Colorectal Liver Metastasis

Foreword
Foreword
Foreword
Preface
Acknowledgments
Contents
Contributors
Part I: Introduction
1: History of Treatment of Colorectal Liver Metastases
1.1 Introduction
1.2 Early Liver Surgery for Colorectal Liver Metastases
1.2.1 Anatomy
1.2.2 Intraoperative Hemorrhage Control
1.2.3 Tumour Identification
1.3 Surgical Outcomes
1.4 Cytotoxic and Biologic Agents
1.5 Improved Patient Selection Based on Tumour Biology
1.6 Conclusion
References
Part II: Surgery
2: Liver Anatomy
2.1 Introduction
2.2 Functional “Unit” of the Liver
2.2.1 Liver Segment and Terminology
2.2.2 Liver Segmentation and Portal Territory
2.2.3 Intersegmental Plane
2.3 Portal Vein and Hepatic Vein
2.3.1 Symmetrical Configuration of Portal and Venous Ramification Patterns
2.3.2 Variation of Portal Vein and Hepatic Vein
2.3.3 Venous Drainage Map
2.4 Biliary Tract, Hepatic Artery, and Glissonian Pedicle
2.4.1 Biliary Tract
2.4.2 Hepatic Artery
2.4.3 Glissonian Pedicle, Plate Systems, and Laennec’s Capsule
2.5 Caudate Lobe (Segment 1)
2.6 Conclusion
References
3: Exposure for Hepatectomy
3.1 Introduction
3.2 Incisions
3.2.1 Midline Laparotomy
3.2.2 J Incision (Makuuchi Incision)
3.3 “Inverted-L” or Modified Makuuchi Incision
3.4 Other Incisions
3.5 Conclusion
References
4: Parenchymal Preservation in the Operative Management of Colorectal Liver Metastases
4.1 Introduction
4.2 Perioperative Outcomes
4.2.1 Perioperative Morbidity
4.2.2 Perioperative Mortality
4.3 Oncologic Outcomes
4.3.1 Margins
4.3.2 Recurrence and Survival
4.3.3 Salvageability
4.4 Special Considerations
4.4.1 Genomic Profiling
4.4.2 Minimally Invasive Surgery
4.5 Conclusion
References
5: Simulation and Navigation
5.1 Introduction
5.2 Simulation
5.2.1 Three-Dimensional Simulation Software and Virtual Hepatectomy
5.3 Navigation
5.3.1 Intraoperative Ultrasound
5.3.2 Indocyanine Green Fluorescent Imaging
5.3.3 Real-Time Virtual Sonography
5.3.4 Navigation Software and Augmented Reality
5.4 Conclusion
References
6: Advanced Techniques in Multiple Metastases: Fiduciary Markers and Completion Ablation
6.1 Introduction
6.2 Fiducial Marker Placement
6.2.1 Indication
6.2.2 Procedure
6.2.3 Results
6.3 Completion Ablation (Planned Incomplete Resection and Postoperative Completion Ablation)
6.3.1 Definition of Completion Ablation
6.3.2 Indication
6.3.3 Procedure
6.3.4 Results
6.4 Conclusions
References
7: Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: Experience of MD Anderson Cancer Center
7.1 Introduction
7.2 The MD Anderson Cancer Center Approach
7.3 The MD Anderson Cancer Center “Fast-Track” Approach
7.4 Outcomes After Two-Stage Hepatectomy
7.5 Conclusion and Future Aims
References
8: Two-Stage Hepatectomy for Bilobar Colorectal Liver Metastases: Experience of Hôpital Paul-Brousse
8.1 Introduction
8.2 Two-Stage Hepatectomy
8.2.1 Indication
8.2.2 Surgical Procedures of TSH
8.2.3 Chemotherapy
8.2.4 Dropout from the TSH Strategy
8.2.5 Short-Term Outcome
8.2.6 Long-Term Outcome
8.2.7 Surgery for Recurrence
8.2.8 Case Presentation
8.3 Conclusion
References
9: One-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: Experience of the University of Tokyo
9.1 Introduction
9.2 Preoperative Evaluation
9.2.1 Diagnostic Approach
9.2.2 Evaluation of Liver Function and Future Liver Remnant Volume
9.3 Intraoperative Inspection of CLMs
9.4 Outcomes after One-Stage Hepatectomy
9.5 Future Perspective of One-Stage Hepatectomy
9.6 Conclusion
References
10: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) for Colorectal Liver Metastasis
