肝移植治療原發(fā)性肝

肝移植治療原發(fā)性肝第1頁(yè)/共69頁(yè)肝移植治療原發(fā)性肝癌

第2頁(yè)/共69頁(yè)主要內(nèi)容肝癌肝移植的療效肝癌肝移植的手術(shù)適應(yīng)證選擇肝癌肝移植術(shù)后腫瘤復(fù)發(fā)的影響因素肝癌肝移植術(shù)后腫瘤復(fù)發(fā)的預(yù)防肝癌肝移植術(shù)后腫瘤復(fù)發(fā)的治療第3頁(yè)/共69頁(yè)肝癌肝移植的療效第4頁(yè)/共69頁(yè)中國(guó)大陸肝癌肝移植效果Benign(51.8%)

76.7%83.8%78.8%76.1%71.6%55.8%49.2%Malignant(48.2%)Cumulativesurvival(%)Survivaltime(month)BenigndiseasesvsMalignantdiseases:PLogrank<0.001第5頁(yè)/共69頁(yè)我中心肝癌肝移植的結(jié)果n=1717第6頁(yè)/共69頁(yè)我中心肝癌肝移植的結(jié)果第7頁(yè)/共69頁(yè)合并門靜脈癌栓的肝癌Ⅰ組（75例）：癌栓未累及門靜脈主干Ⅱ組（53例）：癌栓累及門靜脈主干鄭虹，高偉，朱志軍，等。肝移植治療肝細(xì)胞癌合并門靜脈癌栓的療效評(píng)價(jià)。中華器官移植雜志，2009，30：484-486。第8頁(yè)/共69頁(yè)伴淋巴結(jié)轉(zhuǎn)移的肝癌N=28第9頁(yè)/共69頁(yè)混合細(xì)胞型肝癌（n=14）陳洪磊，鄭虹，王政祿，等。肝移植治療混合細(xì)胞型肝癌14例。中國(guó)腫瘤臨床，2009，36：486-489第10頁(yè)/共69頁(yè)肝癌肝移植的手術(shù)適應(yīng)證選擇第11頁(yè)/共69頁(yè)肝癌肝移植的手術(shù)適應(yīng)證第12頁(yè)/共69頁(yè)肝癌肝移植的手術(shù)適應(yīng)證Authorsn篩選標(biāo)準(zhǔn)5y-OSMazzaferro,NEJM1996Milan標(biāo)準(zhǔn)

48Single＜5cm,3nodles＜3cm74%(4y)Yao,Hepatology2001UCSF64Single＜6.5cm,3nodles＜4.5cm73%Mazzaferro,LancetOncol20091556Up-to-seven,withoutmicrovascularinvasion71.2%第13頁(yè)/共69頁(yè)關(guān)于Milan標(biāo)準(zhǔn)1996年提出，5年存活率達(dá)70%影像學(xué)檢查對(duì)Milan標(biāo)準(zhǔn)的誤診率高達(dá)15%~46%很多超出Milan標(biāo)準(zhǔn)的患者可因肝臟移植獲益第14頁(yè)/共69頁(yè)關(guān)于Milan標(biāo)準(zhǔn)第15頁(yè)/共69頁(yè)關(guān)于Milan標(biāo)準(zhǔn)第16頁(yè)/共69頁(yè)關(guān)于Milan標(biāo)準(zhǔn)第17頁(yè)/共69頁(yè)關(guān)于Milan標(biāo)準(zhǔn)第18頁(yè)/共69頁(yè)關(guān)于Milan標(biāo)準(zhǔn)第19頁(yè)/共69頁(yè)UCSF標(biāo)準(zhǔn)2001年，California大學(xué)提出單發(fā)腫瘤直徑<6.5cm

