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.
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.
Front Cover 1
Transplantation: A Companion to Specialist Surgical Practice 4
Copyright 5
Contents 6
Contributors 8
Series Editors' preface 10
Editor's preface 12
Evidence-based practice in surgery 14
Chapter 1: Controversies in the ethics of organ transplantation 16
Introduction 16
Key terminology 16
Fundamental principles of bioethics 16
Other terms 16
Death, organ donation, patient autonomy and the choice to donate 17
When does death occur? 17
Futility, the patient's best interests, and the decision to withdraw life-sustaining treatments 18
Donor pain, distress and individuals' rights after death 18
The conflict between donation and dignity in death 19
Relatives' right to veto the act of organ donation 19
The paradigm of uncontrolled DCD donation – still with ethical challenges 20
Early approach to the bereaved 20
Pre-consent preservation measures 20
Preservation measures and the potential to restore cerebral circulation 20
The extremes of deceased donation 21
Allocation of organs 21
Benefit (utility) 21
Fairness (equity) 22
Transparency 22
Legality 22
Societal mandate 22
Flexibility 22
The implications of variable organ quality 23
Balance of donor and recipient risk 23
Autonomy and patient choice in allocation 24
Practical incorporation of patient choice in an allocation system 25
Ethical presentation of risk: where, when and how? 25
Living donation 26
Altruistic donation 26
Implications of the living donor work-up 27
Human organs as a commodity: incentivisation and payment for organ donation 27
References 31
Chapter 2: Organ donation in the UK: recent progress and future challenges 33
Introduction 33
Recent progress 33
Legal issues 34
Ethics 34
Disseminating donation activity data 35
Healthcare regulator assessments 35
Progress 39
Future challenges 40
Increased consent/authorisation rates 41
Increased diagnosis of brain stem death 42
Increased donation after circulatory death 43
Greater involvement of emergency departments 43
Increased referral according to minimum notification criteria 44
Better donor management 44
Other issues 45
Managing expectations 45
The potential donor pool 46
Donor characteristics 46
Summary/conclusions 46
Acknowledgements 47
References 47
Chapter 3: Immunology of graft rejection 49
Introduction 49
Basic concepts and nomenclature of immunology 49
Recognition of danger 49
Histocompatibility 49
Major histocompatibility complexes 50
Assembly of the MHC–peptide complex 50
Other histocompatibility genes in rejection 50
T cells 52
CD8-positive T cells 52
CD4-positive T cells 52
Early inflammatory response 52
Ischaemia–reperfusion injury 52
Ischaemic injury 52
Reperfusion injury 54
Sterile inflammation 54
Adaptive immune response to IRI 54
The alloimmune response 54
Recognition of alloantigen by T cells 54
Direct allorecognition 54
Indirect allorecognition 55
Semi-direct allorecognition 55
Co-stimulation 55
Co-inhibitory molecules 56
T-cell synapse 56
TCR signalling 56
T-cell differentiation: the role of cytokines 56
T-cell responses 57
T helper 1 (Th1) response 57
T helper 2 (Th2) response 57
T helper 17 (Th17) response 58
T regulatory (Treg) response 58
The effector arm of the immune response 58
Migration of activated leucocytes 58
Cell-to-cell interactions 58
Chemokines 58
Cellular mechanisms of injury 59
Antigen-specific cytotoxic CD8-positive T cells 59
Natural killer (NK) cells 59
Macrophages 59
B cells 59
Endothelial cells 60
Rejection of the allograft 60
Cell-mediated rejection 60
Antibody-mediated rejection (AMR) 61
Classification of rejection 62
Future developments 63
Tolerance 63
Accommodation 63
Xenotransplantation 63
Tissue engineering 64
Improvements in IRI 64
Acknowledgements 65
References 65
Chapter 4: Testing for histocompatibility 69
Introduction 69
Immunity 69
Histocompatibility 69
Sensitisation 70
HLA: history of clinical application and technical development 70
HLA genes and proteins: structure and genetics relevant to transplantation 72
HLA reactive antibodies, causes of sensitisation and antibody epitopes 74
Antibodies and rejection 74
Alloimmunisation to HLA proteins 75
Establishing antibody reactivity 75
Crossmatching 76
Clinical relevance of HLA reactive antibodies 76
