DEVELOPMENTS IN ONCOLOGY

Transcription

1 LIVER CANCER

2 DEVELOPMENTS IN ONCOLOGY F.J. Cleton and J.W.I.M. Simons, eds.: Genetic Origins of Tumour Cells J. Aisner and P. Chang, cds.: Cancer Treatment and Research B.W. Ongerboer de Visser, D.A. Bosch and W.M.H. van Woerkom-Eykenboom, eds.: Neuro-oncology: Clinical and Experimental Aspects X. K. Hellmann, P. Hilgard and S. Eccles, eds.: Metastasis: Clinical and Experimental Aspects H.F. Seigler, ed.: Clinical Management of Melanoma P. Correa and W. Haenszel, eds.: Epidemiology of Cancer of the Digestive Tract L.A. Liotta and I.R. Hart, eds.: Tumour Invasion and Metastasis J. Banoczy, ed.: Oral Leukoplakia C. Tijssen, M. Halprin and L. Endtz, eds.: Familial Brain Tumours F.M. Muggia, C.W. Young and S.K. Carter, eds.: Anthracycline Antibiotics in Cancer B.W. Hancock, ed.: Assessment of Tumour Response X. D.E. Peterson and S. Sonis, cds.: Oral Complications of Cancer Chemotherapy R. Mastrangelo, D.G. Pop lack and R. Riccardi, eds.: Central Nervous System Leukemia. Prevention and Treatment '\. Polliack, cd.: Human Leukemias. Cytochemical and Ultrastructural Techniques in Diagnosis and Research W. Davis, C. Maltoni and S. Tanneberger, eds.: The Control of Tumor Growth and its Biological Bases A.P.M. Heintz, C. Th. Griffiths and J.B. Trimbos, eds.: Surgery in Gynecological Oncology M.P. Hacker, E.B. Douple and I. Krakoff, cds.: Platinum Coordination Complexes in Cancer Chemotherapy MJ. van Zwieten. The Rat as Animal Model in Breast Cancer Research: A Histopathological Study of Radiationand Hormone-Induced Rat Mammary Tumors B. Lowenberg and A. Hogenbeck, eds.: Minimal Residual Disease in Acute Leukemia I. van der Waal and G.B. Snow, eds.: Oral Oncology B.W. Hancock and A.M. Ward, eds.: Immunological Aspects of Cancer K.V. Honn and B.F. Sloane, cds.: Hemostatic Mechanisms and Metastasis K.R. Harrap, W. Davis and A.N. Calvert, eds.: Cancer Chemotherapy and Selective Drug Development X. V.D. Velde, J.H. Come lis and P.H. Sugarbaker, eds.: Liver Metastasis D.J. Ruiter, K. Welvaart and S. Ferrone, cds.: Cutaneous Melanoma and Precursor Lesions S.B. Howell, ed.: Intra-Arterial and Intracavitary Cancer Chemotherapy D.L. Kisner and J.F. Smyth, eds.: Interferon Alpha-2: Pre-Clinical and Clinical Evaluation P. Furmanski,J.C. Hager and M.A. Rich, eds.: RNA Tumor Viruses, Oncogenes, Human Cancer and AIDS: On the Frontiers of Understanding J.E. Talmadge, I.J. Fidler and R.K. Oldham: Screening for Biological Response Modifiers: Methods and Rationale J.c. Bottino, R.W. Opfell and F.M. Muggia, eds.: Liver Cancer. 0-89R P.K. Pattengale, R.J. Lukes and C.R. Taylor, cds.: Lymphoproliferative Diseases: Pathogenesis, Diagnosis, Therapy F. Cavalli, G. Bonadonna and M. Rozencweig, eds.: Malignant Lymphomas and Hodgkin's Disease

3 LIVER CANCER EDITED BY JOSEPH C. BOTTINO New York University Medical Center RICHARD W. OPFELL University of California, Irvine Medical Center FRANCO M. MUGGIA New York University Medical Center u " MARTINUS NIJHOFF PUBLISHING A MEMBER OF THE KLUWER ACADEMIC PUBLISHERS GROUP BOSTON /DORDRECHT /LANCASTER

