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1、子宫内膜癌治疗相关问题子宫内膜癌治疗相关问题- -妇产妇产科课件科课件n子宫内膜癌新分期n子宫内膜癌淋巴结切除必要性n子宫内膜癌子宫切除的范围全国高等院校教材妇产科学乐杰主编林仲秋编写p275I期子宫内膜癌应行筋膜外子宫切除术及双附件切除术 盆腔及腹主动脉旁淋巴结切除和（或）取样术下列情况之一，应行盆腔及腹主动脉旁淋巴结切除和（或）取样术可疑淋巴结增大 宫颈受累 CA125显著升高特殊组织类型 癌灶累及宫腔面积超过50% 低分化 深肌层受累CochraneDatabaseSystRev.2010Jan20;(1):CD007585.Lymphadenectomyforthemanagement
2、ofendometrialcancer.MayK,BryantA,DickinsonHO,KehoeS,MorrisonJUniversityofOxford,WomensCentreNoevidencethatlymphadenectomydecreasestheriskofdeathordiseaserecurrencecomparedwithnolymphadenectomyinwomenwithpresumedstageIdisease.Theevidenceonseriousadverseeventssuggeststhatwomenwhoreceivelymphadenectomy
3、aremorelikelytoexperiencesurgicallyrelatedsystemicmorbidityorlymphoedema/lymphocystformation.JNatlCancerInst.2008Dec3;100(23):1707-16.Epub2008Nov25Systematicpelviclymphadenectomyvs.nolymphadenectomyinearly-stageendometrialcarcinoma:randomizedclinicaltrial.Rome,ItalyCONCLUSION:Althoughsystematicpelvi
4、clymphadenectomystatisticallysignificantlyimprovedsurgicalstaging,itdidnotimprovedisease-freeoroverallsurvival.Lancet.2009Jan10;373(9658):125-36.Epub2008Dec16.Efficacyofsystematicpelviclymphadenectomyinendometrialcancer(MRCASTECtrial):arandomisedstudy.Collaborators(180)AmosC,BlakeP,BransonA,BuckleyC
5、H,RedmanCW,ShepherdJ,DunnG,HeintzP,YarnoldJ,JohnsonP,MasonM,RuddR,BadmanP,BegumS,ChadwickN,CollinsS,GoodallK,JenkinsJ,LawK,MookP,SandercockJ,GoldsteinC,UscinskaB,CruickshankM,ParkinDE,CrawfordRA,LatimerJ,MichelM,ClarkeJ,DobbsS,McClellandRJ,PriceJH,ChanKK,MannC,RandR,FishA,LambM,GoodfellowC,TahirS,Sm
6、ithJR,GornallR,Kerr-WilsonR,SwinglerGR,LaveryBA,ChanKK,KehoeS,FlavinA,EddyJ,Davies-HumphriesJ,HockingM,Sant-CassiaLJ,PearsonS,ChapmanRL,HodgkinsJ,ScottI,GuthrieD,PersicM,DanielFN,YiannakisD,AlloubMI,GilbertL,HeslipMR,NordinA,SmartG,CowieV,KatesmarkM,MurrayP,EddyJ,GornallR,SwinglerGR,FinnCB,MoloneyM,
7、FarthingA,HanochJ,MasonPW,McIndoeA,SoutterWP,TebbuttH,MorganJS,VaseyD,CruickshankDJ,NevinJ,KehoeS,McKenzieIZ,GieC,DaviesQ,IrelandD,KirwanP,DaviesQ,LambM,KingstonR,KirwanJ,HerodJ,FianderA,LimK,HeadAC,LynchCB,BrowningAJ,CoxC,MurphyD,DuncanID,MckenzieC,CrockerS,NietoJ,PatersonME,TidyJ,DuncanA,ChanS,Wil
8、liamsonKM,WeekesA,AdeyemiOA,HenryR,LaurenceV,DeanS,PooleD,LindMJ,DealeyR,GodfreyK,HatemMM,LopesA,MonaghanJM,NaikR,EvansJ,GillespieA,PatersonME,TidyJ,IndT,LaneJ,OatesS,RedfordD,FordM,FishA,Larsen-DisneyP,JohnsonN,BolgerA,KeatingP,Martin-HirschP,RichardsonL,MurdochJB,JeyarajahA,LambM,McWhinneyN,Farthi
