Hepatocellular Carcinoma (eBook)

Preface to 2nd Edition 7
Preface to 1st Edition 9
Contents 11
Contributors 13
Epidemiology of Hepatocellular Carcinoma 17
ABSTRACT 17
1. GLOBAL INCIDENCE OF HEPATOCELLULAR CARCINOMA 18
2. RISK FACTORS OF HEPATOCELLULAR CARCINOMA 23
3. GENETIC EPIDEMIOLOGY OF HCC 34
REFERENCES 37
Environmental Carcinogens and Risk for Human Liver Cancer 42
ABSTRACT 42
1. INTRODUCTION 43
2. MOLECULAR BIOMARKERS FOR ENVIRONMENTAL CARCINOGENS 44
3. ENVIRONMENTAL ETIOLOGY OF HCC 45
4. METHODS FOR BIOMARKER MEASUREMENT 47
5. VALIDATION OF BIOMARKERS OF ENVIRONMENTAL CARCINOGENS 49
6. BIOMARKERS IN HUMAN INVESTIGATIONS 51
7. INTERVENTION TRIALS USING AFLATOXIN BIOMARKERS 56
8. DNA MUTATIONS MEASURED IN HUMAN PLASMA AND HCC 57
9. SUMMARY 59
ACKNOWLEDGMENTS 61
REFERENCES 61
Primary Liver Cancer: Chemical Carcinogenesis 69
ABSTRACT 69
1. INTRODUCTION 70
2. LIVER CANCER IS AN IMPORTANT BIOLOGICAL PROBLEM 71
3. CHEMICAL CARCINOGENS 73
4. PATHOGENESIS OF HCC 88
5. ETIOLOGY IN THE HUMAN 93
REFERENCES 102
Molecular Mechanisms of Hepatocellular Carcinoma: Insights to Therapy 122
ABSTRACT 122
1. INTRODUCTION 123
2. RECEPTOR TYROSINE KINASES AND THEIR LIGANDS 127
3. INTRACELLULAR SIGNAL TRANSDUCERS 130
4. OTHER THERAPEUTIC TARGETS: PRESENT AND FUTURE 134
REFERENCES 136
Genomic Profiling of Human Hepatocellular Carcinoma 144
ABSTRACT 144
1. HEPATOCELLULAR CARCINOMA: CLINICAL CONCERNS 145
2. GENE EXPRESSION PROFILING: CURRENT TECHNOLOGIES 146
3. HCC MICROARRAY STUDIES: EMERGING CONCEPTS 148
4. CANDIDATE SERUM MOLECULAR MARKERS 169
5. SUMMARY 176
ACKNOWLEDGMENTS 182
REFERENCES 182
Pathologic Aspects of Hepatocellular Tumors 196
ABSTRACT 196
1. INTRODUCTION 197
2. FOCAL NODULAR HYPERPLASIA 197
3. HEPATOCELLULAR ADENOMA 201
4. HEPATOCELLULAR DYSPLASIA 205
5. HEPATOCELLULAR CARCINOMA 207
6. PATHOLOGIC VARIANTS OF HEPATOCELLULAR CARCINOMA 220
7. HEPATOBLASTOMA 228
REFERENCES 231
Hepatocellular Carcinoma Associated with Hepatitis B Virus 247
ABSTRACT 247
1. HBV AND HCC 249
2. HBV AND PATHOGENESIS OF HCC 251
3. INCIDENCE OF HCC 251
4. HCC IN ASIAN AMERICANS 252
5. PREVENTION OF HCC 254
6. SUMMARY 257
7. MOLECULAR BIOLOGY OF HCC ASSOCIATED WITH HBV 257
REFERENCES 262
Hepatitis C and Hepatocellular Carcinoma 270
ABSTRACT 271
1. INTRODUCTION 271
2. EPIDEMIOLOGY 272
3. PATHOLOGY 273
4. PRIMARY PREVENTION OF HCC 276
5. SURVEILLANCE 276
