2015年6月案子未开工risk factors lymph node metastasis in ovarianfor systematic

Riskfactorsforlymphnodemetastasisinovariancancer:implicationsforsystematiclymphadenectomyPurpose:ThepurposeofthisstudywastoassesstheriskfactorsrelatedwithlymphMethods:WeretrospectivereviewedpatientsdiagnosedwithovariancancerbetweenJanuary2004andJanuary2012.Demographicsandpathologicfindingscorrelationswithlymphnodemetastaseswereassessed.Results:Atotalof256patientsunderwentcompletesurgicalstaging,includinglymphadenectomywerethereforeyzed.Themeannumberoflymphnodesobtainedbylymphadenectomywas20.5(range:2-57),andnodalmetastaseswerefoundin84patients(32.8%).Themeannumberofpositivelymphnodeswas3(range:1-40)inpatientswithlymphnodemetastasis.Atunivariateysis,histologytype(serousvs.non-serous),grade(G1vs.G2-3),andlevelofCA-125atdiagnosis(≤740U/mLvs.>740U/mL)weresignificantriskfactorsforlymphnodemetastases.Atmultivariateysis,histologytype(oddsratio[OR]2.728,95%confidenceinterval[CI]1.072-6.945,P=0.035),grade(OR1.897,95%CI1.209-2.977,P=0.005),andlevelofCA-125atdiagnosis(OR3.858,95%CI2.143-6.947,P<0.001)maintainedastatisticallysignificantassociationwithlymphnodemetastases.Thenodalmetastasesratescorrespondingto0,1,2,and3riskfactorswere0,4.0%,29.9%,and61.8%,respectively(P<0.001).Thenodalmetastasesratesof0-1riskfactorweresignificantlylowerthanthoseof2-3riskfactors(3.7%vs.40.6%;P<0.001).Conclusion:Histologytype,grade,andlevelofCA125atdiagnosisareidentifiablefactorsthatcanhelpthesurgeondecidewhethertoperformcomprehensivesurgicalstagingwithsystematiclymphadenectomy.:Ovariancancer;Lymphnodemetastases;Lymphadenectomy;CA-125;HistologytypeOvariancancerisahighlyfatalgynecologiccancerandthefifthleadingcauseofcancermortalityinwomen,with21,980newcasesand14,270deathsoccurringintheUnitedStatesin2014(1).In,ovariancanceristhetenthcancerincidencerateof7.95per100,000womenduring2009(2).Mostpatientswithovariancancerhaveadvanceddiseaseatthetimeofdiagnosisowingtoasymptomaticnatureforearlystagetumors,resultinginapoorlong-timesurvival(3,4).手术治疗仍是癌的最重要治疗方式，但是关于lymphadenectomy的价值一直以来都存在着争议。癌的淋状态会影响患者的生存(5-7)，因此成为癌InternationalFederationofGynecologyandObstetrics（FIGO）分期的重要指标之一，淋转移的患者分期至少为III期(8-9)。Thusrecognizingtheimportanceoftheprognosticvalueoflymphnodemetastasis,thesystematiclymphadenectomywasincludedintheguidelinesinFIGOstagingsystemRandomizedstudiesshowedthatsystematiclymphadenectomydetectsnodalmetastasesin13.6%-30.3%ofpatientswithovariancancer(10,11).Itwasfoundthattumorinvolvementoflymphnodewas14.2%(range6.1–29.6%)ofpatientswithclinicalstagesI–IIovariancancer(12).但目前仍缺乏确切的指标来预测癌患者nodemetastasesinFIGOstagesItoIIIovariancanceranddeterminetheinfluenceriskfactorsontheincidenceoflymphnodesmetastasesandevaluatetheroleofsystematiclymphadenectomy.PatientsandFromDecember2004toMarch2012,atotalof256patientswithprimaryovariancancerwhounderwentcytoreductivesurgeryattheSunYat-SenUniversityCancerCenter(SYSUCC)wereretrospectivelyyzed.Cytoreductivesurgerywasconsideredtohaveachievedoptimaldebulkingwhentheresidualdiseasewas<1cm.Patientswithsynchronousormetachronoustumors,borderlinetumorsandstage(stageIV)ovariancancerwereexcluded.Otherpatientswithmissingdatawerealsoexcluded.ThestudywasapprovedbytheethicscommitteeofSYSUCC.Allpatientsprovidedwrittenconsentforstorageoftheirinformationinthehospitaldatabase,andfortheresearchuseoftheinformation.ClinicopathologicalPreoperativeserumCA-125levelsweremeasuredwithinoneweekbeforestaginglaparotomyusingaradioimmunoassaykit.TheuppernormalvalueofserumCA-125levelswas35U/mL.Afterthediagnosisofovariancarcinoma,patientsunderwentsurgicalstagingincludingbilalsalo-oophorectomyandtotalabdominalhysterectomy;washingcytology;randommultipleperitonealbiopsies;omentectomy;andsystematicpelvicand/orpara-aorticlymphadenectomy.Clinicopathologicalfactorswereusedtoassesstheriskoflymphnodemetastases.Factorsexaminedincludedage,menopausalstatus,histologicaltype,histologicalgrade,andserumCA-125atdiagnosis.Thetumorswerestagedaccordingtothe2013FIGOstagingsystemandhistologicallydeinedaccordingtoWorldHealthOrganization(WHO)classification.StatisticalTheχ2andFisher’sexacttestswereusedtoyzethedifferencesbetweenqualitativedata.Theoptimumcut-offpointfortheCA-125wasdeterminedbyuseofthereceiveroperatingcharacteristic(ROC)curve.Theindependenteffectsofclinicalandpathologicalfactorsonlymphnodemetastasiswerethendeterminedbymultiplelogisticregressionysis,inwhichfactorsthatwerestatisticallysignificantinunivariateysiswereenteredintomultiplelogisticregressionysis.AP-value0.05wasconsideredsignificantinallyses.AlldatawereyzedtheSPSSstatisticalsoftwarepackage,version17.0(IBMCorporation,Armonk,NY,USA).256例。Table1summarizestheclinicopatholgiccharacteristicsofthe256patients。所有患者中位发病56岁（19-76岁，57.8%（148/256）的患者为绝期女性，81.3%（208/256）的患者为浆液癌，andbyFIGOcriteria30.0%(82/256)wereinstageI,25.8%(66/256)instageII,and42.2%(108/256)patientsinstageIII.Tumorgradewasgrade1in10.9%patients(28/256),grade2in49.2%patients(126/256),andgrade3in39.9%patients(102/256).Themeannumberoflymphnodesobtainedbylymphadenectomywas20.5(range:2-57),andnodalmetastaseswerefoundin84patients(32.8%).Themeannumberofpositivelymphnodeswas3(range:1-40)inpatientswithlymphnodemetastasis.ThemedianandmeanvalueofpreoperativeserumCA-125levelswere330.3U/mL,and1254.6U/mL(range:12-18277U/mL),respectively.Theoptimalcut-offpointsofCA-125wereyzedusingROCcurve.Theresultsshowedthat740U/mLwastheoptimalcut-offpointforlymphnodemetastasis(AreaUnderrocCurve=0.655,P<0.001).Therefore,theoptimalcutoffvalueof740wasvalidatedasariskfactorforysisoflymphnodemetastasistoevaluatetheroleofsystematiclymphadenectomy.Table1showstheriskfactorsforlymphnodemetastasesatunivariateysis.Histologytype(serousvs.non-serous),grade(G1vs.G2-3),andserumlevelofatdiagnosisCA-125(≤740U/mLvs.