9、ngA,MasonPW,KitchenerH,BeynonJL,HogstonP,LowEM,WoolasR,AndersonR,MurdochJB,NivenPA,Kerr-WilsonR,ChinK,FlynnP,FreitesO,NewmanGH,McNallyO,CullimoreJ,OlaitanA,MouldT,MenonV,RedmanCW,GeorgeM,HatemMH,EvansA,FianderA,HowellsR,LimK,CawdellG,WarwickAP,EustaceD,GilesJ,LeesonS,NevinJ,vanWijkAL,KarolewskiK,Kli
10、mekM,BlecharzP,McConnellD.Hysterectomyandbilateralsalpingo-oophorectomy(BSO)isthestandardsurgeryforstageIendometrialcancer.Systematicpelviclymphadenectomyhasbeenusedtoestablishwhetherthereisextra-uterinediseaseandasatherapeuticproceduremedianfollow-upof37months(IQR24-58)191womenhaddied:88/704standar
11、dsurgerygroup103/704lymphadenectomygroup251Recurrentdisease107/704standardsurgerygroup144/704lymphadenectomygroup)INTERPRETATIONnoevidenceofbenefitintermsofoverallorrecurrence-freesurvivalforpelviclymphadenectomyinwomenwithearlyendometrialcancer.Pelviclymphadenectomycannotberecommendedasroutineproce
12、durefortherapeuticpurposesoutsideofclinicaltrials.子宫内膜癌淋巴结切除利与弊子宫内膜癌淋巴结切除利与弊争论争论“由来已久由来已久”！早期：淋巴结转移率较低早期：淋巴结转移率较低国内国内n n中山肿瘤：临床中山肿瘤：临床7.9%7.9%,8.6%, 38.4%,8.6%, 38.4%n n浙江肿瘤：临床浙江肿瘤：临床4.4%4.4%,14%,14%，34.8% 34.8% 国外国外n nStagebStagebStagebStageb（a a a a）G G G G1-2 1-2 1-2 1-2 或或或或 IaGIaGIaGIaG3 3 3 3：
13、转移率转移率转移率转移率 0-2%0-2%0-2%0-2%n nStagebStagebStagebStageb（a a a a）G G G G3 3 3 3或或或或 IcIcIcIc（b b b b）G G G G1 1 1 1：转移率转移率转移率转移率16%-20%16%-20%16%-20%16%-20%早期：早期：LNDLND并未降低复发并未降低复发 改善生存改善生存n n1996年10月到2006年3月n n意大利多个中心的514例术前FIGO分期为期子宫内膜癌患者n n随机分配接受盆腔淋巴结切除术（n=264）或者不进行此手术（n=250） “冲锋在前冲锋在前”的意大利研究的意大利
14、研究生存上没有差异生存上没有差异 5 5年年DFS 5DFS 5年年OSOSn n未接受淋巴结切除术未接受淋巴结切除术 81.7% 90.0%81.7% 90.0%n n接受淋巴结切除术接受淋巴结切除术 81% 85.9%81% 85.9%复发时间和复发率相似复发时间和复发率相似 复发时间 复发率 （mth） （49mth）未进行淋巴结切除 13mth 33例（13.2%）淋巴结切除术者为 14mth 34例（12.9%）复发部位相似复发部位相似LND手术并发症明显增加手术并发症明显增加n n在手术时间和住院时间上，两组有显著的统计学差异n n接受盆腔淋巴结切除术的患者有较高的早期和晚期术后并
15、发症率，两组出现并发症的患者分别为81例和34例。改变观念改变观念 无容置疑无容置疑n n子宫内膜癌治疗正朝个性化治疗发展n n已有充足证据证明期子宫内膜癌患者，淋巴结切除术不能带来任何生存获益。特殊患者手术难度增加，风险增加n n肥胖n n高龄n n心血管疾病n n糖尿病淋巴结真的可以不切除吗？n nLesionsitesandregionLesionsitesandregionn nDepthofmyometrialinvasionDepthofmyometrialinvasionn nCervicalinvasionCervicalinvasionn nExtrauterineinvas
16、ionornot,singleormultipleExtrauterineinvasionornot,singleormultiplen nPathologicalgradeandclassificationPathologicalgradeandclassificationn nLymphvascularinvasion(LVI)Lymphvascularinvasion(LVI)淋巴转移相关因素病灶大小与淋巴结转移病灶大小与淋巴结转移n nTumorSizeTumorSizen nLNmets:LNmets: 2cm4%2cm4%2cm15%2cm15%entireuterinecavit
17、y35%entireuterinecavity35%n n5-y survival: 5-y survival: 2cm - 98% 2cm - 98% 2cm - 84% 2cm - 84% entire uterine cavity - 64% entire uterine cavity - 64% 建议有指征的行腹膜后淋巴结切除术建议有指征的行腹膜后淋巴结切除术腹膜后淋巴结切除指征腹膜后淋巴结切除指征1.1.术前B超、MRI等估计深肌层受侵2.2.术前病理分级为G33.3.术前临床分期II期以上4.4.术中探查腹膜后淋巴结可疑转移5.5.术中发现侵肌1/26.6.术中发现宫腔50%以上有