多發(fā)腫瘤<3個(gè)，每個(gè)腫瘤直徑<4.5cm

腫瘤直徑總和<8cm5年存活率達(dá)75%YaoFY,FerrellL,BassNM,etal.Livertransplantationforhepatocellularcarcinoma:expansionofthetumorsizelimitsdoesnotadverselyimpactsurvival.Hepatology.2001;33:1394–1403.第20頁(yè)/共69頁(yè)UCSF標(biāo)準(zhǔn)DuffyJP,VardanianA,BenjaminE,etal.Livertransplantationcriteriaforhepatocellularcarcinomashouldbeexpanded：A22-yearexperiencewith467patientsatUCLA.AnnalsofSurgery,2007,246:502-511.第21頁(yè)/共69頁(yè)UCSF標(biāo)準(zhǔn)第22頁(yè)/共69頁(yè)UCSF標(biāo)準(zhǔn)JuMK,ChoiGH,HuhKH,etal.UCSFcriteriabypre-transplantradiologicstudycannotassuresimilarpost-transplantresultsofhepatocellularcarcinomawithinMilancriteria.Hepatogastroenterology.2010Jul-Aug;57(101):819-25.第23頁(yè)/共69頁(yè)UCSF標(biāo)準(zhǔn)法國(guó)14個(gè)移植中心，459例患者1985年至1998年符合UCSF標(biāo)準(zhǔn)的患者5年生存率低于符合Milan標(biāo)準(zhǔn)的患者，但無(wú)統(tǒng)計(jì)學(xué)差異5年生存率低于50%，不宜使用UCSF報(bào)道5年無(wú)瘤生存率80%DecaensT，Roudot-ThoravalF,Hadni-BressonS,etal.ImpactofUCSFcriteriaaccordingtopre-andpost-OLTtumorfeatures:analysisof479patientslistedforHCCwithashortwaitingtime.LiverTranspl.2006Dec;12(12):1761-9.YaoFY,XiaoL,BassNM,etal.Livertransplantationforhepatocellularcarcinoma:validationoftheUCSF-expandedcriteriabasedonpreoperativeimaging.AmJTransplant.2007,7(11):2587-96.第24頁(yè)/共69頁(yè)新Milan標(biāo)準(zhǔn)Up-to-sevencriteria腫瘤最大直徑與腫瘤個(gè)數(shù)之和不超過(guò)75年生存率達(dá)71.2%MazzaferroV,LlovetJM,MiceliR,etal.PredictingsurvivalafterlivertransplantationinpatientswithhepatocellularcarcinomabeyondtheMilancriteria:aretrospective,exploratoryanalysis.LancetOncol2009;10:35.第25頁(yè)/共69頁(yè)肝癌肝移植的手術(shù)適應(yīng)證

新Milan標(biāo)準(zhǔn)Contourplotofthe5-yearoverall-survivalprobabilityaccordingtosizeofthelargesttumour,numberoftumours,andpresenceorabsenceofmicrovascularinvasion第26頁(yè)/共69頁(yè)新Milan標(biāo)準(zhǔn)第27頁(yè)/共69頁(yè)新Milan標(biāo)準(zhǔn)第28頁(yè)/共69頁(yè)無(wú)門靜脈癌栓腫瘤累計(jì)直徑≤8cm術(shù)前AFP<400ng／ml組織學(xué)分級(jí)為高／中分化n=1955-yOS:70.7%5-yDFS:62.4%Transplantation,2008,85:1726-32杭州標(biāo)準(zhǔn)第29頁(yè)/共69頁(yè)單發(fā)腫瘤直徑≤9cm多發(fā)腫瘤≤3個(gè)且每個(gè)≤5cm、所有腫瘤直徑總和≤9cm無(wú)大血管侵犯、淋巴結(jié)轉(zhuǎn)移及肝外轉(zhuǎn)移JCancerResClinOncol.2009

N=1078“上海復(fù)旦標(biāo)準(zhǔn)”（SHFD）第30頁(yè)/共69頁(yè)肝癌肝移植的手術(shù)適應(yīng)證選擇第31頁(yè)/共69頁(yè)如何選擇手術(shù)適應(yīng)證目前的選擇標(biāo)準(zhǔn)主要基于腫瘤形態(tài)學(xué)特點(diǎn)，如腫瘤大小，數(shù)目腫瘤生物學(xué)行為對(duì)預(yù)后具有重要影響，如組織學(xué)分級(jí)，微血管侵犯腫瘤形態(tài)學(xué)與生物學(xué)行為并不完全一致因此，對(duì)腫瘤血清標(biāo)記物、分子標(biāo)記物、基因改變的研究成為熱點(diǎn)第32頁(yè)/共69頁(yè)活體肝移植手術(shù)適應(yīng)證LeeSG,HwangS,MoonDB,etal.Expandedindicationcriteriaoflivingdonorlivertransplantationforhepatocellularcarcinomaatonelarge-volumecenter.LiverTranspl，2008;14:935.ItoT,TakadaY,UedaM,etal.Expansionofselectioncriteriaforpatientswithhepatocellularcarcinomainlivingdonorlivertransplantation.LiverTranspl2007;13:1637.SugawaraY,TamuraS,MakuuchiM.Livingdonorlivertransplantationforhepatocellularcarcinoma:TokyoUniversityseries.DigDis2007;25:310.第33頁(yè)/共69頁(yè)如何選擇活體肝移植手術(shù)適應(yīng)證活體肝移植供者存在一定的致病性（14%-21%）和致死性（0.25%-1%）許多超出Milan標(biāo)準(zhǔn)的肝癌患者可因肝移植獲益活體肝移植器官來(lái)源具有定向性多數(shù)學(xué)者認(rèn)為，5年生存率至少應(yīng)>50%第34頁(yè)/共69頁(yè)肝癌肝移植術(shù)后腫瘤復(fù)發(fā)