>740U/mL)weresignificantriskfactorsforlymphnodemetastases,whileageandmenopausalstatuswerenot.Serousadenocarcinomahadthehighestincidenceofnodemetastaseswhencomparedwithotherhistologictypes(37.5%vs.12.5%%,P=0.001).Nolymphnodemetastaseswerefoundinpatientswithwelldifferentiatedtumors.Astatisticallysignificantdifferenceintheincidenceoflymphnodemetastaseswasobservedamongpatientswithmoderay-andpoorlydifferentiatedtumorscomparedtothosewithwelldifferentiatedtumors(36.5%-37.3%vs.0%;P<0.001).PatientswithCA-125≤740U/mLatdiagnosisconferredariskoflymphnodemetastasessignificantlylowerthanCA-125>740U/mLatdiagnosis(22.4%vs.53.5%,P<0.001).Atmultivariateysis,histologytype(oddsratio[OR]2.728,95%interval[CI]1.072-6.945,P=0.035),grade(OR1.897,95%CI1.209-2.977,P=andserumlevelofCA-125atdiagnosis(OR3.858,95%CI2.143-6.947,P<0.001)maintainedastatisticallysignificantassociationwithlymphnodemetastases.Forthesethreeindependentriskfactorsweregrouped,thenodalmetastasesratescorrespondingto0,1,2and3riskfactorswere0,4.0%,29.9%and61.8%,respectivelylow-riskgroup,andpatientswith2-3riskfactorswereconsideredhigh-riskgroup.Thenodalmetastasesratesoflow-riskgroupweresignificantlylowerthanthoseofhigh-riskgroup(3.7%vs.40.6%;P<0.001).Thepredictiveperformanceofthemodelwasinvestigated.UsingtheROCcurvewasconstructed,andthecalculatedareaunderthecurvewas0.740(P<0.001).Accordingtothegroupsofriskfactors,48patientswerenon-serousovariancancerswith6patientswithnodalmetastases,all6patientswithG2-3stageand4patientswithserumlevelofCA-125atdiagnosis>740U/mL,withtheprobabilityoflymphnodemetastasiswas66.7%(4/6)inhigh-riskgroupofpatientswithnon-serousovariancancer.在本研究中我们探讨了影响癌患者pelvicorpara-aorticnodesmetastases的，结果发现histologytype,gradeandlevelofCA-125atdiagnosis是影响淋转移的独立。癌的淋清扫价值一直以来都存在着争议，1988年的FIGO发布的surgicalstagingschemeforovariancancerthatincludedpelvicandpara-aorticlymphnodesamplingorlymphadenectomy.However,thebenefitoflymphadenectomyinovariancancerpatientsisstillcontroversial.Thereareseriouspost-operativecomplicationsassociatedwithlymphadenectomy,suchaslymphedemainthelowerextremitiesandpelviclymphcystswith itantinfectionandthesecandevelopintochronicconditions(13-15).Meta分析的研究发现lymphadenectomycanovariancancerbutnotinearlystage(FIGOI-IIstage)epithelialovariancancerorpatientswithresidualtumor≤2cm(16).随机对照试验的结果亦未发现lymphadenectomy具有生存获益（10。淋清扫术发现5-10%的I-II期的患者有淋转移，由此改变分期(17-19)。因此，我们认为lymphadenectomyisessentialforaccuratestagingandhasaprognosticandpotentiallytherapeuticrole.Chanetal.reportedanincreaseinthepercentageofpatientswhounderwentsystematiclymphadenectomyduringsurgicalstagingforovariancancerinthelastdecadeusingSurveillance,EpidemiologyandEndResultsdata(20).结的状态评估对于癌患者的分期具有重要的意义但亦不是所有患者均需行淋清扫术。Inarandomizedstudyshowedthatsystematiclymphadenectomydetectsnodalmetastasesin8/59(13.6%)womenwithnoevidenceofresidualtumorandin30/99(30.3%)womenwhohadanyresidualtumorattheendofprimary(10).Itwas22%inanotherrandomizedstudy(11).Inthepresentretrospectivestudy,32.8%werelymphnodemetastases.可见大部分的癌患者并无淋转移。目前对于影响癌淋转移的仍没有明确的定义研究已发histologicalgrade,histology,bilalityofadnexaldisease,menopause,thepreoperativeserumCA-125levelandlymphnodeinvolvementonimagingstudies等的并不统一(17,19,21,22,23)我们的研究结果发现histologytype,grade,andlevelofCA125atdiagnosis是影响淋转移的独立。研究发现1/3-1/4的浆液的患者淋转移到腹膜后间隙，而粘液很少淋转移(23)。