INTRO TO ORGAN TRANSPLANTATION (2ED) - 2nd Edition

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April 24, 2012 16:5 9in x 6in Introduction to Organ Transplantation, 2nd Edition b1297-fm

If we excel in anything, it is in our capacity for translating

idealism into action.
Charles H Mayo, MD

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April 24, 2012 16:5 9in x 6in Introduction to Organ Transplantation, 2nd Edition b1297-fm

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April 24, 2012 16:5 9in x 6in Introduction to Organ Transplantation, 2nd Edition b1297-fm

Dedicated to my children: David, Alexandra,

Andrea and Gabi.

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Contents

Contributors xix

Foreword xxiii

1. History of Organ and Cell Transplantation 1

Nadey S. Hakim and Vassilios Papalois
1.1 HLA and Transplantation Immunology . . . . . . . . . 1
1.1.1 Initial use of cell culture methodologies to detect
major histocompatibility complex (MHC)
products . . . . . . . . . . . . . . . . . . . . . . 2
1.1.2 Genomic organization of the HLA complex . . . 2
1.1.3 Organizations . . . . . . . . . . . . . . . . . . . 2
1.2 Organ Donation and Sharing . . . . . . . . . . . . . . . 3
1.2.1 The early kidney programmes . . . . . . . . . . 3
1.2.2 The exchange programmes . . . . . . . . . . . . 3
1.2.3 The donors . . . . . . . . . . . . . . . . . . . . 4
1.2.4 Brain death . . . . . . . . . . . . . . . . . . . . 4
1.2.5 The nonrenal organs . . . . . . . . . . . . . . . 4
1.3 The History of Kidney Transplantation . . . . . . . . . 5
1.3.1 1902–1912: Experimental efforts of Ullmann
and Carrel . . . . . . . . . . . . . . . . . . . . . 5
1.3.2 1906–1913: Initial kidney transplants from animals
to humans . . . . . . . . . . . . . . . . . . . . . 5
1.3.3 1936: First unsuccessful kidney transplant
between humans . . . . . . . . . . . . . . . . . 5

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1.3.4 1943–1944: Medawar’s explanation of graft

destruction due to ‘biological incompability’,
as described by Carrel . . . . . . . . . . . . . . . 6
1.3.5 1947–1953: Initial unsuccessful allotransplants
after World War II . . . . . . . . . . . . . . . . 6
1.3.6 1959: First successful kidney transplant between
nonidentical twins . . . . . . . . . . . . . . . . 7
1.3.7 1960: First successful kidney transplant between
nontwin siblings . . . . . . . . . . . . . . . . . 7
1.3.8 1960–1961: First successful kidney
transplant between nonsiblings . . . . . . . . . . 7
1.3.9 1961–1962: First kidney transplants using
azathioprine . . . . . . . . . . . . . . . . . . . . 7
1.3.10 1962: First successful cadaveric kidney transplant
using immunosuppression . . . . . . . . . . . . . 8
1.4 The History of Liver Transplantation . . . . . . . . . . . 8
1.5 Multi-Visceral Transplants . . . . . . . . . . . . . . . . 9
1.6 The History of Pancreas Transplantation . . . . . . . . . 9
1.6.1 Clinical chronology . . . . . . . . . . . . . . . . 10
1.6.2 Evolution of recipient selection and programme
development . . . . . . . . . . . . . . . . . . . 10
1.7 The Development of Islet Transplantation . . . . . . . . 10
1.7.1 The first successful islet isolation
and transplantation . . . . . . . . . . . . . . . . 10
1.7.2 Development of techniques for identification,
tissue culture and cryopreservation of islet tissue,
and assessment of islet viability and function . . . 11
1.7.3 Clinical islet transplantation . . . . . . . . . . . . 11
1.8 The History of Intestinal Transplantation . . . . . . . . . 12
1.8.1 The world experience . . . . . . . . . . . . . . 12
1.8.2 The Pittsburgh experience . . . . . . . . . . . . 12
1.8.3 Future prospects . . . . . . . . . . . . . . . . . 12
1.9 The History of Heart Transplantation and Heart
Valve Transplantation . . . . . . . . . . . . . . . . . . . 13
1.9.1 Clinical heart transplantation in humans . . . . . 13
1.9.2 Heart valve transplantation . . . . . . . . . . . . 13
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Contents xi

1.10 Lung Transplantation . . . . . . . . . . . . . . . . . . . 14

1.10.1 Living-related lobar lung transplantation . . . . . 14
1.11 Bone Marrow Transplantation . . . . . . . . . . . . . . 14
1.11.1 Early attempts at BMT . . . . . . . . . . . . . . 14
1.11.2 The new era . . . . . . . . . . . . . . . . . . . 15
1.11.3 New developments . . . . . . . . . . . . . . . . 15
1.12 Arm Transplantation . . . . . . . . . . . . . . . . . . . 15
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

