Hepatocellular Carcinoma

Foreword
Foreword
Preface
Contents
Part I: Overview
	1: Epidemiological Aspects of Hepatocellular Carcinoma
		1.1	 Incidence and Mortality
		1.2	 Prevalence
		1.3	 Survival of Patients Diagnosed with Hepatocellular Carcinoma
		1.4	 Main Risk Factors for Hepatocellular Carcinoma
		1.5	 Conclusion
		References
	2: Molecular and Genetic Mechanisms of Hepatocellular Carcinoma
		2.1	 Introduction
		2.2	 Genetic Landscape of Hepatocellular Carcinoma
		2.3	 Hepatocellular Carcinoma and Mendelian Disorders
		References
	3: Role of the Immune System in Hepatocellular Carcinoma
		3.1	 General Aspects
		3.2	 Innate Immune System
			3.2.1	 Macrophages
			3.2.2	 Myeloid-Derived Suppressor Cells
			3.2.3	 Kupffer Cells
			3.2.4	 Neutrophils
			3.2.5	 Natural Killer Cells
			3.2.6	 Dendritic Cells
		3.3	 Adaptive Immune System
			3.3.1	 Interleukins and Chemokines
		3.4	 Conclusions
		References
	4: Underlying Liver Disease
		4.1	 Introduction
		4.2	 Viruses and Hepatocellular Carcinoma
			4.2.1	 Hepatitis B Virus
			4.2.2	 Hepatitis C Virus
			4.2.3	 Hepatitis Delta Virus
		4.3	 Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis
		4.4	 Alcoholic Fatty Disease
		4.5	 Hereditary Hemochromatosis
		4.6	 Autoimmune Hepatitis and Primary Biliary Cholangitis
		4.7	 Wilson Disease
		4.8	 Alpha 1-Antitrypsin Deficiency
		References
Part II: Diagnosis
	5: Imaging of Hepatocellular Carcinoma
		5.1	 Role of Ultrasound and Contrast-Enhanced Ultrasound
		5.2	 Computed Tomography Technique
		5.3	 Magnetic Resonance Imaging Technique and Contrast Agents
		5.4	 Imaging Features of Hepatocellular Carcinoma
		5.5	 Liver Imaging Reporting and Data System (LI-RADS)
		5.6	 Treatment Response: mRECIST and LI-RADS
			5.6.1	 LI-RADS Treatment Response Algorithm
		References
	6: Pathology of Hepatocellular Carcinoma
		6.1	 Introduction
		6.2	 Main Gross Pattern of Hepatocellular Carcinoma
		6.3	 Histology
		6.4	 Grading, Staging, and Metastases
		6.5	 Immunohistochemistry
		6.6	 Variants
		6.7	 Differential Diagnosis
		References
	7: Hepatological Evaluation and Biomarkers
		7.1	 Introduction
			7.1.1	 Etiologies of Liver Disease: Metabolic-Associated Fatty Liver Disease
		7.2	 Methods to Evaluate Liver Function and Hepatic Reserve Before Surgery
			7.2.1	 Predictors of Post-hepatectomy Liver Failure
			7.2.2	 Biomarkers and Dynamic Test to Recognize Liver Function and Its Reserve Capacity
			7.2.3	 MELD Score
			7.2.4	 Fibrosis Biomarkers and Noninvasive Evaluation of Portal Hypertension
		7.3	 Conclusion
		References
Part III: Treatment
	8: Percutaneous and Laparoscopic-Assisted Ablation of Hepatocellular Carcinoma
		8.1	 Introduction
		8.2	 Treatment Indications
		8.3	 Ablation Techniques
		8.4	 Oncological Outcomes
		References
	9: Endovascular Treatments of Hepatocellular Carcinoma
		9.1	 Introduction
		9.2	 Transarterial Chemoembolization
			9.2.1	 Technical Variations
		9.3	 Transarterial Radioembolization
			9.3.1	 Technical Considerations
			9.3.2	 Lessons Learned
			9.3.3	 Indications and Clinical Utility
