CHOLANGIOCARCINOMA

CHOLANGIOCARCINOMA

Library of Congress Cataloging-in-Publication Data

Contents

Preface

Chapter 1: Cholangiocarcinoma: Introduction

Aichi Cancer Center, Kanokoden, Chikusa-ku, Nagoya, Japan

Abstract

1. History of Surgical Challenges to Perihilar Cholangiocarcinoma

2. Anatomical Research of the Intrahepatic Bile Ducts

3. Advances in Surgical Techniques

4. Future Perspective

References

Chapter 2: Surgical Anatomy of the Biliary Tract

Abstract

Introduction

Typical Biliary Anatomy

Variations of Biliary Anatomy

Biliary Confluence and Common Hepatic Duct

The Gallbladder and Cystic Duct

Cystic Artery and Right Hepatic Artery

Conclusion

References

Chapter 3: New Insights into Epidemiology of Cholangiocarcinoma

Abstract

Introduction: Biases in Cholangiocarcinoma Epidemiology

Cholangiocarcinoma Worldwide Epidemiology

New Insights on Risk Factors of IH- and EH-CCA

Geoepidemiology of Cholangiocarcinoma, and Prevention Strategies

Conclusion

References

Chapter 4: Risk Factors of Cholangiocarcinoma

Abstract

Introduction

Bile Duct Disorders

Bile Duct Cysts

Primary Sclerosing Cholangitis (PSC)

Caroli’s Disease and Caroli Syndrome

Hepatolithiasis, Choledocholithiasis and Cholangitis

Parasitic Infestations

Liver Diseases

Cirrhosis and Nonalcoholic Fatty Liver Disease

Chronic Viral Hepatitis

Hemochromatosis and Wilson’s Disease

Personal and Environmental Risk Factors

Cigarette Smoking

Alcohol

Obesity and Diabetes Mellitus

Toxins and Asbestos

Genetic Polymorphisms

Conclusion

References

Chapter 5: Molecular Biology of Cholangiocarcinoma

Abstract

Introduction

Molecular Pathogenesis

Chromosomal Changes

Epigenetics

microRNAs (miRNAs)

Conclusion

References

Chapter 6: Carcinogenesis of Cholangiocarcinoma

Abstract

Introduction

Cell(s) of Origin and Primitive Liver Tumours

Stem Cell Niches in the Liver and Biliary Tree

Proposed Classification of Primitive Liver Tumours Based on Cells of Origin

Conclusion

References

Chapter 7: Histopathology of Cholangiocarcinoma

Abstract

Introduction

Macroscopy

Intrahepatic Cholangiocarcinoma

Hilar and Extrahepatic Cholangiocarcinoma

Histopathology

Grading

Histological Variants

Differential Diagnosis

Metastatic Adenocarcinoma

Hepatocellular Carcinoma

Bile Duct Adenoma/Peribiliary Gland Hamartoma

Biliary Adenofibroma

Von Meyenburg Complexes (Bile Duct Hamartomas)

Immunohistochemistry

Mucin Expression

Prognostic Immunohistochemical Markers

Pre-Cancerous and Early Lesions

Pathological Staging

Intrahepatic Cholangiocarcinoma

Hilar Cholangiocarcinoma (Klatskin Tumour)

Extrahepatic Cholangiocarcinoma

Conclusion

References

Chapter 8: Staging of Cholangiocarcinoma

Abstract

Introduction

Staging Intrahepatic Cholangiocarcinoma (iCCA)

Staging Perihilar Cholangiocarcinoma (pCCA)

Staging Distal Cholangiocarcinoma (dCCA)

Conclusion

References

Chapter 9: Clinical Features of Intrahepatic Cholangiocarcinoma

Abstract

Introduction

Clinical Signs and Symptoms at the Presentation

Associated Pathologies and CCA Clinical Presentation

Conclusion

References

Chapter 10: Extrahepatic Cholangiocarcinoma: Clinical Features

Abstract

Introduction

Specific Risk Factors for Hilar and Distal CCA

Extrahepatic Cholangiocarcinoma: Clinical Features

Conclusion

References

Chapter 11: Circulating Biomarkers

Abstract

Tumor Markers: Where We Are and Where We Are Going

Efficacy vs. Effectiveness: A Clinical Issue

What Clinical Practice Guidelines on Cholangiocarcinoma Say

What Review Articles Say

Future Directions

Conclusion

References

Chapter 12: Ultrasonography (US) / Contrast-Enhanced Ultrasonography (CEUS) for Cholangiocarcinoma

Abstract

Introduction

Perihilar Cholangiocarcinoma (Klatskin Tumor). Appearance at Conventional US

Distal Cholangiocarcinoma

Ceus of Extrahepatic CC

Intrahepatic Cholangiocarcinoma (ICC). Appearance at Conventional Ultrasound (B-mode US)

