This open access book offers a comprehensive review of hepatocellular carcinoma (HCC) with a particular focus on the pathobiology and clinical aspects of the disease, including diagnosis and treatment. HCC is becoming one of the most common causes of cancer-related death worldwide. It is the fifth most common malignancy in men and the ninth in women, with an estimated 500,000 to 1 million new cases annually around the world. Independent of its cause, cirrhosis is considered a major clinical and histopathological risk factor for HCC development. Five percent of all cirrhotic patients develop HCC every year. Diagnostic tools for HCC include blood tests, high-quality imaging studies and liver biopsy. The treatment of HCC depends on the size and location of the HCC and includes surgical resection, liver transplantation, endovascular approaches, percutaneous ablation, and medical treatments. The book is organized into four parts – overview, diagnosis, management strategies, and recommendations – and aims to provide surgeons and clinicians with a valuable resource for complete and up-to-date research on the clinical aspects and management of HCC.
Author(s): Giuseppe Maria Ettorre
Series: Updates in Surgery
Publisher: Springer
Year: 2022
Language: English
Pages: 216
City: Cham
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
