Transplantation Ist Department of Surgery, St. Anne’s University Hospital Brno Transplantation uA medical procedure in which an organ, part of an organ or tissue is transferred from one place to another or from one body to another uTo replace a damaged or missing organ uThe aim to restore functions uGraft - tissue that is transplanted without reconstruction of the vascular bed (skin, muscle,…) uTransplant - organ transplantation with concomitant reconstruction of vascular bed uIn practice, both terms are used as synonyms History u1902 Ulmann – kidney transplantation in a dog u1912 Carrel and Guthrie – have developed a transplantation technique based on a perfect vascular stitch u1933 Voronoj – kidney transplantation from deceased to young woman with renal failure due to mercury poisoning (graft did not restore function, recipient died) u1943 Medawar – knowledge of the immunological cause of rejection u1958 Dausset – discovery of histocompatible antigens (HLA) uIntroduction of immunosuppressive therapy (whole body irradiation, later medication) u1963 Starzl – has contributed to the development of liver transplants u1963 Hardy – first lung transplantation u1966 Kelly and Lillehei – pancreatic transplantation u1967 Barnard – first successful heart transplant using Shumway technique u u Types of transplantation by tissue origin uAutograft (autotransplantation) uTransplant of tissue to the same person uThere is no risk of graft rejection uSkin, blood vessels uAllograft (allotransplantation) uBetween two genetically non-identical members of the same species uThere is a risk of graft rejection, immunosuppressants are needed uDonor uRecipient uXenograft (xenotransplantation) uFrom one species to another (e.g. porcine heart valve transplant) uIsograft (syngeneic) uFrom a donor to a genetically identical recipient (such as an identical twin) uDo not trigger an immune response uImplantation uTransplantation of artificial, synthetic tissue Types of transplants by location uOrthotopic transplantation uThe previous organ is removed and the transplant is placed at that location in the body (e.g. heart into the mediastinum) uHeterotopic transplantation uThe transplant is placed in a different location in the host than it had been in the donor – e.g. kidney transplant is placed in the anterior part of the lower abdomen, in the pelvis Immunological aspects uMHC (Major Histocompatibility Complex) – the genetic system responsible for recognizing one's own from the alien uIn humans, the major histocompatibility system is the HLA complex (Human Leucocyte Antigen) – complex of genes that determine surface antigens u5 HLA complexes – HLA-A, HLA-B, HLA-C, HLA-D, HLA-DR uConsensus in tissue HLA antigens between donor and recipient facilitates graft acceptance and prevents or attenuates post-transplant immune response uGraft from HLA identical sibling recipient tolerates uGraft from HLA unrelated individual is not tolerated uThe greater HLA conformity, the longer graft survival uIdentification of HLA antigens – tissue typing uSerological and cellular methods replace DNA typing. uHvG – host versus graft – recipient's immune response against histocompatible antigens of graft Immunological aspects uGvH – graft versus host – transplantation of immunocompetent cells, graft's T-lymphocytes response against recipient antigens uHematopoietic stem cells uSmall intestine, lungs, sometimes liver (contain a lot of lymphatic tissue) uRejection does not occur: uAutotransplantation uSyngeneic transplantation uTissue transplants that do not express histocompatible antigens (bones, tendons, cartilage) uTransplantation to immunologically privileged place – lymphocytes can't get there (e.g. brain, eye, gonades) uImmunosuppressants uChemotherapeutics – corticosteroids, cyclosporin A, FK506 (Tacrolimus), Rapamycin, Sanghlifehrin A, Azathioprine, Mycophenolate, mofetil, Cyclophosphamide, Deoxyspergualin, Chlorambucil, Methotrexate, Brequinar, Leflunomid, FTY720, Tautomycetin, uMonoclonal, polyclonal antibodies – antilymphocytic globulin, antithymocyte globulin, OKT3, CAMPATH, anti-CD25, anti-CD4, anti-CD8, anti-CD2, anti-LFA3 uTotal body irradiation Transplant rejection uHyperacute uThe existence of preformed antibodies against donor antigens uGraft destruction within minutes to hours uVascular thrombosis and necrosis uThe crossmatch is a protection uAccelerated uLower antibody titer, within 5 days after transplantation uAcute uMost common, within three months and later uActivation of T-lymphocytes