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Book Details
Abstract
Transplantation meets the needs of surgeons in higher training and practising consultants for a contemporary and evidence-based account of this sub-specialty that is relevant to their general surgical practice. It is a practical reference source incorporating the most current information on recent developments, management issues and operative procedures. The text is thoroughly referenced and supported by evidence-based recommendations wherever possible, distinguishing between strong evidence to support a conclusion, and evidence suggesting that a recommendation can be reached on the balance of probabilities.
This is a title in the Companion to Specialist Surgical Practice series whose eight volumes are an established and highly regarded source of information for the specialist general surgeon.
- The Companion to Specialist Surgical Practice series provides a current and concise summary of the key topics within each major surgical sub-specialty.
- Each volume highlights evidence-based practice both in the text and within the extensive list of references at the end of every chapter.
- An expanded authorship team across the series includes additional European and World experts with an increased emphasis on global practice.
- The contents of the series have been extensively revised in line with recently published evidence.
- Modern techniques in transplantation and new forms of immunosuppression are emphasised throughout this volume.
- The substantial interest in new organ perfusion and in the preservation techniques in organ donation and transplantation are reflected in a new chapter written by an international expert.
- All the chapters reflect transplant care as a multi-disciplinary team of clinicians working in a collaborative fashion.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Transplantation: A Companion to Specialist Surgical Practice | iii | ||
| Copyright | iv | ||
| Contents | v | ||
| Contributors | vii | ||
| Series Editors' preface | ix | ||
| Editor's preface | xi | ||
| Evidence-based practice in surgery | xiii | ||
| Chapter 1: Controversies in the ethics of organ transplantation | 1 | ||
| Introduction | 1 | ||
| Key terminology | 1 | ||
| Fundamental principles of bioethics | 1 | ||
| Other terms | 1 | ||
| Death, organ donation, patient autonomy and the choice to donate | 2 | ||
| When does death occur? | 2 | ||
| Futility, the patient's best interests, and the decision to withdraw life-sustaining treatments | 3 | ||
| Donor pain, distress and individuals' rights after death | 3 | ||
| The conflict between donation and dignity in death | 4 | ||
| Relatives' right to veto the act of organ donation | 4 | ||
| The paradigm of uncontrolled DCD donation – still with ethical challenges | 5 | ||
| Early approach to the bereaved | 5 | ||
| Pre-consent preservation measures | 5 | ||
| Preservation measures and the potential to restore cerebral circulation | 5 | ||
| The extremes of deceased donation | 6 | ||
| Allocation of organs | 6 | ||
| Benefit (utility) | 6 | ||
| Fairness (equity) | 7 | ||
| Transparency | 7 | ||
| Legality | 7 | ||
| Societal mandate | 7 | ||
| Flexibility | 7 | ||
| The implications of variable organ quality | 8 | ||
| Balance of donor and recipient risk | 8 | ||
| Autonomy and patient choice in allocation | 9 | ||
| Practical incorporation of patient choice in an allocation system | 10 | ||
| Ethical presentation of risk: where, when and how? | 10 | ||
| Living donation | 11 | ||
| Altruistic donation | 11 | ||
| Implications of the living donor work-up | 12 | ||
| Human organs as a commodity: incentivisation and payment for organ donation | 12 | ||
| References | 16 | ||
| Chapter 2: Organ donation in the UK: recent progress and future challenges | 18 | ||
| Introduction | 18 | ||
| Recent progress | 18 | ||
| Legal issues | 19 | ||
| Ethics | 19 | ||
| Disseminating donation activity data | 20 | ||
| Healthcare regulator assessments | 20 | ||
| Progress | 24 | ||
| Future challenges | 25 | ||
| Increased consent/authorisation rates | 26 | ||
| Increased diagnosis of brain stem death | 27 | ||
| Increased donation after circulatory death | 28 | ||
| Greater involvement of emergency departments | 28 | ||