10.1 Introduction
10.2 Evolution of ALPSS as a New Surgical Strategy
10.3 ALPPS for Colorectal Liver Metastases
10.4 When Is ALPPS for CLM Functionally Indicated?
10.4.1 Where Do We Come From? Functional Resectability in the Pre-ALPPS Era
10.4.2 Functional Resectability With ALPPS
10.5 ALPPS for CLM in a Curative Intention
10.6 ALPPS in a Multimodal Treatment of CLM
10.7 Conclusion
References
11: Open Resection Technique
11.1 Introduction
11.2 Anaesthesia
11.3 General Principles
11.4 Access—Incision, Retraction, and Mobilization
11.5 Intra-Operative Ultrasound
11.6 Laparoscopy
11.7 Pringle Manoeuvre
11.8 Liver Dissection/Transection
11.9 Inflow Control
11.10 CUSA
11.11 Intrahepatic Ligation
11.12 Outflow Control
11.13 Sealing the Parenchyma
11.14 Wound Closure
11.15 Special Situations
11.16 Conclusion
References
12: Laparoscopic Liver Resection Technique: The Norwegian Experience
12.1 Introduction
12.2 Laparoscopic Liver Resection for Colorectal Liver Metastases
12.2.1 Selection and Limitations
12.2.2 Surgical Techniques
12.2.2.1 Laparoscopic Nonanatomic Resection (Cauliflower Technique)
12.2.2.2 Left Lateral Sectionectomy
12.2.2.3 Laparoscopic Left Hemihepatectomy
Liver Mobilization
Control of Vascular Inflow
Parenchymal Transection
Outflow Control
12.2.2.4 Laparoscopic Right Hemihepatectomy
Liver Mobilization
Vascular Inflow Control
Parenchymal Transection
Hepatic Venous Outflow Control
12.3 Conclusion/Personal Opinion
References
13: Laparoscopic Liver Resection Technique: French Experience
13.1 Introduction
13.2 Perioperative and Short-Term Outcomes
13.3 Oncologic and Long-Term Outcomes
13.4 Repeat Liver Resection
13.5 Synchronous Resection of CLM
13.6 Two-Stage Hepatectomy (TSH)
13.7 Associating Liver Partition with Portal Vein Ligation (ALPPS)
13.8 Technical Tips and Tricks
13.8.1 Positioning
13.8.2 Incisions, Exploration, and Exposure
13.8.3 Transection Techniques
13.8.4 Extraction, Drainage, and Closure
13.9 Conclusions
References
14: Laparoscopic Anatomical Liver Resection Technique: The Japanese Experience
14.1 Introduction
14.2 Techniques Based on the Anatomical Landmarks for LALR
14.2.1 Glissonean Approach
14.2.1.1 Anatomical Landmarks for Glissonean Approach
14.2.1.2 Techniques of Glissonean Approach for LAR at Ageo Central General Hospital
Left Hepatectomy
Right Anterior Sectionectomy
Laparoscopic Parenchymal-Sparing Anatomical Liver Resection (Lap-PSAR)
14.2.2 Parenchymal Transection on the Intersegmental Planes
14.2.2.1 Anatomical Landmarks for the Hepatic Veins
Inferior Phrenic Vein (IPV)
Arantius Ligament
14.2.2.2 Approaches for Exposing the HVs
14.2.2.3 Parenchymal Transection under Indocyanine Green (ICG) Fluorescence Image Guidance at Ageo Central General Hospital
14.3 Future Prospects (The Long-Term Advantages of LLR for CRLM)
14.4 Conclusion
References
15: Is There a Place for Robotic Resection?
15.1 Introduction
15.2 Rationale for Minimally Invasive Resection of Colorectal Liver Metastases
15.2.1 Laparoscopic Hepatectomy
15.2.2 Theoretical Advantages of a Robotic Approach
15.3 Learning Curve
15.4 Robotic Hepatectomy Outcomes
15.4.1 Robotic Versus Open Perioperative Outcomes
15.4.2 Robotic Versus Laparoscopic Perioperative Outcomes
15.4.3 Oncologic Outcomes
15.4.4 Cost
15.5 Limitations of Robotic Hepatectomy
15.6 Robotic Surgery in Practice: Our Approach
15.6.1 Patient Selection for Robotic Hepatectomy
15.6.2 Technical Aspects of Robotic Hepatectomy
15.6.2.1 Positioning and Setup
15.6.2.2 Intraoperative Ultrasound
15.6.2.3 Instrumentation and General Principles
15.6.2.4 Right Hepatectomy
15.6.2.5 Left Hepatectomy
15.6.2.6 Partial Hepatectomy
15.6.2.7 Perioperative Management for Robotic Hepatectomy
15.7 Future Directions
15.8 Conclusion
References
16: Advanced Resection Technique with Vascular Reconstruction
16.1 Introduction