6. STANDARDIZED RECALL PROCEDURES 283
7. SCREENING INTERVAL 283
8. COST-EFFECTIVENESS 284
9. PREVENTION OF RECURRENCE 285
REFERENCES 286
Metabolic Disease and Hepatocellular Carcinoma 293
ABSTRACT 294
1. INTRODUCTION 294
2. OXIDATIVE STRESS 296
3. ALCOHOLIC LIVER DISEASE AND HEPATOCELLULAR CARCINOMA 297
4. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), NONALCOHOLIC STEATONECROSIS ( NASH), AND HEPTOCELLULAR CARCINOMA ( HCC) 299
5. HEMOCHROMATOSIS AND WILSON'S DISEASE AND HCC 301
6. AFLATOXIN-ASSOCIATED HCC 302
7. ALPHA 1 ANTITRYPSIN DEFICIENCY AND HCC 303
8. FAMILIAL INTRAHEPATIC CHOLESTASIS 304
9. BILE ACID SYNTHEIC DISORDERS AND HEPATOCELLULAR CARCINOMA 305
10. DEFECTS IN CARBOHYDRATE METABOLISM 305
11. TYROSINEMIA TYPE I 307
12. THE PORPHYRIAS 307
13. CYSTIC FIBROSIS 309
14. ALAGILLE'S SYNDROME 309
15. LINKED SIDEROBLASTIC ANEMIA 309
16. FANCONI ANEMIA 310
17. TYPE II DIABETES MELLITUS 310
18. HEREDITARY FRUCTOSE INTOLERANCE 310
19. HEREDITARY HEMORRHAGIC TELEANGIECTASIA 310
20. ADENOSINE DEAMINASE DEFICIENCY 311
21. STEROID-INDUCED HCC 311
22. SUMMARY 311
REFERENCES 311
Clinical Features and a Clinician's Diagnostic Approach to Hepatocellular Carcinoma 318
ABSTRACT 318
1. INTRODUCTION 319
2. CLINICAL FEATURES 319
3. SCREENING FOR HCC 323
4. DIAGNOSTIC APPROACH 325
5. ROLE OF LIVER BIOPSY - "TO NEEDLE OR NOT TO NEEDLE" 326
6. PRIMARY AND SECONDARY CHEMOPREVENTION OF HCC 329
7. CONCLUSIONS 332
REFERENCES 332
Screening and Biomarkers for Hepatocellular Carcinoma 336
ABSTRACT 336
1. INTRODUCTION 337
2. SCREENING/SURVEILLANCE FOR HEPATOCELLULAR CARCINOMA 337
3. EFFICACY OF SURVEILLANCE 343
4. NOVEL BIOMARKERS 344
REFERENCES 352
Use of Imaging Techniques to Screen for Hepatocellular Carcinoma 358
ABSTRACT 358
1. MONITORING THE CIRRHOTIC PATIENT 359
2. FOCAL LESIONS IN THE CIRRHOTIC LIVER 359
3. HEPATOCELLULAR CARCINOMA 365
4. ACCURACY OF SONOGRAPHY, CT, AND MR AS SCREENING MODALITIES 370
5. WHY, WHEN, AND HOW TO SCREEN 371
REFERENCES 374
MRI for Detection and Evaluation of Hepatocellular Carcinoma 377
ABSTRACT 377
1. FOCAL IMAGING FINDINGS IN CIRRHOTIC LIVER 379
2. MRI: PULSE SEQUENCES AND GENERAL CONSIDERATIONS 381
3. CHARACTERISTICS OF HCC 383
4. REPORTING FINDINGS SUSPICIOUS FOR HCC 386
5. CONCLUDING STATEMENTS 389
REFERENCES 389
Ultrasound of Hepatocellular Carcinoma: The Important Contribution of Contrast Enhancement 395
ABSTRACT 395
