedicine.medscape.com/article/ 1170810 overview. ORGANIZATIONS

American Academy of Neurology (AAN), 1080 Montreal Avenue, Saint Paul, MN, 55116, 651 695 2717, 800 879 1960, 651 695 2791, http://www.aan.com/. American Physical Therapy Association (APTA), 1111 North Fairfax Street, Alexandria, VA, 22314 1488, 703 684 APTA (2782), 800 999 APTA (2782), 703 684 7343, http://www.apta.org//AM/Template.cfm? Section Home. National Institute of Neurological Disorders and Stroke (NINDS), P.O. Box 5801, Bethesda, MD, 20824, 800 352 9424, 301 496 5751, http://www.ninds.nih.gov/ index.htm. National Organization for Rare Disorders (NORD), P.O. Box 1968, Danbury, CT, 06813 1968, 203 744 0100, 800 999 NORD, 203 798 2291, http://www.rare diseases.org.

Paul A. Johnson, Ed.M. Rebecca J. Frey, PhD

Langerhans cell histiocytosis see Histiocytosis X 785

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PERIODICALS

Laparoscopy

Laparoscopy Definition Laparoscopy is a type of surgical procedure in which a small incision is made, usually in the navel, through which a viewing tube (laparoscope) is inserted. The viewing tube has a small camera on the eyepiece. This allows the doctor to examine the abdominal and pelvic organs on a video monitor connected to the tube. Other small incisions can be made to insert instruments to perform procedures. Laparoscopy can be done to diagnose conditions or to perform certain types of operations. It is less invasive than regular open abdominal surgery (laparotomy).

in the diagnosis, staging, and treatment for a variety of cancers. As of 2009, the use of laparoscopy to completely remove cancerous growths and surrounding tissues (in place of open surgery) is still debated. The procedure is being studied to determine if it is as effective as open surgery in complex operations. Laparoscopy is also being investigated as a screening tool for ovarian cancer. Laparoscopy is widely used in procedures for noncancerous conditions that in the past required open surgery, such as removal of the appendix (appendectomy) and gallbladder removal (cholecystectomy). Diagnostic procedure

Purpose Since the late 1980s, laparoscopy has been a popular diagnostic and treatment tool. The technique dates back to 1901, when it was reportedly first used in a gynecologic procedure performed in Russia. In fact, gynecologists were the first to use laparoscopy to diagnose and treat conditions relating to the female reproductive organs: uterus, fallopian tubes, and ovaries. Laparoscopy was first used with cancer patients in 1973. In these first cases, the procedure was used to observe and biopsy the liver. Laparoscopy plays a role

As a diagnostic procedure, laparoscopy is useful in taking biopsies of abdominal or pelvic growths, as well as lymph nodes. It allows the doctor to examine the abdominal area, including the female organs, appendix, gallbladder, stomach, and the liver. Laparoscopy is used to determine the cause of pelvic pain or gynecological symptoms that cannot be confirmed by a physical exam or ultrasound. For example, ovarian cysts, endometriosis, ectopic pregnancy, or blocked fallopian tubes can be diagnosed using this procedure. It is an important tool when trying to determine the cause of infertility. Operative procedure While laparoscopic surgery to completely remove cancerous tumors, surrounding tissues, and lymph nodes is used on a limited basis, this type of operation is widely used in noncancerous conditions that once required open surgery. These conditions include: 







This surgeon is performing a laparoscopic procedure on a patient. (Photo Researchers, Inc. Reproduced by permission.)

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Tubal ligation. In this procedure, the fallopian tubes are sealed or cut to prevent subsequent pregnancies. Ectopic pregnancy. If a fertilized egg becomes embedded outside the uterus, usually in the fallopian tube, an operation must be performed to remove the developing embryo. This often can be done with laparoscopy. Endometriosis. This is a condition in which tissue from inside the uterus is found outside the uterus in other parts of (or on organs within) the pelvic cavity. This can cause cysts to form. Endometriosis is diagnosed with laparoscopy, and in some cases the cysts and other tissue can be removed during laparoscopy. Hysterectomy. This procedure to remove the uterus can, in some cases, be performed using laparoscopy. The uterus is cut away with the aid of the laparoscopic G A LE EN CY C LO PE DI A O F C AN C ER 3

    





 

Whate is your complication rate? What is the purpose of this procedure? How often do you do laparoscopies? What type of anesthesia will be used? Will a biopsy be taken during the laparoscopy if anything abnormal is seen? If more surgery is needed, can it be done with a laparoscope? What area will be examined with the laparoscope? What are the risks? How long is the recovery time?















instruments and then the uterus is removed through the vagina. Ovarian masses. Tumors or cysts in the ovaries can be removed using laparoscopy. Appendectomy. This surgery to remove an inflamed appendix required open surgery in the past. It is now routinely performed with laparoscopy. Cholecystectomy. Like appendectomy, this procedure to remove the gallbladder used to require open surgery. Now it can be performed with laparoscopy, in some cases.

In contrast to open abdominal surgery, laparoscopy usually involves less pain, less risk, less scarring, and faster recovery. Because laparoscopy is so much less invasive than traditional abdominal surgery, patients can leave the hospital sooner. Cancer staging Laparoscopy can be used in determining the spread of certain cancers. Sometimes it is combined with ultrasound. Although laparoscopy is a useful staging tool, its use depends on a variety of factors, which are considered for each patient. Types of cancers where laparoscopy may be used to determine the spread of the disease include: 

Liver cancer. Laparoscopy is an important tool for determining if cancer is present in the liver. When a patient has non-liver cancer, the liver is often checked to see if the cancer has spread there. Laparoscopy can identify up to 90% of malignant lesions that have spread to that organ from a cancer located elsewhere in the body. While computed tomography

G A LE EN CY C LO PE DI A O F C AN CE R 3

Cancer treatment Laparoscopy is sometimes used as part of a palliative cancer treatment. This type of treatment is not a cure, but can often lessen the symptoms. An example is the feeding tube, which cancer patients may have if they are unable to take in food by mouth. The feeding tube provides nutrition directly into the stomach. Inserting the tube with a laparoscopy saves the patient the ordeal of open surgery.

Precautions As with any surgery, patients should notify their physicians of any medications they are taking (prescription, over-the-counter, or herbal) and of any allergies. Precautions vary due to the several different purposes for laparoscopy. Patients should expect to rest for several days after the procedure, and should set up a comfortable environment in their homes (with items such as pain medication, heating pads, feminine products, comfortable clothing, and food readily accessible) prior to surgery.

Description Laparoscopy is a surgical procedure that is done in the hospital under anesthesia. For diagnosis and biopsy, local anesthesia is sometimes used. In operative procedures, such as abdominal surgery, general anesthesia is required. Before starting the procedure, a 787

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(CT) can find cancerous lesions that are 0.4 in (10 mm) in size, laparoscopy is capable of locating lesions that are as small as 0.04 in (1 millimeter). Pancreatic cancer. Laparoscopy has been used to evaluate pancreatic cancer for years. In fact, the first reported use of laparoscopy in the United States was in a case involving pancreatic cancer. Esophageal and stomach cancers. Laparoscopy has been found to be more effective than magnetic resonance imaging (MRI) or computed tomography (CT) in diagnosing the spread of cancer from these organs. Hodgkin’s disease. Some patients with Hodgkin’s disease have surgical procedures to evaluate lymph nodes for cancer. Laparoscopy is sometimes selected over laparotomy for this procedure. In addition, the spleen may be removed in patients with Hodgkin’s disease. Laparoscopy is the standard surgical technique for this procedure, which is called a splenectomy. Prostate cancer. Patients with prostate cancer may have the nearby lymph nodes examined. Laparoscopy is an important tool in this procedure.

Laparoscopy

Risks

KEY T ERM S Biopsy—Microscopic evaluation of a tissue sample. The tissue is closely examined for the presence of abnormal cells. Cancer staging—Determining the course and spread of cancer. Cyst—An abnormal lump or swelling that is filled with fluid or other material. Palliative treatment—A type of treatment that does not provide a cure, but eases the symptoms. Tumor—A growth of tissue, benign or malignant, often referred to as a mass.

Laparoscopy is a relatively safe procedure, especially if the physician is experienced in the technique. The risk of complication is approximately 1%. The procedure carries a slight risk of puncturing a blood vessel or organ, which could cause blood to seep into the abdominal cavity. Puncturing the intestines could allow intestinal contents to seep into the cavity. These are serious complications and major surgery may be required to correct the problem. For operative procedures, there is the possibility that it may become apparent that open surgery is required. Serious complications occur at a rate of only 0.2%. Rare complications include: 

catheter is inserted through the urethra to empty the bladder, and the skin of the abdomen is cleaned. After the patient is anesthetized, a hollow needle is inserted into the abdomen in or near the navel, and carbon dioxide gas is pumped through the needle to expand the abdomen. This allows the surgeon a better view of the internal organs. The laparoscope is then inserted through this incision to look at the internal organs. The image from the camera attached to the end of the laparoscope is seen on a video monitor. Sometimes, additional small incisions are made to insert other instruments that are used to lift the tubes and ovaries for examination or to perform surgical procedures.

Preparation Patients should not eat or drink after midnight on the night before the procedure.

Aftercare After the operation, nurses will check the vital signs of patients who had general anesthesia. If there are no complications, the patient may leave the hospital within four to eight hours. (Traditional abdominal surgery requires a hospital stay of several days). There may be some slight pain or throbbing at the incision sites in the first day or so after the procedure. The gas that is used to expand the abdomen may cause discomfort under the ribs or in the shoulder for a few days. Depending on the reason for the laparoscopy in gynecological procedures, some women may experience some vaginal bleeding. Many patients can return to work within a week of surgery and most are back to work within two weeks. 788

  

hemorrhage inflammation of the abdominal cavity lining abscess problems related to general anesthesia

Laparoscopy is generally not used in patients with certain heart or lung conditions, or in those who have some intestinal disorders, such as bowel obstruction.

Normal results In diagnostic procedures, normal results would indicate no abnormalities or disease of the organs or lymph nodes that were examined.

Abnormal results A diagnostic laparoscopy may reveal cancerous or benign masses or lesions. Abnormal findings include tumors or cysts, infections (such as pelvic inflammatory disease), cirrhosis, endometriosis, fibroid tumors, or an accumulation of fluid in the cavity. If a doctor is checking for the spread of cancer, the presence of malignant lesions in areas other than the original site of malignancy is an abnormal finding. See also Endoscopic retrograde cholangiopancreatography; Gynecologic cancers; Liver biopsy; Lymph node biopsy; Nutritional support; Tumor grading; Tumor staging; Ultrasonography. Resources BOOKS

Kurtz, Robert C., and Robert J. Ginsberg. ‘‘Cancer Diag nosis: Endoscopy.’’ In Cancer: Principles & Practice of Oncology, edited by Vincent T. DeVita, Jr. Philadel phia: Lippincott, Williams & Wilkins, 2004, 725 27. Lefor, Alan T. ‘‘Specialized Techniques in Cancer Manage ment.’’ In Cancer: Principles & Practice of Oncology, edited by Vincent T. DeVita Jr., et al., 6th ed. Phila delphia: Lippincott, Williams & Wilkins, 2004, 739 57. G A LE EN CY C LO PE DI A O F C AN C ER 3

Iannitti, David A. ‘‘The Role of Laparoscopy in the Man agement of Pancreatic Cancer.’’ Home Journal Library Index. [cited June 27, 2009]. http://bioscience.org/1998/ v3/e/iannitti/e181 185.htm.

Carol A. Turkington Rhonda Cloos, R.N.

KEY T ERMS Cytochrome P450— Enzymes present in the liver that metabolize drugs. Epilepsy—Neurological disorder characterized by recurrent seizures. Metastasize—The process by which cancer spreads from its original site to other parts of the body. QT prolongation—Potentially dangerous heart condition that affects the rhythm of the heart beat and alters the ECG reading of the heart.

Lapatinib Definition Lapatinib is an anti-cancer drug designed to treat cancer of the breast. Lapatinib inhibits tumor cellular signaling by antagonizing a signaling pathway effecting tumor cell development. The tumor cells lapatinib is used against have a receptor on their cell surface called the human epidermal growth factor receptor type 2 (HER2).

Purpose Lapatinib is used to treat advanced or metastatic breast cancer that has high levels of the growth factor receptor HER2 on the tumor cell surface. Lapatinib is used in patients who have received prior therapy including drugs that are an anthracycline, a taxane, and trastuzumab and now need a new agent to treat their cancer.

Description Lapatinib is an anticancer drug that acts on receptor tyrosine kinases to inhibit the growth of tumors. Receptor tyrosine kinases are receptors for growth factors that are a natural part of cell development and necessary for normal cell growth. When tyrosine kinase receptors are activated, they initiate chemical signals that tell the cell how to grow and develop. Normal tyrosine kinase receptors turn on and off as needed for usual amounts of growth. However, when cells have constantly activated tyrosine kinase receptors, it can lead to abnormal growth and cancer. Drugs in the class of lapatinib inhibit these overly active tyrosine kinase receptors. Lapatinib is an inhibitor of two growth factor receptors, HER2 and epidermal growth factor receptor (EGFR). Both receptors are tyrosine kinases. Lapatinib is used in combination with the drug capecitabine for the treatment of advanced or metastatic HER2 breast cancer. The combination of capecitabine and lapatinib has an additive anti-cancer effect. G A LE EN CY C LO PE DI A O F C AN CE R 3

Receptor tyrosine kinase—Cell surface receptors that interact with growth factors and hormones to affect the normal life cycle of a cell. Tuberculosis—Potentially fatal infectious disease that commonly affects the lungs, is highly contagious, and is caused by an organism known as mycobacterium.

Lapatinib is manufactured by GlaxoSmithKline under the trade name Tykerb. Studies have shown that lapatinib is an effective drug, affecting both time to tumor progression and progression-free survival. The term time to tumor progression describes a period of time from when disease is diagnosed (or treated) until the disease starts to get worse. Progression-free survival describes the length of time during and after treatment in which a patient is living with a disease that does not get worse. Both time to tumor progression and progression-free survival may be used in a clinical study or trial to help find out how well a new treatment works. In studies done on lapatinib, patients receiving lapatinib in combination with capecitabine had a longer median time to tumor progression and a longer median progression-free survival than those receiving placebo or capecitabine alone.

Recommended dosage Lapatinib is taken as an oral medication once a day. Lapatinib should not be taken with food and needs to be administered at least one hour apart from meals (one hour before or after meals). Lapatinib may be given in combination with the drug capecitabine. The usual adult dose of lapatinib is 1.25 g per day. If a dose is missed the patient should seek the advice of their physician and not double their next dose. It is important that the medication not be taken more than once daily. In patients with severe liver impairment the dose of lapatinib may need to be reduced to 750 mg a day. Treatment with lapatinib is continued until disease 789

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progression occurs or until unacceptable levels of toxicity occur, whichever comes first.

QUESTIONS TO ASK YOUR PHARMACIST

Precautions 

Lapatinib is not recommended for use in pregnant women. Birth control is recommended while using this drug. Lapatinib is a pregnancy Category D drug. Category D describes drugs in which there is evidence of potential human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. For Category D drugs, medical necessity must be great enough to warrant risking harm to the fetus. Lapatinib is both a teratogen and lethal to fetuses in animal studies. Lapatinib is contraindicated for use in breast feeding women. Lapatinib is only used in adults as the safety for use in patients less than 18 years of age has not been established. Lapatinib is absorbed through the skin and lungs if breathed in powder form. Women who are pregnant or who may become pregnant should not handle lapatinib or breathe the dust from the tablets. Lapatinib may cause a heart condition that affects the rhythm of the heartbeat known as QT prolongation. Sometimes QT prolongation can cause a serious cardiac condition that includes a fast and irregular heartbeat, with severe dizziness and fainting. The risk of developing QT prolongation syndrome may be increased if the patient is taking other drugs that also affect the rhythm of the heart, or if the patient has cardiac problems. Low blood levels of potassium or magnesium may also increase risk of QT prolongation. Lapatinib toxicity may cause other adverse side effects affecting heart function, and multiple other medical heart conditions may result from use of lapatinib. Lapatinib may not be suitable for patients with a history of certain types of heart failure. Caution must be used for lapatinib treatment in patients with liver disease or impairment. The liver is responsible for metabolizing lapatinib into inactive compounds. If this metabolism is impaired, higher levels of lapatinib in the bloodstream may cause toxicity. Patients with liver impairment may need a lower dose for treatment. Caution may be needed in patients with kidney impairment as safety and effectiveness has not been fully established in this group of patients.

Side effects Lapatinib is used when the medical benefit is judged to be greater than the risk of side effects. The most frequent side effects of lapatinib treatment are diarrhea, dry skin, rash, upset stomach, fatigue, 790









How long will I need to take this drug before you can tell if it helps for me? How often do I have to have blood work and other laboratory tests done to check the effect the drug is having? Is this drug safe to take with the other drugs that I am currently taking? What side effects should I watch for? When should I call the doctor about them? Are there any clinical trials of this drug combined with other therapies that might benefit me?

diarrhea, nausea, and vomiting. Lapatinib also commonly causes hand foot syndrome, caused by leakage of lapatinib out of small blood vessels in the hands and feet. During some types of chemotherapy, small amounts of medication in the blood stream leak out of capillaries in the palms of the hands and the soles of the feet. Drug leakage is increased by heat exposure or friction. The result is redness, tenderness, and sometimes peeling of the skin of the palms and soles. The appearance of sunburn, numbness, and tingling may develop, and may interfere with the activity level of the patient. Less commonly, lapatinib therapy may cause insomnia, body aches, and inflammation of the tissue lining the inside of the mouth. Lapatinib may cause abnormal liver function tests, liver disease, difficulty breathing, lung disease and inflammation, heart failure, and the heart condition called prolonged QT interval.

Interactions Patients should make their doctor aware of any and all medications or supplements they are taking before using lapatinib. Lapatinib interacts with many other drugs. Some drug interactions may make lapatinib unsuitable for use, while others may be monitored and attempted. Lapatinib may have dangerous additive effects with other drugs that also cause QT prolongation. Drugs that interact with lapatinib in this way include amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, and macrolide antibiotics such as erythromycin. Lapatinib is metabolized by a set of liver enzymes known as cytochrome P450 (CYP-450) subtype 3A4. G A LE EN CY C LO PE DI A O F C AN C ER 3

Drugs that act to inhibit the action of CYP-450 subtype 3A4 may cause undesired increased levels of lapatinib in the body. This could lead to toxic doses. Some examples are antibiotics such as clarithromycin, antifungal drugs such as ketoconazole, antiviral drugs such as indinavir, antidepressants such as fluoxetine, and some cardiac agents such as verapamil. Grapefruit juice may also increase the amount of lapatinib in the body. Patients should avoid drinking grapefruit juice or eating grapefruit while taking lapatinib. Resources BOOKS

Goodman and Gilman’s The Pharmacological Basis of Ther apeutics, Eleventh Edition. McGraw Hill Medical Publishing Division, 2006. Tarascon Pharmacopoeia Library Edition. Jones and Bartlett Publishers, 2009. OTHER

Epocrates. Lapatinib. http://www.epocrates.com. Medscape. Lapatinib. http://www.medscape.com. RxList. Lapatinib. http://www.rxlist.com. ORGANIZATIONS

FDA U.S. Food and Drug Administration. 10903 New Hampshire Ave, Silver Spring, MD 20993. (888)INFO FDA. http://www.fda.gov. National Cancer Institute. 6116 Executive Boulevard, Room 3036A, Bethesda, MD 20892 8322. (800)4 CANCER. http://www.cancer.gov.

Maria Basile, Ph.D.

Laryngeal cancer Definition Laryngeal cancer is cancer of the larynx or voice box.

Description The larynx is located where the throat divides into the esophagus and the trachea. The esophagus is the G A LE EN CY C LO PE DI A O F C AN CE R 3

Laryngeal cancer

Drugs that induce, or activate these enzymes increase the metabolism of lapatinib. This results in lower levels of therapeutic lapatinib, thereby negatively affecting treatment of cancer. For this reason drugs that induce CYP-450 subtype 3A4 may not be used with lapatinib. This includes some anti-epileptic drugs such as carbamazepine, some anti-inflammatory drugs such as dexamethasone, anti-tuberculosis drugs such as rifampin, and the herb St. John’s Wort.

A pathology photograph of an extracted tumor found on the larynx. (Photograph by William Gage. Custom Medical Stock Photo. Reproduced by permission.)

tube that takes food to the stomach. The trachea, or windpipe, takes air to the lungs. The area where the larynx is located is sometimes called the Adam’s apple. The larynx has two main functions. It contains the vocal cords, cartilage, and small muscles that make up the voice box. When a person speaks, small muscles tighten the vocal cords, narrowing the distance between them. As air is exhaled past the tightened vocal cords, it creates sounds that are formed into speech by the mouth, lips, and tongue. The second function of the larynx is to allow air to enter the trachea and to keep food, saliva, and foreign material from entering the lungs. A flap of tissue called the epiglottis covers the trachea each time a person swallows. This blocks foreign material from entering the lungs. When not swallowing, the epiglottis retracts, and air flows into the trachea. During treatment for cancer of the larynx, both of these functions may be lost. Cancers of the larynx develop slowly. About 95% of these cancers develop from thin, flat cells similar to skin cells called squamous epithelial cells. These cells line the larynx. Gradually, the squamous epithelial cells begin to change and are replaced with abnormal cells. These abnormal cells are not cancerous but are pre-malignant cells that have the potential to develop into cancer. This condition is called dysplasia. Most people with dysplasia never develop cancer. The condition simply goes away without any treatment, especially if the person with dysplasia stops smoking or drinking alcohol. The larynx is made up of three parts, the glottis, the supraglottis, and the subglottis. Cancer can start in 791

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KEY T ERM S Dysplasia—The abnormal change in size, shape or organization of adult cells. Lymph—Clear, slightly yellow fluid carried by a network of thin tubes to every part of the body. Cells that fight infection are carried in the lymph. Lymphatic system—Primary defense against infection in the body. The lymphatic system consists of tissues, organs, and channels (similar to veins) that produce, store, and transport lymph and white blood cells to fight infection. Lymph nodes—Small, bean-shaped collections of tissue found in a lymph vessel. They produce cells and proteins that fight infection, and also filter lymph. Nodes are sometimes called lymph glands. Malignant—Cancerous. Cells tend to reproduce without normal controls on growth and form tumors or invade other tissues. Metastasize—Spread of cells from the original site of the cancer to other parts of the body where secondary tumors are formed.

any of these regions. Treatment and survival rates depend on which parts of the larynx are affected and whether the cancer has spread to neighboring areas of the neck or distant parts of the body. The glottis is the middle part of the larynx. It contains the vocal cords. Cancers that develop on the vocal cords are often diagnosed very early because even small vocal cord tumors cause hoarseness. In addition, the vocal cords have no connection to the lymphatic system. This means that cancers on the vocal cord do not spread easily. When confined to the vocal cords without any involvement of other parts of the larynx, the cure rate for this cancer is 75–95%. The supraglottis is the area above the vocal cords. It contains the epiglottis, which protects the trachea from foreign materials. Cancers that develop in this region are usually not found as early as cancers of the glottis because the symptoms are less distinct. The supraglottis region has many connections to the lymphatic system, so cancers in this region tend to spread easily to the lymph nodes and may spread to other parts of the body (lymph nodes are small bean-shaped structures that are found throughout the body; they produce and store infection-fighting cells). In 25–50% of people with cancer in the supraglottal region, the 792

Q U E S T I O N S T O A S K TH E DOC TOR 

  

  



 



What stage is my cancer, and what exactly does that mean? What are possible treatments for my cancer? How long will my treatment last? What are some of the changes in my activities that will occur because of my treatment? What is daily life like after a laryngectomy? How will I speak? I’ve heard about clinical trials using radiation and drugs to treat cancer of the larynx. Where can I find out more about these trials? What changes in my lifestyle can I make to help improve my chances of beating this cancer? How often will I have to have check-ups? What is the likelihood that I will survive this cancer? Can you suggest any support groups that would be helpful to me or my family?

cancer has already spread to the lymph nodes by the time they are diagnosed. Because of this, survival rates are lower than for cancers that involve only the glottis. The subglottis is the region below the vocal cords. Cancer starting in the subglottis region is rare. When it does, it is usually detected only after it has spread to the vocal cords, where it causes obvious symptoms such as hoarseness. Because the cancer has already begun to spread by the time it is detected, survival rates are generally lower than for cancers in other parts of the larynx.

Demographics About 12,000 new cases of cancer of the larynx develop in the United States each year. Each year, about 3,600 die of the disease. Laryngeal cancer is between four and five times more common in men than in women. Almost all men who develop laryngeal cancer are over age 55. Laryngeal cancer is about 50% more common among African-American men than among other Americans. It is thought that older men are more likely to develop laryngeal cancer than women because the two main risk factors for acquiring the disease are lifetime habits of smoking and alcohol abuse. More G A LE EN CY C LO PE DI A O F C AN C ER 3

Causes and symptoms Laryngeal cancer develops when the normal cells lining the larynx are replaced with abnormal cells (dysplasia) that become malignant and reproduce to form tumors. The development of dysplasia is strongly linked to life-long habits of smoking and heavy use of alcohol. The more a person smokes, the greater the risk of developing laryngeal cancer. It is unusual for someone who does not smoke or drink to develop cancer of the larynx. Occasionally, however, people who inhale asbestos particles, wood dust, paint or industrial chemical fumes over a long period of time develop the disease. The symptoms of laryngeal cancer depend on the location of the tumor. Tumors on the vocal cords are rarely painful, but cause hoarseness. Anyone who is continually hoarse for more than two weeks or who has a cough that does not go away should be checked by a doctor. Tumors in the supraglottal region above the vocal cords often cause more, but less distinct symptoms. These include:      



persistent sore throat pain when swallowing difficulty swallowing or frequent choking on food bad breath lumps in the neck persistent ear pain (called referred pain; the source of the pain is not the ear) change in voice quality

Tumors that begin below the vocal cords are rare, but may cause noisy or difficult breathing. All the symptoms above can also be caused other cancers as well as by less serious illnesses. However, if these symptoms persist, it is important to see a doctor and find their cause, because the earlier cancer treatment begins, the more successful it is.

alcohol use. The doctor also does a physical examination, paying special attention to the neck region for lumps, tenderness, or swelling. The next step is examination by an otolaryngologist, or ear, nose, and throat (ENT) specialist. This doctor also performs a physical examination, but in addition will also want to look inside the throat at the larynx. Initially, the doctor may spray a local anesthetic on the back of the throat to prevent gagging, then use a long-handled mirror to look at the larynx and vocal cords. This examination is done in the doctor’s office. It may cause gagging but is usually painless. A more extensive examination involves a laryngoscopy. In a laryngoscopy, a lighted fiberoptic tube called a laryngoscope that contains a tiny camera is inserted through the patient’s nose and mouth and snaked down the throat so that the doctor can see the larynx and surrounding area. This procedure can be done with a sedative and local anesthetic in a doctor’s office. More often, the procedure is done in an outpatient surgery clinic or hospital under general anesthesia. This allows the doctor to use tiny clips on the end of the laryngoscope to take biopsies (tissue samples) of any abnormal-looking areas. Laryngoscopies are normally painless and take about one hour. Some people find their throat feels scratchy after the procedure. Since laryngoscopies are done under sedation, patients should not drive immediately after the procedure, and should have someone available to take them home. Laryngoscopy is a standard procedure that is covered by insurance. The locations of the samples taken during the laryngoscopy are recorded, and the samples are then sent to the laboratory where they are examined under the microscope by a pathologist who specializes in diagnosing diseases through cell samples and laboratory tests. It may take several days to get the results. Based on the findings of the pathologist, cancer can be diagnosed and staged. Once cancer is diagnosed, other tests will probably be done to help determine the exact size and location of the tumors. This information is helpful in determining which treatments are most appropriate. These tests may include: 

Diagnosis On the first visit to a doctor for symptoms that suggest laryngeal cancer, the doctor first takes a complete medical history, including family history of cancer and lifestyle information about smoking and G A LE EN CY C LO PE DI A O F C AN CE R 3



Endoscopy. Similar to a laryngoscopy, this test is done when it appears that cancer may have spread to other areas, such as the esophagus or trachea. Computed tomography (CT or CAT) scan. Using x-ray images taken from several angles and computer modeling, CT scans allow parts of the body to be seen as a cross section. This helps locate and size the 793

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men smoke and drink more than women, and more African-American men are heavy smokers than other men in the United States. However, as smoking becomes more prevalent among women, it seems likely that more cases of laryngeal cancer in females will be seen.

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tumors, and provides information on whether they can be surgically removed.  Magnetic resonance imaging (MRI). MRI uses magnets and radio waves to create more detailed crosssectional scans than computed tomography. This detailed information is needed if surgery on the larynx area is planned.  Barium swallow. Barium is a substance that, unlike soft tissue, shows up on x rays. Swallowed barium coats the throat and allows x-ray pictures to be made of the tissues lining the throat.  Chest x ray. Done to determine if cancer has spread to the lungs. Since most people with laryngeal cancer are smokers, the risk of also having lung cancer or emphysema is high.  Fine needle aspiration (FNA) biopsy. If any lumps on the neck are found, a thin needle is inserted into the lump, and some cells are removed for analysis by the pathologist.  Additional blood and urine tests. These tests do not diagnose cancer, but help to determine the patient’s general health and provide information to determine which cancer treatments are most appropriate.

treatment. In cancer of the larynx, the definitions of the early stages depend on where the cancer started. STAGE I. The cancer is only in the area where it started and has not spread to lymph nodes in the area or to other parts of the body. The exact definition of stage I depends on where the cancer started, as follows: 

Supraglottis: The cancer is only in one area of the supraglottis and the vocal cords can move normally.



Glottis: The cancer is only in the vocal cords and the vocal cords can move normally.



Subglottis: The cancer has not spread outside of the subglottis.

STAGE II. The cancer is only in the larynx and has not spread to lymph nodes in the area or to other parts of the body. The exact definition of stage II depends on where the cancer started, as follows: 

Supraglottis: The cancer is in more than one area of the supraglottis, but the vocal cords can move normally.



Glottis: The cancer has spread to the supraglottis or the subglottis or both. The vocal cords may or may not be able to move normally.



Subglottis: The cancer has spread to the vocal cords, which may or may not be able to move normally.

Treatment team An otolaryngologist and an oncologist (cancer specialist) generally lead the treatment team. They are supported by radiologists to interpret CT and MRI scans, a head and neck surgeon, and nurses with special training in assisting cancer patients. A speech pathologist is often involved in treatment, both before surgery to discuss various options for communication if the larynx is removed, and after surgery to teach alternate forms of voice communication. A social worker, psychologist, or family counselor may help both the patient and the family meet the changes and challenges that living with laryngeal cancer brings. At any point in the process, the patient may want to get a second opinion from another doctor in the same specialty. This is a common practice and does not indicate a lack of faith in the original doctor, but simply a desire for more information. Some insurance companies require a second opinion before surgery is done.

STAGE III. Either of the following may be true: 

The cancer has not spread outside of the larynx, but the vocal cords cannot move normally, or the cancer has spread to tissues next to the larynx.



The cancer has spread to one lymph node on the same side of the neck as the cancer, and the lymph node measures no more than 3 centimeters (just over 1 inch). STAGE IV. Any of the following may be true:



The cancer has spread to tissues around the larynx, such as the pharynx or the tissues in the neck. The lymph nodes in the area may or may not contain cancer.



The cancer has spread to more than one lymph node on the same side of the neck as the cancer, to lymph nodes on one or both sides of the neck, or to any lymph node that measures more than 6 centimeters (over 2 inches).



The cancer has spread to other parts of the body.

Clinical staging, treatments, and prognosis Staging Once cancer of the larynx is found, more tests will be done to find out if cancer cells have spread to other parts of the body. This is called staging. A doctor needs to know the stage of the disease to plan 794

RECURRENT. Recurrent disease means that the cancer has come back (recurred) after it has been treated. It may come back in the larynx or in another part of the body.

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Treatment is based on the stage of the cancer as well as its location and the health of the individual. Generally, there are three types of treatments for cancer of the larynx. These are surgery, radiation, and chemotherapy. They can be used alone or in combination based in the stage of the caner. Getting a second opinion after the cancer has been staged can be very helpful in sorting out treatment options and should always be considered. SURGERY. The goal of surgery is to cut out the tissue that contains malignant cells. There are several common surgeries to treat laryngeal cancer.

Stage III and stage IV cancers are usually treated with total laryngectomy. This is an operation to remove the entire larynx. Sometimes other tissues around the larynx are also removed. Total laryngectomy removes the vocal cords. Alternate methods of voice communication must be learned with the help of a speech pathologist. Smaller tumors are sometimes treated by partial laryngectomy. The goal is to remove the cancer but save as much of the larynx (and corresponding speech capability) as possible. Very small tumors or cancer in situ are sometimes successfully treated with laser excision surgery. In this type of surgery, a narrowly targeted beam of light from a laser is used to remove the cancer. Advanced cancer (Stages III and IV) that has spread to the lymph nodes often requires an operation called a neck dissection. The goal of a neck dissection is to remove the lymph nodes and prevent the cancer from spreading. There are several forms of neck dissection. A radical neck dissection is the operation that removes the most tissue. Several other operations are sometimes performed because of laryngeal cancer. A tracheotomy is a surgical procedure in which an artificial opening is made in the trachea (windpipe) to allow air into the lungs. This operation is necessary if the larynx is totally removed. A gastrectomy tube is a feeding tube placed through skin and directly into the stomach. It is used to give nutrition to people who cannot swallow or whose esophagus is blocked by a tumor. People who have a total laryngectomy usually do not need a gastrectomy tube if their esophagus remains intact. RADIATION. Radiation therapy uses high-energy rays, such as x rays or gamma rays, to kill cancer cells. The advantage of radiation therapy is that it preserves the larynx and the ability to speak. The

G A LE EN CY C LO PE DI A O F C AN CE R 3

disadvantage is that it may not kill all the cancer cells. Radiation therapy can be used alone in early stage cancers or in combination with surgery. Sometimes it is tried first with the plan that if it fails to cure the cancer, surgery still remains an option. Often, radiation therapy is used after surgery for advanced cancers to kill any cells the surgeon might not have removed. There are two types of radiation therapy. External beam radiation therapy focuses rays from outside the body on the cancerous tissue. This is the most common type of radiation therapy used to treat laryngeal cancer. With internal radiation therapy, also called brachytherapy, radioactive materials are placed directly on the cancerous tissue. This type of radiation therapy is a much less common treatment for laryngeal cancer. External radiation therapy is given in doses called fractions. A common treatment involves giving fractions five days a week for seven weeks. Clinical trials are underway to determine the benefits of accelerating the delivery of fractions (accelerated fractionation) or dividing fractions into smaller doses given more than once a day (hyperfractionation). Side effects of radiation therapy include dry mouth, sore throat, hoarseness, skin problems, trouble swallowing, and diminished ability to taste. CHEMOTHERAPY. Chemotherapy is the use of drugs to kill cancer cells. Unlike radiation therapy, which is targeted to a specific tissue, chemotherapy drugs are either taken by mouth or intravenously (through a vein) and circulate throughout the whole body. They are used mainly to treat advanced laryngeal cancer that is inoperable or that has metastasized to a distant site. Chemotherapy is often used after surgery or in combination with radiation therapy. Clinical trials are underway to determine the best combination of treatments for advanced cancer.

The two most common chemotherapy drugs used to treat laryngeal cancer are cisplatin and 5-fluorouracil (5-FU or fluorouracil). There are many side effects associated with chemotherapy drugs, including nausea and vomiting, loss of appetite (anorexia), hair loss (alopecia), diarrhea, and mouth sores. Chemotherapy can also damage the blood-producing cells of the bone marrow, which can result in low blood cell counts, increased chance of infection, and abnormal bleeding or bruising. Prognosis Cure rates and survival rates can predict group outcomes, but can never precisely predict the outcome 795

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for a single individual. However, the earlier laryngeal cancer is discovered and treated, the more likely it will be cured. Cancers found in stage 0 and stage 1 have a 75– 95% cure rate depending on the site. Late stage cancers that have metastasized have a very poor survival rate, with intermediate stages falling somewhere in between. People who have had laryngeal cancer are at greatest risk for recurrence (having cancer come back), especially in the head and neck, during the first two to three years after treatment. Check-ups during the first year are needed every other month, and four times a year during the second year. It is rare for laryngeal cancer to recur after five years of being cancer-free.

laryngectomy and the need to breathe through a hole in the neck called a stoma. Several alternative methods of sound production, both mechanical and learned, are available, and should be discussed with a speech pathologist. Support groups also exist for people who have had their larynx removed. Coping with speech loss and care of the stoma is discussed more extensively in the laryngectomy entry. Chemotherapy brings with it a host of unwanted side effects, many of which disappear after the chemotherapy stops. For example, hair will re-grow, and until it does, a wig can be used. Medications are available to treat nausea and vomiting. Side effects such as dry skin are treated symptomatically.

Clinical trials

Alternative and complementary therapies Alternative and complementary therapies range from herbal remedies, vitamin supplements, and special diets to spiritual practices, acupuncture, massage, and similar treatments. When these therapies are used in addition to conventional medicine, they are called complementary therapies. When they are used instead of conventional medicine, they are called alternative therapies. Complementary or alternative therapies are widely used by people with cancer. One large study published in the Journal of Clinical Oncology in July 2000, found that 83% of all cancer patients studied used some form of complementary or alternative medicine as part of their cancer treatment. No specific alternative therapies have been directed toward laryngeal cancer. However, good nutrition and activities that reduce stress and promote a positive view of life have no unwanted side effects and appear to be beneficial in boosting the immune system in fighting cancer. Unlike traditional pharmaceuticals, complementary and alternative therapies are not evaluated by the United States Food and Drug Administration (FDA) for either safety or effectiveness. These therapies may have interactions with traditional pharmaceuticals. Patients should be wary of ‘‘miracle cures’’ and notify their doctors if they are using herbal remedies, vitamin supplements or other unprescribed treatments. Alternative and experimental treatments normally are not covered by insurance.

Coping with cancer treatment Cancer treatment, even when successful, has many unwanted side effects. In laryngeal cancer, the biggest side effects are the loss of speech due to total 796

Clinical trials are government-regulated studies of new treatments and techniques that may prove beneficial in diagnosing or treating a disease. Participation is always voluntary and at no cost to the participant. Clinical trials are conducted in three phases. Phase 1 tests the safety of the treatment and looks for harmful side effects. Phase 2 tests the effectiveness of the treatment. Phase 3 compares the treatment to other treatments available for the same condition. The selection of clinical trials underway changes frequently. Clinical trials for laryngeal cancer currently focus treating advanced cancers by combining radiation and surgical therapy, radiation and chemotherapy, and different combinations of chemotherapy drugs. Other studies are examining the most effective timing and duration of radiation therapy. Current information on what clinical trials are available and where they are being held is available by entering the search term ‘‘laryngeal cancer’’ at the following web sites: 





National Cancer Institute: http://cancertrials.nci. nih.gov or (800) 4-CANCER National Institutes of Health Clinical Trials: http:// clinicaltrials.gov Center Watch: A Clinical Trials Listing: http://www. centerwatch.com

Prevention By far, the most effective way to prevent laryngeal cancer is not to smoke. Smokers who quit smoking also significantly decrease their risk of developing the disease. Other ways to prevent laryngeal cancer include limiting the use of alcohol, eating a wellbalanced diet, seeking treatment for prolonged G A LE EN CY C LO PE DI A O F C AN C ER 3

Laryngeal nerve palsy Description

Special concerns Being diagnosed with cancer is a traumatic event. Not only is one’s health affected, one’s whole life suddenly revolves around trips to the doctor for cancer treatment and adjusting to the side effects of these treatments. This is stressful for both the cancer patient and his or her family members. It is not unusual for family members to feel resentful of the changes that occur in the family, and then feel guilty about feeling resentful. The loss of voice because of laryngeal surgery may be the most traumatic effect of laryngeal cancer. Losing the ability to communicate easily with others can be isolating. Support groups and psychological counseling is helpful for both the cancer patient and family members. Many national organizations that support cancer education can provide information on inperson or on-line support and education groups. See also Alcohol consumption; Cigarettes; Smoking cessation. Resources PERIODICALS

Ahmad, I., B. N. Kumar, K. Radford, J. O’Connell, and A. J. Batch. ‘‘Surgical Voice Restoration Following Abla tive Surgery for Laryngeal and Hypopharyngeal Car cinoma.’’ Journal or Laryngology and Otolaryngology 114 (July 2000): 522 5. OTHER

‘‘Laryngeal Cancer.’’ CancerNet. [cited July 19, 2009]. http:// www.graylab.ac.uk/cancernet/201519.html#3_STAGE EXPLANATION. ‘‘What you Need to Know About Cancer of the Larynx.’’ CancerNet November 2000. [cited July 19, 2009]. http:// www.cancernet.nci.nih.gov. ORGANIZATIONS

American Cancer Society. National Headquarters, 1599 Clifton Rd. NE, Atlanta, GA 30329. 800 (ACS) 2345. http://www.cancer.org. National Cancer Institute. Cancer Information Service. Bldg. 31, Room 10A19, 9000 Rockville Pike, Bethesda, MD 20892. (800) 4 CANCER. http://www.nci.nih.gov/ cancerinfo/index.html. National Cancer Institute Office of Cancer Complementary and Alternative Medicine. . National Center for Complementary and Alternative Med icine. P. O. Box 8218, Silver Spring, MD 20907 8281. (888) 644 6226. .

Tish Davidson, A.M. G A LE EN CY C LO PE DI A O F C AN CE R 3

Laryngeal nerve palsy is damage to the recurrent laryngeal nerve (or less commonly the vagus nerve) that results in paralysis of the larynx (voice box). Paralysis may be temporary or permanent. Damage to the recurrent laryngeal nerve is most likely to occur during surgery on the thyroid gland to treat cancer of the thyroid. Laryngeal nerve palsy is also called recurrent laryngeal nerve damage. The vagus nerve is one of 12 cranial nerves that connect the brain to other organs in the body. It runs from the brain to the large intestine. In the neck, the vagus nerve gives off a paired branch nerve called the recurrent laryngeal nerve. The recurrent laryngeal nerves lie in grooves along either side of the trachea (windpipe) between the trachea and the thyroid gland. The recurrent laryngeal nerve controls movement of the larynx. The larynx is located where the throat divides into the esophagus, a tube that takes food to the stomach, and the trachea (windpipe) that takes air to the lungs. The larynx contains the apparatus for voice production: the vocal cords, and the muscles and ligaments that move the vocal cords. It also controls the flow of air into the lungs. When the recurrent laryngeal nerve is damaged, the movements of the larynx are reduced. This causes voice weakness, hoarseness, or sometimes the complete loss of voice. The changes may be temporary or permanent. In rare life-threatening cases of damage, the larynx is paralyzed to the extent that air cannot enter the lungs.

Causes Laryngeal nerve palsy is an uncommon side effect of surgery to remove the thyroid gland (thyroidectomy). It occurs in 1–2% of operations for total thyroidectomy to treat cancer, and less often when only part of the thyroid is removed. Damage can occur to either one or both branches of the nerve, and it can be temporary or permanent. Most people experience only transient laryngeal nerve palsy and recover their normal voice within a few weeks. Laryngeal nerve palsy can also occur from causes unrelated to thyroid surgery. These include damage to either the vagus nerve or the laryngeal nerve, due to tumors in the neck and chest or diseases in the chest such as aortic aneurysms. Both tumors and 797

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heartburn, and avoiding inhaling asbestos and chemical fumes.

Laryngectomy

aneurysms press on the nerve, and the pressure causes damage.

