外科学教学课件：Transplantation

TransplantationBasicConceptsHistoryTransplantationImmunityOrganProcurementOrganTransplantationLiverTransplantationTransplantationTransplantation:

themovingofcell,tissueor

organ

fromonebodytoanotherorfroma

donor

sitetoanotherlocationontheperson'sownbodyGraft:

thecells,tissueororganthataretransplanted

Donor:

thedonationofthegraftRecipient:thereceiverofthegraftBasicConceptsTypesoftransplatation

AccordingtothegeneticgeneIsograft,syngeneictransplantationTransplantationfromageneticallyidenticaldonorAllograft,allotranplantation

Transplantationfromageneticallynon-identicaldonorofthesamespecies

Xenograft,xenotransplantationTransplantationfromonespeciestoanotherAccordingtotherelationbetweenthedonorandreciepentAutograftTransplantationbetweenthesamepersonAllograftTransplantationbetweentwogeneticallynon-identicalmembersofthesamespecies

BasicConceptsTypesoftransplatationAccordingtotheimplantationsiteOrthotopictransplantationHeterotopictransplantationAccordingtothegraftsourcesCadavericdonortransplantationLivingdonortransplantationAccordingto

graftpropertiesCelltransplantationTissuetransplantationOrgantransplantationBasicConceptsBasic

ConceptsHistoryTransplantationImmunityOrganProcurementOrganTransplantationLiverTransplantationTransplantation

ExploratoryStageJohnHuuterperformedthechickentestisautotransplantationin18thcenturyBungerperformedtheantelopecornealallotransplantaionin1835Ulmannperformedthekidneyauto-andexno-transplantationusingthevascularsheathingmethodin1902Carrel&GuthrieperformedthecatkidneytransplantationusingthevascularanastomosismethodVoronovperformedthehumancadavericrenaltransplantation

in1933,48hourssurvivalHumeperformedthe9casesofcadavericrenaltransplantation,oneofthemsurvivedfor5monthsHistoryNolongtermsurvivorsduetothelackofknowledgeofrejectionClinicalStageMurrayperformedthe1st

successfulkidneytransplantationin1954Starzlperformedthe1stlivertransplantationin1963Hardyperformedthe1stlungtransplantationin1963

Lilleheiperformedthe1st

pancreastransplantationin1966

Barnardperformedthe1sthearttransplantationin1967Cooleyperformedthe1stcombinedheartandlungtransplantationin1968Detterlingperformedthe1stsmallintestinaltransplantation

in1968HistoryThomasE.StarzlChristianBarnardRichardLilleheiJosephE.MurrayBreakthroughsVascularanastomosistechniquePreservationsolutionCollinssolution(1969),UWsolution(1987)ImmunosuppressantIn1961,

AzathioprineIn1963,Prednisone(steroids)In1966,Anti-lymphocyteglobulinIn1971,CyclophosphamideIn1972,CyclosporinAIn1984,Tacrolimus

HistoryAlexisCarrelwon1912'sNobelPrizeBasic

ConceptsHistoryTransplantationImmunityOrganProcurementOrganTransplantationLiverTransplantationTransplantationThebody’simmuneresponsetoaforeigngraftisaspecificimmuneresponseprocess,includingthecellularimmuneresponsemediatedbyT-lymphocytesandthehumoralimmuneresponsemediatedbyantibodysubstances.TransplantationImmunityTransplantationantigenMajorhistocompatibilityantigen(MHC)Locatedonchromosome6th,themostimportantantigenInthehumanbody,alsoknownashumanleukocyteantigen(HLA)Minorhistocompatibilityantigen(mHantigen)Endothelialglycoproteins:ABObloodtypeantigenPresentinthevascularendotheliumTargetingthevascularmediatedbyantibody

TransplantationImmunityTransplantationImmunity

ImmunologicrejectionCD4+Tcell

antibody

Thedonor’sABO

antigen

Thedonor’sMHC

antigen

CD8+Tcell

MHCclassⅡantigen

MHCclassⅠantigen

Antigen

T

cell

B

cell

1stsignal2ndsignalAPCco-stimulatorymoleculeTcellactivation

TransplantationToleranceTorealizetheinjury-freeofthegraftspecificimmunityandretainthenormalfunctionoftherecipient’simmunesystematthesametime.

TransplantationImmunityTheultimategoalImmunerejectionsyndromeHyperacuterejectionOccurswithinminutesofreestablishingbloodsupplytotheorgan.Causedbyperformedantibodies.PreventedbyABOmatchingandlymphocytotoxiccrossmatch.AcceleratedvascularrejectionItisavascularthrombosisthatcausedbytherapidgenerationofthenewantibodytothedonor’santigenandisalsoknownasvascularrejection,rarelyoccurredwithin1weekaftertransplantation.