against graft antigens with interstitial inflammation uGraft function is decreased uIncrease of immunosuppressive therapy uChronic uGradual deterioration of graft function due to vascular changes uPredominantly humoral factors uMonths to years Rejection uDeterioration of laboratory parameters (e.g. increas of urea, creatinine) uDecrease in graft function (e.g. diuresis) uVerification by needle biopsy uDecrease in graft function can caused e.g. nephrotoxicity of cyclosporine Transplantation centers in the Czech Republic uIKEM Prague uKidneys, heart, pancreas, liver, small intestine, uterus uUH Motol Prague uLungs, kidneys uCKTCH Brno uHeart, liver, kidneys uUH Olomouc uKidneys uUH Ostrava uKidneys uUH Hradec Králové uKidneys uUH Pilsen uKidneys u Conditions for transplantation 1. surgical technique uRevascularization by vascular anastomoses uConnection of organ ducts (ureter, bile duct, pancreatic duct), intestinal anastomoses or respirátory tract uGrafting without damage uPreservation of graft function by intensive care uComplicatons: uFistula of ducts uGraft thrombosis (mostly leads to graft loss) uOppression of ureter caused by accumulation of lymph around the transplanted kidney u Conditions for transplantation 2. source of organs uLiving donors uPaired organ (kidneys) or part of organ (liver) uClose relative (parents, children, siblings) uEmotionally related (husband and wife) uUnrelated donor uDeceased donors uSudden death, esp. craniotrauma, spont. bleeding, ischemia after resuscitation, after drowning, in some cases meningitis or a primary brain tumor uWarm ischemia uTime from organ procurement to start of perfusion with perfusion solution uStart: MAP < 50 mmHg or SpO2 70% uEnd: start flushing uRapid cell damage uMost organs tolerate only a few minutes, it should not exceed 30 minutes uNearly zero warm ischemia can be achieved in donors with a beating heart uCold ischemia uStart: start flushing uEnd: restoration of blood flow uIt should not exceed 36 to 48 hours uTolerance time (kidneys up to 36 hours), (heart, liver, pancreas, lungs 6-12 hours) uGraft half-life: was defined as the time taken for 1/2 of the grafts functioning at 1 year to fail uOrgan Transplant Act u Clinical determination of brain death uBrain death uis the complete loss of brain function (including involuntary activity necessary to sustain life). It differs from persistent vegetative state, ordinary coma, condition known as locked-in syndrome uExclusion of factors affecting consciousness uE.g. hypothermia, hypoxia, intoxication, effect of drugs, hypoglycemia uNeurological examination uThe assessment is carried out by two physicians with specialized competence u Clinical determination of brain death uExamination of brainstem reflexes uPupillary light reflex uCorneal reflex uOculocephalic reflex uGlowing reflex uCough reflex uOculovestibular reflex uApnea test Apnea test uTo confirm breathing center malfunction uDisconnecting the patient from ALV uCO2 is accumulated, which physiologically stimulates the respiratory center uIf damaged, the patient is unable to ventilate spontaneously uIn COPD patients, it may not be valid, elevated CO2 may not be a sufficient incentive to activate the center Clinical determination of brain death uParaclinic examinations uCT angiography – partially preserved circulation may occur in decompressive craniotomies, ventricular drainage and small children uEvoked potential test uTranscranail Doppler ultrasound uDigital subtraction angiography uCerebral perfusion scintigraphy uElectroencephalography u u u Another donor examination uVirology + Serology: TPHA, HBsAg, anti - HBc total, antibodies against HIV 1 a 2, anti CMV (IgM a IgA), EBV. uBiochemical profile: Na, K, Cl, Gly, urea, creatinine, osmolality, AST, ALT, ALP, GGT, Bilirubin, Albumin, CB, AMS, CK, CKMB, Trop-T, Myoglobin, CRP. uBlood count, coagulation, blood type, Rh factor uAstrup uElectrocardiography uECHO uCoronarography uX-ray uAbdominal ultrasound uExaminations are indicated in cooperation with the transplant coordinator Absolute contraindications to transplantation uBacterial sepsis (except milder forms) uAIDS uTuberculosis uHBV uHCV uMalignancy (except isolated brain, skin, in situ cervix carcinoma) uLong-term hemodialysis uPatient disagreement with transplantation uImpossibility to identify the patient uNoncompliance of recipient Donor care uRule 100 uBlood pressure 100/80 mmHg uDiuresis 100ml/h (according to the patient's weight) uNormothermia uHb >100g/l uNormoglycemia uSaturation 