Laryngectomy Definition

Treatments Once the recurrent laryngeal nerve is damaged, there is no specific treatment to heal it. With time, most cases of recurrent laryngeal palsy improve on their own. In the event of severe damage, the larynx may be so paralyzed that air cannot flow past it into the lungs. When this happens, an emergency tracheotomy must be performed to save the patient’s life. A tracheotomy is a surgical procedure to make an artificial opening in the trachea (windpipe) to allow air to bypass the larynx and enter the lungs. If paralysis of the larynx is temporary, the tracheotomy hole can be surgically closed when it is no longer needed. Some normal variation in the location of the recurrent laryngeal nerve occurs among individuals. Occasionally the nerves are not located exactly where the surgeon expects to find them. Choosing a board certified head and neck surgeon who has had a lot of experience with thyroid operations is the best way to prevent laryngeal nerve palsy.

Alternative and complementary therapies There are no alternative or complementary therapies to heal laryngeal nerve palsy. The passage of time alone restores speech to most people. Some alternatives for artificial speech exist for people whose loss of speech is permanent. See also Laryngectomy.

Purpose Normally a laryngectomy is performed to remove tumors or cancerous tissue. In rare cases, it may be done when the larynx is badly damaged by gunshot, automobile injuries, or similar violent accidents. Laryngectomies can be total or partial. Total laryngectomies are done when cancer is advanced. The entire larynx is removed. Often if the cancer has spread, other surrounding structures in the neck, such as lymph nodes, are removed at the same time. Partial laryngectomies are done when cancer is limited to one spot. Only the area with the tumor is removed. Laryngectomies may also be performed when other cancer treatment options, such as radiation therapy or chemotherapy, fail.

Precautions Laryngectomy is done only after cancer of the larynx has been diagnosed by a series of tests that allow the otolaryngologist (a specialist often called an ear, nose, and throat doctor) to look into the throat and take tissue samples (biopsies) to confirm and stage the cancer. People need to be in good general health to undergo a laryngectomy, and will have standard preoperative blood work and tests to make sure they are able to safely withstand the operation.

Description

Resources PERIODICALS

Harti, Dana M., and Daniel F. Brasnu. ‘‘Recurrent laryng eal nerve paralysis:Current concepts and treatment.’’ Ear, Nose and Throat Journal 79, no. 12 (December 2000): 918. OTHER

Grebe, Werner, M.D. ‘‘Thyroid Operations.’’ Endocrine Web.com. [cited July 19, 2009]. http://www.endocri neweb.com/surthyroid.html. University of Virginia Health System. ‘‘Surgical Tutorial: Surgical Approach for a Thyroid Mass.’’ University of Virginia Health System, Department of Surgery. [cited July 19, 2009]. http://hsc.virginia.edu/surgery/ tutorialsurgthyroid.html.

Tish Davidson, A.M. 798

Laryngectomy is the partial or complete surgical removal of the larynx, usually as a treatment for cancer of the larynx.

The larynx is located slightly below the point where the throat divides into the esophagus, which takes food to the stomach, and the trachea (windpipe), which takes air to the lungs. Because of its location, the larynx plays a critical role in normal breathing, swallowing, and speaking. Within the larynx, vocal folds (often called vocal cords) vibrate as air is exhaled past, thus creating speech. The epiglottis protects the trachea, making sure that only air gets into the lungs. When the larynx is removed, these functions are lost. Once the larynx is removed, air can no longer flow into the lungs. During this operation, the surgeon removes the larynx through an incision in the neck. The surgeon also performs a tracheotomy. He makes an artificial opening called a stoma in the front of the neck. The upper portion of the trachea is brought to G A LE EN CY C LO PE DI A O F C AN C ER 3

Larynx—Also known as the voice box, the larynx is composed of cartilage that contains the apparatus for voice production. This includes the vocal cords and the muscles and ligaments that move the cords. Lymph nodes—Accumulations of tissue along a lymph channel, which produce cells called lymphocytes that fight infection. Tracheostomy—A surgical procedure in which an artificial opening is made in the trachea (windpipe) to allow air into the lungs.

the stoma and secured, making a permanent alternate way for air to get to the lungs. The connection between the throat and the esophagus is not normally affected, so after healing, the person whose larynx has been removed (called a laryngectomee) can eat normally. However, normal speech is no longer possible. Several alternate means of vocal communication can be learned with the help of a speech pathologist.

Preparation As with any surgical procedure, the patient will be required to sign a consent form after the procedure is thoroughly explained. Many patients prefer a second opinion, and some insurers require it. Blood and urine studies, along with chest x ray and EKG may be ordered as the doctor deems necessary. The patient also has a pre-operative meeting with an anesthesiologist. If a complete laryngectomy is planned, it may be helpful to meet with a speech pathologist and/or an established laryngectomee for discussion of postoperative expectations and support.

Aftercare A person undergoing a laryngectomy spends several days in intensive care (ICU) and receives intravenous (IV) fluids and medication. As with any major surgery, the blood pressure, pulse, and respirations are monitored regularly. The patient is encouraged to turn, cough, and deep breathe to help mobilize secretions in the lungs. One or more drains are usually inserted in the neck to remove any fluids that collect. These drains are removed after several days. It takes two to three weeks for the tissues of the throat to heal. During this time, the laryngectomee cannot swallow food and must receive nutrition through a tube inserted through the nose and down G A LE EN CY C LO PE DI A O F C AN CE R 3

Q U E S T I O N S TO A S K T H E DOCTOR 









Is laryngectomy my only viable treatment option? What specific lifestyle changes will I have to make? Is there a support group in the area that can assist me post-surgery? How long will it be until I can verbally communicate? What are my options? How sizable is the risk of recurring cancer?

the throat into the stomach. During this time, even people with partial laryngectomies are unable to speak. When air is drawn in normally through the nose, it is warmed and moistened before it reaches the lungs. When air is drawn in through the stoma, it does not have the opportunity to be warmed and humidified. In order to keep the stoma from drying out and becoming crusty, laryngectomees are encouraged to breathe artificially humidified air. The stoma is usually covered with a light cloth to keep it clean and to keep unwanted particles from accidentally entering the lungs. Care of the stoma is extremely important, since it is the person’s only way to get air to the lungs. After a laryngectomy, a healthcare professional will teach the laryngectomee and his or her caregivers how to care for the stoma. Immediately after a laryngectomy, an alternate method of communication such as writing notes, gesturing, or pointing must be used. A partial laryngectomy patient will gradually regain some speech several weeks after the operation, but the voice may be hoarse, weak, and strained. A speech pathologist will work with a complete laryngectomee to establish new ways of communicating. There are three main methods of vocalizing after a total laryngectomy. In esophageal speech the laryngectomee learns how to ‘‘swallow’’ air down into the esophagus and creates sounds by releasing the air. This method requires quite a bit of coordination and learning, and produces short bursts (7 or 8 syllables) of low-volume sound. Tracheoesophageal speech diverts air through a hole in the trachea made by the surgeon. The air then passes through an implanted artificial voice prosthesis (a small tube that makes a sound when air goes through 799

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KE Y T ERM S

Laryngoscopy

it). Recent advances have been made in implanting voice prostheses that produce good voice quality. The third method of artificial sound communication involves using a hand-held electronic device that translates vibrations into sounds. There are several different styles of these devices, but all require the use of at least one hand to hold the device to the throat. The choice of which method to use depends on many things including the age and health of the laryngectomee, and whether other parts of the mouth, such as the tongue, have also been removed. Many patients resume daily activities after surgery. Special precautions must be taken during showering or shaving. Special instruction and equipment is also required for those who wish to swim or water ski, as it is dangerous for water to enter the windpipe and lungs through the stoma.

Resources ORGANIZATIONS

American Cancer Society. National Headquarters, 1599 Clifton Road NE, Atlanta, GA 30329. (800) ACS 2345.http://www.cancer.org. Cancer Information Service. National Cancer Institute, Building 31, Room 10A19, 9000 Rockville Pike, Bethesda, MD 20892. (800)4 CANCER. http:// www.nci.nih.gov/cancerinfo/index.html. International Association of Laryngectomees(IAL). http:// www.larynxlink.com/. National Institute on Deafness and Other Communication Disorders. National Institutes of Health, 31 Center Drive, MSC 2320, Bethesda, MD 20892 2320. http:// www.nidcd.nih.gov. The Voice Center at Eastern Virginia Medical School. Nor folk, VA 23507 http://www.voice center.com.

Regular follow-up visits are important following treatment for cancer of the larynx because there is a higher-than-average risk of developing a new cancer in the mouth, throat, or other regions of the head or neck. Many self-help and support groups are available to help patients meet others who face similar problems.

Risks Laryngectomy is often successful in curing early stage cancers. However it does cause lifestyle changes. Laryngectomees must learn new ways of speaking. They must be continually concerned about the care of their stoma. Serious infections can occur if water or other foreign material enters the lungs through an unprotected stoma. Also, women who undergo partial laryngectomy or who learn some types of artificial speech will have a deep voice similar to that of a man. For some women this presents psychological challenges.

Normal results Ideally, removal of the larynx will remove all cancerous material. The person will recover from the operation, make lifestyle adjustments, and return to an active life.

Abnormal results Sometimes cancer has spread to surrounding tissues and it is necessary to remove lymph nodes, parts of the tongue, or other cancerous tissues. As with any major operation, post-surgical infection is possible. Infection is of particular concern to laryngectomees who have chosen to have a voice prosthesis implanted, and is one of the major reasons for having to remove the device. 800

Kathleen Dredge Wright Tish Davidson, A.M.

Laryngoscopy Definition Laryngoscopy refers to a procedure used to view the inside of the larynx (the voice box).

Description The purpose and advantage of seeing inside the larynx is to detect tumors, foreign bodies, nerve or structural injury, or other abnormalities. Two methods allow the larynx to be seen directly during the examination. In one, a flexible tube with a fiber-optic device is threaded through the nasal passage and down into the throat. The other method uses a rigid viewing tube passed directly from the mouth, through the throat, into the larynx. A light and lens affixed to the endoscope are used in both methods. The endoscopic tube may also be equipped to suction debris or remove material for biopsy. Bronchoscopy is a similar, but more extensive procedure in which the tube is continued through the larynx, down into the trachea and bronchi.

Preparation Laryngoscopy is done in the hospital with a local anesthetic spray to minimize discomfort and suppress the gag reflex. Patients are requested not to eat for several hours before the examination. G A LE EN CY C LO PE DI A O F C AN C ER 3

Laxatives Laryngoscopy. Multiple images of epiglottis, vocal cords, and interior of trachea and bronchus. (Custom Medical Stock Photo. Reproduced by permission.)

Abnormal results

KE Y T ERM S Endoscopic tube—A tube that is inserted into a hollow organ permitting a physician to see the inside it.

An abnormal finding, such as a tumor or an object lodged in the tissue, would either be removed or described for further medical attention. Jill S. Lasker

Aftercare If the throat is sore, soothing liquids or lozenges will probably relieve any temporary discomfort.

Risks This procedure carries no serious risks, although the patient may experience soreness of the throat or cough up small amounts of blood until the irritation subsides.

Laxatives Definition A laxative is a drug that helps relieve constipation.

Purpose Normal results A normal result would be the absence of signs of disease or damage. G A LE EN CY C LO PE DI A O F C AN CE R 3

Laxatives are used to prevent or treat constipation. They are also used to prepare the bowel for an examination or surgical procedure. 801

Laxatives

Docusate calcium/docusate sodium

KEY T ERM S Cathartic—A general term for any agent that causes the bowel to empty. Cathartics are also known as purgatives. Constipation—Difficult or infrequent bowel movements. Diarrhea—Frequent, watery stools. Electrolyte levels—In the bloodstream, electrolyte levels are the amounts of certain acids, bases, and salts. Abnormal levels of certain electrolyes can be life-threatening. Encephalopathy—A brain disease. Peristalsis—Wave-like movement of the colon to pass feces along.

Docusate, a non-prescription laxative, helps a patient avoid constipation by softening the stool. It works by increasing the penetration of fluids into the stool by emulsifying feces, water and fat. Docusate prevents constipation and softens bowel movements and fecal impactions. This laxative should relieve constipation within one to three days. Lactulose Lactulose, a prescription laxative, reduces constipation and lowers blood ammonia levels. It works by drawing fluid into the intestine, raising the amount of water in the stool, and preventing the colon from absorbing ammonia. It is used to help people who suffer from chronic constipation.

Tetany—Muscle spasms that can be life-threatening.

Description Laxatives work in different ways, by stimulating colon movement, adding bulk to the contents of the colon, or drawing fluid or fat into the intestine. Some laxatives work by combining these functions. Most primary care physicians recommend that patients try the bulk-producing laxatives first before taking saline or stimulant laxatives. Bisacodyl Bisacodyl is a non-prescription stimulant laxative. It reduces short-term constipation and is also used to prepare the colon or rectum for an examination or surgical procedure. The drug works by stimulating colon movement (peristalsis); constipation is usually relieved within 15 minutes to one hour after administration of a suppository form and in 6 to 12 hours after taking the drug orally. Calcium polycarbophil Calcium polycarbophil is a non-prescription bulkforming laxative that is used to reduce both constipation and diarrhea. It draws water to the intestine, enlarging the size of the colon and thereby stimulating movement. It reduces diarrhea by taking extra water away from the stool. This drug should relieve constipation in 12 to 24 hours and have maximum effect in three days. Colitis patients should see a reduction in diarrhea within one week. 802

Psyllium Psyllium is a non-prescription bulk-forming laxative that reduces both constipation and diarrhea. It mixes with water to form a gel-like mass that can be easily passed through the colon. Constipation is relieved in 12 to 24 hours and maximum relief is achieved after several days. Senna/senokot Senna/senokot is a non-prescription laxative that reduces constipation by promoting colon movement. It is used to treat bouts of constipation and to prepare the colon for an examination or surgical procedure. This laxative reduces constipation in eight to 10 hours. New and investigational treatments for constipation Some newer options for the treatment of chronic constipation are being developed by various groups of researchers. These include such alternative therapies as biofeedback; newer drugs like tegaserod (Zelnorm) and prucalopride, which stimulate peristalsis; a nerve growth factor known as neurotrophin-3; and electrical stimulation of the colon.

Recommended dosage Laxatives may be taken by mouth or rectally (suppository or enema). Bisacodyl 

Adults or children over 12 years: 5–15 mg taken by mouth in morning or afternoon (up to 30 mg for surgical or exam preparation). G A LE EN CY C LO PE DI A O F C AN C ER 3







Adult (rectal): 10 mg. Children age 2 to 11 years: 10 mg rectally as single dose. Children over three years: 5–10 mg by mouth as single dose. Children under two years: 5 mg rectally as single dose. Calcium polycarbophil







Adult: 1 g by mouth every day, up to four times a day as needed (not to exceed 6 g by mouth in a 24-hour time period). Children age 6 to 12 years: 500 mg by mouth twice a day as needed (not to exceed 3 g in a 24-hour time period). Children age 3 to 6 years: 500 mg twice a day by mouth, as needed (not to exceed 1.5 g in a 24-hour time period). Docusate





 







Adult (docusate sodium): 50–300 mg by mouth per day. Adult (docusate calcium or docusate potassium): 240 mg by mouth as needed. Adult (docusate sodium enema): 5 ml. Children over 12 years (docusate sodium enema): 2 ml. Children age 6 to 12 years (docusate sodium): 40–120 mg by mouth per day. Children age 3 to 6 years (docusate sodium): 20– 60 mg by mouth per day. Children under 3 years (docusate sodium): 10–40 mg by mouth every day. Lactulose FOR CONSTIPATION:.

 

Adult: 15–60 ml by mouth every day. Children: 7.5 ml by mouth every day. FOR ENCEPHALOPATHY:.





Adult: 20–30 g three or four times a day until stools become soft. Retention enema: 30–45 ml in 100 ml of fluid. Infants and children: Parents should follow physician’s directions for infants and children with encephalopathy. Psyllium



Adult: 1–2 teaspoons mixed in 8 ounces of water two or three times a day by mouth, followed by 8 ounces

G A LE EN CY C LO PE DI A O F C AN CE R 3



water; or one packet in 8 ounces water two or three times a day, followed by 8 ounces of water. Children over 6 years: 1 teaspoon mixed in 4 ounces of water at bedtime. Senna/senokot



  





Adult (Senokot): 1 to 8 tablets taken by mouth per day or 1/2–4 teaspoons of granules mixed in water or juice. Adult (rectal suppository): 1 to 2 at bedtime. Adult (syrup): 1–4 teaspoons at bedtime. Adult (Black Draught): 3/4 ounce dissolved in 2.5 ounces liquid given between 2 P.M. and 4 P.M. on the day prior to a medical exam or procedure. Children: Parents should ask their doctor as dosage is based on weight. Black Draught is not to be used by children. Children age 1 month to 1 year (Senokot): 1.25–2.5 ml of syrup at bedtime.

Precautions The doctor should be informed of any prior allergic drug reaction, especially prior reactions to any laxatives. Pregnancy is also a concern. Animal studies have shown laxatives to have adverse effects on pregnancy, but no human studies regarding pregnancy are currently available. These drugs are only given in pregnancy after the risks to the fetus have been taken under consideration. Nursing mothers should use caution and consult their doctors before receiving these drugs. Bisacodyl should not be administered to patients with rectal fissures, abdominal pain, nausea, vomiting, appendicitis, abdominal surgery, ulcerated hemorrhoids, acute hepatitis, fecal impaction, or blockage in the biliary tract. Calcium polycarbophil should not be given to anyone with a gastrointestinal blockage (obstruction). Both psyllium and docusate calcium/docusate sodium should be avoided by patients with intestinal blockage, fecal impaction, or nausea and vomiting. Lactulose should be avoided by patients who are elderly, have diabetes mellitus, eat a low galactose diet, or whose general health is poor. Senna/senokot is inadvisable for patients with congestive heart failure, gastrointestinal bleeding, intestinal blockage, abdominal pain, nausea and vomiting, appendicitis, or prior abdominal surgery. The American College of Toxicology states that cathartics should not be used as a means of clearing 803

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Laxatives

poisons from the digestive tract of a poisoning victim. Although some physicians have administered these laxatives along with activated charcoal in order to reduce the body’s absorption of the poison, this treatment is no longer recommended.

Lactulose Common side effects include:   

Side effects Laxatives may have side effects. Some, such as nausea and vomiting, are more common than others. Side effects related to specific laxatives are described in this section. With repeated use, people may become dependent on laxatives. All side effects should be reported to a doctor.

   

Psyllium Common side effects include: 

Bisacodyl



Common side effects:



nausea  vomiting  loss of appetite (anorexia)  cramps 



 



Common side effects include:    

severe muscle spasms (tetany) Calcium polycarbophil

abdominal bloating (distention)  gas  laxative dependency 

nausea vomiting loss of appetite abdominal cramping Less common side effects include:

 

Side effects may include:

abdominal cramping blockage of the esophagus or intestine Senna/senokot



Life-threatening:

nausea vomiting loss of appetite diarrhea Less common side effects include:

Less common side effects: muscle weakness  diarrhea  electrolyte changes  rectal burning (when suppositories are used).

nausea vomiting loss of appetite abdominal cramping bloating belching diarrhea

 

diarrhea gas urine that is pink-red or brown-black in color abnormal electrolyte levels Life-threatening:



Severe muscle spasms (tetany)

Life-threatening: 

Interactions

gastrointestinal obstruction Docusate calcium/docusate sodium Side effects include:

bitter taste in the mouth irritated throat  nausea  cramps  diarrhea  loss of appetite  rash  

804

Laxatives may interact with other drugs. Sometimes, the laxative can interfere with proper absorption of another drug. A patient must notify their doctor or pharmacist if he or she is already taking any medications so that the proper laxative can be selected or prescribed. Specific drug interactions are: 





Bisacodyl: Antacids, H2 blockers, and some herbal remedies (lily of the valley, pheasant’s eye, squill). Calcium polycarbophil: (lowers the absorption of) tetracycline. Docusate calcium/docusate sodium: Unknown. G A LE EN CY C LO PE DI A O F C AN C ER 3





Lactulose: Neomycin and other laxatives. Psyllium: Cardiac glycosides, oral anticoagulants, and salicylates. Senna/senokot: Disulfiram should never be taken with this drug. Also, senna/senokot lowers the absorption of other drugs taken by mouth.

Resources BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Diarrhea and Constipation.’’ In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2007. Karch, A. M. Lippincott’s Nursing Drug Guide. Springhouse, PA: Lippincott Williams & Wilkins, 2003.

Description Leiomyosarcomas can start in any organ that contains smooth muscle, but can be found in the walls of the stomach, large and small intestines, esophagus, uterus, or deep within the abdomen (retroperitoneal). But for perspective, smooth muscle cancers are quite rare: Less than 1% of all cancers are leiomyosarcomas. Very rarely, leiomyosarcomas begin in blood vessels or in the skin. Most leiomyosarcomas are in the stomach. The second most common site is the small bowel, followed by the colon, rectum, and esophagus.

Demographics

PERIODICALS

DiPalma, J. A. ‘‘Current Treatment Options for Chronic Constipation.’’ Reviews in Gastroenterological Disor ders 4, Supplement 2 (2004): S34 S42. Newton, G. D., W. S. Pray, and N. G. Popovich. ‘‘New OTC Drugs and Devices 2003: A Selective Review.’’ Journal of the American Pharmaceutical Association 44 (March April 2004): 211 225. ‘‘Position Paper: Cathartics.’’ Journal of Toxicology: Clinical Toxicology 42 (March 2004): 243 253. Schiller, L. R. ‘‘New and Emerging Treatment Options for Chronic Constipation.’’ Reviews in Gastroenterological Disorders 4, Supplement 2 (2004): S43 S51. Talley, N. J. ‘‘Management of Chronic Constipation.’’ Reviews in Gastroenterological Disorders 4 (Winter 2004): 18 24. ORGANIZATIONS

American Society of Health System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657 3000. www.ashp.org. National Digestive Diseases Information Clearinghouse. 2 Information Way, Bethesda, MD 20892 3570. nddic @aerie.com. http://www.niddk.nih.gov/Brochures/ NDDIC.htm. United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857 0001. (888) INFO FDA. www.fda.gov.

Rhonda Cloos, R.N. Rebecca J. Frey, Ph.D.

Leiomyosarcoma Definition Leiomyosarcoma is cancer that consists of smooth muscle cells and small cell sarcoma tumor. The cancer begins in smooth muscle cells that grow uncontrollably and form tumors. G A LE EN CY C LO PE DI A O F C AN CE R 3

Leiomyosarcomas do occur in the breast and uterus, but they are very rare. Uterine sarcomas comprise less than 1% of gynecological malignancies and 2–5% of all uterine malignancies. Of these numbers, leiomyosarcomas are found in only 0.1% of women of childbearing age who have tumors of the uterus. Less than 2% of tumors in women over age 60 who are undergoing hysterectomy are leiomyosarcomas.

Causes and symptoms The exact causes of leiomyosarcoma are not known, but there are genetic and environmental risk factors associated with it. Certain inherited conditions that run in families may increase the risk of developing leiomyosarcoma. High-dose radiation exposure, such as radiotherapy used to treat other types of cancer, has also been linked to leiomyosarcoma. It is possible that exposure to certain chemical herbicides may increase the risk of developing sarcomas, but this association has not been proven. Since leiomyosarcoma can occur in any location, the symptoms are different and depend on the site of the tumor. When leiomyosarcoma begins in an organ in the abdomen, such as the stomach or small bowel, the physician may be able to feel a large lump or mass when he examines the abdomen. When leiomyosarcoma affects a blood vessel, it may block the flow of blood to the body part supplied by the artery. Commonly occurring symptoms include:     

painless lump or mass painful swelling abdominal pain weight loss nausea and vomiting 805

Leiomyosarcoma



Leiomyosarcoma Surgery to remove a leiomyosarcoma in the tissue near a kidney. (Custom Medical Stock Photo. Reproduced by permission.)

Diagnosis Some patients who have leiomyosarcomas may be visiting the doctor because they have discovered a lump or mass or swelling on a body part. Others have symptoms related to the internal organ that is affected by the leiomyosarcoma. For example, a tumor in the stomach may cause nausea, feelings of fullness, internal bleeding, and weight loss. The patient’s doctor will take a detailed medical history to find out about the symptoms. The history is followed by a complete physical examination with special attention to the suspicious symptom or body part. Depending on the location of the tumor, the doctor may order imaging studies such as x ray, computed tomography (CT) scan, and magnetic resonance imaging (MRI) to help determine the size, shape, and exact location of the tumor. A biopsy of the tumor is necessary to make the definitive diagnosis of leiomyosarcoma. The tissue sample is examined by a pathologist (specialist in the study of diseased tissue). 806

Types of biopsy The type of biopsy done depends on the location of the tumor. For some small tumors, the doctor may perform an excisional biopsy, removing the entire tumor and a margin of surrounding normal tissue. Most often, the doctor will perform an incisional biopsy, a procedure that involves cutting out only a piece of the tumor that is used to determine its type and grade.

Treatment team Patients with leiomyosarcoma are usually cared for by a multidisciplinary team of health professionals. The patient’s family or primary care doctor may refer the patient to other specialists, such as surgeons and oncologists (specialists in cancer medicine), radiologic technicians, nurses, and laboratory technicians. Depending on the tumor location and treatment plan, patients may benefit from rehabilitation therapy with physical therapists and nutritional counseling from dieticians. G A LE EN CY C LO PE DI A O F C AN C ER 3

Biopsy—The surgical removal and microscopic examination of living tissue for diagnostic purposes. Chemotherapy—Treatment of cancer with synthetic drugs that destroy the tumor either by inhibiting the growth of cancerous cells or by killing them.

Q U E S T I O N S TO A S K T H E DOCTOR   



What stage is the leiomyosarcoma? What are the recommended treatments? What are the side effects of the recommended treatment? Is treatment expected to cure the disease or only to prolong life?

Oncologist—A doctor who specializes in cancer medicine. Pathologist—A doctor who specializes in the diagnosis of disease by studying cells and tissues under a microscope. Radiation therapy—Treatment using high energy radiation from x-ray machines, cobalt, radium, or other sources. Stage—A term used to describe the size and extent of spread of cancer.

Leiomyosarcomas on the arms and legs may be treated by amputation (removal of the affected limb) or by limb-sparing surgery to remove the tumor. These tumors may also be treated with radiation therapy, chemotherapy, or a combination of both. Generally, tumors inside the abdomen are surgically removed. The site, size, and extent of the tumor determine the type of surgery performed. Leiomyosarcomas of organs in the abdomen may also be treated with radiation and chemotherapy.

Clinical staging, treatments, and prognosis Staging The purpose of staging a tumor is to determine how far it has advanced. This is important because treatment varies depending on the stage. Stage is determined by the size of the tumor, whether the tumor has spread to nearby lymph nodes, whether the tumor has spread elsewhere in the body, and what the cells look like under the microscope. Examining the tissue sample under the microscope, using special chemical stains, the pathologist is able to classify tumors as high grade or low grade. High-grade tumors have the more rapidly growing cells and so are considered more serious. Tumors are staged using numbers I through IV. The higher the number, the more the tumor has advanced. Stage IV leiomyosarcomas have involved either lymph nodes or have spread to distant parts of the body.

Side effects The surgical treatment of leiomyosarcoma carries risks related to the surgical site, such as loss of function resulting from amputation or from nerve and/or muscle loss. There also are risks associated with any surgical procedure, such as reactions to general anesthesia or infection after surgery. The side effects of radiation therapy depend on the site being radiated. Radiation therapy can produce side effects such as fatigue, skin rashes, nausea, and diarrhea. Most of the side effects lessen or disappear completely after the radiation therapy has been completed. The side effects of chemotherapy vary depending on the medication, or combination of anticancer drugs, used. Nausea, vomiting, anemia, lower resistance to infection, and hair loss (alopecia) are common side effects. Medication may be given to reduce the unpleasant side effects of chemotherapy. Alternative and complementary therapies

Treatment Treatment for leiomyosarcoma varies depending on the location of the tumor, its size and grade, and the extent of its spread. Treatment planning also takes into account the patient’s age, medical history, and general health. G A LE EN CY C LO PE DI A O F C AN CE R 3

Many patients explore alternative and complementary therapies to help to reduce the stress associated with illness, improve immune function, and feel better. While there is no evidence that these therapies specifically combat disease, activities such as biofeedback, relaxation, therapeutic touch, massage therapy, 807

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KE Y T ERM S

Leucovorin

and guided imagery have been reported to enhance well-being. Prognosis The outlook for patients with leiomyosarcoma varies. It depends on the location and size of the tumor and its type and extent of spread. Some patients, such as those who have had small tumors located in or near the skin surgically removed, have excellent prognoses. Their 5-year survival is greater than 90%. Among patients with leiomyosarcomas in organs in the abdomen, survival is best when the tumor has been completely removed. In general, high-grade tumors that have spread widely throughout the body are not associated with favorable survival rates.

Coping with cancer treatment Fatigue is one of the most common complaints during cancer treatment and recovery. Many patients benefit from learning energy-conserving approaches to accomplish their daily activities. They should be encouraged to rest when tired and take breaks from strenuous activities. Planning activities around times of day when energy is highest is often helpful. Mild exercise, small, frequent nutritious snacks, and limiting physical and emotional stress also help to combat fatigue. Depression, emotional distress, and anxiety associated with the disease and its treatment may respond to counseling from a mental health professional. Many cancer patients and their families find participation in mutual aid and group support programs helps to relieve feelings of isolation and loneliness. By sharing problems with others who have lived through similar difficulties, patients and families can exchange ideas and coping strategies.

Prevention Since the causes of leiomyosarcoma are not known, there are no recommendations about how to prevent its development. It is linked to radiation exposure; however, much of this excess radiation exposure is the result of therapy to treat other forms of cancer. Among families with an inherited tendency to develop soft tissue sarcomas, careful monitoring may help to ensure early diagnosis and treatment of the disease.

Special concerns Leiomyosarcoma, like other cancer diagnoses, may produce a range of emotional responses. Education, counseling, and participation in support group programs may help to reduce feelings of fear, anxiety and hopelessness. For many patients suffering from spiritual distress, visits with clergy members and participation in organized prayer may offer comfort. Resources BOOKS

Pelletier, Kenneth R. The Best of Alternative Medicine. New York: Simon & Schuster, 2000. PERIODICALS

Ishida, J., et al. ‘‘Primary Leiomyosarcoma of the Greater Omentum.’’ Journal Of Clinical Gastroenterology 28, no. 2 (March 1999): 167 170. OTHER

National Cancer Institute Clinical Cancer Trials. . ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, GA 30329. (800) 227 2345. Cancer Research Institute. 681 Fifth Avenue, New York, NY 10022. (800) 992 2623. National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422 6237.

Clinical trials Several clinical studies were underway as of 2001. For example, doctors at Memorial Sloan-Kettering Cancer Center were using specific chemotherapeutic drugs to treat patients with leiomyosarcoma that cannot be removed by surgery or has recurred. These drugs, gemcitabine, docetaxel, and filgrastim (G-CSF), work by stopping tumor cells from dividing, so they cannot grow. To learn more about this clinical trial and the availability of others, patients and families may wish to contact Memorial Sloan-Kettering Cancer Center at (212) 639-6555, or visit the National Cancer Institute (NCI) website at http://cancertrials. nci.nih.gov. 808

Barbara Wexler, M.P.H.

Letrozole see Aromatase inhibitors

Leucovorin Definition Leucovorin (also known as Wellcovorin and citrovorum factor or folinic acid) is a drug that can be used either to protect healthy cells from G A LE EN CY C LO PE DI A O F C AN C ER 3

Purpose Leucovorin is most often used in cancer patients undergoing either methotrexate or fluorouracil chemotherapy. Methotrexate is used to treat a wide range of cancers including breast cancer, head and neck cancers, acute leukemias, and Burkitt’s lymphoma. Fluorouracil is used in combination with leucovorin to treat colorectal cancer. When leucovorin and methotrexate are used together, this therapy often is called leucovorin rescue because leucovorin rescues healthy cells from the toxic effects of methotrexate. In patients with colorectal cancer, however, leucovorin increases the anti-cancer effect of fluorouracil. Leucovorin also is used to treat megaloblastic anemia, a blood disorder in which red blood cells become larger than normal, and to treat accidental overdoses of drugs such as methotrexate.

Description Leucovorin is a faster acting and stronger form of folic acid, and has been used for several decades. Folic acid also is known as vitamin B9, and is needed for the normal development of red blood cells. In humans, dietary folic acid must be reduced metabolically to tetrahydrofilic acid (THFA) to exert its vital biochemical functions. The coenzyme THFA and its subsequent other cofactors participate in many important reactions including DNA synthesis. Leucovorin rescue Some chemotherapy drugs, such as methotrexate (Mexate, Folex), work by preventing cells from using folic acid. Methotrexate therapy causes cancer cells to develop a folic acid deficiency and die. However, normal cells also are affected by folic acid deficiency. As a result, patients treated with drugs such as methotrexate often develop blood disorders and other toxic side effects. When these patients are given leucovorin, it goes into normal cells and rescues them from the toxic effects of the methotrexate. Leucovorin cannot enter cancer cells, however, and they continue to be killed by methotrexate. Leucovorin also works by rescuing healthy cells in patients who take an accidental overdose of drugs similar to methotrexate. Combination therapy Patients with colorectal cancer frequently are treated with fluorouracil (Adrusil). Fluorouracil, G A LE EN CY C LO PE DI A O F C AN CE R 3

Leucovorin

chemotherapy or to enhance the anti-cancer effect of chemotherapy.

KEY T ERMS Folic acid—Vitamin B9. Leucovorin rescue—A cancer therapy where the drug leucovorin protects healthy cells from toxic chemotherapy.

commonly called 5-FU, is effective, but only works for a short time once it is in the body. Leucovorin enhances the effect of fluorouracil by increasing the time that it stays active. As a result, the combination of the two drugs produces a greater anti-cancer effect than fluorouracil alone.

Recommended dosage Leucovorin can be given as an injection, intravenously, or as oral tablets. For rescue therapy, leucovorin usually is given intravenously or orally within 24 hours of methotrexate treatment. Dosage varies from patient to patient. When used in combination with fluorouracil, leucovorin is given to the patient intravenously first, followed by fluorouracil treatment. To treat unintentional folic acid antagonist overdose, leucovorin is usually given intravenously as soon as possible after the overdose. Patients with megaloblastic anemia receive oral leucovorin.

Precautions Patients with anemia, or any type of blood disorder, should tell their doctors. Leucovorin can treat only anemia caused by folic acid deficiency. Patients with other types of anemia should not take leucovorin. The effect of leucovorin on the fetus is not known, and it is not known if the drug is found in breast milk. Leucovorin should therefore be used with caution during pregnancy. Elderly patients treated with leucovorin and fluorouracil for advanced colorectal cancer are at greater risk for developing severe side effects.

Side effects The vast majority of patients do not experience side effects from leucovorin therapy. Side effects are usually caused by the patient’s chemotherapy, not by leucovorin. In rare cases, however, some patients can develop allergic reactions to the drug. These include skin rash, hives, and itching. In 2004, Swiss researchers found that oral desensitization may work in cases of severe allergic reaction to leucovorin. 809

Leukemias, acute

Interactions Although there are no listed drug interactions for leucovorin, patients should tell their doctors about any over the counter or prescription medication they are taking, particularly medication that can cause seizures. Resources PERIODICALS

‘‘Oral Desensitization May Work in Some Cases of Allergy to Leucovorin.’’ Drug Week November 14, 2003: 128.

Alison McTavish, M.Sc. Teresa G. Odle

Leukapheresis see Pheresis Leukemia see Acute erythroblastic leukemia; Acute lymphocytic leukemia; Acute myelocytic leukemia; Chronic lymphocytic Leukemia; Leukemia, Acute; leukemia, chronic

Leukemias, acute Definition Acute leukemia is a type of cancer in which excessive quantities of abnormal white blood cells are produced.

Demographics Leukemias account for 2% of all cancers. Because leukemia is the most common form of childhood cancer, it is often regarded as a disease of childhood. However, leukemias affect far more adults than children. Half of the cases adult leukemia occur in people who are 60 years of age or older. Chronic leukemia is diagnosed slightly more often than acute leukemia in adults. According to the estimates of the American Cancer Society (ACS), approximately 45,000 new cases of leukemia are diagnosed each year in the United States. An estimated 22,000 people will die from leukemia in 2009. In adults, the most common types of leukemia are acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Leukemia accounts for about one-third of cancer cases in children. The most commonly diagnosed type of leukemia in children is acute 810

lymphocytic leukemia (ALL) which is more prevalent in early childhood with a peak incidence between the ages of 2 and 4 years of age. Chronic leukemia is rare in children.

Description Medical science classifies acute leukemia by the type of white blood cell that undergoes mutation. The most common of these are: 



Acute lymphoblastic leukemia (ALL), in which excessive quantities of lymphoblasts, or immature lymphocyte white blood cells, are produced. ALL is also referred to as acute lymphocytic leukemia. Acute myeloblastic leukemia (AML), also known as acute myeloid leukemia and acute nonlymphocytic leukemia (ANLL), in which excessive quantities of other types of immature white blood cells are produced.

Acute leukemias progress rapidly, while the chronic leukemias progress more slowly. The cells that make up blood are produced in the bone marrow and the lymphatic system. Bone marrow is the spongy tissue found in the large bones of the body. The lymphatic system includes the spleen (an organ in the upper abdomen), the thymus (a small gland beneath the breastbone), and the tonsils (a mass of lymphatic tissue located in the throat). In addition, the lymphatic vessels (tiny tubes that branch like blood vessels into all parts of the body) and lymph nodes (pea-shaped organs that are found along the network of lymphatic vessels) are also part of the lymphatic system. Lymph is a milky fluid that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest. The cells found in the blood include red blood cells (RBCs) that carry oxygen and other materials to all tissues of the body; white blood cells (WBCs) that fight infection; and platelets, which play an important role in the clotting of the blood. White blood cells can be further subdivided into three main types: granulocytes, monocytes, and lymphocytes. The granulocytes, as their name suggests, have particles (granules) inside them. These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms, such as bacteria. Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens. Lymphocytes are the third type of white blood cell. There are two primary types of lymphocytes—T G A LE EN CY C LO PE DI A O F C AN C ER 3

Bone marrow makes stem cells, which are the precursors of the different blood cells. These stem cells mature through stages into RBCs, WBCs, or platelets. In acute leukemias, the maturation process of the white blood cells is interrupted. The immature cells (or ‘‘blasts’’) proliferate rapidly and begin to accumulate in various organs and tissues, thereby affecting their normal function. This uncontrolled proliferation of the immature cells in the bone marrow affects the production of the normal red blood cells and platelets as well. As noted, there are two types of acute leukemias— acute lymphocytic leukemia and acute myelogenous leukemia. Different types of white blood cells are involved in the two leukemias. In acute lymphocytic leukemia (ALL), it is the T or the B lymphocytes that are involved. The B cell leukemias are more common than T cell leukemias. Acute myelogenous leukemia, also known as acute nonlymphocytic leukemia (ANLL), is a cancer of the monocytes and/or granulocytes. Risk factors

similarities to the human immunodeficiency virus (HIV), is believed to be the causative agent for a rare form of ALL. The Epstein Barr virus, which causes mononucleosis, has also been linked to a form of ALL. The number of treatment-related cases of AML (individuals previously treated for cancer with chemotherapy and/or radiation therapy) is increasing particularly in survivors of childhood and adolescent cancers such as Hodgkin disease, lymphoma, sarcoma, testicular cancer and breast cancer. ALL is more common among Caucasians than among African-Americans, while acute myeloid leukemia (AML) affects both races equally. The incidence of acute leukemia is slightly higher among men than women. People with Jewish ancestry have a higher likelihood of getting leukemia. A higher incidence of leukemia has also been observed among persons with Down syndrome and some other genetic abnormalities. Exposure to ionizing radiation, such as occurred in Japan after the atomic bomb explosions, has been shown to increase the risk of getting leukemia. Electromagnetic fields are suspected of being a possible cause, as are certain organic chemicals, such as benzene. Having a history of diseases that damage the bone marrow, such as aplastic anemia, or a history of cancers of the lymphatic system puts people at a high risk for developing acute leukemias. Similarly, the use of anticancer medications, immunosuppressants, and the antibiotic chloramphenicol are also considered risk factors for developing acute leukemias. The symptoms of leukemia are generally vague and non-specific. A patient may experience all or some of the following symptoms: 

Several risk factors have been identified as playing a role in the development of acute leukemia including:



exposure to ionizing radiation exposure to medical radiation such as the radiation used to treat cancer patients previous treatment with certain types of chemotherapy agents history of Down syndrome and other genetic factors history of cigarette smoking exposure to certain chemicals such as benezene



 



  

       

Causes and symptoms The cause of most leukemias is not known. Leukemia occurs in both sexes and all ages. The human T-cell leukemia virus (HTLV-I), a virus with G A LE EN CY C LO PE DI A O F C AN CE R 3

   

weakness or chronic fatigue fever of unknown origin, chills and flu-like symptoms weight loss that is not due to dieting or exercise frequent bacterial or viral infections headaches skin rash non-specific bone pain easy bruising bleeding from gums or nose blood in urine or stools swollen and tender lymph nodes and/or spleen abdominal fullness night sweats petechiae, or tiny red spots under the skin more rarely, sores in the eyes or on the skin 811

Leukemias, acute

lymphocytes and B lymphocytes—with different functions in the immune system. B cells protect the body by making antibodies. Antibodies are proteins that can attach to the surfaces of bacteria and viruses. This ‘‘attachment’’ sends signals to many other cell types to come and destroy the antibody-coated organism. T cells protect the body against viruses. When a virus enters a cell, it produces certain proteins that are projected onto the surface of the infected cell. T cells recognize these proteins and make certain chemicals that are capable of destroying the virus-infected cells. In addition, T cells can destroy some types of cancer cells.

Leukemias, acute

Diagnosis Examination For a successful outcome, treatment for acute leukemia must begin as soon as possible, but there are no screening tests available. If the doctor has reason to suspect leukemia, he or she will conduct a very thorough physical examination to look for enlarged lymph nodes in the neck, underarm, and pelvic region. Swollen gums, enlarged liver or spleen, bruises, or pinpoint red rashes all over the body are some of the signs of leukemia. Tests Urine and blood tests may be ordered to check for microscopic amounts of blood in the urine and to obtain a complete differential blood count. This count will give the numbers and percentages of the different cells found in the blood. An abnormal blood test might suggest leukemia; however, the diagnosis must be confirmed by more specific tests. Standard imaging tests, such as x rays, computed tomography scans (CT scans), and magnetic resonance imaging (MRI) may be used to check whether the leukemic cells have invaded other areas of the body, such as the bones, chest, kidneys, abdomen, or brain. Sophisticated cytogenetic studies, which examine the number and shape of chromosomes in the DNA of individual blast (immature) cells, should be conducted in addition to the immunophenotyping of cells of the bone marrow. This procedure involves applying various stains to the marrow cells. These stains help doctors identify some of the proteins lying on the surface of the cells. Procedures The doctor may perform a bone marrow biopsy to confirm the diagnosis of leukemia. During the biopsy, a cylindrical piece of bone and marrow is removed. The tissue is generally taken out of the hipbone. These samples are sent to the laboratory where they are examined under a microscope by a hematologist, oncologist, or pathologist. In addition to the diagnostic biopsy, another biopsy will also be performed during the treatment phase of the disease to see if the leukemia is responding to therapy. A spinal tap (lumbar puncture) is another procedure that the doctor may order to diagnose leukemia. In this procedure, a small needle is inserted into the spinal cavity in the lower back 812

to withdraw some cerebrospinal fluid and to look for leukemic cells.

Treatment As noted, treatment must be begun as soon as possible. The goal of treatment is remission, or an arresting of the disease process of the leukemia. There are two phases of treatment for leukemia. The first phase is called induction therapy. As the name suggests, during this phase, the primary aim of the treatment is to reduce the number of leukemic cells as much as possible and induce a remission in the patient. Once the patient shows no obvious signs of leukemia (no leukemic cells are detected in blood tests and bone marrow biopsies), the patient is said to be in remission. The second phase of treatment is then initiated. This is called consoliation or maintenance therapy, and the goal is to kill any remaining cancer cells and to maintain the remission for as long as possible. Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. It is usually the treatment of choice in leukemia, and is used to relieve symptoms and achieve longterm remission of the disease. Generally, combination chemotherapy, in which multiple drugs are used, is more efficient than using a single drug for the treatment. Some drugs may be administered intravenously through a vein in the arm; others may be given by mouth in the form of pills. If the cancer cells have invaded the brain, then chemotherapeutic drugs may be put into the fluid that surrounds the brain through a needle in the brain or back. This is known as intrathecal chemotherapy. Because leukemia cells can spread to all the organs via the blood stream and the lymphatic vessels, surgery is not considered an option for treating leukemias. Radiation Radiation therapy, which involves the use of x rays or other high-energy rays to kill cancer cells and shrink tumors, may be used in some cases. For acute leukemias, the source of radiation is usually outside the body (external radiation therapy). If the leukemic cells have spread to the brain, radiation therapy can be given to the brain. Targeted therapies and other biologic therapies, such as the use of monoclonal antibodies, are increasingly being utilized in the treatment of acute leukemia. For example, the monoclonal antibody, rituximab (Rituxan) may be used to treat adult ALL patients whose leukemic cells are positive for the CD20 G A LE EN CY C LO PE DI A O F C AN C ER 3





 



 

What type of acute leukemia do I or does my child have? How common is this particular type of acute leukemia? How is this type of leukemia treated? Can this type be treated in my community or should I be referred to a treatment center that specializes in my particular type of acute leukemia? How rigorous will my treatment be? What kind of side effects can I expect from treatment? How long will my treatments last? What is the long-term prognosis for my type of leukemia?

antigen. Some patients with Philadelphia chromosome positive ALL may receive the targeted therapy agents imatinib (Gleevec) or dasatinib (Sprycel) to treat their leukemia.

Prognosis Like all cancers, the prognosis for leukemia depends on the patient’s age and general health. According to statistics, more than 60% of patients with leukemia survive for at least a year after diagnosis. Acute myelocytic leukemia (AML), with a five year overall survival rate of only 22%, has a poorer prognosis rate than acute lymphocytic leukemias (ALL) and the chronic leukemias. In the last 20 years, the five-year survival rate for patients with ALL has increased from 42–66%. Interestingly enough, since most childhood leukemias are of the ALL type, chemotherapy has been highly successful in their treatment. This is because chemotherapeutic drugs are most effective against actively growing cells. Due to the new combinations of anticancer drugs being used, the survival rates among children with ALL have improved dramatically. Ninety-five percent of all childhood ALL patients will enter remission, and 60–88% will remain in remission after five years, depending upon the type. T-cell ALL is considered curable in half of all cases, while B-cell ALL is rarely, if ever curable. G A LE EN CY C LO PE DI A O F C AN CE R 3

Many cancers can be prevented by changes in lifestyle or diet, which will reduce the risk factors. However, in leukemias, there are no such known risk factors. Therefore, at the present time, no way is known to prevent leukemias from developing. People who are at an increased risk for developing leukemia because of proven exposure to ionizing radiation or exposure to the toxic liquid benzene, and people with Down syndrome, should undergo periodic medical checkups. Resources PERIODICALS

Belson, M., Kingsley, B., & Holmes, A.‘‘Risk Factors for Acute Leukemia in Children: A Review.’’ Environ Health Perspect 115 (2007):138 45. Brown, P., Hunger, S.P., Smith, F.O., Carroll, W.L., & Reaman, G.H.‘‘Novel Targeted Drug Therapies for the Treatment of Childhood Acute Leukemia’’Expert Rev Hematol 2 (2009):145 58. Pui, CH., Robinson, L.L., & Look, A.T.‘‘Acute Lympho blastic Leukemia’’ Lancet 371 no.9617 (March 22, 2008): 166 78. Stock, W.‘‘Clinical Trials in Adult AML’’Clin Adv Hematol Oncol 7 (2009):8 10. OTHER

National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology Acute Myeloid Leukemia [cited October 2, 2009] https://www.nccn.org/professionals/ physician_gls/PDF/aml.pdf. University of Pennsylvania Cancer Center. Oncolink. http:// cancer.med.upenn.edu. ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, Georgia 30329. (800) 227 2345. http://www.cancer.org. Cancer Research Institute. 681 Fifth Avenue, New York, N.Y. 10022. (800) 992 2623. http://www.cancer research.org. The Leukemia & Lymphoma Society. 1311 Mamaroneck Ave., Suite 310 White Plains, NY 10605. (800) 955 4572. www.leukemia lymphoma.org.

Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Leukemias, chronic Definition Chronic leukemia is a type of cancer in which excessive quantities of abnormal white blood cells are produced, usually slowly, often over a period of years. 813

Leukemias, chronic

Prevention

QUESTIONS TO ASK YOUR DOCTOR

Leukemias, chronic

The most common types of chronic leukemia are chronic lymphocytic leukemia (CLL) and chronic myelocytic leukemia (CML).

Demographics Leukemias account for about 2% of all cancers. Because leukemia is the most common form of childhood cancer, it is often regarded as a disease of childhood. However, leukemias affect far more adults than children. Half of the cases of adult leukemia occur in people who are 60 years of age or older. Chronic leukemia is diagnosed slightly more often than acute leukemia in adults. According to the estimates of the American Cancer Society (ACS), approximately 45,000 new cases of leukemia are diagnosed each year in the United States. An estimated 22,000 people will die from leukemia in 2009.

by CML. The average age at diagnosis is 67 years. CML can affect people of any age although it very rarely appears in children. The American Cancer Society estimates about 5,000 new cases of CML will be diagnosed in the United States in 2009 and 450 deaths will occur from the disease in that year. Between 1973 and 1991, the rate at which CML appeared in the United States decreased slightly.

Description Medical science classifies chronic leukemia by the type of white blood cell that undergoes mutation. The most common of these are: 



In adults, the most common types of leukemia are acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Leukemia accounts for about one-third of cancer cases in children. The most commonly diagnosed type of leukemia in children is acute lymphocytic leukemia (ALL) which is more prevalent in early childhood with a peak incidence between the ages of 2 and 4 years of age. Chronic leukemia is rare in children. Eighty percent of cases of CLL are observed in patients who are 60 years or older, with an average age at diagnosis of 72 years. Rarely is CLL diagnosed in a patient who is less than 40 years of age. CLL almost never occurs in children. The incidence of this disease increases with age. According to estimates of the American Cancer Society, approximately 15,000 new cases of CLL will be diagnosed in 2009. About 4,000 Americans will die of CLL in 2009. Average lifetime risk of developing CLL is one-half of 1% or about 1 in 200. CLL affects both sexes. Among patients younger than 65, the disease is slightly more common in men. However, among patients older than 75 years of age, CLL appears almost equally among men and women. Over the past 50 years, the incidence rate of CLL has increased significantly. However, many scientists think this increase is not necessarily due to the disease being more common than in the past, but instead due to the fact that the disease is now more likely to be accurately diagnosed when it does occur. Fifty years ago, only one of ten CLL patients was diagnosed during early stages. Today, half of all CLL patients are diagnosed in the early stage of the disease. CML accounts for about 15% of all leukemias. The average lifetime risk of developing CML is about 1 in 500. Slightly more men than women are affected 814

Chronic lymphocytic leukemia (CLL), in which mature-appearing white blood cells called lymphocytes are produced. Chronic myeloid (or myelogenous) leukemia (CML), also known as chronic granulocytic leukemia (CGL), is the result of uncontrolled proliferation of white blood cells called granulocytes.

Chronic leukemias are typically much less rapidgrowing than acute leukemia, and affect adults far more often than children. In fact, nearly all the people who develop CLL are over 50 years of age. CML is also a disease primarily of middle-aged to elderly people. The cells that make up blood are produced in the bone marrow and the lymph system. The bone marrow is the spongy tissue found in the large bones of the body. The lymph system includes the spleen (an organ in the upper abdomen), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat). The lymph vessels (tiny tubes that branch like blood vessels into all parts of the body) and lymph nodes (small pea-shaped organs that are found along the network of lymph vessels) are also part of the lymph system. The lymph itself is a milky fluid that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest. The cells found in the blood are the red blood cells (RBCs), which carry oxygen and other materials to all tissues of the body; white blood cells (WBCs), which fight infection; and the platelets, which play an important role in the clotting of the blood. The white blood cells can be further subdivided into three main types: granulocytes, monocytes, and lymphocytes. The granulocytes have particles (granules) inside them that contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms such as bacteria. G A LE EN CY C LO PE DI A O F C AN C ER 3

The lymphocytes form the third type of white blood cell. The two primary types of lymphocytes, T lymphocytes and B lymphocytes, have different functions within the immune system. The B cells protect the body by making antibodies, which are proteins that can attach to the surfaces of bacteria and viruses. This attachment sends signals to many other cell types to destroy the antibody-coated organism. The T cells protect the body against viruses. When a virus enters a cell, it produces certain proteins that are projected onto the surface of the infected cell. The T cells recognize these proteins and make certain chemicals that are capable of destroying the virus-infected cells. In addition, the T cells can destroy some types of cancer cells. The bone marrow makes stem cells, which are the precursors of the different blood cells. Stem cells mature into RBCs, WBCs, or platelets. In chronic leukemias, blood cells suddenly begin to proliferate rapidly and begin to accumulate in various organs and tissues, thereby affecting their normal function. This uncontrolled proliferation of the immature cells in the bone marrow affects the production of the normal red blood cells and platelets as well. Different types of white blood cells are involved in chronic lymphocytic leukemia and chronic myeloid leukemia. Although some blasts, or immature cells (the hallmark of acute leukemia), are also present in chronic leukemia, it is the T or B lymphocytes that gradually mutate and become cancerous. The scenario is similar for chronic myelogenous leukemia, also known as chronic granulocytic leukemia (CGL), which occurs when unusually large numbers of granulocytes begin to appear in the bloodstream. Risk factors There are very few established risk factors related to the development of CLL. Results of some research studies related to the link between chemical exposure and the development of CLL implicate exposure to Agent Orange, an herbicide used in the Vietnam War, and long-term exposure to pesticides as possible causes of CLL. Family history also appears to be a risk factor for CLL. First-degree relatives (parents, siblings, and children) of CLL patients are two to four times more likely to be diagnosed with CLL as people who have no family history of CLL. As with CLL there are very few established risk factors related to the development of CML. The only known risk factor for the development of CML is G A LE EN CY C LO PE DI A O F C AN CE R 3

exposure to high-dose radiation such as radiation from an atomic blast or from a nuclear reactor accident.

Causes and symptoms Leukemia occurs in both sexes and in all ages. The human T-cell leukemia virus (HTLV-I), a virus with similarities to the human immunovirus (HIV), is believed to be the causative agent for some kinds of leukemias. To date, the cause of most leukemias is not known. Lymphoid leukemias are more common among Caucasians than among African-Americans, while myeloid leukemias affects both races equally. The incidence of leukemia is slightly higher among men than women. A higher incidence of leukemia has also been observed among persons with Down syndrome and some other genetic abnormalities. Patients with chronic myeloid leukemia often show a chromosome abnormality called the Philadelphia chromosome that occurs when one chromosome attaches to another. Exposure to ionizing radiation, such as occurred in Japan after the atomic bomb explosions, has been shown to increase the risk of getting leukemia. Electromagnetic fields are suspected of being a possible cause, as are certain organic chemicals such as benzene. Having a history of diseases that damage the bone marrow, such as aplastic anemia, or a history of cancers of the lymphatic system puts people at a high risk for developing leukemias. Similarly, the use of anticancer medications, immunosuppressants, and the antibiotic chloramphenicol are also considered risk factors for developing leukemias. In 2003, the Institute of Medicine (IOM) released a report based upon scientific studies that found ‘‘sufficient evidence of an association’’ between CLL and exposure to herbicides during the Vietnam War. This report came from a Veterans Administration (VA) request to IOM to explore some similarities between CLL and non-Hodgkin’s lymphoma. Non-Hodgkin’s lymphoma has already been linked to Agent Orange exposure and is recognized by VA as a presumptive condition. The symptoms of chronic leukemia are generally vague and non-specific, and are frequently overlooked until they are noticed on routine physical examination, especially when a routine blood test such as a complete blood count (CBC) is performed. A CBC may show unusually large numbers of a certain type of lymphocyte in the blood. Chronic leukemias may go for years without manifesting any symptoms at all, but also can develop symptoms similar to acute leukemias. 815

Leukemias, chronic

Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens.

Leukemias, chronic

Chronic myeloid leukemia, in particular, has a two- or three-stage progression, a chronic phase that can last for several years, an accelerated phase, and a terminal blastic phase, a malignant phase in which immature granulocytes are suddenly generated in huge numbers, producing similar symptoms to acute leukemia. In such cases, a patient may experience all or some of the following symptoms:

number of white blood cells. Somewhat less than half of CML patients will also have high numbers of blood platelets. Most CML patients have mild anemia. The composition of the bone marrow in CML patients also differs from that of a healthy person. The marrow is described as being hypercellular. This means that the number of cells present in the bone marrow is unusually great.

weakness or chronic fatigue  fever of unknown origin, chills, and flu-like symptoms  unexplained weight loss  frequent bacterial or viral infections  viscous (sticky) blood (which slows down the supply to various organs)  headache  non-specific bone pain  easy bruising  bleeding from gums or nose  blood in urine or stools  swollen and tender lymph nodes and/or spleen  abdominal fullness  night sweats  petechiae, or tiny red spots under the skin  priapism, or persistent, painful erection of the penis  rarely, sores in the eyes or on the skin

Laboratory findings indicate when a CML patient enters the accelerated phase from the chronic phase of CML. In the chronic phase, there are less than 10% blasts or immature cells in the blood or the bone marrow. Once there are more than 10% but less than 20% blasts detected in the blood or bone marrow of the patient with CML, the patient is said to be in the accelerated phase of the disease. When greater than 20% blasts are detected in the blood or the bone marrow the CML patient is said to be in the blast phase. Other names for this phase are the acute phase or blast crisis. In this phase, the CML acts more like an aggressive acute form of leukemia.



Diagnosis Examination There are often no symptoms present for chronic leukemia, and there are no screening tests available. If the physician has reason to suspect leukemia, a very thorough physical examination will be conducted to look for enlarged lymph nodes in the neck, underarm, and pelvic region. Swollen gums, enlarged liver or spleen, bruises, or pinpoint red rashes all over the body are some of the signs of leukemia. Tests Urine and blood tests may be ordered to check for microscopic amounts of blood in the urine and to obtain a complete differential blood count, which gives the numbers and percentages of the different cells found in the blood. An abnormal blood test might suggest leukemia. However, the diagnosis has to be confirmed by more specific tests. The presence of the Philadelphia (Ph) chromosome is a crucial factor in the diagnosis of CML. People who have CML have an unusually high 816

Some CLL patients will have a condition called hypogammaglobulinemia which can be detected by blood tests. Immunoglobulins are normal parts of the body’s immune system, the system used to fight off infections. Patients with hypogammaglobulinemia have very low levels of all of the various types of immunoglobulins. The physician may also order immunophenotyping tests. This involves taking a sample of the blood and looking at what types of cells of the immune system are being affected by the CLL. Approximately 19 out of 20 CLL patients have the B-cell type of CLL. In addition, the doctor may look for abnormalities in the chromosomes of affected cells. Patients exhibiting no chromosomal abnormalities have a better prognosis than those who do have such abnormalities. Standard imaging tests such as x rays, computed tomography (CT) scans, and magnetic resonance imaging (MRI) may be used to check whether the leukemic cells have invaded other areas of the body, such as the bones, chest, kidneys, abdomen, or brain. Procedures The physician may perform a bone marrow biopsy, during which a small piece of bone and marrow is removed, generally taken from hipbone. A spinal tap (lumbar puncture) is another procedure that may be ordered. In this procedure, a small needle is inserted into the spinal cavity in the lower back to withdraw some cerebrospinal fluid and to look for leukemic cells. G A LE EN CY C LO PE DI A O F C AN C ER 3

Treatment for CML In recent years, targeted therapy, specifically the tyrosine kinase inhibitors, have become the standard treatment of choice for CML and have revolutionized the treatment of CML. These drugs seem to work best for those in the chronic phase of the disease although they may also be effective for patients with more advanced disease. In 2009, National Comprehensive Cancer Center (NCCN) practice guidelines for the treatment of CML recommend primary treatment with the tyrosine kinase inhibitor, imatinib mesylate (Gleevec), for newly diagnosed patients with Philadelphia chromosome or BCR-ABL positive chronic phase CML. Gleevec targets the one special protein almost all CML cells possess. Nearly all CML patients respond to Gleevec with responses often lasting for many years. Follow-up clinical studies indicate most patients who received the drug and who were followed for five years or more years are experiencing a high response rate without relapse of the disease. Gleevec is given in pill form and is usually taken once per day with food. Some side effects include diarrhea, nausea, fatigue, muscle pain, and skin rashes. Another side effect is edema around the eyes, feet, or abdomen. Chemotherapy use in CML is now reserved for patients as part of treatment preceding stem cell transplants. Radiation therapy is used only sparingly in the treatment of CML. It may be used to shrink an enlarged spleen, to treat pain caused by an increase in leukemia cells in the bone marrow or in low doses as pre-treatment for stem cell transplant. Because of the apparent long-term effectiveness of Gleevec in sustaining remission in most CML patients, the role of stem cell transplant in the treatment of CML is being re-examined. Currently, NCCN guidelines recommend allogeneic stem cell transplant in CML as an alternative treatment option for patients who are not able to achieve remission after 3 months of Gleevec or other targeted therapy, for those patients who achieve no response or for those who relapse 6, 12, or 18 months after achieving initial remission on Gleevec therapy and finally, for those patients who are already on Gleevec yet who progress from the chronic phase to the accelerated phase or the blast crisis phase of CML. The current treatment recommendation by phase of CML are: chronic phase - treatment with Gleevec; accelerated phase—Gleevec has brought about remission in this phase but remission may not be long-term. Chemotherapy may be used to induce remission prior to undergoing stem cell transplant; blast phase - high G A LE EN CY C LO PE DI A O F C AN CE R 3

dose Gleevec may be effective for patients who haven’t been treated previously. Newer tyrosine kinase inhibitors dasatinib and nilotinib may be more effective in this phase but that has not yet been conclusively determined. Patients who do not respond to Gleevec or to the newer agents may be offered stem cell transplants. The transplant is more likely to be effective if the CML can be brought into remission prior to the transplant. Treatment for CLL Because the long-term prognosis for many patients with CLL is excellent, many patients (about 1/3) receive no treatment at all at first. Many patients (1/3) go for years before developing aggressive disease that requires treatment. Another 1/3 will require immediate treatment intervention at the time of diagnosis. Treatment for CLL is typically initiated in a stepwise progression from the least invasive method of monitoring blood work and symptoms at regular intervals, known as watchful waiting, to treatment with chemotherapy and/or stem cell transplantation. Decisions to initiate treatment are based on stage of disease, presence of symptoms, and activity of the disease. At this time, in 2009, patients with limited stage disease should not be treated until they become symptomatic. Treatment for early stage CLL should be started only when one of the following conditions appears: 



 

 

Symptoms of the disease are growing worse, for example, there is a greater degree of fever, weight loss, night sweats, and so forth. The spleen is enlarging or enlargement of the spleen has become painful. Disease of the lymph nodes has become more severe. The condition of the bone marrow has deteriorated and there is anemia and a marked reduction in the number of blood platelets for reasons not specifically related to the condition of the bone marrow. The population of lymphocytes is rapidly growing. The patient is experiencing numerous infections caused by bacteria.

Therapy for CLL usually starts with chemotherapy. Depending on the stage of the disease, single or multiple drugs may be given. Drugs commonly prescribed include fludarabine, cladribine, chlorambucil and cyclophosphamide. The standard first-line therapy in 2009 is fludarabine and cyclophosphamide used in combination. Another combination is a regimen consisting of the monoclonal antibody rituximab and/or cyclophosphamide. Another monoclonal antibody, alemtuzumab, may be used when patients are refractory to fludarabine-based regimens. Close 817

Leukemias, chronic

Treatment

Leukoencephalopathy

QUESTIONS TO ASK YOUR DOC TOR   

 



What type of chronic leukemia do I have? How will the leukemia be treated? Can I receive treatment in my community or should I consider receiving treatment in a specialized treatment center? How long will my treatment last? What side effects can I expect from the treatment? What is my long-term prognosis?

monitoring for life-threatening infections is important when the patient is receiving alemtuzumab. Another option for CLL patients is allogenic stem cell transplantation. This option is typically reserved for patients less than 65 years old because of the intensity of the conditioning regimen and due to the considerable risk for mortality. Clinical trials are ongoing to evaluate the effectiveness of newer agents to treat CLL including flavopiridol and lenalidomide.

Prognosis The newer, more effective drugs now used to treat CML first became available in 2001. Currently, there are no long term data to predict how long patients treated with these drugs will survive. However, one large study conducted with patients who were treated with Gleevec revealed that 90% of patients were still alive and in remission with no evidence of leukemia after 5 years of treatment. Longer follow-up of these patients is still needed and is ongoing. For many CLL patients, the prognosis is based on stage at diagnosis. Using the Binet and Rai staging systems criteria, patients staged as low risk usually survive more than 10 years. Patients staged as intermediate risk usually survive about 7 years. Patients staged as high risk usually survive about 2 to 5 years. The average patient survives 9 or more years after diagnosis.

leukemia should be encouraged to undergo periodic medical evaluations. Resources BOOKS

Caligaris Cappio, Federico, and Riccardo Dalla Favera Chronic Lymphocytic Leukemia New York: Springer, 2005. PERIODICALS

Maddocks, K.J.,& Lin, T.S.‘‘Update in the Management of Chronic Lymphocytic Leukemia.’’J Hematol Oncol 2 (2009):29. Jabbour, E., Cortes, J.E., et al.‘‘Current and Emerging Treatment Options in Chronic Myeloid Leukemia.’’ Cancer 109 (2007):2171 81. Hochhaus, A., Druker, B., Sawyers, C., et al. ‘‘Favorable Long term Follow up Results Over 6 Years for Response, Survival, and Safety with Imatinib Mesylate Therapy in Chronic phase Chronic Myeloid Leukemia after Failure with Interferon alpha Treatment.’’ Blood 111 (2008):1039 43. Robak, T.‘‘Novel Drugs for Chronic Lymphoid Leukemias: Mechanism of Action and Therapeutic Activity.’’Curr Med Chem 16 (2009):2212 34. Schiffer, C.A.‘‘BCR ABL Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia’’N Engl J Med 357 (2007):258 65. OTHER

National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology v.2. 2010 Chronic Myelogenous Leukemia [cited October 2, 2009] http://www.nccn.org/ professionals/physician_gls/PDF/cml.pdf Oncolink. University of Pennsylvania Cancer Center. http:// cancer.med.upenn.edu. ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, Georgia 30329. (800) 227 2345. http://www.cancer.org. Cancer Research Institute. One Exchange Place, 55 Broad way, Suite 1802 New York, N.Y. 10006. (800) 992 2623. http://www.cancerresearch.org. The Leukemia & Lymphoma Society. 1311 Mamaroneck Ave., White Plains, NY 10605. (800) 955 4572. http:// www.leukemia lymphoma.org

Melinda Granger Oberleitner, R.N., D.N.S., A.P.R.N., C.N.S.

Prevention There is no known way to prevent chronic leukemia. People who are at an increased risk for developing chronic leukemia because of proven exposure to radiation, Agent Orange or long-term exposure to pesticides and people with a family history of chronic 818

Leukoencephalopathy Description Leukoencephalopathy is a disease occurring primarily in the white matter of the brain that involves G A LE EN CY C LO PE DI A O F C AN C ER 3

The symptoms of leukoencephalopathy reflect the mental deterioration that occurs as, at multiple sites within the brain, the myelin cover of nerve cells is eroded, leaving nerve cells exposed and with no protective insulation. Patients may exhibit problems with speech and vision, loss of mental function, uncoordinated movements, and extreme weakness and fatigue. Patients may have no desire to eat. The disease is usually progressive; patients continue to lose mental function, may have seizures, and finally lapse into a coma before death. Some patients stabilize, however, although loss of neurologic function is usually irreversible. Leukoencephalopathy as it relates to cancer patients is primarily associated with methotrexatechemotherapy, which is used in treatment of many different types of cancer. Some other medications, including cytarabine, fludarabine, carmustine and fluorouracil in conjunction with levamisole. The disease may appear years after the administration of methotrexate. Although rare, the incidence of leukoencephalopathy is increasing, as stronger drugs are developed and increased survival times allow time for the side effects of the treatments to appear. A devastating type of leukoencephalopathy, called multifocal, or disseminated, necrotizing leukoencephalopathy, has been shown to occur primarily when methotrexate or cytarabine therapy is used in conjunction with a large cumulative dose of whole head irradiation. This disease is characterized by multiple sites of necrosis of the nerve cells in the white matter of the brain, involving both the myelin coating and the nerve cells themselves. Although some patients may stabilize, the course is usually progressive, with patients experiencing relentless mental deterioration and, finally, death. Although leukoencephalopathy is primarily associated with methotrexate therapy, this disease has also been observed in association with other chemotherapeutic drugs (like intrathecal cytarabine) and occasionally been reported in association with cancers that have not yet been treated. Another, particularly lethal, type of leukoencephalopathy called progressive multifocal leukoencephalopathy (PML) is an opportunistic infection that occurs in cancer patients who experience long-term immunosuppression as a result of the cancer (as in leukemia or lymphoma) or as a result of G A LE EN CY C LO PE DI A O F C AN CE R 3

chemotherapy or immunosuppressive drugs. PML results when, due to chronic immunosuppression, the JC virus, widely found in the kidneys of healthy people, becomes capable of entering the brain. The virus infects the cells that produce myelin and causes multiple sites in the brain of nerve cells without the protective fatting coating. For reasons that are not completely clear, PML has a rapid and devastating clinical course, with death occurring typically less than six months after diagnosis.

Causes It is only relatively recently that longer survival times for cancer patients have enabled scientists to identify an association of leukoencephalopathy with intensive chemotherapy (particularly methotrexate), especially when combined with large doses of whole head radiation. The causes of the neural degeneration observed are still not completely understood. Most cases of leukoencephalopathy observed have occurred in patients who received methotrexate (either directly into the brain, through a tube in the skull, or intravenously) or who have received large doses of radiation to the head. Up to 50% of children who have received both treatments have developed necrotizing leukoencephalopathy, which differs from regular leukoencephalopathy in that the multiple sites of demyelinization also involve necrosis (the death of cells due to the degradative action of enzymes). Deterioration of the nerve tissue in necrotizing leukoencephalopathy appears to begin with the nerve and then spread into the myelin coating. The method of action in PML is also not well understood. Long-term immunosuppression somehow appears to create an environment where the JC virus that inhabits most healthy human kidneys can mutate into a form that gains access to the brain. When in the brain, the virus infects and kills the cells that produce the myelin that forms a protective coating around the nerve.

Treatments Unfortunately, there is no cure for any form of leukoencephalopathy, and no treatments approved. Although some medications have shown some effect against the deterioration involved in this disease, those identified have been highly toxic themselves, and none so far have been effective enough to justify use. The treatment of people with this disorder, therefore, tends to concentrate on alleviating discomfort. Since there are no effective treatments, prevention must be emphasized. As the risks of certain treatment 819

Leukoencephalopathy

defects in either the formation or the maintenance of the myelin sheath, a fatty coating that protects nerve cells. Leukoencephalopathy has several different forms and causes.

Leukotriene inhibitors

choices have become more defined, physicians must pursue careful treatment planning to produce optimal chance of tumor eradication while avoiding increased risk of the onset of a fatal and incurable side effect. This is especially true in children. The cases observed have largely been in children, which implies that the developing brain is at higher risk of developing treatment-associated leukoencephalopathy. Alternative and complementary therapies There are no commonly used alternative treatments, although since the disease is incurable, there is little risk involved in trying nontraditional medications. Complementary therapies (yoga, t’ai chi, etc.) that improve patient wellbeing are appropriate if the patient finds them helpful. Resources BOOKS

Abeloff, Martin. Clinical Oncology. 2nd ed. Camden Town: Churchhill Livingstone, Inc., 2004. Mandell, Gerald. Principles and Practice of Infectious Dis eases. 5th ed. St. Louis: Harcourt Health Sciences Group, 2000.

KEY T ERMS Asthma—Disorder involving chronic inflammation in which the airways are narrowed in a reversible manner making it difficult to breathe normally, especially during acute exacerbations known as asthma attacks. Bronchi—Airway passage in the respiratory system that conducts air into the lungs. Bronchospasm—Spasm of the smooth muscles surrounding the bronchi causing constriction and obstructed airways. Cytochrome P450—Enzymes present in the liver that metabolize drugs. Phenylketonuria—Disorder of metabolism involving a deficiency in liver enzymes that metabolize the amino acid phenylalanine, causing it to accumulate and resulting in severe medical problems. QT prolongation—Potentially dangerous heart condition that affects the rhythm of the heart beat and alters the ECG reading of the heart.

OTHER

‘‘Progressive Multifocal Leukoencephalopathy.’’ A Healthy Me. [cited July 5, 2009]. http://www.ahealthyme.com/ article/gale/100083914.

Wendy Wippel, M.Sc.

Asthma induced by exercise may also be treated by leukotriene inhibitors. Allergy symptoms of sneezing, runny nose, and wheezing may be treated by leukotriene inhibitors.

Description

Leukotriene inhibitors Definition Leukotriene inhibitors are drugs used to treat asthma and allergy symptoms. Leukotrienes are fatty compounds that function as part of the immune system, and cause inflammation and constriction of the airways. Leukotriene inhibitors act to prevent this mechanism and open the airways to facilitate breathing. The three main leukotriene inhibitors are the drugs montelukast, zafirlukast, and zileuton.

Purpose Leukotriene inhibitors are mainly used to treat chronic asthma as part of maintenance therapy. Maintenance therapy helps keep acute asthma attacks from happening and maintains a baseline of open airways. Leukotriene inhibitors are not used to treat acute asthma attacks, only prevent them from happening. 820

Leukotriene inhibitors are used to treat respiratory conditions that are caused by obstruction of the airways. Breathing involves the passage of air through the nose or mouth, down the trachea within the throat and into air passages called bronchi that lead into the lungs. Obstruction of the airways may be due to the constriction of the smooth muscle that lines the bronchi, causing a condition known as bronchospasm (spasm of the smooth muscle). Relaxation of the smooth muscle allows opening of the airway, thereby facilitating the breathing process. Leukotrienes are released by the body during an allergic reaction or in patients with asthma, and cause contraction of the bronchial airway smooth muscle, as well as inflammation and mucous production. All of these effects disrupt breathing and are ameliorated by leukotriene inhibitors. Multiple leukotriene inhibitors are available, including the drugs montelukast, zafirlukast, and zileuton. Montelukast is manufactured by Merck under the trade name Singulair. Zafirlukast is G A LE EN CY C LO PE DI A O F C AN C ER 3

Recommended dosage The dose of montelukast used for asthma maintenance therapy or allergy symptoms is 10 mg taken orally in the evening. For asthma induced by exercise in patients who are not already on montelukast maintenance therapy, the dose is 10 mg given at least two hours before exercise with a maximum dose of 10 mg per day. The same dose is used for both adults and children greater than 15 years of age. For children from 6 to 14 years of age a dose of 5 mg a day is used. For children from 1 to 5 years of age a dose of 4 mg a day is used, available as a chewable tablet or as powder that may be mixed with food. Montelukast is not appropriate for use in children less than 1 year of age. The dose of zafirlukast used for asthma maintenance therapy is 20 mg taken orally twice a day. The maximum dose used is 40 mg per day. The same dose is used for both adults and children greater than 12 years of age. For children from 5 to 11 years of age a dose of 10 mg twice a day is used. Doses are taken 1 hour before or 2 hours after meals. Zafirlukast is not appropriate for use in children less than 5 years of age. The dose of zileuton used for asthma maintenance therapy is 1,200 mg taken orally twice a day. The G A LE EN CY C LO PE DI A O F C AN CE R 3

maximum dose used is 2,400 mg per day. The same dose is used for both adults and children greater than 12 years of age. Doses are taken within an hour of meals. Zafirlukast is not appropriate for use in children less than 12 years of age.

Precautions Leukotriene inhibitors are used as a part of asthma maintenance and are not effective for acute asthma attacks. However, treatment with leukotriene inhibitors is not stopped during acute asthma exacerbations when other drugs are necessary for the acute attack. Leukotriene inhibitors may not be appropriate for use in patients with existing liver disease, anxiety, depression, dream disorders, hallucinations, alcoholism, mood swings, or tremors. Use of leukotriene inhibitors during breastfeeding is not recommended. Montelukast and zafirlukast are pregnancy category B drugs. Pregnancy category B drugs are drugs in which there is no evidence of fetal risk in studies done on animals and there are no studies done in pregnant women, or drugs in which there is evidence of fetal harm in animal studies but studies done in pregnant women have not shown risk. These drugs may be used during pregnancy as fetal harm is possible but unlikely. Zafirlukast is not approved for use in children less than five years of age. Montelukast is not approved for use in children less than 1 year of age. The chewable form of montelukast may not be appropriate for use in children with the metabolic disorder phenylketonuria. Zafirlukast may cause a heart condition that affects the rhythm of the heartbeat known as QT prolongation. Sometimes QT prolongation can cause a serious cardiac condition that includes a fast and irregular heartbeat, with severe dizziness and fainting. The risk of developing QT prolongation syndrome may be increased if the patient is taking other drugs that also affect the rhythm of the heart, or if the patient has cardiac problems. Low blood levels of potassium or magnesium may also increase risk of QT prolongation. Zileuton is a pregnancy category C drug, and is used during pregnancy only when medically necessary. A pregnancy category C drug is one for which studies done in animals have shown potential harm to a fetus but there is not sufficient data in humans. If the potential benefits for the patient outweigh the potential risks to the fetus, the drug may be used during pregnancy. Zileuton is not approved for use in children less than 12 years of age. Use of zileuton in children may cause mood changes, patients in this age range should be 821

Leukotriene inhibitors

manufactured by AstraZeneca Pharmaceuticals under the trade name Accolate. Zileuton is manufactured by Cornerstone Therapeutics under the trade name Zyflo. Leukotriene inhibitors specifically target the receptor for leukotrienes (body chemicals that induce inflammation) present on cell surfaces in the respiratory tract. Leukotriene inhibitors are a type of chemical receptor that sits on the outer membrane of cells present in the respiratory system. These receptors activate a sequence of cellular events known as a chemical cascade or signaling pathway. It is these signaling pathways that are responsible for many normal body functions. Drugs or natural chemicals that bind to and activate the receptor signaling pathway are known as receptor agonists. Drugs or natural chemicals that bind to the receptor and block them from creating a signaling pathway are known as receptor antagonists, because they antagonize the effects of that receptor. Leukotriene receptors bind leukotriene agonists to create signaling cascades that are a natural part of the immune response and create inflammation of the airways. In patients with asthma and allergies this natural inflammatory process is excessive and creates uncomfortable symptoms. Leukotriene inhibitors antagonize the leukotriene receptor by binding and prevent the signaling pathway for inflammation from happening, restoring a normal balance.

Leukotriene inhibitors

QUESTIONS TO ASK YOUR PHARMACIST 









How long will I need to take this drug before you can tell if it helps for me? How often do I have to have blood work and other laboratory tests done to check the effect the drug is having? Is this drug safe to take with the other drugs that I am currently taking? What side effects should I watch for? When should I call the doctor about them? Are there any clinical trials of this drug combined with other therapies that might benefit me?

monitored cautiously. Use of zileuton in females greater than 65 years of age may cause alterations in liver enzymes that need to be monitored.

Side effects Leukotriene inhibitors generally have very few side effects and are well tolerated. Headaches are the most common symptom. Leukotriene inhibitors may be associated with the side effects of upset stomach, irritation of the nasal passages, dizziness, nausea, inflammation of the sinuses, sore throat, abdominal pain and cramping, vomiting, diarrhea, liver disease, muscle pain, rash, upper respiratory infections. Very rarely leukotriene inhibitors may cause aggressive behavior, anxiety, depression, dream disorders, hallucinations, insomnia, suicidal thoughts, and tremors. Montelukast and zafirlukast have been associated with the severe side effects of liver failure, alterations of the immune system, and inflammation of the blood vessels. Montelukast has been associated with bronchitis, weakness, and vision disturbances.

Interactions Leukotriene inhibitors are metabolized by a set of liver enzymes known as cytochrome P450 (CYP450). Multiple subtypes of CYP450 metabolize leukotriene inhibitors, with subtype 3A4 as the main metabolizer. Drugs that induce, or activate these enzymes increase the metabolism of leukotriene inhibitors. This results in lower levels of therapeutic leukotriene inhibitors, thereby negatively affecting treatment. For this reason drugs that induce CYP450 subtype 3A4 may not be used with leukotriene inhibitors. This includes some anti-epileptic drugs such as carbamazepine, some 822

anti-inflammatory drugs such as dexamethasone, anti-tuberculosis drugs such as rifampin, and the herb St. John’s Wort. Drugs that act to inhibit the action of CYP450 subtype 3A4 may cause undesired increased levels of leukotriene inhibitors in the body. This could lead to toxic doses. Some examples are antibiotics such as clarithromycin, antifungal drugs such as ketoconazole, antiviral drugs such as indinavir, antidepressants such as fluoxetine, and some cardiac agents such as verapamil. Grapefruit juice may also increase the amount of leukotriene inhibitors in the body. Patients should avoid drinking grapefruit juice or eating grapefruit while taking leukotriene inhibitors. Zafirlukast may have dangerous additive effects with other drugs that also cause QT prolongation. Drugs that interact with zafirlukast in this way include cisapride, amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, and macrolide antibiotics such as erythromycin. Interactions with the blood thinning drug warfarin may increase risk of bleeding. Leukotriene inhibitors may also interact with other drugs to increase their toxicity. Interactions with the blood thinning drug warfarin may increase risk of bleeding. The dose of the bronchodilator theophylline needs to be reduced when initiating leukotriene inhibitor therapy to prevent toxicity. The blood pressure and cardiac drug propranolol and related compounds may cause toxicity when used with leukotriene inhibitors. Resources BOOKS

Goodman and Gilman’s The Pharmacological Basis of Ther apeutics, Eleventh EditionMcGraw Hill Medical Pub lishing Division, 2006. Tarascon Pharmacopoeia Library EditionJones and Bartlett Publishers, 2009. OTHER

Epocrates. Montelukast. http://www.epocrates.com. Epocrates. Zafirlukast. http://www.epocrates.com. Epocrates. Zileuton. http://www.epocrates.com. Medscape. Montelukast. http://www.medscape.com. Medscape. Zafirlukast. http://www.medscape.com. Medscape. Zileuton. http://www.medscape.com. RxList. Montelukast. http://www.rxlist.com. RxList. Zafirlukast. http://www.rxlist.com. RxList. Zileuton. http://www.rxlist.com. ORGANIZATIONS

American Academy of Allergy, Asthma, and Immunology. 611 East Wells St., Milwaukee, WI 53202. (800) 822 2762. http://www.aaaai.org. G A LE EN CY C LO PE DI A O F C AN C ER 3

KEY T ERMS Endometrial tissue—The tissue lining the uterus that is sloughed off during a woman’s menstrual period. Fibroid—A benign smooth muscle tumor of the uterus. Gonadotropin releasing hormone (GnRH)—A hormone produced in the brain that controls the release of other hormones that are responsible for reproductive function.

Maria Basile, Ph.D.

Prostate gland—A small gland in the male genitals that contributes to the production of seminal fluid.

Leuprolide acetate Definition Leuprolide acetate is a synthetic (man-made) hormone that acts similarly to the naturally occurring gonadotropin releasing hormone (GnRH). It is available under the tradename Lupron.

Purpose Leuprolide acetate is used primarily to counter the symptoms of advanced prostate cancer in men when surgery to remove the testes or estrogen therapy is not an option or is unacceptable to the patient. It is often used to ease the pain and discomfort of women suffering from endometrosis, advanced breast cancer, or advanced ovarian cancer. Two less common uses of this drug are the treatment of anemia caused by bleeding uterine fibroids, and the treatment of early onset (precocious) puberty.

Description Leuprolide acetate is a man-made protein that mimics many of the actions of gonadotropin releasing hormone. In men, it decreases blood levels of the male hormone testosterone. In women, it decreases blood levels of the female hormone estrogen.

Recommended dosage for prostate cancer In men, there are three methods of dosing: daily injections, a monthly injection, or an annual implanted capsule. In the case of daily injections, 1 mg of leuprolide acetate is injected under the skin (subcutaneously). In the case of monthly injections, an implanted capsule that contains 7.5 mg of leuprolide acetate is injected into a muscle. In the case of an annual implanted capsule, the capsule contains 72 mg of leuprolide acetate. Both the monthly and the annual G A LE EN CY C LO PE DI A O F C AN CE R 3

capsules are specially designed to slowly release the drug into the patient’s bloodstream over the specified time. The monthly capsule dissolves completely over the course of the month. The annual capsule must be removed after 12 months. In the case of self-administered daily injections, a patient who misses a dose should take that dose as soon as it is noticed. However, if he or she does not remember until the next day, the missed dose should be skipped. Dosages should not be doubled.

Precautions People taking leuprolide acetate should not drive a car, cook, or engage in any activity that requires alertness until they have been taking the medication long enough to be sure how it affects them. Leuprolide acetate may cause birth defects if taken during pregnancy, and may be passed to an infant via breast milk. Therefore, women who are pregnant or nursing should not take leuprolide acetate without first consulting their doctors. Leuprolide acetate will also interfere with the chemical actions of birth control pills. For this reason, sexually active women who do not wish to become pregnant should use some form of birth control other than birth control pills.

Side effects In patients of both sexes, common side effects of leuprolide acetate include: 

tumor flare, which is exhibited as bone pain (due to a temporary initial increase in testosterone/estrogen before its production is finally decreased) 823

Leuprolide acetate

Asthma and Allergy Foundation of America. 1233 20th Street, NW, Suite 402, Washington, DC 20036. (800) 727 8462. http://www.aafa.org. FDA U.S. Food and Drug Administration. 10903 New Hampshire Ave, Silver Spring, MD 20993. (888)INFO FDA. http://www.fda.gov. National Heart, Lung and Blood Institute. P.O. Box 30105, Bethesda, MD 20824 0105. (301) 251 1222. http:// www.nhlbi.nih.gov.

Levamisole



sweating accompanied by feelings of warmth (hot flashes)



lack of energy (lethargy)



depression, or other mood changes



headache



enlargement of the breasts



decreased sex drive

Levamisole Definition Levamisole is used to treat colon cancer, specifically stage III colon cancer. Levamisole takes the full name of levamisole hydrochloride, and it is also known by the brand name Ergamisol.

Purpose Other common side effects in women include: 

light, irregular vaginal bleeding



no menstrual period



pelvic pain



vaginal dryness and/or itching



emotional instability



increase in facial or body hair



deepening of the voice

Less common side effects, in patients of either sex, include: 

burning or itching at the site of the injection



nausea and vomiting



insomnia



weight gain



swollen feet or lower legs



constipation

Other side effects in men can include impotence and decreased testicle size. A doctor should be consulted immediately if the patient experiences any of the above symptoms.

Interactions There are no known interactions of leuprolide acetate with any food or beverage. People taking leuprolide acetate should consult their physician before taking any other prescription drug, over-the-counter drug, or herbal remedy. People currently taking any other hormone or steroid-based medications should not take leuprolide acetate without first consulting their physician. See also Endometrial cancer. Paul A. Johnson, Ed.M. 824

Levamisole is used to treat patients with stage III colon cancer after they have had surgery to remove the tumor, or as much of the tumor as possible. In stage III colon cancer, the cancer has spread to nearby lymph nodes. Levamisole is approved for use with fluorouracil (specifically, 5-fluorouracil), a drug that is thought to prevent cells from replicating, or making more of themselves, by interfering with the manufacture of the hereditary material the cells carry. The use of levamisole with fluorouracil makes it an adjuvant therapy, or one that when used in conjunction with another drug seems to increase the defenses of the patient.