4 Copyright by Martinus Nijhoff Publishing, Boston Softcover reprint of the hardcover 1st edition 1985 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any fortn or by any means, mechanical, photocopying, recording, or otherwise, without written permission of the publisher, Martinus Nijhoff Publishing, 190 Old Derby Street, Hingham, Massachusetts Distributors for North America: Kluwer Academic Publishers 190 Old Derby Street Hingham, MA Distributors for all other countries: Kluwer Academic Publishers Group Distribution Centre P.O. Box AH Dordrecht The Netherlands Library of Congress Cataloging-in-Publication Data Main entry under title: Liver cancer. (Developments in oncology) 1. Liver Cancer. I. Bottino, Joseph c., II. Opfell, Richard W. III. Muggia, Franco M. [DNLM: 1. Liver Neoplasms-therapy. WI DE998N / WI 735 L7817] RC280.L5L ' ISBN-13: DOl: / e-isbn-13:

5 CONTENTS Contributing authors Preface xv VB I. PATHOLOGY AND NATURAL HISTORY 1. Pathology of liver tumors 3 Z.D. GOODMAN AND K.G. ISHAK 2. Natural history of liver cancer 21 G. FALKSON AND B. COETZER II. DIAGNOSIS OF LIVER CANCER 3. Radiologic techniques for detection and evaluation of liver cancer 35 E. LEWIS AND S. WALLACE 4. Nuclear medicine aspects of primary and secondary liver cancer 69 J.W. FROELICH, J.H. THRALL, AND D.P. SWANSON III. SURGERY IN LIVER CANCER 5. Surgical anatomy of the liver and biliary tree 87 D.M. NAGORNEY AND J.A. VAN HEERDEN 6. Surgical therapy of liver cancer 99 R. OTTOW, D.A. AUGUST, AND P.H. SUGARBAKER 7. Hepatic artery ligation for liver cancer 143 N.J. PETRELLI AND A. MITTLEMAN v

6 vi Contents 8. Hepatic artery embolization for liver cancer 157 c. CHARNSANGAVEJ, S. WALLACE, C.H. CARRASCO, AND W. BECHTEL 9. Surgical aspects of intrahepatic artery therapy 179 J.E. NIEDERHUBER IV. CHEMOTHERAPY OF LIVER CANCER 10. Chemotherapy of liver cancer 197 J.J. LOKICH 11. New chemotherapeutic agents in liver cancer 217 F.M. MUGGIA AND M.D. GREEN 12. Intraperitoneal chemotherapy: a possible role in the treatment of hepatic metastases 225 J.L. SPEYER 13. Pharmacologic studies of hepatic intra-arterial chemotherapy 237 w.o. ENSMINGER AND J.W. GYVES 14. Regional chemotherapy of liver cancer 247 R.W. OPFELL AND J. BOWEN 15. Regional arterial therapy in the management of primary liver neoplasms 263 Y.Z. PATT, c. CHARNSANGEVEJ, M. SOSKI, AND G.M. MAVLIGIT, 16. Pumps and catheters for intrahepatic artery therapy 275 J.C. BOTTINO 17. Adjuvant therapy for prevention of liver metastases 285 H.W. BRUCKNER V. RADIATION THERAPY OF LIVER CANCER 18. Radiation therapy of hepatobiliary tumors 297 S.A. LEIBEL VI. COMBINED MODALITY THERAPY 19. Combination chemotherapy and whole liver irradiation for hepatic tumors 315 M.A. FRIEDMAN 20. Therapy of metastatic carcinoid tumor and the carcinoid syndrome 325 C.G. MOERTEL 21. Regional-arterial chemotherapy or arterial embolization in the management of various stages of colon cancer 341 Y. PATT, c. CHARSANGAVEJ, A. BODDIE, G.M. MAVLIGIT, M. SOSKI, AND S. WALLACE 22. Thermochemotherapy of liver metastases 357 K.P. RAMMING AND F. K STORM 23. Combined hepatic arterial occlusion and chemotherapy for primary or secondary tumors of the liver 371 C.P. KARAKOUSIS Index 387

7 CONTRIBUTING AUTHORS David A. August, M.D. Department of Surgery Yale University School of Medicine 333 Cedar Street New Haven, CT William Bechtel, M.D. Department of Diagnostic Radiology The University of Texas M.D. Anderson Hospital and Tumor Institute 6723 Bertner A venue Houston, TX A. Boddie, M.D. Department of Surgery The University of Texas System Cancer Center M.D. Anderson Hospital and Tumor Institute 6723 Bertner Avenue Houston, TX Vll