99% uFluid resuscitation uMaintaining ions and acid-base balance uVenous access: CVC, NG tube, PUC, arterial catheter uTo inform survivors Physiological angiography Liver transplantation uThe first successful liver transplantation in 1967 (USA) uThe first liver transplantation in the Czech republic in 1983 in St. Anne’s University Hospital Brno led by prof. Kořístka uIn the Czech Republic two centers - IKEM Prague and CKTCH Brno uMost common indications: biliary cirrhosis, alcoholic, chronic active hepatitis, sclerosing cholangoitis, congenital atresia of the biliary tract, Wilson‘s disease, alpha-1-antitrypsin deficiency, Budd-Chiari syndrome and hemochromatosis uControversial in primary malignancies due to frequent relapses uOrthotopically uOften only one lobe or segment in children uTechnically demanding – liver artery, portal vein, inferior vena cava, bile ducts uEconomic demands - the need for a number of blood derivative transfers – portal hypertensis, coagulation disorders uNeed 10-15 per million inhabitants per year u85 candidates were on the waiting list in 3.5.2019 u58 liver transplants were performed in CKTCH, 158 in IKEM in 2018 https://www.researchgate.net/figure/Available-surgical-techniques-for-liver-transplantation-A-Illus tration-shows-the_fig1_270964176 Heart transplantation uThe first successful heart transplantation was performed by Christiaan Neethling Barnard in 1967 uIn the Czech Republic two centers - IKEM Prague and CKTCH Brno uMost commonly indicated in idiopathic dilated cardiomyopathy or ischemic disease (with a prognosis of survival less than 1 year), unmanageable arrhythmias uUsually orthotopically (heterotopically supports the heart function of the recipient) uRemaining posterior atrial wall with orifices of venae cavae and pulmonary veins, left atrial anastomosis, septum, right atrium, aorta and pulmonary artery uNeed about 15 per million inhabitants u76 candidates were on the waiting list in 3.5.2019 uNumber of transplants in 2018: 39 IKEM, 35 CKTCH https://medical-dictionary.thefreedictionary.com/orthotopic+transplantation https://medmovie.com/library_id/3255/topic/ahaw_0093a/ https://www.sciencedirect.com/science/article/pii/S0959289X17304211 Kidney transplantation uFirst kidney transplant between identical twins in Paris and Boston in 1958 uFastest development due to the possibility of hemodialysis during graft failure uIndication - 4th stage of chronic renal insufficiency uGlomerulopathy, chronic tubular disease, diabetic nephropathy, polycystosis uHeterotopic transplantation to the iliac fossa - blood vessels on the iliac artery and vein, ureter on the bladder uMostly one kidney, rarely transplant of both uThe original kidney is left unless it is a source of infection, hypertension or polycystosis uLiving donor transplants have significantly better results, ideally before hemodialysis uThe kidney usually works immediately after transplantation, sometimes later (days, weeks), in 1/10 never Kidney transplantation Lung transplantation uIn the Czech Republic since 1997, FN Motol uBefore transplantation mostly dependence on oxygen therapy uIndications: idiopathic pulmonary fibrosis, exogenous allergic alveolitis, histiocytosis X, sarcoidosis, pulmonary emphysema, COPD, cystic fibrosis, pulmonary hypertension uOne side, both sides, complexed with the heart, lobar is not performed in the Czech Republic uUse of extracorporeal circulation uComplications: pulmonary edema, pneumonia, arrhythmia, rejection uIn the Czech Republic 30-50 per year u u Lung transplantation https://www.mayoclinic.org/tests-procedures/lung-transplant/about/pac-20384754 https://accesssurgery.mhmedical.com/content.aspx?sectionid=72434315&bookid=1317 Pancreas transplant uIKEM in the Czech Republic uMostly in patients who have had or are waiting for a kidney transplant. Isolated pancreatic transplantation when the risks of poorly controllable diabetes outweigh the risks of long-term immunosuppression. uA successful pancreas transplant will eliminate the need for insulin injections, reduce or eliminate dietary and activity restrictions due to diabetes, and decrease or eliminate the risk of severe low blood sugar reactions uArtery is anastomosed to right external iliac artery uTerminal diabetic nephropathy, type I diabetes mellitus, seldom type II uExtraperitoneal, intraperitoneal uThe need to resolve exocrine secretion – most often the graft duodenum is connected to the jejunal loop, the connection to the bladder is associated with greater