			9.3.4	 Downstaging
			9.3.5	 Bridging
			9.3.6	 Palliation
		9.4	 Conclusion
		References
	10: Indications for Surgery in Cirrhotic Patients
		10.1	 Introduction
		10.2	 Hepatic Functional Reserve Assessment
			10.2.1	 Child-Turcotte-Pugh Score
			10.2.2	 Model for End-Stage Liver Disease
			10.2.3	 Indocyanine Green Clearance Test
			10.2.4	 Other Liver Function Scoring Systems
			10.2.5	 Evaluation of Portal Hypertension
			10.2.6	 Extent of Liver Resection and Functional Remnant Liver Volume Evaluation
		10.3	 Indications According to Tumor Stage, Survival Benefit, and Technical Considerations
		10.4	 Need for a Multidisciplinary Evaluation in High-Volume Centers
		References
	11: Laparoscopic Approach for the Treatment of Hepatocellular Carcinoma
		11.1	 Introduction
		11.2	 Short-Term Outcomes
		11.3	 Long-Term Outcomes
		11.4	 Advanced Cirrhosis and Portal Hypertension
		11.5	 Major Hepatectomies
		11.6	 Repeat Surgery
		11.7	 Elderly Patients
		11.8	 Difficulty Scores
		11.9	 Laparoscopic Approach for Local Ablation Therapy
		11.10	 Conclusion
		References
	12: Robotic Approach for the Treatment of Hepatocellular Carcinoma
		12.1	 Introduction
		12.2	 Patient Selection and Indications
		12.3	 Surgical Technique and Learning Curve
			12.3.1	 Patient Positioning and System Set-Up
			12.3.2	 Use of Indocyanine Green-Based Fluorescence
			12.3.3	 Parenchymal Transection
		12.4	 Postoperative Outcomes
		12.5	 Role of Robotics in Transplant Oncology
		12.6	 Conclusions
		References
	13: Ultrasound-Guided Liver Resection and Parenchymal-Sparing Surgery
		13.1	 Introduction
		13.2	 The Role of Ultrasound in Liver Surgery
			13.2.1	 Intraoperative Tumor Staging
			13.2.2	 Surgical Planning and Resection Guidance
		13.3	 Parenchymal Sparing Surgery for Hepatocellular Carcinoma: Surgical Technique
			13.3.1	 Ultrasound-Guided Minor Anatomical Resections
			13.3.2	 Ultrasound-Guided Non-anatomical Resections
		13.4	 Conclusion
		References
	14: Surgical Margins for Hepatocellular Carcinoma
		14.1	 Introduction
		14.2	 Pathophysiology of Hepatocellular Carcinoma
		14.3	 Anatomical Resections for Hepatocellular Carcinoma
		14.4	 Recurrence Following Surgery for Hepatocellular Carcinoma
		14.5	 Surgical Margins for Hepatocellular Carcinoma
		14.6	 Conclusions
		References
	15: Major Hepatectomies for  Hepatocellular Carcinoma
		15.1	 Introduction
		15.2	 Preoperative Management
		15.3	 Postoperative Outcomes of Major Hepatectomies for Hepatocellular Carcinoma
		15.4	 Oncological Outcomes of Major Hepatectomies for Hepatocellular Carcinoma
		15.5	 Laparoscopic Major Hepatectomies for Hepatocellular Carcinoma
		15.6	 Conclusions
		References
	16: R1-Vascular Surgery for Hepatocellular Carcinoma
		16.1	 Introduction
		16.2	 Anatomic Resection: Forty Years of Studies
		16.3	 To Expose or Not to Expose the Tumor on Cut Surface?
		16.4	 R1-Vascular Surgery Is the Roadmap for Parenchymal-Sparing Hepatectomy
		16.5	 Conclusions
		References
	17: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS)