2. Ethical Issues in Transplantation 21

Miran Epstein
2.1 The Political Economy of Transplantation . . . . . . . . 24
2.1.1 The demand for organs . . . . . . . . . . . . . . 25
2.1.2 The supply of organs . . . . . . . . . . . . . . . 27
2.2 Two Great Solutions . . . . . . . . . . . . . . . . . . . 30
2.3 The Ethical Discourse: Procurement of Organs . . . . . 32
2.3.1 Prosthetic implants . . . . . . . . . . . . . . . . 32
2.3.2 Xenogeneic organs . . . . . . . . . . . . . . . . 33
2.3.3 Human organs . . . . . . . . . . . . . . . . . . 37
2.4 The Ethical Discourse: Distribution of Organs . . . . . . 51
2.4.1 Prosthetic implants . . . . . . . . . . . . . . . . 51
2.4.2 Xenogeneic organs . . . . . . . . . . . . . . . . 53
2.4.3 Human organs . . . . . . . . . . . . . . . . . . 53
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

3. HLA, The Human Major Histocompatibility Complex 59

Jacques Colombani
3.1 Variability and Polymorphism . . . . . . . . . . . . . . 61
3.2 Importance of HLA Compatibility in Transplantation . . 67
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

4. Skin Transplantation 71
Shahid A. Khan, John R. C. Telfer and Dai M. Davies
4.1 Alternative Skin Cover . . . . . . . . . . . . . . . . . . 72
4.2 Allograft Skin . . . . . . . . . . . . . . . . . . . . . . . 72
4.2.1 Allograft skin as a biological dressing . . . . . . . 73
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4.2.2 Allograft skin as temporary skin cover . . . . . . 73

4.2.3 Allograft skin for definitive skin cover . . . . . . 74
4.2.4 Sources of allograft skin . . . . . . . . . . . . . . 76
4.2.5 Artificial skin . . . . . . . . . . . . . . . . . . . 77
4.3 Transplant of Composite Tissues Involving Skin . . . . . 78
4.4 The Future . . . . . . . . . . . . . . . . . . . . . . . . 79
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

5. Renal Transplantation 83
Nicos Kessaris and Nadey S. Hakim
5.1 History . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.2 Live Donor Renal Transplantation . . . . . . . . . . . . 84
5.3 Live Donor Evaluation . . . . . . . . . . . . . . . . . . 85
5.4 Donor Nephrectomy . . . . . . . . . . . . . . . . . . . 85
5.5 Complications . . . . . . . . . . . . . . . . . . . . . . 88
5.6 Cadaveric Renal Transplantation . . . . . . . . . . . . . 89
5.7 Deceased Heart-Beating Donor (HBD) . . . . . . . . . 90
5.8 Non-Heart-Beating Donor (NHBD) . . . . . . . . . . . 90
5.9 Renal Transplantation . . . . . . . . . . . . . . . . . . 91
5.9.1 Recipient evaluation . . . . . . . . . . . . . . . 91
5.10 Renal Transplant Procedure . . . . . . . . . . . . . . . 92
5.11 Complications . . . . . . . . . . . . . . . . . . . . . . 93
5.11.1 Short-term complications . . . . . . . . . . . . . 93
5.11.2 Long-term complications . . . . . . . . . . . . . 98
5.12 Antibody-Incompatible Transplantation . . . . . . . . . 99
5.12.1 ABO-incompatible transplantation . . . . . . . . 99
5.13 HLA-Incompatible Transplantation . . . . . . . . . . . 100
5.14 Pair Exchange and Non-Directed Altruistic Donation . . 101
5.15 Immunosuppression . . . . . . . . . . . . . . . . . . . 101
5.15.1 Immunosuppressive drugs . . . . . . . . . . . . . 101
5.15.2 Depleting antibodies . . . . . . . . . . . . . . . 103
5.16 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . 103
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
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6. Pancreas Transplantation 111

