Hepatocellular Carcinoma

The following sections are included:

• Preface

• Acknowledgments

• Contents

• List of Contributors

The following sections are included:

• Introduction

• Geographic Distribution

• Risk Factors
  • Age and gender
  • Genetic and congenital abnormalities
  • Cirrhosis
  • Hepatitis B virus (HBV)
  • Hepatitis C virus (HCV)
  • Other hepatitis viruses
  • Plant carcinogens
  • Chemical carcinogens
  • Radiation and Thorotrast
  • Miscellaneous factors

• Precancerous Changes and Hepatocarcinogenesis

• Relationship of Etiological Agents and Molecular Events

• References

This chapter presents modern terminology of liver anatomy and resection. It is also an introduction to surgical anatomy of the liver. No single chapter can describe the anatomy of the liver in detail. The intention is to provide an anatomical foundation for performing liver resection and a terminological foundation for describing those procedures so that surgeons around the world can understand each other when they communicate orally or in writing. Surgically unimportant anatomic features are omitted. The chapter has two parts. The first part deals with terminology; the anatomical concepts introduced are those necessary to explain the basis of the terminology selected. The second part deals more formally with surgical anatomy.

The following sections are included:

• Introduction

• Passive/Steady-State Tests
  • Bilirubin
  • Transaminases
  • Alkaline phosphatase
  • Albumin
  • Prothrombin time
  • Prognostic clinicolaboratory scoring
  • Child–Pugh score
  • Model for End-stage Liver Disease (MELD)
  • Okuda score and Calvet system

• Bioenergetic Tests
  • Peripheral blood redox state
  • Tissue adenine nucleotide and mitochondrial analysis
  • Magnetic resonance spectroscopy

• Radiological Imaging and Qualitative Assessments

• Dynamic Tests
  • Clearance tests
  • Indocyanine green (ICG) test
  • Microsomal capacity tests
    • Aminopyrine
    • Lidocaine and MEGX
  • Hexose sugar metabolic capacity
    • Galactose elimination capacity
    • Glucose load: redox tolerance test
    • Fructose tolerance test
  • Hepatobiliary uptake and excretion scintigraphy
  • Asialoglycoprotein receptor scintigraphy
  • Regenerative capacity: portal vein embolization

• Longitudinal Evaluation After Hepatectomy

• References

The following sections are included:

• Is There a Need to Prevent Hepatocellular Carcinoma?

• Definition of Cancer Prevention

• Etiology of Hepatocellular Carcinoma
  • Chronic hepatitis B virus infection
  • Chronic hepatitis C virus infection
  • Cirrhosis
  • Aflatoxins
  • Iron storage diseases
  • Nonalcoholic steatohepatitis (NASH)
  • Microcystins
  • Membranous obstruction of the inferior vena cava
  • Inherited metabolic disorders
    • Alpha-1 antitrypsin deficiency
    • Hereditary tyrosinemia type 1
    • Glycogen storage diseases
    • Type II hypercitrullinemia
    • Wilson's disease

• Prevention of Hepatocellular Carcinoma
  • Primary prevention
    • Immunization against hepatitis B virus infection
    • Immunization against hepatitis C virus infection
    • Other forms of primary prevention against hepatitis B and C virus infections
    • Prevention of exposure to aflatoxin B1 (AFB₁)
    • Dietary iron overload in the African
    • Nonalcoholic steatohepatitis (NASH)
    • Blue-green algae and microcystins
    • Membranous obstruction of the inferior vena cava
  • Secondary prevention
    • Chemoprevention of aflatoxin B₁-induced hepatocellular carcinoma
    • Polyprenoic acid
    • Other chemoprevention possibilities
    • Iron storage diseases
    • α1 antitrypsin (α1AT) deficiency
    • Glycogen storage disease
    • Hereditary tyrosinemia type 1
    • Type II hypercitrullinemia
    • Wilson's disease
  • Tertiary prevention
    • Use of interferon-α in preventing hepatitis C virus-induced hepatocellular carcinoma
    • Use of interferon-α in preventing chronic hepatitis B virus–induced hepatocellular carcinoma
    • Glycyrrhizin
    • Inherited metabolic diseases

• Prevention of Recurrence of Hepatocellular Carcinoma

• References

The following sections are included:

• Introduction

• Screening Tests

• Surveillance Interval

• Target Populations

• Who Should Not Be Screened?