Mass Forming Type

Periductal Infiltrating Type

Intraductal Growing Type

Appearance of iCC at Contrast Enhanced Ultrasound (CEUS)

Conclusion

References

Chapter 13: Endoscopic Retrograde Cholangiopancreatography (ERCP) and Echoendoscopy for Cholangiocarcinoma

Abstract

Introduction

Endoscopic Ultrasound (EUS)

Role of EUS/FNA in the Diagnosis of CCA

Safety of EUS-FNA in CCA

Role of EUS-FNA in the Staging of CCA

Role of ERCP in the Diagnosis of CCA

Complications of ERCP

New Imaging Modalities

Intraductal Ultrasonography (IDUS)

Peroral Cholangioscopy

Optimal Coherence Tomography

Conofocal Laser Endomicroscopy

Conclusion

References

Chapter 14: Percutaneous Transhepatic Cholangiography (PTC) for Cholangiocarcinoma

Abstract

Introduction

Percutaneous Transhepatic Cholangiography

Indications

Technical Procedure

Diagnostic Efficacy and Limits

Complications

PTC/PTBD and Tissue Sampling

Percutaneous Transhepatic Biliary Drainage

Preoperative PTB

Percutaneous Stenting

Plastic Stents (PS)

Self-Expandable Metallic Stents (SEMS)

Technique

Complications

Covered Stents

Percutaneous versus Endoscopic Therapy

Percutaneous Intraluminal Brachytherapy

Conclusion

References

Chapter 15: Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) for Cholangiocarcinoma

Abstract

Introduction

Imaging Techniques Used in Classifying in Cholangiocarcinoma

MDCT

MDCT Limitations

MRI

Intrahepatic Cholangiocarcinoma

(iCCA)

Diagnosis of iCCA

Perihilar Cholangiocarcinoma (pCCA)

Diagnosis of pCCA

Distal Cholangiocarcinoma (dCCA)

Diagnosis of dCCA

Early Detection of CCA in High-Risk Patients

Conclusion

References

Chapter 16: Positron Emission Tomography (PET) for Cholangiocarcinoma

Abstract

Introduction

Warburg Effect As the Base of Increased Glucose Metabolism in Cancer

Historical Points of PET Imaging

Biochemical Pathway of [18F] FDG

Utility of SUV

The Role of FDG-PET in Clinical Oncology

Principles of Administration of PET Radiopharmaceuticals

Weaknesses of PET and Practical Solution to Bypass It

PET Imaging in Cholangiocarcinoma

Assessment of T Value

Ability of PET to Differentiate Benign and Malignant Pathology

Assessment of N and M Values

Conclusion

References

Chapter 17: Surgical Treatment for Intrahepatic Cholangiocarcinoma

Abstract

Introduction

Classification

Surgical Treatment

Prognostic Risk Factors

Tumor Number

Lymph Node Metastases

Resection Margins

Vascular Invasion

Relapse of Disease

Conclusion

References

Chapter 18: Surgical Treatment for Hilar Cholangiocarcinoma

Abstract

Introduction

Preoperative Management

Surgical Strategy

Preoperative Biliary Drainage

Preoperative Portal Vein Embolization (PVE)

Preoperative Evaluation of the Functional Reserve of the Remnant Liver

Other Preoperative Optimizations

Standard Surgery

Extended Surgery

Hepatic Trisectionectomy

Combined Vascular Resection

Hepatopancreatoduodenectomy

Conclusion

References

Chapter 19: Lymphadenectomy for Cholangiocarcinoma

Abstract

Introduction

Prognostic Relevance of Lymphadenectomy

Type and Extent of Lymphadenectomy

Conclusion

References

Chapter 20: Portal Vein Embolization and Cholangiocarcinoma

Abstract

Introduction

Indications and Technique

Ipsilateral vs Contralateral Approach for PVE

Transileocolic Approach for PVE

Transjugular Approach for PVE

Percutaneous Transhepatic Approaches for PVE

Timing of PVE in the Case of Hyperbilirubinemia and Use of Percutaneous Biliary Drainage

PVE versus Portal Vein Ligation

Liver Volume and Function Measurement

Indocyanine Green (ICG) Test and PVE

Clinical Outcomes after PVE

Conclusion

References

Chapter 21: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) for Cholangiocarcinoma

Abstract

Introduction

ALPPS Procedure and Rationale

ALPPS Results

Conclusion

References

Chapter 22: Liver Transplantation for Cholangiocarcinoma

Abstract

List of Abbreviations

Introduction

Early Experience and Rationale for the Current Protocol

Mayo Clinic Protocol

Selection/Transplant Eligibility Criteria

Neoadjuvant Therapy

Complications of Neoadjuvant Therapy

Staging Procedure

Transplantation Procedure Outline

Vascular and Biliary Complications Post Liver Transplant

Contemporary Outcomes of OLT for pCCA

Predictors of Pre-Transplant Dropout and Post-Transplant Recurrence

Measures to Improve Outcomes

Avoidance of Transperitoneal Tumor Sampling

Extension of the Donor Pool

Pancreatoduodenectomy

Donor Organ Prioritization

Adjuvant Therapy

Liver Transplantation for iCCA and Mixed Hepatocellular-Cholangiocellular Carcinoma (HCC-CCA)