Ditto等和Powless等发现浆液的淋，移率为28%-30%内膜样出现淋转移为10.5%，但粘液未发现淋转移(19,23)。Takeshima等的研究发现浆液癌、透明细胞癌、子膜样、粘液的淋转移率分别为36.7%，16.9%，15.6%和7.7%12.5%的患者淋转移，粘液患者的淋转移率为20（4/20内1.1%（2/18，10淋转移多因素分析结果提示浆液癌为影响癌患者淋转移的危险因素。Powless等及Baann等均证实浆液癌为影响淋转移的，因素，而其他研究并未发现病理类型为影响淋转移的(19,21,22)。结合我们的研究，对于术中病理证实为浆液癌的患者，应高度注意淋转Kleppe等的研究中，grade1,grade2,andgrade3disease的淋转移率分别为4.0%，16.5%，和20.0%(12)。Baann等的研究亦提示grade3期为影响淋转移的独立。但也有研究得出了的结果(19,22)。我们的研究认为grade2-3是影响淋转移的独立，同时提示grade1的患者可能可以避免淋清扫。SerumCA-125levelisknownasaclinicalprognosticfactorforsurvivalandresponsetotreatmentinpatientswithepithelialovariancancer(25-27).多个研究发现CA-125可以作为预测淋转移的(28-30).Nevertheless,therehavebeenfewstudiesonthepredictionofnodalmetastasisinovariancancerusingthepreoperativeserumCA-125level.Kim等发现preoperativeserumCA-125level(>535U/mL)isariskfactorforlymphnodemetastasisinpatientswithepithelialovariancancer(22).Sudolmus等则发现CA125是预测癌淋转移的，thebestcut-offpointwas72U/mL(21).而Ditto等则未发现CA125并不是淋转（19尽管cut-offpoint和前面的研究不同但均提示CA125在评估癌患者的淋巴我们在发现发现含有0,1,2,and3riskfactors的淋转移率分别为0,29.9%,and61.8%,respectively(P<0.001)。根据含有的个数进一步分为low-riskgroup(0-1riskfactor)andhigh-riskgroup(2-3riskfactor),结果显示高危组患者的淋转移率显著高于低危组的患者(40.6%vs.3.7%;P<0.001)，提示根据进行分组来预测淋转移是可行的但是仍需要的研究来加Therearesomelimitationsofthecurrentstudy.Frist，Thiswasasinglecenterretrospectivestudyandhenceissubjecttoinherentbiases,thusthefindingsmaynotbeapplicabletothegeneralpopulation.Nevertheless,thepredictorsinthisstudycouldbethepatientsenrolledinthepresentstudywasunderwentcytoreductivesurgerywhichachievedoptimaldebulkingwhentheresidualdiseasewas<1cm.Therefore,themetastaticpatientswithFIGOstageIVwereexcludedinthepresentstudy.histologytype,grade,andlevelofCA125diagnosis是影响淋转移的独立.Sincethetherapeuticefficacyofsystematiclymphadenectomytoimprovesurvivalremainscontroversial.Thedecisiontoperformcompletesurgicalstagingwithlymphnodedissectioncanbemadewiththehelpofseveralprognosticriskfactorsidentifiablebeforeand/orduringsurgery.SiegelR,MaJ,JemalA.Cancerstatistics,2014.CACancerJClin.2014;64(1):9-ChenW,ZhengR,ZhangS,ZhaoP,LiG,WuL,HeJ.Theincidencesandmortalitiesofmajorcancersin,2009.ChinJCancer.2013;32(3):106-12.JemalA,ThomasA,MurrayT,ThunM.Cancerstatistics,2002.CACancerJClin.cancer:theNationalOvarianCancerEarlyDetectionProgram(NOCEDP).CancerTreatRes.2002;107:3-28.BaannC,BruckerSY,KraemerB,RothmundR,StaeblerA,FendF,WallwienerD,GrischkeEM.Theprognosticrelevanceofnodemetastasesinoptimallycytoreducedadvancedovariancancer.JCancerResClinOncol.2015Mar5.[Epubaheadofprint]BaannC,BaannR,BruckerSY,StaeblerA,FendF,GrischkeEM,WallwienerD.RoleofPelvicandPara-aorticLymphNodeMetastasesinOptimallyCytoreducedAdvancedOvarianCancer.AnticancerRes.AtasevenB,GrimmC,HarterP,PraderS,TrautA,HeitzF,duBoisA.Prognosticvalueoflymphnoderatioinpatientswithadvancedepithelialovariancancer.GynecolOncol.2014;135(3):435-40.PratJ.Ovarian,fallopiantubeandperitonealcancerstaging:RationaleandexnationofnewFIGOstaging2013.BestPractResClinObstetGynaecol.2015.pii:S1521-6934(15)00053-X.ZeppernickF,Meinhold-HeerleinI.ThenewFIGOstagingsystemforovarian,fallopiantube,andprimaryperitonealcancer.ArchGynecolObstet.Dell'AnnaT,SignorelliM,Benedetti-PaniciP,MaggioniA,FossatiR,FruscioR,MilaniR,BoccioloneL,BudaA,MangioniC,ScambiaG,AngioliR,CampagnuttaE,GrassiR,LandoniF.Systematiclymphadenectomyinovariancanceratsecond-looksurgery:arandomisedclinicaltrial.BrJCancer.2012;107(5):785-92.MaggioniA,BenedettiPaniciP,Dell'AnnaT,LandoniF,LissoniA,PellegrinoA,RossiRS,ChiariS,CampagnuttaE,GreggiS,AngioliR,ManciN,CalcagnoM,ScambiaG,FossatiR,FlorianiI,TorriV,GrassiR,MangioniC.Randomisedstudyofsystematiclymphadenectomyinpatientswithepithelialovariancancermacroscopicallyconfinedtothepelvis.BrJCancer.2006;95(6):699-704.KleppeM,WangT,VanGorpT,SlangenBF,KruseAJ,KruitwagenRF.LymphnodemetastasisinstagesIandIIovariancancer:areview.GynecolOncol.AchouriA,HuchonC,BatsAS,BensaidC,NosC,LécuruF.Complicationsoflymphadenectomyforgynecologiccancer.EurJSurgOncol.2013;39(1):81-6.InternationalSocietyofLymphology.Thediagnosisandtreatmentofperipherallymphedema:2013ConsensusoftheInternationalSocietyofLymphology.Lymphology2013;46(1):1-11.TodoY,YamamotoR,MinobeS,SuzukiY,TakeshiU,NakataniM,AoyagiY,OhbaY,OkamotoK,KatoH.Riskfactorsforpostoperativelower-extremitylymphedemainendometrialcancersurvivorswhohadtreatmentincludinglymphadenectomy.GynecolOncol.2010;119(1):60-4.GaoJ,YangX,ZhangY.Systematiclymphadenectomyinthetreatmentofepithelialovariancancer:ameta-ysisofmultipleepidemiologystudies.JpnJClinOncol.2015;45(1):49-60.BaannC,KrämerB,BruckerSY,StäblerA,FendF,WallwienerD,GrischkeEM,RothmundR.Relevanceofpelvicandpara-aorticnodemetastasesinearly-stageovariancancer.AnticancerRes.2014;34(11):6735-8.OshitaT,ItamochiH,NishimuraR,NumaF,TakeharaK,HiuraM,TanimotoH,NomaJ,HayaseR,MurakamiA,FujimotoH,KanamoriY,KitadaF,ShitsukawaK,NagajiM,MinagawaY,FujiwaraM,KigawaJ.Clinicalimpactofsystematicpelvicandpara-aorticlymphadenectomyforpT1andpT2ovariancancer:aretrospectivesurveybytheSankaiGynecologyStudyGroup.IntJClinOncol.DittoA,MartinelliF,ReatoC,KusamuraS,SolimaE,FontanelliR,HaeuslerE,RaspagliesiF.Systematicpara-aorticandpelviclymphadenectomyinearlystageepithelialovariancancer:aprospectivestudy.AnnSurgOncol.2012;19(12):3849-ChanJ,FuhK,ShinJ,CheungM,PowellC,ChenLM,KappD,OsannK.Thetreatmentand esofearly-stageepithelialovariancancer:havewemadeanyprogress?BrJCancer.2008;98(7):1191-6.SudolmuşS,KöroğluN,YıldırımG,ÜlkerV,GülkılıkA,DansukR.CanCA-125predictlymphnodemetastasisinepithelialovariancancersinTurkishpopulation?DisMarkers.2014;2014:492537.KimHS,ParkNH,ChungHH,KimJW,SongYS,KangSB.SignificanceofpreoperativeserumCA-125levelsinthepredictionoflymphnodemetastasisinepithelialovariancancer.ActaObstetGynecolScand.2008;87(11):1136-42.PowlessCA,AlettiGD,Bakkum-GamezJN,ClibyWA.Riskfactorsforlymphnodemetastasisinapparentearly-stageepithelialovariancancer:implicationsforsurgicalstaging.GynecolOncol.2011;122(3):536-40.TakeshimaN,HiraiY,UmayaharaK,FujiwaraK,TakizawaK,HasumiK.Lymphnodemetastasisinovariancancer:differencebetweenserousandnon-serousprimarytumors.GynecolOncol.2005;99(2):427-3