• Does Screening Reduce HCC-related Mortality?

• Dealing with Abnormal Screening Test Results

• A Screening Program

• Summary

• References

The following sections are included:

• Introduction

• Clinical Presentation: Epidemiologic Differences

• Clinical Presentation: Signs and Symptoms

• References

The following sections are included:

• Introduction

• Oncofetal Antigens and Glycoprotein Antigens
  • Alpha-fetoprotein, alpha-fetoprotein–L3, and monosialylated alpha-fetoprotein
  • Glypican-3

• Enzymes and Isoenzymes
  • Gamma-glutamyl transferase
  • Alpha-L-fucosidase
  • Des-gamma-carboxy prothrombin
  • Golgi protein 73 (GP73)

• Growth Factors and Cytokines
  • Vascular endothelial growth factor
  • Interleukin-8
  • Transforming growth factor-beta 1
  • Tumor-specific growth factor

• Combined Multiple Tumor Markers

• Genes
  • Alpha-fetoprotein (AFP) mRNA
  • Gamma-glutamyl transferase (GGT) mRNA
  • Oncogenes, tumor suppressors, and telomerase reverse transcriptase

• Conclusions

• References

The following sections are included:

• Introduction

• Incidence and Etiology

• Pathology and Imaging Features of HCC

• The Imaging of HCC
  • Ultrasonography
  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Angiography
  • Positron emission tomography (PET)

• Conclusions

• References

The following sections are included:

• Introduction

• Gross Appearance

• Microscopic Appearances
  • Architectural variants
  • Cytological variants
  • Cytoplasmic inclusions

• Grading

• Natural History and Spread

• Prognostic Features

• Precursor Lesions
  • Small HCC
  • Dysplasia
  • Dysplastic nodules
  • Hepatocellular adenoma

• Benign Lesions
  • Focal nodular hyperplasia (FNH)
  • Nodular regenerative hyperplasia

• Combined HCC and Cholangiocarcinoma

• Liver Carcinoma in Children
  • Childhood HCC
  • Hepatoblastoma

• Immunohistology

• Conclusions

• References

The following sections are included:

• Introduction

• Molecular Analysis of Hepadnavirus Infection and HCC
  • The life cycle of HBV and the genomes of HBV and HCV
  • Insertional mutagenesis and cis-activation of cellular genes by HBV DNA
  • Trans-activation of cellular genes by HBV DNA

• Interactions Between Chemical Carcinogens, HBV, and Cellular Genes

• “Yin–Yang” (Negative and Positive) Regulation of Hepatocarcinogenesis: Alterations of Proto-oncogenes, Tumor Suppressors, and Other Critical Genes in HCC

• Genomic Instability and Chromosomal Alterations in HCC
  • Allelotyping
  • Comparative genomic hybridization analysis
  • Chromosome 16q and E-cadherin
  • Chromosome 17p and p53
  • Chromosome 13q and Rb and BRCA2
  • Chromosome 8p and the platelet-derived growth factor (PDGF) receptor β–like tumor suppressor
  • Chromosome 9p and p16
  • Other chromosomal alterations
  • Reactivation of telomerase activity in HCC

• Reactive Oxygen Species and HCC
  • Chronic viral infections and ROSs
  • Carcinogens and ROSs
  • Xenobiotics and ROSs
  • Growth factors, oncogenes, and ROSs
  • Enzymes for metabolizing ROSs
  • Human HCC and ROSs

• Gene Profiling, Microarray, and Proteomics in HCC

• Gene Transfer and Immunotherapy in HCC

• Conclusions

• References

The following sections are included:

• Introduction

• TNM

• Okuda

• Groupe d'Etude de Traitement du Carcinome Hepatocellulaire (GRETCH)

• Cancer of the Liver Italian Program (CLIP)

• Barcelona Clinic Liver Cancer (BCLC)

• Chinese University Prognostic Index (CUPI)

• Japanese Integrated Staging (JIS)

• Modified CLIP and JIS Staging Systems

• 2002 Consensus Conference

• Discussion

• References

The following sections are included:

• Introduction

• Assessment of Tumor Extent
  • Size of HCC
  • HCC with adjacent organ involvement
  • HCC with vascular invasion

• Assessment of General Condition of Patient

• Assessment of Liver Functional Reserve

• Conclusion

• References

The following sections are included:

• Introduction

• Problems Associated with Cirrhotic Liver Resection for HCC

• Strategies and Solutions for Problems in Cirrhotic Liver Resection
  • Preoperative assessment
    • Patient selection criteria
    • Determination of extent of liver resection
  • Intraoperative assessment
    • Controlling bleeding and limiting blood transfusion in cirrhotic patients
  • Postoperative assessment
    • Patient management
    • Infection control
    • Policy of intra-abdominal drain

• Conclusions

• References

The following sections are included:

• Introduction

• General Remarks on PVE
  • Technique of PVE
    • Transileocolic venous approach
    • Transhepatic approach
  • Embolization materials
  • Portal pressure after PVE
  • Clinical course after PVE
  • Volumetric changes after PVE
  • Histological changes after PVE
  • Functional changes after PVE

• PVE for HCC
  • Indication of PVE for HCC patients
  • Role of transcatheter arterial chemoembolization (TACE)
  • Effect of PVE on diseased liver
  • Results of hepatic resection after PVE

• Conclusions

• References

The following sections are included:

• Introduction

• Technical Aspects
  • Ultrasound liver anatomy

• Indications
  • Liver exploration
    • Detection and differentiation of liver nodules
    • Tumor location
  • Resection guidance
    • Types of surgical approaches
    • Liver parenchymal dissection
    • Postresectional control

• Conclusions

• References

The following sections are included:

• Patient Assessment for Partial Liver Resection

• Radiological Imaging

• Histological Diagnosis by Fine-Needle Aspiration Biopsy

• Patient Selection

• Preoperative Evaluation of Liver Functional Reserve

• HCC without Chronic Liver Disease

• HCC with Chronic Liver Disease
  • Extent of resection
  • Improvement of surgical resection
    • Intermittent inflow occlusion
    • Anterior approach

• Recurrence Following Resection of HCC

• Results of Liver Resection

• Liver Resection and Liver Transplantation (LT)

• References

The following sections are included:

• Introduction

• Theoretical Advantages of the Anterior Approach

• The Hanging Maneuver: Principles and Technical Procedure

• Results of the Anterior Approach and of the Liver Hanging Maneuver

• Conclusions

• References

The following sections are included:

• Introduction

• Rationale for Segment-based Liver Resection

• Technique of Segment-based Liver Resection
  • Surface anatomy + IOUS
  • Preliminary control of the vascular pedicles of the segment to be removed
  • Ultrasound-guided puncture of portal vein branch and injection of dye
  • Selective portal venous occlusion using a balloon catheter through a branch of the superior mesenteric vein

• Nonanatomical Liver Resection

• References

The following sections are included:

• Introduction

• Different Approaches to the Glissonian Sheaths
  • Intrafascial or hilar (extrahepatic) approach
  • Extrafascial approach
  • Transfissural (or intrahepatic) approach
    • Principles of the anterior intrahepatic approach
    • Posterior intrahepatic approach (through the dorsal fissure)
  • Approach to the confluence, the right main pedicle, and the right medial pedicle
  • Approach to the right lateral pedicle

• Hepatectomies

• Sectorectomies and Segmentectomies

• Indications and Discussion

• References

The following sections are included:

• Introduction

• Indications

• Operative Procedure
  • Identification of tumor-bearing segment/subsegment
  • Recognition of the correct ligation point on the portal branch
  • Resection of the liver parenchyma under intermittent blood inflow occlusion
  • Anatomic resection of segment 8
  • Other types of segmentectomies

• Prognostic Impact of Segmentectomy/Subsegmentectomy

• Acknowledgments

• References

The following sections are included:

• Introduction

• Anatomy

• Surgical Approaches to Caudate Lobectomy

• Isolated Resection of the Caudate Lobe by the Bilateral Approach
  • Indications
  • Surgical procedures
  • Mobilization of the liver
  • Taping the IVC
  • Taping the common trunk of the MHV and LHV
  • Taping the RHV
  • Detachment from the surrounding structures
  • Detachment from the IVC and the third porta hepatis
  • Detachment from the hilum and the first porta hepatis
  • Detachment from the neighboring liver, hepatic veins, and second porta hepatis

• Isolated Resection of the Caudate Lobe by the Anterior Approach
  • Indications
  • Surgical procedure