18、病灶累及7.7.子宫内膜浆乳癌、透明细胞癌等一定要切除腹主动脉旁淋巴结吗？一定要切除腹主动脉旁淋巴结吗？n nEurJGynaecolOncol.2007;28(2):98-102.EurJGynaecolOncol.2007;28(2):98-102.n n PrinceofWalesHospital,Shatin,HongKongPrinceofWalesHospital,Shatin,HongKongn nIsaorticlymphadenectomynecessaryintheIsaorticlymphadenectomynecessaryinthemanagementofendome
19、trialcarcinoma?managementofendometrialcarcinoma?n n75(46.0%)pelviclymphadenectomyalone75(46.0%)pelviclymphadenectomyalonen n88(54.0%)hadbothpelvicandaortic88(54.0%)hadbothpelvicandaorticlymphadenectomylymphadenectomyn n35(21.5%)nodalmetastases35(21.5%)nodalmetastasesn npositivepelvic26(16.0%)positiv
20、epelvic26(16.0%)n npositiveaortic24(27.3%)positiveaortic24(27.3%)n nIsolatedaorticmetastases17cases(19.3%)Isolatedaorticmetastases17cases(19.3%)n n35patientswithnodalmetastasesn nrecurrencedevelopedin15(42.9%)n nandallexceptonediedwithinfiveto50monthsn nTherecurrenceratewashigher(63.6%)amongpatients
21、withupperaorticlymphnodemetastasesn nallthosewhorecurreddiedofdiseasewithinsevento28months.CONCLUSIONSn naorticlymphadenectomyprovidesbothdiagnosticandtherapeuticvalueinthemanagementofendometrialcarcinomawithhighmetastaticrisk.TodoYTodoYetal.etal.Survivaleffectofpara-aorticlymphadenectomyinSurvivale
22、ffectofpara-aorticlymphadenectomyinendometrialcancer(SEPALstudy):aretrospectivecohortendometrialcancer(SEPALstudy):aretrospectivecohortanalysis.analysis.Lancet.2010Apr3;375(9721):1165-72Lancet.2010Apr3;375(9721):1165-72n n 671patientswithendometrialcarcinoma671patientswithendometrialcarcinoman nsyst
23、ematicpelviclymphadenectomy(n=325)systematicpelviclymphadenectomy(n=325)n npelvicandpara-aorticlymphadenectomy(n=346)pelvicandpara-aorticlymphadenectomy(n=346)n n INTERPRETATION:Combinedpelvicandpara-INTERPRETATION:Combinedpelvicandpara-aorticlymphadenectomyisrecommendedasaorticlymphadenectomyisreco
24、mmendedastreatmentforpatientswithendometrialcarcinomaoftreatmentforpatientswithendometrialcarcinomaofintermediateorhighriskofrecurrence.intermediateorhighriskofrecurrence. 期子宫内膜癌子宫切除范围期子宫内膜癌子宫切除范围33I I期子宫内膜癌期子宫内膜癌子宫切除范围：子宫切除范围： 全子宫切除术？筋膜外子宫切除术？二者异同？全子宫切除术？筋膜外子宫切除术？二者异同？ 次广泛子宫切除术？次广泛子宫切除术？FIGO 2009 F
25、IGO 2009 子宫内膜癌分期改变子宫内膜癌分期改变影响子宫内膜癌子宫切除范围的选择吗？影响子宫内膜癌子宫切除范围的选择吗？局限于子宫的内膜癌手术选择局限于子宫的内膜癌手术选择争议：局限于子宫，宫颈累及？广泛子宫切除术？争议：局限于子宫，宫颈累及？广泛子宫切除术？子宫切除范围值得探讨子宫切除范围值得探讨内膜癌病变局限于子宫内膜癌病变局限于子宫-手术方式手术方式Disease limited to uterusMedically inoperable operableTumor directed RTTotal hysterectomy and bilateral salpingo-oopho
