Total versus subtotal gastrectomy for distal gastric cancer

However, lower mortality rate of recurrence was probably related to the criteria of these two procedures. Keywords: total gastrectomy, subtotal ... Journals WhyPublishWithUs? 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Weofferrealbenefitstoourauthors,includingfast-trackprocessingofpapers.Learnmore PromotionalArticleMonitoring RegisteryourspecificdetailsandspecificdrugsofinterestandwewillmatchtheinformationyouprovidetoarticlesfromourextensivedatabaseandemailPDFcopiestoyoupromptly.Learnmore SocialMedia       BacktoJournals»OncoTargetsandTherapy»Volume9 Listen OriginalResearch Totalversussubtotalgastrectomyfordistalgastriccancer:meta-analysisofrandomizedclinicaltrials            FulltextMetricsGetPermissionCitethisarticle AuthorsKongL,YangN,ShiL,ZhaoG,WangM,ZhangY Received18April2016 Acceptedforpublication19August2016 Published7November2016 Volume2016:9Pages6795—6800 DOIhttps://doi.org/10.2147/OTT.S110828 CheckedforplagiarismYes ReviewbySingleanonymouspeerreview Peerreviewercomments2 Editorwhoapprovedpublication: DrWilliamC.Cho DownloadArticle[PDF]  LinglingKong,*NianzhaoYang,*LianghuiShi,GuohaiZhao,MinghaiWang,YishengZhangDepartmentofGeneralSurgery,TheFirstAffiliatedYijishanHospitalofWannanMedicalCollege,Wuhu,People’sRepublicofChina*Theseauthorscontributedequallyto thisworkObjectives:Thismeta-analysisofrandomizedcontrolledtrialswasconductedtogiveamorepreciseestimationoftheefficacyanddrawbacksoftotalgastrectomy(TG)versussubtotalgastrectomy(SG)forprovendistalgastriccancer.Methods:TheelectronicdatabasesCochraneandPubMed(updatedonApril10,2016)weresearchedforrandomizedcontrolledtrialscomparingTGwithSGassurgicalproceduresfordistalgastriccancer.Fiveoutcomevariableswereanalyzed,includingpostoperativecomplications,anastomoticfistularate,hospitalmortalityrate,mortalityrateofrecurrence(thepatient’sdeathiscausedbytherecurrenceofgastriccancer,ratherthancausedbyotherdiseases),and5-yearsurvivalrate.Randomorfixedeffectmodelwasusedtoperformthismeta-analysis.Results:Sixtrials,including573casestreatedwithTGand791casestreatedwithSG,wereincluded.ComparedwithpatientsintheSGgroup,patientsintheTGgroupdidnotshowahigherrateofpostoperativecomplications(oddsratio[OR]:1.46,95%confidenceinterval[CI]:0.71–3.03,P=0.30).However,patientsintheTGgroupshowedasignificantlyhigherrateofanastomoticfistulathanpatientsintheSGgroup(OR:3.78,95%CI:1.97–7.27,P<0.0001).Hospitalmortalityrate,whichwasanalyzedinfourtrials,including510TGversus729SGpatients,showednosignificantdifferencebetweenthetwogroups(OR:1.80,95%CI:0.85–3.78,P=0.12).Importantly,therewasnosignificantdifferenceinthe5-yearsurvivalbetweenthetwogroups(OR:0.68,95%CI:0.39–1.19,P=0.18).Mortalityrateofrecurrence,whichwasalsoanalyzedinthreetrials,including396TGversus407SGpatients,showedasignificantlyhigherrateintheTGgroup(OR:0.07,95%CI:0.01–0.13,P=0.03).Conclusion:Thismeta-analysisdemonstratedthatpostoperativecomplications,hospitalmortalityrate,and5-yearsurvivalrateinTGpatientswassimilartotheSGgroup.Furthermore,SGwasassociatedwithsignificantlyfeweranastomoticfistulaandlowermortalityrateofrecurrencecomparedwithTG.However,lowermortalityrateofrecurrencewasprobablyrelatedtothecriteriaofthesetwoprocedures.Keywords:totalgastrectomy,subtotalgastrectomy,gastriccancer,randomizedcontrolledtrials