TransplantationImmunityImmunerejectionsyndromeAcuterejectionItisaT-cellmediatedimmuneresponsethatoftenoccurswithinthe1stmonth.Thesignsofgraftdysfunctionsuggestit.Thebiopsyisthe“goldstandard”fordiagnosis.ChronicrejectionItisseenyearsafterthetransplant,withgradualandinsidiouslossofgraftfunction.Itmaybecausedbytheinjuryofvascularendothelialcellsandnon-immuneinjurymechanism.Thetreatmentisre-transplant.Graftversushostdisease(GVHD)Itismanifestedasfever,rashanddiarrhea.Themortalityrateisveryhigh.TransplantationImmunityImmunosuppressiveagent

AdrenocorticalhormoneForinduction,maintenanceandsalvagetreatmentForexample:Methylprednisolone(MP),PrednisoneAzathioprineInhibitionofDNAsynthesisoflymphocytesSideeffect:leucopenia,infection,causecancerandreducesexual

functionandfertilityMycophenolicacidInhibittheclassicsynthesispathwayofpurinenucleotidesForexample:Myfortic,CellCeptTransplantationImmunityImmunosuppressiveagentCalcineurininhibitors(milestone)Inhibitthethecalciumdependentphosphorylationandtheactivationof

transcriptionfactorbybindingcalmodulincomplex,preventcytokineexpressionwhichcanactivateIL-2andotherTcells,andtheninhibittheactivationandproliferationofTcellsForexample:Tacrolimus(Prograf)

CyclosporineA(Neoral)TORinhibitorsRapamycinAnti-lymphocyteglobulinPolyclonal:ATGMonoclonal:Simulect/Zenapax/OKT3TransplantationImmunityCommonlyusedimmunosuppressiveprogramWithhormoneTacrolimus(CyclosporineA)+Mycophenolicacid+corticosteroidsWithouthormoneInducedbyMonoclonalAnti-lymphocyteglobulinTacrolimus(CyclosporineA)+MycophenolicacidTransplantationImmunityBasic

ConceptsHistoryTransplantation

ImmunityOrganProcurementOrganTransplantationLiverTransplantationTransplantationSourcesofdonorLivingdonor(Relatives)Deceaseddonor(CardiacorBraindead)Classification:Chinese-I:Donationafterbraindead(DBD)Chinese-II:Donationaftercardiacdead(DCD)Chinese-III:Donationafterbraindeathpluscardiacdeath(DBCD)OrganProcurementGeneralcriteriaofdonorOrganProcurementAGELung,

Pancreas<55yHeart<60yKidney<65yLiver<70ySevereinfectionHIVMalignanttumorImmunologicalcriteriaofdonor(Topreventsevererejection)ABO

bloodtypeSameorcompatible;livertransplantationcanbeincompatibleLymphocytotoxicitycrossmatchingBetweenrecipientserumanddonorlymphocytesThehistoryofbloodtransfusion,pregnancyortransplantationcanmakethetest(+)

whichmaycausesevererejectionHLA

matchingHLA-A、BandHLA-DR

betweenrecipientanddonorIfnotmatch,candecreasethetransplantationoutcome6sitesofHLAmatchingiscloselyrelatedtothesurvivalrateofrenalandbonemarrowtransplantationOrganProcurementOrganharvestandpreservationHarvestprincipleShortenthewarmischemiatimeasfaraspossibleMinimizethemechanicaldamageoforganandthedestructionoftheimportantstructure

OrganProcurementOrganharvestandpreservation

PreservationprincipleLowtemperature(4°C）Usingappropriatepreservationsolutiontopreventcellswelling(UW

solution,HTKsolution)OrganpreservationperfusiondeviceShortenthecoldischemiatimeasfaraspossible

OrganProcurementBasic

ConceptsHistoryTransplantation

ImmunityOrganProcurementOrganTransplantationLiverTransplantationTransplantationKidneytransplantation

Indications:end-stagerenaldiseaseChronicglomerulonephritis,Polycystickidneydisease,Diabetic

nephropathy,etcFeaturesOperationisrelativelysimple,costless,andifoperationisfailure,patientcantakedialysisorre-transplantationforsurvival.

OrganTransplantationHearttransplantationIndications:end-stageheartdiseaseSpontaneousischemicheartdisease,Congenitalheartdisease,Valvulopathy,Viralmyocarditis,etcFeaturesOperationisrelativelysimplebutcostly,thepost-operationmanagementismorecomplicated,organpreservationconditionandischemiatimedemandingisstrict,andcardiacbiopsyfrequentlymayoverwhelmedthepatient.