16.2 Rational for Resection and Reconstruction
16.3 Advanced Technique for Resection of CLM
16.3.1 Tumours Located in the Posterosuperior Segments
16.3.2 Resection of Tumours Located at Central Upper Segments with Reconstruction of Hepatic Veins Confluence
16.3.3 Central Lower Tumours with Portal and Biliary Reconstruction
16.4 R1 Resection by Necessity Versus Complex Resection with Vascular Reconstruction
16.5 Oncological Results of Complex Resection with Vascular Reconstruction in CLM
16.6 Conclusion
References
17: Resection Margins
17.1 Introduction
17.2 Resection Margins in Colorectal Liver Metastases
17.2.1 Resection Margins Status as a Predictor of Tumour Recurrence and Overall Survival
17.2.2 Resection Margins and Perioperative Chemotherapy
17.2.3 Resection Margins and Parenchymal-Sparing Hepatectomy
17.2.4 Resection Margins and Minimally Invasive Hepatectomy
17.2.5 Resection Margins and Somatic Gene Mutations
17.2.6 R1 Resection as a Predictor of Recurrence at the Hepatic Resection Margin
17.3 Conclusion
References
18: R1 Vascular Surgery
18.1 Introduction
18.2 Tumours and the Intrahepatic Vessels
18.2.1 Tumour in Contact with Glissonean Pedicle
18.2.2 Tumour in Contact with Hepatic Vein
18.3 The Outflow
18.3.1 Vessel Guided Hepatectomies
18.3.1.1 Systematic Extended Right Posterior Sectionectomy
18.3.1.2 Mini-Mesohepatectomy
18.3.1.3 Transversal Hepatectomies
Rollercoaster Hepatectomy
Transverse Hepatectomy with HV Resection
18.3.1.4 Liver Tunnel
18.3.1.5 Parenchyma Sparing Major Hepatectomies
18.4 Conclusions
References
19: Prevention and Treatment of Perihepatic Fluid Collection Including Two-Step Air Leak Test
19.1 Introduction
19.2 Diagnosis and Management of Fluid Collections and Bile Leaks
19.3 Bile Leak Prevention Tests
19.4 Air Leak Test
19.5 Conclusions
References
20: Synchronous Presentation of Primary and Colorectal Liver Metastasis: Classic, Reverse, and Combined
20.1 Introduction
20.2 Primary Tumour-First Approach
20.3 Liver-First Approach
20.4 Simultaneous Combined Approach
20.4.1 Type of Approach for Simultaneous Resection
20.5 Conclusion
References
21: Approach to Synchronous Lung and Liver Metastases and Single-Incision Combined Resection
21.1 Introduction
21.2 Transdiaphragmatic Resection of Lung Metastases
21.2.1 Patient Selection
21.2.2 Technique of Transdiaphragmatic Resection
21.2.3 Clinical Outcomes
21.2.4 Benefits of Simultaneous Resection
21.2.5 Future Directions
21.3 Conclusion
References
22: Perioperative Chemotherapy: Review of Randomized Trials and Recommended Approach
22.1 Introduction
22.2 Early Trials
22.3 EORTC 40983 (EPOC) Trial
22.4 New EPOC Trial
22.5 JCOG0603 Trial
22.6 Other Trials
22.7 Conclusions from the Available Evidence
22.8 Ongoing Uncertainties
22.8.1 Timing
22.8.2 Choice of Regimen
22.8.3 Duration of Treatment
22.8.4 Impact on Overall Survival
22.9 Summary and Recommendations
References
23: Disappearing Liver Metastasis
23.1 Introduction
23.2 Defining Disappearing Colorectal Liver Metastasis
23.3 Intraoperative Assessment of DLM
23.4 Management and Outcomes of DLM
23.5 Conclusion
References
24: Downsizing Chemotherapy for Liver Metastases from Colorectal Cancer
24.1 Introduction
24.2 Defining the Resectability Perspective of the Patient
24.3 Conversion Chemotherapy to Achieve the Resectability: The Onco-Surge Approach
24.4 What Are Favorable Conditions for an OncoSurge Approach?
24.5 The Increasing Evolution of the Surgical Indications for CLM
24.6 How Can We Manage Surgery of Patients Who Showed Progression during First-Line Chemotherapy?
24.7 How Can we Manage Patients with Unresectable Disease after Downsizing Chemotherapy: The Development of New Surgical Procedures
24.8 Multidisciplinary Team (MDT) Approach for CLM
24.9 Clinical Case
24.10 Conclusions
References
25: Is There a Place for Debulking?
