Hepatocellular Carcinoma

Contents......Page 12
Preface......Page 8
Acknowledgments......Page 10
List of Contributors......Page 16
Introduction......Page 24
Geographic Distribution......Page 25
Risk Factors......Page 26
Age and gender......Page 27
Genetic and congenital abnormalities......Page 29
Hepatitis B virus (HBV)......Page 31
Hepatitis C virus (HCV)......Page 32
Other hepatitis viruses......Page 33
Chemical carcinogens......Page 34
Miscellaneous factors......Page 35
Precancerous Changes and Hepatocarcinogenesis......Page 37
Relationship of Etiological Agents and Molecular Events......Page 38
References......Page 41
The importance of hepatic terminology......Page 48
First-order division......Page 49
Second-order division......Page 50
Third-order division......Page 53
Hepatic arteries and liver resections......Page 55
Prevailing pattern and anomalies of bile ducts draining the right hemiliver......Page 58
Prevailing pattern and important variations of bile ducts draining the left hemiliver......Page 60
Portal vein and liver resections......Page 62
Hepatic veins and liver resections......Page 65
Portal sheaths and liver plates......Page 69
Effect of pathological conditions on anatomical structures......Page 70
Addendum Regarding Liver Anatomy and Terminology......Page 71
References......Page 72
Introduction......Page 74
Bilirubin......Page 77
Albumin......Page 78
Prognostic clinicolaboratory scoring......Page 79
Model for End-stage Liver Disease (MELD)......Page 80
Bioenergetic Tests......Page 81
Peripheral blood redox state......Page 83
Tissue adenine nucleotide and mitochondrial analysis......Page 84
Magnetic resonance spectroscopy......Page 85
Radiological Imaging and Qualitative Assessments......Page 88
Clearance tests......Page 89
Indocyanine green (ICG) test......Page 90
Microsomal capacity tests......Page 92
Lidocaine and MEGX......Page 93
Glucose load: redox tolerance test......Page 94
Asialoglycoprotein receptor scintigraphy......Page 95
Regenerative capacity: portal vein embolization......Page 96
Longitudinal Evaluation After Hepatectomy......Page 97
References......Page 102
Is There a Need to Prevent Hepatocellular Carcinoma?......Page 108
Definition of Cancer Prevention......Page 109
Etiology of Hepatocellular Carcinoma......Page 110
Chronic hepatitis B virus infection......Page 111
Chronic hepatitis C virus infection......Page 113
Cirrhosis......Page 114
Aflatoxins......Page 115
Iron storage diseases......Page 116
Microcystins......Page 118
Alpha-1 antitrypsin deficiency......Page 119
Glycogen storage diseases......Page 120
Wilson’s disease......Page 121
Immunization against hepatitis B virus infection......Page 122
Other forms of primary prevention against hepatitis B and C virus infections......Page 125
Prevention of exposure to aflatoxin B1 (AFB1)......Page 127
Membranous obstruction of the inferior vena cava......Page 129
Chemoprevention of aflatoxin B1-induced hepatocellular carcinoma......Page 130
Polyprenoic acid......Page 133
Iron storage diseases......Page 134
Type II hypercitrullinemia......Page 135
Use of interferon-α in preventing hepatitis C virus–induced
hepatocellular carcinoma......Page 136
Use of interferon-α in preventing chronic hepatitis B virus–induced
hepatocellular carcinoma......Page 138
Glycyrrhizin......Page 139
Prevention of Recurrence of Hepatocellular Carcinoma......Page 140
References......Page 141
Introduction......Page 152
Screening Tests......Page 153
Surveillance Interval......Page 154
Target Populations......Page 155
Does Screening Reduce HCC-related Mortality?......Page 156
Dealing with Abnormal Screening Test Results......Page 157
A Screening Program......Page 159
Summary......Page 160
References......Page 161
Clinical Presentation: Epidemiologic Differences......Page 166
References......Page 177
Introduction......Page 182
Oncofetal Antigens and Glycoprotein Antigens......Page 184
Gamma-glutamyl transferase......Page 188
Alpha-L-fucosidase......Page 189
Des-gamma-carboxy prothrombin......Page 190
Golgi protein 73 (GP73)......Page 192
Interleukin-8......Page 193
Tumor-specific growth factor......Page 194
Alpha-fetoprotein (AFP) mRNA......Page 195
Gamma-glutamyl transferase (GGT) mRNA......Page 196
Oncogenes, tumor suppressors, and telomerase reverse transcriptase......Page 197
Conclusions......Page 198
References......Page 200
Incidence and Etiology......Page 206