• Special Procedures for Special Conditions
  • Retrograde caudate lobectomy
  • Dissection of the SHVs through a thickened caudate margin

• Tips and Tricks for a Safe Caudate Lobe Resection
  • Adequate abdominal incision
  • Taping of major veins
  • IVC control with fingers
  • Application of the liver hanging maneuver

• References

The following sections are included:

• Introduction

• Indications

• Patient and Instrument Positioning
  • Patient positioning and trocar placement
  • Instrumentation

• Procedures
  • Limited resection
  • Laparoscopic left lateral sectionectomy
  • Laparoscopic left hepatectomy
  • Right hepatectomy
  • Hand-assisted technique

• Results

• Complications

• The Role of Laparoscopic Liver Resection

• Conclusions

• References

The following sections are included:

• Introduction

• Inflow Occlusion of the Portal Triad (Pringle Maneuver)
  • Technique
  • Indications

• Selective Vascular Inflow Occlusion
  • Technique
  • Indications

• Total Vascular Exclusion
  • Technique
  • Indications

• Complications of Vascular Clamping

• Protective Strategies Against Prolonged Ischemia During Vascular Clamping
  • Intermittent portal triad clamping
  • Ischemic preconditioning with continuous inflow occlusion
  • Intermittent portal triad clamping versus ischemic preconditioning
  • Continuous inflow occlusion under in situ hypothermia

• Conclusions

• Acknowledgment

• References

The following sections are included:

• Introduction

• Kelly Clamp Technique

• Ultrasonic Dissection

• Staplers

• Hydrojet

• Dissecting Sealer (TissueLink)

• Radiofrequency Energy

• LigaSure

• Harmonic Scalpel

• Minimizing Blood Loss
  • Application of clips
  • Wedge resection with parenchymal compression
  • Vascular isolation
  • Total vascular isolation
  • Low central venous pressure

• Comparisons of Liver Transection Techniques

• References

The following sections are included:

• Introduction

• Principles

• Design of the Habib 4X

• Operations
  • Preoperative assessment
  • Operation
    • Position of patient
    • Incision
    • Examination and mobilization of the liver
  • Right hepatectomy
    • Dissection
    • Transection of liver parenchyma
  • Left hepatectomy
    • Dissection
    • Transection of liver parenchyma
  • Left lateral sectionectomy
    • Dissection
    • Transection of liver parenchyma
  • Tumorectomy or segmentectomy

• Postoperative Care
  • Complications

• References

The following sections are included:

• Introduction

• Rationale for Cytoreduction

• Outcome of Cytoreductive Surgery for HCC

• Modalities of Cytoreductive Surgery

• Cytoreduction by Radiofrequency Ablation (RFA)

• Cytoreduction for Extrahepatic Disease

• Challenges of Cytoreductive Surgery for HCC

• Conclusions

• References

The following sections are included:

• Introduction

• The History of Cryosurgery

• Mechanism of Tissue Destruction by Freezing
  • In vitro freezing of cells
  • In vitro freezing of tissue
  • In vivo freezing of tumors
    • Animal models
    • Human liver tumors

• Single Versus Double Freeze–Thaw Cycles

• Hepatic Inflow Occlusion

• Patient Selection: Indications for Hepatic Cryotherapy in HCC

• Techniques
  • Preoperative investigation and preparation
  • Surgical technique
    • Equipment and personnel
    • Operative approach
    • Cryoprobe placement and freezing process
    • Cryotherapy close to blood vessels
    • Laparoscopic cryosurgery

• Morbidity and Mortality Following Hepatic Cryosurgery
  • Intraoperative hypothermia
  • Cardiac rhythm disturbances
  • Cracking of the treated lesion
  • Fever
  • Pleural effusion and chest infection
  • Subphrenic or hepatic abscess
  • Biloma or bile fistula
  • Postoperative changes in serum liver function tests (LFTs) and platelet count
  • Cryoshock

• Efficacy of the Treatment of HCC with Cryosurgery

• Conclusions

• References

The following sections are included:

• Historical Overview and Introduction

• Epidemiology

• Clinical Presentation and Diagnosis

• Diagnostic Imaging Evaluation

• Staging (TNM, Okuda, CLIP, BCLC)

• Prognostic Factors and Selection Criteria

• Organ Allocation (MELD, UNOS)