25.1 Introduction
25.2 Early Recurrence After Curative Intent Surgery: Inadvertent Cytoreduction?
25.3 Localized Treatments for Unresectable Disease: Planned Cytoreduction
25.4 Conclusions
References
26: Liver Transplantation
26.1 Introduction
26.2 Transplantation for Malignant Disease
26.3 Patient Selection
26.3.1 Features of the Liver Metastases
26.3.2 Features of the Primary Tumour
26.3.3 Chemotherapy
26.3.4 Radiology
26.3.5 Time Interval
26.4 Outcomes
26.4.1 Overall Survival
26.4.2 Disease-Free Survival and Recurrence
26.5 The Scarcity of Liver Grafts
26.6 Future Directions
26.7 Conclusion
References
27: Prognostic Models for Colorectal Liver Metastases
27.1 Introduction
27.2 Prognostic Models in Colorectal Liver Metastases
27.2.1 Prognostic Factors in Patients with Resectable Colorectal Liver Metastases: A Changing Landscape
27.2.2 From Prognostic Factors to Prognostic Models in the Era of Morphology
27.2.3 From Morphological to Molecular Prognostication
27.3 Conclusion
References
28: Personalized Prognostic Model (Contour Prognostic Model)
28.1 Introduction
28.2 Use of Contour Plots for Hepatocellular Carcinoma
28.2.1 Liver Transplantation
28.2.2 Liver Resection, Transarterial Chemoembolization, and Ablation
28.3 Prognostic Model for Resection of Colorectal Liver Metastases
28.4 Contour Prognostic Model for Resection of Colorectal Liver Metastasis: A Model Based on Continuous Number and Diameter of CLM
28.5 External Validation of our Contour Prognostic Model Using an International Multi-Institution Cohort
28.6 Conclusion
References
29: Conditional Recurrence-Free Survival
29.1 Introduction
29.2 Conditional RFS
29.2.1 Conditional Survival and Conditional RFS
29.2.2 Changing Risk of Recurrence Over Time and Conditional RFS
29.2.3 Studies of Conditional OS for CLM
29.3 Conclusion
References
30: Repeat Hepatectomy for Colorectal Liver Metastases
30.1 Introduction
30.2 Epidemiology of Recurrence After Hepatectomy
30.2.1 Practical Feasibility of Repeat Hepatectomy
30.3 Early and Long-Term Outcomes After Repeat Hepatectomy
30.4 Predictors of Survival After Repeat Hepatectomy
30.5 Practical Questions Before Repeat Hepatectomy
30.5.1 Should Chemotherapy Be Given Before Repeat Hepatectomy?
30.5.2 Diagnosis of Chemotherapy-Induced Liver Toxicity Before Repeat Hepatectomy
30.6 Technical Aspects of Repeat Hepatectomy
30.6.1 Surgery or Ablation
30.6.2 The Technical Difficulty of Repeat Hepatectomy
30.6.3 How to “Re” Tape the Hepatic Pedicle?
30.6.4 Laparoscopic Approach
30.7 After Repeat Hepatectomy
30.8 Sparing Parenchyma Policy: A Key Factor of the Strategy
30.9 Conclusion
References
Part III: Systemic and Regional Therapy
31: Initial Systemic Chemotherapy for Metastatic Colorectal Cancer
31.1 Introduction
31.2 Fluoropyrimidines: Backbone of Chemotherapy in Colorectal Cancer
31.2.1 Bolus and Infusional Fluorouracil, Capecitabine
31.2.2 Oxaliplatin-Based Doublet Chemotherapy
31.2.3 Irinotecan-Based Doublet Chemotherapy
31.3 Doublet Chemotherapy Combinations with Biologics
31.3.1 Anti-VEGF Therapy: Bevacizumab
31.3.2 Anti-EGFR Therapy: Cetuximab and Panitumumab
31.4 Triplet Chemotherapy
31.5 Approach to Current First-Line Metastatic Colorectal Regimens
31.5.1 Microsatellite Stable, RAS/BRAF Wild Type, Left-Sided
31.5.2 Microsatellite Stable, RAS/BRAF Mutated
31.5.3 Microsatellite Instability High Tumours: Immunotherapy
31.6 Special Considerations for Liver Metastases
31.7 Conclusions
31.8 Future Directions
References
32: Treatment Refractory Metastatic Colorectal Cancer
32.1 Introduction
32.2 Second-Line Therapy
32.3 Anti-VEGF Therapy
32.4 Anti-EGFR Therapy
32.5 Molecularly Driven Therapy
32.5.1 BRAF Mutations
32.5.2 Deficient-Mismatch Repair (dMMR) or Microsatellite Instability High (MSI-H)
32.5.3 ERBB2(HER2) Amplification/Overexpression