8 viii Contributing authors Joseph C. Bottino, M.D. Rita and Stanley H. Kaplan Cancer Center New York University Medical Center 550 First Avenue New York, NY Joseph Bowen, M.D. Suite Phoenix A venue Waterbury, CT Howard W. Bruckner, M.D. Medicine (Oncology) and Neoplastic Diseases Mount Sinai School of Medicine 1 Gustave Levy Place New York, NY C. Humberto Carrasco, M.D. Department of Diagnostic Radiology The University of Texas M.D. Anderson Hospital and Tumor Institute 6723 Bertner Avenue Houston, TX Chusilp Charnsangavej, M.D. Department of Diagnostic Radiology The University of Texas M.D. Anderson Hospital and Tumor Institute 6723 Bertner Avenue Houston, TX Buks Coetzer, M.D. Department of Cancer Chemotherapy HF Verwoerd Hospital and University of Pretoria Private Bag x169 Pretoria, 0001 Republic of South Africa William D. Ensminger, Ph.D., M.D. University of Michigan Medical School Upjohn Center for Clinical Pharmacology Ann Arbor, MI 48109

9 ix Geoffrey Falkson, M.D. Department of Cancer Chemotherapy HF Verwoerd Hospital and University of Pretoria Private Bag x169 Pretoria, 0001 Republic of South Africa Michael A. Friedman, M.D. Clinical Investigations Branch Division of Cancer Treatment National Cancer Institute Bethesda, MD Jerry W. Froelich, M.D. Henry Ford Hospital Department of Radiology Detroit, MI Zachary D. Goodman, MAJ, MC, USA Department of Hepatic Pathology Armed Forces Institute of Pathology Washington, DC Michael Green, M.D. Rita & Stanley H. Kaplan Cancer Center New York University Medical Center 550 First Avenue New York, NY John W. Gyves, M.D. Cancer Pharmacology Program University of Michigan Medical School Upjohn Center for Clinical Pharmacology Ann Arbor, MI Kamal G. Ishak, M.D., ph.d. Department of Hepatic Pathology Armed Forces Institute of Pathology Washington, DC Constantine P. Karakousis, M.D. Department of Surgical Oncology New York State Department of Health Roswell Park Memorial Institute

10 x Contributing authors 666 Elm Street Buffalo, NY Steven Leibel, M.D. Department of Radiation Oncology University of California San Francisco, CA Errol Lewis, M.D. Department of Diagnostic Radiology The University of Texas M.D. Anderson Hospital and Tumor Institute 6723 Bertner Avenue Houston, TX Jacob J. Lokich, M.D. Section of Medical Oncology New England Deaconess Hospital Harvard Medical School Boston, MA Giora M. Mavligit, M.D. Department of Clinical Immunology and Biological Therapy The University of Texas System Cancer Center M.D. Anderson Hospital and Tumor Institute 6723 Bertner Avenue Houston, TX Arnold Mittelman, M.D. Department of Surgery Roswell Park Memorial Institute 666 Elm Street Buffalo, NY Charles G. Moertel, M.D. Mayo Clinic and Mayo Foundation Rochester, MN Franco M. Muggia, M.D. Rita & Stanley H. Kaplan Cancer Center New York University Medical Center 550 First Avenue New York, NY 10016

11 xi David M. Nagorney, M.D. Department of Surgery Mayo Clinic 200 1st Street, S.W. Rochester, MN John E. Niederhuber, M.D. University of Michigan Medical Center Ann Arbor, MI Richard W. Opfell, M.D. Clinical Oncology Program University of California, Irvine Medical Center Orange, CA Reyer T. Ottow, M.D. Colorectal Cancer Section Surgery Branch Division of Cancer Treatment National Cancer Institute National Institutes of Health Bethesda, MD Yehuda Z. Patt, M.D. Department of Clinical Immunology and Biological Therapy The University of Texas System Cancer Center M.D. Anderson Hospital and Tumor Institute 6723 Bertner Avenue Houston, TX Nicholas J. Petrelli, M.D. Department of Surgical Oncology Roswell Park Memorial Institute 666 Elm Street Buffalo, NY Kenneth P. Ralluning, M.D. Division of Surgical Oncology John Wayne Clinic Johnson Comprehensive Cancer Center UCLA School of Medicine Los Angeles, CA 90024