| Increased referral according to minimum notification criteria | 29 | ||
| Better donor management | 29 | ||
| Other issues | 30 | ||
| Managing expectations | 30 | ||
| The potential donor pool | 31 | ||
| Donor characteristics | 31 | ||
| Summary/conclusions | 31 | ||
| Acknowledgements | 32 | ||
| References | 32 | ||
| Chapter 3: Immunology of graft rejection | 34 | ||
| Introduction | 34 | ||
| Basic concepts and nomenclature of immunology | 34 | ||
| Recognition of danger | 34 | ||
| Histocompatibility | 34 | ||
| Major histocompatibility complexes | 35 | ||
| Assembly of the MHC–peptide complex | 35 | ||
| Other histocompatibility genes in rejection | 35 | ||
| T cells | 37 | ||
| CD8-positive T cells | 37 | ||
| CD4-positive T cells | 37 | ||
| Early inflammatory response | 37 | ||
| Ischaemia–reperfusion injury | 37 | ||
| Ischaemic injury | 37 | ||
| Reperfusion injury | 39 | ||
| Sterile inflammation | 39 | ||
| Adaptive immune response to IRI | 39 | ||
| The alloimmune response | 39 | ||
| Recognition of alloantigen by T cells | 39 | ||
| Direct allorecognition | 39 | ||
| Indirect allorecognition | 40 | ||
| Semi-direct allorecognition | 40 | ||
| Co-stimulation | 40 | ||
| Co-inhibitory molecules | 41 | ||
| T-cell synapse | 41 | ||
| TCR signalling | 41 | ||
| T-cell differentiation: the role of cytokines | 41 | ||
| T-cell responses | 42 | ||
| T helper 1 (Th1) response | 42 | ||
| T helper 2 (Th2) response | 42 | ||
| T helper 17 (Th17) response | 43 | ||
| T regulatory (Treg) response | 43 | ||
| The effector arm of the immune response | 43 | ||
| Migration of activated leucocytes | 43 | ||
| Cell-to-cell interactions | 43 | ||
| Chemokines | 43 | ||
| Cellular mechanisms of injury | 44 | ||
| Antigen-specific cytotoxic CD8-positive T cells | 44 | ||
| Natural killer (NK) cells | 44 | ||
| Macrophages | 44 | ||
| B cells | 44 | ||
| Endothelial cells | 45 | ||
| Rejection of the allograft | 45 | ||
| Cell-mediated rejection | 45 | ||
| Antibody-mediated rejection (AMR) | 46 | ||
| Classification of rejection | 47 | ||
| Future developments | 48 | ||
| Tolerance | 48 | ||
| Accommodation | 48 | ||
| Xenotransplantation | 48 | ||
| Tissue engineering | 49 | ||
| Improvements in IRI | 49 | ||
| Acknowledgements | 50 | ||
| References | 50 | ||
| Chapter 4: Testing for histocompatibility | 54 | ||
| Introduction | 54 | ||
| Immunity | 54 | ||
| Histocompatibility | 54 | ||
| Sensitisation | 55 | ||
| HLA: history of clinical application and technical development | 55 | ||
| HLA genes and proteins: structure and genetics relevant to transplantation | 57 | ||
| HLA reactive antibodies, causes of sensitisation and antibody epitopes | 59 | ||
| Antibodies and rejection | 59 | ||
| Alloimmunisation to HLA proteins | 60 | ||
| Establishing antibody reactivity | 60 | ||
| Crossmatching | 61 | ||
| Clinical relevance of HLA reactive antibodies | 61 | ||
| Antibodies before kidney transplantation | 61 | ||
| De novo donor-specific antibodies after kidney transplantation | 62 | ||
| HLA reactive antibodies in transplantation of other organs | 62 | ||
| Antibody removal to facilitate transplantation | 62 | ||
| Other antibodies and their clinical relevance | 62 | ||
| Organ allocation and histocompatibility | 63 | ||
| Conclusion | 64 | ||
| References | 65 | ||
| Chapter 5: Immunosuppression with the kidney as paradigm | 67 | ||
| Introduction | 67 | ||
| Calcineurin inhibitors | 67 | ||
| Ciclosporin | 67 | ||
| Tacrolimus | 68 | ||
| Antimetabolites | 69 | ||
| mTOR inhibitors | 70 | ||
| Biological agents | 72 | ||
| Depleting antibodies | 73 | ||
| Equine antithymocyte globulin | 73 | ||
| Muromonab CD3 | 74 | ||
| Rabbit antithymocyte globulin | 74 | ||
| Alemtuzumab | 75 | ||
| Non-depleting antibodies and biologicals | 76 | ||
| Daclizumab | 76 | ||
| Basiliximab | 76 | ||
| Belatacept | 78 | ||
| Strategies to lower toxicity | 82 | ||
| Corticosteroid-sparing regimens | 82 | ||
| CNI minimisation | 84 | ||
| Looking ahead | 85 | ||
| References | 86 | ||
| Chapter 6: Preservation and perfusion of abdominal organs for transplantation | 89 | ||
| Introduction | 89 | ||
| Development of preservation techniques | 90 | ||
| Static cold storage | 90 | ||
| University of Wisconsin solution | 92 | ||
| Histidine–tryptophan–ketoglutarate solution | 92 | ||