Conclusion

References

Chapter 23: Radiotherapy and Brachytherapy for Unresectable Cholangiocarcinoma

Abstract

Introduction

Pre-Operative Treatment

Definitive Treatment

Treatment Comparisons

Conclusion

References

Chapter 24: Transarterial Chemoembolization (TACE)

Abstract

Introduction

1.1. History of TACE

1.2. Cholangiocarcinoma (CCC)

2. TACE for CCC

2.1. Indications and Criteria

2.2. Contraindications

3. Procedure

3.1. Preprocedural Evaluation

3.2. Technique

3.3. After the Procedure

3.4. Possible Complications

Complications of the Technique

Side Effects of Embolization

4. Pharmacology

4.1. Drug Options

4.2. Drug Review

4.2.1. Mitomycin C

4.2.2. Cisplatin

4.2.3. Gemcitabine

4.2.4. Lipidol

4.2.5. Embolic Agent

5. Results and Prognosis

5.1. RECIST

5.2. Survival

Conclusion

References

Chapter 25: Radiofrequency Ablation (RFA) for Unresectable Cholangiocarcinoma

Abstract

Introduction

Principles of Radiofrequency Ablation

The Role and Efficacy of Radiofrequency Ablation Regarding Cholangiocarcinoma

Effectiveness and Local Tumour Control

Prognostic Factors

Recurrence Data

Survival Data

Complications

Conclusion

References

Chapter 26: Yttrium-90 Microsphere Radioembolization for Unresectable Cholangiocarcinoma

Abstract

Introduction

Technical Aspects: Mode of Action of Radioembolization

Patient Selection for Radioembolization

Pretreatment Evaluation

90Y Radioembolization Procedure

Dosimetry and 90y Microsphere Activity Selection

Post-Treatment Assessment and Follow-Up

Treatment Outcomes and Survival

Side Effects and Complications

Conclusion

References

Chapter 27: Photodynamic Therapy in Cholangiocarcinoma

Abstract

Introduction

Principle

Technique of Photodynamic Therapy

Conclusion

References

Chapter 28: Chemotherapy in Patients with Advanced Cholangiocarcinoma

Abstract

1. Introduction

2. Chemotherapy vs Best Supportive Care

3. First-Line Chemotherapy

3.1. Fluoropyrimidine-based Chemotherapy

3.2. Gemcitabine-Based Chemotherapy

3.3. First-line Controlled Randomised Trials

3.4. Prognostic Factors for First-line Chemotherapy Outcomes

4. Second-Line Chemotherapy

5. Neoadjuvant Chemotherapy

Conclusion

References

Chapter 29: Targeted Therapies for Cholangiocarcinoma

Abstract

1. Introduction

2. Lessons from Preclinical Research: Looking for Potential Targets

2.1. Tumour Sequencing

2.2. Animal Models

3. Potential Pathways to Be Targeted in Cholangiocarcinoma: Translational Research-Based Rationale and Status of Clinical Development

A. Angiogenesis

Clinical Trials

Bevacizumab

Sorafenib

Sunitinib

Cediranib

Vandetanib

B. HER Family: EGFR and HER2

Clinical Trials

Cetuximab

Panitumumab

Erlotinib

Lapatinib

Trastuzumab

C. Targeting the Stroma: Epithelial–Mesenchymal Transition: Wnt/βcatenin; HGF/MET and Hedgehog

D. KRAS-Braf-MEK-ERK Pathway

Clinical Trials

Selumetinib

ARRY-438162

E. PI3K/AKT/mTOR

Clinical Trials

F. Proteasome

Clinical Trials

Bortezomib

Conclusion

References

Chapter 30: Adjuvant Treatment and Follow-up Strategies

Abstract

Introduction

Prognostic Factors

Adjuvant Treatments

Randomised Controlled Trials

Metanalysis and Main Retrospectives Series: Chemotherapy

Metanalysis: Radiotherapy and Chemoradiation

Length of Treatment

Elderly Patients

Predictive Factors to Response

Follow-up Strategies

Conclusion

References

Chapter 31: Palliative Care for Cholangiocarcinoma

Abstract

Introduction

Palliative Care in Biliary Tract Cancer

Palliative Care in End-Stage Liver Disease

Conclusion

References

Chapter 32: Diagnostic and Therapeutic Algorithms for Cholangiocarcinoma

Abstract

Introduction

Diagnostic Algorithm

Therapeutic Algorithm

Conclusion

References

Index