32.6 Third-Line Therapy and beyond
32.7 Summary
References
33: Targeted Therapy with Anti-EGFR and Anti-VEGF Therapy and Beyond
33.1 Introduction to Targeted Therapy
33.2 Anti-EGFR Therapy: Cetuximab and Panitumumab
33.2.1 Cetuximab
33.2.2 Panitumumab
33.2.3 Anti-EGFR Therapy and Tumour Sidedness
33.3 Anti-VEGF Therapy: Bevacizumab, Ramucirumab, Aflibercept
33.3.1 Bevacizumab
33.3.2 Ramucirumab
33.3.3 Aflibercept
33.4 Anti-EGFR Rechallenge
33.5 Anti-VEGF Rechallenge
33.6 Targeted Therapy Beyond Anti-EGFR and Anti-VEGF Multikinase Inhibitors
33.6.1 BRAF Inhibition
33.6.2 MEK and BRAF Inhibition
33.6.3 Microsatellite Instability High (MSI-H)
33.6.4 HER2 Directed Therapy
33.6.5 NTRK Fusion Inhibitors
33.7 Conclusions
References
34: Adjuvant Systemic Chemotherapy
34.1 Introduction
34.2 Prospective Clinical Trials for Adjuvant Chemotherapy
34.2.1 FFCD ACTBTH AURC 9002 Trial: Evaluation of Single-Agent Fluoropyrimidine as an Adjuvant Therapy
34.2.2 EORTC 40983: Addition of Oxaliplatin to Adjuvant Therapy with Fluoropyrimidine
34.2.3 Meta-Analyses for Adjuvant Chemotherapy in Liver-Limited Metastatic Colorectal Cancer
34.3 Agents Not Recommended as Adjuvant Therapy for Resected Liver-Limited Metastatic Colorectal Cancer
34.3.1 Irinotecan
34.3.2 Anti-EGFR Therapies
34.3.3 Anti-VEGF Therapies
34.4 Future Strategies for Adjuvant Therapies in Treatment of Liver-Limited Metastatic Colorectal Cancer: The Potential for Circulating Tumour DNA
34.5 Conclusion
References
35: Immunotherapy
35.1 Introduction
35.2 Background
35.2.1 History
35.2.1.1 Inheritance and the Lynch Syndrome
35.2.2 Errors in DNA Replication: Microsatellites, CpG Islands, and POLE/D1 Mutations
35.2.3 Next-Generation Sequencing
35.2.4 New Approaches
35.3 Current Applications
35.3.1 Globally for all Colon Cancer
35.3.2 Early-Stage Disease
35.3.3 Late-Stage Disease
35.3.4 Colorectal Cancer Liver Metastases
35.4 Scope of the Problem
35.5 Optimal Sequencing of Therapy
35.6 Time to Response
35.6.1 Management of Toxicities
35.6.2 Evaluation of Response
35.6.2.1 Radiology
35.6.2.2 Circulating Cell-Free DNA (cfDNA) and Circulating Tumour DNA (ctDNA)
35.6.2.3 CEA
35.7 Developing and Future Applications
35.7.1 New-Generation of Immune Checkpoint Inhibitors
35.7.2 Alteration of the TME
35.7.2.1 Adoptive T-Cell Therapy
35.7.2.2 Vaccines
35.7.2.3 Gut Microbiome
35.7.3 Combination of either Chemotherapy or Radiation Therapy with Immunotherapy
35.8 Conclusion
References
36: Hepatic Artery Infusion Therapy: The European Experience
36.1 Introduction
36.2 First-Line Intra-arterial Hepatic Chemotherapy in Advanced Metastatic Colorectal Cancer
36.2.1 Infusional 5-Fluorouracil (5FU)
36.2.2 Pirarubicin
36.2.3 Oxaliplatin
36.3 Conversion to Surgery and Rescue HAI Chemotherapy
36.3.1 HAI Protocols for Previously Treated Patients
36.3.2 Expected Efficacy Outcomes
36.3.3 Timing of Administration of HAI Chemotherapy Along the Course of LM-CRC Management
36.3.4 Toward Precision HAI Chemotherapy in Individual LM-CRC Patients
36.3.4.1 Early Tumour Response
36.3.4.2 Pharmacokinetics
36.3.4.3 Pharmacogenetics
36.3.4.4 Circulating DNA
36.3.5 Antitumour Immunity
36.3.6 Chemotherapy Schedule
36.3.6.1 HAI Oxaliplatin or Triplet
36.3.7 HAI as Conventional or Chrono-modulated Delivery
36.4 Adjuvant Intra-arterial Hepatic Chemotherapy for Resected Liver Metastases
36.4.1 Adverse Events of HAI
36.5 Trans-arterial Chemoembolization (TACE)
36.6 Conclusion
References
37: Infusional Therapy: American Experience
37.1 Introduction
37.1.1 Rationale for Intra-arterial Chemotherapy
37.2 Technique
37.2.1 Special Anatomic Considerations
37.2.2 Confirming Appropriate Catheter Function
37.2.3 Complications
37.3 Infusional Chemotherapy in the Adjuvant Setting
37.4 Treatment of Unresectable Disease
37.4.1 Hepatic Artery Infusion Chemotherapy Alone
