Organ-Transplantation-器官移植.ppt

Organ-Transplantation-器官移植.ppt

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1,OrganTransplantation,JunOuyang,MD,PhDtheFirstAffiliatedHospitalofSoochowUniversity,2,OrganTransplantation（Tx）wasoneofthemostoutstandingmedicalachievementsofthe20thcentury.Asthedevelopmentinthefieldofsurgicaltechniques,immunotherapyresearchandnewimmunosuppressives,OrganTxhasbecomeaeffectivemethodtohealtheendstageorganfailurepatients.,3,Upto2008，over121,000organTxintheworldKidneyTx112745,longestsurvival45ysLiverTx20178,ls31ysHeartTx87543,ls28ysLungTx18576,ls19ysP-kTx16041ls26ys,4,therelationshipbetweentransplantsurgeon,nephrologistsandimmunologistshasservedasamodelformultidisciplinaryteamcare.KidneyTxisthepioneerdisciplineinsolidorganTx.KidneyTxcantrulyrestorepatientswithend-stagerenaldisease.,5,KidneyTx,6,Histroy,1936,S-UVoronoyarmKTx1953,FranceHamburgerliving-relative-donorKTx。

1954,US,twinsKTX.1959-1962,understandingtheroleofimmunotherapy,（Aza）Middle60s,crossmatchingbetweendonor-recipient.,7,KtxinChina,1962,firstcadaverdonorKTx（Dr.Wu）Upto2008,over70,000,ls28ys,8,KTxinourhospital,1976-1977animalexperimental（dog,pig）1978firstcadaverdonorKTxLs26ys2005,livingdonorKTx,9,End-StageRenalDisease（ESRD）,IncidenceandPrevalence:

startingrenalreplacementtherapyeachyearforESRDisabout300permilliononpopulation.ThemedianageofthesenewESRDpatientsis65years.BoththeprevalenceandtheincidenceofESRDaremorecommoninelderlythaninyoungpatients,inmenthaninwomen.,10,FrequentcauseofESRD,InChina,themostcommoncauseisglomerulonephritis,followedinorderbydiabetes,hypertension.InUSA,diabetesisespeciallycommonamongnativeAmericansandhypertensionishighamongAfricanAmericans.,11,TreatmentOptionsforESRD,Thetreatmentsthatarechosenforanindividualpatientarethosethatwillallowthelongestextensionofusefullife.RenalreplacementtherapyincludesrenalTxandmaintenancedialysis.RenalTxisthepreferredmethodoftherapyformostpatientswithESRDbecauseitismorecosteffectiveandallowsareturntoamorenormallifestylethanmaintenancedialysisdoes.,12,BarriersoforganTx,SourcesofDonorGraftRejectionOperativetechniques,13,SourcesofDonorKidneys,Livingnonrelateddonors（hb/non-hb）Livingrelateddonors（heartbeating）Cadaverdonors（non-heartbeating）,14,Livingdonorsvscadaverdonors,ResultsbetterLessrejectionsLegalbenefitsLongersurvivaltime,15,ThedonormustbeABO-compatiblewiththerecipient.Livingdonorsshouldbeingoodhealthbothphysicallyandpsychologically.Aboveall,thelivingdonorshouldbeavolunteerandmustclearlyunderstandthenatureoftheproceduresothatinformedconsenttotheoperationcanbegiven.Donorsmustbeoflegalage.,16,LivingDonors,Overthelastdecade,morethan10,000peoplehavedonatedkidneysforTx.Themainrisktoadonoristheanesthesiaandtheoperationitself.Themostcommoncomplicationfollowingnephrectomy-exceptforminoratelectasis-iswoundinfection,whichoccursinlessthan1%ofcasesandisusuallysuperficial.,17,Onthebasisofthepreoperativeevaluation,Drsmustbeabletoassurethelivingdonorofnearlynormalrenalfunctionafterunilateralnephrectomy.Onevaluation,ifoneofthepotentialdonorskidneysisbetterthantheother,thebetterkidneyisleftwiththedonor,18,Cadaverdonors,Sinceonly30%ofrecipientshaveasuitablelivingdonor,theonlywaytoprovideTxtomostpatientsistousecadaverkidneys.Itisessentialtothesuccessoftheprocedurethatthetransplantedorganbeofgoodquality.Itisalsoimportantthatthedonorhaverelativelynormalrenalfunctionatthetimeofdeath.Phenoxybenzamineoranothervasodilatordrugisoftengiventopreventrenalvasospasmduringtheagonalphase.,19,Thecriteriaforanidealcadaverkidneydonorarenormalrenalfunction,nohypertensionrequiringtreatment,nodiabetesmellitus,nomalignancyotherthanaprimarybraintumorortreatedsuperficialskincancer,nogeneralizedviralorbacterialinfection,acceptableurinalysis,agebetween6and45years,andnegativeassaysforsyphilis,hepatitis,HIV,andhumanT-lymphoproliferativevirus.,20,SelectionofRecipients,Theidealrecipientisonewhohasnoseriousinfectionsorlowerurinarytractdisease,withminimalandreversiblesystemicdiseasesecondarytorenalfailure.Recipientswiththefollowingprimaryrenaldiseaseshavebeensuccessfullytransplanted:

glomerulonephritis,pyelonephritis,polycystickidneydisease,malignanthypertension,refluxpyelonephtis,Goodpasturessyndrome,congenitalrenalhypoplasia,renalcorticalnecrosis,FabryssyndromeandAlportssyndrome.,21,Successfultransplantshavebeenachievedinpatientswithcertainsystemicdiseasesinwhichthekidneyisoneoftheendorgans（cystinosis,systemiclupuserythematosusandtype1diabetes）.RenalTxisgenerallycontraindicatedinoxalosisbecausethediseaserecursthetransplantquickly.Onceapatienthasbeenselectedasatransplantcandidate,eitherhemodialysisorchronicambulatoryperitonealdialysisisusuallystarted.,22,BilateralnephrectomypriortoTxhasbeenperformedlessfrequentlyinrecentyears.Theindicationsforpreliminarynephrectomy:

severehypertensionuncontrolledbydialysisormedicationanatomicabnormalitiesoftheurinarytractwithorwithoutinfection（eg,hydronephrosis,ureteralreflux）polycystickidneydiseasewithdocumentedrecurringinfectionsorrecurringepisodesofgrosshematuriarequiringtransfusions.,BilateralnephrectomypriortoTx,23,KidneyPreservation,WarmischemicinjuryisduetofailureofoxidativephosphorylationandcelldeathduetoATPdepletion.Whenthesodium-potassiumpumpisimpaired,sodiumchlorideandwaterpassivelydiffuseintothecells,resultingincellularswellingandthe“no-reflow”phenomenonafterrenalrevascularization.,24,PrinciplesofSimpleColdStorageofKidneys,Cellularenergyrequirementsaresignificantlyreducedbyhypothermia.Thisisdonebysurfacecooling,hypothermicpulsatileperfusion,orflushingwithanicecoldsolutionfollowedbycoldstorage.Makingtheflushsolutionslightlyhyperosmolarwithimpermeantsolutessuchasmannitol,lactobionate,raffinose,orhydroxyethylstarchhelpspreventendothelialcellswellingandthe“no-reflow”phenomenon.（UW,HC-Asolution）minimizecellularswellingwiththeimpermeantsoluteslactobionate,raffinose,andhydroxyethylstarch.,25,Histocompatibility,ThehistocompatibilitysystemsofgreatestimportanceinrenaltransplantationaretheABObloodgroupandthemajorhistocompatibilitycomplex（MHC）RecipientcirculatingcytotoxicantibodiesagainsttheMHCantigensofaspecificdonoraredetectedbypretransplantationcross-matchingtechniques,andapositivecomplement-dependentTcelllymphocytotoxicitycross-matchisconsideredtobeacontraindicationtorenaltransplantationwhentheserumusedisrecentlyobtainedfromthetransplantationcandidate.,26,Crossmatching,ABOcompatibleHLAcompatiblepositivecomplement-dependentTcelllymphocytotoxicitycross-matchPRA,27,Operativetechniques,Greatcareshouldbetakeninremovalofthelivingdonorkidney.Everyattemptshouldbemadetominimizerenalischemiaanddamagetotheureter.Renalischemiamaybeminimizedbyhydratingthedonorandadministeringanosmoticdiuretictopromoteaurineflowrateof3-4ml/minatthetimeofnephrectomy.,28,RecipientOperation,ThesurgicaltechniqueofrenalTxinvolvesanastomosesoftherenalarteryandveinandureter.Inadults,thetransplantkidneyisplacedintheiliacfossathroughanobliquelowerabdominalincision.Theiliacandhypogastricarteriesandtheiliacveinaremobilizedasindicatedfortheproposedspecificsideanastomosis.,29,30,KidneyTx,hypogastricA,iliacA,iliacV,iliacV,31,Anend-to-sideanastomosisisperformedbetweenrenalarteryandthehypogastricarteryunlessthelatteristooarteriosclerotic.Whenmultiplearteriesarepresentincadaverdonor,thekidneyaretransplantedwithanastomosesofaCarrellpatchofdonoraortacontainingthemultiplerenalarteriestothecommon（orexternal）iliacarery.,32,Insmallchildrenandinfants,amidlineabdominalincisionisusedandthececumandascendingcolonaremobilizedmedially.Exposingtheaortaandvenacava.End-to-sideanastomosesoftherenalvesselstothevenacavaandaortaarethenaccomplishedandthekidneyissecuredinitsretroperitoneallocationbyapproximatingthepreviouslydividedposteriorparietalperitoneumoverthetransplantedkidney.,33,Urinarytractcontinuitycanbeestablishedbypyeloureterostomy,ureteroureterostomyorureteroneocystostomy.WehaveusedureteroneocystostomybyamodifiedPolitano-Leadbettersubmucosaltunneltechniqueinover500renaltransplantswithveryfewcomplications.,34,Renalgraftrejection,35,GraftRejectionCategories,Themajorhazardforthepostoperativeallografirecipientisrejection.Mostrejectionsoccurwithinthefirst3months.,36,HyperacuterejectionAcceleratedrejectionAcuterejectionChronicrejection,Fourkindsofrejection,37,Hyperacuterejection,Itisduetopreformedcytotoxicantibodiesagainstdonorlymphocytesorrenalcells.Thisreactionbeginssoonaftercompletionoftheanastomosisandcompletegraftdestructionoccursin24-48hours.Thereisnoeffectivemethodoftreatingthisreaction.Pretransplantcrossmatchtestingcaneliminatethistypeofrejection.,38,Acceleratedrejection,Thisreactionusuallyappearswithin5daysafteraperiodofgoodfunction.Itisbelievedtoberelatedtosubliminalpreformedcytotoxicantibodiesagainstdonorcellsnotdetectedbytheusualcytotoxicitytechniques.,39,Acuterejection,Itisthemostcommontypeofrejectionepisodeduringthefirst3monthsafterTx.Itisprimarilyanimmunecellularreactionagainstforeignantigens.Thistypeofrejectionprocessmayb