Pathology and Imaging Features of HCC......Page 207
Ultrasonography......Page 216
Computed tomography (CT)......Page 219
Magnetic resonance imaging (MRI)......Page 223
Angiography......Page 229
Positron emission tomography (PET)......Page 230
References......Page 233
Gross Appearance......Page 238
Architectural variants......Page 241
Cytological variants......Page 244
Cytoplasmic inclusions......Page 246
Grading......Page 247
Natural History and Spread......Page 248
Small HCC......Page 250
Dysplasia......Page 251
Dysplastic nodules......Page 253
Hepatocellular adenoma......Page 254
Focal nodular hyperplasia (FNH)......Page 255
Nodular regenerative hyperplasia......Page 256
Combined HCC and Cholangiocarcinoma......Page 257
Hepatoblastoma......Page 258
Immunohistology......Page 259
Conclusions......Page 261
References......Page 262
Introduction......Page 266
The life cycle of HBV and the genomes of HBV and HCV......Page 268
Insertional mutagenesis and cis-activation of cellular genes by HBV DNA......Page 271
Trans-activation of cellular genes by HBV DNA......Page 272
Interactions Between Chemical Carcinogens, HBV, and Cellular Genes......Page 274
“Yin–Yang” (Negative and Positive) Regulation of Hepatocarcinogenesis: Alterations of Proto-oncogenes, Tumor Suppressors, and Other Critical Genes in HCC......Page 276
Genomic Instability and Chromosomal Alterations in HCC......Page 279
Comparative genomic hybridization analysis......Page 280
Chromosome 16q and E-cadherin......Page 281
Chromosome 13q and Rb and BRCA2......Page 282
Chromosome 9p and p16......Page 283
Reactivation of telomerase activity in HCC......Page 284
Reactive Oxygen Species and HCC......Page 285
Carcinogens and ROSs......Page 286
Growth factors, oncogenes, and ROSs......Page 287
Human HCC and ROSs......Page 288
Gene Profiling, Microarray, and Proteomics in HCC......Page 289
Gene Transfer and Immunotherapy in HCC......Page 294
References......Page 295
Introduction......Page 302
TNM......Page 304
Okuda......Page 307
Cancer of the Liver Italian Program (CLIP)......Page 308
Barcelona Clinic Liver Cancer (BCLC)......Page 310
Chinese University Prognostic Index (CUPI)......Page 314
Japanese Integrated Staging (JIS)......Page 315
Modified CLIP and JIS Staging Systems......Page 318
Discussion......Page 320
References......Page 321
Introduction......Page 326
Assessment of Tumor Extent......Page 327
HCC with adjacent organ involvement......Page 329
HCC with vascular invasion......Page 330
Assessment of Liver Functional Reserve......Page 331
References......Page 335
Introduction......Page 340
Problems Associated with Cirrhotic Liver Resection for HCC......Page 341
Patient selection criteria......Page 343
Determination of extent of liver resection......Page 344
Controlling bleeding and limiting blood transfusion in cirrhotic patients......Page 348
Patient management......Page 352
Policy of intra-abdominal drain......Page 353
References......Page 354
Introduction......Page 360
Technique of PVE......Page 362
Transileocolic venous approach......Page 363
Transhepatic approach......Page 364
Embolization materials......Page 365
Portal pressure after PVE......Page 367
Volumetric changes after PVE......Page 368
Functional changes after PVE......Page 370
Indication of PVE for HCC patients......Page 371
Role of transcatheter arterial chemoembolization (TACE)......Page 372
Effect of PVE on diseased liver......Page 373
Results of hepatic resection after PVE......Page 375
References......Page 377
Introduction......Page 382
Technical Aspects......Page 383
Ultrasound liver anatomy......Page 384
Detection and differentiation of liver nodules......Page 387
Tumor location......Page 391
Types of surgical approaches......Page 392
Liver parenchymal dissection......Page 399
Postresectional control......Page 405
References......Page 406
16. Surgical Treatment Jacques Belghiti......Page 410
Radiological Imaging......Page 411
Patient Selection......Page 413
Preoperative Evaluation of Liver Functional Reserve......Page 415
HCC with Chronic Liver Disease......Page 417
Improvement of surgical resection......Page 418
Anterior approach......Page 419
Results of Liver Resection......Page 420
Liver Resection and Liver Transplantation (LT)......Page 421
References......Page 423
Introduction......Page 432
Theoretical Advantages of the Anterior Approach......Page 433
The Hanging Maneuver: Principles and Technical Procedure......Page 435