Antibodies before kidney transplantation 76
De novo donor-specific antibodies after kidney transplantation 77
HLA reactive antibodies in transplantation of other organs 77
Antibody removal to facilitate transplantation 77
Other antibodies and their clinical relevance 77
Organ allocation and histocompatibility 78
Conclusion 79
References 80
Chapter 5: Immunosuppression with the kidney as paradigm 82
Introduction 82
Calcineurin inhibitors 82
Ciclosporin 82
Tacrolimus 83
Antimetabolites 84
mTOR inhibitors 85
Biological agents 87
Depleting antibodies 88
Equine antithymocyte globulin 88
Muromonab CD3 89
Rabbit antithymocyte globulin 89
Alemtuzumab 90
Non-depleting antibodies and biologicals 91
Daclizumab 91
Basiliximab 91
Belatacept 93
Strategies to lower toxicity 97
Corticosteroid-sparing regimens 97
CNI minimisation 99
Looking ahead 100
References 101
Chapter 6: Preservation and perfusion of abdominal organs for transplantation 104
Introduction 104
Development of preservation techniques 105
Static cold storage 105
University of Wisconsin solution 107
Histidine–tryptophan–ketoglutarate solution 107
Celsior solution 107
Institut-Georges-Lopez-1 solution 107
Hypothermic machine preservation 109
Kidney 109
State of the art 109
Donation after brain death 110
Controlled donation after circulatory death 110
Uncontrolled donation after circulatory death 111
Expanded criteria donors 111
New developments and the future 112
Liver 113
State of the art 113
Controlled donation after circulatory death 114
Uncontrolled donation after circulatory death 114
New developments and the future 115
Pancreas 117
State of the art 117
New developments and the future 118
Intestine 119
State of the art 119
New developments and the future 119
Evidence in the field of organ preservation and perfusion 120
Conclusion 121
References 121
Chapter 7: Recent trends in kidney transplantation 128
Introduction 128
Demand inflation or supply recession? 128
Innovations in living donation 129
Incompatible transplantation 130
ABO-incompatible transplantation 130
HLA-incompatible transplantation 133
Trends in deceased kidney donation 133
Optimising donor organ quality 134
Kidney allocation – new principles, same old challenges? 135
Trends in surgical technique 135
Donor surgery 135
Kidney implantation 136
Current practice and challenges in immunosuppression 136
Conclusion 137
References 138
Chapter 8: Liver transplantation 142
Introduction 142
Indications for liver transplantation 144
Acute fulminant liver failure 144
Budd–Chiari syndrome 145
Chronic liver disease 145
General considerations 145
Hepatitis C virus (HCV) infection 147
Hepatitis B virus (HBV) infection 147
Hepatocellular carcinoma (HCC) 147
Alcoholic liver disease 148
Primary biliary cirrhosis (PBC) 148
Primary sclerosing cholangitis (PSC) 148
Non-alcoholic fatty liver disease (NAFLD) 149
Liver transplant immunology 149
Technical considerations 150
Organ procurement 150
Graft implantation 150
Immunosuppressive agents 152
Induction agents 152
Primary immunosuppressants 152
Adjunct immunosuppressive agents 153
Azathioprine 153
Mycophenolic acid 153
mTOR Inhibitors 153
Corticosteroids 153
Post-transplant complications 153
Perioperative complications (first 30 days) 154
Preservation/reperfusion injury 154
Primary non-function (PNF) 154
Haemorrhage 154
Hepatic artery thrombosis (HAT) 155
Portal vein thrombosis (PVT) 155
Biliary complications: bile leaks 155
Early (first 6 months) complications 155
Biliary strictures 155
Acute rejection 156
Infections 156
Late complications ( > 6 months)
Malignancy 158
Late surgical complications 158
Biliary strictures 159
Vascular complications 159
Chronic rejection 159
Conclusion 159
References 160
Chapter 9: Pancreas transplantation 164
Introduction 164
Indications for pancreas transplantation 164
Pancreas transplantation for type II diabetes 164
Pancreas transplantation from living donors 165
Patient selection for pancreas transplantation 165
Simultaneous pancreas–kidney transplantation (SPK) 165
Pancreas after kidney transplantation (PAK) 166
Pancreas transplantation alone (PTA) 167
Pancreas transplantation activity worldwide 168
The pancreas donor and the organ retrieval procedure 169
Criteria for eligibility for pancreas donors 169
Pancreas retrieval operation 172
The pancreas transplant operation 173