的影響因素第35頁(yè)/共69頁(yè)預(yù)后相關(guān)因素腫瘤大小淋巴結(jié)轉(zhuǎn)移情況血管侵潤(rùn)情況

影像學(xué)檢查結(jié)果

顯微鏡檢查結(jié)果組織學(xué)分級(jí)原發(fā)病灶數(shù)量年齡>60歲γ羧基凝血酶原血清濃度（研究中）第36頁(yè)/共69頁(yè)TNM分期對(duì)預(yù)后的影響MarshJW,DvorchikI,BonhamCA,etal.IsthepathologicTNMstagingsystemforpatientswithhepatomapredictiveofoutcome?Cancer2000;88(3):538–43.第37頁(yè)/共69頁(yè)手術(shù)方式對(duì)預(yù)后的影響FisheraRA,KulikbLM,FreisecCE,etal.Hepatocellularcarcinomarecurrenceanddeathfollowinglivinganddeceaseddonorlivertransplantation.AmericanJournalofTransplantation2007;7:1601–1608.第38頁(yè)/共69頁(yè)手術(shù)方式對(duì)預(yù)后的影響LiC,WenTF,YanLN,etal.Outcomeofhepatocellularcarcinomatreatedbylivertransplantation:comparisonoflivingdonoranddeceaseddonortransplantation.HepatobiliaryPancreatDisInt，2010,9:366-369.第39頁(yè)/共69頁(yè)手術(shù)方式對(duì)預(yù)后的影響VakiliK,PomposelliJJ,CheahYL,etal.LivingDonorLiverTransplantationforHepatocellularCarcinoma:IncreasedRecurrencebutImprovedSurvival..Livertransplantation,2009,15:1861-1866.第40頁(yè)/共69頁(yè)手術(shù)方式對(duì)預(yù)后的影響HwangS,LeeSG,AhnCS,etal.Small-sizedlivergraftdoesnotincreasetheriskofhepatocellularcarcinomarecurrenceafterlivingdonorlivertransplantation.TransplantationProceedings,2007,

39:1526–1529.第41頁(yè)/共69頁(yè)手術(shù)方式對(duì)預(yù)后的影響理論上講，小體積移植物的缺血再灌注損傷和肝再生導(dǎo)致的血管生成可能促進(jìn)腫瘤進(jìn)展但目前臨床實(shí)際影響并不明確目前臨床證據(jù)表明，移植物類型對(duì)肝移植術(shù)后腫瘤進(jìn)展并無(wú)或僅有輕微影響第42頁(yè)/共69頁(yè)等待時(shí)間對(duì)預(yù)后的影響ChaoSD,RobertsJP,FarrM,etal.Shortwaitlisttimedoesnotadverselyimpactoutcomefollowinglivertransplantation

forhepatocellularcarcinoma.AmericanJournalofTransplantation2007;7:1594–1600.第43頁(yè)/共69頁(yè)肝癌肝移植術(shù)后腫瘤