OrganTransplantationPancreastransplantationIndicationSeverediabeteswithend-stagerenaldiseaseStatusofposttotalpancreatectomyFeaturesThemajorityofpancreastransplantationaresimultaneouspancreas-kidneytransplantationandhasahighrateofpostoperativecomplication.Buttheprognosisisverygood.

OrganTransplantationIntestinaltransplantationIndication:ShortbowelsyndromecausedbymassivesmallbowelresectionTheprognosisispoorduetotheseverrejectionandgraft

failure.LungtransplantationIndication:end-stagelungdiseaseTheprognosisisalsopoorduetothesevereinfectionandobstructivebronchitis.OrganTransplantationBasic

ConceptsHistoryTransplantation

ImmunityOrganProcurementOrganTransplantationLiverTransplantationTransplantationIndications

LiverTransplantationBenignend-stageliverdisease

PosthepatitiscirrhosisAlcoholiccirrhosisPrimarybiliarycirrhosis(PBC)Primarysclerosingcholangitis(PSC)Congenitalmetabolicliverdisease(Wilson’s

disease,α-1antitrypsindeficiency,Glycogendepositiondisease,etc）FulminanthepaticfailureBudd-ChiarisyndromePolycysticliverMalignantend-stageliverdiseaseLivercancerwithdecompensatedcirrhosisLivercancerlocatedinspeicalregionLiverTransplantationContraindicationsUncontrolledmetastaticcanceroutsideliverUncontrolledinfections(bacteria,fungusandvirus)ActivedrugoralcoholabuseSeriousheart,pulmonaryorotherdiseaseInfectionwithHIVUncontrolledpsychologicalmetamorphosisormentaldiseaseLiverTransplantationHistoryProf.StarzlfromUSAperformedthe1stlivertransplantationin1966.Therehasaccumulatedmorethan200,000casesinthewholeworld.1-yearsurvivalratewas90%andthelongestsurvivaltimeofrecipientwas35years.

The3wavesofdevelopmentinChinaProf.XiaSuiShenginWuHanTongJihospitaolandProf.LinYanZhenfinishedthefirstexplorationin1977.

Finished72casesofoperationbutonly13casessucceededin1991-1998.Thematurestagefrom1999.Globaldistributionoflivertransplantation,2010ThenumberoflivertransplantationofChinaranks2ndintheworld,onlyaftertheU.S.A.(WHOdata)TheproblemoforganshortageismoreseriousinChinawhichhasalargepopulationofliverdisease.

TheChineselivertransplantationrateissignificantlylowerthanthatofthedevelopedcountriesandregions.NumberoflivertransplantationinChinesemainland1980-2011AnnualdistributionoflivertransplantationinChinesemainland,2000-2011TheShanghai’snumberandrateoflivertransplantationbothrank1stinChina.RegionaldistributionoflivertransplantationinChinesemainland,1980-2011GeneralsituationoflivertransplantationinRenJiHospitalThenumberofthelivertransplantationhasranked1stinShanghaifor8yearsfrom2006andranked1stinChinafor4yearsfrom2010.RenJihospitalisalsothebiggestpediatriclivertransplantationcenterinChina.totalnumber1-yearsurvival3-yearsurvival5-yearsurvivaltotalnumber170387.6%83.3%81.9%ThepostoperativesurvivalrateofRenJihospitalwassignificantlyhigherthanthatofthenationalaveragelevelbyCLTRdata(1-and5-yearsurvivalratewas77.97%and60.53%,respectively).LiverTransplantationRemovethenativeliverLiverTransplantationRemovethenativeliverLiverTransplantationTrimthegraftatbacktableLiverTransplantationImplantthegraft

LiverTransplantationLivingdonorlivertransplantation(LDLT)Prof.SilvanoRaiafromBrazilperformedthe1stLDLTin1988.LDLTcanalleviatetheproblemoftheorganshortageeffectivelyandrepresentsthemostadvancedtechnologyinliversurgery.

LiverTransplantationLDLTThevolumeproportionofeachliversegment:Rightlobe(S5、6、7、8):65%Leftlobe:S4

20%，S2-3

15%TheliverhasaPowerfulcapacitytoregenerate.LiverTransplantation1196.9804.4392.9RightlobeLDLTLiverTransplantationIRHVRHVRPVRHAOccludeRHA

andRPVfordemarcationRightlobeLDLTLiverTransplantationV8V5CryopreservedvesselRightlobeLDLTLiverTransplantation2008.7.131stcas