37.4.2 HAI Chemotherapy Combined with Systemic Chemotherapy
37.4.3 Conversion to Resectable
37.5 Conclusion
References
Part IV: Radiology, Interventional Radiology and Radiation
38: Optimal Diagnostic Imaging of CLM for Surgical Candidates
38.1 Introduction
38.2 Different Modalities for Detection and Staging of Liver Metastases
38.2.1 Ultrasonography (US)
38.2.2 Multidetector Computed Tomography (MDCT)
38.2.3 Magnetic Resonance (MR) Imaging
38.2.4 Positron Emission Tomography (PET) Combined with CT or MR Imaging
38.3 Algorithm for the Pretreatment Staging of CLM
38.4 Evaluation of Treatment Response of CLM
38.4.1 Imaging Biomarkers
38.4.2 Liver Injury Associated with Chemotherapy of CLM
38.5 Conclusion
References
39: Prevention of Postoperative Hepatic Insufficiency
39.1 Introduction
39.2 Definition of Postoperative Hepatic Insufficiency and Risk Factors
39.3 Preoperative Risk Assessment
39.3.1 Volumetry
39.3.2 Static Functional Measures for Risk Assessment
39.3.3 Dynamic Functional Measures for Risk Assessment
39.3.4 Combination of Dynamic and Static Measures for Expanding Surgical Indication
39.4 Strategy to Prevent Postoperative Hepatic Insufficiency
39.4.1 Portal Vein Embolization
39.4.2 Two-Stage Hepatectomy (Including ALPPS)
39.4.3 Duration of Chemotherapy
39.5 Conclusions
References
40: Portal Vein Embolization with and without Hepatic Vein Occlusion
40.1 Introduction
40.2 Portal Vein Embolization
40.2.1 Indication for PVE
40.2.2 Hypertrophy
40.2.3 PVE Safety
40.2.4 PVE and Liver Resection
40.3 Portal Vein Embolization with Hepatic Vein Embolization
40.3.1 Technique of HVE
40.3.2 Hypertrophy
40.3.3 Procedure-Related Morbidity
40.3.4 Liver Resection After LVD
40.3.5 Comparison Between PVE Alone and PVE with HVE
40.4 Conclusion
References
41: Radiofrequency Ablation, Electroporation, and Microwave Ablation
41.1 Introduction
41.2 Liver Ablation
41.2.1 Ablation Technologies
41.2.1.1 Radiofrequency Ablation
41.2.1.2 Microwave Ablation
41.2.1.3 Irreversible Electroporation
41.2.2 Patient Selection
41.2.3 Preablation Imaging and Imaging Guidance Modalities
41.2.3.1 Preablation Imaging Modalities
41.2.3.2 Imaging Guidance Modalities
41.2.3.3 Computed Tomography
41.2.3.4 Ultrasound
41.2.3.5 Positron Emission Tomography/Computed Tomography
41.2.3.6 Magnetic Resonance Imaging
41.2.4 Studies on CLM Ablation
41.3 Conclusion
References
42: Radiation Therapy
42.1 Introduction
42.2 Radiation Therapy for Colorectal Liver Metastasis
42.3 Conclusion
References
43: Yttrium-90 Radioembolization for Metastatic Colorectal Cancer
43.1 Introduction
43.2 Principles of Y-90
43.3 Dosimetry Considerations
43.3.1 Empirical Methods
43.3.2 MIRD Method
43.3.3 Partition Model
43.4 Treatment Assessment
43.5 Results
43.5.1 Y-90 as an Adjunct to First-Line Chemotherapy in Patients with mCRC
43.5.2 Y90 for Patients Refractory to First-Line Chemotherapy in Patients with mCRC
43.5.3 Y-90 Radiation Segmentectomy for mCRC
43.5.4 Induction of Future Liver Remnant [FLR] Hypertrophy in Surgical Patients
43.5.5 Combination of SIRT and First-Line Chemotherapy to Improve Resectability in Surgical Patients with Unresectable Liver-only mCRC
43.5.6 Safety of Surgical Resection After Y-90
43.6 Conclusion
References
Untitled
Part V: Surgical Pathology and Molecular Pathology
44: Hepatic Injury from Chemotherapy
44.1 Introduction
44.2 Patterns of Hepatic Lesions and Their Association to Specific Chemotherapy Drug Regimens Used for CLM Treatment
44.2.1 Steatosis
44.2.1.1 Chemotherapy Associated Steatosis (CAS) by 5-Fluorouracil (5-FU)
44.2.2 Steatohepatitis
44.2.2.1 Chemotherapy Associated Steatohepatitis (CASH) by Irinotecan
44.3 Sinusoidal Obstruction Syndrome and Associated Lesions
44.3.1 Chemotherapy Associated SOS (SOS) by Oxaliplatin
44.4 Reversibility of Chemotherapy-Related Liver Injury