Description Levamisole was first made (by laboratory synthesis) in 1966, and since then it has been used in veterinary medicine to eliminate intestinal, or lower gut, parasites in domestic animals. It was found to be immunostimulant in 1972 and approved for use for colon cancer in 1990. The drug seems to have a number of benefits for the patient. It increases the response of T cells, or cells belonging to the lymphatic system that can fight cancer cells. It also seems to increase the activity of cells that attack and destroy invading or cancer cells, including both monocytes and macrophages. Because of the response levamisole brings from T cells, causing them to be more active, it falls into the category of drugs known as biological response modifiers.

Recommended dosage The drug is given orally in tablet form. Tablets contain 50 milligrams of levamisole hydrochloride, and a standard dose is one tablet every eight hours for three days. Thereafter, the patient takes the same three-day course every two weeks for about a year. Dosage must be adjusted according to the count of white blood cells and platelets in a patient’s blood. In some cases, levamisole can be continued, even when fluorouracil must be stopped. G A LE EN CY C LO PE DI A O F C AN C ER 3

Adjuvant therapy—Addition of a drug to another course of drug therapy to increase or enhance the immune response of a patient. Macrophage—Large cell-eating cell. Monocyte—A specialized type of white blood cell that attacks other cells, and acts as a phagocyte. Neutrophil—A specialized type of white blood cell that attacks other cells, and acts as a phagocyte. Parasite—An organism that lives by taking its nourishment from another organism. Phagocyte—Cell-eating cell. T cell—A cell in the lymphatic system that contributes to immunity by attacking foreign bodies, such as bacteria and viruses, directly.

Li-Fraumeni syndrome Definition Li-Fraumeni syndrome (LFS) is a genetic disorder caused by a hereditary mutation in a cancer susceptibility gene. Individuals with LFS have an increased risk for developing certain types of cancer, often at younger ages than is typically observed in the general population.

Description Li-Fraumeni syndrome (LFS) was first described by Dr. Frederick Li and Dr. Joseph Fraumeni in 1969. It is caused by mutations in the TP53 gene, located on chromosome 17. The types of mutations that cause LFS are known as hereditary mutations, and therefore can be inherited, or passed from a parent to a child.

Cancer risks

Precautions The drug can cause changes in the composition of the blood, which can be fatal. For example, agranulocytosis, also known as neutropenia, may develop. The condition refers to a drop in a kind of white blood cells known as neutrophils that are important in the defense against bacteria and fungus. Thus, the patient becomes more likely to get a bacterial or fungal infection.

Side effects Nausea and vomiting, diarrhea, hair loss (alopecia), and changes in the composition of the white blood cells, such as neutropenia, are among the most common side effects.

Interactions Levamisole often interacts with alcohol in the same way that the drug disulfiram, which is used to discourage alcohol consumption in alcoholics (alcohol deterrent), does. The reaction is extremely unpleasant, and alcohol use is best avoided when levamisole is being taken. The drug also interacts with warfarin, which is often given to heart patients to reduce the chance of blood clots forming. Levamisole can interfere with the action of warfarin, allowing blood clots to form; therefore, adjustments in the amount of warfarin heart patients take may be necessary if they are also taking levamisole. Diane M. Calabrese G A LE EN CY C LO PE DI A O F C AN CE R 3

The TP53 gene is a tumor suppressor gene. When an individual inherits a mutation in this type of gene from one of his or her parents, there is an increased risk for developing certain kinds of cancer. The most common kinds of cancer associated with LFS are sarcomas, or tumors that arise in connective tissue, like bone or cartilage. Females with LFS have an increased risk for developing breast cancer. Males and females may also be at risk for developing leukemia, melanoma, colon, pancreatic, and brain cancer. They may also develop adrenalcorticoid tumors, which develop on the outer surface of the adrenal glands. These cancers often occur at younger ages than are typically observed in the general population, often before age 45. Some individuals with LFS may develop certain cancers, such as brain tumors, sarcomas, or adrenalcorticoid tumors in childhood. In addition, individuals

Age of onset for cancers associated with Li-Fraumeni syndrome Age of onset

Type of cancer

Infancy Under five years of age Childhood and young adulthood Adolescence Twenties to thirties

Development of adrenocortical carcinoma Development of soft-tissue sarcomas Acute leukemias and brain tumors Osteosarcomas Premenopausal breast cancer is common

(Table by GGS Creative Resources. Cengage Learning, Gale.)

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Li-Fraumeni syndrome

KE Y T ERM S

Li-Fraumeni syndrome

K E Y TE R M S Adrenalcorticoid tumors—Cancer that arises on the outer surface of the adrenal glands. Adrenal glands—Structures located on top of the kidneys that secrete hormones. Cancer—The process by which cells grow out of control and subsequently invade nearby cells and tissue. Cancer susceptibility gene—The type of genes involved in cancer. If a mutation is identified in this type of gene it does not reveal whether or not a person has cancer, but rather whether an individual has an increased risk (is susceptible) to develop cancer (or develop cancer again) in the future. Chromosome—Structures found in the center of a human cell on which genes are located. Gene—Packages of DNA that control the growth, development and normal function of the body. Genetic counselor—A specially trained health care provider who helps individuals understand if a disease (such as cancer) is running in their family and their risk for inheriting this disease. Genetic

with a mutation in the TP53 gene have a higher risk for developing multiple primary cancers. For example, a person with LFS who develops a sarcoma at a young age and survives that cancer has an increased risk for developing a second, or possibly even a third different kind of cancer.

Genetic counseling and testing Genetic testing for mutations in the TP53 gene is usually performed on a blood sample from the relative in the family who has had one of the cancers associated with LFS at a young age. One of the most effective ways to test for mutations in the TP53 gene is by sequencing, a process whereby the chemical components of a patient’s DNA is compared to that of DNA that is known to be normal. If the entire DNA code of the TP53 gene is sequenced, it is believed that the majority (98%) of the (mutations) that are responsible for Li-Fraumeni syndrome can be identified. However, as the process of sequencing is a difficult and often time-consuming process, it is not always performed for every patient. Often, only specific areas of the TP53 gene, where there is most likely to be a mutation associated with LFS, are analyzed. The 826

counselors also discuss the benefits, risks and limitations of genetic testing with patients. Leukemia—Cancer that arises in blood cells. Mammogram—A screening test that uses x rays to look at a woman’s breasts for any abnormalities, such as cancer. Mutation—An alteration in the number or order of the DNA sequence of a gene. Penetrance—The likelihood that a person will develop a disease (such as cancer), if he or she has a mutation in a gene that increases the risk for developing that disorder. Sarcoma—Cancer that occurs in connective tissue, such as cartilage or bone. Sequencing—A method of performing genetic testing where the chemical order of a patient’s DNA is compared to that of normal DNA. Tumor suppressor gene—Genes that typically prevent cells from growing out of control and forming tumors that may be cancerous. Ultrasound—A test that uses sound waves to examine organs in the body

length of time to receive results depends on the extent of testing that is performed and the laboratory that is used. Due to the fact that some of the cancers associated with LFS can occur at very young ages, there is a question as to whether genetic testing should be an option for at-risk children. Typically, genetic testing is not offered to anyone under the age of 18. However, because there are some screening options available for children with LFS, it is thought that the option of testing could not be denied if a parent feels that it is important for his or her son or daughter’s future health. Groups such as the National Society of Genetic Counselors are beginning to explore the issue of genetic testing in minors (those under age 18) for mutations in cancer susceptibility gene, especially if these minors would be at risk for developing childhood cancers. It is important to understand the various categories of results that are associated with undergoing genetic testing for mutations in the TP53 gene. A positive result indicates the presence of a genetic mutation that is known to be associated with an increased risk for developing the types of cancer associated with G A LE EN CY C LO PE DI A O F C AN C ER 3











  



What is the likelihood that the cancer in my family is due to a mutation in a cancer susceptibility gene, particularly the TP53 gene? If my family is found to have Li-Fraumeni syndrome, what is the chance that I carry a mutation in the TP53 gene? What are the benefits, limitations and risks of undergoing genetic testing? What is the cost of genetic testing and how long will it take to obtain results? If I undergo genetic testing, will my insurance company pay for testing? If so, will I want to share my results with them? What does a positive test result mean for me? What does a negative test result mean for me? If I test positive for a mutation in a cancer susceptibility gene, what are the best options available for screening and prevention? What research studies may I be eligible to participate in? What legislation is in effect to protect me against discrimination by my insurer or employer?

LFS. Once this kind of mutation has been found in an individual, it is possible to test this person’s relatives, such as the children, for the presence or absence of that particular mutation. Individuals who have a mutation in the TP53 gene have a 50% chance of passing on this mutation to their children. Even if a patient has a mutation in the TP53 gene, it does not mean that he or she will definitely develop one of the cancers that are associated with Li-Fraumeni. However, the risk for those with the mutation is much higher than for someone in the general population. The likelihood that a person will develop cancer if they have a mutation in a cancer susceptibility gene like TP53 is called penetrance. If the first person tested within a family is not found to have an alteration in the TP53 gene, his or her result is negative. Often this result is called indeterminate, because a negative test result cannot completely rule out the possibility of hereditary cancer being present within a family. The interpretation of this type of result can be very complex. For example, a negative result may mean that the method used to detect mutations in the TP53 gene may not be sensitive G A LE EN CY C LO PE DI A O F C AN CE R 3

Screening and prevention options With the exception of screening for breast cancer, there are no effective means to screen for and/or prevent the cancers that are associated with Li-Fraumeni syndrome. However, researchers have developed some screening guidelines for those with LFS. For men and women, it is recommended that they undergo a thorough physical exam with their doctor every year. This should include skin and colon cancer screening along with a complete exam of the nervous system. Women should also undergo breast cancer screening, which consists of annual mammograms, self-breast exams, and breast exams by a physician or health care provider. Individuals with Li-Fraumeni syndrome may choose to undergo screening more often and at an earlier age then people in the general population. For children with a TP53 mutation, it is recommended that they also undergo a complete physical exam once a year by their physician. This should include an analysis of their urine and blood and an abdominal ultrasound. See also Genetic testing. Resources OTHER

‘‘Li Fraumeni Support Group.’’ Oncolink. 5 April 2001. [cited June 27, 2009]. http://cancer.med.upenn.edu/dis ease/misc/. ‘‘Li Fraumeni Syndrome.’’ GeneClinics. 16 Dec. 1998. [cited June 27, 2009]. http://www.geneclinics.com. ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta, GA 30329. (800)ACS 2345. http://www.cancer.org. National Cancer Institute. 31 Center Dr., MSC 2580, Bethesda, MD 20892 2580. (800) 4 CANCER. http:// www.nci.nih.gov. National Society of Genetic Counselors. 233 Canterbury Dr., Wallingord, PA 19086 6617. (610) 872 7608. http://www.nsgc.org.

Tiffani A. DeMarco, M.S. 827

Li-Fraumeni syndrome

QUESTIONS TO ASK THE DOCTOR

enough to identify all mutations. Additionally, the mutation might be located in a part of the gene that is difficult to analyze. It may also mean that a person has a mutation in another cancer susceptibility gene that has not yet been discovered or is very rare. Finally, a negative result could mean that the person tested does not have an increased risk for developing cancer because of a mutation in a single cancer susceptibility gene.

Limb salvage

Limb salvage

Q U E S T I O N S T O A S K TH E DOC TOR

Definition Limb salvage is a type of surgery that removes a cancerous tumor or lesion while preserving the nearby muscles, tendons, and blood vessels.



 

Purpose Doctors perform limb salvage to remove cancer and avoid amputation, while preserving the patient’s appearance and the greatest possible degree of function in the affected limb. The procedure is most commonly performed for bone tumors and bone sarcomas, but is also commonly performed for soft tissue sarcomas affecting the extremities. This complex alternative to amputation is used to cure cancers that are slow to spread from the limb where they originate to other parts of the body, or that have not invaded soft tissue.

Precautions Limb salvage should only be performed by experienced surgeons with specialized expertise. It should also be limited to cases in which the surgery would restore more and longer-lasting function than could be achieved by amputating the affected limb and fitting the patient with an artificial replacement (prosthesis). If the cancer’s location makes it impossible to remove the malignancy without damaging or removing vital organs, essential nerves, key blood vessels, or if it is impossible to reconstruct a limb that will function satisfactorily, salvage surgery may not be an appropriate treatment. Biopsy is a critical component of limb-salvage surgery. A poorly planned or improperly performed biopsy can limit the patient’s surgical options and make amputation unavoidable.

Description Also called limb-sparing surgery, limb salvage involves removing the cancer and about an inch of healthy tissue surrounding it, and, if bone was removed, replacing the removed bone. The replacement can take the form of synthetic metal rods or plates (prostheses), pieces of bone (grafts) taken from the patient’s own body (autologous transplant), or pieces of bone removed from a donor body (cadaver) and frozen until needed for transplant (allograft). In time, transplanted bone grows into the patient’s remaining bone. Chemotherapy, radiation, or a 828

Why do you think limb salvage will be successful in my case? How will I look and feel after the operation? Will I be able to enjoy my favorite sports and other activities after the operation?

combination of both treatments may be used to shrink the tumor before surgery is performed. Stages of surgery Limb salvage is performed in three parts. Doctors remove the cancer and a margin of healthy tissue, implant a prosthesis or bone graft (when necessary), and close the wound by transferring soft tissue and muscle from other parts of the patient’s body to the surgical site. This treatment cures some cancers as successfully as amputation. Surgical techniques BONE TUMORS. Doctors remove the malignant lesion and a cuff of normal tissue (wide excision) to cure low-grade tumors of bone or its components. To cure high-grade tumors, they also remove muscle, bone, and other tissues affected by the tumor (radical resection). SOFT TISSUE SARCOMAS. Doctors use limb-sparing surgery to treat about 80% of soft tissue sarcomas affecting extremities. The surgery removes the tumor, lymph nodes or tissues to which the cancer has spread, and at least one inch of healthy tissue on all sides of the tumor.

Radiation and/or chemotherapy may be administered before or after the operation. Radiation may also be administered during the operation by placing a special applicator against the surface from which the tumor has just been removed, and inserting tubes containing radioactive pellets at the site of the tumor. These tubes remain in place during the operation and are removed several days later. To treat a soft tissue sarcoma that has spread to the patient’s lung, the doctor may remove the original tumor, administer radiation or chemotherapy treatments to shrink the lung tumor, and surgically remove the lung tumor. G A LE EN CY C LO PE DI A O F C AN C ER 3

Doctors use expandable prostheses to perform limb-salvage surgery on children who have not stopped growing (skeletal immaturity). These children may need as many as four additional operations, at intervals of six to 12 months, to expand the prostheses as their limbs lengthen. Because expandable prostheses have been available only since the 1980s, the long-term effects of using them are unknown.

Preparation Before deciding that limb salvage is appropriate for a particular patient, the doctor considers what type of cancer the patient has, the size and location of the tumor, how the illness has progressed, and the patient’s age and general health. After determining that limb salvage is appropriate for a particular patient, the doctor makes sure that the patient understands what the outcome of surgery is likely to be, that the implant may fail, and that additional surgery—even amputation—may be necessary. Preoperative rehabilitation Physical and occupational therapists help prepare the patient for surgery by introducing the musclestrengthening, ambulation, and range of motion (ROM) exercises the patient will begin performing right after the operation.

Aftercare During the five to ten days the patient remains in the hospital following surgery, nurses monitor sensation and blood flow in the affected extremity and watch for signs that the patient may be developing pneumonia, pulmonary embolism, or deep-vein thrombosis. The doctor prescribes broad-spectrum antibiotics for at least the first 48 hours after the operation and often prescribes medication (prophylactic anticoagulants) and antiembolism stockings to prevent blood clots. A drainage tube placed in the wound for the first 24–48 hours prevents blood (hematoma) and fluid (seroma) from accumulating at the surgical site. As postoperative pain becomes less intense, mild narcotics or anti-inflammatory medications replace the epidural catheter or patient-controlled analgesic pump used to relieve pain immediately after the operation. G A LE EN CY C LO PE DI A O F C AN CE R 3

Exercise intervention Limb salvage requires extensive surgical incisions, and patients who have these operations need extensive rehabilitation. The amount of bone removed and the type of reconstruction performed dictate how soon and how much the patient can exercise, but most patients begin muscle-strengthening, continuous passive motion (CPM), and ROM exercises the day after the operation and continue them for the next 12 months. A patient who has had upper-limb surgery can use the opposite side of the body to perform hand and shoulder exercises. Patients should not do active elbow or shoulder exercises for two to eight weeks after having surgery involving the bone between the shoulder and elbow (humerus). Rehabilitation following lowerextremity limb salvage focuses on strengthening the muscles that straighten the legs (quadriceps), maintaining muscle tone, and gradually increasing weightbearing so that the patient is able to stand on the affected limb within three months of the operation. A patient who has had lower-extremity surgery may have to learn a new way of walking (gait retraining) or wear a lift in one shoe. Goals of rehabilitation Physical and occupational therapy regimens are designed to help the patient move freely, function independently, and accept changes in body image. Even patients who look the way they did before surgery are likely to feel that the operation has altered their appearance. Before a patient goes home from the hospital or rehabilitation center, the doctor decides whether the patient needs a walker, brace, cane, or other device, and should make sure that the patient can climb stairs. Also, the doctor should emphasize the life-long importance of preventing infection and give the patient written instructions about how to prevent infection and what to do if infection does develop.

Risks The major risks associated with limb salvage include superficial or deep infection at the site of the surgery; loosening, shifting, or breakage of implants; rapid loss of blood flow or sensation in the affected limb; and severe blood loss and anemia from the surgery. Postoperative infection is a serious problem. Chemotherapy or radiation can weaken the immune system, and extensive bone damage can occur before the 829

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Limb salvage for children

Lip cancers

infection is identified. Tissue may die (necrosis) if the surgeon used a large piece of tissue (flap) to close the wound. This is most likely to occur if the surgical site was treated with radiation before the operation. Treatment for postoperative infection involves removing the graft or implant, inserting drains at the infected site, and giving the patient oral or intravenous antibiotic therapy for as long as 12 months. Doctors may have to amputate the affected limb.

Normal results

OTHER

‘‘Adult Soft Tissue Sarcoma.’’ ‘‘Bone Cancer.’’ CancerNet. 2000. [cited July 11, 2009]. http:// www.cancernet.nci.nih.gov. ‘‘Bone Cancer.’’ ACS Cancer Resource Center American Cancer Society. 2000. [cited July 11, 2009]. http:// www3.cancer.org. ‘‘Sarcoma.’’ ACS Cancer Resource Center. American Cancer Society. March 22, 2000. [cited July 11, 2009]. http:// www3.cancer.org. ‘‘Soft Tissue Sarcoma.’’ Memorial Sloan Kettering Cancer Center. 2001. [cited July 11, 2009]. http:// www.mskcc.org/.

A patient who has had limb-sparing surgery will remain disease-free as long as a patient whose affected extremity has been amputated. Salvaged limbs always function better than artificial ones. However, it takes a year for patients to learn to walk again following lower-extremity limb salvage, and patients who have undergone upper-extremity salvage must master new ways of using the affected arm or hand. Successful surgery reduces the frequency and severity of patient falls and of the fractures that often result from disease-related changes in bone. Although successful surgery results in limbs that look and function very much like normal, healthy limbs, it is not unusual for patients to feel that their appearance has changed.

Abnormal results Some patients will need additional surgery within five years of the first operation. Some will eventually require amputation. Post-operation directives from the patient’s physician may include the following items: 

Patients may be told that they should never jog, lift heavy objects, or play racquet sports.



Wearing a splint or cast can damage nerves and veins in the affected limb.



Implants can loosen, shift to a new position, or break.

Maureen Haggerty

Lip cancers Definition Lip cancer is a malignant tumor, or neoplasm, that originates in the surface layer cells of the epithelial tissue in the upper or lower lip.

Description The upper and lower lips are the well-defined red (often called vermilion) areas that surround the opening to the mouth. They contain muscles and special cells (receptors) that are sensitive to heat and cold and feeling. Largely taken for granted, the lips are important in identifying types of food to the brain and in getting food into the mouth. Lips also play a crucial role in speech.

See also Chondrosarcoma; Ewing’s sarcoma; Osteosarcoma. Resources BOOKS

Ignatavicius, Donna D., et al. Medical Surgical Nursing Across the Health Care Continuum. 3rd ed. Philadel phia: W. B. Saunders Company, 1999. 830

Squamous cell carcinoma on lip. (Custom Medical Stock Photo. Reproduced by permission.)

G A LE EN CY C LO PE DI A O F C AN C ER 3

Biopsy—A procedure in which a tissue sample is taken from the body for examination. Epithelial tissue—The collection of cells that form coverings for the surfaces of the body. Immunity—Ability to resist the effects of agents, such as bacteria and viruses, that cause disease. Lymph node—A concentration of lymphatic tissue and part of the lymphatic system that collects fluid from around the cells and returns it to the blood vessels, and helps with the immune response. Squamous cells—Flat epithelial cells, which usually make up the outer layer of epithelial tissue, the layer farthest away from the surface the epithelium covers.

A malignant tumor, or neoplasm, that originates in the cells of one of the lips is a cancer of the lip. Lip cancer almost always begins in the flat, or squamous, epithelial cells. Epithelial cells form coverings (tissues) for the surfaces of the body. Skin, for example, has an outer layer of epithelial tissue. If a part of the lip is affected by cancer and must be removed by surgery, there will be significant changes in eating ability and speech function. The more lip tissue removed, the greater the disturbances to the normal patterns of talking and eating.

Demographics Nine out of 10 cases of lip cancer are diagnosed in people over the age of 45. Age, or the aging process, may contribute to the way the cancer develops. As a line of cells gets older, the genetic material in a cell loses some of its ability to repair itself. When the repair system is operating normally, damage to the genetic material, or DNA, caused by ultraviolet light from the sun is quickly weeded out. When the system fails, changes in the genetic material are kept, and they multiply when a cell divides. If the genetic material cannot repair itself, damage caused by exposure to environmental factors such as sunlight and chemicals can quickly set in motion the uncontrolled growth of cells. The effects of factors that are known to cause lip cancer, such as smoking and exposure to sunlight, also add up as a person ages. Thus, the combination of a breakdown in the repair system in the genetic material and the considerable periods of time (decades) over G A LE EN CY C LO PE DI A O F C AN CE R 3

Lip cancers

KE Y T ERM S

Q U E S T I O N S TO A S K T H E DOCTOR    

Is this cancer curable? What is the stage of the cancer? What is the likelihood the cancer will recur? Is there a clinical trial in which I should participate?

which a person is exposed to cancer agents probably causes lip cancers. However, researchers are still investigating how lip cancers start. Men are at greater risk for lip cancer than women. Depending on where they live, men are two or three times more likely to be diagnosed than women. Fairskinned people are more likely to get lip cancer than those with dark skin. For reasons not yet understood, people in Asia have a much lower risk of lip cancer than those living on other continents. In many parts of Asia, lip cancer is extremely rare. In North America, nearly 13 out of 100,000 men will be diagnosed with lip cancer during their lifetime. In Australia, about 13.5 men per 100,000 will be diagnosed. The frequency of lip cancer is often lumped together with oral cancer, although lip cancer is probably much more like skin cancer in origin. There are about 30,000 new diagnoses of mouth and lip cancer in the United States each year. About 38% percent of all cancers of the mouth begin in the lower lip; on the other hand, cancers of the upper lip are more aggressive than those of the lower lip. In some places, such as South Australia, women are experiencing a striking increase in lip cancer diagnoses. There are several theories to explain the trend. Among them, perhaps fewer women regularly wear hats, which offer protection from the sun. Women might also be forgoing lipstick, which serves as another barrier to sunlight.

Causes and symptoms Exposure to sunlight and smoking, particularly pipe smoking, increases the risk of developing lip cancer. However, the way they do so is not understood. Alcohol consumption is tied to oral cancers and may contribute to lip cancer as well. Much of the evidence about the link between time spent in the sun and lip cancer comes from a look at those who are most likely to be diagnosed. Among 831

Lip cancers

them are farmers, golfers, and others who spend long periods of time outdoors. Lip cancer seems to share some properties with skin cancer in the way it originates. Yet several studies suggest that it takes more than exposure to sun to increase the risk of lip cancer. Viral infection is a risk factor, as is reduced immunity, which is a condition that may be caused by viral infection. A team of researchers in the Netherlands recently reported a link between liver transplants and a higher risk of lip and skin cancer following the transplant. The results are not unexpected. In this procedure, drugs are used to suppress, or lower, the activity of a recipient’s immune system so that a donor organ will be accepted. Thus, the immunity of the organ recipient is low, and lower immunity is linked to lip cancer. Individuals with acquired immunodeficiency syndrome (AIDS) are at a greater risk for lip cancer. People infected with herpes simplex viruses, papilloma viruses and other viruses may also be at greater risk. Vitamin deficiency may also be a factor that contributes to lip cancer. The sorts of vitamins found in fruits and vegetables, particularly carotene, the substance the body uses to form vitamins A and C, seem to be important in preventing lip cancer. Particular symptoms of this cancer include white spots, sores, or lumps on the lip. Pain can also be a symptom, particularly pain in a lymph node near the affected part of the lip. This is a troubling symptom, since it indicates that the cancer has metastasized (spread) beyond the lip.

treatment. A surgeon will remove the cancer. Not all oncologists are surgeons, so it is likely that the team will include a medical oncologist, who coordinates treatment, as well as a surgical oncologist, who performs the surgery. Because surgery on the lip can interfere with eating and talking, most teams include a nutritionist and a speech pathologist. Scars and alterations of facial features can produce changes in body image, and a psychiatrist or social worker may participate in the team to help a patient cope with such changes. It is possible that a dentist or oral surgeon will also play a role. Nurses who administer chemotherapy and monitor the status of patients will be involved, as will radiation technicians and a radiation oncologist. If reconstruction of a lip is necessary because of the amount of tissue removed or the size of a scar, a plastic surgeon will be added to the team.

Clinical staging, treatments, and prognosis The ability to see a suspicious area on the lips and to detect lip cancer early combine to form the staging process. (One inch equals 2.5 cm.) 





Diagnosis

Stage I: The cancer is less than one inch in diameter and has not spread. Stage II: The cancer is up to approximately two inches in diameter and has not spread. Stage III: The cancer is either larger than two inches or has spread to a lymph node on the side of the neck that matches the primary location of the lip cancer. The lymph node is enlarged, but not much more than an inch. Stage IV: One or more of several things can occur. There may be a spread of cancer to the mouth or to the areas around the lip, more than one lymph node with cancer, or metastasis (spread) to other parts of the body.

Dentists frequently identify a suspicious spot, sore, or lump on the lip. A good dental exam includes an examination of the lips and the mouth. X ray and biopsy, the taking of a tissue sample for analysis, can be used to determine whether or not cancer is present.



Because spots and sores on the lips can be shortlived, people should not be alarmed by every change that appears. However, when there is a change that occurs and stays, it should be investigated. If the next scheduled dental visit is several months away, a special appointment with the dentist or a physician should be made. Dentists should tell their patients, particularly older ones, how to undertake a regular self-exam of the lips between check-ups.

The outlook for recovery from lip cancer is very good if it is diagnosed early. For stage I and stage II cancers, surgery to remove the cancer or radiation treatment of the affected area is sometimes all that is required to produce a cure. Decisions about which method to use depend on many factors, but the size of the tumor and the tolerance a patient has for radiation or chemotherapy are particularly important. The larger the tumor, the more urgent is its removal. Smaller tumors can be treated with radiation or other methods in an effort to shrink them before surgery. In some cases, surgery might be avoided. For stage III cancer with lymph node involvement, the cancerous lymph nodes are also removed.

Treatment team A physician who specializes in oncology, the study and treatment of cancer, will probably take the lead on 832

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speech difficulty, patients should be ready with additional means, such as TYY phone service.

There are many new and promising types of treatment for lip cancer. For example, heat kills some cancer cells, and a treatment known as hyperthermia uses heat to eliminate cancer in some patients.

If a significant portion of lip is removed, speech therapy may be necessary to relearn how to make certain sounds. Scars and alterations of the lips usually can be reduced or hidden entirely with the techniques available from plastic surgery, so any alteration in appearance because of lip cancer is typically transient.

Because lip cancers are well-studied and often successfully treated, the best practices for dealing with the cancer, or a suspected cancer, are specific. In the case of how to extract and study tissue to determine whether a suspicious growth is malignant (biopsy), size is an extremely useful guide. It is possible to take tissue from a suspected lip cancer for examination, or biopsy, by simply piercing and extracting tissue with a large, hollow needle. The technique is called a punch biopsy. However, the method is not recommended for any tumor that is thicker than about one-sixteenth of an inch. For thicker tumors, a tissue sample is better taken by cutting into the tumor, that is, making an incision. The success with identifying lip cancer early and eliminating it means that it is not a big killer. Only four in 2.5 million people die from lip cancer each year, or about 112 individuals in the entire United States population. In contrast, cancers in the oral cavity, including on the tongue, cause more than 8,000 deaths in the United States each year. Alternative and complementary therapies Because there seems to be some link between a chronic absence of vitamins A and C in the diet and lip cancer, some complementary therapies promote taking massive amounts of the vitamins, or megavitamins. The value of such therapy has not been demonstrated. In order to avoid possible side effects or harmful interactions with standard cancer treatment, patients should always notify their treatment team of any over-the-counter or herbal remedies that they are taking.

A change in appearance after the removal of a lip cancer can lead to concerns about body image, and social interaction may suffer. A support group can help. Discussions with a social worker, loved ones, or other patients who have undergone similar treatment can be of major benefit.

Reconstruction of the lip will help with appearance, but it might not make it easier to talk, especially if muscle tissue is removed during the surgery to eliminate the cancer. In many cases, the reconstruction process actually damages more muscle and sensory tissue. New methods of reconstructive surgery are being developed to avoid such an outcome. Some of these newer methods involve grafts of skin and muscle taken from the forearm or the area of the cheek near the angle of the jawbone. In general, reconstruction of the lower lip is more difficult than reconstruction of the upper lip. Appetite may be affected before, during and after treatment. Before treatment, the presence of a tumor can interfere with the tasting of food, and food might not seem as appealing as it once did. During treatment, particularly radiation treatment, the area of the lips and mouth might be sore and make eating difficult. After treatment, a loss of sensation in the part of the lip affected can reduce appetite. A nutritionist can help with supplements for those who experience significant weight loss and who do not have an appetite.

Clinical trials The Cancer Information Service at the National Institutes of Health offers information about clinical trials that are looking for volunteers. The service can be reached at http://cancertrials.nci.nih.gov or (800) 422-6237.

Prevention Coping with cancer treatment The doctor and patient should discuss the need for a way to communicate if speech is impaired after surgery. A pad and pencil may be all that is needed for a short interval. If there will be a long period of G A LE EN CY C LO PE DI A O F C AN CE R 3

The best preventive measures are minimizing sun exposure and avoiding tobacco and alcohol. Eating plenty of fruits and vegetables is a good measure. Even though the importance of fruits and vegetables is not proven to prevent lip cancer, overall fruits and 833

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Chemotherapy may be used at any stage, but it is particularly important for stage IV cancer. In some cases, chemotherapy is used before surgery, just as radiation is, to try to eliminate the cancer without cutting, or at least to make it smaller before it is cut out (excised). After surgery, radiation therapy and chemotherapy are both used to treat patients with stage IV lip cancer, sometimes in combination.

Liver biopsy

vegetables are demonstrated cancer-fighters. Any precaution that is taken against contracting human immunodeficiency virus (HIV), which causes AIDS, is also likely to reduce the chance of developing lip cancer.

Special concerns Certain diseases can mimic a possible lip cancer. They must be ruled out if a suspicious spot is found. This is particularly true in areas where diseases that cause lesions, or sores, on the lips are found. One such disease is histoplasmosis capsulatum, which is caused by a fungus. It sometimes produces an ulcer, or lesion, on the lip that leads to suspicion of lip cancer. Sometimes lip cancer cannot be cured. It may keep recurring. It may also metastasize, particularly to the lungs. But overall, lip cancer is considered highly curable. Talking openly with the physician in charge of care is important in order for the patient to understand the course of the disease and be prepared to make decisions. See also Oropharyngeal cancer. Resources

ORGANIZATIONS

American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS). 310 South Henry Street, Alexan dria, VA 22314. (703) 299 9291. http:// www.facemd.org. American Society of Plastic Surgeons (ASPS). 444 East Algonquin Road, Arlington Heights, IL 60005. (847) 228 9900. http://www.plasticsurgery.org. Support for People with Oral and Head and Neck Cancer (SPOHNC). P.O. Box 53, Locust Valley, NY 11560 0053. (800) 377 0928. http://www.spohnc.org.

Diane M. Calabrese, Ph.D. Rebecca J. Frey, Ph.D.

Liver biopsy Definition A liver biopsy is a medical procedure performed to obtain a small piece of liver tissue for diagnostic testing. Liver biopsies are sometimes called percutaneous liver biopsies, because the tissue sample is obtained by going through the patient’s skin.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Disorders of the Oral Region: Neoplasms.’’ Section 9, In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laborato ries, 2007. PERIODICALS

Adler, N., A. Amir, and D. Hauben. ‘‘Modified von Bruns’ Technique for Total Lower Lip Reconstruction.’’ Der matologic Surgery 30 (March 2004): 433 437. Brennan, P., et al. ‘‘Secondary Primary Neoplasms Follow ing Non Hodgkin’s Lymphoma in New South Wales, Australia.’’ British Journal of Cancer 82 (April 2000): 1344 7. Bucur, A., and L. Stefanescu. ‘‘Management of Patients with Squamous Cell Carcinoma of the Lower Lip and Neck.’’ Journal of Craniomaxillofacial Surgery 32 (February 2004): 16 18. Dupin, C., S. Metzinger, and R. Rizzuto. ‘‘Lip Reconstruc tion after Ablation for Skin Malignancies.’’ Clinics in Plastic Surgery 31 (January 2004): 69 85. Gardetto, A., K. Erdinger, and C. Papp. ‘‘The Zygomatic Flap: A Further Possibility in Reconstructing Soft Tis sue Defects of the Nose and Upper Lip.’’ Plastic and Reconstructive Surgery 113 (February 2004): 485 490. Haagsma, E.B., et al. ‘‘Increased Cancer Risk After Liver Transplantation: A Population Based Study.’’ Journal of Hepatology 34 (January 2001): 84 91. 834

Purpose A liver biopsy is usually done to diagnose a tumor, or to evaluate the extent of damage that has occurred to the liver because of chronic disease. Biopsies are often performed to identify abnormalities in liver tissues after imaging studies have failed to yield clear results.

A false-color scanning electron micrograph (SEM) of hepatocyte cells of the liver that secrete bile. (Photograph by John Bavosi. Custom Medical Stock Photo. Reproduced by permission.)

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Which medications should I stop taking before the biopsy? How soon can I return to my normal activities after the biopsy? How soon will I get my results?

A liver biopsy may be ordered to evaluate any of the following conditions or disorders:   

  



jaundice cirrhosis hemochromatosis, which is a condition of excess iron in the liver repeated abnormal results from liver function tests unexplained swelling or enlargement of the liver primary cancers of the liver, such as hepatomas, cholangiocarcinomas, and angiosarcomas metastatic cancers of the liver

Precautions Some patients should not have percutaneous liver biopsies. They include patients with any of the following conditions:   

  

a platelet count below 60,000 a longer-than-normal prothrombin time a liver tumor that contains a large number of blood vessels a history of unexplained bleeding a watery (hydatid) cyst an infection in either the cavity around the lungs, or the diaphragm

Description Percutaneous liver biopsy is done with a special hollow needle, called a Menghini needle, attached to a suction syringe. Doctors who specialize in the digestive system or liver will sometimes perform liver biopsies. But in most cases, a radiologist (a doctor who specializes in x rays and imaging studies) performs the biopsy. The radiologist will use computed tomography scan (CT scan) or ultrasound to guide the choice of the site for the biopsy. An hour or so before the biopsy, the patient may be given a sedative to help relaxation. He or she is then asked to lie on the back with the right elbow to the side G A LE EN CY C LO PE DI A O F C AN CE R 3

KEY T ERMS Biopsy—A procedure where a piece of tissue is removed from a patient for diagnostic testing. Menghini needle—A special needle used to obtain a sample of liver tissue. Percutaneous biopsy—A biopsy in which a needle is inserted and a tissue sample removed through the skin. Prothrombin time—A blood test that determines how quickly a person’s blood will clot. Vital signs—A person’s essential body functions, usually defined as the pulse, body temperature, and breathing rate.

and the right hand under the head. The patient is instructed to lie as still as possible during the procedure. He or she is warned to expect a sensation resembling a punch in the right shoulder, but to hold still in spite of the momentary feeling. The doctor marks a spot on the skin where the needle will be inserted and thoroughly cleanses the right side of the upper abdomen with an antiseptic solution. The patient is then given an anesthetic at the biopsy site. The needle with attached syringe is inserted into the patient’s chest wall. The doctor then draws the plunger of the syringe back to create a vacuum. At this point the patient is asked to take a deep breath, exhale the air and hold their breath at the point of complete exhalation. The needle is inserted into the liver and withdrawn quickly, usually within two seconds or less. The negative pressure in the syringe draws or pulls a sample of liver tissue into the biopsy needle. As soon as the needle is withdrawn, the patient can breathe normally. Pressure is applied at the biopsy site to stop any bleeding, and a bandage will be placed over it. The entire procedure takes 10 to 15 minutes. Test results are usually available within a day.

Preparation Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are known to thin the blood and interfere with clotting. These medications should be avoided for at least a week before the biopsy. Four to eight hours before the biopsy, patients should stop eating and drinking. The patient’s blood will be tested prior to the biopsy to make sure that it is clotting normally. Tests 835

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QUESTIONS TO ASK THE DOCTOR

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will include a platelet count and a prothrombin time. Doctors will also ensure that the patient is not taking any other medications, such as blood thinners like Coumadin, that might affect blood clotting.

Aftercare Liver biopsies are outpatient procedures in most hospitals. After the biopsy, patients are usually instructed to lie on their right side for about two hours. This provides pressure to the biopsy site and helps prevent bleeding. A nurse will check the patient’s vital signs at regular intervals. If there are no complications, the patient is sent home within about four to eight hours. Patients should arrange to have a friend or relative take them home after discharge. Bed rest for a day is recommended, followed by a week of avoiding heavy work or strenuous exercise. The patient can resume eating a normal diet. Some mild soreness in the area of the biopsy is normal after the anesthetic wears off. Irritation of the muscle that lies over the liver can also cause mild discomfort in the shoulder for some patients. Tylenol can be taken for minor soreness, but aspirin and NSAIDs are best avoided. Patients should call their doctor if they have severe pain in the abdomen, chest or shoulder, difficulty breathing, or persistent bleeding. These signs may indicate that there has been leakage of bile into the abdominal cavity, or that air has been introduced into the cavity around the lungs.

Risks The risks of a liver biopsy are usually very small. When complications do occur, over 90% are apparent within 24 hours after the biopsy. The most significant risk is internal bleeding. Bleeding is most likely to occur in elderly patients, in patients with cirrhosis, or in patients with a tumor that has many blood vessels. Other complications from percutaneous liver biopsies include the leakage of bile or the introduction of air into the chest cavity (pneumothorax). There is also a small chance that an infection may occur, or an internal organ such as the lung, gallbladder, or kidney could be punctured.

Normal results After the biopsy, the liver sample is sent to the pathology laboratory for study under a microscope. A normal (negative) result would find no evidence of cancer or other disease in the tissue sample. 836

Abnormal results Changes in liver tissue that are visible under the microscope indicate abnormal results. Possible causes for the abnormality include the presence of a tumor, or a disease such as hepatitis. Resources BOOKS

Brown, Kyle E., et al. ‘‘Liver Biopsy: Indications, Techni que, Complications and Interpretation’’ In Liver Dis ease. Diagnosis and Management, edited by Bacon, Bruce R., and Adrian M. Di Bisceglie. Philadelphia, PA: Churchill Livingstone, 2000. Reddy, K. Rajender, and Lennox J. Jeffers. ‘‘Evaluation of the Liver. Liver Biopsy and Laparoscopy.’’ In Schiff’s Diseases of the Liver, edited by Eugene R. Schiff, et al. Philadelphia, PA: Lippincott Raven, 1999. PERIODICALS

Bravo, Arturo A., et al. ‘‘Liver Biopsy’’ New England Journal of Medicine 344, no. 7 (February 15, 2001): 495 500.

Lata Cherath, Ph.D.

Liver cancer Definition Liver cancer is a relatively rare form of cancer but has a high mortality rate. Liver cancers can be classified into two types. They are either primary, when the cancer starts in the liver itself, or metastatic, when the cancer has spread to the liver from some other part of the body.

Description and demographics Primary liver cancer Primary liver cancer is a relatively rare disease in the United States, representing about 2% of all malignancies and 4% of newly diagnosed cancers. Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world as of 2004. It is much more common outside the United States, representing 10% to 50% of malignancies in Africa and parts of Asia. Rates of HCC in men are at least two to three times higher than for women. In high-risk areas (East and Southeast Asia, sub-Saharan Africa), men are even more likely to have HCC than women. According to the American Cancer Society, 22,620 people in the United States will be diagnosed with primary liver cancer in 2009, and 18,160 persons will die from the disease. The incidence of primary G A LE EN CY C LO PE DI A O F C AN C ER 3

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Colored computed tomography (CT) scan of axial section through the abdomen showing liver cancer. The vertebra appears dark blue, the liver is large and appears light blue, and the light patches on the liver are the cancerous tumors. (Copyright Department of Clinical Radiology, Salisbury District Hospital, Science Source/Photo Researchers, Inc. Photo reproduced by permission.)

liver cancer has been rising in the United States and Canada since the mid-1990s, most likely as a result of the rising rate of hepatitis C infections. TYPES OF PRIMARY LIVER CANCER. In adults, most primary liver cancers belong to one of two types: hepatomas, or hepatocellular carcinomas (HCC), which start in the liver tissue itself; and cholangiomas, or cholangiocarcinomas, which are cancers that develop in the bile ducts inside the liver. About 80–90% of primary liver cancers are hepatomas. In the United States, about five persons in every 200,000 will develop a hepatoma (70–75% of cases of primary liver cancers are HCC). In Africa and Asia, over 40 persons in 200,000 will develop this form of cancer (more than 90% of cases of primary liver are HCC). Two rare types of primary liver cancer are mixed-cell tumors and Kupffer cell sarcomas.

One type of primary liver cancer, called a hepatoblastoma, usually occurs in children younger than four years of age and between the ages of 12 and 15. Unlike liver cancers in adults, hepatoblastomas have a good chance of being treated successfully. Approximately 70% of children with hepatoblastomas experience complete cures. If the tumor is detected early, the survival rate is over 90%. Metastatic liver cancer The second major category of liver cancer, metastatic liver cancer, is about 20 times more common in G A LE EN CY C LO PE DI A O F C AN CE R 3

Light micrograph of a section through a primary carcinoma from a human liver. Healthy liver cells are normally arranged in roughly hexagonal structures called lobules. In this cancerous liver, the lobules are disintegrating, and abnormal fibrous tissue has proliferated around them. (Copyright John Burbridge, Science Source/Photo Researchers, Inc. Reproduced by permission.)

the United States than primary liver cancer. Because blood from all parts of the body must pass through the liver for filtration, cancer cells from other organs and tissues easily reach the liver, where they can lodge and grow into secondary tumors. Primary cancers in the colon, stomach, pancreas, rectum, esophagus, breast, lung, or skin are the most likely to metastasize (spread) to the liver. It is not unusual for the metastatic cancer in the liver to be the first noticeable sign of a cancer that started in another organ. After cirrhosis, metastatic liver cancer is the most common cause of fatal liver disease.

Causes and symptoms Risk factors The exact cause of primary liver cancer is still unknown. In adults, however, certain factors are known to place some individuals at higher risk of developing liver cancer. These factors include: 837

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What type of liver cancer do I have? What is the stage of the disease? What are the treatment choices? Which do you recommend? Why? What are the risks and possible side effects of each treatment? What are the chances that the treatment will be successful? What new treatments are being studied in clinical trials? How long will treatment last? Will I have to stay in the hospital? Will treatment affect my normal activities? If so, for how long? What is the treatment likely to cost?