Introduction Gastriccancerisoneofthemostcommondigestivetractmalignanciesworldwide,andsurgicalresectionistheonlytherapeuticmodalityforcure.1Theresectionmethodincludestotalgastrectomy(TG)andsubtotalgastrectomy(SG).SinceBillrothperformedthefirstSGin1881andSchlatterthefirstTGin1897,thebestsurgicalprocedureforadenocarcinomaofthedistalstomachhasbeenasubjectofdebateformorethanacentury.2–4 TheroutineuseofTGwasacceptedforthreemainreasons:5–71)TGcouldreducethelikelihoodofrecurrenceduetopossibleinadequatelymphnodesremoval;2)itcouldremoveallmulticentriccarcinomafociinthegastricremnant;and3)itcouldeliminatetheriskofmetachronousadenocarcinomathatmaydevelopinthegastricremnant.Additionally,somestudiesdemonstratedthatTGwaspreferabletoSG,becausepatientstreatedwithTGhadlonger5-yearsurvivalthanpatientstreatedwithSG.8–10Ontheotherhand,advocatesofSGclaimedthatroutineuseofTGincreasedoperativemorbidityandhospitalmortality,andhadnoadvantageoverSGintermsof5-yearoncologicalresults.11–13 Thedebateoverthetypeofcurativeresectionfordistalgastriccancerbasedonanumberofretrospectivepublishedstudies,andpatients’criteriaofeligibilityweredifferent.Therefore,withrespecttothetrialscomparingTGversusSG,well-designedrandomizedcontrolledtrials(RCTs)arenecessary.Untilnow,onlyafewRCTs3,8,14,15havereportedthedataontheshort-andlong-termoutcomesofTGfordistalgastriccancerincomparisontoSG,andtheresultsreportedintheseRCTswerediscordant. Therefore,amorepreciseestimationoftheoutcomesofTGincomparisontoSGisnecessary.Toourknowledge,thereisnometa-analysisoftheevidencegatheredfromtheoutcomesofTGandSGsurgeryfordistalgastriccancer.Thismeta-analysismaygivetheanswerintermsofthebestavailablescientificevidencetodate.Thepostoperativecomplicationrate,anastomoticfistularate,hospitalmortalityrate,mortalityrateofrecurrence,and5-yearsurvivalrateofTGincomparisontoSGwereestimatedinthisstudy. Methods Searchstrategy TheelectronicliteraturesearcheswereconductedusingCochraneandPubMed(updatedonApril10,2016).Searchtermsincluded:“totalgastrectomy”,“subtotalgastrectomy”,“gastriccancer”,and“Randomizedcontrolledtrials”.Alltitles,abstracts,andfull-textarticleswereevaluatedbytworeviewersindependently.Tobeeligible,thestudieshadtomeetthefollowingcriteria:1)RCTsofanysizethatinvestigatedTGversusSGinpatientswithcancerindistalstomach;2)reportedonrelevantshort-orlong-termoutcomesoftrial;and3)publishedinpeer-reviewedjournalsinEnglishlanguage. Dataextraction Thedataextractionandcriticalappraisalfromalltheeligiblestudieswascarriedoutindependentlybytwoinvestigators.Thefollowingvariableswereextractedfromtheincludedstudiesifavailable:firstauthor’sname,publicationyear,thenumberofpatientsinTGandSGgroups,overallcomplicationrateofthetwogroups,anastomoticfistularateofthetwogroups,mortalityrateofthetwogroups,mortalityrateofrecurrenceofthetwogroups,and5-yearsurvivalrateofthetwogroups.Theextracteddatawerediscusseduntilconsensuswasachieved. Statisticalanalysis Theoddsratios(ORs)and95%confidenceintervals(CIs)wereusedtoassessalloutcomes.13WeassessedtheheterogeneitybetweenstudiesbyusingtheQstatistic,whichindicatesthepresenceofheterogeneitywhenP<0.10.Iftheresultsofstudieshadnoheterogeneity,thefixed-effectsmodel(theMantel–Haenszelmethod)wasusedtocalculatethepooledORs.Otherwise,arandom-effectsmodel(theDerSimonianandLairdmethod)wasusedformeta-analysis.StatisticalsignificancewasconsideredwhenP<0.05.AllstatisticalanalyseswereconductedusingtheReviewManagerversion5.1.6(CochraneCollaboration,Oxford,UK)softwarepackage. Results