1. PRINCIPLES OF Transplantation Surgery
M K Alam MS, FRCS
Professor of Surgery
Al Maarefa Colleges

2. ILOs Define terminologies used in organ transplantation
At the end of this presentation students should be able to:
Define terminologies used in organ transplantation
Describe the immunological basis of organ transplantation, organ matching, & immunosuppression.
Summarize indications, contraindications, and outcome of common organ transplantation.

3. History of organ transplantation
Rapidly expanding & important surgical specialty
300 AD: Cosmos & Damian attempted a leg transplant.
1778: John Hunter coined the term ‘transplant’
1933: Voronoy 1st human renal transplant- failed due to ABO incompatibility
1945: Hume 1st short-lived functioning renal allograft
1950: Lawler 1st long-term survivor renal transplant
1963: Starzl 1st human liver allograft
1967: Starzl 1st long-term survivor liver transplantation
1967: Barnard 1st successful heart transplant
1981: Shumway 1st successful heart-lung transplant
1988: Grant 1st long-term survivor of small bowel transplant

4. Transplantation
Indication- when no alternative treatments are available
Improves quality of life
Improves survival
Cooperation of several disciplines Surgeons, anaethetists, immunologists & physicians

5. Two main obstacles to transplantation
Recipients immune response
Shortage of donor organs

6. Terminology
Autograft: Free transplantation of tissue from one part of the body to another in the same individual.
Isograft: Transfer of tissue between genetically identical individual- identical twins.
Allograft: Organ transplanted from individuals of same species- main class of transplantation in humans
Xenograft: Organ transfer between dissimilar species. Tissue is chemically treated to make it non-antigenic (porcine heart valve).

7. Terminology
Orthotopic graft: Donor organ transplanted to the diseased organ site- liver.
Heterotopic graft: Donor organ transplanted at a site different from normal anatomical position Kidney in iliac fossa.
Artificial (hybrid) organ implantation: Bio-artificial organs (combination of biomaterials & living cells)- experimental technique

8. Donor organs
Cadaver graft: Organs retrieved from an individual pronounced brain dead according to a defined criteria, while heart continue to beat, ventilatory & other support maintained
Living donors:
-Related donors- parent or siblings
-Unrelated donors- voluntary or to make money

9. Basic immunology of organ transplantation
Auto & isografts - do not elicit immune response.
Genetic differences between donor & recipient-major importance.
Main antigens triggering rejection are coded in a group of genes known as- MHC (major histocompatibility complex). Located on short arm of chromosome 6
MHC class 1 are on all nucleated cells & platelets-(named HLA A,B, & C)
MHC class 2 on B-cells, macrophage, monocyte & antigen-presenting cells (APC)- HLA DR, DP & DQ
Blood group antigens (ABO system) can also trigger humoral rejection.

10. Immune response Inflammation- center of rejection process.
Reperfusion→ endothelial activation→ infiltration of inflammatory cells particularly macrophages.

11. Afferent arm of immune response
Presentation of donor HLA antigens to recipient’s T-cells receptor (TCR) “allorecognition” leads to T-cell activation.
Recognized as foreign by recipient T-cells.
Clonal expansion of T-cells.
Differentiation T- cells into:
CD4 positive (helper): Helping B-cell → plasma cells to make antibody, and activate phagocytosis.
CD8 positive (effector)- Control level and quality of immune response.
CD4- central role in rejection process.

12. Efferent arm of immune response
Donor organ damage- efferent arm response
Humoral mechanism- antibody produced by B- lymphocytes (under influence by cytokines released by T-cells CD4) bind foreign antigen → cell lysis.
Cellular mechanism- by cytotoxic T-cells, macrophage, natural killer cells (large granular lymphocyte) & neutrophils.

13. Clinical patterns of rejection
Hyperacute: Within 24 hours due to preformed antibody (IgG) against donor HLA antigens. Overcome by pre-transplant screening.
Acute: within 6 months in up to 50% grafts. Characterized by infiltration of activated T cells and inflammatory cells.
Chronic: >6 months, progressive decline in function. Multifactorial damage-(immune mediated, toxicity from immunosuppression, viral infection) cellular atrophy, fibrosis.

14. Organ matching
ABO compatibility: ABO red cell antigen is also expressed on most tissue cells.
HLA tissue typing: HLA antigen A,B,& DR on the donor and recipient on lymphocytes
HLA typing most useful in renal transplant
Direct cross match- incubating donor lymphocyte with recipient plasma. Detects preformed antibodies.