| Celsior solution | 92 | ||
| Institut-Georges-Lopez-1 solution | 92 | ||
| Hypothermic machine preservation | 94 | ||
| Kidney | 94 | ||
| State of the art | 94 | ||
| Donation after brain death | 95 | ||
| Controlled donation after circulatory death | 95 | ||
| Uncontrolled donation after circulatory death | 96 | ||
| Expanded criteria donors | 96 | ||
| New developments and the future | 97 | ||
| Liver | 98 | ||
| State of the art | 98 | ||
| Controlled donation after circulatory death | 99 | ||
| Uncontrolled donation after circulatory death | 99 | ||
| New developments and the future | 100 | ||
| Pancreas | 102 | ||
| State of the art | 102 | ||
| New developments and the future | 103 | ||
| Intestine | 104 | ||
| State of the art | 104 | ||
| New developments and the future | 104 | ||
| Evidence in the field of organ preservation and perfusion | 105 | ||
| Conclusion | 106 | ||
| References | 106 | ||
| Chapter 7: Recent trends in kidney transplantation | 113 | ||
| Introduction | 113 | ||
| Demand inflation or supply recession? | 113 | ||
| Innovations in living donation | 114 | ||
| Incompatible transplantation | 115 | ||
| ABO-incompatible transplantation | 115 | ||
| HLA-incompatible transplantation | 118 | ||
| Trends in deceased kidney donation | 118 | ||
| Optimising donor organ quality | 119 | ||
| Kidney allocation – new principles, same old challenges? | 120 | ||
| Trends in surgical technique | 120 | ||
| Donor surgery | 120 | ||
| Kidney implantation | 121 | ||
| Current practice and challenges in immunosuppression | 121 | ||
| Conclusion | 122 | ||
| References | 123 | ||
| Chapter 8: Liver transplantation | 127 | ||
| Introduction | 127 | ||
| Indications for liver transplantation | 129 | ||
| Acute fulminant liver failure | 129 | ||
| Budd–Chiari syndrome | 130 | ||
| Chronic liver disease | 130 | ||
| General considerations | 130 | ||
| Hepatitis C virus (HCV) infection | 132 | ||
| Hepatitis B virus (HBV) infection | 132 | ||
| Hepatocellular carcinoma (HCC) | 132 | ||
| Alcoholic liver disease | 133 | ||
| Primary biliary cirrhosis (PBC) | 133 | ||
| Primary sclerosing cholangitis (PSC) | 133 | ||
| Non-alcoholic fatty liver disease (NAFLD) | 134 | ||
| Liver transplant immunology | 134 | ||
| Technical considerations | 135 | ||
| Organ procurement | 135 | ||
| Graft implantation | 135 | ||
| Immunosuppressive agents | 137 | ||
| Induction agents | 137 | ||
| Primary immunosuppressants | 137 | ||
| Adjunct immunosuppressive agents | 138 | ||
| Azathioprine | 138 | ||
| Mycophenolic acid | 138 | ||
| mTOR Inhibitors | 138 | ||
| Corticosteroids | 138 | ||
| Post-transplant complications | 138 | ||
| Perioperative complications (first 30 days) | 139 | ||
| Preservation/reperfusion injury | 139 | ||
| Primary non-function (PNF) | 139 | ||
| Haemorrhage | 139 | ||
| Hepatic artery thrombosis (HAT) | 140 | ||
| Portal vein thrombosis (PVT) | 140 | ||
| Biliary complications: bile leaks | 140 | ||
| Early (first 6 months) complications | 140 | ||
| Biliary strictures | 140 | ||
| Acute rejection | 141 | ||
| Infections | 141 | ||
| Late complications ( > 6 months) | 143 | ||
| Malignancy | 143 | ||
| Late surgical complications | 143 | ||
| Biliary strictures | 144 | ||
| Vascular complications | 144 | ||
| Chronic rejection | 144 | ||
| Conclusion | 144 | ||
| References | 145 | ||
| Chapter 9: Pancreas transplantation | 149 | ||
| Introduction | 149 | ||
| Indications for pancreas transplantation | 149 | ||
| Pancreas transplantation for type II diabetes | 149 | ||
| Pancreas transplantation from living donors | 150 | ||
| Patient selection for pancreas transplantation | 150 | ||
| Simultaneous pancreas–kidney transplantation (SPK) | 150 | ||
| Pancreas after kidney transplantation (PAK) | 151 | ||
| Pancreas transplantation alone (PTA) | 152 | ||
| Pancreas transplantation activity worldwide | 153 | ||
| The pancreas donor and the organ retrieval procedure | 154 | ||
| Criteria for eligibility for pancreas donors | 154 | ||
| Pancreas retrieval operation | 157 | ||
| The pancreas transplant operation | 158 | ||
| General considerations | 158 | ||
| Management of exocrine secretions | 159 | ||
| Management of the venous drainage | 159 | ||
| Immunosuppression in pancreas transplantation | 160 | ||