complications, polymer obliteration of the outlet, ligation uComplications: metabolic, urological, hematological, gastrointestinal, surgical Pancreas transplant Pancreatic islet cell transplant uIEQ/kg – islet equivalent– one IEQ is considered equivalent to a pancreatic islet with a diameter of 150 μm uThe Edmonton protocol - involves isolating islets from a cadaveric donor pancreas using a mixture of enzymes called Liberase uEach recipient receives islets from one to as many as three donors uIslet cells taken from a deceased donor's pancreas are injected into a portal vein that takes blood to the liver uMore than one injection of transplanted islet cells may be needed uPatients with diabetic nephropathy and obese are contraindicated u u Dermal transplantation uAuto-, allo-, xenotransplantation uBy thickness uSplit – thickness – including the epidermis and part of the dermis. uIt can be processed through a skin mesher which makes apertures onto the graft, allowing it to expand up to nine times its size. uThe donor site heals by re-epithelialisation from the dermis and surrounding skin and requires dressings. uFull – thickness – consists of the epidermis and the entire thickness of the dermis. uThe donor site is either sutured closed directly or covered by a split-thickness skin graft. uComposite graft – is a small graft containing skin and underlying cartilage or other tissue uScalpel, Wattson knife, airdermatom, electrodermatome uMeshing uExtensive wounding or trauma, burns, areas of extensive skin loss due to infection, specific surgeries that may require skin grafts for healing to occur Dermal transplantation Corneal transplantation uFirst in 1905 in Olomouc uPerforating keratoplasty – corneal transplantation in full thickness uLamellar keratoplasty – removal of only the damaged or diseased epithelium and stroma, leaving the endothelium intact, in cases where only the more superficial layers are damaged uIndications uOptical – transparency restore uTectonic – preservation of the integrity of the bulb when the cornea is thinning with imminent perforation uTherapeutic – severe inflammations uCosmetic – blind eyes with leukoma uImmunosuppressive treatment is usually discontinued after removal of stitches between 11-13. month uDonor-recipient compatibility is not required Corneal transplantation Stem cell transplant uCollecting stem cells: uStem cells from the bone marrow - most often taken from the pelvic bones uStem cells from the peripheral blood – rowth factors, such as G-CSF or plerixafor, may be given for a few days to stimulate stem cells to grow faster and move into the blood from the bone marrow. Machine separates and collects stem cells from the blood. uStem cells from the umbilical cord uStem cells are given through a central venous catheter and they settle in the bone marrow and begin to multiply and mature uAutologous, Allogeneic, Syngeneic uIndications: acute myeloid leukemia, acute lymphocytic leukemia, non-Hodgkin‘s lymphoma, malignant lymphogranuloma, myelodysplastic syndrome, myelofibrosis, chronic lymphocytic leukemia, chronic myeloid leukemia, severe aplastic anemia, myeloma, congenital haematopoietic disorders uGraft vs. host disease uMore than 350 centers in Europe are performing over 18,000 transplantations a year Small intestine transplantation uFour indications: ua loss of two of the six major routes of venous access umultiple episodes of catheter-associated life-threatening sepsis ufluid and electrolyte abnormalities in the face of maximal medical therapy uparenteral nutrition associated liver disease uIntestinal failure is usually the result of one of the following: ushort bowel syndrome uchronic intestinal pseudo-obstruction uintra-abdominal non-metastasizing tumors uThe most common causes for intestinal failure in the adult: ischemia, Crohn‘s disease, trauma, motility disorder, tumor, volvulus uThe most common causes for intestinal failure in the pediatric: necrotizing enterocolitis, gastroschisis, omphalocele, intestinal atresia, volvulus, intestinal pseudo-obstruction, microvillus inclusion disease, intractable diarrhea of infancy, autoimmune enteritis, intestinal polyposis, Hirschprung disease uComplete parenteral nutrition – complications limit permanent use – hepatic impairment, steatosis, fibrosis, cirrhosis, liver failure, catheter sepsis uMultivisceral transplantation: intestine, liver, stomach, duodenum, pancreas Small intestine transplantation Others uUterus uFace uBones and tendons uHeart valves uBlood vessels uPenis uHand