26、rectomyLympho nodes dissection pelvic+para aorticThe current NCCN Clinical Practice Guideline recommendspracticing radical hysterectomy only when cervical infiltrationis suspected on MRI or when confirmed by cervical biopsy.2009NCCNn nFIGO: FIGO: 筋膜外子宫切除术筋膜外子宫切除术n nGOG2010:Womenwithendometrialcancer
27、sshouldGOG2010:Womenwithendometrialcancersshouldundergoundergototal abdominal hysterectomytotal abdominal hysterectomyandbilateralandbilateralsalpingo-oophorectomy(TAH-BSO),pelvic/paraaorticsalpingo-oophorectomy(TAH-BSO),pelvic/paraaorticdissectiondissectionn n妇科常见恶性肿瘤治疗指南：筋膜外子宫切除术妇科常见恶性肿瘤治疗指南：筋膜外子宫
28、切除术n n林巧稚妇科肿瘤学：全子宫切除术林巧稚妇科肿瘤学：全子宫切除术n n中国妇产科学（曹泽毅主编）：筋膜外子宫切除术中国妇产科学（曹泽毅主编）：筋膜外子宫切除术 I 期子宫内膜癌期子宫内膜癌-手术方式手术方式 I 期子宫内膜癌-手术方式n nGanToKagakuRyoho.1995Aug;22(9):1163-8.GanToKagakuRyoho.1995Aug;22(9):1163-8.Total hysterectomyTotal hysterectomyisdoneforcasesofstage0,isdoneforcasesofstage0,modified radical h
29、ysterectomymodified radical hysterectomyforstageI,forstageI,radical radical hysterectomyhysterectomyforstageII,andradicalhysterectomyforstageII,andradicalhysterectomycombinedwithresectionofthemetastaticlesionsforcombinedwithresectionofthemetastaticlesionsforstageIIIandIVstageIIIandIVn nZhonghuaFuCha
30、nKeZaZhi.ZhonghuaFuChanKeZaZhi.2002Feb;37(2):90-3.2002Feb;37(2):90-3.Surgical methodSurgical methodisnotthemainfactorinfluencedisnotthemainfactorinfluencedthesurviveofstageIendometrialcarcinoma.thesurviveofstageIendometrialcarcinoma.为什么不行广泛或次广泛子宫切除术为什么不行广泛或次广泛子宫切除术MauroSignorelli,etal.MauroSignorell
31、i,etal.GynecologicOncology2009GynecologicOncology2009ModifiedRadicalHysterectomyVersusExtrafascialHysterectomyintheModifiedRadicalHysterectomyVersusExtrafascialHysterectomyintheTreatmentofStageIEndometrialCancerTreatmentofStageIEndometrialCancer RecurrenceRecurrenceClassIClassIhysterectomy(hysterect
32、omy(n n =263)=263)ClassIIClassIIhysterectomy(hysterectomy(n n =257)=257)NOrecurrenceNOrecurrence231(87.8)231(87.8)228(88.7)228(88.7)WIthrecurrenceWIthrecurrence32(12.2)32(12.2)29(11.3)29(11.3)DFSHR(95%CI)DFSHR(95%CI)87.7%(1.0ref)87.7%(1.0ref)89.7%(0.91)89.7%(0.91)(0.551.51)(0.551.51)OSHR(95%CI)OSHR(
33、95%CI)88.9%(1.0ref)88.9%(1.0ref)92.2%(0.77)92.2%(0.77)(0.441.33)(0.441.33) 筋膜外子宫切除术筋膜外子宫切除术n n目的目的 toensurethatthetoensurethatthecervixisentirelycervixisentirelyremovedremovedn n适应症：子宫内适应症：子宫内膜癌，早期宫颈膜癌，早期宫颈癌癌n n与全子宫切除术与全子宫切除术异同？异同？n n定义？定义？n n手术中要点？手术中要点？ 筋膜外子宫切除术筋膜外子宫切除术n n方法：方法：n nThe position of