復(fù)發(fā)的預(yù)防第44頁(yè)/共69頁(yè)術(shù)前治療術(shù)前治療的目的控制腫瘤生長(zhǎng)和血管侵潤(rùn)新輔助治療減少患者移植術(shù)后復(fù)發(fā)風(fēng)險(xiǎn)腫瘤降期，使移植成為可能第45頁(yè)/共69頁(yè)術(shù)前治療—TACENoconvincingargumentsshowingthatTACEreducestherateofdropoutbeforeLTNoconvincingargumentsshowingthatTACEimprovesthesurvivalafterLTAlthoughTACEinducedcompletetumornecrosisinsomepatientsBelghitiJ,CarrBI,GreigPD,etal.TreatmentbeforeLiverTransplantationforHCC.AnnalsofSurgicalOncology,2008,15:993–1000.第46頁(yè)/共69頁(yè)術(shù)前治療—TACEDownstagingofHCCbyTACEispossibleinone-thirdtoone-halfofLTcandidatesButthesepatientshavehigherdropoutrates,higherrecurrenceratesThereisnosufficientevidencethatpretransplantTACEmaydelineatethepossibilityofexpandingcurrentselectioncriteriaforOLTinpatientswithHCCBelghitiJ,CarrBI,GreigPD,etal.TreatmentbeforeLiverTransplantationforHCC.AnnalsofSurgicalOncology,2008,15:993–1000.第47頁(yè)/共69頁(yè)術(shù)前治療—射頻消融PretransplantRFablationforHCCasastrategytoreducedropouthasbeenaddressedinthreestudiesthereisnodatademonstratingthatRFimprovesthesurvivalafterLTBelghitiJ,CarrBI,GreigPD,etal.TreatmentbeforeLiverTransplantationforHCC.AnnalsofSurgicalOncology,2008,15:993–1000.第48頁(yè)/共69頁(yè)術(shù)前治療—肝切除合并HBV感染的肝癌患者，行肝切除后腫瘤復(fù)發(fā)，80%符合Milan標(biāo)準(zhǔn)，可行挽救性肝移植合并HCV感染的肝癌患者，行肝切除后腫瘤復(fù)發(fā)，60%超出Milan標(biāo)準(zhǔn)PoonRT,FanST,LoCM,etal.long-termsurvivalandpatternofrecurrenceafterresectionofsmallhepatocellularcarcinomainpatientswithpreservedliverfunction:implicationsforastrategyofsalvagetransplantation.AnnSurg2002;235:373–82.ChiricaM,DurandF,SommacaleD,etal.Long-termoutcomeafterresectionforsmallHCCinpatientswithhepatitisCvirusinfection:argumentsforastrategyofresectionasabridgetotransplantationratherthansalvagetransplantation.Hepatology2004;(suppl4);40:162A.第49頁(yè)/共69頁(yè)術(shù)前治療—肝切除優(yōu)勢(shì)可以得到更多的病理學(xué)證據(jù)（如分化程度，有無(wú)微血管侵犯，有無(wú)衛(wèi)星灶等），更有效的預(yù)測(cè)肝移植的預(yù)后并選擇手術(shù)時(shí)機(jī)第50頁(yè)/共69頁(yè)術(shù)前治療—新輔助化療SoderdahlG,Backman,IsoniemiH,etal.Aprospective,randomized,multi-centretrialofsystemicadjuvantchemotherapyversusnoadditionaltreatmentinlivertransplantationforhepatocellulararcinoma.EuropeanSocietyforOrganTransplantation,2006,19:288–294.第51頁(yè)/共69頁(yè)TACE聯(lián)合索拉菲尼BMCCancer2008,8:349doi:10.1186/1471-2407-8-349第52頁(yè)/共69頁(yè)免疫抑制方案的選擇TosoC,MeraniS,BigamDL,etal.Sirolimus-basedimmunosuppressionisassociatedwithincreasedsurvivalafterlivertransplantationforhepatocellularcarcinoma.Hepatology2010;51:1237-1243.第53頁(yè)/共69頁(yè)免疫抑制方案的選擇Vivarelli

M,CucchettiA,BarbaGL,etal.Livertransplantationforhepatocellularcarcinomaundercalcineurininhibitors.AnnSurg2008;248:857–862.第54頁(yè)/共69頁(yè)免疫抑制方案的選擇ChinnakotlaS,DavisGL,VasaniS,Impactofsirolimusontherecurrenceofhepatocellularcarcinomaafterlivertransplantation.LiverTranspl,2009,15:1834-1842.第55頁(yè)/共69頁(yè)免疫抑制方案的選擇Hepatocellularcarcinomarecurrence–freesurvivalinrecipientstreatedwithsirolimus-basedimmunosuppression.Abbreviation:CNI,calcineurininhibitor.ZimmermanMA,TrotterJF,Wachsetal.Sirolimus-basedimmunosuppressionfollowinglivertransplantationforhepatocellularcarcinoma.LiverTranspl2008,14:633-638.第56頁(yè)/共69頁(yè)免疫抑制方案的選擇VivarelliM,DazziA,ZanelloM,etal.

Effectofdifferentimmunosuppressiveschedulesonrecurrence-freesurvivalafterlivertransplantationforhepatocellularcarcinoma.Transplantation2010;89:227–231.第57頁(yè)/共69頁(yè)免疫抑制方案的選擇第58頁(yè)/共69頁(yè)免疫抑制方案的選擇第59頁(yè)/共69頁(yè)肝癌肝移植術(shù)后腫瘤

復(fù)發(fā)的治療第60頁(yè)/共69頁(yè)腫瘤復(fù)發(fā)后的生存率ShinWY,SuhKS,LeeHW,etal.PrognosticfactorsaffectingsurvivalafterrecurrenceinadultlivingdonorlivertransplantationforhepatocellularCarcinoma.Livertransplantation,16:678-684,2010.第61頁(yè)/共69頁(yè)腫瘤復(fù)發(fā)后生存的影響因素ShinWY,SuhKS,LeeHW,etal.PrognosticfactorsaffectingsurvivalafterrecurrenceinadultlivingdonorlivertransplantationforhepatocellularCarcinoma.Livertransplantation,16:678-684,2010.第62頁(yè)/共69頁(yè)治療方法對(duì)預(yù)后的影響KornbergA,KupperB,TannapfelA,etal.Long-termsurvivalafterrecurrenthepatocellularcarcinomainlivertransplantpatients:Clinicalpatternsandoutcomevariables.EurJSurgOncol.2010;36(3):275-80.第63頁(yè)/共69頁(yè)全身化療Overallsurvival(OS)Kaplan–Meiercurve(n=24)inpatientsreceivingpalliativ