44.5 Conclusion
References
45: Imaging Response Evaluation
45.1 Introduction
45.2 Importance of Baseline, Pretreament Imaging
45.3 Imaging Response After Systemic Chemotherapy
45.4 Size-Based Criteria
45.4.1 Definition
45.4.2 Limitations/Pitfalls
45.4.3 Disappearing Liver Metastasis
45.5 Non-size-Based Morphological Criteria
45.5.1 Radiographic Observation After Bevacizumab
45.5.2 Rad-Pathologic Correlation
45.5.3 Definition and Validation of the Criteria
45.5.4 Additional Points Regarding the Morphologic Criteria
45.5.5 Progression After Morphologic Response
45.5.6 Correlation of Imaging Response and Histologic Growth Pattern
45.6 Imaging Response After Immunotherapy
45.7 Role of Functional Imaging
45.8 Assessment of Chemotherapy-Induced Liver Toxicity
45.9 Response Assessment After Locoregional Therapy
45.9.1 Ablation
45.9.2 Transarterial Radioembolization
45.10 Conclusion
References
46: Pathological Response Criteria
46.1 Histopathology Evaluation of Resected Colorectal Metastases After Neoadjuvant Chemotherapy
46.2 Macroscopic Examination and Sampling
46.3 Microscopic Examination
46.3.1 Histopathologic Response to Neoadjuvant Therapy
46.3.1.1 Pathologic Response Defined as Residual Tumour Cell Burden
46.3.1.2 Tumour Regression Grade (TGR)
46.3.2 Histologic Growth Patterns
46.3.2.1 Tumour Cell Thickness at the Tumour-Normal Interface
46.3.2.2 Histologic Pattern at the Tumour-Normal Liver Interface
46.4 Conclusion
References
47: Histopathological Patterns of Progression and Vessel Co-option
47.1 Introduction
47.2 Utilization of Antiangiogenic Therapy for Patients with CRLM
47.3 Histopathological Growth Patterns in Liver Metastasis
47.3.1 Vessel Co-option
47.3.2 Three Distinct Growth Patterns
47.3.3 Vessel Co-option in Replacement Pattern Mediates Resistance to Antiangiogenic Therapy and Progression in CRLM
47.4 Clinical Implications of Histopathological Growth Patterns in CRLM
47.5 Conclusion
References
48: Colorectal Liver Micrometastases
48.1 Introduction
48.2 Micrometastases
48.2.1 Pathology Description
48.2.2 Risk Factors for Developing Micrometastases
48.2.3 Impact on Survival
48.3 Surgical Management
48.4 Conclusion
References
49: Liquid Biopsy
49.1 Introduction
49.2 ctDNA and Resection of CRLM
49.3 ctDNA and Liver Directed Therapy
49.4 Residual Disease
49.5 ctDNA and Treatment Response
49.6 Limitations
49.7 Future Directions
References
Part VI: Genetic Sequencing and Clinical Implication
50: Multigene Testing for Prognostication and Therapeutic Actionability
50.1 Introduction
50.2 Multigene Testing Technology and Analysis
50.3 Mismatch Repair
50.4 Primary Tumour Sidedness
50.5 Somatic Gene Mutations
50.5.1 RAS
50.5.2 BRAF
50.5.3 ERBB2/HER2 Amplification
50.5.4 SMAD4
50.5.5 FBXW7
50.5.6 Concurrent Mutations
50.6 Implications of Gene Mutations for Surgical Practice
50.7 Conclusions
References
51: Cancer-Related Signaling Pathway and Prognosis
51.1 Introduction
51.2 Alterations in Pathways and Member Genes in Patients Undergoing CLM Resection
51.3 Cancer-Related Signaling Pathway and Member Genes
51.4 Pathway/Predominant Member Gene and Clinical Heterogeneity
51.5 Risk Stratification of Resection and Liver Transplantation for CLM
51.6 Conclusion
References
Part VII: Ultrasound and Operating Room Settings
52: Intraoperative Ultrasound
52.1 Introduction
52.2 Equipment
52.2.1 Probes
52.3 Liver Exploration
52.3.1 IOUS Semiology
52.3.1.1 Glissonean Pedicles
52.3.1.2 Hepatic Vein
52.3.2 Diagnosis and Staging
52.3.2.1 Contrast-Enhanced IOUS
52.4 Resection Guidance
52.4.1 Definition of the Resection Areas
52.4.2 Liver Parenchyma Dissection
52.4.3 Postresection Evaluation
52.5 Complementary Guidance Modalities
52.6 Conclusions
References
53: Hybrid Room for Combined Procedures
53.1 Introduction
53.2 Image-Guided Minimally Invasive Procedures