Descriptionofeligibletrials Sixclinicaltrials8,14–18publishedinfourarticleswereconsideredsuitableforthismeta-analysis.ThestudysizeintwoRCTsfromEuropewaslargerthan100patientsexceptfortheAsiantrial(including54patients).Alltrialsreportedanappropriatedmethodofrandomization.Noneofthestudiesreportedthemethodofblinding.Sixstudiescontained1,364pooledpatients,ofwhom573wereallocatedtotheTGgroup,791totheSGgroup.ThedetailedinformationofeachincludedstudyisshowninTable1. Table1CharacteristicsofincludedstudiesAbbreviations:N,numbers;RCT,randomizedcontrolledtrial;SG,subtotalgastrectomy;TG,totalgastrectomy. Thepatientswereexcludedfromthestudyif:1)curativeresectioncouldnotbeperformedandthusconservativesurgerywasperformed;2)curativeresectioncouldnotbeperformedformacroscopiclymphnodeinvolvementofthecardioesophagealjunctionorsplenopancreaticregion;3)linitisplastica;4)lymphoma;5)suspectedsuperficialcarcinoma;and6)patientswithheartfailure,renalinsufficiency,severediabetesorarteritis,obesity(>20%ofnormalbodyweight),recentmyocardialinfarction,andlivercirrhosis,patientswhounderwentlaparoscopicsurgery,andpatientswhodiedwithin30daysaftersurgery.Theinclusioncriteriawere:1)cancerofthedistalhalfofthestomach;2)absenceofhepaticorperitonealspreadofthetumorormetastaticdepositsinthethirdnodallevel,accordingtotheJapaneseclassification;and3)absenceofunresectableinfiltrationofcontiguousorgans. Thereconstructivemethodsvaryfromtrialtotrial.InGouzi’spaper,TGrepairwasperformedbyastandardRoux-en-Yesophagojejunostomy.8ReconstructionofSGwasperformedbyaBillrothIIgastrojejunostomy.Whereas,Robertsonetal14restoredtheintestinalcontinuitybyanend-to-sideesophagojejunostomy,usingacircularstapler,witha40cmjejunalRouxlimb. PooledefficacyofTGversusSG Sixclinicaltrialscontaining1,364patients(TG=573,SG=791)wereanalyzed.ComparedwithpatientsintheSGgroup,patientsintheTGgroupdidnotshowahigherrateofpostoperativecomplications(OR:1.46,95%CI:0.71–3.03,P=0.30)(Figure1).However,patientsintheTGgroupshowedasignificantlyhigherrateofanastomoticfistulathanpatientsintheSGgroup(OR:3.78,95%CI:1.97–7.27,P<0.0001)(Figure2).Furthermore,therewasnosignificantdifferenceinthehospitalmortalityratebetweenthetwogroups(OR:1.80,95%CI:0.85–3.78,P=0.12)(Figure3).Importantly,therewasnosignificantdifferenceinthe5-yearsurvivalbetweenthetwogroups(OR:0.68,95%CI:0.39–1.19,P=0.18)(Figure4). Figure1Meta-analysisofpostoperativecomplicationsinrandomizedtrialsoftotalgastrectomyversussubtotalgastrectomy.Abbreviations:CI,confidenceinterval;M–H,Mantel–Haenszel. Figure2Meta-analysisofanastomoticfistulainrandomizedtrialsoftotalgastrectomyversussubtotalgastrectomy.Abbreviations:CI,confidenceinterval;M–H,Mantel–Haenszel. Figure3Meta-analysisofhospitalmortalityrateoftotalgastrectomyversussubtotalgastrectomy.Abbreviations:CI,confidenceinterval;M–H,Mantel–Haenszel. Figure4Meta-analysisof5-yearsurvivalrateoftotalgastrectomyversussubtotalgastrectomy.Abbreviations:CI,confidenceinterval;M–H,Mantel–Haenszel. Mortalityrateofrecurrence,whichwasanalyzedinthreetrials14,15,18thatincluded803pooledpatients,ofwhom396TGversus407SGpatients,showedasignificantlyhigherrateintheTGgroup(OR:0.07,95%CI:0.01–0.13,P=0.03)(Figure5),withnobetween-studyheterogeneity(P=0.14,I2=49%)(Figure5).ThedetailedinformationofthepooleddataisshowninTable2. Figure5Meta-analysisofmortalityofrecurrenceinrandomizedtrialsoftotalgastrectomyversussubtotalgastrectomy.Abbreviations:CI,confidenceinterval;M–H,Mantel–Haenszel. Table2SummarystatisticsofpooleddatacomparingtotalgastrectomyversussubtotalgastrectomyAbbreviations:CI,confidenceinterval;OR,oddsratio. Discussion