Liver Metastases (eBook)

Liver Metastases 2
Preface 5
Contents 6
Contributors 8
Radiological Imaging of Liver Metastases 11
Introduction 11
Diagnosis and Staging of Liver Metastasis 11
Radiologic-Pathologic Correlation 12
Imaging Modalities for the Detection of Hepatic Metastases 13
Ultrasound 14
Computed Tomography 14
Magnetic Resonance Imaging 14
Differential Diagnosis 16
Hemangioma 16
Focal Steatosis 16
Sub-Centimeter Focal Lesions 16
Staging of Hepatic Metastases in Potentially Resectable Patients 17
Evaluation of Possible Liver Metastases 17
Possible Hilar Lymph Node Involvement 17
Vascular Invasion 18
Liver Volumetry 19
Presence of Extrahepatic Disease 19
Follow-Up for Recurrent Metastatic Disease 20
Follow-Up of Patients After Surgical Resection of CRC Hepatic Metastases 20
Imaging and Follow-Up After Radiofrequency Ablation 20
References 22
Biology of Colorectal Cancer Liver Metastases 24
Colorectal Hepatic Metastases Formation 24
Alteration of Cell-Cell and Cell-Matrix Interactions 24
Epithelial to Mesenchymal Transition 24
Invasion and Metastasis 27
Src in CRC Metastasis 27
Migration and Motility 27
Growth factors and Tumor Angiogenesis 28
Vascular Endothelial Growth Factor 28
Liver Metastases and Apoptosis 29
Anti-Angiogenic Treatment of Liver Metastases 29
Anti-VEGF Therapy 29
Inhibitors of Epidermal Growth factor 30
Summary 31
References 31
Surgery for Colorectal Metastases 34
Introduction 34
Selection of Patients for Hepatic Resection 34
Patients’ General Medical Fitness 34
Assessment of Tumor Resectability and Anticipated Extent of Resection 34
Definition of Resectability-A Changing Paradigm 35
Multinodular and/or Bilateral Disease 35
Size > 5 cm
Surgical Margin 35
Hepatic and Pulmonary Metastases 35
Other Sites of Extrahepatic Disease 36
Prognostic Factors 36
Ensuring Sufficient Functional Hepatic Reserve and Strategies to Increase Resectability 37
Measuring the Future Liver Remnant (FLR) 37
Portal Vein Embolization (PVE) 37
Two-Stage Hepatectomy 37
Repeat Hepatectomy 38
Anesthesia and Operative Considerations 38
Anesthesia 38
Methods for Parenchymal Transection 39
Intraoperative Ultrasound (IOUS) 40
Anatomic Versus Wedge Resection 40
Evolving Role of Laparoscopic Hepatectomy 40
Surgery in the Era of Multimodality Therapy 41
Systemic Chemotherapy for Initially Irresectable Disease 41
Systemic Chemotherapy for Initially Resectable Disease 41
Chemotherapy-Induced Liver Injury 41
Biologic Agents 43
Management of Synchronous Colorectal Liver Metastases 44
Conclusions 44
References 45
Destructive Therapies for Colorectal Cancer Metastases 48
Introduction 48
Cryoablation 48
Radiofrequency Ablation 49
Microwave Coagulation Therapy 54
Other Ablation Therapies 55
Percutaneous Ethanol Injection (PEI) 55
Interstitial Laser Photocoagulation 55
High-Intensity Focused Ultrasound 55
Radiation Therapy 56
Conclusions 56
References 57
Systemic Therapy for Non-operable Colorectal Cancer Metastases 59
Systemic Treatment Strategies 59
Chemotherapeutic Agents 59
5-Fluorouracil 59
Capecitabine 60
Irinotecan 61
Oxaliplatin 61
Monoclonal Antibodies 62
Bevacizumab 62
Cetuximab* 63
Panitumumab* 63
Recommendations for Systemic Treatments 64
Localized Treatment Strategies 64
Hepatic Artery Infusion 64
Neoadjuvant Chemotherapy 65
Conclusion 65
References 65
Locoregional Chemotherapy for Hepatic Metastasis of Colorectal Cancer 67
Introduction 67
Placement Technique 67
Historical Perspective 69