53.3 Equipment Definitions
53.3.1 C-Arm Fluoroscopy
53.3.2 CT Angiography and Angio-CT Suite
53.4 Clinical Applications for Liver Surgery
53.4.1 Procedure Planning
53.4.2 Navigation
53.4.3 Fast-Track Two-Stage Hepatectomy
53.4.4 Intraoperative Ablation Under Cross-Sectional Imaging Guidance
53.4.5 Management of Complications
53.5 Conclusions
References
Part VIII: Role of Multidisciplinary Team and Recovery and Surveillance Strategy
54: Multidisciplinary Liver Tumour Board
54.1 Introduction
54.2 The Multidisciplinary Tumour Board, Its Beginnings and Evolution
54.3 Decision-Making Members of the Multidisciplinary Liver Tumour Board (MDLTB)
54.4 Process and Workflow
54.5 Leadership and Team Dynamics
54.6 Impact of the MDLTB
54.7 Summary
References
55: Role of Advanced Practice Providers in Enhancing Perioperative and Intraoperative Patient Care
55.1 Introduction
55.2 The Role of APPs in Perioperative Care
55.3 Preoperative Care
55.3.1 New Patient Access
55.3.2 Coordination of Care and Patient Education
55.4 Intraoperative Care
55.4.1 APP Surgical Assist Role
55.4.2 Fellow/Resident Training
55.5 Postoperative Management
55.5.1 Inpatient Care/Management
55.5.2 Postoperative Pathways in Managing Complications
55.5.3 Immediate Postoperative Care and Clinic Follow-Up
55.5.4 Surveillance and Survivorship Care of CLM Patients
55.6 APP Productivity and Value
55.7 Conclusion
References
56: Enhanced Recovery in Liver Surgery
56.1 Introduction
56.2 Preoperative Evaluation and Prehabilitation
56.3 Patient Education and Engagement
56.4 Perioperative Nutrition and Early Feeding
56.5 Goal-Directed Fluid Therapy
56.6 Perioperative Pain Control
56.7 Ambulation: Early Removal of Tubes
56.8 Patient-Reported Outcomes and Return to Intended Oncologic Therapy
56.9 Summary
References
57: Improved Survival After CLM Resection over 20 Years
57.1 Introduction
57.2 Refinements of Surgical Management and Technique
57.2.1 Planning of Liver Resection
57.2.2 Avoiding Hepatic Insufficiency
57.2.3 Minimizing Postoperative Complication
57.2.4 New Classification for Liver Resection: Three-Level Complexity Classification
57.3 Advancements in Medical Treatments
57.4 Clinical Implication of Molecular Biology
57.5 Changes in Overall Survival After CLM Resection
57.6 Conclusions
References
58: The LiverMetSurvey Registry
58.1 Introduction
58.2 Missions and Organization of the LiverMetSurvey Registry
58.2.1 Study Population and Aims of the Registry
58.2.2 Nomination of a Scientific Committee
58.2.3 Participating Centers
58.2.4 Managing and Protecting the Data
58.2.5 Services to Participating Centers
58.2.6 Sponsorship
58.3 Key Learnings from LiverMetSurvey
58.3.1 Unpublished Data
58.3.1.1 Study Population and Overall Survival
58.3.2 Early and Long-Term Outcomes After Surgery
58.3.3 The Prognostic Impact of Number and Maximal Tumour Size
58.3.4 CLM with Concomitant Extrahepatic Disease (EHD)
58.3.5 Preoperative Chemotherapy
58.3.6 Published Studies
58.3.6.1 Patient and Tumour-Related Prognostic Factors
58.3.6.2 Onco-surgical Strategies
58.3.7 Impact of Preoperative Bevacizumab
58.3.7.1 Extended Indications
58.3.7.2 Impact of Underlying Liver Steatosis
58.3.7.3 Technical Issues
58.4 Conclusion
References
Untitled
59: Circulating Tumour DNA and Risk-Stratified Surveillance Strategies for Patients with Colorectal Liver Metastases
59.1 Introduction
59.2 ctDNA: An Emerging Biomarker for Patients with CLM
59.2.1 The Case for ctDNA in Metastatic Colorectal Cancer
59.2.2 ctDNA and Surgical Management of CLM
59.3 Future Directions
59.4 Risk-Stratified Surveillance for Recurrent Disease After Hepatectomy for CLM
59.4.1 Current Recommendations and Changing Risk of Recurrence
59.4.2 Proposed Surveillance Algorithm After Resection of CLM
59.5 Conclusion
References
Index