Results of the Anterior Approach and of the Liver Hanging Maneuver......Page 438
References......Page 440
Introduction......Page 442
Rationale for Segment-based Liver Resection......Page 443
Technique of Segment-based Liver Resection......Page 445
Surface anatomy + IOUS......Page 446
Preliminary control of the vascular pedicles of the segment to be removed......Page 447
Selective portal venous occlusion using a balloon catheter through a branch of the superior mesenteric vein......Page 448
References......Page 449
Introduction......Page 452
Intrafascial or hilar (extrahepatic) approach......Page 453
Extrafascial approach1,4–10......Page 454
Principles of the anterior intrahepatic approach......Page 456
Approach to the confluence, the right main pedicle, and the right medial pedicle......Page 458
Hepatectomies......Page 462
Sectorectomies and Segmentectomies......Page 465
Indications and Discussion......Page 466
References......Page 468
Introduction......Page 470
Indications......Page 471
Operative Procedure......Page 473
Identification of tumor-bearing segment/subsegment......Page 474
Recognition of the correct ligation point on the portal branch......Page 476
Resection of the liver parenchyma under intermittent blood inflow occlusion......Page 477
Anatomic resection of segment 8......Page 479
Other types of segmentectomies......Page 481
Prognostic Impact of Segmentectomy/Subsegmentectomy......Page 482
References......Page 484
Introduction......Page 488
Anatomy......Page 489
Surgical Approaches to Caudate Lobectomy......Page 492
Indications......Page 493
Taping the IVC......Page 494
Detachment from the IVC and the third porta hepatis......Page 495
Detachment from the hilum and the first porta hepatis......Page 496
Detachment from the neighboring liver, hepatic veins, and second porta hepatis......Page 497
Indications......Page 500
Surgical procedure......Page 501
Retrograde caudate lobectomy......Page 506
Dissection of the SHVs through a thickened caudate margin......Page 508
Application of the liver hanging maneuver......Page 510
References......Page 511
Introduction......Page 514
Indications (See Table 1)......Page 515
Instrumentation......Page 517
Limited resection......Page 519
Laparoscopic left lateral sectionectomy......Page 520
Right hepatectomy......Page 521
Results......Page 522
Complications......Page 523
The Role of Laparoscopic Liver Resection......Page 524
Conclusions......Page 525
References......Page 526
Introduction......Page 530
Technique......Page 531
Indications......Page 534
Technique......Page 535
Total Vascular Exclusion......Page 536
Technique......Page 537
Complications of Vascular Clamping......Page 539
Protective Strategies Against Prolonged Ischemia During Vascular Clamping......Page 540
Intermittent portal triad clamping......Page 541
Ischemic preconditioning with continuous inflow occlusion......Page 542
Intermittent portal triad clamping versus ischemic preconditioning......Page 543
Continuous inflow occlusion under in situ hypothermia......Page 544
Acknowledgment......Page 545
References......Page 546
Introduction......Page 552
Kelly Clamp Technique......Page 553
Ultrasonic Dissection......Page 554
Staplers......Page 555
Hydrojet......Page 557
Radiofrequency Energy......Page 559
LigaSure......Page 561
Harmonic Scalpel......Page 563
Wedge resection with parenchymal compression......Page 564
Vascular isolation......Page 565
Total vascular isolation......Page 566
Low central venous pressure......Page 567
Comparisons of Liver Transection Techniques......Page 568
References......Page 570
Introduction......Page 574
Principles......Page 575
Design of the Habib 4X......Page 576
Position of patient......Page 579
Dissection......Page 580
Transection of liver parenchyma......Page 582
Tumorectomy or segmentectomy......Page 586
Complications......Page 587
References......Page 589
Introduction......Page 592
Rationale for Cytoreduction......Page 593
Outcome of Cytoreductive Surgery for HCC......Page 595
Cytoreduction by Radiofrequency Ablation (RFA)......Page 597
Challenges of Cytoreductive Surgery for HCC......Page 599
References......Page 600
Introduction......Page 606
The History of Cryosurgery......Page 608
In vitro freezing of tissue......Page 609
Animal models......Page 610
Single Versus Double Freeze–Thaw Cycles......Page 611
Patient Selection: Indications for Hepatic Cryotherapy in HCC......Page 612
