Transplantation Surgery

M K Alam MS, FRCS

ILOs

• At the end of this presentation students should be able to:

• Define terminology used in transplantation surgery.

• Describe immunological basis of organ transplantation.

• State steps in organ matching & retrieval.

• Describe methods of immunosuppression.

• State in brief about individual organ transplantation.

Transplantation

• No alternative treatments are available

• Improves quality of life and

• Improves survival

• Needs cooperation of several disciplines- surgeons, anaethetists, immunologists & physicians

Two main obstacles to transplantation

• Recipients immune response

• Shortage of donor organs

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).

Terminology

• Orthotopic graft: Donor organ transplanted to the

diseased organ site- liver transplant.

• 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

Donor organs

• Cadaver graft: Organ retrieved from an individual

who has been pronounced dead according to a

defined criteria.

• Living donors:

-Related donors- parent or siblings

-Unrelated donors- voluntary or to make money

Immune response

• Auto & isografts - do not elicit immune response.

• Inflammation- at the center of rejection process.

• Reperfusion→ endothelial activation→ infiltration

of inflammatory cells particularly macrophages.

• Major histocompatibility complex encodes

transplant antigen which are similar to serum HLA

(human leucocyte antigen)

Afferent arm of immune response• Presentation of donor MHC antigen to recipient T-

cells receptor (TCR) 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. B-cell• CD4- central role in rejection process.

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).

• Cellular mechanism- by cytotoxic T-cells, macrophage, natural killer cells (large granular lymphocyte) & neutrophils.

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.

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.

Organ retrieval

• Cadaver: Heart beating, ventilation supported• Retrieval after cardiac arrest provided rapid organ

perfusion can be achieved.• Organ function in donors must be 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.

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

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

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): Used 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)

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.

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.

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%

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.

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.

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.

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.

Thank you!