1. INTRODUCTION 396
2. GRAY-SCALE AND DOPPLER ULTRASOUND 397
3. CONTRAST-ENHANCED ULTRASOUND 402
4. CONCLUSION 411
REFERENCES 412
Percutaneous Ethanol Injection 415
ABSTRACT 415
1. INTRODUCTION 416
2. PRINCIPLES AND TECHNIQUES 416
3. EVALUATION OF THERAPEUTIC EFFICACY 418
4. COMPLICATIONS 420
5. RESULTS 421
6. CONCLUSIONS AND CURRENT INDICATIONS 422
REFERENCES 425
Radiofrequency Ablation of Hepatocellular Carcinoma 429
ABSTRACT 429
1. INTRODUCTION 430
2. RFA HISTORICAL BACKGROUND 431
3. MECHANISM OF ABLATION 432
4. RFA EQUIPMENT 433
5. EVALUATION AND PATIENT SELECTION 434
6. PROCEDURE 435
7. RFA VS HEPATECTOMY FOR HCC 436
8. RFA VS TACE VS COMBINED RFA+TACE FOR HCC 438
9. RFA VS PEI FOR HCC 438
10. RFA PRIOR TO LIVER TRANSPLANTATION 439
11. RECURRENCE, MORALITY, AND LONG-TERM SURVIVAL AFTER RFA FOR HCC 440
12. COMPLICATIONS FROM RFA 449
13. SUMMARY 452
REFERENCES 453
Resection of Hepatocellular Carcinoma 460
ABSTRACT 460
1. INTRODUCTION 461
2. INDICATIONS FOR RESECTION 461
3. PREOPERATIVE ASSESSMENT 462
4. TECHNIQUES OF LIVER RESECTION 464
5. CURRENT RESULTS OF HEPATIC RESECTION 466
6. ADJUVANT THERAPIES 467
7. CONCLUSIONS 469
REFERENCES 469
Liver Transplantation for Hepatocellular Carcinoma 473
ABSTRACT 473
1. INTRODUCTION 474
2. HISTORICAL ASPECTS OF LIVER TRANSPLANTATION FOR HCC 475
3. RISK FACTORS 476
4. STAGING OF HCC 476
5. MOLECULAR PROFILING OF HCC 480
6. MICRODISSECTION-GUIDED BROAD PANEL MUTATIONAL ANALYSIS 482
7. LOCOREGIONAL THERAPY FOR HEPATOCELLULAR CARCINOMA: A BRIDGE TO TRANSPLANT 487
8. CURRENT RECOMMENDATION FOR TRANSPLANTATION 489
REFERENCES 490
Living Donor Liver Transplantation for Hepatocellular Carcinoma 497
ABSTRACT 498
1. INTRODUCTION 498
2. PERSPECTIVES OF LIVING DONOR LIVER TRANSPLANTATION 499
3. LIVING DONOR LIVER TRANSPLANTATION FOR HCC 504
4. COMPARATIVE STUDIES BETWEEN LIVING AND DECEASED DONOR LIVER TRANSPLANTATION FOR HCC 523
5. SUMMARY 525
REFERENCES 526
Medical Therapy of HCC 532
ABSTRACT 532
1. PRINCIPLES 533
2. SPECIAL CONSIDERATIONS FOR THE ONCOLOGIST 546
3. HEPATIC ARTERY CHEMOTHERAPY AND CHEMOEMBOLIZATION 547
4. SAFETY CONSIDERATIONS OF HEPATIC ARTERY CHEMO- OCCLUSION 551
5. RESULTS OF HEPATIC ARTERY CHEMOTHERAPY AND CHEMOEMBOLIZATION 552
6. SYSTEMIC CHEMOTHERAPY 556
7. OTHER SYSTEMIC THERAPIES 556
8. WHAT IS NEEDED NEXT? 560
9. FUTURE DIRECTIONS 562
REFERENCES 564