General considerations 173
Management of exocrine secretions 174
Management of the venous drainage 174
Immunosuppression in pancreas transplantation 175
Acute rejection following pancreas transplantation 176
Diagnosis of acute rejection 176
Management of acute rejection 177
Impact of acute rejection on outcome 178
Complications of pancreas transplantation 178
Introduction 178
Vascular complications 178
Thrombosis 178
Haemorrhage 179
Infective complications 180
Allograft pancreatitis 180
Complications specific to bladder drainage 180
Outcome following pancreas transplantation 181
Introduction 181
Factors influencing pancreas transplantation outcome 182
Recipient age 182
Re-transplantation 182
HLA matching 182
Management of exocrine secretions: management of venous drainage 183
Immunosuppression 183
Donor factors 183
Long-term outlook following pancreas transplantation 184
Pancreas transplantation and life expectancy 184
Influence of pancreas transplantation on diabetic complications 185
Nephropathy 185
Retinopathy 185
Neuropathy 185
Cardiovascular disease 185
References 186
Chapter 10: Islet transplantation 190
Introduction 190
Patient selection and assessment 191
Islet isolation 192
The islet transplant 193
Immunosuppression and outcomes 194
Barriers to long-term function 195
Islets as a cell therapy 196
References 196
Chapter 11: Cardiothoracic transplantation 199
Introduction 199
Indications for heart transplantation 199
Aetiology of heart disease 199
Introduction 199
Ischaemic heart disease 200
Non-ischaemic cardiomyopathy 200
Congenital heart disease 200
Recipient evaluation and selection 200
Selection criteria 200
Contraindications 202
Other options 203
Cardiac resynchronisation treatment (CRT) 203
Implantable cardio defibrillators (ICDs) 203
Ventricular assist devices 203
Donor selection and matching 204
Donor age 204
Cardiac function 204
Donor disease 204
Size matching 205
ABO compatibility 205
Immunological matching 205
Donor heart procurement 205
Heart transplantation ( Figs 11.1 and 11.2) 206
Special situations 207
Heart transplantation for congenital heart disease 207
Heterotopic heart transplantation 207
Perioperative management 207
Graft function 207
Immunosuppression 208
Infection prophylaxis and treatment 208
Survival 208
Cause of death after heart transplantation 208
Cardiac allograft vasculopathy 209
Malignancy 209
Hypertension 210
Chronic renal dysfunction 210
Heart and lung transplantation (HLT) 210
Recipient selection criteria 210
Pulmonary hypertension without congenital heart disease 210
Eisenmenger's syndrome 210
Heart–lung operation 211
Survival 211
Future direction in heart transplantation 211
Lung transplantation 211
Choice of lung transplant procedure 211
Lung recipient assessment and selection 212
Lung donor criteria and selection 214
Ex vivo lung perfusion 214
Lung recipient–donor matching 214
Lung retrieval and preservation 215
Single lung implantation 216
Bilateral sequential lung implantation 216
Peri- and postoperative care for lung transplants 217
Outcomes and complications of lung transplantation 218
Recent advances and controversies 219
References 221
Chapter 12: Transplant infectious disease 225
Introduction and general concepts 225
Viruses: epidemiology, prophylaxis, diagnosis and treatment 229
Epidemiology 229
Prophylaxis 230
Diagnosis 234
Treatment 234
Bacteria: epidemiology, prophylaxis, diagnosis and treatment 235
Epidemiology 235
Prophylaxis 235
Diagnosis 235
Treatment 235
Fungi: epidemiology, prophylaxis, diagnosis and treatment 236
Epidemiology 236
Prophylaxis 236
Diagnosis 237
Treatment 237
Parasites: epidemiology, prophylaxis, diagnosis, and treatment 238
Epidemiology 238
Prophylaxis 238
Diagnosis 238
Treatment 239
Pre-transplant infectious disease evaluation 239
Donor-derived infections 240
Lifestyle and infection: food, pets, travel and sexuality 241
References 243
Chapter 13: Chronic transplant dysfunction 246
Introduction 246
Organ-specific findings 246
Heart 246
Liver 248
Lung 249
Management 250
Pancreas 250
Kidney 251
Why and how does IF/TA occur? Clinical insights 251
The aetiology of chronic graft injury 252
Peri-transplant factors: beyond our control? 253
Post-transplant immunity: acute rejection 253
Post-transplant immunity: antibody-mediated rejection 254