| Acute rejection following pancreas transplantation | 161 | ||
| Diagnosis of acute rejection | 161 | ||
| Management of acute rejection | 162 | ||
| Impact of acute rejection on outcome | 163 | ||
| Complications of pancreas transplantation | 163 | ||
| Introduction | 163 | ||
| Vascular complications | 163 | ||
| Thrombosis | 163 | ||
| Haemorrhage | 164 | ||
| Infective complications | 165 | ||
| Allograft pancreatitis | 165 | ||
| Complications specific to bladder drainage | 165 | ||
| Outcome following pancreas transplantation | 166 | ||
| Introduction | 166 | ||
| Factors influencing pancreas transplantation outcome | 167 | ||
| Recipient age | 167 | ||
| Re-transplantation | 167 | ||
| HLA matching | 167 | ||
| Management of exocrine secretions: management of venous drainage | 168 | ||
| Immunosuppression | 168 | ||
| Donor factors | 168 | ||
| Long-term outlook following pancreas transplantation | 169 | ||
| Pancreas transplantation and life expectancy | 169 | ||
| Influence of pancreas transplantation on diabetic complications | 170 | ||
| Nephropathy | 170 | ||
| Retinopathy | 170 | ||
| Neuropathy | 170 | ||
| Cardiovascular disease | 170 | ||
| References | 171 | ||
| Chapter 10: Islet transplantation | 175 | ||
| Introduction | 175 | ||
| Patient selection and assessment | 176 | ||
| Islet isolation | 177 | ||
| The islet transplant | 178 | ||
| Immunosuppression and outcomes | 179 | ||
| Barriers to long-term function | 180 | ||
| Islets as a cell therapy | 181 | ||
| References | 181 | ||
| Chapter 11: Cardiothoracic transplantation | 184 | ||
| Chapter 12: Transplant infectious disease | 210 | ||
| Introduction and general concepts | 210 | ||
| Viruses: epidemiology, prophylaxis, diagnosis and treatment | 214 | ||
| Epidemiology | 214 | ||
| Prophylaxis | 215 | ||
| Diagnosis | 219 | ||
| Treatment | 219 | ||
| Bacteria: epidemiology, prophylaxis, diagnosis and treatment | 220 | ||
| Epidemiology | 220 | ||
| Prophylaxis | 220 | ||
| Diagnosis | 220 | ||
| Treatment | 220 | ||
| Fungi: epidemiology, prophylaxis, diagnosis and treatment | 221 | ||
| Epidemiology | 221 | ||
| Prophylaxis | 221 | ||
| Diagnosis | 222 | ||
| Treatment | 222 | ||
| Parasites: epidemiology, prophylaxis, diagnosis, and treatment | 223 | ||
| Epidemiology | 223 | ||
| Prophylaxis | 223 | ||
| Diagnosis | 223 | ||
| Treatment | 224 | ||
| Pre-transplant infectious disease evaluation | 224 | ||
| Donor-derived infections | 225 | ||
| Lifestyle and infection: food, pets, travel and sexuality | 226 | ||
| References | 228 | ||
| Chapter 13: Chronic transplant dysfunction | 231 | ||
| Introduction | 231 | ||
| Organ-specific findings | 231 | ||
| Heart | 231 | ||
| Liver | 233 | ||
| Lung | 234 | ||
| Management | 235 | ||
| Pancreas | 235 | ||
| Kidney | 236 | ||
| Why and how does IF/TA occur? Clinical insights | 236 | ||
| The aetiology of chronic graft injury | 237 | ||
| Peri-transplant factors: beyond our control? | 238 | ||
| Post-transplant immunity: acute rejection | 238 | ||
| Post-transplant immunity: antibody-mediated rejection | 239 | ||
| Diagnosis of antibody-mediated rejection: acute and chronic | 239 | ||
| Associations of antibody and CGI | 240 | ||
| Post-transplant factors: viral infections | 241 | ||
| Cytomegalovirus (CMV) infection | 241 | ||
| Polyomavirus infection | 241 | ||
| Post-transplant factors: immunosuppression | 242 | ||
| Post-transplant stressors | 242 | ||
| Hypertension | 242 | ||
| Dyslipidaemia | 243 | ||
| Post-transplant diabetes mellitus | 243 | ||
| Anaemia | 244 | ||
| Pathophysiology | 244 | ||
| What are the targets that mediate chronic injury? | 245 | ||
| What is the source of matrix? | 245 | ||
| The contributions of the innate immune response | 246 | ||
| The management of chronic graft injury in the kidney | 248 | ||
| Principles of management | 248 | ||
| Abrogating matrix deposition: a novel option for CGI management? | 248 | ||
| Diagnostic strategies in monitoring for CGI | 249 | ||
| Allograft biopsy | 249 | ||
| Assays of whole blood: serum antibodies | 250 | ||
| Assays of whole blood: proteins | 250 | ||
| Assays of whole blood: gene expression | 250 | ||
| Assays of whole blood: cellular functional analysis | 251 | ||
| Assays of urine: gene and proteomic approaches | 251 | ||
| References | 252 | ||
| Index | 257 |