15. Organ retrieval Cadaver: Heart beating, ventilation supported
Retrieval after cardiac arrest, rapid organ perfusion
Organ function in donors established. e.g. Kidney Normal urine output (except oliguria due to dehydration), analysis, urea & creatinine.
Live related: Kidney, liver, pancreas, lung, small intestine Must justify operative risk.

16. General contraindication to organ donation
Age > 90
HIV disease
Disseminated cancer
Melanoma
Treated cancer within 3 years of donation
Neurodegenerative disease due to infection- CJD

17. Organ specific contraindication to organ donation
Liver: Acute hepatitis, cirrhosis, portal vein thrombosis.
Kidney: Chronic kidney disease, long term dialysis, renal malignancy, previous renal transplant.
Pancreas: Insulin dependent diabetes, pancreatic malignancy

18. Immunosuppression
Achieve a balance between prevention of rejection and morbidity-side effects, risk malignancy
Steroids: 1st line for acute rejection. Side effects of long term use.
Azathioprine (AZA): For acute cellular rejection in renal transplant Myelosuppression, GI symptoms.
Mycophenolate mofetil: Prevents lymphocyte activation, replaced AZA in renal transplant
Calcineurin inhibitors: Cyclosporin- acts by inhibiting cytokines which activates lymphocytes. Nephrotoxicity, hypertension, hyperglycemia, hyperlipidemia. Tacrolimus- Better outcome in kidney & liver transplant. Nephrotoxic, neurotoxic, diabetes, alopecia.
Sirolimus: Inhibits T cell activation. Limited use due to toxicity
Antibody: Induction therapy at the time of transplantation to provide immediate immunosuppression after transplantation.( antithymocyte globulin, alemtuzumab, interleukin-2 antibody)

19. Complications of immunosuppression
Susceptibility to infections: TB, candida, pneumocytis carinii, cytomegalovirus, EB virus, measles, herpes.
Risk of malignancy: SCC, Lymphoma
Specific side effects of individual agent or regimen.

20. Organ donation Deceased donation- according to country rules
Donor management: Cardiovascular stability, and maintaining organ function- optimal fluid, maintaining BP, & minimal inotrope support.
Organ preservation: Cold storage by intravascular flush with chilled preservation fluid- UW fluid (University of Wisconsin) or Eurocollins solution. Preservation time- Kidney 24 hrs. , liver 20 hrs.

21. Renal transplantation
Indication: End stage renal disease
Patient assessment: Absolute contraindications- malignancy, active infection Relative contraindications- advance age, severe cv disease, non-compliance with immunosuppressive therapy. Diabetes, hypertension, amyloidosis can also affect the transplanted kidney.
Outcome: 1- year graft survival 90%
5- year graft survival 70%
Peri-operative mortality- 2-5%

22. Liver transplantation
Indication: Chronic liver disease with signs of decompensation (OV, ascites, jaundice, coagulopathy, SBP, hypoalbuminaemia)
Common aetiology : Adults- alcohol, HBV, HCV, primary biliary cirrhosis, sclerosing cholangitis, HCC, acute liver failure due to paracetamol toxicity, viral Children- biliary atresia, Wilson’s disease.
Patient assessment: Expected 50% chance of 5 year post-transplant survival.

23. Liver transplantation
Living donor: A portion of liver removed for transplant in children or small recipient. Donor liver regenerates to full size and function. Donor mortality- 0.5%.
Post-op. management of rejection: Usually around day 7- rising transaminases. Biopsy to confirm rejection. Treated by methylprednisolone for 3 days. Complete rejection rare.
Outcome: 1 year survival 90%, 5-year survival 66% Need for long term immunosuppression Most patients report good quality of life.

24. Pancreas transplantation
Indication: Type I diabetes mellitus
SPK – simultaneous pancreas- kidney transplant
PTA- pancreas transplant alone
Outcome: 1-year pancreas graft survival 82%.
Pancreatic islets cell transplantation- more then one pancreas is needed to treat one patient.

25. Heart & lung transplant
Heart: Coronary related heart failure, cardiomyopathy, valvular disease, congenital HD.
Lung: COPD, cystic fibrosis, pulmonary fibrosis. Most challenging of all transplants.
Outcome: Heart- 65% at 5 years, 50% at 10 years & 30% at 15 years. Lung- 50% at 5 years and 25% at 10 years.

26. Thank you!