12 xu Contributing authors Marilyn Soski, R.N. Department of Clinical Immunology and Biological Therapy The University of Texas System Cancer Center M.D. Anderson Hospital and Tumor Institute 6723 Bertner A venue Houston, TX James L. Speyer, M.D. Rita & Stanley H. Kaplan Cancer Center New York University Medical Center 550 First A venue New York, NY F. Kristian Storm, M.D. Division of Surgical Oncology John Wayne Clinic Johnson Comprehensive Cancer Center UCLA School of Medicine Los Angeles, CA Paul H. Sugarbaker, M.D. Colorectal Cancer Section Surgery Branch Division of Cancer Treatment National Cancer Institute National Institutes of Health Bethesda, MD Dennis P. Swanson, R.Ph., M.S. Henry Ford Hospital Department of Radiology Detroit, MI James H. Thrall, M.D. Henry Ford Hospital Department of Radiology Detroit, MI Jonathan A. van Heerden, M.D., F.A.C.S. Department of Surgery Mayo Clinic Rochester, MN

13 Sidney Wallace, M.D. Department of Diagnostic Radiology The University of Texas M.D. Anderson Hospital and Tumor Institute 6723 Bertner Avenue Houston, TX xiii

14 PREFACE Neoplastic disease confined to the liver is an important worldwide problem. In the industrialized nations, metastatic disease of the most common cancers involves the liver in upwards of 50% of cases. Primary hepatic tumors are virtually epidemic in most third world countries and certainly constitute one of the ten most common causes of cancer deaths on a worldwide scale. Amazingly, little specific attention has been devoted to therapeutic approaches of liver and biliary tumors until recently. We attribute this apparent lack of interest to the uniformly poor prognosis of patients so afflicted, and attribute the renewed interest to the exciting new developments in diagnostic and therapeutic technology as well as in tumor biology. The purpose of this book is to collect in one volume an integrated selection of articles that would provide the therapist with a comprehensive, yet practical, overview of liver cancer. We believe the contributors to the book are superbly qualified experts on the various subjects and provide in-depth information on respective fields. The editing process for us was not only educational but thrilling as the high quality and complementary nature of the chapters became evident as we received them. Because many areas in the field of liver cancer are controversial, the reader will notice that contradictory opinions are presented by some of the authors. Our hope is to stimulate the reader as well as to demonstrate several areas of controversy. At the same time, we think the readers will be pleased with the overall continuity of the chapters. We attempted to keep the general aspects of the xv

15 xvi Preface text practical with emphasis on clarity of the discussions and adequacy of illustration. This text will prove useful both for the general oncologist as well as those with a specific interest in liver cancer. We thank all of the authors for their contribution and assistance in bringing this publication together in a timely fashion.

16 I. PATHOLOGY AND NATURAL HISTORY

17 1. PATHOLOGY OF LIVER TUMORS ZACHARY D. GOODMAN and KAMAL G. ISHAK INTRODUCTION In evaluating a tumor in the liver, the pathologist should ask several questions that have a direct bearing on possible therapy. 1. Is the tumor primary or metastatic? 2. If primary, is the tumor benign or malignant? 3. If benign, is the tumor one that may produce symptoms or life-threatening complications, making resection advisable? 4. If malignant, is the tumor one with a very poor prognosls or one with a relatively favorable prognosis? 5. Is the tumor likely to be localized or to be multicentric or to have spread extensively, precluding resection? 6. Is the tumor vascular in origin and therefore likely to have hemorrhagic complications? 7. Is the surrounding liver tissue normal or diseased? An accurate histologic diagnosis [1] (on an adequate biopsy) usually provides the answer to most of these questions. The opinions or assertions contained herein arc the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. The authors thank Mrs. Martha Collard for assistance in the preparation of the manuscript. IC. BOlliflO, R.W. Op/el!, and F.M. Muggia (eds.), LIVER C4!\'CER..11! r \ ~ hresen'ed. l s Martillus.Vtj'holJ Publishing, Bostofl/Dordr{'cht/LancQster. 3