Diagnosis of antibody-mediated rejection: acute and chronic 254
Associations of antibody and CGI 255
Post-transplant factors: viral infections 256
Cytomegalovirus (CMV) infection 256
Polyomavirus infection 256
Post-transplant factors: immunosuppression 257
Post-transplant stressors 257
Hypertension 257
Dyslipidaemia 258
Post-transplant diabetes mellitus 258
Anaemia 259
Pathophysiology 259
What are the targets that mediate chronic injury? 260
What is the source of matrix? 260
The contributions of the innate immune response 261
The management of chronic graft injury in the kidney 263
Principles of management 263
Abrogating matrix deposition: a novel option for CGI management? 263
Diagnostic strategies in monitoring for CGI 264
Allograft biopsy 264
Assays of whole blood: serum antibodies 265
Assays of whole blood: proteins 265
Assays of whole blood: gene expression 265
Assays of whole blood: cellular functional analysis 266
Assays of urine: gene and proteomic approaches 266
References 267
Index 272
Controversies in the ethics of organ transplantation
Marc J. Clancy and Alex T. Vesey
Introduction
• Clinical transplantation remains a relatively young field, yet it has created considerable ethical debate. Development of clinical programmes has required the rapid parallel development of ethical frameworks to justify the steps taken in the name of patient benefit.
• In many ways, the rate of technological advance has exceeded the development of the ethical, cultural and legal framework within which transplantation takes place. This has resulted in a variety of fascinating ethical debates but also represents a barrier to fully realising the potential of transplantation.
• All transplant professionals have a responsibility to be aware of the many ethical issues that surround transplantation and organ donation. It is also desirable for such professionals to be familiar with the terminology used to describe and discuss the ethics of transplantation.
• Good ethical practice should always be integral to efforts made to advance the science of transplantation. Interaction with stakeholders, lawmakers and those who determine public policy will be essential to the development of optimal future programmes.
Key terminology
Fundamental principles of bioethics
Beneficence Doing good for the patient must be the central moral objective for all healthcare staff.
Non-maleficence All effort must be made to avoid causing harm or distress to patients and their families. A central principle in organ donation is that donors are by definition ‘harmed’ in order to facilitate donation. This harm must be weighed up against the good that results from transplantation.
Autonomy The patient's autonomy must be respected. The individual has a (near) absolute right to determine their own fate – including that of their organs after death.
Justice Healthcare professionals should strive to seek fairness. Particularly relevant to transplantation where multiple conflicts of interest exist between various stakeholder groups.
Other terms
Deontology From the Greek ‘deon’ meaning obligation or duty. The ethical position which judges the morality of an action or belief on its adherence to a rule, e.g. ‘do no harm’ or ‘always strive to save a life’.
Consequentialism Contrasts with deontology; judging the morality of actions according to their consequences.
Utilitarianism The ethical position that the value of a particular course of action is determined by how much ‘good’ or happiness results, the total ‘good’ usually referring to the world as a whole.
Altruism In a transplant context, the voluntary wish of the individual to make the ‘gift’ of donation of their organs (or equivalent) without expectation of reward.
Dignity A complex and difficult term to define but, in this context, one reflecting the unique and precious status of the human being and the ethical requirement not to treat the individual disrespectfully or harmfully in both life and death.
Futility A concept that relates to a patient who has reached a point when there is no realistic prospect of a successful outcome, whatever their medical care.
Equity The concept of fairness/justice often used in connection with the way organs are allocated and utilised. Also applied to access to transplant for different individuals.