		17.1	 Introduction
		17.2	 Indications for ALPPS
		17.3	 Technical Aspects
		17.4	 Outcomes
		17.5	 Conclusions
		References
	18: “Re-Do” Surgery for Hepatocellular Carcinoma: Indications and Results
		18.1	 Introduction
		18.2	 Types and Mechanisms of Hepatocellular Carcinoma Recurrence
		18.3	 Repeat Hepatectomy or Salvage Liver Transplant?
		18.4	 Repeat Hepatectomy Versus Other Treatments
		18.5	 Repeated Repeat Hepatectomy
		18.6	 Predictors of Recurrence After Repeat Hepatectomy
		18.7	 The Role of Minimally Invasive Surgery
		18.8	 Resection of Hepatocellular Carcinoma Recurrence After Liver Transplantation
		18.9	 Conclusions
		References
	19: Liver Transplantation for Hepatocellular Carcinoma
		19.1	 Introduction
		19.2	 Liver Transplantation for Hepatocellular Carcinoma: The Milan Criteria
		19.3	 Expanding Indications and Improving Results of Liver Transplantation for Hepatocellular Carcinoma
			19.3.1	 Role of Neoadjuvant Therapies: Bridging to Liver Transplantation, Salvage, and Pre-emptive Liver Transplantation
			19.3.2	 Beyond the Milan Criteria
			19.3.3	 Downstaging of Hepatocellular Carcinoma Before Liver Transplantation
			19.3.4	 Role of Adjuvant Treatments
		19.4	 Organ Allocation in Patients with Hepatocellular Carcinoma
		19.5	 Future of Liver Transplantation for Hepatocellular Carcinoma
		References
	20: Downstaging Strategies Prior to Liver Transplantation
		20.1	 Introduction
		20.2	 Indications
			20.2.1	 Morphological Criteria
			20.2.2	 Combining the Morphological with the Biological Criteria
			20.2.3	 The Issue of Portal Vein Thrombosis
		20.3	 When
		20.4	 How
			20.4.1	 Transarterial Chemoembolization
			20.4.2	 Transarterial Radioembolization
			20.4.3	 Ablative Therapies
			20.4.4	 Surgery
			20.4.5	 Combination Methods
		20.5	 Conclusions
		References
	21: Hepatocellular Carcinoma Medical Therapy
		21.1	 Introduction
		21.2	 First-Line Therapy
			21.2.1	 Single Agents
			21.2.2	 Combination Therapies
		21.3	 Second-Line Therapies
			21.3.1	 Single Agents
			21.3.2	 Emerging Combination Therapies
		21.4	 Conclusion
		References
Part IV: Special Considerations and Recommendations
	22: Surveillance for Patients at Risk of Developing Hepatocellular Carcinoma
		22.1	 Introduction
		22.2	 Effect of Surveillance on Outcomes
			22.2.1	 Surveillance Application
		22.3	 High Risk Groups
			22.3.1	 Patient with Cirrhosis
			22.3.2	 Patient with Hepatitis B Virus Infection Without Cirrhosis
			22.3.3	 Patients with Hepatitis C Virus Infection and Advanced Fibrosis
			22.3.4	 Patients with Non-alcoholic Steatohepatitis or Non-alcoholic Fatty Liver Disease
			22.3.5	 Patients Successfully Treated for Hepatitis C or B Virus Infection
		22.4	 Approach to Surveillance
			22.4.1	 Ultrasound in Combination with Serum Alpha-Fetoprotein
				22.4.1.1	 Cut-Off Value of Serum Alpha-Fetoprotein Applied to Surveillance
				22.4.1.2	 The Six-Month Interval
			22.4.2	 Proposed Imaging Techniques and Serology Markers for Surveillance
		References
	23: Hepatocellular Carcinoma Recurrence: How to Manage
		23.1	 Introduction
		23.2	 Clinical Setting and Risk Factors
		23.3	 Diagnostic Tools and Oncologic Monitoring
		23.4	 Clinical Decision-Making and Surgical Management
		23.5	 Conclusion
		References
	24: Liver Biopsy: How and When
		24.1	 Introduction
		24.2	 Indications and Technique
			24.2.1	 Contraindications and Risk Factors
			24.2.2	 Percutaneous Liver Biopsy
			24.2.3	 Transvenous/Transjugular Liver Biopsy
			24.2.4	 Endoscopic Ultrasound-Guided Liver Biopsy
			24.2.5	 Laparoscopic Liver Biopsy
			24.2.6	 Risk of Complications
			24.2.7	 Risk of Tumoral Seeding
		24.3	 Biopsy for Diagnosis of Hepatocellular Carcinoma
		24.4	 Biologic Information Obtainable from Biopsy
		24.5	 Role of Biopsy for Surgical Resection of Hepatocellular Carcinoma
		24.6	 Role of Biopsy for Liver Transplantation in Hepatocellular Carcinoma
		24.7	 Conclusions
		References
	25: Anesthesiologic Management During Surgery for Hepatocellular Carcinoma
		25.1	 Introduction
		25.2	 Preoperative Evaluation and Assessment of Liver Disease Severity
			25.2.1	 Risk Scores
			25.2.2	 Portal Hypertension
		25.3	 General Anesthesia
			25.3.1	 Vascular and Bleeding Control and Hemodynamic Monitoring
			25.3.2	 Acid-Base Issues
			25.3.3	 Coagulation and Blood Products
		25.4	 Pain Control
		25.5	 Postoperative Course
		25.6	 Conclusion
		References