34、the uretersThe position of the uretersisdeterminedbyisdeterminedbypalpationwithoutfreeingtheuretersfromtheirpalpationwithoutfreeingtheuretersfromtheirbeds.beds.n nTheparametriumistransectedmedialtotheTheparametriumistransectedmedialtotheureter,butlateraltothecervix,keepingtheureter,butlateraltothece
35、rvix,keepingtheparacervical ring intactparacervical ring intact. .n nTheuterosacralandvesicouterineligamentsareTheuterosacralandvesicouterineligamentsaretransectedclosetotheuterus.transectedclosetotheuterus.n nThereisnoremovalofparacolposandThereisnoremovalofparacolposanda minimal a minimal part of
36、vaginapart of vaginaisresectedatfornixlevel.isresectedatfornixlevel.病变累及宫颈手术范围的选择n nII期子宫内膜癌子宫切除范围首选广泛子宫切除术（IIIII型子宫根治术）n n累及宫颈粘膜，现在归为I期，子宫切除范围？n n累及粘膜和间质如果应该选择不同的手术范围，如何术前鉴别诊断之？n n宫颈是否累及？是否间质浸润？术前诊断困难40分期分期改变改变带来带来的新的新问题问题累及宫颈粘膜（I期）？n nOLDOLD：ICIC差差于于IIAIIAn nNEWNEW：IIII差差于所有于所有I I期期n nIIAIIA期宫旁期宫旁
37、累及？累及？ 宫颈癌早期宫颈癌早期手术范围手术范围n n如何识别粘如何识别粘膜累及还是膜累及还是间质浸润间质浸润FIGO1988FIGO1988FIGO2009FIGO2009I I期期IAIAIBIBICIC(56757)(56757)91%91%89%89%77%77%90%90%78%78%IIIAIIIAIIIBIIIBIIICIIICIIIC1IIIC1IIIC2IIIC259%59%36%36%54%(3120)54%(3120)56%56%36%36%- -57%57%49%49%累累及及宫宫颈颈粘粘膜膜（ 一一期期）？诊断和鉴别宫颈粘膜累及还是间质浸润分段诊刮或宫腔镜检查分段诊
38、刮或宫腔镜检查宫颈管阴性宫颈管阴性宫颈上皮浸润宫颈上皮浸润I 型子宫切除术型子宫切除术MR局限于颈管内膜局限于颈管内膜侵犯宫颈间质侵犯宫颈间质II或或III型子宫切除术型子宫切除术宫颈间质浸润宫颈间质浸润 宫颈累及时子宫切除范围选择n n指 南：广泛子宫切除术n n局限于子宫归为一类局限于子宫归为一类n nII II期子宫内膜癌期子宫内膜癌:筋膜外或广泛子宫切除术筋膜外或广泛子宫切除术n nKOREAKOREA， JAPANJAPAN：ChoosethesurgicalextentofhysterectomythroughtheirChoosethesurgicalextentofhyster
39、ectomythroughtheirowndispositionanddonotstrictlyadheretheresultsofpreowndispositionanddonotstrictlyadheretheresultsofpreoperativeevaluation.operativeevaluation.n nJAPANESEgroupJAPANESEgroupmorethan70%ofinstitutesneverperformRHwithoutmorethan70%ofinstitutesneverperformRHwithoutregardingthepreoperativ
40、estatusofcervicalinvolvementregardingthepreoperativestatusofcervicalinvolvement(Watanabe)(Watanabe)n nNORTHAMERICANNORTHAMERICAN：20-30%center20-30%centerII期子宫内膜癌RH 手术的必要性II期子宫内期子宫内膜癌手术方膜癌手术方式的选择式的选择II期子宫内膜癌RH 手术的必要性n nDepth of myometrialDepth of myometrialinvasionandpelvicorinvasionandpelvicorparaao
41、rticparaaorticlymph nodelymph nodepositivityweresignificantlypositivityweresignificantlycorrelatedwithcorrelatedwithparamatrialinvolvement.paramatrialinvolvement. n nOfthe19patientswithpelviclymphnodeOfthe19patientswithpelviclymphnodemetastasis,8patients(42.1%)hadconcomitantPMI.metastasis,8patients(42.1%)hadconcomitantPMI.n nConversely,ofthe10patientswithPMI,8(80.0%)Conversely,ofthe10patientswithPMI,8(80.0%)hadlymphnodemetastasis.hadlymphnodemetastasis.