18 4 I. Pathology and natural history BENIGN HEPATOCELLULAR TUMORS Hepatocellular adenornaand focal nodular hyperplasia There has been and continues to be confusion between these two lesions in the minds of many clinicians as well as pathologists. Although similar in some ways, these benign hepatocellular tumors differ in etiopathogenesis, natural history, and recommended treatment. The gross and microscopic pathology generally allows ready distinction. Hepatocellular adenoma (HCA) occurs almost exclusively in women in the reproductive age group. Over 90% are associated with oral contraceptive steroid (OC) use, and the risk of developing this tumor is directly related to the duration of OC therapy [2,3,4,5]. A common clinical presentation, seen in about one-third of patients, is an acute abdomen, due to infarction within the tumor or rupture with hemoperitoneum, that can prove fatal. Consequently, it is usually recommended that these tumors be resected, if possible. Some cases have totally regressed following cessation of OC use [6]' but there are rare instances of hepatocellular carcinoma developing in pre-existing hepatocellular adenomas [5,7]' constituting a second reason for definitive therapy. Focal nodular hyperplasia (FNH) is also more frequent in women, but about one-third occurs in men, and it occurs at all ages, including childhood [5,8,9]. Any relationship to OC use is probably coincidental. These tumors are seldom symptomatic and are almost always discovered incidentally. They are not thought to have any malignant potential. The gross features are often helpful in distinguishing HCA (figure 1-1) from FNH (figure 1-2). Both are usually single but may be multiple, and both occur Figure 1-1. Hepatocellular adenoma, resection specimen. The tumor is relatively large (17 em) and spherical with a smooth cut surface and a fibrous capsule. The variegated appearance is the result of bile production by some parts of the tumor and necrosis in other parts (AFlP ).

19 1. Pathology of liver tumors 5 Figure 1-2. Focal nodular hyperplasia, cut surface. The lesion is relatively small (2.5 X 4 em), unencapsulated, and lobulated with a central stellate scar (AFIP ). more often in the right lobe than the left. HCA is relatively large, usually 5 to 10 cm or larger. Focal nodular hyperplasia seldom is more than 3 em in diameter, although rare tumors may be quite large and on occasion have occupied an entire lobe. Both tumors often protrude from the surface of the liver, but HCA is dome-shaped, while FNH is umbilicated. On cut section, HCA is flat and smooth and often has areas of hemorrhage. FNH has a central stellate scar with radiating septa and lobules that bulge above the cut surface. Microscopically, both HCA and FNH are growths of benign hepatocytes. HCA is composed of sheets ofhepatocytes with abundant, relatively clear cytoplasm, and small, normal-appearing nuclei (figure 1-3). Necrosis and hemorrhage may be present and are not considered signs of malignancy in the absence of nuclear atypia. FNH shows the central stellate scar containing large arteries and veins (never present in HCA) with thin radiating septa separating nodules of normal hepatocytes (figure 1-4). The septa contain many small bile ducts. The two lesions are sufficiently different so that distinction between them is seldom difficult if the entire tumor has been resected. Biopsies can be more difficult, particularly small needle biopsies. However, if the surgeon conveys a clear gross description to the pathologist, an accurate diagnosis can nearly always be made. Benign cholangiocellular tumors Bile duct adenomas and von Myenberg complexes are fairly common. Bile duct adenoma is usually single and less than 1 cm in diameter; von Myenberg complexes are frequently multiple and not visible to the naked eye. Both are clinically insignificant. They only cause problems when mistaken for metastatic carcinoma by the unwary. Microscopically, a bile duct adenoma is a discrete proliferation of

20 6 1. Pathology and natural history Figure 1-3. Hepatocellular adenoma. The tumor is an encapsulated sheet-like growth of benign hepatocytes that are larger and paler than the surrounding liver on the right of the photomicrograph (X 40, AFIP ). Figure 1-4. Focal nodular hyperplasia. There is a central scar containing large blood vessels. Fibrous septa separate irregular nodules of normal appearing hepatocytes (X 25, AFIP ). small benign bile ducts (figure 1-5) while a von Myenberg complex has serpigenous duct-like structures in a fibrous stroma adjacent to a normal portal tract. Biliary cystadenomas are rare tumors that occur in the major intra- and extrahepatic bile ducts, predominantly in middle-aged women [10]. They can produce