Randomized Clinical Trials 69
Primary Therapy 69
Secondary Therapy 70
Adjuvant Therapy Postresection 71
Ablative Techniques 71
Newer Agents Via HAI 72
Summary 73
References 74
Oncosurgical Strategies for Unresectable Liver Metastases 76
Introduction 76
Definition of Unresectability 76
Improving Resectability 77
Downstaging with Preoperative Chemotherapy 77
Conversion to Resectability 77
Chemotherapy Combined with Biological Agents 78
Risks Related to Preoperative Chemotherapy 78
Increasing Resectability with Specific Techniques 79
Portal Vein Embolization (PVE) 79
Local Treatment Modalities 80
Two-Stage Hepatectomy 80
Extreme Liver Resections 81
Treatment Strategies 81
Summary 81
Case Report: Hepatic Resection Combined with Local Treatment 82
Case Report: Two-Stage Hepatectomy and Portal Vein Embolization 82
Case Report: Two-Stage Hepatectomy, Portal Vein Embolization, and Radiofrequency Ablation 84
References 87
Adjuvant Chemotherapy 89
Introduction 89
Adjuvant Chemotherapy 89
Hepatic Arterial Infusion of Chemotherapy with or Without Systemic Chemotherapy After Resection of Hepatic Metastases 89
Systemic Chemotherapy After Resection of Hepatic Metastases 90
Neoadjuvant Chemotherapy 91
The Rationale for Neoadjuvant Chemotherapy in Patients with Resectable Liver Metastases 91
The Potential Drawbacks of Neoadjuvant Chemotherapy 92
Complete Response Before Surgery 92
Chemotherapy-Associated Hepatotoxicity 92
Results of Neoadjuvant Chemotherapy in Patients with Resectable Liver Metastases 93
Neoadjuvant Therapies Including Targeted Agents 94
Conclusions 94
References 94
Biologicals for Colorectal Cancer Metastases 96
EGFR-Targeted Therapy 96
EGFR Antibodies in Pretreated Patients with Metastatic Colorectal Cancer 96
Toxicity of EGFR Antibodies 97
Preclinical Markers for Efficacy 97
EGFR Antibodies in Untreated Patients 97
EGFR Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer 97
Anti-Angiogenetic Therapy 99
VEGF Antibody 99
VEGFR and Multiple Tyrosine Kinase Inhibitors 100
References 100
Internal Radiation for the Treatment of Liver Metastases 103
Introduction 103
Radioactive Material 104
Radiation Treatment Planning 104
Empiric Method 105
Dose Delivery 106
Laboratory Studies 106
Imaging Studies 106
Hepatic Angiography 106
Nuclear Medicine Studies 107
Toxicity 107
Patient Selection 107
Colorectal Cancer Metastases 108
Breast Cancer Metastases 109
Neuroendocrine Tumor Metastases 109
Discussion 109
References 111
Surgical Treatment of Colorectal Liver Metastases in Elderly Patients 114
Epidemiology Of Aging And Colorectal Cancer In The Western World 114
Physiological Changes In The Aging Liver 115
Comorbidity 115
Techniques In Hepatic Resection 116
Outcome 116
Summary 118
References 118
Health-Related Quality of Life and Palliative Care in Colorectal Liver Metastases 120
Background 120
What Is Health-Related Quality of Life? 121
Measurements of Health-Related Quality of Life 121
The Modular Approach to HRQoL Measures 121
The European Organisation for Research and Treatment of Cancer (EORTC) Core QL Questionnaire (QLQ-C30) 122
The Functional Assessment of Cancer Therapy-General (FACT-G) 122
Development of a Questionnaire Module Specific to Patients with Colorectal Liver Metastases 122
Methodological Issues in HRQoL: Implications for Advanced Colorectal Cancer Clinical Trials 122
Lack of A Priori Hypothesis About Possible QoL Changes Before Commencing The Trial 123
Rationale for Selecting a Specific Measure 123