Asim Syed and Nadey S. Hakim
6.1 Indications for Pancreas Transplantation . . . . . . . . . 111
6.2 Procurement and Preservation of the Pancreas . . . . . . 112
6.3 Blood Supply . . . . . . . . . . . . . . . . . . . . . . . 113
6.4 Preservation Solution . . . . . . . . . . . . . . . . . . . 114
6.5 Recipient Operation . . . . . . . . . . . . . . . . . . . 114
6.6 Immunosuppression . . . . . . . . . . . . . . . . . . . 116
6.7 Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . 116
6.8 Effects of Pancreas Transplantation on Secondary
Complications of Diabetes and Quality of Life . . . . . . 118
6.9 Quality of Life (QoL) . . . . . . . . . . . . . . . . . . . 118
6.10 Surgical Complications of Pancreas Transplantation . . . 119
6.10.1 Bleeding . . . . . . . . . . . . . . . . . . . . . 120
6.10.2 Intra-abdominal infections . . . . . . . . . . . . 120
6.10.3 Graft pancreatitis . . . . . . . . . . . . . . . . . 120
6.10.4 Anastomotic leak . . . . . . . . . . . . . . . . . 121
6.11 The Future . . . . . . . . . . . . . . . . . . . . . . . . 121
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

7. Liver Transplantation 125

Madhava Pai and Ruben Canelo
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . 125
7.2 Indications . . . . . . . . . . . . . . . . . . . . . . . . 126
7.3 Contraindications . . . . . . . . . . . . . . . . . . . . . 129
7.4 Organ Allocation . . . . . . . . . . . . . . . . . . . . . 130
7.5 Donor Selection . . . . . . . . . . . . . . . . . . . . . 131
7.6 Donor Hepatectomy . . . . . . . . . . . . . . . . . . . 133
7.7 Recipient Operation . . . . . . . . . . . . . . . . . . . 133
7.7.1 Domino liver grafts (DLT) . . . . . . . . . . . . 137
7.8 Living Donor Liver Transplantation . . . . . . . . . . . 137
7.8.1 Minimal graft volume and small-for-size
syndrome . . . . . . . . . . . . . . . . . . . . . 138
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7.9 Immunosuppression . . . . . . . . . . . . . . . . . . . 138

7.9.1 Induction therapy . . . . . . . . . . . . . . . . . 138
7.9.2 Maintenance therapy . . . . . . . . . . . . . . . 138
7.10 Complications After Liver Transplantation . . . . . . . 139
7.10.1 Liver-related causes of morbidity
and mortality . . . . . . . . . . . . . . . . . . . 139
7.10.2 Liver-unrelated causes of morbidity
and mortality . . . . . . . . . . . . . . . . . . . 140
7.11 Transplant Outcomes . . . . . . . . . . . . . . . . . . . 141
7.11.1 Overall outcomes . . . . . . . . . . . . . . . . . 141
7.11.2 Extended criteria and non-heart-beating
donors (NHBDs) . . . . . . . . . . . . . . . . . 142
7.11.3 Living donor . . . . . . . . . . . . . . . . . . . 142
7.11.4 Domino liver grafts (DLT) . . . . . . . . . . . . 143
7.11.5 Quality of life (QoL) . . . . . . . . . . . . . . . 143
7.12 Summary . . . . . . . . . . . . . . . . . . . . . . . . . 143
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

8. Heart Transplantation 151

Varun R. Kshettry and Vibhu R. Kshettry
8.1 History . . . . . . . . . . . . . . . . . . . . . . . . . . 151
8.2 Indications . . . . . . . . . . . . . . . . . . . . . . . . 152
8.3 Surgical Technique . . . . . . . . . . . . . . . . . . . . 155
8.3.1 Donor . . . . . . . . . . . . . . . . . . . . . . . 155
8.3.2 Recipient . . . . . . . . . . . . . . . . . . . . . 156
8.4 Post-Operative Care . . . . . . . . . . . . . . . . . . . 157
8.4.1 Intensive care unit . . . . . . . . . . . . . . . . 157
8.4.2 Immunosuppression . . . . . . . . . . . . . . . . 157
8.4.3 Complications . . . . . . . . . . . . . . . . . . 158
8.5 Results of Heart Transplantation . . . . . . . . . . . . . 163
8.6 Future Directions . . . . . . . . . . . . . . . . . . . . . 164
8.6.1 Mechanical heart replacement . . . . . . . . . . 164
8.6.2 Bio-technologies . . . . . . . . . . . . . . . . . 164
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
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9. Corneal Transplantation 169

Chad K. Rostron
9.1 Corneal Structure and Function . . . . . . . . . . . . . 171
9.2 Indications for Penetrating Keratoplasty . . . . . . . . . 172
9.2.1 Endothelial failure . . . . . . . . . . . . . . . . 172
9.2.2 Keratoconus . . . . . . . . . . . . . . . . . . . 172
9.2.3 Infection and other indications . . . . . . . . . . 173
9.3 Technique of Penetrating Keratoplasty . . . . . . . . . . 173
9.4 Post-Operative Management . . . . . . . . . . . . . . . 174
9.5 Donor Tissue Selection and Preservation . . . . . . . . . 175
9.6 Post-Operative Course of the Graft . . . . . . . . . . . 178
9.6.1 Graft rejection . . . . . . . . . . . . . . . . . . 179
9.7 Tissue-Matched Corneal Grafting . . . . . . . . . . . . 181
9.8 Partial Thickness or Lamellar Keratoplasty . . . . . . . . 182
9.9 Freeze-Dried or Lyophilised Corneal Tissue . . . . . . . 184
9.10 Epithelial Transplantation . . . . . . . . . . . . . . . . . 184
9.11 Endothelial Transplantation . . . . . . . . . . . . . . . . 187
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 188

