Download Transplantation Surgery

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 disciplinessurgeons, anaethetists, immunologists & physicians
Two main obstacles to transplantation
• Recipients immune response
• Shortage of donor organs
Terminology (Graft types)
• 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 nonantigenic (porcine heart valve).
Terminology(Graft techniques)
• 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: Bioartificial 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 Tcells 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
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
(Creutzfeldt–Jakob disease or bovine spongiform encephalopathy or BSE)
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 of drugs , risk of developing 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.
Complications of immunosuppression
• Increased susceptibility to infection- 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.
• 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!