Male sex.



Age over 60 years.



Ethnicity. Asian Americans with cirrhosis have four times as great a chance of developing liver cancer as Caucasians with cirrhosis, and African Americans have twice the risk of Caucasians. In addition, Asians often develop liver cancer at much younger ages than either African Americans or Caucasians.



Exposure to substances in the environment that tend to cause cancer (carcinogens). These include: a substance produced by a mold that grows on rice and peanuts (aflatoxin); thorium dioxide, which was once used as a contrast dye for x rays of the liver; vinyl chloride, used in manufacturing plastics; and cigarette smoking.



Use of oral estrogens for birth control.



Hereditary hemochromatosis. This is a disorder characterized by abnormally high levels of iron storage in the body. It often develops into cirrhosis.



Cirrhosis. Hepatomas appear to be a frequent complication of cirrhosis of the liver. Between 30% and 70% of hepatoma patients also have cirrhosis. It is estimated that a patient with cirrhosis has 40 times the chance of developing a hepatoma than a person with a healthy liver.



Exposure to hepatitis viruses: Hepatitis B (HBV), Hepatitis C (HCV), Hepatitis D (HDV), or Hepatitis G (HGV). It is estimated that 80% of worldwide HCC is associated with chronic HBV infection. In

838

Africa and most of Asia, exposure to hepatitis B is an important factor; in Japan and some Western countries, exposure to hepatitis C is connected with a higher risk of developing liver cancer. In the United States, nearly 25% of patients with liver cancer show evidence of HBV infection. Hepatitis is commonly found among intravenous drug abusers. The increase in HCC incidence in the United States is thought to be due to increasing rates of HBV and HCV infections due to increased sexual promiscuity and illicit drug needle sharing. The association between HDV and HGV and HCC is unclear as of the early 2000s. Symptoms of liver cancer The early symptoms of primary, as well as metastatic, liver cancer are often vague and not unique to liver disorders. The long period between the beginning of the tumor’s growth and the first signs of illness is the major reason why the disease has a high mortality rate. At the time of diagnosis, patients are often fatigued, with fever, abdominal pain, and loss of appetite (anorexia). They may look emaciated and generally ill. As the tumor enlarges, it stretches the membrane surrounding the liver (the capsule), causing pain in the upper abdomen on the right side. The pain may extend into the back and shoulder. Some patients develop a collection of fluid, known as ascites, in the abdominal cavity. Others may show signs of bleeding into the digestive tract. In addition, the tumor may block the ducts of the liver or the gall bladder, leading to jaundice. In patients with jaundice, the whites of the eyes and the skin may turn yellow, and the urine becomes dark–colored.

Diagnosis Physical examination If the doctor suspects a diagnosis of liver cancer, he or she will check the patient’s history for risk factors and pay close attention to the condition of the patient’s abdomen during the physical examination. Masses or lumps in the liver and ascites can often be felt while the patient is lying flat on the examination table. The liver is usually swollen and hard in patients with liver cancer; it may be sore when the doctor presses on it. In some cases, the patient’s spleen is also enlarged. The doctor may be able to hear an abnormal sound (bruit) or rubbing noise (friction rub) if he or she uses a stethoscope to listen to the blood vessels that lie near the liver. The noises are caused by the pressure of the tumor on the blood vessels. G A LE EN CY C LO PE DI A O F C AN C ER 3

Blood tests may be used to test liver function or to evaluate risk factors in the patient’s history. Between 50% and 75% of primary liver cancer patients have abnormally high blood serum levels of a particular protein (alpha-fetoprotein or AFP). The AFP test, however, cannot be used by itself to confirm a diagnosis of liver cancer, because cirrhosis or chronic hepatitis can also produce high alpha–fetoprotein levels. Tests for alkaline phosphatase, bilirubin, lactic dehydrogenase, and other chemicals indicate that the liver is not functioning normally. About 75% of patients with liver cancer show evidence of hepatitis infection. Again, however, abnormal liver function test results are not specific for liver cancer. Imaging studies Imaging studies are useful in locating specific areas of abnormal tissue in the liver. Liver tumors as small as an inch across can now be detected by ultrasound or computed tomography scan (CT scan). Imaging studies, however, cannot tell the difference between a hepatoma and other abnormal masses or lumps of tissue (nodules) in the liver. A sample of liver tissue for biopsy is needed to make the definitive diagnosis of a primary liver cancer. CT or ultrasound can be used to guide the doctor in selecting the best location for obtaining the biopsy sample. Chest x rays may be used to see whether the liver tumor is primary or has metastasized from a primary tumor in the lungs. Liver biopsy Liver biopsy is considered to provide the definite diagnosis of liver cancer. A sample of the liver or tissue fluid is removed with a fine needle and is checked under a microscope for the presence of cancer cells. In about 70% of cases, the biopsy is positive for cancer. In most cases, there is little risk to the patient from the biopsy procedure. In about 0.4% of cases, however, the patient develops a fatal hemorrhage from the biopsy because some tumors are supplied with a large number of blood vessels and bleed very easily.

Clinical staging Currently, the pathogenesis of HCC is not well understood. It is not clear how the different risk factors for HCC affect each other. In addition, the environmental factors vary from region to region.

Treatment Treatment of liver cancer is based on several factors, including the type of cancer (primary or metastatic); stage (early or advanced); the location of other primary cancers or metastases in the patient’s body; the patient’s age; and other coexisting diseases, including cirrhosis. For many patients, treatment of liver cancer is primarily intended to relieve the pain caused by the cancer but cannot cure it. Surgery Few liver cancers in adults can be cured by surgery because they are usually too advanced by the time they are discovered. If the cancer is contained within one lobe of the liver, and if the patient does not have either cirrhosis, jaundice, or ascites, surgery is the best treatment option. Patients who can have their entire tumor removed have the best chance for survival. Unfortunately, only about 5% of patients with metastatic cancer (from primary tumors in the colon or rectum) fall into this group. If the entire visible tumor can be removed, about 25% of patients will be cured. The operation that is performed is called a partial hepatectomy, or partial removal of the liver. The surgeon will remove either an entire lobe of the liver (a lobectomy) or cut out the area around the tumor (a wedge resection). A newer technique that is reported to be safe and effective is laparoscopic radiofrequency ablation (RFA). RFA is a technique in which the surgeon places a special needle electrode in the tumor under guidance from MRI or CT scanning. When the electrode has been properly placed, a radiofrequency current is passed through it, heating the tumor and killing the cancer cells. RFA can be used to treat tumors that are too small or too inaccessible for removal by conventional open surgery. Chemotherapy

Laparoscopy The doctor may also perform a laparoscopy to help in the diagnosis of liver cancer. First, the doctor makes a small cut in the patient’s abdomen and inserts a small, lighted tube called a laparoscope to view the area. A small piece of liver tissue is removed and examined under a microscope for the presence of cancer cells. G A LE EN CY C LO PE DI A O F C AN CE R 3

Some patients with metastatic cancer of the liver can have their lives prolonged for a few months by chemotherapy, although cure is not possible. If the tumor cannot be removed by surgery, a tube (catheter) can be placed in the main artery of the liver and an implantable infusion pump can be installed. The pump allows much higher concentrations of the cancer drug to be carried to the tumor than is possible with chemotherapy carried 839

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Laboratory tests

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through the bloodstream. The drug that is used for infusion pump therapy is usually floxuridine (FUDR), given for 14-day periods alternating with 14-day rests. Systemic chemotherapy can also be used to treat liver cancer. The medications usually used are 5-fluorouracil (Adrucil, Efudex) or methotrexate (MTX, Mexate). Systemic chemotherapy does not, however, significantly lengthen the patient’s survival time.

the National Cancer Institute (NCI). The NCI has conducted trials on cancell, laetrile, and some other alternative therapies and found no anticancer activity. These treatments have varying effectiveness and safety considerations. Patients using any alternative remedy should first consult their doctors in order to prevent harmful side effects or interactions with traditional cancer treatment.

Radiation therapy Radiation therapy is the use of high-energy rays or x rays to kill cancer cells or to shrink tumors. Its use in liver cancer, however, is only to give short-term relief from some of the symptoms. Liver cancers are not sensitive to radiation, and radiation therapy will not prolong the patient’s life. Liver transplantation Removal of the entire liver (total hepatectomy) and liver transplantation can be used to treat liver cancer. However, there is a high risk of tumor recurrence and metastases after transplantation. In addition, most patients have cancer that is too far advanced at the time of diagnosis to benefit from liver transplantation. Other therapies Other therapeutic approaches include: Hepatic artery embolization with chemotherapy (chemoembolization).  Alcohol ablation via ultrasound-guided percutaneous injection.  Ultrasound-guided cryoablation.  Immunotherapy with monoclonal antibodies tagged with cytotoxic agents.  Gene therapy with retroviral vectors containing genes expressing cytotoxic agents.

Prognosis Liver cancer has a very poor prognosis because it is often not diagnosed until it has metastasized. Fewer than 10% of patients survive three years after the initial diagnosis; the overall five-year survival rate for patients with hepatomas is around 4%. Most patients with primary liver cancer die within six months of diagnosis, usually from liver failure; fewer than 5% are cured of the disease. Patients with liver cancers that metastasized from cancers in the colon live slightly longer than those whose cancers spread from cancers in the stomach or pancreas. As of 2004, African American and Hispanic patients have much lower 5-year survival rates than Caucasian patients. It is not yet known, however, whether cultural differences as well as biological factors may be partly responsible for the variation in survival rates.



Alternative and complementary therapies

Coping with cancer treatment Side effects of treatment, nutrition, emotional well-being, and other issues are all parts of coping with cancer. There are many possible side effects for a cancer treatment that include:     

Many patients find that alternative and complementary therapies help to reduce the stress associated with illness, improve immune function, and boost spirits. While there is no clinical evidence that these therapies specifically combat disease, such activities as biofeedback, relaxation, therapeutic touch, massage therapy and guided imagery have no side effects and have been reported to enhance well-being. Several other healing therapies are sometimes used as supplemental or replacement cancer treatments, such as antineoplastons, cancell, cartilage (bovine and shark), laetrile, and mistletoe. Many of these therapies have not been the subject of safety and efficacy trials by 840

   

constipation delirium fatigue fever, chills, sweats nausea and vomiting mouth sores, dry mouth, bleeding gums pruritus (itching) affected sexuality sleep disorders

Anxiety, depression, feelings of loss, post-traumatic stress disorder, affected sexuality, and substance abuse are all possible emotional side-effects. Patients should seek out a support network to help them through treatment. Loss of appetite before, during, and after a treatment can also be of concern. Other complications of coping with cancer treatment include fever and pain. G A LE EN CY C LO PE DI A O F C AN C ER 3

As of 2004, the National Cancer Institute is sponsoring 55 clinical trials of treatments for primary liver cancer in adults and 13 trials for treatments of primary liver cancer in children. These trials allow researchers to investigate new types of radiation therapy and chemotherapy, new drugs and drug combinations, biological therapies, ways of combining various types of treatment for liver cancer, side effect reduction, and quality of life. Information on clinical trials can be acquired from the National Cancer Institute at http://www.nci.nih.gov or (800) 4-CANCER.

Prevention There are no useful strategies at present for preventing metastatic cancers of the liver. Primary liver cancers, however, are 75–80% preventable. Current strategies focus on widespread vaccination for hepatitis B, early treatment of hereditary hemochromatosis (a metabolic disorder), and screening of high-risk patients with alpha-fetoprotein testing and ultrasound examinations. Lifestyle factors that can be modified in order to prevent liver cancer include avoidance of exposure to toxic chemicals and foods harboring molds that produce aflatoxin. Most important, however, is avoidance of alcohol and drug abuse. Alcohol abuse is responsible for 60–75% of cases of cirrhosis, which is a major risk factor for eventual development of primary liver cancer. Hepatitis is a widespread disease among persons who abuse intravenous drugs. See also Alcohol consumption; CT-guided biopsy; Hepatic arterial infusion; Immunologic therapy.

Harrison, L. E., T. Reichman, B. Koneru, et al. ‘‘Racial Discrepancies in the Outcome of Patients with Hepa tocellular Carcinoma.’’ Archives of Surgery 139 (Sep tember 2004): 992 996. Nguyen, M. H., A. S. Whittemore, R. T. Garcia, et al. ‘‘Role of Ethnicity in Risk for Hepatocellular Carcinoma in Patients with Chronic Hepatitis C and Cirrhosis.’’ Clinical Gastroenterology and Hepatology 2 (September 2004): 820 824. Stuart, Keith E., MD. ‘‘Hepatic Carcinoma, Primary.’’ eMedicine July 20, 2004. http://www.emedicine.com/ med/topic2664.htm. OTHER

American Cancer Society (ACS). Cancer Facts & Figures 2004.http://www.cancer.org/downloads/STT/ CAFF_finalPWSecured.pdf. ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta, GA 30329. (800) 227 2345. http://www.cancer.org. American Institute for Cancer Research (AICR). 1759 R St. NW, Washington, DC 20009. (800) 843 8114. http:// www.aicr.org. American Liver Foundation. 908 Pompton Ave., Cedar Grove, NJ 07009. (800) 223 0179. Cancer Care, Inc. 275 Seventh Ave., New York, NY 10001.(800) 813 HOPE. http://www.cancercare.org. Cancer Hope Network. Suite A., Two North Rd., Chester, NJ 07930. (877) HOPENET. http:// www.cancerhopenetwork.org. Hospicelink. Hospice Education Institute, 190 Westbrook Rd., Essex, CT, 06426 1510. (800) 331 1620. http:// www.hospiceworld.com. National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422 6237. http://www.nci.nih.gov. The Wellness Community. Suite 412, 35 E. Seventh St., Cincinnati, OH 45202. (888) 793 9355. http:// www.wellness community.org.

Resources

Rebecca J. Frey, Ph.D. Laura Ruth, Ph.D.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Primary Liver Cancer.’’ In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2007.

Liver cancer, secondary see Metastasis Liver scan see Nuclear medicine scans

PERIODICALS

Berber, E., A. Senagore, F. Remzi, et al. ‘‘Laparoscopic Radiofrequency Ablation of Liver Tumors Combined with Colorectal Procedures.’’ Surgical Laparoscopy, Endoscopy and Percutaneous Techniques 14 (August 2004): 186 190. Cahill, B. A., and D. Braccia. ‘‘Current Treatment for Hep atocellular Carcinoma.’’ Clinical Journal of Oncology Nursing 8 (August 2004): 393 399. Decadt, B., and A. K. Siriwardena. ‘‘Radiofrequency Abla tion of Liver Tumours: Systematic Review.’’ Lancet Oncology 5 (September 2004): 550 560. G A LE EN CY C LO PE DI A O F C AN CE R 3

Lobectomy Definition A lobectomy is the removal of a lobe of one of the organs, usually referring to the brain, the lung, or the liver. 841

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Clinical trials

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Q U E S T I O N S T O A S K TH E DOC TOR    



Left upper lobectomy. A surgeon is using a stapling device to ligate (tie or bind) the left upper bronchus. The lobar veins and arteries have already been ligated. (Custom Medical Stock Photo. Reproduced by permission.)

Purpose Lobectomies are usually performed to prevent the spread of cancer from one part of an organ to other parts or to other parts of the body. Lobectomies also are performed on patients with severe seizure disorders (such as some forms of epilepsy) to prevent further seizures. However, there are differences in each of the three organs on which lobectomies may be performed.

Description The brain Each lobe of the brain performs a different function, and when part of the brain is removed, it does not grow back. However, other parts of the brain can take over some, or all, of the function of the missing part of the brain. Depending on the part of the brain removed, the effects may be quite severe, or nearly nonexistent. Left upper lobectomy. A surgeon is using a stapling device to ligate (tie or bind) the left upper bronchus. The lobar veins and arteries have already been ligated. The most commonly referenced brain lobectomy in the medical literature is the removal of the temporal lobe. Temporal lobectomy usually is performed to prevent debilitating seizures. Seizures are commonly caused by temporal lobe epilepsy, but can also be caused by brain tumors in the temporal lobe. Thus, lobectomy of the temporal lobe in patients with a temporal lobe tumor reduces or eliminates seizures, and has the beneficial side effect of removing the tumor mass. 842

What benefits can I expect from this operation? What are the risks of this operation? What are the normal results of this operation? What happens if this operation doesn’t go as planned? What is the expected recovery time?

The lung Lobectomies of the lung also are called pulmonary lobectomies. Each part of the lung performs the same function: it exchanges oxygen for carbon dioxide in the blood. There are many different lobes of the lung, however, and some lobes exchange more oxygen than others. Lobes of the lung do not regenerate after they are removed. Therefore, removal of a large portion of the lung may cause a person to need oxygen or ventilator support for the rest of his or her life. However, removal of a small portion of the lung may result in very little change to the patient’s quality of life. A test (a quantitative ventilation/perfusion scan, or quantitative V/Q scan) may be used before surgery to help determine how much of the lung can safely be removed. The outcome of lung lobectomies also depends on the general health of the entire lung; emphysema and smoking would have a negative impact on the health of a patient’s lung. The surgeon may perform the surgery with video assistance and special tools to decrease pain and speed patient recovery following surgery. The liver A lobectomy of the liver is also called a hepatic lobectomy. The liver plays a major role in digestion, in the transformation of food into energy, and in filtering and storing blood. It processes nutrients and drugs, produces bile, controls the level of glucose (sugar) in the blood, detoxifies blood, and regulates blood clotting. Unlike the brain and the lung, the liver may regrow, or regenerate, after part of the liver has been removed. In addition, since every part of the liver performs the same functions, the liver is the organ whose function is least likely to be severely affected by lobectomy, in the long term, because it regenerates. However, as the liver is central to the body’s functions, G A LE EN CY C LO PE DI A O F C AN C ER 3

Precautions Brain lobectomies should not be performed unless the patient has been unable to control seizures through medication. Additionally, the seizures must be caused by a single, relatively small, localized part of the brain that can be resected without severe damage. Lung lobectomies should only be performed on patients with early stage non-small cell carcinoma of the lung, or as part of a combination of therapies at later stages. Since even a ‘‘complete removal’’ of the tumor does not result in an overwhelming survival rate after five years, other therapies also may be considered. Small cell cancer of the lung does not respond to surgical intervention. Patients with liver disease that is too extensive may need a liver transplant rather than a liver lobectomy. Patients with blood clotting problems, either due to chemotherapeutic agents or for other reasons, should have these problems addressed before surgery.

Preparation Before surgery, patients should not take aspirin or ibuprofen for one week. Patients also should consult their physician about any blood-thinning medications such as coumadin or warfarin. The night before surgery, patients will usually be asked not to eat or drink after a certain time.

Aftercare Each surgery offers different aftercare challenges. Patients may need to be hospitalized for some time after the operation. Patients with portions of their brain removed may require rehabilitation of a physical, mental, or emotional nature depending on the portion of the brain that has been removed. Patients who have had portions of their lungs removed probably will require a tube in their chest to drain fluid, and may require a machine to help them breathe. They also may require oxygen, either on a temporary or permanent basis. Patients who have had hepatic lobectomies also may have drainage tubes, and may also have initial dietary restrictions. Physicians should be consulted for the specifics of aftercare in each individual situation.

Risks Specific risks vary from surgery to surgery and should be discussed with a physician. In general, any surgery requiring a general anesthetic may, G A LE EN CY C LO PE DI A O F C AN CE R 3

uncommonly, result in death. Improperly performed brain surgery may result in permanent brain damage. Depending on the surgeon and the size of the tissue removed, patients may be at risk for some types of brain damage. As previously mentioned, patients having part of a lung removed may have difficulty breathing and may require the use of oxygen. Patients also may experience infection (pneumonia), or blood clots. Liver resection (surgery) may result in the following complications: coma, slow return of normal bowel function, and biliary leakage.

Normal results Most patients who undergo temporal lobectomy experience few or no seizures after surgery (some estimates range from about 70% to about 90% success rate). Unfortunately, lung lobectomy is not as successful. 50% of cancer patients with completely removable stage I non-small cell cancer of the lung survive five years after the procedure. If the cancer has progressed beyond this stage, or if the cancer is not completely removable, the chances for survival drop significantly. The results of liver resection vary. The possible outcomes of each surgical type should be discussed with the patient’s physician. Generally, the less severe the cancer, and the less tissue that needs to be removed, the better the outcome.

Abnormal results Abnormal results vary from operation to operation and should be discussed thoroughly with the patient’s physician before surgery. Patients who undergo temporal lobectomy may, rarely, die as a result of the operation (a complication in less than 1% of patients). Patients also may have problems with their vision, or problems with speech. Abnormal results from the removal of part of the lung could include pneumonia or blood clots (which may result in stroke, heart attack, or other problems) after the surgery. Also, a small percentage of patients undergoing lung lobectomy die during or soon after the surgery. The percentage of patients who suffer death varies from about 3–6% depending on the amount of lung tissue removed. Finally, abnormal outcomes from liver resection can include coma, death, and problems with liver function. Resources PERIODICALS

Namori, Hiroaki, et al. ‘‘Thoracoscopic Lobotomy for Lung Cancer with a Largely Fused Fissure.’’ Chest 9, no. 10 (February 2003): 19 23. 843

Lobectomy

removal of too much of the liver at once may result in coma or death.

Lomustine

Tatum, W. O., and S. R. Benbadis. ‘‘The Neurosurgical Treatment of Epilepsy.’’ Archives of Family Medicine 9, no. 10 (November December 2000): 1142 1147.

KEY T ERMS Antineoplastic—A drug that prevents the growth of a neoplasm by interfering with the maturation or proliferation of the cells of the neoplasm. Neoplasm—New abnormal growth of tissue.

OTHER

Harrison’s Principles of Internal Medicine online, Chap ter 90: Neoplasms of the lung.http://www.harrisonson line.com/. Koike, Atsushi, M.A., Hiroyuki Shimizu, M.D., Ichiro Suzuki, M.D., Buichi Ishijima, M.D., and Morihiro Sugishita, Dr. H.S., Dr. M.S. ‘‘Preserved musical abil ities following right temporal lobectomy.’’ Journal of Neurosurgery. December 1996. [cited July 24, 2005]. http://www.c3.hu/mavideg/jns/1 4 prev1.html. ‘‘Lung Surgery.’’ Healthsquare.com.http://www.health square.com/htm.

Michael Zuck, Ph.D. Teresa G. Odle

Lomustine Definition Lomustine is one of the anticancer (antineoplastic) drugs in a class called alkylating agents. It is available under the brand name CeeNU. Another commonly used name is CCNU.

Purpose Lomustine is primarily used to treat brain tumors and Hodgkin’s disease, which is a type of cancer that affects the lymph nodes and spleen.

Description Lomustine chemically interferes with the synthesis of genetic material (DNA and RNA) of cancer cells, which prevents these cells from being able to reproduce and continue the growth of the cancer.

Recommended dosage Lomustine is taken orally (in pill form). The dosage is typically 100–130 mg per square meter of body surface area once every 6 weeks. Lomustine should be taken on an empty stomach just prior to bedtime to prevent possible nausea and/or vomiting. Patients should avoid alcohol one hour before and shortly after taking lomustine. 844

Hodgkins disease—A disease characterized by enlargement of the lymph nodes and spleen.

Precautions Lomustine can cause an allergic reaction in some people. Patients with a prior allergic reaction to lomustine should not take this drug. Lomustine can cause harm to the fetus if a woman is taking this drug during pregnancy. Women of childbearing potential should use appropriate contraceptive measures to prevent pregnancy while on lomustine. There have been reports of infertility in men taking this drug due to testicular damage. It is not known if lomustine is excreted in breast milk. Because of the potential of severe adverse effect, it is recommended that breastfeeding women should discuss with their physician the risk versus benefit of breastfeeding while taking lomustine.

Side effects Common side effects of lomustine include nausea and/or vomiting, as well as an increased susceptibility to infection due to decreased production in the cells that fight infections. Patients should avoid crowds or exposure to any individuals who may have infections. Also, an increased risk of bleeding can occur due to decreased production of the platelets that are involved with the blood clotting process. Less common side effects that may also occur include loss of appetite (anorexia), diarrhea, temporary hair loss (alopecia), and skin rash. A doctor should be consulted immediately if the patient experiences any of the following effects:       

black, tarry or bloody stools blood in the urine confusion persistent cough fever and chills sore throat red spots on the skin G A LE EN CY C LO PE DI A O F C AN C ER 3



shortness of breath unusual bleeding or bruising

Interactions Lomustine should not be taken in combination with any prescription drug, over-the-counter drug, or herbal remedy without prior consultation with a physician.

Lorazepam is available as 0.5-milligram (mg), 1mg, and 2-mg tablets and in an intramuscular or intravenous injectable form. It is available as a generic drug. U.S. brand names  

Canadian brand names

Paul A. Johnson, Ed.M. 

Loperamide see Antidiarrheal agents

    

Lorazepam Definition Lorazepam is a mild tranquilizer in the benzodiazepine class of drugs. It is used to treat anxiety, nausea and vomiting, insomnia, and seizures.



   

 







Purpose



Lorazepam is used:



to treat anxiety to control muscle spasms that sometimes accompany severe pain to treat insomnia prior to the administration of chemotherapy to decrease the incidence of nausea and vomiting in combination with other drugs to help control nausea and vomiting associated with cancer treatment prior to surgery or other procedures to relieve anxiety, induce drowsiness and sedation, and reduce memories of the procedure in its injectable form, to control seizures

The lorazepam dosage is adjusted to the smallest dose that relieves symptoms. The usual recommended dosages are: 



 

G A LE EN CY C LO PE DI A O F C AN CE R 3

Ativan Lorans Lorazepam Lorivan Sinestron Tavor Temesta

Recommended dosage

Description Benzodiazepines depress the central nervous system primarily by enhancing the function of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits the transmission of nerve impulses in the brain and spinal cord. Lorazepam differs from other benzodiazepines, such as diazepam (Valium) and chlordiazepoxide (Librium), in that it is shorteracting and does not accumulate in the body with repeated doses.

Ativan Apo-Lorazepam Novo-Lorazepam Nu-Loraz PMS-Lorazepam Riva-Lorazepam International brand names





Ativan Lorzepam Intensol









1–6 mg every 8–12 hours to relieve anxiety, with a maximum total daily dosage of 10 mg in two to three divided doses 0.05 mg per kilogram (kg) body weight every four to eight hours in infants and children for anxiety and sedation 2–4 mg at bedtime as a sleep aid 0.5–2 mg per day in divided doses for elderly or debilitated patients 0.5–1 mg every six to eight hours to control nausea and vomiting related to cancer or other medical treatments 2 mg 30 minutes prior to receiving chemotherapy and an additional 2 mg every four hours as needed to prevent stomach upset 0.05 mg per kg, up to 2 mg per intravenous dose, in children aged 2–15 prior to chemotherapy 2.5–5 mg prior to surgery 845

Lorazepam



Lorazepam



4 mg intravenously for seizures; increased to 8 mg in unresponsive patients

A missed dose should be taken as soon as possible, but two doses should not be taken at the same time. Lorazepam can be taken with or without food.

Precautions Patients should not drive, operate machinery or appliances, or perform hazardous activities that require mental alertness until they have a sense of how lorazepam affects them. Lorazepam injection may impair performance and driving ability for 24–48 hours. Lorazepam, like other drugs of this type, can cause physical and psychological dependence. Patients should not increase the dosage or frequency of this drug on their own, nor should they stop taking this medication suddenly. Instead, when stopping the drug, the dosage should gradually be decreased and then discontinued. Stopping lorazepam abruptly can cause agitation, irritability, insomnia, convulsions, and other withdrawal symptoms. Pediatric

 

Lorazepam should be used with caution in patients with:     

Geriatric

Drowsiness and sleepiness are common and expected effects of lorazepam. Possible side effects include dizziness, unsteadiness, clumsiness, or weakness. Patients may have difficulty walking and be prone to falls for up to eight hours after receiving a lorazepam injection, so they should request assistance. Less common side effects of lorazepam include:  

       

Lorazepam injection may impair driving ability and performance for a longer period in older patients. The elderly dosage is normally lower, with a maximum initial dose of 2 mg. Pregnant or breastfeeding Pregnant women and those trying to become pregnant should not take lorazepam. This drug has been associated with fetal malformations when taken during the first three months of pregnancy. It can cause respiratory depression if administered near the time of delivery. Women should not breastfeed while taking lorazepam, since it passes into breast milk.

 

       

Lorazepam should not be used by patients with:



depression confusion agitation nightmares impaired coordination personality changes changes in urinary patterns chest pain heart palpitations Symptoms of lorazepam overdose include:



846

decreased sex drive nausea headache insomnia rash vomiting dry mouth constipation yellowing eyes vision changes hallucinations redness and pain at the injection site high or low blood pressure and partial blockage of the airways following injection

Serious side effects that require a physician’s attention include:

Other conditions and allergies narrow-angle glaucoma  pre-existing depression of the central nervous system  severe uncontrolled pain

kidney or liver disease myasthenia gravis lung disease alcohol intoxication a history of drug or alcohol abuse

Side effects



Lorazepam is not usually given to children under age 12. Children between the ages of 12 and 18 can be given oral lorazepam, although it is only approved as an antianxiety medication by the U.S. Food and Drug Administration (FDA) for those 18 and older. Intravenous lorazepam may be administered to children prior to chemotherapy.

severe low blood pressure allergies to benzodiazepines

 

confusion coma G A LE EN CY C LO PE DI A O F C AN C ER 3

QUESTIONS TO ASK YOUR PHARMACI ST 

    

Will lorazepam interact with my other medications? Can I drink alcohol while taking lorazepam? What if I forget a dose? Can I take lorazepam on an as-needed basis? Can I take more than the prescribed dose? Can I stop taking lorazepam abruptly?



slowed reflexes



difficulty breathing Geriatric

Patients over age 50 may experience greater and longer sedation after administration of lorazepam. These side effects may subside with continued use or dosage reduction.

Interactions Alcohol and other central nervous system depressants can increase the drowsiness associated with lorazepam. Central nervous system depressants include some pain and over-the-counter (OTC) medications, as well as the herbs kava, St. John’s wort, gotu kola, and valerian. Patients should check with their doctor before beginning any new medication, herb, or supplement. Alcohol should be avoided when taking lorazepam, since the drug diminishes alcohol tolerance. Lorazepam injection may impair driving ability and performance for a longer period in those taking other central nervous system depressants, including some pain medications. Patients should refrain from alcohol for 24–48 hours after a lorazepam injection. When injected, lorazepam may also interact with scopolamine, causing drowsiness, odd behavior, and hallucinations. Resources BOOKS

Hales, Robert E., et al. What Your Patients Need To Know About Psychiatric Medications. Washington, DC: American Psychiatric Publishing, 2007. Toufexis, Donna, and Sayamwong E. Hammac. Anti Anxiety Drugs. New York: Chelsea House Publishers, 2006. G A LE EN CY C LO PE DI A O F C AN CE R 3

Giersch, Anne, et al. ‘‘Impairment of Contrast Sensitivity in Long Term Lorazepam Users.’’ Psychopharmacology 186, no. 4 (July 2006): 594 600. Hung, Yi Yung, and Tiao Lai Huang. ‘‘Lorazepam and Diazepam Rapidly Relieve Catatonic Features in Major Depression.’’ Clinical Neuropharmacology 29, no. 3 (May June 2006): 144 147. Izaute, M., and E. Bacon. ‘‘Effects of the Amnesic Drug Lorazepam on Complete and Partial Information Retrieval and Monitoring Accuracy.’’ Psychopharma cology 188, no. 4 (November 2006): 472 481. Kamboj, Sunjeev K., and H. Valerie Curran. ‘‘Neutral and Emotional Episodic Memory: Global Impairment After Lorazepam or Scopolamine.’’ Psychopharmacol ogy 188, no. 4 (November 2006): 482 488. Pomara, Nunzio, et al. ldquo;Dose Dependent Retrograde Facilitation of Verbal Memory in Healthy Elderly After Acute Oral Lorazepam Administration.’’ Psychophar macology 185, no.4 (May 2006): 487 494. Yacoub, Adee, and Andrew Francis. ‘‘Neuroleptic Malig nant Syndrome Induced by Atypical Neuroleptics and Responsive to Lorazepam.’’ Neuropsychiatric Disease and Treatment 2, no. 2 (2006): 235 240. OTHER

American Society of Health System Pharmacists. ‘‘Loraze pam.’’ MedlinePlus. http://www.nlm.nih.gov/medline plus/druginfo/meds/a682053.html. ‘‘Lorazepam.’’ University of Maryland Medical Center. http://www.umm.edu/altmed/drugs/lorazepam 077600.htm U.S. Food and Drug Administration. ‘‘Drug Details: Lorazepam.’’ Drugs@FDA. http://www.accessdata. fda.gov/scripts/cder/drugsatfda/index.cfm?fuse action Search.DrugDetails. ORGANIZATIONS

American Academy of Child & Adolescent Psychiatry, 3615 Wisconsin Avenue, NW , Washington, DC, 20016 3007, (202) 966 7300, (202) 966 2891, http://www. aacap.org. National Institute of Mental Health, 6001 Executive Boule vard, Room 8184, MSC 9663, Bethesda, MD, 20892 9663, (301) 443 4513, (866) 615 6464 , (301) 443 4279, [email protected], http://www.nimh.nih.gov. U.S. Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD, 20993 0002, (888) INFO FDA, http://www.fda.gov.

Debra Wood, RN Teresa G. Odle Ajna Hamidovic, PharmD Ruth A. Wienclaw, PhD Margaret Alic, PhD

Loss of Appetite see Anorexia 847

Lorazepam

PERIODICALS

Low molecular weight heparins

Low molecular weight heparins Definition Low molecular weight heparins (LMWHs) belong to a class of medications known as blood thinners. They are used to stop blood clots from forming and growing.

Purpose LMWHs are used to prevent and treat blood clots in persons undergoing certain types of surgery, recent heart attack, severe chest pain caused by disease of heart vessels usually from fat deposits (unstable angina), and people who have blood clots in their veins (also known as deep vein thrombosis or DVT) or lungs (also known as pulmonary embolism or PE). As of 2001, there are three drugs that belong to the class of LMWHs: enoxaparin, dalteparin, and tinzaparin. All three have the same mechanism of action, but differ in their doses, structures, and Food and Drug Administration (FDA) indicated uses. Many cancer patients can become prone to hypercoagulation, or overactive thickening and clotting of the blood. This makes the patient more likely to experience deep vein thrombosis, possibly leading to death.

Description LMWHs only became available in the mid-1990s, with enoxaparin (Lovenox) being the first and most studied drug in its class. Dalteparin (Fragmin) was the second LMWH to become available and tinzaparin (Innohep) is the latest addition to this class. These medicines work by inhibiting certain clotting factors in the blood (Factor Xa and thrombin) and preventing blood clots from forming and getting bigger. LMWHs are closely related to heparin, which is one of the oldest blood thinners available. These drugs have an advantage over heparin in that they have longer duration in the body, more predictable effects after a given dose, require less blood tests to check for their effectiveness and side effects, and do not have to be given in the hospital setting only. LMWHs have been found to be safe and effective in blood clot prevention after general surgery, orthopedic surgery, neurosurgery, multiple trauma, hip fracture, certain types of stroke, unstable angina, heart attack and treatment DVT and PE. These drugs are usually given with warfarin (Coumadin) for treatment of blood clots and with aspirin for prevention of complications after heart attack or angina attack. Besides 848

KEY T ERMS Deep vein thrombosis—Also known as DVT, a condition in which a blood clot (thrombus) formed in one part of the circulation, becomes detached and lodges at another point (usually in one of the veins of the legs or arms). People may feel pain, redness, and swelling at the site where the blood clot lodges in. This condition is treated with blood thinning drugs such as LMWHs, heparin, or warfarin. Pulmonary embolism—Also known as PE, a condition in which a blood clot usually formed in of the leg veins becomes detached and lodges in the lung artery or one of its branches. Patients may be coughing up blood and experience trouble breathing. This condition is treated with blood thinning drugs such as LMWHs, heparin, or warfarin.

their use for blood clot prevention and treatment, there have been some research studies in animals and humans to suggest that they may prevent cancer by decreasing the blood supply needed for the tumor to grow. The effects of LMWHs on patients with cancer and blood clots are being investigated. In 2004, clinical trails suggested that LMWHs might interfere with tumor growth and cancer spread, but further study was needed.

Recommended dosage Administration These medicines are given by injection beneath the skin (subcutaneous injection) and should not be injected directly into the vein or muscle. Injections can be given around the navel, upper thigh or buttock. The injection site should be changed daily. Massaging of the site before injection with an ice cube can decrease excessive bruising. Doses and indications differ between three medicines. These drugs can not be used interchangeably for one another. Adults PREVENTION OF BLOOD CLOTS AFTER ORTHOPEDIC SURGERY. The usual dose of tinzaparin is 50 units per

kg daily starting two hours before surgery and continuing for 7–10 days. Doses of 75 units per kg per day have also been studied. G A LE EN CY C LO PE DI A O F C AN C ER 3

agents. The usual enoxaparin dose is 30 mg every 12 hours starting 12–24 hours after surgery in patients undergoing hip or knee surgery. Alternatively, 40 mg once a day with the first dose given approximately 12 hours before surgery can be used in patients undergoing hip replacement surgery. The average duration of the initial phase of treatment is 7–10 days (up to 14 days). After the initial phase, 40 mg once a day for three weeks is recommended. For people undergoing hip replacement surgery, 5,000 units of dalteparin are given 10–14 hours before surgery, then 5,000 units 4–8 hours after surgery, followed by 5,000 units daily. The therapy is usually continued for five to ten days (up to 14 days). A physician should be consulted for alternative dosing regimens. PREVENTION OF DVT IN PATIENTS AT HIGH RISK FOR BLOOD CLOTS AFTER ABDOMINAL SURGERY.. Enoxa-

parin is usually given at a dose of 40 mg once daily with the first dose given two hours before surgery for seven to ten days, up to 12 days. In patients who are at moderate to high risk of blood clots, the usual dose of dalteparin is 2,500 units daily generally given for five to ten days. The first dose should be given one to two hours before surgery. In patients who are at high to very high risk of blood clots (those with cancer or history of DVT or PE) 5,000 units are given on the evening before surgery, followed by 5,000 units/day for five to ten days. A physician should be consulted for alternative dosing schedules. Tinzaparin is usually dosed at 3,500 units daily starting two hours before surgery and continuing for seven to ten days. TREATMENT OF DVT WITH OR WITHOUT PE. Enoxaparin doses of 1 mg per kg twice a day are given when people are treated at home. People who are treated in the hospital can be given 1 mg per kg twice a day or 1.5 mg per kg at the same time once a day. Warfarin is usually given to finish treatment and the two drugs overlap for about 72 hours until good response to warfarin is confirmed by blood tests.

The usual dose of dalteparin in people who are also getting aspirin is 120 units per kg (up to a maximum 10,000 units) every 12 hours. Treatment should continue until the patient is stable for five to eight days. Children TREATMENT OF DVT WITH OR WITHOUT PE. Children younger than two months of age should receive enoxaparin 1.5 mg per kg every 12 hours. Children older than two months of age should receive enoxaparin 1 mg per kg every 12 hours. A physician will do a blood test four to six hours after the dose to check for effectiveness. PREVENTION OF BLOOD CLOTS. The usual dose of enoxaparin is 0.75 mg per kg every 12 hours for children younger than two months and 0.5 mg per kg every 12 hours for children older than two months of age. A physician will do a blood test four to six hours after the dose to check for effectiveness.

Precautions The use of LMWHs should be avoided in persons undergoing any procedure involving spinal puncture or anesthesia. Using these medicines before these procedures has caused severe bruising and bleeding into the spine and can lead to paralysis. The use of these medicines should be avoided in patients with allergies to LMWHs, heparin, or pork products, allergies to sulfites or benzyl alcohol, people with active major bleeding, and people with a history of heparin-induced low blood platelet count (also known as heparin-induced thrombocytopenia or HIT). LMWHs should be used with caution in the following persons:    



Tinzaparin is usually dosed at 175 units per kg daily for six days or until good response to warfarin is confirmed by blood tests.



UNSTABLE ANGINA OR HEART ATTACK. In patients



who are also getting aspirin the usual dose of enoxaparin is 1 mg per kg every 12 hours for a minimum of two days (usually two to eight days). G A LE EN CY C LO PE DI A O F C AN CE R 3

people with bleeding disorders people with a history of recent stomach ulcers people who recently had brain, spine, or eye surgery people on other blood thinners (such as warfarin, aspirin, ibuprofen, naproxen) because of increased risk of bleeding people with kidney or liver disease (the dose of LMWHs may need to be decreased) breast-feeding mothers (it is not known if these medicines cross into breast milk) women who are pregnant, unless benefits to the mother outweigh the risks to the baby

A doctor should be contacted immediately if any of these symptoms develop: 849

Low molecular weight heparins

PREVENTION OF BLOOD CLOTS AFTER HIP OR KNEE REPLACEMENT SURGERY. Doses vary between different

Lumbar puncture

tingling, weakness, numbness or pain  blood in the urine or stool  itching, swelling, skin rash, trouble breathing  unusual bleeding or bruising

Purpose



A physician may perform blood tests during therapy with LMWHs to prevent side effects. Blood tests to check for effectiveness of these medicines are usually not needed, except in children, people with kidney disease, and overweight persons.

Side effects The most common side effects of LMWHs include irritation and pain at the injection site, easy bruising and bleeding, fever, increase in liver enzyme tests usually without symptoms, and allergic reactions. Severe painful erection sometimes requiring surgery has been reported with tinzaparin in some patients. LMWHs can lower platelet counts, which may necessitate discontinuation.

Interactions LMWHs should be used with caution in people on other oral blood thinners (aspirin, non-steroidal anti-inflammatory drugs, warfarin, and ticlopidine) because of increased risk of bleeding. If using both drugs together is necessary, the patients must be closely monitored. Resources PERIODICALS

‘‘Low molecular Weight Heparins May Interfere With Tumor Growth and Metastasis.’’ Drug Week (July 2, 2004): 269.