Percutaneous Interventional Technique for Intra- arterial Chemoembolization 574
ABSTRACT 574
1. INTRODUCTION 575
2. PATIENT SELECTION AND PREPARATION 577
3. HEPATIC ARTERIAL ANATOMY ESSENTIAL TO TACE 578
4. VARIANT ARTERIAL ANATOMY 578
5. PROCEDURE 580
6. EMBOLIZATION AGENTS 583
7. COMPLICATIONS FROM TACE 586
8. ADVANCED CATHETERIZATION TECHNIQUES AND ADJUVANT THERAPY 586
9. RADIOEMBOLIZATION OF LIVER TUMORS 589
10. CONCLUSION 589
REFERENCES 591
Molecular Targeted Therapies for HCC 594
ABSTRACT 594
1. MOLECULAR PATHWAYS 596
2. RATIONAL THERAPIES 601
3. UNANSWERED QUESTIONS 611
REFERENCES 616
Radiation Therapy for Hepatocellular Carcinoma 620
ABSTRACT 620
1. OVERVIEW 621
2. PHYSICS OF RADIATION THERAPY 622
3. RADIOBIOLOGY 626
4. RADIATION EFFECTS IN THE LIVER 627
5. CLINICAL STUDIES 628
REFERENCES 640
Psychosocial Issues in Hepatocellular Carcinoma 646
ABSTRACT 646
1. PSYCHOSOCIAL EVALUATION AND TREATMENT OF DISTRESS IN ONCOLOGY 647
2. THE ROLE OF BEHAVIOR IN THE DEVELOPMENT OF HCC 648
3. EVALUATION OF PSYCHOLOGICAL AND CANCER- RELATED SYMPTOMS 649
4. COMMON PRESENTING PROBLEMS IN HCC 678
5. CANCER-RELATED SYMPTOMS AND TREATMENT RECOMMENDATIONS 685
6. SPECIAL ISSUES 693
ACKNOWLEDGMENTS 697
REFERENCES 697
Putting It All Together 717
1. SCREENING FOR HCC 718
2. THE ROLE OF BIOPSY 719
3. WHAT IF THE FIRST BIOPSY COMES BACK NEGATIVE FOR CANCER OR IS INCONCLUSIVE? 719
4. METASTATIC DISEASE INVOLVING THE LUNGS, BONES, OR BRAIN 720
5. WHAT IS THE BEST TREATMENT FOR ONE TO TWO HEPATIC LESIONS, EACH 3 CM OR LESS? 720
6. WHAT ARE THE TREATMENT OPTIONS FOR ONE TO TWO LESIONS OF ANY SIZE, WITHOUT CIRRHOSIS OR WITH CIRRHOSIS BUT NORMAL LIVER FUNCTION TESTS? 720
7. WHO SHOULD OR CAN RECEIVE A LIVER TRANSPLANT? 721
8. WHAT ARE THE TREATMENT OPTIONS FOR ONE LESION GREATER THAN 5CM OR THREE LESIONS WITH ONE OR MORE GREATER THAN 3CM? 722
9. A PATIENT WITH MULTIPLE LESIONS, ANY GREATER THAN 5CM AND WITHOUT METASTASES, WHO HAS A BLOOD GROUP/ MATCHED FAMILY MEMBER WILLING TO ACT AS A LIVING- RELATED DONOR 722
10. MULTIFOCAL HCC WITH TUMORS CONFINED TO THE LIVER WITH OR WITHOUT PORTAL VEIN THROMBOSIS AND BILIRUBIN LESS THAN 2.0 MG/ DL 722
11. A PATIENT WITH ANY TUMOR, NOT FOR TRANSPLANT, WITH CHILD B OR C CIRRHOSIS, ENCEPHALOPATHY, OR BILIRUBIN GREATER THAN 3.0 MG/ DL 723
12. CLINICAL EVALUATION AND WORKUP FOR LIVER TRANSPLANT 723
13. NEEDED CLINICAL TRIALS 723
REFERENCES 724
Subject Index 725