Baseline Data and Missing Data 123
Timing 123
Data Analysis and Interpretation 123
Reporting Results 123
Psychological Distress 124
Anxiety 125
Depression 125
Screening for Depression 126
Hospital Anxiety and Depression Scale (HADS) 126
Edinburgh Depression Scale (EDS) 126
Social Functioning and Quality of Life 127
Spiritual Aspects of Quality of Life 127
Predictive Value of Qol Parameters: The Emergence of Social Functioning 127
Liver Metastases and Palliative Care: Advanced Stages 128
Pain 128
Jaundice 128
Nausea 128
Pruritus 129
Poor Appetite 129
Confusion and the Terminal Phase 129
Caregivers and Palliative Care in Liver Metastases 129
Summary 130
References 130
Carcinoid Liver Metastases: The Carcinoid Syndrome 132
Introduction 132
Detecting Metastatic Carcinoid Disease 132
Treatment of Carcinoid Liver Metastases 133
Resection 133
Chemoembolisation 134
Somatostatin Analogues 134
Targeted Nuclear Treatments 135
Systemic Therapies 136
Quality of Life 136
References 136
Gastrointestinal Stromal Tumors 140
Introduction 140
Pathology 140
Light Microscopy and Immunohistochemistry 140
Molecular Pathology 141
Epidemiology 141
Organ Specific Studies 142
Clinical Disease 142
Diagnosis 142
Imaging 142
Biopsy 143
Endoscopic Ultrasound 143
Treatment 143
Surgery 143
Risk of Recurrence 144
Laparoscopy 144
Cytotoxic Chemotherapy 144
Imatinib Mesylate 144
Imatinib for the Treatment of Locally Advanced and Metastatic GIST 145
Mutational Assessment and Use of Imatinib 145
Results from Escalating Doses of Imatinib 146

Duration of Therapy 146
Surgery Plus Imatinib 146
Neoadjuvant Imatinib or Surgery 146
Assessing Response to Imatinib 147
Sunitinib Malate 147
Mechanisms of Drug Resistance 147
Additional Systemic Agents 148
Hepatic Arterial Chemoembolization 148
Conclusions 149
References 149
Surgery for Breast Cancer Liver Metastases 152
Introduction 152
Metastatic Disease 152
Patient Selection 153
Liver Resection Of Breast Cancer Metastases 154
Liver Ablation Of Breast Cancer Metastases 155
Conclusion 156
References 156
Liver-Directed Therapy for Metastatic Melanoma to the Liver 158
Introduction 158
Melanoma: Primary Tumor Site 158
Ocular 158
Cutaneous 159
Therapeutic Options for Melanoma Hepatic Metastases 160
Systemic Chemotherapy 160
Locoregional Therapies 161
Hepatic Artery Infusion Therapy 161
Transarterial Hepatic Artery Chemoembolization 163
Isolated Hepatic Perfusion 164
Surgical Resection 166
Conclusion 168
References 169
Non-colorectal Gastrointestinal Liver Metastases 172
Introduction 172
Esophageal and Gastroesophageal Junction Cancer 173
Background and Epidemiology 173
Presentation and Diagnosis 173
Role of Surgery 174
Role of Adjuvant Therapies 174
Recent Novel Approaches 174
Gastric Cancer 175
Background and Epidemiology 175
Presentation and Diagnosis 175
Role of Surgery 175
Role of Adjuvant Therapies 175
Recent Novel Approaches 176
Duodenal and Small Bowel Cancer 176
Background and Epidemiology 176
Presentation and Diagnosis 176
Role Of Surgery 176
Role of Adjuvant Therapies 177
Recent Novel Approaches 177
Biliary Cancers 177
Background And Epidemiology 177
Presentation and Diagnosis 177
Role of Surgery 178
Role of Adjuvant Therapies 178
Recent Novel Approaches 178
Pancreatic Cancer 178
Background and Epidemiology 178
Presentation and Diagnosis 179
Role of Surgery 179
Role of Adjuvant Therapies 179
Recent Novel Approaches 179
Conclusion 179
References 180
Index 182