Olga Bessmertny, Pharm.D. Teresa G. Odle

Lumbar puncture Definition Lumbar puncture (LP) is the technique of using a needle to withdraw cerebrospinal fluid (CSF) from the spinal canal. CSF is the clear, watery liquid that protects the central nervous system from injury and cushions it from the surrounding bone structure. It contains a variety of substances, particularly glucose (sugar), protein, and white blood cells from the immune system. 850

Lumbar puncture (spinal tap) is used to diagnose some malignancies, such as certain types of brain cancer and leukemia, as well as other medical conditions that affect the central nervous system. It is sometimes used to assess patients with certain psychiatric symptoms and conditions. It is also used for injecting chemotherapy directly into the CSF. This type of treatment is called intrathecal therapy. Other medical conditions diagnosed with lumbar puncture include:   





viral and bacterial meningitis syphilis, a sexually transmitted disease bleeding (hemorrhaging) around the brain and spinal cord multiple sclerosis, a disease that affects the myelin coating of the nerve fibers of the brain and spinal cord Guillain-Barre´ syndrome, an inflammation of the nerves

Precautions In some circumstances, a lumbar puncture to withdraw a small amount of CSF for analysis may lead to serious complications. Lumbar puncture should be performed only with extreme caution, and only if the benefits are thought to outweigh the risks, in certain conditions. For example, in people who have blood clotting (coagulation) or bleeding disorders or who are on anticoagulant treatment, lumbar puncture can cause bleeding that can compress the spinal cord. The term for this condition is spinal subdural hematoma, and it is a rare complication. However, it is of concern to some cancer patients whose low platelet counts (thrombocytopenia) make them more susceptible to bleeding. In some cases, these patients are given a platelet transfusion prior to lumbar puncture, but this procedure is still under investigation. A 1984– 88 study, supported in part by the National Cancer Institute, researched the risk of lumbar puncture on children with acute lymphoblastic leukemia (ALL). No serious lumbar puncture complications were observed in this study of over 5,000 children. Lumbar puncture has been shown to be less precise than some other methods in monitoring intracranial fluid pressure. A transducer provides more accurate information about changes in the flow of blood and cerebrospinal fluid within the brain. A traumatic lumbar puncture (TLP) occurs when a blood vessel is inadvertently ruptured during the procedure. If this happens as part of a diagnostic G A LE EN CY C LO PE DI A O F C AN C ER 3

Lumbar puncture

Q U E S T I O N S T O A S K TH E DOC TOR   



 

What is the purpose of my lumbar puncture? What aftercare will be needed? Will lumbar puncture be used for chemotherapy, and if so, how often will I receive treatments? What are the risks for diagnostic procedures or treatments through lumbar puncture? What do the test results mean? What techniques are suggested to relax children before and after a lumbar puncture?

small amount of fluid. The most common position is for the patient to lie on his or her side with the back at the edge of the exam table, head and chin bent down, knees drawn up to the chest, and arms clasped around the knees. (Small infants and people who are obese may need to curve their spines in a sitting position.) People should talk to their doctors if they have any questions about their position because it is important to be comfortable and to remain still during the entire procedure. In fact, the doctor will explain the procedure to the patient (or guardian) so that the patient can agree in writing to have it done (informed consent). If the patient is anxious or uncooperative, a short-acting sedative may be given. During a lumbar puncture, the doctor drapes the back with a sterile covering that has an opening over the puncture site and cleans the skin surface with an antiseptic solution. Patients receive a local anesthetic to minimize any pain in the lower back. The doctor inserts a thin hollow needle in the space between two vertebrae of the lower back and slowly advances it through ligamentous tissues toward the spine. A steady flow of clear cerebrospinal fluid, normally the color of water, will begin to fill the needle as soon as it enters the spinal canal. The doctor measures the cerebrospinal fluid pressure with a special instrument called a manometer and withdraws several vials of fluid for laboratory analysis. The amount of fluid collected depends on the type and number of tests needed to diagnose a particular medical disorder. In some cases, the doctor must remove and reposition the needle. This occurs when there is not an even flow of fluid, the needle hits bone or a blood vessel, or the patient reports sharp, unusual pain. 852

KEY T ERMS Acute lymphoblastic leukemia (ALL)—A type of leukemia, also called acute lymphocytic leukemia, primarily in children, affecting lymphocytes. Encephalitis—An inflammation or infection of the brain and spinal cord caused by a virus or as a complication of another infection. Guillain-Barre´ syndrome—An inflammation involving nerves that affects the extremities. The inflammation may spread to the face, arms, and chest. Immune system—Protects the body against infection. Intrathecal therapy—Injecting chemotherapy directly into the CSF using lumbar puncture. Manometer—A device used to measure fluid pressure. Meningitis—An infection or inflammation of the membranes or tissues that cover the brain and spinal cord, and caused by bacteria or a virus. Multiple sclerosis—A disease that destroys the covering (myelin sheath) of nerve fibers of the brain and spinal cord. Spinal canal—The cavity or hollow space within the spine that contains cerebrospinal fluid. Thrombocytopenia—Reduced platelet levels. Vertebrae—The bones of the spinal column. There are 33 along the spine, with five (called L1 L5) making up the lower lumbar region.

Preparation Patients can go about their normal activities before a lumbar puncture. Experts recommend that patients relax before the procedure to release any muscle tension, since the lumbar puncture needle must pass through muscle tissue before it reaches the spinal canal. A patient’s level of relaxation before and during the procedure plays a critical role in the test’s success. Relaxation may be difficult for those patients who face frequent lumbar punctures, such as children with leukemia. In these cases, it is especially important for the child to receive psychological support before and after each procedure. It may be helpful to praise a child who remained still and quiet during the procedure, and to remind the child of his or her good behavior before the next lumbar puncture. G A LE EN CY C LO PE DI A O F C AN C ER 3

After the procedure, the doctor covers the site of the puncture with a sterile bandage. Patients must avoid sitting or standing and remain lying down for as long as six hours after the lumbar puncture. They should also drink plenty of fluids to help prevent lumbar puncture headache, which is discussed in the next section.

Risks The most common side effect of lumbar puncture is a headache. This problem occurs in 10–20% of adult patients and in up to 40% of children. It is caused by decreased CSF pressure related to a small leak of CSF through the puncture site. These headaches usually are a dull pain, although some people report a throbbing sensation. A stiff neck and nausea may accompany the headache. A lumbar puncture headache typically begins within a few hours to two days after the procedure and usually persists a few days, although it can last several weeks or months. In some cases, the headache can be prevented by lying flat for an hour after the lumbar puncture, and taking in more fluids for 24 hours after the procedure. Since an upright position worsens the pain, lying flat also helps control the pain, along with prescription or non–prescription pain relief medication, preferably one containing caffeine. In rare cases, the puncture site leak is ‘‘patched’’ using the patient’s own blood. People may also experience back pain. Headaches and backaches appear to be more common in adolescents than in younger children, and more common in girls than in boys. Patients who receive anticancer drugs through lumbar puncture sometimes have nausea and vomiting. Intrathecal methotrexate can cause mouth sores. Some of these symptoms may be relieved by antinausea drugs prescribed by the physician. In a very few cases, lumbar puncture in infants can lead to such complications as paraplegia. These complications are associated with the smaller size of the infant’s central nervous system and increased difficulty in avoiding certain parts of the spinal cord when performing an LP. People should talk to their doctors about complications from a lumbar puncture. In most cases, this procedure is safe and effective. Some patients experience pain, difficulty urinating, infection, or leakage of cerebrospinal fluid from the puncture site after the procedure. G A LE EN CY C LO PE DI A O F C AN CE R 3

Normal results Normal CSF is clear and colorless. It may be straw or yellow–colored if there is excess protein, which may occur with cancer or inflammation. It may be cloudy in infections; blood–tinged if there was recent bleeding; or yellow to brown (xanthochromic) if caused by an older instance of bleeding. A series of laboratory tests analyze the CSF for a variety of substances to rule out cancer or other medical disorders of the central nervous system. The following are normal values for commonly tested substances:    



 

CSF pressure: 50–180 mm H2O Glucose: 40–85 mg/dL Protein: 15–50 mg/dL Leukocytes (white blood cells) total less than 5 per mL Lymphocytes (specific type of white blood cell): 60–70% Monocytes (a kind of white blood cell): 30–50% Neutrophils (another kind of white blood cell): none

Normally, there are no red blood cells in the CSF unless the needle passes though a blood vessel on route to the CSF. If this is the case, there should be more red blood cells in the first tube collected than in the last.

Abnormal results A lumbar puncture is sometimes used as part of a diagnostic cancer workup. Abnormal test result values in the pressure or any of the substances found in the cerebrospinal fluid may suggest a number of medical problems including a tumor or spinal cord obstruction; hemorrhaging or bleeding in the central nervous system; infection from bacterial, viral, or fungal microorganisms; or an inflammation of the nerves. If there is a tumor in the meninges (membranes around the brain and spinal cord), the CSF may have higher protein levels, lower glucose levels, and a mild increase in lymphocytes (pleocytosis). It is important for patients to review the results of a cerebrospinal fluid analysis with their doctor and to discuss any treatment plans. See also Acute lymphocytic leukemia; Brain and central nervous system tumors. Resources BOOKS

Braunwald, Eugene, et al., editors. Harrison’s Principles of Internal Medicine. 15th ed. New York: McGraw Hill, 2001. 853

Lumbar puncture

Aftercare

Lumpectomy

PERIODICALS

Czosnyka, M., and J. D. Pickard. ‘‘Monitoring and Inter pretation of Intracranial Pressure.’’ Journal of Neurol ogy, Neurosurgery, and Psychiatry 75 (June 2004): 813 821. Ebinger, F., C. Kosel, J. Pietz, and D. Rating. ‘‘Headache and Backache after Lumbar Puncture in Children and Adolescents: A Prospective Study.’’ Pediatrics 113 (June 2004): 1588 1592. Gajjar, Amar, et al. ‘‘Traumatic Lumbar Puncture at Diag nosis Adversely Affects Outcome in Childhood Acute Lymphoblastic Leukemia.’’ Blood 15 (November 2000): 3381 84. Howard, Scott C., et al. ‘‘Safety of Lumbar Puncture for Children With Acute Lymphoblastic Leukemia and Thrombocytopenia.’’ Journal of the American Medical Association (JAMA) 284 (November 2000): 2222 24. Tubbs, R. S., M. D. Smyth, J. C. Wellons, III, and W. J. Oakes. ‘‘Intramedullary Hemorrhage in a Neonate after Lumbar Puncture Resulting in Paraplegia: A Case Report.’’ Pediatrics 113 (May 2004): 1403 1405. Zun, L. S., R. Hernandez, R. Thompson, and L. Downey. ‘‘Comparison of EPs’ and Psychiatrists’ Laboratory Assessment of Psychiatric Patients.’’ American Journal of Emergency Medicine 22 (May 2004): 175 180. ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave., St. Paul, MN 55116 2325. (800) 879 1960. http:// www.aan.com.

Martha Floberg Robbins Rebecca J. Frey, Ph.D.

recommending surgery. The patient’s psychological outlook, as well as her lifestyle and preferences, should also be taken into account when treatment decisions are made. The extent and severity of a cancer is evaluated or ‘‘staged’’ according to a fairly complex system. Staging considers the size of the tumor and whether the cancer has spread to other areas, such as the chest wall, the lymph nodes, and/or to distant parts of the body. Women with early stage breast cancers are usually better candidates for lumpectomy. In most cases, a course of radiation therapy after surgery is part of the treatment. Chemotherapy or antiestrogens also may be prescribed. Many studies have compared the survival rates of women who have had removal of a breast (mastectomy) with those who have undergone lumpectomy and radiation therapy. The data demonstrate that for women with comparable stages of breast cancer, survival rates are similar between the two groups, but the risk of the cancer recurring in the breast is slightly higher with lumpectomy. A 2003 study confirmed that younger women who have lumpectomies have a higher risk of tumor recurrence than those who have mastectomies. In some instances, women with later stage breast cancer may be able to have lumpectomy. Chemotherapy may be administered before surgery to decrease tumor size and the chance of spread in selected cases.

Precautions

Lumpectomy Definition A lumpectomy is a type of surgery for breast cancer. It is considered ‘‘breast-conserving’’ surgery because in a lumpectomy, only the malignant tumor and a surrounding margin of normal breast tissue are removed. Lymph nodes in the armpit (axilla) also may be removed. This procedure is called lymph node dissection.

Purpose Lumpectomy is a surgical treatment for newly diagnosed breast cancer. It is estimated that at least 50% of women with breast cancer are good candidates for this procedure. The location, size, and type of tumor are of primary importance when considering breast cancer surgery options. The size of the breast is another factor the surgeon considers when 854

A number of factors may prevent or prohibit a breast cancer patient from having a lumpectomy. The tumor itself may be too large or located in an area where it would be difficult to remove with good cosmetic results. Sometimes several areas of cancer are found in one breast, so the tumor cannot be removed as a single lump. A cancer that has already attached itself to nearby structures, such as the skin or the chest wall, needs more extensive surgery. Certain medical or physical circumstances also may eliminate lumpectomy as a treatment option. Sometimes lumpectomy may be attempted, but the surgeon is unable to remove the tumor with a sufficient amount of normal tissue surrounding it. This may be termed ‘‘persistently positive margins,’’ or ‘‘lack of clear margins,’’ referring to the margin of unaffected tissue around the tumor. Lumpectomy is not used for women who have had a previous lumpectomy and have a recurrence of the breast cancer. The need for radiation therapy after lumpectomy makes this surgery medically unacceptable for some G A LE EN CY C LO PE DI A O F C AN C ER 3

Lumpectomy

Lumpectomy

Skin flap

Pectoralis major muscle

Lump

Incision

Mammary glands

A.

B.

Scar tissue

C.

During a lumpectomy, a small incision is made around the area of the lump (A). The skin is pulled back, and the tumor removed (B). The incision is closed (C). (Illustration by GGS Information Services. Cengage Learning, Gale.)

women. For instance, radiation therapy cannot be administered to pregnant women because it may injure the fetus. If, however, delivery would be completed prior to the need for radiation, pregnant women may undergo lumpectomy. Women with collagen vascular disease, such as lupus erythematosus or scleroderma, would experience scarring and damage to their connective tissue if exposed to radiation treatments. A G A LE EN CY C LO PE DI A O F C AN CE R 3

woman who has already had therapeutic radiation to the chest area for other reasons cannot have additional exposure for breast cancer therapy. Some women may choose not to have a lumpectomy for other reasons. They may strongly fear a recurrence of breast cancer, and may consider a lumpectomy too risky. Others feel uncomfortable with a 855

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breast that has had a cancer, and they experience more peace of mind with the entire breast removed. The need for radiation therapy may also be a barrier due to non-medical concerns. Some women simply fear this type of treatment and choose more extensive surgery so that radiation will not be required. The commitment of time, usually five days a week for six weeks, may not be acceptable for others. This may be due to financial, personal, or job-related constraints. Finally, in geographically isolated areas, a course of radiation therapy may require lengthy travel, and perhaps unacceptable amounts of time away from family and other responsibilities.

Description Lumpectomy is an imprecise term. Any amount of tissue, from 1–50% of the breast, may be removed and called a lumpectomy. Breast conservation surgery is a frequently used synonym for lumpectomy. Partial mastectomy, quadrantectomy, segmental excision, wide excision, and tylectomy are other, less commonly used names for this procedure. A lumpectomy is frequently done in a hospital setting (especially if lymph nodes are to be removed at the same time), but specialized outpatient facilities are sometimes preferred. The surgery is usually done while the patient is under general anesthesia. Local anesthetic with additional sedation may be used for some patients. The tumor and surrounding margin of tissue is removed and sent to the pathologist. The surgical site is closed. If axillary lymph nodes were not removed in a prior biopsy, a second incision is made in the armpit. The fat pad that contains lymph nodes is removed from this area and is also sent to the pathologist for analysis. This portion of the procedure is called an axillary lymph node dissection; it is critical for determining the stage of the cancer. Typically, 10 to 15 nodes are removed, but the number may vary. Surgical drains may be left in place in either location to prevent fluid accumulation. The surgery may last from one to three hours. The patient may stay in the hospital one or two days, or return home the same day. This generally depends on the extent of the surgery and the medical condition of the patient, as well as physician and patient preferences. A woman usually goes home with a small bandage. The inner part of the surgical site usually has dissolvable stitches. The skin may be sutured or stitched; or the skin edges may be held together with steristrips, which are special thin, clear pieces of tape. 856

KEY T ERMS Lymph node—A small mass of tissue in the form of a knot or protuberance. They are the primary source of lymph fluid, which serves in the body’s defense by removing toxic fluids and bacteria.

Preparation Routine preoperative preparations, such as having nothing to eat or drink the night before surgery, are typically ordered for a lumpectomy. Information about expected outcomes and potential complications is also part of preparation for lumpectomy, as it is for any surgical procedure. It is especially important that women know about sensations they might experience after the operation, so the sensations are not misinterpreted as signs of further cancer or poor healing. If the tumor is not able to be felt (not palpable), a pre-operative localization procedure is needed. A fine wire, or other device, is placed at the tumor site, using x ray or ultrasound for guidance. This is usually done in the radiology department of a hospital. The woman is most often sitting up and awake, although some sedation may be administered.

Aftercare After a lumpectomy, patients are usually cautioned against lifting anything that weighs more than five pounds for several days. Other activities may be restricted (especially if the axillary lymph nodes were removed) according to individual needs. Pain is often enough to limit inappropriate motion. Women are often instructed to wear a well-fitting support bra both day and night for approximately one week after surgery. Pain is usually well controlled with prescribed medication. If it is not, the patient should contact the surgeon, as severe pain may be a sign of a complication, which needs medical attention. A return visit to the surgeon is normally scheduled approximately ten days to two weeks after the operation. Studies have shown that women improve their survival rates after lumpectomy if they stop smoking. Radiation therapy is usually started as soon as feasible after lumpectomy. Other additional treatments, such as chemotherapy or hormone therapy, may also be prescribed. The timing of these is specific to each individual patient. G A LE EN CY C LO PE DI A O F C AN C ER 3

The risks are similar to those associated with any surgical procedure. Risks include bleeding, infection, asymmetry, anesthesia reaction, or unexpected scarring. A lumpectomy also may cause loss of sensation in the breast. The size and shape of the breast will be affected by the operation. Fluid can accumulate in the area where tissue was removed, requiring drainage. If lymph node dissection is performed, there are several potential complications. A woman may experience decreased feeling in the back of her armpit. She may also experience other sensations, including numbness, tingling, or increased skin sensitivity. An inflammation of the arm vein, called phlebitis, can occur. There may be injury to the nerves controlling arm motion. Approximately 2–10% of patients develop lymphedema (swelling of the arm) after axillary lymph node dissection. This swelling of the arm can range from mild to very severe. It can be treated with elastic bandages and specialized physical therapy, but it is a chronic condition, requiring continuing care. Lymphedema can arise at any time, even years after surgery. A new technique often eliminates the need for removing many axillary lymph nodes. Sentinel lymph node mapping and biopsy is based on the idea that the condition of the first lymph node in the network, which drains the affected area, can predict whether the cancer may have spread to the rest of the nodes. It is thought that if this first, or sentinel, node is cancer-free, there is no need to look further. Many patients with early-stage breast cancers may be spared the risks and complications of axillary lymph node dissection as the use of this approach continues to increase.

Normal results When lumpectomy is performed, it is anticipated that it will be the definitive surgical treatment for breast cancer. Other forms of therapy, especially radiation, are often prescribed as part of the total treatment plan. A 2003 study reported that radiation of the entire breast produces better results than radiation of part of the breast. The expected outcome after lumpectomy and radiation is no recurrence of the breast cancer, however, women who have had lumpectomies, particularly those who were young at the time of treatment, should continue to see their physicians for regular breast cancer check-ups, since the cancer can recur.

distally (in a part of the body far from the original site). Recurrence may be discovered soon after lumpectomy or years after the procedure. For this reason, it is important for patients to be regularly and closely monitored by their physicians. A 2003 report showed that magnetic resonance imaging (MRI) is accurate in detecting any cancer left in the breast after lumpectomy. Women should continue to have regular mammograms. While the scar tissue from lumpectomy and radiation therapy can make mammograms less comfortable, a special cushion was approved by the U.S. Food and Drug Administration in 2003 that reduces discomfort in women who have had breast conserving surgery. Resources BOOKS

Love, Susan M., with Karen Lindsey. Dr. Susan Love’s Breast Book. 3rd ed. Cambridge: Perseus Publishing, 2000. Robinson, Rebecca Y., and Jeanne A. Petrek. A Step by Step Guide to Dealing With Your Breast Cancer. New York: Carol Publishing Group, 1999. PERIODICALS

Ford, Steve. ‘‘Lumpectomy Associated With Higher Long term Risk of Recurrence than Mastectomy.’’ Practice Nurse November 28, 2003: 50. Jancin, Bruce. ‘‘Cushion Lessens Mammogram Pain After Lumpectomy (Pain Decreased 54%).’’ OB GYN News February 15, 2003: 9 11. ‘‘MR Accurate in Detecting Residual Disease Following Lumpectomy.’’ Women’s Health Weekly May 29, 2003: 14. Norton, Patrice G.W. ‘‘More Data Support Breast Conser vation Over Mastectomy (For Phase I or II Cancer).’’ Family Practice News January 15, 2003: 31. ‘‘Smoking Decreases Survival of Patients Treated with Lumpectomy and Radiation.’’ Cancer Weekly Novem ber 11, 2003: 36. ‘‘Study: Whole breast Irradiation After Lumpectomy Has Clear Long term Benefits.’’ Cancer Weekly November 11, 2003: 39.

Ellen S. Weber, M.S.N. Teresa G. Odle

Lung biopsy Definition

Abnormal results An unforeseen outcome of lumpectomy may be recurrence of the breast cancer, either locally or G A LE EN CY C LO PE DI A O F C AN CE R 3

Lung biopsy is a procedure for obtaining a small sample of lung tissue for examination. The tissue is usually examined under a microscope, and may be sent 857

Lung biopsy

Risks

Lung biopsy

to a microbiological laboratory for culture. Microscopic examination is performed by a pathologist.

Purpose A lung biopsy is usually performed to determine the cause of abnormalities, such as nodules that appear on chest x rays. It can confirm a diagnosis of cancer, especially if malignant cells are detected in the patient’s sputum or bronchial washing. In addition to evaluating lung tumors and their associated symptoms, lung biopsies may be used to diagnose lung infections, especially tuberculosis and Pneumocystis pneumonia, drug reactions, and chronic diseases of the lungs such as sarcoidosis and pulmonary fibrosis. A lung biopsy can be used for treatment as well as diagnosis. Bronchoscopy, a type of lung biopsy performed with a long, flexible slender instrument called a bronchoscope, can be used to clear a patient’s air passages of secretions and to remove airway blockages.

Demographics Lung cancer is the leading cause of cancer-related deaths in the United States. About 213,380 patients were newly diagnosed with lung cancer in 2007 (about 114,760 in men and 98,620 in women). It is expected to claim nearly 160,390 lives in 2007 (89,510 in men and 70,880 in women). Lung cancer kills more people than cancers of the breast, prostate, colon, and pancreas combined. Cigarette smoking accounts for nearly 90% of cases of lung cancer in the United States.

Description Overview The right and left lungs are separated by the mediastinum, which contains the heart, trachea, lymph nodes, and esophagus. Lung biopsies sometimes involve mediastinoscopy. Types of lung biopsies Lung biopsies are performed using a variety of techniques, depending on where the abnormal tissue is located in the lung, the health and age of the patient, and the presence of lung disease. A bronchoscopy is ordered if a lesion identified on the x ray seems to be located on the wall (periphery) of the chest. If the suspicious area lies close to the chest wall, a needle biopsy can be done. If both methods fail to diagnose the problem, an open lung biopsy may be performed. When there is a question about whether the lung 858

cancer or suspicious mass has spread to the lymph nodes in the mediastinum, a mediastinoscopy is performed. BRONCHOSCOPIC BIOPSY. During the bronchoscopy, a thin, lighted tube (bronchoscope) is passed from the nose or mouth, down the windpipe (trachea) to the air passages (bronchi) leading to the lungs. Through the bronchoscope, the physician views the airways, and is able to clear mucus from blocked airways, and collect cells or tissue samples for laboratory analysis. NEEDLE BIOPSY. The patient is mildly sedated, but awake during the needle biopsy procedure. He or she sits in a chair with arms folded in front on a table. An x-ray technician uses a computerized axial tomography (CAT) scanner or a fluoroscope to identify the precise location of the suspicious areas. Markers are placed on the overlying skin to identify the biopsy site. The skin is thoroughly cleansed with an antiseptic solution, and a local anesthetic is injected to numb the area. The patient will feel a brief stinging sensation when the anesthetic is injected.

The physician makes a small incision, about half an inch (1.25 cm) in length. The patient is asked to take a deep breath and hold it while the physician inserts the biopsy needle through the incision into the lung tissue to be biopsied. The patient may feel pressure, and a brief sharp pain when the needle touches the lung tissue. Most patients do not experience severe pain. The patient should refrain from coughing during the procedure. The needle is withdrawn when enough tissue has been obtained. Pressure is applied at the biopsy site and a sterile bandage is placed over the incision. A chest x ray is performed immediately after the procedure to check for potential complications. The entire procedure takes 30–60 minutes. OPEN BIOPSY. Open biopsies are performed in a hospital operating room under general anesthesia. Once the anesthesia has taken effect, the surgeon makes an incision over the lung area, a procedure called a thoracotomy. Some lung tissue is removed and the incision is closed with sutures. Chest tubes are placed with one end inside the lung and the other end protruding through the closed incision. Chest tubes are used to drain fluid and blood, and re-expand the lungs. They are usually removed the day after the procedure. The entire procedure normally takes about an hour. A chest x ray is performed immediately after the procedure to check for potential complications. VIDEO-ASSISTED THORACOSCOPIC SURGERY. A minimally-invasive technique, video-assisted thoracoscopic surgery (VATS) can be used to biopsy lung and

G A LE EN CY C LO PE DI A O F C AN C ER 3

patient’s arm to deliver medications or fluids as necessary. A hollow tube, called an endotracheal tube, is passed through the patient’s mouth into the airway leading to the lungs. Its purpose is to deliver the general anesthetic. The chest area is cleansed with an antiseptic solution. In the mediastinoscopy procedure, the neck is also cleansed to prepare for the incision.

MEDIASTINOSCOPY. This procedure is performed under general anesthesia. A 2–3 inch (5–8 cm) incision is made at the base of the neck. A thin, hollow, lighted tube, called a mediastinoscope, is inserted through the incision into the space between the right and the left lungs. The surgeon removes any lymph nodes or tissues that look abnormal. The mediastinoscope is then removed, and the incision is sutured and bandaged. A mediastinoscopy takes about an hour.

Patients who will undergo surgical diagnostic and treatment procedures should be encouraged to stop smoking and stop using tobacco products. The patient needs to make the commitment to be a nonsmoker after the procedure. Patients able to stop smoking several weeks before surgical procedures have fewer postoperative complications. Smoking cessation programs are available in many communities. The patient should ask a health care provider for more information if he or she needs help with smoking cessation.

Diagnosis/Preparation Diagnosis Before scheduling a lung biopsy, the physician performs a careful evaluation of the patient’s medical history and symptoms, and performs a physical examination. Chest x rays and sputum cytology (examination of cells obtained from a deep-cough mucus sample) are other diagnostic tests that may be performed. An electrocardiogram (EKG) and laboratory tests may be performed before the procedure to check for blood clotting problems, anemia, and blood type, should a transfusion become necessary. Preparation During a preoperative appointment, usually scheduled within one to two weeks before the procedure, the patient receives information about what to expect during the procedure and the recovery period. During this appointment or just before the procedure, the patient usually meets with the physician (or physicians) performing the procedure (the pulmonologist, interventional radiologist, or thoracic surgeon). A chest x ray or CAT scan of the chest is used to identify the area to be biopsied. About an hour before the biopsy procedure, the patient receives a sedative. Medication may also be given to dry up airway secretions. General anesthesia is not used for this procedure. For at least 12 hours before the open biopsy, VATS, or mediastinoscopy procedures, the patient should not eat or drink anything. Prior to these procedures, an intravenous line is placed in a vein in the G A LE EN CY C LO PE DI A O F C AN CE R 3

Smoking cessation

Informed consent Informed consent is an educational process between health care providers and patients. Before any procedure is performed, the patient is asked to sign a consent form. Prior to signing the form, the patient should understand the nature and purpose of the diagnostic procedure or treatment, its risks and benefits, and alternatives, including the option of not proceeding with the test or treatment. During the discussions, the health care providers are available to answer the patient’s questions about the consent form or procedure.

Aftercare Needle biopsy Following a needle biopsy, the patient is allowed to rest comfortably. He or she may be required to lie flat for two hours following the procedure to prevent the risk of bleeding. The nurse checks the patient’s status at two-hour intervals. If there are no complications after four hours, the patient can go home once he or she has received instructions about resuming normal activities. The patient should rest at home for a day or two before returning to regular activities, and should avoid strenuous activities for one week after the biopsy. Open biopsy, VATS, or mediastinoscopy After an open biopsy, VATS, or mediastinoscopy, the patient is taken to the recovery room for observation. The patient receives oxygen via a face mask or nasal cannula. If no complications develop, the patient 859

Lung biopsy

mediastinal lesions. VATS may be performed on selected patients in place of open lung biopsy. While the patient is under general anesthetia, the surgeon makes several small incisions in the his or her chest wall. A thorascope, a thin, hollow, lighted tube with a tiny video camera mounted on it, is inserted through one of the small incisions. The other incisions allow the surgeon to insert special instruments to retrieve tissue for biopsy.

Lung biopsy

is taken to a hospital room. Temperature, blood oxygen level, pulse, blood pressure, and respiration are monitored. Chest tubes remain in place after surgery to prevent the lungs from collapsing, and to remove blood and fluids. The tubes are usually removed the day after the procedure. The patient may experience some grogginess for a few hours after the procedure. He or she may have a sore throat from the endotracheal tube. The patient may also have some pain or discomfort at the incision site, which can be relieved by pain medication. It is common for patients to require some pain medication for up to two weeks following the procedure. After receiving instructions about resuming normal activities and caring for the incision, the patient usually goes home the day after surgery. The patient should not drive while taking narcotic pain medication. Patients may experience fatigue and muscle aches for a day or two because of the general anesthesia. The patient can gradually increase activities, as tolerated. Walking is recommended. Sutures are usually removed after one to two weeks. The physician should be notified immediately if the patient experiences extreme pain, light-headedness, or difficulty breathing after the procedure. Sputum may be slightly bloody for a day or two after the procedure. Heavy or persistent bleeding requires evaluation by the physician.

Risks Lung biopsies should not be performed on patients who have a bleeding disorder or abnormal blood clotting because of low platelet counts, or prolonged prothrombin time (PT) or partial thromboplastin time (PTT). Platelets are small blood cells that play a role in the blood clotting process. PT and PTT measure how well blood is clotting. If clotting times are prolonged, it may be unsafe to perform a biopsy because of the risk of bleeding. If the platelet count is lower than 50,000/cubic mm, the patient may be given a platelet transfusion as a temporary relief measure, and a biopsy can then be performed. In addition, lung biopsies should not be performed if other tests indicate the patient has enlarged alveoli associated with emphysema, pulmonary hypertension, or enlargement of the right ventricle of the heart (cor pulmonale). The normal risks of any surgical procedure include bleeding, infection, or pneumonia. The risk of these complications is higher in patients undergoing 860

open biopsy procedures, as is the risk of pneumothorax (lung collapse). In rare cases, the lung collapses because of air that leaks in through the hole made by the biopsy needle. A chest x ray is done immediately after the biopsy to detect the development of this potential complication. If a pneumothorax occurs, a chest tube is inserted into the pleural cavity to reexpand the lung. Signs of pneumothorax include shortness of breath, rapid heart rate, or blueness of the skin (a late sign). If the patient has any of these symptoms after being discharged from the hospital, it is important to call the health care provider or emergency services immediately. Bronchoscopic biopsy Bronchoscopy is generally safe, and complications are rare. If they do occur, complications may include spasms of the bronchial tubes that can impair breathing, irregular heart rhythms, or infections such as pneumonia. Needle biopsy Needle biopsy is associated with fewer risks than open biopsy because it does not involve general anesthesia. Some hemoptysis (coughing up blood) occurs in 5% of needle biopsies. Prolonged bleeding or infection may also occur, although these are very rare complications. Open biopsy Possible complications of an open biopsy include infection or pneumothorax. If the patient has very severe breathing problems before the biopsy, breathing may be further impaired following the operation. Patients with normal lung function prior to the biopsy have a very small risk of respiratory problems resulting from or following the procedure. Mediastinoscopy Complications due to mediastinoscopy are rare. Possible complications include pneumothorax or bleeding caused by damage to the blood vessels near the heart. Mediastinitis, infection of the mediastinum, may develop. Injury to the esophagus or larynx may occur. If the nerves leading to the larynx are injured, the patient may be left with a permanently hoarse voice. All of these complications are rare.

Normal results Normal results indicate no evidence of infection in the lungs, no detection of lumps or nodules, and cells that are free from cancerous abnormalities. G A LE EN CY C LO PE DI A O F C AN C ER 3

Q U E S T I O N S TO A S K T H E DOCTOR 

Fiberoptic bronchoscopy is performed by pulmonologists, physician specialists in pulmonary medicine. CAT guided needle biopsy is done by interventional radiologists, physician specialists in radiological procedures. Thoracic surgeons perform open biopsies and VATS. Specially trained nurses, x-ray, and laboratory technicians assist during the procedures and provide pre- and postoperative education and supportive care. The procedures are performed in an operating or procedure room in a hospital.





  



Abnormal results of needle biopsy, VATS, and open biopsy may be associated with diseases other than cancer. Nodules in the lungs may be due to active infections such as tuberculosis, or may be scars from a previous infection. In 33% of biopsies using a mediastinoscope, the biopsied lymph nodes prove to be cancerous. Abnormal results should always be considered in the context of the patient’s medical history, physical examination, and other tests such as sputum examination, and chest x rays before a final diagnosis is made.



 





 

Morbidity and mortality rates The risk of death from needle biopsy is rare. The risk of death from open biopsy is one in 3,000 cases. In mediastinoscopy, death occurs in fewer than one in 3,000 cases.

 



Why is this procedure being performed? Are there any alternative options to having this procedure? What type of lung biopsy procedure is recommended? Is minimally invasive surgery an option? Will the patient be awake during the procedure? Who will be performing the procedure? How many years of experience does this physician have? How many other lung biopsies has the physician performed? Can medications be taken the day of the procedure? Can the patient have food or drink before the procedure? If not, how long before the procedure should these activities be stopped? How long is the hospitalization? After discharge, how long will it take to recover from the procedure? How is pain or discomfort relieved after the procedure? What types of symptoms should be reported to the physician? When can normal activities be resumed? When cam driving be resumed? When can the patient return to work? When will the results of the procedure be given to the patient? How often are follow-up physician visits needed after the procedure?

Alternatives The type of alternative diagnostic procedures available depend upon each patient’s diagnosis. Some people may be eligible to participate in clinical trials, research programs conducted with patients to evaluate a new medical treatment, drug, or device. The purpose of clinical trials is to find new and improved methods of treating different diseases and special conditions. For more information on current clinical trials, visit the National Institutes of Health’s ClinicalTrials.gov at http://www.clinicaltrials.gov or call (888) FINDNLM [(888) 346-3656] or (301) 594- 5983. The National Cancer Institute (NCI) has conducted a clinical trial to evaluate a technology—low-dose helical computed tomography—for its effectiveness in G A LE EN CY C LO PE DI A O F C AN CE R 3

screening for lung cancer. One study concluded that this test is more sensitive in detecting specific conditions related to lung cancer than other screening tests. Resources BOOKS

Abeloff, MD et al. Clinical Oncology. 3rd ed. Philadelphia: Elsevier, 2004. Mason, RJ et al. Murray & Nadel’s Textbook of Respiratory Medicine. 4th ed. Philadelphia: Saunders, 2007. ORGANIZATIONS

American Association for Respiratory Care (AARC). 11030 Ables Lane, Dallas, TX 75229. E mail: [email protected]. http://www.aarc.org. 861

Lung biopsy

W H O PE R F O R M S TH I S PROCEDURE A ND WHERE I S I T PERFO R MED?

Lung cancer, non-small cell

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, GA 30329. (800) 227 2345 or (404) 320 3333. http:// www.cancer.org. American College of Chest Physicians. 3300 Dundee Road, Northbrook, IL 60062 2348. (847) 498 1400. http:// www.chestnet.org. American Lung Association and American Thoracic Soci ety. 1740 Broadway, New York, NY 10019 4374. (800) 586 4872 or (212) 315 8700. http://www.lungusa.org and http://www.thoracic.org. Cancer Research Institute. 681 Fifth Avenue, New York, NY 10022. (800) 992 2623. http:// www.cancerresearch.org. Lung Line National Jewish Medical and Research Center. 14090 Jackson Street, Denver, CO 80206. (800) 222 5864. E mail: [email protected]. http:// www.nationaljewish.org. National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422 6237. http://www.nci.nih.gov. National Heart, Lung and Blood Institute. Information Center. P.O. Box 30105, Bethesda, MD 20824 0105. (301) 251 2222. http://www.nhlbi.nih.gov. OTHER

Dailylung.com. http://www.dailylung.com. Chest Medicine On Line. http://www.priory.com/ chest.htm. National Lung Health Education Program. http:// www.nlhep.com. Pulmonary Forum. http://www.pulmonarychannel.com. Pulmonarypaper.org. P.O. Box 877, Ormond Beach, FL 32175. (800) 950 3698. http:// www.pulmonarypaper.org.

False-color chest x ray showing evidence of cancerous masses (orange shadows) in both lungs. (Copyright CNRI, Science Source/Photo Researchers, Inc. Reproduced by permission.)

Barbara Wexler Angela M. Costello Rosalyn Carson-DeWitt, MD

Lung cancer, non-small cell Definition Non-small cell lung cancer (NSCLC) is a disease in which the cells of the lung tissues grow uncontrollably and form tumors.

Demographics Worldwide, lung cancer is the most common cancer in males, and the fifth most common cancer in women. The worldwide mortality rate for patients with lung cancer is 86%. In the United States, lung cancer is the leading cause of death from cancer among both men and women. The World Health 862

Large-cell anaplastic carcinoma of the lung. (Copyright Biophoto Associates, Science Source/Photo Researchers, Inc. Reproduced by permission.)

Organization estimates that the worldwide mortality from lung cancer will increase to three million by the year 2025. Of those three million deaths, almost two and a half million will result from non-small cell lung cancer. The American Cancer Society (ACS) estimates that 219,440 Americans will develop lung cancer in 2009, 116,090 men and 103,350 women. Of these patients, 159,000 will die of the disease. G A LE EN CY C LO PE DI A O F C AN C ER 3

Description There are two kinds of lung cancers, primary and secondary. Primary lung cancer starts in the lung itself, and is divided into small cell lung cancer and nonsmall cell lung cancer. Small cell lung cancers are shaped like an oat and called oat-cell cancers; they are aggressive, spread rapidly, and represent 20% of lung cancers. Non-small cell lung cancer represents almost 80% of all primary lung cancers. Secondary lung cancer is cancer that starts somewhere else in the body (for example, the breast or colon) and spreads to the lungs. The lungs The lungs are located along with the heart in the chest cavity. The lungs are not simply hollow balloons but have a very organized structure consisting of hollow tubes, blood vessels and elastic tissue. The hollow tubes, called bronchi, are highly branched, becoming smaller and more numerous at each branching. They end in tiny, blind sacs made of elastic tissue called alveoli. These sacs are where the oxygen a person breathes in is taken up into the blood, and where carbon dioxide moves out of the blood to be breathed out. Normal healthy lungs are continually secreting mucus that not only keeps the lungs moist, but also protects the lungs by trapping foreign particles like dust and dirt in breathed air. The inside of the lungs is covered with small hairlike structures called cilia. The cilia move in such a way that mucus is swept up out of the lungs and into the throat. Lung cancer Most lung cancers start in the cells that line the bronchi, and can take years to develop. As they grow larger they prevent the lungs from functioning normally. The tumor can reduce the capacity of the lungs, or block the movement of air through the bronchi in the lungs. As a result, less oxygen gets into the blood and patients feel short of breath. Tumors may also block the normal movement of mucus up into the throat. As a result, mucus builds up in the lungs and infection may develop behind the tumor. Once lung G A LE EN CY C LO PE DI A O F C AN CE R 3

cancer has developed it frequently spreads to other parts of the body. The speed at which non-small cell tumors grow depends on the type of cells that make up the tumor. The following three types account for the vast majority of non-small cell tumors: 





Adenocarcinomas are the most common and often cause no symptoms. Frequently they are not found until they are advanced. Squamous cell carcinomas usually produce symptoms because they are centrally located and block the lungs. Undifferentiated large cell and giant cell carcinomas tend to grow rapidly, and spread quickly to other parts of the body.

Causes and symptoms Causes Tobacco smoking accounts for 87% of all lung cancers. Giving up tobacco can prevent most lung cancers. Smoking marijuana cigarettes is considered another risk factor for cancer of the lung. Second hand smoke also contributes to the development of lung cancer among nonsmokers. Certain hazardous materials that people may be exposed to in their jobs have been shown to cause lung cancer. These include asbestos, coal products, and radioactive substances. Air pollution may also be a contributing factor. Exposure to radon, a colorless, odorless gas that sometimes accumulates in the basement of homes, may cause lung cancer in a tiny minority of patients. In addition, patients whose lungs are scarred from other lung conditions may have an increased risk of developing lung cancer. Symptoms Lung cancers tend to spread very early, and only 15% are detected in their early stages. The chances of early detection, however, can be improved by seeking medical care at once if any of the following symptoms appear:    

  



a cough that does not go away chest pain shortness of breath recurrent lung infections, such as bronchitis or pneumonia bloody or brown-colored spit or phlegm (sputum) persistent hoarseness significant weight loss that is not due to dieting or vigorous exercise; fatigue and loss of appetite unexplained fever 863

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The incidence of lung cancer is beginning to fall in developed countries. This may be a result of antismoking campaigns. In developing countries, however, rates continue to rise, which may be a consequence of both industrialization and the increasing use of tobacco products.

Lung cancer, non-small cell

Treatment

Although these symptoms may be caused by diseases other than lung cancer, it is important to consult a doctor to rule out the possibility of lung cancer. If lung cancer has spread to other organs, the patient may have other symptoms such as headaches, bone fractures, pain, bleeding, or blood clots.

Diagnosis

Staging Treatment for non-small cell lung cancer depends primarily on the stage of the cancer. Staging is a process that tells the doctor if the cancer has spread and the extent of its spread. The most commonly used treatments are surgery, radiation therapy, and chemotherapy.

Physical examination and diagnostic tests The doctor will first take a detailed medical history and assess risk factors. During a complete physical examination the doctor will examine the patient’s throat to rule out other possible causes of hoarseness or coughing, and will listen to the patient’s breathing and chest sounds. If the doctor has reason to suspect lung cancer, particularly if the patient has a history of heavy smoking or occupational exposure to irritating substances, a chest x ray may be ordered to see if there are any masses in the lungs. Special imaging techniques, such as computed tomography (CT) scans or magnetic resonance imaging (MRI), may provide more precise information about the size, shape, and location of any tumors.

Non-small cell lung cancer has six stages: 











Surgery

Sputum analysis Sputum analysis is a noninvasive test that involves microscopic examination of cells that are coughed up from the lungs. This test can diagnose at least 30% of lung cancers, even if tumors are not visible on chest x rays. In addition, the test can detect cancer in its very early stages, before it spreads to other regions. The sputum test does not provide any information about the location of the tumor.

Surgery is the standard treatment for the earlier stages of non-small cell lung cancer. The surgeon will decide on the type of surgery, depending on how much of the lung is affected. There are three different types of surgical procedures: 



Lung biopsy Lung biopsy is the most definitive diagnostic tool for cancer. It can be performed in three different ways. Bronchoscopy involves the insertion of a slender, lighted tube, called a bronchoscope, down the patient’s throat and into the lungs. This test allows the doctor to see the tubes inside the lungs, and to obtain samples of lung tissue. If a needle biopsy is to be performed, the location of the tumor is first identified using a computerized tomography (CT) scan or magnetic resonance imaging (MRI). The doctor then inserts a needle through the chest wall and collects a sample of tissue from the tumor. In the third procedure, known as surgical biopsy, the chest wall is opened up and a part of the tumor, or all of it, is removed. A doctor who specializes in the study of diseased tissue (a pathologist) examines the tumor to identify the cancer’s type and stage. 864

Occult carcinoma. Cancer cells have been found in the sputum, but no tumor has yet been found. Stage 0. A small group of cancerous cells have been found in one location. Stage I. The cancer is only in the lung and has not spread anywhere else. Stage II. The cancer has spread to nearby lymph nodes. Stage III. The cancer has spread to more distant lymph nodes, and/or other parts of the chest like the diaphragm. Stage IV. The cancer has spread to other parts of the body.



Wedge resection is the removal of a small part of the lung. Lobectomy is the removal of one lobe of the lung. (The right lung has three lobes and the left lung has two lobes.) Pneumonectomy is the removal of an entire lung.