10. Small Bowel Transplantation 191

Christina D. Bali, Vassilios Papalois and Nadey S. Hakim
10.1 Indications . . . . . . . . . . . . . . . . . . . . . . . . 192
10.2 Small Bowel Procurement and Preservation . . . . . . . 193
10.3 Recipient Operation . . . . . . . . . . . . . . . . . . . 195
10.4 Post-Operative Management . . . . . . . . . . . . . . . 195
10.4.1 Intensive care unit . . . . . . . . . . . . . . . . 195
10.4.2 Immunosuppression . . . . . . . . . . . . . . . . 196
10.4.3 Monitoring of rejection . . . . . . . . . . . . . . 196
10.4.4 Infections . . . . . . . . . . . . . . . . . . . . . 198
10.4.5 Graft-versus-host disease (GvHD) . . . . . . . . 198
10.5 Intestinal Function . . . . . . . . . . . . . . . . . . . . 199
10.6 Results of Small Bowel Transplantation . . . . . . . . . 199
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
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11. Haemopoietic Stem Cell Transplantation 203

Shaun R. McCann
11.1 Historical Perspective . . . . . . . . . . . . . . . . . . . 203
11.2 Biological Perspective . . . . . . . . . . . . . . . . . . . 204
11.3 Practicalities of Bone Marrow Transplantation . . . . . . 204
11.3.1 Allogeneic stem cell transplantation
(Allo SCT) . . . . . . . . . . . . . . . . . . . . 204
11.3.2 Non-myeloablative stem cell (reduced intensity
conditioning) transplantation . . . . . . . . . . . 206
11.4 Haemopoietic Chimaerism . . . . . . . . . . . . . . . . 206
11.5 Choice of Donor . . . . . . . . . . . . . . . . . . . . . 208
11.6 Autologous Stem Cell Transplantation . . . . . . . . . . 209
11.7 Blood Versus Marrow Versus Umbilical Cord
Blood (UCB) . . . . . . . . . . . . . . . . . . . . . . . 210
11.8 Clinical Results . . . . . . . . . . . . . . . . . . . . . . 212
11.8.1 Leukaemia . . . . . . . . . . . . . . . . . . . . 212
11.8.2 Chronic myeloid leukaemia (CML) . . . . . . . 212
11.8.3 Severe aplastic anaemia (SAA) . . . . . . . . . . 213
11.8.4 Thalassaemia and other non-malignant
conditions . . . . . . . . . . . . . . . . . . . . . 214
11.8.5 Autologous grafting . . . . . . . . . . . . . . . . 215
11.9 Clinical Problems . . . . . . . . . . . . . . . . . . . . . 215
11.9.1 Engraftment . . . . . . . . . . . . . . . . . . . . 215
11.9.2 Support care and growth factors . . . . . . . . . 216
11.9.3 Infection . . . . . . . . . . . . . . . . . . . . . 217
11.9.4 Graft-versus-host disease (GvHD) . . . . . . . . 217
11.9.5 Growth and fertility . . . . . . . . . . . . . . . . 219
11.10 Future Directions . . . . . . . . . . . . . . . . . . . . . 219
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 220

12. Recent Advances in Immunosuppressive Drugs

in Organ Transplantation 225
Anthony N. Warrens
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . 225
12.2 Mechanisms of Action of Currently Used
Immunosuppressive Agents . . . . . . . . . . . . . . . . 227
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12.3 The Deployment of New Immunosuppressive Agents

in Clinical Practice . . . . . . . . . . . . . . . . . . . . 227
12.4 Tacrolimus (Prograf) . . . . . . . . . . . . . . . . . . . 228
12.5 Anti-Metabolites . . . . . . . . . . . . . . . . . . . . . 229
12.6 Newer Monoclonal Antibodies . . . . . . . . . . . . . . 230
12.7 Sirolimus (Rapamycin) . . . . . . . . . . . . . . . . . . 231
12.8 Corticosteroids . . . . . . . . . . . . . . . . . . . . . . 232
12.9 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . 232
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 233

Index 237