Preoperative investigation and preparation......Page 614
Equipment and personnel......Page 615
Operative approach......Page 618
Intraoperative ultrasound (IOUS) (Fig. 5)......Page 619
Cryoprobe placement and freezing process......Page 620
Laparoscopic cryosurgery......Page 622
Cracking of the treated lesion......Page 623
Biloma or bile fistula......Page 625
Cryoshock......Page 626
Efficacy of the Treatment of HCC with Cryosurgery (Table 2)......Page 627
Conclusions......Page 628
References......Page 629
Historical Overview and Introduction......Page 636
Epidemiology......Page 637
Clinical Presentation and Diagnosis......Page 639
Diagnostic Imaging Evaluation......Page 640
Staging (TNM, Okuda, CLIP, BCLC)......Page 645
Prognostic Factors and Selection Criteria......Page 649
Organ Allocation (MELD, UNOS)......Page 652
Orthotopic Liver Transplantation......Page 653
Living Donor Liver Transplantation (LDLT)......Page 654
Other Issues......Page 657
References......Page 658
Introduction......Page 668
Percutaneous ethanol injection (PEI)......Page 669
Radiofrequency ablation (RFA)......Page 670
Evaluation of Therapeutic Efficacy......Page 671
Percutaneous ethanol injection......Page 672
Radiofrequency ablation......Page 673
Conclusions......Page 674
References......Page 679
Introduction......Page 684
Transarterial Embolization (TAE)......Page 685
Transarterial Chemoembolization (TACE)......Page 686
Patient selection for TACE......Page 689
Complications of TACE......Page 690
TACE in unresectable HCC......Page 691
Downstaging of unresectable HCC by TACE to become resectable......Page 693
Adjuvant TACE after curative liver resection......Page 694
Neoadjuvant/Adjuvant TACE for liver transplantation......Page 695
TACE combined with other treatments......Page 696
Transarterial Radioembolization (TARE)......Page 697
Iodine-131(131I)–Lipiodol......Page 698
Neoadjuvant/Adjuvant transarterial 131I-lipiodol......Page 700
Yttrium-90 ( 90Y) microspheres......Page 701
Glass-based 90Y microspheres......Page 703
References......Page 705
31. Systemic Chemotherapy ThomasW. T. Leung......Page 718
Introduction......Page 719
Efficacy of Systemic Chemotherapy......Page 720
New Approaches in Systemic Chemotherapy......Page 726
Conclusions......Page 727
References......Page 728
Introduction......Page 732
Neoadjuvant transarterial chemoembolization (TACE)......Page 734
Adjuvant regional therapy......Page 736
Adjuvant regional and systemic therapy......Page 738
Adjuvant transarterial radioembolization (TARE)......Page 739
Adjuvant immunotherapy......Page 741
Chemoprevention with vitamin analog therapy after curative liver resection......Page 742
Neoadjuvant/Adjuvant Therapy in Liver Transplantation for HCC......Page 743
Neoadjuvant TACE......Page 744
Neoadjuvant local ablative therapy......Page 745
Salvage Surgery After Tumor Downstaging of Advanced HCC......Page 746
Indication and prerequisites for salvage surgery and tumor downstaging......Page 747
Results of salvage surgery after tumor downstaging Tumor downstaging with TACE......Page 748
Tumor downstaging with TAC......Page 749
Tumor downstaging with multimodality therapy......Page 750
Prognosis and survival......Page 751
References......Page 753
Introduction......Page 762
Liver resection......Page 763
TAC/TACE......Page 770
TARE/External radiotherapy......Page 772
Combination therapy......Page 775
References......Page 778
34. Palliative Care Winnie Yeo and Anthony T. C. Chan......Page 784
Quality-of-life assessment......Page 787
Cost of palliative care......Page 789
References......Page 791
Introduction......Page 796
Spontaneous Rupture......Page 797
Jaundice......Page 803
Esophageal Variceal Hemorrhage......Page 809
Hypoglycemia......Page 810
Erythrocytosis......Page 811
References......Page 812
Introduction......Page 816
Etiology......Page 817
Management......Page 819
Hepatocyte Transplantation......Page 821
Liver Dialysis (Liver Support)......Page 822
Artificial Liver Support......Page 824
Bioartificial Liver (BAL) Support......Page 825
Liver Transplantation......Page 827
Conclusions......Page 829
References......Page 830
Introduction......Page 836
High-Intensity Focused Ultrasound (HIFU)......Page 837
Conformal Radiotherapy......Page 840
Stereotactic Radiotherapy......Page 842
Proton Beam Therapy......Page 843
References......Page 844
Author Index......Page 850
Index......Page 852