Lung surgery is a major procedure and patients can expect to experience pain, weakness in the chest, and shortness of breath. Air and fluid collect in the chest after surgery. As a result, patients will need help to turn over, cough, and breath deeply. Patients should be encouraged to perform these activities because they help get rid of the air and fluid and speed up recovery. It can take patients several months before they regain their energy and strength. Radiotherapy Patients whose cancer has progressed too far for surgery (Stages III and IV) may receive radiotherapy. Radiotherapy involves the use of high-energy rays to G A LE EN CY C LO PE DI A O F C AN C ER 3

Radiation therapy may produce such side effects as tiredness, skin rashes, upset stomach, and diarrhea. Dry or sore throats, difficulty in swallowing, and loss of hair in the treated area are all minor side effects of radiation. These may disappear either during the course of the treatment or after the treatment is over. Chemotherapy Chemotherapy is also given to patients whose cancer has progressed too far for surgery. Chemotherapy is medication that is usually given intravenously to kill cancer cells. These drugs enter the bloodstream and travel to all parts of the body, killing cancer cells that have spread to different organs. Chemotherapy is used as the primary treatment for cancers that have spread beyond the lung and cannot be removed by surgery. It can also be used in addition to surgery or radiation therapy. Chemotherapy for NSCLC has made significant advances since the early 1980s in improving the patient’s quality of life as well as length of survival. Newer cytotoxic (cell-killing) agents developed in the 1990s, such as the taxanes, are typically combined with either cisplatin or carboplatin as first-line therapy for non-small cell lung cancer. Newer drugs for lung cancer include gefinitib (Iressa) and pemetrexed (Alimta). The FDA approved gefinitib in May 2003 as a treatment for patients with NSCLC who have not responded to platinum-based or taxane chemotherapy. It is taken by mouth and works by inhibiting an enzyme involved in the growth of tumor cells. Pemetrexed, which is given by injection, was approved by the FDA in February 2004 for the treatment of mesothelioma, a type of lung cancer caused by exposure to asbestos fibers. However, the drug appears to be effective in treating other types of lung cancer as well. Chemotherapy is also used as palliative treatment for non-small cell lung cancer. Palliative refers to any type of therapy that is given to relieve the symptoms of a disease but not to cure it.

disease. These trials are studying various new treatment options including: 

  

Chemotherapy with new drugs, and combinations of drugs Courses of chemotherapy prior to surgery Radiotherapy after surgery Chemotherapy and radiotherapy in combination

Information on open clinical trials is available on the Internet from the National Cancer Institute at http://cancertrials.nci.nih.gov. Alternative and complementary therapies Because non-small cell lung cancer has a poor prognosis with conventional medical treatment, many patients are willing to try complementary and alternative therapies. These therapies are used to try to reduce stress, ease side effects and symptoms, or control disease. Two treatments sometimes used are shark cartilage and mistletoe. Although shark cartilage is thought to interfere with the tumor’s blood supply, clinical trials have so far been inconclusive. Mistletoe is a poisonous plant that has been shown to kill cancer cells in the laboratory. Again, however, clinical trials with cancer patients have been inconclusive. Patients who decide to try complementary and alternative therapies should tell their doctors. Some of these therapies may interfere with conventional treatment. Coping with cancer treatment The side effects associated with treatment of nonsmall cell lung cancer can be severe. Patients should ask their doctors about medications to treat nausea and vomiting, and other side effects. It is particularly important to eat a nutritious diet and to drink plenty of fluids. In addition, most patients report feeling very tired and should get plenty of rest. Patients should consider joining local support groups with people who are coping with the same experiences. Many people with cancer find they can share thoughts and feelings with group members that they do not feel comfortable sharing with friends or family. Support groups are also a good source of information about coping with cancer.

Prognosis Clinical trials Patients diagnosed with non-small cell lung cancer should discuss participating in clinical trials with their doctor. There are many clinical trials currently underway that are investigating all different stages of the G A LE EN CY C LO PE DI A O F C AN CE R 3

The prognosis for non-small cell lung cancer is better if the disease is found early, and removed surgically. For patients whose disease is caught in Stage I, the survival rate five years after surgery ranges from 60–80%. Up to 55% of Stage II patients are alive after 865

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kill cancer cells. It is used either by itself or in combination with surgery or chemotherapy. The amount of radiation used depends on the size and the location of the tumor.

Lung cancer, small cell

QUESTIONS TO ASK YOUR DOC TOR 



 







 



What kinds of diagnostic studies will be required to ascertain the type and spread of this tumor? Could there be a genetic component to this tumor? Should other family member be tested? What types of treatments are available? What types of side effects from treatments can I expect? What are your recommendations to help me deal with those side effects? Am I eligible for any clinical trials? Would these be helpful to consider? Are there any lifestyle changes that I should make? What type of diet should I follow? Are there foods I should avoid? Should I avoid any medications? How often should I be checked after treatment has ended? Is there a support group that I can join to hear about other people’s experiences with this disorder?

Mason, RJ et al. Murray & Nadel’s Textbook of Respiratory Medicine. 4th ed. Philadelphia: Saunders, 2007. PERIODICALS

Cohen, M. H., G. A. Williams, R. Sridhara, et al. ‘‘United States Food and Drug Administration Drug Approval Summary: Gefitinib (ZD1839; Iressa) Tablets.’’ Clinical Cancer Research 10 (February 15, 2004): 1212 1218. Fossella, F. V. ‘‘Pemetrexed for Treatment of Advanced Non Small Cell Lung Cancer.’’ Seminars in Oncology 31 (February 2004): 100 105. Frampton, J. E., and S. E. Easthope. ‘‘Gefitinib: A Review of Its Use in the Management of Advanced Non Small Cell Lung Cancer.’’ Drugs 64 (2004): 2475 2492. Ramalingam, S., and C. P. Belani. ‘‘State of the Art Che motherapy for Advanced Non Small Cell Lung Can cer.’’ Seminars in Oncology 31 (February 2004): 68 74. Rigas, J. R. ‘‘Taxane Platinum Combinations in Advanced Non Small Cell Lung Cancer: A Review.’’ Oncologist 9, Supplement 2 (2004): 16 23. OTHER

American Cancer Society (ACS). Cancer Facts & Figures 2004. http://www.cancer.org/downloads/STT/ CAFF_finalPWSecured.pdf. FDA News, February 5, 2004. ‘‘FDA Approves First Drug for Rare Type of Cancer.’’ http://www.fda.gov/bbs/ topics/NEWS/2004/NEW01018.html. ORGANIZATIONS

five years, but only about 30% of Stage III patients make it to five years. Unfortunately, 85% of patients already have at least Stage III cancer by the time they are diagnosed. Many of these patients have disease that is too advanced for surgery. Despite treatment with radiotherapy and chemotherapy, the five-year survival for patients with inoperable disease is extremely low.

Prevention

Alliance for Lung Cancer Advocacy, Support and Educa tion. PO Box 849 Vancouver, WA 98666. (800) 298 2436. http://www.alcase.org. American Lung Association. 1740 Broadway New York, NY 10019. (212) 315 8700. http://www.lungusa.org. National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422 6237. http://www.nci.nih.gov. National Center for Complementary and Alternative Med icine (National Institutes of Health). PO Box 8218, Silver Spring, MD 20907 8218. (888) 644 6226. http:// nccam.nih.gov.

The best way to prevent lung cancer is not to start smoking or to quit smoking. Secondhand smoke from other people’s tobacco should also be avoided. Appropriate precautions should be taken when working with cancer-causing substances (carcinogens). Testing houses for the presence of radon gas, and removing asbestos from buildings have also been suggested as preventive strategies. Resources BOOKS

Abeloff, MD et al. Clinical Oncology. 3rd ed. Philadelphia: Elsevier, 2004. Goldman L, Ausiello D., eds. Cecil Textbook of Internal Medicine. 23rd ed. Philadelphia: Saunders, 2008. 866

Lata Cherath, PhD Alison McTavish, M.Sc. Rebecca J. Frey, PhD

Lung cancer, small cell Definition Small cell lung cancer is a disease in which the cells of the lung tissues grow uncontrollably and form tumors. G A LE EN CY C LO PE DI A O F C AN C ER 3

Lung cancer, small cell

A normal lung (left) and the lung of a cigarette smoker (right). (ª by A. Glauberman/Science Source/Photo Researchers, Inc. Reproduced by permission.)

Demographics Lung cancer is a growing global epidemic. Worldwide, lung cancer is the second most common cancer among both men and women and is the leading cause of cancer death in both sexes. The worldwide mortality rate for patients with lung cancer is 86%. Of the 160,000 deaths from lung cancer that occur annually in the United States, about 40,000 are caused by small cell lung cancer. Although there are differences in mortality rates between ethnic groups, this is mainly due to differences in smoking habits.

Description Lung cancer is divided into two main types: small cell and non-small cell. Small cell lung cancer is the least common of the two, accounting for only about 10–15% of all lung cancers. In the past, the disease was called oat cell cancer because, when viewed under a microscope, the cancer cells resemble oats. This type of lung cancer grows quickly and is more likely to spread to other organs in the body. G A LE EN CY C LO PE DI A O F C AN CE R 3

Lung cancer cells dividing. (Custom Medical Stock Photo. Reproduced by permission.)

The lungs are located along with the heart in the chest cavity. The lungs are not simply hollow balloons, but have a very organized structure consisting of 867

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hollow tubes, blood vessels, and elastic tissue. The hollow tubes, called bronchi, are multi-branched, becoming smaller and more numerous at each branching. They end in tiny, blind sacs made of elastic tissue called alveoli. These sacs are where the oxygen a person breathes in is taken up into the blood, and where carbon dioxide moves out of the blood to be breathed out. Normal, healthy lungs are continually secreting mucus that not only keeps the lungs moist, but also protects the lungs by trapping foreign particles like dust and dirt in breathed air. The inside of the lungs is covered with small, hair-like structures called cilia. The cilia move in such a way that mucus is swept up out of the lungs and into the throat. Small cell lung tumors usually start to develop in the central bronchi. They grow quickly and prevent the lungs from functioning at their full capacity. Tumors may block the movement of air through the bronchi in the lungs. As a result, less oxygen gets into the blood and patients feel short of breath. Tumors may also block the normal movement of mucus into the throat. As a result, mucus builds up in the lungs and infection may develop behind the tumor.

Causes and symptoms Causes Tobacco smoking accounts for nearly 90% of all lung cancers. The risk of developing lung cancer is increased for smokers who start at a young age, and for those who have smoked for a long time. The risk also increases as more cigarettes are smoked, and when cigarettes with higher tar content are smoked. Smoking marijuana cigarettes is also a risk factor for lung cancer. These cigarettes have a higher tar content than tobacco cigarettes. Certain hazardous materials that people may be exposed to in their jobs have been shown to cause lung cancer. These include asbestos, coal products, and radioactive substances. Air pollution may also be a contributing factor. Exposure to radon, a colorless, odorless gas that sometimes accumulates in the basement of homes, may cause lung cancer in some patients. In addition, patients whose lungs are scarred from other lung conditions may have an increased risk of developing lung cancer. Although the exact cause of lung cancer is not known, people with a family history of lung cancer appear to have a slightly higher risk of contracting the disease. 868

Symptoms Small cell lung cancer is an aggressive disease that spreads quickly. Symptoms depend on the tumor’s location within the lung, and on whether the cancer has spread to other parts of the body. More than 80% of small cell lung cancer patients have symptoms for only three months or less, and few cases are detected early. The following symptoms are the most commonly reported by small cell lung cancer patients at the time of their diagnosis:     

a persistent cough chest pain shortness of breath and wheezing persistent hoarseness fatigue and loss of appetite

Although some patients may experience bloody spit or phlegm, this symptom is more commonly seen in patients with other types of lung cancer. Small cell tumors often press against a large blood vessel near the lungs called the superior vena cava (SVC), causing a condition known as SCV syndrome. This condition may cause patients to retain water, cough, and have shortness of breath. Because small cell lung cancer often spreads quickly to the bones and central nervous system, patients may also have bone pain, headaches, and seizures. Small cell lung cancer can cause several hormonal disorders. About 40% of patients begin to secrete an anti-diuretic hormone at the wrong time. This hormone causes the body to retain water, which may result in the patient experiencing confusion, seizures, or coma. Less common are the development of Cushing’s syndrome and the Eaton-Lambert syndrome. Symptoms of Cushing’s syndrome include obesity, severe fatigue, high blood pressure, backache, high blood sugar, easy bruising, and bluish-red stretch marks on the skin. Eaton-Lambert syndrome is a neuromuscular disorder that causes muscle weakness, fatigue, and a tingling sensation on the skin. All of these hormonal disorders usually diminish after the lung tumor is successfully treated.

Diagnosis If lung cancer is suspected, the doctor will take a detailed medical history that checks both symptoms and risk factors. During a complete physical examination, the doctor will examine the patient’s throat to rule out other possible causes of hoarseness or coughing, and listen to the patient’s breathing and the sounds made when the patient’s chest and upper back are tapped. A chest x ray may be ordered to G A LE EN CY C LO PE DI A O F C AN C ER 3

Sputum analysis involves microscopic examination of the cells that are either coughed up from the lungs, or are collected through a special instrument called a bronchoscope. The sputum test does not, however, provide any information about the location of the tumor and must be followed by other tests. Lung biopsy is the most definitive diagnostic tool for cancer. It can be performed in several different ways. The doctor can perform a bronchoscopy, which involves the insertion of a slender, lighted tube, called a bronchoscope, down the patient’s throat and into the lungs. In addition to viewing the passageways of the lungs, the doctor can use the bronchoscope to obtain samples of the lung tissue. In another procedure known as a needle biopsy, the location of the tumor is first identified using a CT scan or MRI. The doctor then inserts a needle through the chest wall and collects a sample of tissue from the tumor. In the third procedure, known as surgical biopsy, the chest wall is opened up and a part of the tumor, or all of it, is removed for examination.

Treatment Staging Staging procedures are important in lung cancer because they tell doctors whether patients have disease only in their lungs, or whether the cancer has spread to other parts of the body. To establish the cancer stage, doctors have to perform various tests. These may include bone marrow aspiration and biopsy, CT scans of the chest and abdomen, MRI scans of the brain, and radionuclide bone scans. All of these tests determine the extent to which the cancer has spread. Once the stage is determined, doctors can decide on a course of treatment, and can have a better idea of the patient’s prognosis. Unlike other types of lung cancer, the staging of small cell lung cancer is relatively simple. This is because approximately 70% of patients already have metastatic disease when they are diagnosed, and small differences in the amount of tumor found in the lungs do not change the prognosis. Small cell lung cancer is usually divided into three stages: 

Limited stage: The cancer is found only in one lung and in lymph nodes close to the lung.

G A LE EN CY C LO PE DI A O F C AN CE R 3



Extensive stage: The cancer has spread beyond the lungs to other parts of the body.



Recurrent stage: The cancer has returned following treatment.

Without treatment, small cell lung cancer has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2–4 months. Compared with other cell types of lung cancer, small cell lung cancer has a greater tendency to be widely disseminated by the time of diagnosis, but is much more responsive to chemotherapy and irradiation. Treatment of small cell lung cancer depends on whether the patient has limited, extensive, or recurrent disease. Treatment usually involves radiotherapy and chemotherapy. Surgery is rarely used for this type of lung cancer because the tumor is usually too advanced. Patients with limited-stage disease are usually treated with chemotherapy. Combinations of two or more drugs have a better effect than treatment with a single drug. Up to 90% of patients with this stage of disease will respond to chemotherapy. The chemotherapy most commonly prescribed is a combination of the drugs etoposide (Vepesid) and cisplatin (Platinol). Combining chemotherapy with chest radiotherapy and/or occasionally surgery has also prolonged survival for limited-stage patients. In addition to chest radiotherapy, some patients are also treated with radiation therapy to the brain, even if no cancer is found there. This treatment, called prophylactic cranial irradiation (PCI), is given to prevent tumors from forming in the brain. The combination of etoposide and cisplatin chemotherapy with chest radiation therapy and PCI has increased the two-year survival of limited-stage small cell lung cancer patients to almost 50%. Combinations of different chemotherapy agents are also used for treating extensive-stage small cell lung cancer. However, compared with limited-stage patients, the percentage of extensive-stage patients who respond to therapy is lower. Commonly used drug combinations include cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), and vincristine (Oncovin), or etoposide and cisplatin. The addition of radiation therapy to chemotherapy does not improve survival in these patients. However, radiation therapy is used for the palliative (pain relief) treatment of symptoms of metastatic lung cancer, particularly brain and bone tumors. 869

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check for masses in the lungs. Special imaging techniques, such as computed tomography (CT) scans or magnetic resonance imaging (MRI), may provide more precise information about the size, shape, and location of any tumors.

Lung cancer, small cell

Patients who have recurrent small cell lung cancer often become resistant to chemotherapy. These patients are treated with palliative radiotherapy. Their doctor may also recommend that they take part in a clinical trial of a new therapy. Patients whose relapse occurs more than six months after their initial treatment, however, may still respond to traditional chemotherapy.

QUESTIONS TO ASK YOUR DOC TOR 



Coping with cancer treatment The side effects associated with treatment of small cell lung cancer can be severe. Patients should ask their doctor about medications to treat nausea and vomiting and other side effects. It is particularly important to eat a nutritious diet and to drink plenty of fluids. In addition, most patients report feeling very tired and should get plenty of rest. Clinical trials Most of the improvements in the survival of patients with small cell lung cancer are the result of clinical trials. Ongoing trials are investigating new chemotherapy and radiotherapy regimens. In addition, entirely new types of therapy, such as gene therapy and biological therapy, are now being tested. Patients with a lung cancer diagnosis should ask their doctor about participating in a clinical trial. Information on open clinical trials is available on the Internet from the National Cancer Institute at http://cancertrials.nci.nih.gov. Alternative treatment Many cancer patients have tried using shark cartilage to treat their disease. Shark cartilage is thought to interfere with the tumor’s blood supply. A clinical trial using this treatment in lung cancer patients is ongoing. Information on this and other alternative treatments is available on the Internet from the National Center for Complementary and Alternative Medicine. Patients who decide to try complementary and alternative therapies should tell their doctor. Some of these therapies may interfere with conventional treatment.

Prognosis Small cell lung cancer is a very aggressive disease. Without treatment, limited-stage patients will survive for three to six months, while extensive-stage patients will survive six to 12 weeks. However, small cell lung cancer is much more responsive to chemotherapy and radiation therapy than other types of lung cancer. 870

 



 

 



What kinds of diagnostic studies will be required to ascertain the type and spread of this tumor? Could there be a genetic component to this tumor? Should other family member be tested? What types of treatments are available? What types of side effects from treatments can I expect? What are your recommendations to help me deal with those side effects? Am I eligible for any clinical trials? Would these be helpful to consider? Are there any lifestyle changes that I should make? What type of diet should I follow? Are there foods I should avoid? Should I avoid any medications? How often should I be checked after treatment has ended? Is there a support group that I can join to hear about other people’s experiences with this disorder?

Among patients treated with chemotherapy, 70–90% have a major response to treatment. Survival in patients responding to therapy is four to five times longer than in patients without treatment. In addition, two years after the start of therapy, about 10% of patients remain free of disease. In general, women tend to have a better prognosis than men. Patients whose disease has spread to the central nervous system or liver have a much worse prognosis. Although the overall survival at five years is 5–10%, survival is higher in patients with limited stage disease. About 70% of patients who are disease free after two years do not relapse. After five to 10 disease-free years, relapses are rare.

Prevention The best way to prevent lung cancer is either not start smoking, or quit smoking. Secondhand smoke from other people’s tobacco should also be avoided. Appropriate precautions should be taken when working with substances that can cause cancer (carcinogens). Testing houses for the presence of radon gas, and removing asbestos from buildings have also been suggested as preventive strategies. G A LE EN CY C LO PE DI A O F C AN C ER 3

Lymph node biopsy

Resources BOOKS

Abeloff, MD et al. Clinical Oncology. 3rd ed. Philadelphia: Elsevier, 2004. Goldman L, Ausiello D., eds.Cecil Textbook of Internal Medicine. 23rd ed. Philadelphia: Saunders, 2008. Mason, RJ et al. Murray & Nadel’s Textbook of Respiratory Medicine. 4th ed. Philadelphia: Saunders, 2007. ORGANIZATIONS

Alliance for Lung Cancer Advocacy, Support, and Educa tion. P.O. Box 849, Vancouver, WA 98666. (800) 298 2436. http://www.alcase.org. American Lung Association.1740 Broadway New York, NY 10019. (212) 315 8700. http://www.lungusa.org. National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422 6237. http://www.nci.nih.gov. National Center for Complementary and Alternative Med icine (National Institutes of Health). P.O. Box 8218, Silver Spring, MD 20907 8218. (888) 644 6226. http:// nccam.nih.gov.

Lata Cherath, PhD Alison McTavish, MSc

Lung metastasis see Metastasis Lung surgery see Lobectomy; Pneumonectomy; Thoracotomy

Lymph node biopsy Definition A lymph node biopsy is a procedure in which all or part of a lymph node is removed and examined to determine if there is cancer within the node.

Purpose The lymph system is the body’s primary defense against infection. It consists of the spleen, tonsils, thymus, lymph nodes, lymph vessels, and the clear, slightly yellow fluid called lymph. These components produce and transport white blood cells called lymphocytes and macrophages that rid the body of infection. The lymph system is also involved in the production of antibodies. Antibodies are proteins that fight bacteria, viruses, and other foreign materials that enter the body. The lymph vessels are similar to veins, only instead of carrying blood as veins do, they circulate lymph to most tissues in the body. Lymph nodes are about 600 small, bean-shaped collections of tissue G A LE EN CY C LO PE DI A O F C AN CE R 3

Close-up view of normal lymph nodes and fatty tissue. (Custom Medical Stock Photo. Reproduced by permission.)

found along the lymph vessel. They produce cells and proteins that fight infection, and clean and filter lymph. Lymph nodes are sometimes called lymph glands, although they are not true glands. When someone talks about having swollen glands, they are actually referring to lymph nodes. Normal lymph glands are no larger than 0.5 in (1.3 cm) in diameter and are difficult to feel. However, lymph nodes can enlarge to greater than 2.5 in (6 cm) and can become sore. Most often the swelling is caused by an infection, but it can also be caused by cancer. Cancers can metastasize (spread) through the lymph system from the site of the original tumor to distant parts of the body where secondary tumors are formed. The purpose of a lymph node biopsy is to determine the cause of the swelling and/or to see if cancer has begun to spread through the lymph system. This information is important in staging the cancer and devising a treatment plan.

Precautions Women who are pregnant should inform their doctor before a lymph node biopsy, although pregnancy will not affect the results.

Description There are three kinds of lymph node biopsy. Sentinel lymph node mapping and biopsy is a promising new technique that is discussed in its own entry. Fine needle aspiration (FNA) biopsy, often just called needle biopsy, is done when the lymph node of interest is near the surface of the body. A hematologist (a doctor who specializes in blood diseases) usually performs the test. In FNA biopsy, a needle is inserted through the 871

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Q U E S T I O N S T O A S K TH E DOC TOR   



What kind of biopsy are you going to do? What will this tell me about my cancer? If you are doing an open biopsy, will you be removing any other structures at the same time? If you are, how will that affect my recovery from the operation?

skin and into the lymph node, and a sample of tissue is drawn out of the node. This material is preserved and sent to the laboratory for examination. Advantages of a needle biopsy are that the test is minimally invasive. Only a local anesthetic is used, the procedure generally takes less than half an hour, and there is little pain afterwards. The disadvantage is that cancer may not be detected in the small sample of cells removed by the needle. Open lymph node biopsy is a surgical procedure. It is done by a surgeon under general anesthesia on lymph nodes in the interior of the body and under local anesthesia on surface lymph nodes where FNA biopsy is considered inadequate. Once there is adequate anesthesia, the surgeon makes a small cut and removes either the entire lymph node or a slice of tissue that is then sent to the laboratory for examination. Results in both kinds of biopsies take one to three days. Open biopsy can be advantageous in that it is easier to detect and identify the type of cancer in a large piece of tissue. Also, lymph nodes deep in the body can be sampled. Disadvantages include a longer recovery time, soreness at the biopsy site for several days, and the use of deeper anesthesia, increasing the risks to the patient. The procedure is done in a hospital or outpatient surgery center and takes about an hour, with additional time to recover from general anesthesia.

KEY T ERMS Lymph nodes—Small, bean-shaped organs located throughout the lymphatic system. The lymph nodes store special cells that can trap cancer cells or bacteria that are traveling through the body in lymph. Also called lymph glands. Lymphocytes—Small white blood cells that bear the major responsibility for carrying out the activities of the immune system; they number about 1 trillion. Malignant—Cancerous. Cells tend to reproduce without normal controls on growth and form tumors or invade other tissues. Spleen—An organ located at the left side of the stomach that acts as a reservoir for blood cells and produces lymphocytes and other products involved in fighting infection. Thymus—An organ near the base of the neck that produces cells that fight infection. It is at its largest at puberty, then declines in size and function during adult life. Tonsils—Small masses of tissue at the back of the throat.

Aftercare Little aftercare is needed in a needle biopsy other than a bandage to keep the biopsy site clean. Patients who have general anesthesia for an open biopsy often feel drowsy and tired for several days following the procedure, and should not plan to drive home after biopsy. The incision site must be kept clean and dry, and a follow-up visit to check on healing is usually necessary.

Risks There are few risks associated with lymph node biopsy. The main risks are excessive bleeding (usually only in people with blood disorders) and allergic reaction to general anesthesia (rare). Occasionally the biopsy site becomes infected.

Normal results Preparation No particular preparation is necessary for a needle biopsy. For an open biopsy, patients need standard pre-operative blood tests and other tests to evaluate general health. The doctor should be informed about any medications (prescription, non-prescription, or herbal) the patient is taking, as well as past bleeding problems or allergies to medication or anesthesia. 872

Normal lymph nodes are small and flat. When examined under the microscope, they show no signs of cancer or infection.

Abnormal results Abnormal lymph nodes are usually enlarged and contain cancerous (malignant) cells and/or show signs of infection. G A LE EN CY C LO PE DI A O F C AN C ER 3

Resources OTHER

ThriveOnline. [cited June 12, 2001]. http://thriveonline.oxy gen.com/medical/library/article/003933.html. ORGANIZATIONS

American Cancer Society. National Headquarters, 1599 Clifton Road NE, Atlanta, GA 30329. 800(ACS) 2345). http://www.cancer.org. Cancer Information Service. National Cancer Institute, Building 31, Room 10A19, 9000 Rockville Pike, Bethesda, MD 20892. (800)4 CANCER. http:// www.nci.nih.gov/cancerinfo.

Tish Davidson, A.M.

Lymph node dissection Definition Lymph node dissection (lymphadenectomy) is the surgical removal of lymph nodes in order to assess the spread of cancer.

Purpose The lymph system is the body’s primary defense against infection. It consists of the spleen, tonsils, thymus, lymph nodes, lymph vessels, and the clear, slightly yellow fluid called lymph. These components produce and transport cells and proteins that help rid the body of infection.

The lymph vessels are similar to veins, only instead of carrying blood as veins do, they circulate lymph to tissues in the body. There are about 600 small, bean-shaped collections of tissue found along the lymph vessels. These are called lymph nodes. They produce cells and proteins that fight infection. They also clean and filter foreign cells, such as bacteria or cancer cells, out of the lymph. Cancer cells can break off from the original tumor and metastasize (spread) through the lymph system to distant parts of the body, where secondary tumors are formed. The purpose of a lymph node dissection is to remove the lymph nodes that have trapped cancer cells so that the extent of spread can be determined. Lymph node dissection is done for many different types of cancers, including cancers of the head and neck, breast, prostate, testes, bladder, colon, and lung. About 200 lymph nodes are in the head and neck and another 30 to 50 are in the armpit. More are located in the groin area. Lymph nodes are sometimes called lymph glands, although they are not true glands. When someone talks about having swollen glands, they are referring to swollen lymph nodes. Normally lymph nodes are no larger than 0.5 in (1.3 cm) in diameter and are difficult to feel. However, when lymph nodes trap bacteria or cancer cells, they can increase in size to greater than 2.5 in (6 cm). Most often, hot and painful swollen nodes are caused by trapped bacteria. Swollen lymph nodes caused by cancer are usually painless.

Precautions This operation usually will not be performed if the cancer has already metastasized to another site. In this case, removing the lymph nodes will not effectively contain the cancer. As with any surgery, women who are pregnant should inform their doctors before a lymph node dissection.

Description

Diseased lymph nodes. (Custom Medical Stock Photo. Reproduced by permission.)

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Lymph node dissection is usually done by a surgeon in a hospital setting, under general anesthesia. An incision is made and tissue is pulled back to reveal the lymph nodes. The surgeon is guided in what to remove by the location of the original cancer. Sample lymph nodes may be sent to the laboratory for examination. If the excised nodes do contain malignant cells, this would indicate that the cancer has spread beyond the original site, and recommendations can then be made regarding further therapy. 873

Lymph node dissection

See also Lymph node dissection; Radical neck dissection.

Lymph node dissection

Axillary dissection

Incision

Pectoralis major muscle

Lymph nodes

B.

A.

Scar tissue

C.

(Illustration by Argosy Publishing. Cengage Learning, Gale.)

Preparation Tests may be done before the operation to determine the location of the cancer and which nodes should be removed. These tests may include lymph node biopsies, CT (computed tomography) scans, and MRI scans. In addition, standard pre-operative 874

blood and liver function tests are performed. The patient will meet with an anesthesiologist before the operation, and should notify the anesthesiologist about all drug allergies and all medication (prescription, non-prescription, or herbal) that he or she is taking. G A LE EN CY C LO PE DI A O F C AN C ER 3



 









How will you determine which lymph nodes should be removed? How should I prepare for this procedure? Are there precautions I can take to help prevent lymphedema? How will lymph node dissection affect my daily life? Will you be removing anything else besides lymph nodes during this operation? About how long will I have to stay in the hospital? Will having my lymph nodes removed increase my chances of getting infections?

Aftercare How long a person stays in the hospital after lymph node dissection depends on how many lymph nodes were removed, their location, and whether surgery to remove the primary tumor or other structures was performed at the same time. Drains are inserted under the skin to remove the fluid that accumulates after the lymph nodes have been removed, and patients are usually able to return home with the drains still in place. Some patients are able to leave the same day or the day following the procedure. An accumulation of lymph fluid that causes swelling, a condition known as lymphedema, is the most feared side effect of lymph node dissection. If swelling occurs, patients should consult their doctors immediately. Swelling may indicate that a new tumor is blocking a lymph vessel, or that a side effect of lymph node dissection is present. Treatment for lymphedema in people with cancer is different than treatment of lymphedema that arises from other causes. In cancer patients, it is essential to alleviate swelling without spreading cancer cells to other parts of the body, therefore an oncologist (cancer specialist) should be consulted before beginning any treatment.

KEY T ERMS Computed tomography (CT or CAT) scan—Using x rays taken from many angles and computer modeling, CT scans help determine the size and location of tumors and provide information on whether they can be surgically removed. Magnetic resonance imaging (MRI)—MRI uses magnets and radio waves to create detailed crosssectional pictures of the interior of the body. Malignant—Cancerous. Cells tend to reproduce without normal controls on growth and form tumors or invade other tissues. Metastasize—Spread of cells from the original site of the cancer to other parts of the body where secondary tumors are formed.

and causes them to swell. Removing lymph nodes and lymph vessels through lymph node dissection increases the likelihood that the capacity of the lymph transport system will be exceeded. Lymphedema can occur days or weeks after lymph node dissection. Radiation therapy also increases the chance of developing lymphedema, so those people who have radiation therapy following lymph node dissection are at greatest risk of experiencing this side effect. Lymphedema slows healing, causes skin and tissue damage, and when left untreated can result in the development of hard or fibrous tissue. People with lymphedema are also at risk for repeated infection, because pools of lymph in the tissues provide a perfect spot for bacteria to grow. In severe cases, untreated lymphedema can develop into a rare form of cancer called lymphangiosarcoma. Other risks associated with lymph node dissection are the same as for all major surgery: potential bleeding, infection, and allergic reaction to anesthesia.

Normal results Normal lymph nodes are small and flat and show no cancerous cells under the microscope.

Risks People who have lymph nodes removed are at increased risk of developing lymphedema, which can occur in any part of the body where lymph accumulates in abnormal quantities. When the amount of fluid exceeds the capacity of the lymph system to move it through the body, it leaks into the tissues G A LE EN CY C LO PE DI A O F C AN CE R 3

Abnormal results Abnormal lymph nodes are enlarged and show malignant cells when examined under the microscope. See also Lymph node biopsy; Radical neck dissection. 875

Lymph node dissection

QUESTIONS TO ASK THE DOCTOR

Lymphangiography

Resources ORGANIZATIONS

American Cancer Society, National Headquarters. 1599 Clifton Rd. NE, Atlanta, GA 30329. 800(ACS) 2345. http://www.cancer.org. Cancer Information Service. National Cancer Institute. Building 31, Room 10A19, 9000 Rockville Pike, Bethesda, MD 20892. (800) 4 CANCER. http:// www.nci.nih.gov/cancerinfo/index.html. National Lymphedema Network. Latham Square, 1611 Telegraph Ave., Suite 1111, Oakland, CA 94612 2138. (800) 541 3259. http://www.lymphnet.org.

Tish Davidson, A.M.

Lymphangiogram, lymph node angiogram see Lymphangiography

Lymphangiography Definition Lymphangiography is a type of diagnostic testing technique in which x rays (called lymph node angiograms) and the injection of a contrast medium (a substance that provides a contrast between the tissue or organ being filmed and the medium) are used to visualize lymphatic circulation and the lymph nodes.

False-color lymphangiogram of the abdomen of a person suffering from lymphoma. (Copyright Mehau Kulyk, Science Source/Photo Researchers, Inc. Reproduced by permission.)

Purpose The lymphatic system consists of tissues, organs, and vessels that aid in circulating body fluids and defending the body from damage by foreign substances such as viruses, bacteria, or fungi. However, certain cancers may also spread through the lymphatic system. Thus, lymphangiography is sometimes used to: diagnose the presence or spread of tumors, lymphatic cancer (lymphoma), and other cancers  distinguish primary lymphedema (when swelling in the lymphatic system arises from missing or impaired lymphatic vessels) from secondary lymphedema (swelling caused by damaged lymph vessels or lymph nodes that have been removed)  localize tumors for surgical removal  assess the effectiveness of chemotherapy and radiation therapy in treating problems associated with metastatic (spreading) cancer 

876

Although the results of lymphangiography are considered reliable, additional tests, studies, and clinical observations are necessary to determine a precise diagnosis. By itself, lymphangiography misses cancer in about 20% of cases. One of the major drawbacks of lymphangiography is its failure to fill certain lymphatic channels and groups of lymph nodes—a failure that may be due to infection, injury, or tumor spread. When this filling failure occurs, certain segments of the lymphatic system in the abdomen and pelvis cannot be visualized; thus, metastatic disease can be neither confirmed nor ruled out. Since the late 1990s, conventional lymphangiography (using an iodine oil-based contrast agent) has been used almost exclusively for the staging of urologic pelvic and testicular malignancies. The test may demonstrate metastases within lymph nodes of normal size that are missed on computed tomography (CT) G A LE EN CY C LO PE DI A O F C AN C ER 3

  



 

What is the purpose of the test? How long will the test take? Will I be sedated or get anesthesia before the test? Is there anything special I need to do before the test? Can I drive myself home after testing? When will I get the results?

imaging. Technical innovations in nuclear diagnostics and computer imaging largely replaced lymphangiography with simpler, safer, and more reliable techniques of visualizing the lymphatic system (such as lymphangioscintigraphy, or isotope lymphography).

Precautions Because of the possibility of an adverse reaction to the contrast medium, lymphangiography is usually not administered to patients with lung problems, heart disease, or severe kidney or liver disease. Individuals with allergies to shellfish, iodine, or dye used in other diagnostic tests may receive steroids or antihistamines before the test to decrease the risk of allergic reactions.

Description Lymphangiography testing may be done on an inpatient or outpatient basis. A sedative may be given to help the patient relax. After the skin of each foot is cleaned with an antiseptic, a blue indicator dye (which does not show up on x rays) is injected between the first, second, and third toes of each foot. The dye spreads into the lymphatic system in about 15 to 30 minutes. The thin, bluish lines that appear on the top of each foot delineate the lymphatic vessels. Next, a local anesthetic is injected, and a small incision is made into one of the larger blue lines in each foot. A needle or catheter (a thin flexible tube) is inserted into a vessel in each foot, and an oil-based contrast medium (such as Ethiodol) is injected at a slow, steady rate. A feeling of pressure may occur as the contrast medium is injected, but the patient must lie still to avoid dislodging the needle. A fluoroscope (a device consisting of a fluorescent screen on which the shadows of objects that come G A LE EN CY C LO PE DI A O F C AN CE R 3

KEY T ERMS Contrast medium—A substance that provides a contrast between the tissue or organ being filmed and the medium. Lymph node—A rounded, encapsulated body consisting of an accumulation of lymphatic tissue; found in lymphatic vessels. Lymphoma—A type of lymphatic cancer. Metastases—Cancer cells that have spread from the primary site of malignancy to another location in the body.

between the screen and an attached x-ray apparatus can be viewed) is used to monitor the progress of the contrast medium as it spreads slowly (taking about 60 to 90 minutes) through the lymphatic system, traveling up the legs, into the groin, and along the back of the abdominal cavity. After the contrast agent is injected, the catheter is removed and the incisions are stitched and bandaged. Then x rays are taken of the legs, pelvis, abdomen, and chest areas. The following day, an additional set of x rays is obtained. After the test, the patient’s skin, feces, and urine may have a bluish tint for two to three days (until the marker dye disappears), and there may be some discomfort behind the knees and in the groin area. Test results are reported to the doctor or patient from a few hours to a few days after the procedure.

Preparation There is usually no special preparation needed before lymphangiography—such as restrictions in diet, activity, or medication intake. However, some facilities may require a clear liquid diet for a specified period of time before the test. In addition, for comfort reasons, patients may be asked to empty their bladders before testing. A patient undergoing lymphangiography (or a close family member) must sign a consent form before the test is administered.

Aftercare After testing, the patient’s blood pressure, pulse, breathing status, and temperature are monitored at regular intervals until they are stable. Any lung complications are noted, such as hoarseness or shortness of breath, chest pain, low blood pressure, low-grade fever, and blueness of lips and nailbeds due to clotting of the dye. 877

Lymphangiography

QUESTIONS TO ASK THE DOCTOR

Lymphocyte immune globulin

Bedrest for at least 24 hours following the test is recommended, with feet elevated to help reduce swelling at the incision sites. The incision sites may be sore for several days, and ice packs may be applied to these sites to further reduce swelling. The patient should also inspect the incision sites for infection. Sterile dressings should remain in place for two days, and the incision sites should be kept dry until after the sutures are removed (7 to 10 days after the test).

Risks There is a risk of infection or bleeding caused by introducing the needle or tube through the skin or an allergic reaction—usually not serious— to the contrast medium. There is also a slight risk of oil embolism (obstruction of a blood vessel) due to the oil-based contrast medium. The contrast medium eventually seeps from the lymphatic channels into the general circulation, where it may travel to, and lodge in, the lungs. There is some radiation exposure involved in the procedure. Although pregnant women and children are particularly sensitive to these risks, physicians may order the procedure when the benefits appear to outweigh the risks.

Normal results Normal test results indicate no anatomical or functional abnormalities.

Abnormal results Abnormal results may indicate: filariasis (a tropical disease caused by worms living in the lymphatic system)  Hodgkin’s or non-Hodgkin’s lymphoma (cancers of the lymphatic system)  inflammation  metastatic cancer  primary lymphedema  retroperitoneal tumors (tumors lying outside of the peritoneum—the membrane lining the abdominal cavity)  trauma 

Resources BOOKS

Fischbach, Frances Talaska. A Manual of Laboratory and Diagnostic Tests. 6th ed. Philadelphia: Lippincott Williams and Wilkins, 2000. 878

PERIODICALS

Bellin, Marie France, Catherine Beigelman, and Sophie Precetti Morel. ‘‘Iron Oxide Enhanced MR Lymphog raphy: Initial Experience.’’ European Journal of Radi ology June 2000: 257 264. Winterer, Jan Thorsten, Ulrich Blum, Stephan Boos, Stav ros Konstantinides, and Mathia Langer. ‘‘Cerebral and Renal Embolization After Lymphangiography in a Patient with Non Hogkin’s Lymphoma: Case Report.’’ Radiology February 1999: 381 385. ORGANIZATIONS

American College of Radiology. http://www.acr.org. Lymphoma Research Foundation of America. http:// www.lymphomafocus.org.

Genevieve Slomski, Ph.D.

Lymphocyte immune globulin Definition Lymphocyte immune globulin is a drug used to suppress the immune system. Lymphocyte immune globulin is also known by the generic name anti-thymocyte globulin (ATG) and the brand names Atgam and Thymoglobulin. Atgam first received FDA approval in 1981 and Thymoglobulin in 1999. As of 2009, no generic preparations are available.

Purpose Lymphocyte immune globulin is used to treat aplastic anemia and to prevent rejections during bone marrow transplantation. This drug has also been used experimentally to treat advanced non-Hodgkin’s lymphomas and cutaneous T-cell lymphomas.

Description This drug suppresses the immune system by slowing down T cells, cells critical in immunity. Without them, the immune system is essentially paralyzed. Lymphocyte immune globulin contains antibodies that attach to T cells and prevent them from working properly. This drug also decreases the number of T cells in the blood. Lymphocyte immune globulin is made by vaccinating an animal with immature human T cells, then collecting the antibodies made against them. Atgam is made in horses and Thymoglobulin in rabbits. Atgam is labeled for use only in kidney transplantation and aplastic anemia, and Thymoglobulin is G A LE EN CY C LO PE DI A O F C AN C ER 3

Adult respiratory distress syndrome (ARDS)—A lung disease characterized by widespread lung abnormalities, fluid in the lungs, shortness of breath, and low oxygen levels in the blood. Antibodies—Proteins made by the immune system that attach to targeted molecules and cells. Aplastic anemia—Failure of the bone marrow to make enough blood cells. Blood cells—Cells found in the blood, including red blood cells that carry oxygen, white blood cells that fight infections, and platelets that help the blood to clot. Bone marrow—A group of cells and molecules found in the centers of some bones. It makes all of the cells found in the blood, including the cells involved in immunity. Graft-vs-host disease (GVHD)—A disease that develops when immune cells in transplanted bone marrow attack the body. Immune system—The cells and organs that defend the body against infections. Pulmonary edema—A disease characterized by excessive fluid in the lungs and difficulty breathing. Sepsis—An infection that has spread into the blood. Serum sickness—A type of allergic reaction against blood proteins. Serum sickness develops when the immune system makes antibodies against proteins that are not normally found in the body. Skin test—A test used to diagnose allergies. T lymphocyte or T cell—A type of white blood cell. Helper T cells aid other cells of the immune system, while cytotoxic T cells destroy abnormal body cells, including those that have been infected by a virus. Thrombocytopenia—Too few platelets in the blood.

specifically approved only for kidney transplantation. The effectiveness of either drug for treating aplastic anemia in cancer patients, however, is unknown. Lymphocyte immune globulin is often used offlabel to treat graft-versus-host disease (GVHD) after bone marrow transplantation. The drug has been beneficial for GVHD patients in some studies, but its effectiveness has not been conclusively demonstrated. In some clinical trials, it is also being used to prepare G A LE EN CY C LO PE DI A O F C AN CE R 3

Recommended dosage The usual dose of Atgam in adults is 10–30 mg/kg (1 kilogram is 2.2 pounds). Doses of 5–25 mg/kg have been given to a few children. Thymoglobulin, which is about 10 times stronger, has a recommended dose of 1–1.5 mg/kg in adults. Typically these drugs are given daily or every other day for several days or weeks. They are injected into the blood over several hours, under close supervision in the hospital or clinic.

Precautions Patients should not take Atgam if they are allergic to horse proteins or Thymoglobulin if they are allergic to rabbit proteins. Patients should tell their doctors about any current or previous blood cell problems and about all their prescription and over-the-counter drugs. Lymphocyte immune globulin can make infections more serious. Patients should check with their doctors if they have any symptoms of an infection, such as chills, fever, or sore throat. They should also avoid people with contagious diseases and anyone recently vaccinated with an oral polio vaccine. The drug decreases the effectiveness of vaccinations given just before or during treatment. Some types of vaccines are not safe to receive while taking this drug. Lymphocyte immune globulin does not interact with any specific foods. However, patients should check with their doctor for specific recommendations for eating and drinking before the treatment. Patients should be careful in planning their activities, as this drug can cause dizziness.