• Orthotopic Liver Transplantation

• Living Donor Liver Transplantation (LDLT)

• Other Issues

• References

The following sections are included:

• Introduction

• Principles and Techniques
  • Percutaneous ethanol injection (PEI)
  • Radiofrequency ablation (RFA)

• Evaluation of Therapeutic Efficacy

• Results
  • Percutaneous ethanol injection
  • Radiofrequency ablation

• Conclusions

• References

The following sections are included:

• Introduction

• Transarterial Embolization (TAE)

• Transarterial Chemotherapy (TAC)

• Transarterial Chemoembolization (TACE)
  • Patient selection for TACE
  • Complications of TACE
  • TACE in unresectable HCC
  • Downstaging of unresectable HCC by TACE to become resectable
  • TACE as neoadjuvant therapy before curative liver resection
  • Adjuvant TACE after curative liver resection
  • Neoadjuvant/Adjuvant TACE for liver transplantation
  • TACE for recurrent HCC after curative liver resection
  • TACE combined with other treatments

• Transarterial Radioembolization (TARE)
  • Iodine-131(¹³¹I)-Lipiodol
  • Neoadjuvant/Adjuvant transarterial ¹³¹I-lipiodol
  • Rhenium-188–HDD/lipiodol
  • Yttrium-90 (90Y) microspheres
    • Glass-based ⁹⁰Y microspheres
    • Resin-based ⁹⁰Y microspheres

• References

The following sections are included:

• Introduction

• Efficacy of Systemic Chemotherapy

• New Approaches in Systemic Chemotherapy

• Predicting Response to Systemic Chemotherapy

• Conclusions

• References

The following sections are included:

• Introduction

• Neoadjuvant/Adjuvant/Chemoprevention Therapy in Liver Resection for HCC
  • Neoadjuvant transarterial chemoembolization (TACE)
  • Adjuvant regional chemotherapy with or without embolization
    • Adjuvant regional therapy
    • Adjuvant regional and systemic therapy
    • Neoadjuvant plus adjuvant regional therapy
  • Adjuvant systemic chemotherapy
  • Adjuvant transarterial radioembolization (TARE)
  • Adjuvant immunotherapy
  • Chemoprevention with vitamin analog therapy after curative liver resection

• Neoadjuvant/Adjuvant Therapy in Liver Transplantation for HCC
  • Neoadjuvant TACE
  • Neoadjuvant local ablative therapy
  • Neoadjuvant multimodality therapy
  • Neoadjuvant/Adjuvant systemic chemotherapy

• Salvage Surgery After Tumor Downstaging of Advanced HCC
  • Indication and prerequisites for salvage surgery and tumor downstaging
  • Rationale for salvage surgery after successful tumor downstaging
  • Results of salvage surgery after tumor downstaging
    • Tumor downstaging with TACE
    • Tumor downstaging with TAC
    • Tumor downstaging with multimodality therapy
  • Challenges of tumor downstaging
  • Prognosis and survival

• References

The following sections are included:

• Introduction

• Diagnosis

• Treatment
  • Curative therapy
    • Liver resection
  • Palliative therapy
    • TAC/TACE
    • TARE/External radiotherapy
    • Chemoimmunotherapy
    • Combination therapy

• References

The following sections are included:

• Two Aspects in the Assessment of Effectiveness of Palliative Care
  • Quality-of-life assessment
  • Cost of palliative care

• Conclusions

• References

The following sections are included:

• Introduction

• Spontaneous Rupture

• Jaundice

• Esophageal Variceal Hemorrhage

• Paraneoplastic Syndromes
  • Hypoglycemia
  • Erythrocytosis
  • Hypercalcemia
  • Hypercholesterolemia

• References

The following sections are included:

• Introduction

• Definition

• Etiology

• Management

• Hepatocyte Transplantation

• Hepatectomy Prior to Transplantation

• Extracorporeal Liver Perfusion

• Liver Dialysis (Liver Support)

• Artificial Liver Support

• Bioartificial Liver (BAL) Support

• Liver Transplantation

• Conclusions

• References

The following sections are included:

• Introduction

• High-Intensity Focused Ultrasound (HIFU)

• Conformal Radiotherapy

• Stereotactic Radiotherapy

• Proton Beam Therapy

• Conclusions

• References

The following sections are included:

• Author Index

• Index