Sixtrials8,14–18havebeenundertakentoinvestigatetheissuesofefficacyanddrawbacksofTGversusSG.Thismeta-analysisshowedthattheanastomoticfistularateandmortalityrateofrecurrencewashigherintheTGgroupthantheSGgroup.Inaddition,therewasnodifferenceinpostoperativecomplicationrate,hospitalmortalityrate,and5-yearsurvivalratebetweenTGandSGgroups. BothTGandSGaresurgicalproceduresperformedwithcurativeintent.Thesetwosurgicalproceduresarequiteeffectivecurativetreatments,butalsobringagreatnumberofpostoperativecomplications,whichincludesurgicalandnonsurgicalcomplications.TwoRCTsfromHongKong14andItaly15revealedthattheriskofpostoperativecomplicationswasfoundtobehigherintheTGgroupthantheSGgroup.ButRCTsfromFrance8andItaly16demonstratedthatTGdidnotincreasepostoperativecomplicationsincomparisonwithSG.Ourmeta-analysisshowedthattherewasnosignificantdifferenceinpostoperativecomplicationsbetweentheTGandSGgroups.Thepreoperativecriteriaofeligibility,whichexcludedpatientsinpoorconditionfromrandomization,mightexplainthelackofsignificantdifferencesbetweenTGandSG.15 Anastomoticfistularatewasreportedinthreetrials.ThepooleddatarevealedastatisticallysignificantlyhigheranastomoticfistularateintheTGgroup.IntheHongKongtrialledbyRobertsonetal,14threeanastomoticfistulaewererecordedintheTGgroup,whichwereatoesophagojejunaljunction.IntheFrenchtrialledbyGouzietal,812anastomoticfistulaewererecorded,ofwhich7wereintheTGgroupand5inSGgroup.InItaly,inatrialbyDeManzonietal,16threeanastomoticfistulaewererecorded,ofwhichonewasrecordedintheTGgroupandtwointheSGgroup,andthetotalnumbersoftwogroupswere40and77,respectively.Alltheseanastomoticfistulaeweremanagedconservativelywithnutritionalsupportwithfavorableoutcome.8,14IntheItaliantrialledbyBozzettietal,1522anastomoticfistulaewererecorded,ofwhich17wereintheTGand5intheSGgroups.However,thistrialdidnotprovideanyinformationabouttreatment.AccordingtoGouziandRobertson,theprocedureofTGismorecomplicatedandtimeconsuming.Otherwise,comparedtoTG,thereconstructivemethodofSGreflectedricherbloodsupplytothestomach.LargeclinicaltrialsshouldbeconductedtoconfirmthisfindingaboutsignificantdifferenceinanastomoticfistularatebetweenTGandSG. Therewasnosignificantdifferenceofhospitalmortalityratebetweenthetwogroupsinallthetrials,althoughTGsurgicalprocedurewasprolongedandmorecomplex. AlltrialshaverevealedthattherewasasignificantlyhighermortalityrateintheTGgroupcomparedwiththeSGgroup.Lowermortalityrateofrecurrencewasprobablyrelatedtothecriteriaofthesetwoprocedures.Inaddition,highmortalityrateinpatientsundergoingresectionofthestomachwasusuallyrelatedtoanastomoticfistula.8However,allpatientswhosufferedfromanastomoticfistulaintwoRCTsfromHongKongandFranceweremedicallytreatedandhealedwithoutmortality.8,14Fatalcomplicationsmayincreasethemortalityrate,buttheproportionoffatalcomplicationsintheRCTfromItalywasnotsignificantlydifferentbetweentheTGandSGgroups.15Therefore,thepooledresultsshowedthatmortalityratesinTGandSGgroupswerenotstatisticallysignificantlydifferent,althoughpooleddatashowedastatisticallysignificanthigheranastomoticfistularateintheTGgroupcomparedwiththeSGgroup. RecurrenceratewasnotreportedinbothTGandSGgroups.MortalityrateofrecurrenceinbothsurgicalprocedureswasreportedintwoRCTs.3,14Ourmeta-analysisshowedstatisticallysignificantlowermortalityrateofrecurrenceintheSGgroupthantheTGgroup.Toourknowledge,theTGgrouphasshownhigher5-yearsurvivalratethantheSGgroupintworetrospectivestudies.9,10However,thisdifferencehasnotbeenobservedinalltrials.Incontrast,theRCTfromHongKong14showedthatoverallsurvivalwassignificantlybetterintheSGthantheTGgroup(mediansurvival,1,511vs922days,P<0.05).Fortheseinconsistentconclusions,itispossiblethatsomeunknownprognosticfactorswerenotbalancedbetweentheTGandSGgroups.Inthepresentmeta-analysis,nosignificantdifferencein5-yearsurvivalwasobservedbetweentheTGandSGgroups.However,evenearlygastriccancerwasassociatedwithahighfrequencyofsecondprimaries.19ThereforeBozzettietal3,15suggestedthatwithrespecttotheprocedureofchoicefordistalgastriccancer,TGshouldnotberejectedinprinciple. Ontheotherhand,thereareseverallimitationsinthismeta-analysis.First,limitednumberofpatientswithcancerofthemiddleone-thirdofthestomachwererandomizedtoeitheraTGoraSGgroup,althoughamajorityofpatientsintheItaliantrialhadcanceroftheantrum.Second,theSGgroupwithD1lymphadenectomywasnotinlinewiththeTGgroupwithD2lymphadenectomyintheHongKongtrial.Third,theinclusionofstudiespublishedonlyinEnglishisanotherpotentiallimitationofthisanalysis.Fourth,onlytwotrialsmentionedthereconstructivemethod,soitishardtoassesswhetherornotthereconstructivemethodinfluencestheprognosis.Finally,onlyfourRCTswereconductedinthe1990sinsomecountries,andthesampleissmall.Furtherwell-designedrandomizedclinicaltrialswithlargersamplesizearestillneededtogetamorepreciseestimationoftheefficacyanddrawbacksofTGversusSGfordistalgastriccancer. Inconclusion,thepresentstudysuggestedthatpostoperativecomplicationrate,mortalityrate,and5-yearsurvivalrateintheTGgroupweresimilartothatintheSGgroup.Furthermore,SGwasassociatedwithsignificantlylessanastomoticfistulaandlowermortalityrateofrecurrencecomparedwithTG.Therefore,thisstudydemonstratedthatTGisnotsuperiortoSG.Furtherwell-designedrandomizedclinicaltrialswithlargersamplesizearestillneededtogetamorepreciseestimationoftheshort-andlong-termresultsofTGfordistalgastriccancerincomparisontoSG. Acknowledgments ThisprojectwassponsoredbythegrantsfromNationalScienceFoundationofChina(81372828)andScientificResearchFundProjectofIntroductionofTalentsofTheYijishanHospitalAffiliatedtoWannanMedicalCollege(YR201305). Authorcontributions Conceptionanddesign:MHWandYSZ.Furthermore,MHWtakesfullresponsibilityfortheintegrityoftheworkasawhole,frominceptiontopublishedarticle.Acquisition,compilation,andinterpretationofthedata:NZYandLLK;LHSandGHZwereresponsibleforstatisticalanalysisofthisarticle,includingwritingRcodes,interpretationoftheresults,andcomputeroutputofthedata.Allauthorswereinvolvedindraftingthemanuscriptandrevisingitcriticallyforimportantintellectualcontentandhavegivenfinalapprovalfortheversiontobepublished.Furthermore,allauthorshaveparticipatedsufficientlyintheworktotakepublicresponsibilityforitscontent. Disclosure Theauthorsreportnoconflictsofinterestinthiswork. 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