Death, organ donation, patient autonomy and the choice to donate
While living donation has been integral to kidney transplantation for decades, deceased donors have always constituted the majority of transplant activity. Death and its diagnosis seemed a simple and easily understandable concept until complex modern intensive methods and care of transplantation forced society to question it in more detail.
If doctors are striving to save the life of a patient, and yet there exists a possibility that the patient must die and donate their organs (so that other patients may be helped), there may be a perceived conflict of interest for the responsible physician. To avoid this, a clear separation between medical care in life and the facilitation of deceased donation has been established. The pivotal component of this is the establishment of death.
When does death occur?
Substantial ethical debate surrounds the exact definition of death and this is reflected in the variability of definition between societies.1,2
Standard clinical tests for the certification of death include the absence of circulation, respiration, any response to pain or pupillary response to light. However, these tests require a valid setting and need to be confirmed over a sufficient length of time in order to ensure no reasonable possibility of spontaneous reversal. Brain stem death3 allowed certification of death based on irreversible loss of brain stem function. This complex and intensively scrutinised mechanism for individuals to be declared legally dead has allowed organ donation even when the donor has a beating heart and viable organs maintained via mechanical ventilation.
The key ethical principle is that donation should proceed only after death has been established and no prospect of spontaneous autoresuscitation exists.4
Similarly, the decision to cease attempts at life- preserving treatments should be taken in a manner independent of considerations relating to organ donation and be based purely on the concept of patient benefit.
The idea of brain death remains a focus for ethical debate despite its long enshrinement in law. Initially the term ‘brain dead’ was applied, yet the demonstration of viable neuronal tissue was cited as a refutation of this as a valid state of death. This led to a change of terminology, with ‘brain stem dead’ being the currently accepted expression.5
The management of patients to facilitate organ donation either through the donation-after-brain stem-death (DBD) pathway or the alternative donation-after-circulatory-death (DCD) pathway remains one of the biggest ethical debating points of 21st century transplantation and intensive care medicine.
Guidance on the determination and diagnosis of death can be found in the Academy of Royal Colleges Code of Practice for the Diagnosis and Confirmation of Death (2008);6 however, there remains no statutory definition of death in the UK and the working definition, ‘the irreversible loss of the capacity for consciousness combined with irreversible loss of the capacity to breathe’, put forward by the Department of Health, seems both practicable and socially acceptable. However, further clarification of this definition may be of benefit to all stakeholders.
Futility, the patient's best interests, and the decision to withdraw life-sustaining treatments
In a situation where organ donation may be feasible, what constitutes a potential donor's best interests? Before organ donation and transplantation, it was accepted that when a stage of futility was deemed to have been reached, further life-prolonging interventions were not in a dying patient's best interests. This was observed in the early days of transplantation, when continuing intervention was seen as unethical as these interventions were not designed for the benefit of the potential donor. This debate was particularly fierce around the issue of elective ventilation, with a historical conclusion that this was not an ethically desirable course of action.7
However, the nature of futility itself may have been changed by the very existence of the possibility for organ donation. Few citizens in the developed world are unaware that donation of organs after death is a possibility. In the UK, originally through the organ donor card system and more recently through the organ donor register (ODR), the opportunity to document one's wishes relating to organ donation has become increasingly accessible. This opt-in system has donor autonomy at its heart. In states like Spain, however, opt-out is the legal norm,8 when the individual must record a wish to opt out of organ donation or it will be assumed that the wish is to go ahead with this action. Other options such as mandated choice come somewhere in between, and the desirability and likely effect on donation rates of each system are widely debated.9 What is certain, though, is that the stated, informed and autonomous wish of a competent, living person to donate their organs can be regarded as a form of mandate to advance organ donation, even if this action may include interventions traditionally considered futile and therefore unethical.
In this context, what we mean by ‘best interests’ is less clear-cut. Many – including these authors – would regard it as unethical for a...
| Erscheint lt. Verlag | 24.6.2013 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizinische Fachgebiete ► Chirurgie ► Viszeralchirurgie |
| ISBN-10 | 0-7020-4968-9 / 0702049689 |
| ISBN-13 | 978-0-7020-4968-2 / 9780702049682 |
| Haben Sie eine Frage zum Produkt? |
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