Side effects Thymoglobulin and Atgam have very similar side effects. However, Thymoglobulin is approximately twice as likely to decrease the number of white blood cells and three times as likely to result in malaise. Dizziness is much more common with Atgam. Other numerous side effects caused by both drugs include:  



Chills or fever in most patients Risk of developing an infection, which has been seen in up to 30% of patients, and sepsis in approximately 10% Risk of bleeding, due to thrombocytopenia (seen in 30–45% of patients) 879

Lymphocyte immune globulin

KE Y T ERM S

the patient’s body for bone marrow transplantation. This drug produces short partial remissions of some lymphomas in published experiments.

Lymphoma



Rarely, anemia or the destruction of white blood cells other than T cells



Pain, swelling, and redness where the drug is injected (minimized by injecting the drug into the faster-moving blood in a large vein)



Allergic reactions (Serious allergic reactions can cause difficulty breathing, swelling of the tongue, a drop in blood pressure, or pain in the chest, sides, or back. Severe allergic reactions are potentially lifethreatening, but rare; milder allergic reactions can result in itching, hives, or rash. Skin tests are often done to predict the likelihood of an allergic reaction, but are not foolproof.)



Serum sickness, an immune reaction against the drug (Can result in fever, chills, muscle and joint aches, rash, blurred vision, swollen lymph nodes, or kidney problems; serum sickness is common when lymphocyte immune globulin is used alone for aplastic anemia, but fairly rare when it is combined with other drugs that suppress immunity.)



Headaches, pain in the abdomen, diarrhea, nausea or vomiting, fluid retention, weakness, rapid heartbeats, or an abnormal increase in blood potassium (these side effects develop in more than a fifth of all patients during treatment)



Uncommon side effects such as kidney damage, high blood pressure, heart failure, lethargy, abnormal sensations such as prickling in the skin, seizures, pulmonary edema, and adult respiratory distress syndrome



Risk of developing lymphoma or leukemia, if the immune system is greatly suppressed for a long time Side effects in pregnant or nursing women

The effects of this drug on an unborn child are unknown. Doctors are not sure if this drug reaches breast milk. Methods of preventing or reducing side effects Drugs such as antihistamines, acetaminophen, and corticosteroids can prevent or decrease some side effects, including fevers, chills, and allergic reactions. Antibiotics may help to prevent infections.

880

Interactions Combining this drug with other medications that suppress the immune system (including chemotherapy) can severely suppress immunity. Drugs that slow blood clotting, such as aspirin, can increase the risk of bleeding. Any drug that reduces the symptoms of an infection, including aspirin and acetaminophen, can increase the risk that a serious infection will go undetected. See also Myelosuppression; Immune response; Infection and sepsis; Neuropathy. Anna Rovid Spickler, D.V.M., Ph.D.

Lymphoma Definition Lymphoma is the name of a diverse group of cancers of the lymphatic system, a connecting network of glands, organs and vessels whose principle cell is the lymphocyte.

Description When lymphoma occurs, cells in the lymphatic system grow abnormally. They divide too rapidly and grow without any order or control. Too much tissue is formed and tumors begin to grow. Because there is lymph tissue in many parts of the body, the cancer cells may involve the liver, spleen, or bone marrow. Two general types of lymphoma are commonly recognized: Hodgkin’s disease or Hodgkin’s lymphoma (HD), and Non-Hodgkin’s lymphoma (NHL). The two are distinguished by cell type. These differ significantly in respect of their natural histories and their response to therapy. Hodgkin’s disease tends to be primarily of nodal origin. Non-Hodgkin’s lymphomas, unlike HD, can spread beyond the lymphatic system. See also AIDS-related cancers. Kate Kretschmann

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M Magnetic resonance imaging Definition Magnetic resonance imaging (MRI) is one of the newest, and perhaps most versatile, medical imaging technology available. Doctors can get highly refined images of the body’s interior without surgery using MRI. By using strong magnets and pulses of radio waves to manipulate the natural magnetic properties in the body, this technique makes better images of organs and soft tissues than those of other brain scanning technologies. MRI is particularly useful for imaging the brain and spine, as well as the soft tissues of joints and the interior structure of bones, as well as the liver. The entire body is visible with MRI, and the technique poses few known health risks.

Purpose MRI was developed in the 1980s. Its technology has been developed for use in magnetic resonance angiography (MRA), magnetic resonance spectroscopy (MRS), and, more recently, magnetic resonance cholangiopancreatography (MRCP). MRA was developed to study blood flow, whereas MRS can identify the chemical composition of diseased tissue and produce color images of brain function. MRCP is evolving into a potential non-invasive alternative for the diagnostic procedure endoscopic retrograde cholangiopancreatography (ERCP). Advantages DETAIL. MRI creates precise images of the body based on the varying proportions of magnetic elements in different tissues. Very minor fluctuations in chemical composition can be determined. MRI images have greater natural contrast than standard x rays, computed tomography scan (CT scan), or ultrasound, all of which depend on the differing physical properties of tissues. This sensitivity allows MRI to

G A LE EN CY C LO PE DI A O F C AN CE R 3

distinguish fine variations in tissues deep within the body. It is also particularly useful for spotting and distinguishing diseased tissues (tumors and other lesions) early in their development. Often, doctors prescribe an MRI scan to more fully investigate earlier findings of other imaging techniques. SCOPE. The entire body can be scanned, from head to toe and from the skin to the deepest recesses of the brain. Moreover, MRI scans are not obstructed by bone, gas, or body waste, which can hinder other imaging techniques. (Although the scans can be degraded by motion such as breathing, heartbeat, and bowel activity.) The MRI process produces cross-sectional images of the body that are as sharp in the middle as on the edges, even of the brain through the skull. A close series of these twodimensional images can provide a three-dimensional view of the targeted area. Along with images from the cross-sectional plane, the MRI can also provide images sagitally (from one side of the body to the other, from left to right for example), allowing for a better three-dimensional interpretation, which is sometimes very important for planning a surgical approach. SAFETY. MRI does not depend on potentially harmful ionizing radiation, as do standard x ray and computer tomography scans. There are no known risks specific to the procedure, other than for people who might have metal objects in their bodies.

Despite its many advantages, MRI is not routinely used because it is a somewhat complex and costly procedure. MRI requires large, expensive, and complicated equipment; a highly trained operator; and a doctor specializing in radiology. Generally, MRI is prescribed only when serious symptoms or negative results from other tests indicate a need. Many times another test is appropriate for the type of diagnosis needed. Uses Doctors may prescribe an MRI scan of different areas of the body. 881

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BRAIN AND HEAD. MRI technology was developed because of the need for brain imaging. It is one of the few imaging tools that can see through bone (the skull) and deliver high quality pictures of the brain’s delicate soft tissue structures. MRI may be needed for patients with symptoms of a brain tumor, stroke, or infection (like meningitis). MRI may also be needed when cognitive or psychological symptoms suggest brain disease (like Alzheimer’s or Huntington’s diseases, or multiple sclerosis), or when developmental retardation suggests a birth defect. MRI can also provide pictures of the sinuses and other areas of the head beneath the face. In adult and pediatric patients, MRI may be better able to detect abnormalities than compared to computed tomography scanning. SPINE. Spinal problems can create a host of seemingly unrelated symptoms. MRI is particularly useful for identifying and evaluating degenerated or herniated spinal discs. It can also be used to determine the condition of nerve tissue within the spinal cord. JOINT. MRI scanning is most commonly used to diagnose and assess joint problems. MRI can provide clear images of the bone, cartilage, ligament, and tendon that comprise a joint. MRI can be used to diagnose joint injuries due to sports, advancing age, or arthritis. MRI can also be used to diagnose shoulder problems, such as a torn rotator cuff. MRI can also detect the presence of an otherwise hidden tumor or infection in a joint, and can be used to diagnose the nature of developmental joint abnormalities in children. SKELETON. The properties of MRI that allow it to see through the skull also allow it to view the inside of bones. Accordingly, it can be used to detect bone cancer, inspect the marrow for leukemia and other diseases, assess bone loss (osteoporosis), and examine complex fractures. HEART AND CIRCULATION. MRI technology can

be used to evaluate the circulatory system. The heart and blood flow provides a good natural contrast medium that allows structures of the heart to be clearly distinguished. THE REST OF THE BODY. Whereas computed tomography and ultrasound scans satisfy most chest, abdominal, and general body imaging needs, MRI may be needed in certain circumstances to provide better pictures or when repeated scanning is required. The progress of some therapies, like liver cancer therapy, needs to be monitored, and the effect of repeated x-ray exposure is a concern.

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Precautions MRI scans and metal MRI scanning should not be used when there is the potential for an interaction between the strong MRI magnet and metal objects that might be imbedded in a patient’s body. The force of magnetic attraction on certain types of metal objects (including surgical steel) could move them within the body and cause serious injury. Metal may be imbedded in a person’s body for several reasons. MEDICAL. People with implanted cardiac pacemakers, metal aneurysm clips, or who have broken bones repaired with metal pins, screws, rods, or plates must tell their radiologist prior to having an MRI scan. In some cases (like a metal rod in a reconstructed leg), the difficulty may be overcome. INJURY. Patients must tell their doctors if they have bullet fragments or other metal pieces in their body from old wounds. The suspected presence of metal, whether from an old or recent wound, should be confirmed before scanning. OCCUPATIONAL. People with significant work exposure to metal particles (e.g., working with a metal grinder) should discuss this with their doctors and radiologists. The patient may need prescan testing— usually a single, regular x ray of the eyes to see if any metal is present.

Chemical agents Chemical agents designed to improve the picture or allow for the imaging of blood or other fluid flow during MRA may be injected. In rare cases, patients may be allergic to, or intolerant of, these agents, and these patients should not receive them. If these chemical agents are to be used, patients should discuss any concerns they have with their doctor and radiologist. Side effects The potential side effects of magnetic and electric fields on human health remain a source of debate. In particular, the possible effects on an unborn baby are not well known. Any woman who is, or may be, pregnant, should carefully discuss this issue with her doctor and radiologist before undergoing a scan. As with all medical imaging techniques, obesity greatly interferes with the quality of MRI.

Description In essence, MRI produces a map of hydrogen distribution in the body. Hydrogen is the simplest G A LE EN CY C LO PE DI A O F C AN C ER 3

Angiography—Any of the different methods for investigating the condition of blood vessels, usually via a combination of radiological imaging and injections of chemical tracing and contrast agents. Gadolinium—A very rare metallic element useful for its sensitivity to electromagnetic resonance, among other things. Traces of it can be injected into the body to enhance the MRI pictures. Hydrogen—The simplest, most common element known in the universe. It is composed of a single electron (negatively charged particle). It is the nuclear proton of hydrogen that makes MRI possible by reacting resonantly to radio waves while aligned in a magnetic field. Ionizing radiation—Electromagnetic radiation that can damage living tissue by disrupting and destroying individual cells. All types of nuclear decay radiation (including x rays) are potentially ionizing. Radio waves do not damage organic tissues they pass through. Magnetic field—the three-dimensional area surrounding a magnet, in which its force is active. During MRI, the patient’s body is permeated by the force field of a superconducting magnet. Radio waves—Electromagnetic energy of the frequency range corresponding to that used in radio communications, usually 10,000 cycles per second to 300 billion cycles per second. Radio waves are the same as visible light, x rays, and all other types of electromagnetic radiation, but are of a higher frequency.

element known, the most abundant in biological tissue, and one that can be magnetized. It will align itself within a strong magnetic field, like the needle of a compass. The earth’s magnetic field is not strong enough to keep a person’s hydrogen atoms pointing in the same direction, but the superconducting magnet of an MRI machine can. This comprises the magnetic part of MRI. Once a patient’s hydrogen atoms have been aligned in the magnet, pulses of very specific radio wave frequencies are used to knock them back out of alignment. The hydrogen atoms alternately absorb and emit radio wave energy, vibrating back and forth between their resting (magnetized) state and their agitated (radio pulse) state. This comprises the resonance part of MRI. G A LE EN CY C LO PE DI A O F C AN CE R 3

A single MRI exposure produces a two-dimensional image of a slice through the entire target area. A series of these image slices closely spaced (usually less than half an inch) makes a virtual three-dimensional view of the area. Magnetic resonance spectroscopy (MRS) is different from MRI because MRS uses a continuous band of radio wave frequencies to excite hydrogen atoms in a variety of chemical compounds other than water. These compounds absorb and emit radio energy at characteristic frequencies, or spectra, which can be used to identify them. Generally, a color image is created by assigning a color to each distinctive spectral emission. This comprises the spectroscopy part of MRS. MRS is still experimental and is available only in a few research centers. Doctors primarily use MRS to study the brain and disorders like epilepsy, Alzheimer’s disease, brain tumors, and the effects of drugs on brain growth and metabolism. The technique is also useful in evaluating metabolic disorders of the muscles and nervous system. Magnetic resonance angiography (MRA) is another variation on standard MRI. MRA, like other types of angiography, looks specifically at fluid flow within the blood (vascular) system, but does so without the injection of dyes or radioactive tracers. Standard MRI cannot make a good picture of flowing blood, but MRA uses specific radio pulse sequences to capture usable signals. The technique is generally used in combination with MRI to obtain images that show both vascular structure and flow within the brain and head in cases of stroke, or when a blood clot or aneurysm is suspected. MRI technology is also being applied in the evaluation of the pancreatic and biliary ducts in a new study called magnetic resonance cholangiopancreatography (MRCP). MRCP produces images similar to that of endoscopic retrograde cholangiopancreatography (ERCP), but in a non-invasive manner. Because MRCP is new and still very expensive, it is 883

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KE Y T ERM S

The MRI equipment records the duration, strength, and source location of the signals emitted by the atoms as they relax and translates the data into an image on a television monitor. The state of hydrogen in diseased tissue differs from healthy tissue of the same type, making MRI particularly good at identifying tumors and other lesions. In some cases, chemical agents such as gadolinium can be injected to improve the contrast between healthy and diseased tissue.

Magnetic resonance imaging

not readily available in most hospitals and imaging centers. Regardless of the exact type of MRI planned, or area of the body targeted, the procedure involved is basically the same. In a special MRI suite, the patient lies down on a narrow table and is made as comfortable as possible. Transmitters are positioned on the body and the table moves into a long tube that houses the magnet. The tube is as long as an average adult lying down, and is open at both ends. Once the area to be examined has been properly positioned, a radio pulse is applied. Then a two-dimensional image corresponding to one slice through the area is made. The table then moves a fraction of an inch and the next image is made. Each image exposure takes several seconds and the entire exam will last anywhere from 30 to 90 minutes. During this time, the patient must remain still as movement can distort the pictures produced. Depending on the area to be imaged, the radiowave transmitters will be positioned in different locations. For the head and neck, a helmet-like covering is worn on the head.  For the spine, chest, and abdomen, the patient will be lying on the transmitters.  For the knee, shoulder, or other joint, the transmitters will be applied directly to the joint. 

Additional probes will monitor vital signs (like pulse, respiration, etc.) throughout the test. The procedure is somewhat noisy and can feel confining to many patients. As the patient moves through the tube, the patient hears a thumping sound. Sometimes, music is supplied via earphones to drown out the noise. Some patients may become anxious or feel claustrophobic while in the small, enclosed tube. Patients may be reassured to know that throughout the study, they can communicate with medical personnel through an intercom-like system. Recently, open MRIs have become available. Instead of a tube open only at the ends, an open MRI also has opening at the sides. Open MRIs are preferable for patients who have a fear of closed spaces and become anxious in traditional MRI machines. Open MRIs can also better accommodate obese patients, and allow parents to accompany their children during testing. If the chest or abdomen is to be imaged, the patient will be asked to hold his to her breath as each exposure is made. Other instructions may be given to the patient as needed. In many cases, the entire 884

examination will be performed by an MRI operator who is not a doctor. However, the supervising radiologist should be available to consult as necessary during the exam, and will view and interpret the results sometime later.

Preparation In some cases (such as for MRI brain scanning or MRA), a chemical designed to increase image contrast may be given immediately before the exam. If a patient suffers from anxiety or claustrophobia, drugs may be given to help the patient relax. The patient must remove all metal objects (watches, jewelry, eye glasses, hair clips, etc.). Any magnetized objects (like credit and bank machine cards, audio tapes, etc.) should be kept far away from the MRI equipment because they can be erased. The patient cannot bring any personal items such as a wallet or keys into the MRI machine. The patient may be asked to wear clothing without metal snaps, buckles, or zippers, unless a medical gown is worn during the procedure. The patient may be asked not to use hair spray, hair gel, or cosmetics that could interfere with the scan.

Aftercare No aftercare is necessary, unless the patient received medication or had a reaction to a contrast agent. Normally, patients can immediately return to their daily activities. If the exam reveals a serious condition that requires more testing or treatment, appropriate information and counseling will be needed.

Risks MRI poses no known health risks to the patient and produces no physical side effects. Again, the potential effects of MRI on an unborn baby are not well known. Any woman who is, or may be, pregnant, should carefully discuss this issue with her doctor and radiologist before undergoing a scan.

Normal results A normal MRI, MRA, MRS, or MRCP result is one that shows the patient’s physical condition to fall within normal ranges for the target area scanned.

Abnormal results Generally, MRI is prescribed only when serious symptoms or negative results from other tests indicate a need. There often exists strong evidence of a G A LE EN CY C LO PE DI A O F C AN C ER 3

Resources

KEY T ERMS Lymph node—One of a number of small, beanshaped structures that run along the lymphatic system of vessels. The lymph nodes trap cancer cells, along with other cells and fluids. Malignant—Causing worsening or death. Malignant tumors can invade other tissues and organs and spread to other areas of the body.

BOOKS

Faulkner, William H. Tech’s Guide to MRI: Basic Physics, Instrumentation and Quality Control. Malden: Black well Science, 2001. Fischbach, F. T. A Manual of Laboratory and Diagnostic Tests. 6th ed. Philadelphia: Lippincott, 1999. Goldman, L., and Claude Bennett, editors. Cecil Textbook of Medicine. 21st ed. Philadelphia: W. B. Saunders, 2000: pp 977 970. Roth, Carolyn K. Tech’s Guide to MRI: Imaging Procedures, Patient Care and Safety. Malden: Blackwell Science, 2001. PERIODICALS

Carr Locke, D., et al. ‘‘Technology Status Evaluation: Magnetic Resonance Cholangiopancreatography.’’ Gastrointestinal Endoscopy (June 1999): 858 61.

Kurt Richard Sternlof

Male breast cancer Definition Male breast cancer is a malignant tumor that forms in a man’s breast.

Demographics Breast cancer in men is rare, accounting for less than 1% of all breast cancers. Still, the American Cancer Society predicts that about 1,910 American men will be diagnosed with the disease and 440 men will die of it in 2009. Although studies show the number of breast cancer cases in women has decreased in the United States and Europe since the 1960s, the number of breast cancer cases in men have not decreased, but remained stable or slightly increased. The rate of increase in cases begins and steadily rises at age 50 for men. However, the average age for male breast cancer is between 60 and 70 years old, with a median age of 67 years. Men often are diagnosed at a later stage than women. G A LE EN CY C LO PE DI A O F C AN CE R 3

Description Breast cancer is rare in men, but can be serious and fatal. Many people believe that only women can get breast cancer, but men have breast tissue that also can develop cancer. When men and women are born, they have a small amount of breast tissue with a few tubular passages called ducts located under the nipple and the area around the nipple (areola). By puberty, female sex hormones cause breast ducts to grow and milk glands to form at the ends of the ducts. But male hormones eventually prevent further breast tissue growth. Although male breast tissue still contains some ducts, it will have only a few —or no— lobules. Near the breasts of men and women are axillary lymph nodes. These are underarm small structures shaped like beans that collect cells from lymphatic vessels. Lymphatic vessels carry lymph, a clear fluid that contains fluid from tissues, cells from the immune system, and various waste products throughout the body. The axillary lymph nodes are important to breast cancer patients, as they play a role in the spread and staging of breast cancer. Breast cancer is much more common in women, mostly because women have many more breast cells that can undergo cancerous changes and because women are exposed to the effects of female hormones. Infiltrating ductal carcinoma is the most common type of breast cancer in men. It is a type of adenocarcinoma, or a type of cancer that occurs in glandular tissue. Infiltrating ductal carcinoma starts in a breast duct and spreads beyond the cells lining the ducts to other tissues in the breast. Once the cancer begins spreading into the breast, it can spread to other parts of the body. This distant spread is called metastasis. When breast cancer metastasizes to other areas of the body, it can cause serious, life-threatening consequences. For example, breast cancer might spread to the liver or lungs. About 80–90% of all male breast cancers are infiltrating ductal carcinomas. 885

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condition that the scan is designed to detect and assess. Thus, the results will often be abnormal, confirming the earlier diagnosis. At that point, further testing and appropriate medical treatment is needed. For example, if the MRI indicates the presence of a brain tumor, an MRS may be prescribed to determine the type of tumor so that aggressive treatment can begin immediately without the need for a surgical biospy.

Male breast cancer

Ductal carcinoma in situ (DCIS) is not common; it accounts for about 10% of all male breast cancers. It also is an adenocarcinoma. In situ cancers remain in the immediate area where they began, so DCIS remains confined to the breast ducts and does not spread to the fatty tissues of the breast. This means it is likely found early. DCIS also may be called intraductal carcinoma. Other types of breast cancer are very rare in men. Adenocarcinomas that are lobular (forming in the milk glands or lobules) only occur in about 2% of male breast cancer cases because men normally do not have milk gland tissues. Inflammatory breast cancer, a serious form of breast cancer in which the breast looks red and swollen and feels warm, also occurs rarely. Paget’s disease of the nipple, a type of breast cancer that grows from the ducts beneath the nipple onto the nipple’s surface, only accounts for about 1% of female breast cancers. However, slightly more men have this form of breast cancer than women. Sometimes, Paget’s disease is associated with another form of breast cancer. Although not a form of cancer, but a benign condition, gynecomastia is important to mention. It is the most common of all male breast disorders and can be associated with male breast cancer in a rare condition called Klilnefelter’s syndrome. Gynecomastia most often occurs in teenage boys when their hormones change during puberty. Older men also may experience the condition when their hormone balance changes as they age. Gynecomastia is an increase in the amount of breast tissue, or breast tissue enlargement. If a man has Klinefelter’s syndrome, he can develop gynecomastia and increased risk of breast cancer.

Causes and symptoms Scientists do not know what causes most cases of male breast cancer. However, excellent progress is being made in genetic research and in understanding how genes instruct cells to grow, divide, and die. For example, researchers have now mapped all of the genes in the human body. Genes are part of the body’s DNA, which is the chemical that instructs the cells. When DNA or genes carry defects (mutations), they activate changes in the cells, such as rapid cell division, that lead to cancer. Some genes, called tumor suppression genes, cause cells to die. Scientists have identified some genetic mutations that are risk factors for breast cancer. In other cases, environmental, or outside, factors are thought to increase a man’s risk for breast cancer. 886

Mutations of at least two versions of a tumor suppressor gene (BRCA1 and BRCA2) have been identified as causes of breast cancer in women. In men, the BRCA2 mutation is considered responsible for about 15% of breast cancers. Men can inherit genes from either parent. Studies have shown that BRCA1 also may increase a man’s risk for breast cancer, but its role is less certain. These mutations have been shown to increase other cancers in men, including prostate cancer. Klinefelter’s syndrome is a rare genetic cause of breast cancer in men. It results from inheriting an additional X chromosome. Several other factors also may cause male breast cancer. Some conditions, such as the liver disease cirrhosis, can cause an imbalance in a man’s hormones, producing high levels of the female hormone estrogen, which can lead to breast cancer. Exposure to some substances such as high amounts of radiation may contribute to male breast cancer. A 2004 report studied why a cluster of breast cancer cases occurred among a small group of men who worked in the basement office of a multi-story office building. The study linked their breast cancer to exposure to high magnetic fields from a nearby electrical switchgear room in their work space. Many men do not realize they can develop breast cancer; they ignore the symptoms. The most common symptom is a mass, or lump in the chest area, particularly around the nipple. The lump will be firm, not tender or painful. Other signs that may warn of male breast cancer include: 

Skin dimpling or puckering



Changes in the nipple, such as drawing inward (retraction)



Nipple discharge of any kind



Redness or scaling of the nipple or breast skin



Abnormal swelling (or lump) of the breast, nipple, or chest muscle



Prolonged rash or irritation of the nipple that may indicate Paget’s disease

Diagnosis Physicians follow the same steps for diagnosing breast cancer in men as in women, except that routine screening of breast cancer is not done in men. Once symptoms are noticed, however, physicians will proceed in the same way. The physician will conduct a thorough medical history and examination, including questions that may identify risk factors for breast cancer, such as male or female relatives with the G A LE EN CY C LO PE DI A O F C AN C ER 3

The physician also performs a clinical breast examination. This helps locate and study a lump or suspicious area. The physician will feel (palpate) a mass to get an idea of its size, texture, likely location and relation to surrounding skin, muscles and tissues. At this point, the physician already will begin to look for signs that the cancer may have spread to other organs and to the lymph nodes. The physician will palpate lymph nodes and the liver, for instance, to see if they are enlarged. The next step in diagnosis usually is a diagnostic mammogram. Mammography is an x ray of the breast. Mammograms are performed by radiologic technologists who take special training in the procedure. Mammograms are evaluated by radiologists, physicians who receive medical training specifically in interpreting x rays. If the initial mammogram shows suspicious findings, the radiologist may order magnification views to more closely look at the suspicious area. Mammograms can accurately show the tissue in the breast, even more so in men than women, because men do not have dense breasts or benign cysts in their breasts that interfere with the diagnosis. The radiologist also might recommend an ultrasound to follow up on suspicious findings. Ultrasound often is used to image the breasts. Also known as sonography, the technique uses high-frequency sound waves to take pictures of organs and functions in the body. Sound wave echoes can be converted by computer to an image and displayed on a computer screen. Ultrasound does not use radiation. A technologist will perform the ultrasound; it will be evaluated by the radiologist. Biopsies, which involve removing a sample of tissue, are the only definite way to tell if a mass is cancerous. At one time, surgical biopsies were the only option, requiring removal of all or a large portion of the lump in a more complicated procedure. Today, fine-needle aspiration biopsy and core biopsies can be performed. In fine-needle aspiration biopsy, a thin needle is inserted to withdraw fluid from the mass. The physician may use ultrasound or other imaging guidance to locate the mass if necessary. The fluid is tested in a laboratory under a special microscope to determine if it is cancerous. A core biopsy is similar, but involves removing a small cylinder of tissue from the mass through a slightly larger needle. Core biopsy may require local anesthesia. These biopsy techniques usually can be performed in a physician office or outpatient facility. G A LE EN CY C LO PE DI A O F C AN CE R 3

The cells in biopsy samples help physicians determine if the lump is cancerous and the type of breast cancer. A tissue sample also may be used for assigning a grade to the cancer and to test for certain proteins and receptors that aid in treatment and prognosis decisions. If there is discharge from the nipple, the fluid also may be collected and analyzed in a laboratory to see if cancer cells are present in the fluid. Diagnosis of breast cancer spread may require additional tests. For example, a computed tomography (CT) scan may be ordered to check organs such as the liver or kidney for possible metastasized cancer. A chest x ray can initially check for cancer spread to the lungs. Bone scans are nuclear medicine procedures that look for areas of diseased bone. Magnetic resonance imaging (MRI) has been increasingly used in recent years as a follow-up study to mammograms when findings are not clear. However, for metastatic breast cancer, they are more likely to be ordered to check for cancer in the brain and spinal cord. Positron emission tomography (PET) scans also have become more common in recent years. Staging After cancer has been definitively diagnosed, the next step is staging. Staging helps clarify details about the tumor, the adjacent and distant lymph nodes that may be affected, and the adjacent and distant organs that may be affected. This information helps determine what type of treatment is most appropriate. The first step in staging may utilize a technique called sentinel lymph node biopsy. The sentinel node is the first one the cancer cells are likely to reach, so it is the first one checked for cancerous cells. Using a radioactive substance and blue dye injected into the area around the tumor, physicians can track the path of the cells and stage the cancer. The technique has been used for many years on women with breast cancer; research in 2004 showed it worked well for predicting lymph node status in men as well. Cancer staging systems help physicians compare treatments and research and identify patients for clinical trials. Most of all, they help physicians determine treatment and prognosis for individual patients by describing how severe a patient’s cancer is in relation to the primary tumor. The most common system used for cancer is the American Join Committee on Cancer (AJCC) TNM system, which bases staging largely on the spread of the cancer. T stands for tumor and describes the tumor’s size and spread locally, or within the breast and to nearby organs. The letter N stands 887

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disease. The medical history also helps gather details on possible symptoms for breast cancer.

Male breast cancer

for lymph nodes and describes the cancer’s possible spread to and within the lymph node system. In some descriptions below, the cancer may have been found by sentinel node biopsy as microscopic disease in nodes that are in the breasts (rather than the armpits). For simplification, these findings have been grouped with the axillary lymph nodes. M stands for metastasis to note if the cancer has spread to distant organs. Further letters and numbers may follow these three letters to describe number of lymph nodes involved, approximate tumor sizes, or other information. The following is a summary of breast cancer stages: Stage 0: Tis, N0, M0: Ductal carcinoma in situ (DCIS). This is the earliest and least invasive form of breast cancer; the cancer cells are located within a duct and have not invaded surrounding fatty tissue. Stage I: T1, N0, M0: The tumor is less than 1 in. in diameter (2 cm or less) and has not spread to lymph nodes or distant organs. Stage IIA: T0, N1, M0/T2, NO, MO: No tumor is found or the tumor is smaller than 2 cm and cancer is found in one to three axillary lymph nodes (even if no tumor is found), or the tumor is between 2 and 5 cm in diameter but has not spread to the axillary lymph nodes. The cancer has not spread to distant organs. Stage IIIB: T2, N1, M0/T3, NO, MO: The tumor is between 2 and 5 cm in diameter and has spread to one to three axillary lymph nodes or the tumor is larger than 5 cm, has not grown into the chest wall or spread to the lymph nodes or distant organs. Stage IIIA: T0-2, N2, M0/T3, N1, MO: The tumor is smaller than 5 cm in diameter and has spread to four to nine axillary lymph nodes or the tumor is larger than 5 cm and has spread to one to nine axillary lymph nodes. The cancer has not spread to distant organs. Stage IIIB: T4, N0-2, M0: The tumor has grown into the chest wall or the skin and may have spread to no lymph nodes or as many as nine lymph nodes. Cancer has not spread to distant sites. Stage IIIC: T0-4, N3, MO: The tumor is any size, has spread to 10 or more axillary lymph nodes or to one or more lymph nodes under or above the collarbone (clavicle) on the same side as the breast tumor. The cancer has not spread to distant organs. Inflammatory breast cancer: Classified as stage III, unless it has spread to distant organs or lymph nodes not near the breast (which would classify it as Stage IV). Stage IV: T0-4, N0-3, M1: Regardless of the tumor’s size, the cancer has spread to distant organs, such as the liver, bones, or lung, or to lymph nodes far from the breast. 888

Treatment If the axillary lymph nodes were identified as containing cancer at the time of the sentinel lymph node biopsy, they will be removed in an axillary dissection. Sometimes, this is done at the time of the biopsy. For Stage I, surgery often is the only treatment needed for men. Women often have lumpectomies, which remove as little surrounding breast tissue as possible, to preserve some of their breast shape. For men, this is less of a concern, and mastectomy, or surgical removal of the breast, is performed in 80% of all male breast cancers. Men with Stage I tumors larger than 1 cm may receive additional (adjuvant) chemotherapy. Men with Stage II breast cancer also usually receive a mastectomy. If they have cancer in the lymph nodes, they probably will receive adjuvant therapy. Those with estrogen receptor-positive tumors may receive hormone therapy with tamoxifen. The treatment team may recommend adjuvant radiation therapy if the cancer has spread to nearby lymph nodes and/or to the skin. Stage III breast cancer requires mastectomy followed by adjuvant therapy with tamoxifen when hormones are involved. Most patients with Stage III disease also will require chemotherapy and radiation therapy to the chest wall. Men with Stage IV breast cancer will require systemic therapy, or chemotherapy and perhaps hormonal therapy that works throughout the body to fight the cancer in the breast, as well as the cancer cells that have spread. Patients also may receive immunotherapy to help patients fight infection following chemotherapy. Radiation and surgery also may be used to relieve symptoms of the primary cancer and areas where the cancer may have spread. The treatment team also may have to diagnose specific treatments for the metastatic cancers, depending on their sites. If male breast cancer recurs in the breast or chest wall, it can be treated with surgical removal and followed by radiation therapy. An exception is recurrence in the same area, where additional radiation therapy can damage normal tissue. Recurrence of the cancer in distant sites is treated the same as metasteses found at the time of diagnosis. Alternative and complementary therapies Many alternative and complementary therapies can help cancer patients relax and deal with pain, though none to date have been shown to treat or prevent male breast cancer. For example, traditional G A LE EN CY C LO PE DI A O F C AN C ER 3

Q U E S T I O N S TO A S K Y O U R DOCTOR 





 

Coping with cancer treatment It is difficult for some men to accept and cope with a breast cancer diagnosis, since it is a relatively rare and unexpected disease among men. It is important that men work closely with their treatment team to talk about the their concerns and to carefully follow all instructions for care. Support groups and family support are critical in coping with a breast cancer diagnosis. Eating a nutritious diet, stopping use of tobacco, and limiting use of alcohol, can help in recovery from breast cancer. Beginning a regular exercise program when the treatment team recommends also helps. Clinical trials Research currently is underway to test various chemotherapy combinations for male breast cancer at different stages. A clinical trial also is underway to investigate a vaccine for treating patients with metastatic breast cancer. The National Institutes of Health list clinical trials by disease type, including those for which they are recruiting patients. Choosing to participate in a clinical trial is a decision that involves the patient, family, and treatment team.









What kinds of diagnostic studies will be required to ascertain the type and spread of this tumor? How far has my cancer advanced; what stage is it in? Could there be a genetic component to this tumor? Should other family member be tested? What types of treatments are available? What types of side effects from treatments can I expect? What are your recommendations to help me deal with those side effects? Am I eligible for any clinical trials? Would these be helpful to consider? Are there any lifestyle changes that I should make? How often should I be checked after treatment has ended? Is there a support group that I can join to hear about other people’s experiences with this disorder?

distant organs. Men who have a history of breast cancer in their family should pay particular attention to the symptoms of breast cancer and seek immediate medical evaluation. Physicians may be able to test the blood of men with family history for presence of the BRCA2 gene so they may more carefully watch for early signs of breast cancer. Avoiding exposure to radiation also may help present some male breast cancers. Resources BOOKS

Prognosis Prognosis for male breast cancer varies, depending on stage. Generally, prognosis is poorer for men than for women, because men tend to show up for diagnosis when their breast cancer has reached a later stage. The average five-year survival rate for Stage I cancers is 96%. For Stage II, it is 84%. Stage III cancers carry an average five-year survival rate of 52%, and by Stage IV, the rate drops to 24%.

Prevention Some forms of male breast cancer cannot be prevented. But detecting the cancer at an early stage can prevent serious complications, such as spread to G A LE EN CY C LO PE DI A O F C AN CE R 3

Abeloff, MD et al. Clinical Oncology. 3rd ed. Philadelphia: Elsevier, 2004. Khatri, VP and JA Asensio. Operative Surgery Manual. 1st ed. Philadelphia: Saunders, 2003. Townsend, CM et al. Sabiston Textbook of Surgery. 17th ed. Philadelphia: Saunders, 2004. PERIODICALS

‘‘Cluster of Male Breast Cancer Linked to Electromagnetic Field Exposure.’’ Cancer Weekly (Sept. 21, 2004):98. ‘‘Largest Study of its Kind Finds Male Breast Cancer on the Rise.’’ Cancer Weekly (June 15, 2004):32. ‘‘SLN Biopsy Predicts Axillary Lymph Node Status in Male Breast Cancer Patients.’’ Clinical Oncology Week (Aug. 2, 2004):15. Stoppani, Jim. ‘‘Male Breast Cancer.’’ Muscle & Fitness (December 2004):194. 889

Male breast cancer

Chinese medicine offers therapies that stress the importance of balancing energy forces. Many studies also show that guided imagery, prayer, meditation, laughter, and a positive approach to cancer can help promote healing. Early studies have shown that soy and flaxseed may have some preventive properties for breast cancer. However, these trials have been conducted in women. When looking for these therapies, cancer support groups suggest asking for credible referrals and working with the medical treatment team to coordinate alternative and complementary care.

Malignant fibrous histiocytoma

OTHER

‘‘Breast Cancer News. New Findings About Male Breast Cancer.’’ Web page. Susan G. Komen Cancer Foun dation, 2003. ‘‘Facts For Life. Alternative and Complementary Therapy.’’ Brochure/Web page. Susan G. Komen Cancer Foun dation, 2004. ‘‘Facts For Life. Breast Cancer in Men.’’ Brochure/Web page. Susan G. Komen Cancer Foundation, 2004. ‘‘How Is Breast Cancer in Men Diagnosed?’’ Web page. American Cancer Society, 2004. ‘‘How Is Breast Cancer in Men Staged?’’ Web page. American Cancer Society, 2004. ‘‘Male Breast Cancer (PDQ): Treatment, Patient Version.’’ Web page. National Cancer Institute, 2003.

KEY T ERMS Liver function tests (LFTs)—Blood tests that measure the blood serum levels of several enzymes produced by the liver. Sarcoma—A form of cancer that arises from within the supportive tissues, such as bone, cartilage, fat, or muscle. soft tissue. Often, an MFH is not completely removed because it has crossed, undetected, from one fat layer to another neighboring layer.

ORGANIZATIONS

American Cancer Society. 800 ACS 2345. http:// www.cancer.org. The Susan G. Komen Breast Cancer Foundation. 5005 LBJ Freeway, Ste, 250, Dallas, TX 75244. 800 I’M AWARE. http://www.komen.org. Y ME National Breast Cancer Organization. 212 W. Van Buren, Ste. 1000, Chicago, IL. 60607 3098. 800 221 2121. http://www.y me.org.

Teresa G. Odle

Malignant melanoma see Melanoma

Demographics MFHs are diagnosed in six of every one million people each year. MFHs can occur in people of any age, but they are extremely rare in children. MFHs occur in a slightly higher frequency in Caucasians than in people of African descent or Asians. No relationship of MFHs appear to exist to any geographic region. Males are affected in slightly higher numbers than are females. MFHs of the skin are seen almost exclusively in sun-exposed areas of the skin in elderly patients. People affected with certain genetic diseases, such as neurofibromatosis, have a higher incidence of MFHs than unaffected people.

Malignant fibrous histiocytoma

MFHs of the bone are seen almost exclusively in people who have a pre-existing skeletal disorder such as Paget disease or fibrous dysplasia of bone.

Definition Malignant fibrous histiocytoma (MFH), although rare, is the most common abnormal growth of soft tissue (sarcoma) in adults.

Causes and symptoms

MFH occurs as a painless mass most commonly in the skin, arms, legs, kidneys, or the pancreas. More rarely MFH may occur in the bones, heart, breasts, or inside the skull.

The cause, or causes, of MFHs are not known. An elevated risk for the development of MFHs has been linked to the chemical phenoxyacetic acid found in herbicides; to clorphenols found in wood preservatives; and to exposure to asbestos. People who have been exposed to high doses of radiation are also more prone to develop MFHs than the remainder of the population. Research is ongoing to determine if there is a genetic cause of MFHs.

When MFHs spread (metastasize) to other organs, the most common site is the lung, but metastasis to local lymph nodes and to bone have also been reported.

The only direct symptom of MFHs is the presence of an abnormal mass, but some patients may also experience:

MFHs tend to be slow growing and slow to metastasize.



Local recurrence of MFH after surgery to remove the initial tumor is common because MFHs grow along the fat layers that separate different layers of



Description

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abnormally high levels of a certain type of white blood cells (eosinophils) in the blood low blood sugar (hypoglycemia) fever abnormal liver function tests G A LE EN CY C LO PE DI A O F C AN C ER 3

  





Which type of MFH do I have? What is the size of my tumor? Will I require chemotherapy or radiation treatments to shrink my tumor prior to its removal? What is the likelihood of my type of MFH coming back? How often should I seek follow-up examinations?

Diagnosis Prior to removal, MFHs are extremely difficult to distinguish from the other forms of soft tissue sarcoma. The definitive diagnosis of MFH usually occurs after a tumor has been surgically removed. This diagnosis is accomplished by conducting microscopic examinations on the tumor.

Stage one MFHs are generally removed by wide local excision. This technique involves the surgical removal of the tumor and an area of healthy surrounding tissue that is approximately the same size as the tumor itself. Stage two MFHs require wide surgical excision with the removal of wider margins of healthy tissue than those margins removed in the excision of smaller tumors. In some instances, stage two MFHs may require amputation. Post-operative treatment of MFH patients may include chemotherapy or radiation therapy, especially in cases of MFH of the bones and in cases of metastasis to the lungs. In cases of large MFHs, the patient may undergo radiation treatments prior to surgery in an attempt to shrink the size of the tumor prior to excision. Overall survival from MFH is approximately 75% five-year disease-free survival. The prognosis is generally poorer if: 

Treatment team Treatment for MFHs is mostly surgical or observational. Surgeries to remove MFHs are generally performed by orthopedic surgeons. MFHs rarely require any chemotherapies or radiation therapies, however, when these treatments are called for they are directed by a medical oncologist and administered by health care personnel who specialize in these fields.

Clinical staging, treatments, and prognosis



  



the disease has metastasized to the lungs or bones complete tumor removal is not accomplished, or is not possible the patient is of an advanced age the tumor is large the location of the tumor is somewhere other than the arms or legs the tumor is located deep in the body, rather than superficially Alternative and complementary therapies

MFHs are divided into three grades based on the appearance of the tissue within the tumor. Low grade tumors may closely resemble the surrounding normal tissue. Intermediate and high grade tumors may have little resemblance to normal tissue.

There are no effective alternative treatments for MFHs other than surgical removal with or without chemotherapy or radiation treatments.

Additionally, MFHs are divided into two clinical stages based on size. Stage one MFHs are those tumors that are under 5 cm (2 in) in diameter. Stage two MFHs are those tumors larger than 5 cm (2 in) in diameter.

Most patients who undergo wide local excision to remove their tumors can resume their normal activities within a few days of the operation.

A treatment plan is determined after the grade and stage of the tumor has been established. High and intermediate grade tumors generally, regardless of the stage, are surgically removed. Low grade, stage one, tumors may be observed for development to a higher grade or stage rather than removed if it is determined that the risks of anesthetic and surgery G A LE EN CY C LO PE DI A O F C AN CE R 3

Coping with cancer treatment

The loss of a limb may produce feelings of grief that are similar to that felt upon the death of a spouse or close family member. Patients who must undergo amputation to remove their cancer may require extended psychological care to help them to deal with this grief and to help them develop a new, healthy, body image. These patients may also require extended physical therapy to learn to operate without the missing limb or to learn to use a prosthetic device. 891

Malignant fibrous histiocytoma

QUESTIONS TO ASK THE DOCTOR

outweigh the risk of the tumor to the individual patient.

MALT lymphoma

Clinical trials

Description

There were 40 clinical trials underway, in early 2001, aimed at the treatment of MFHs and other soft tissue sarcomas. More information on these trials, including contact information, may be found by conducting a clinical trial search at the website of the National Cancer Institute, CancerNet: http://cancernet.nci.nih.gov/trialsrch.shtml.

Prevention Because the causes of MFHs are not known, there is no known prevention.

Special concerns Repeat surgery may be necessary for MFHs because these tumors sometimes redevelop. Careful monitoring by the medical team will be required. Resources ORGANIZATIONS

Center for Orthopedic Oncology and Musculoskeletal Research, Washington Cancer Institute. 110 Irving St. NW, Washington, DC 20010. (202) 877 3970. [cited July 5, 2005]. ing lopical :.In t imierobi a llozl'ng~s have shown promiS