Anterior Approach vs Conventional Hepatectomy for ...

Importance Tumor relapse after partial hepatectomy for colorectal liver metastasis (CRLM) remains an unsolved issue. Intraoperative manipulation ... AnteriorApproachvsConventionalHepatectomyforResectionofColorectalLiverMetastasis:ARandomizedClinicalTrial|ColorectalCancer|JAMASurgery|JAMANetwork Ourwebsiteusescookiestoenhanceyourexperience.Bycontinuingtouseoursite,orclicking"Continue,"youareagreeingtoourCookiePolicy | Continue [SkiptoNavigation] fulltexticon FullText contentsicon Contents figureicon Figures/Tables multimediaicon Multimedia attachicon SupplementalContent referencesicon References relatedicon Related commentsicon Comments DownloadPDF Comment TopofArticle KeyPoints Abstract Introduction Methods Results Discussion Conclusions ArticleInformation References Figure1. CONSORTDiagramViewLargeDownloadaOnepatienthadapositiveresectionmarginandbloodlossexceeding2000mLsimultaneously.bTwopatientshadpositiveresectionmargins,bloodlossexceeding2000mL,andpreoperativepositivetumorcellssimultaneously.Figure2. Kaplan-MeierPlotsforOverallandDisease-FreeSurvivalViewLargeDownloadThegraphsdepictKaplan-Meierestimatedoverallsurvival(A)anddisease-freesurvival(B)stratifiedbyanteriorapproachvsconventionalhepatectomy(log-ranktest)andKaplan-Meierestimatedoverallsurvival(C)anddisease-freesurvival(D)stratifiedbyperioperativepositiveandnegativefindingsforcirculatingtumorcells(CTC)(log-ranktest). Table1. BaselineCharacteristicsViewLargeDownloadTable2. OperativeDetailsandPerioperativeOutcomesViewLargeDownloadTable3. OncologicalOutcomesViewLargeDownload Supplement1.TrialProtocol Supplement2.eTable1.TumorCellDetectioninBloodSampleseTable2.ComparisonofTumorCellDetectioninBloodandBoneMarrowSampleseTable3.CoxRegressionAnalysis Supplement3.DataSharingStatement 1.Creasy  JM,Sadot  E,Koerkamp  BG,  etal. Actual10-yearsurvivalafterhepaticresectionofcolorectallivermetastases:whatfactorsprecludecure?  Surgery.2018;163(6):1238-1244.doi:10.1016/j.surg.2018.01.004PubMedGoogleScholarCrossref2.deJong  MC,Mayo  SC,Pulitano  C,  etal. Repeatcurativeintentliversurgeryissafeandeffectiveforrecurrentcolorectallivermetastasis:resultsfromaninternationalmulti-institutionalanalysis.  JGastrointestSurg.2009;13(12):2141-2151.doi:10.1007/s11605-009-1050-0PubMedGoogleScholarCrossref3.deJong  MC,Pulitano  C,Ribero  D, 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 K. NonconventionalApproachestoAdvancedLiverCancer:LiverSurgeryApproachedThroughtheMitochondria.MedicalTribune;1992:117-165.16.Liddo  G,Buc  E,Nagarajan  G,Hidaka  M,Dokmak  S,Belghiti  J. Theliverhangingmanoeuvre.  HPB(Oxford).2009;11(4):296-305.doi:10.1111/j.1477-2574.2009.00068.xPubMedGoogleScholarCrossref17.Li  Y,Xu  KS,Li  JS,  etal. Theresearchofno-touchisolationtechniqueonthepreventionofpostoperativerecurrenceandmetastasisofhepatocellularcarcinomaafterhepatectomy.  Hepatogastroenterology.2014;61(131):784-791.PubMedGoogleScholar18.Arrazubi  V,Mata  E,Antelo  ML,  etal. Circulatingtumorcellsinpatientsundergoingresectionofcolorectalcancerlivermetastases:clinicalutilityforlong-termoutcome:aprospectivetrial.  AnnSurgOncol.2019;26(9):2805-2811.doi:10.1245/s10434-019-07503-8PubMedGoogleScholarCrossref19.Seeberg  LT,Waage  A,Brunborg  C, 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 etal. Anteriorapproachtomajorresectionforcolorectallivermetastasis.  JGastrointestSurg.2018;22(11):1928-1938.doi:10.1007/s11605-018-3840-8PubMedGoogleScholarCrossref24.Llado  L,Muñoz  A,Ramos  E,Torras  J,Fabregat  J,Rafecas  A. Theanteriorhanging-approachimprovespostoperativecourseafterrighthepatectomyinpatientswithcolorectallivermetastases:resultsofaprospectivestudywithpropensity-scorematchingcomparison.  EurJSurgOncol.2016;42(2):176-183.doi:10.1016/j.ejso.2015.11.009PubMedGoogleScholarCrossref25.Fritzmann  J,Kirchberg  J,Sturm  D,  etal. RandomizedclinicaltrialofstaplerhepatectomyversusLigaSure™transectioninelectivehepaticresection.  BrJSurg.2018;105(9):1119-1127.doi:10.1002/bjs.10902PubMedGoogleScholarCrossref26.Fretland  AA,Dagenborg  VJ,Bjørnelv  GMW,  etal. Laparoscopicversusopenresectionforcolorectallivermetastases:theOSLO-COMETrandomizedcontrolledtrial.  AnnSurg.2018;267(2):199-207.doi:10.1097/SLA.0000000000002353PubMedGoogleScholarCrossref27.Schnitzbauer  AA,Lang  SA,Goessmann  H,  etal. Rightportalveinligationcombinedwithinsitusplittinginducesrapidleftlateralliverlobehypertrophyenabling2-stagedextendedrighthepaticresectioninsmall-for-sizesettings.  AnnSurg.2012;255(3):405-414.doi:10.1097/SLA.0b013e31824856f5PubMedGoogleScholarCrossref28.Capussotti  L,Ferrero  A,Russolillo  N,Langella  S,LoTesoriere  R,Viganò  L. Routineanteriorapproachduringrighthepatectomy:resultsofaprospectiverandomisedcontrolledtrial.  JGastrointestSurg.2012;16(7):1324-1332.doi:10.1007/s11605-012-1894-6PubMedGoogleScholarCrossref29.Coppa  J,Citterio  D,Cotsoglou  C,  etal. Transhepaticanteriorapproachtotheinferiorvenacavainlargeretroperitonealtumorsresectedenblocwiththerightliverlobe.  Surgery.2013;154(5):1061-1068.doi:10.1016/j.surg.2013.05.027PubMedGoogleScholarCrossref30.Hinz  S,Hendricks  A,Wittig  A,  etal. DetectionofcirculatingtumorcellswithCK20RT-PCRisanindependentnegativeprognosticmarkerincoloncancerpatients:aprospectivestudy.  BMCCancer.2017;17(1):53.doi:10.1186/s12885-016-3035-1PubMedGoogleScholarCrossref31.Koch  M,Kienle  P,Hinz  U,  etal. Detectionofhematogenoustumorcelldisseminationpredictstumorrelapseinpatientsundergoingsurgicalresectionofcolorectallivermetastases.  AnnSurg.2005;241(2):199-205.doi:10.1097/01.sla.0000151795.15068.27PubMedGoogleScholarCrossref32.Soeth  E,Vogel  I,Röder  C,  etal. ComparativeanalysisofbonemarrowandvenousbloodisolatesfromgastrointestinalcancerpatientsforthedetectionofdisseminatedtumorcellsusingreversetranscriptionPCR.  CancerRes.1997;57(15):3106-3110.PubMedGoogleScholar ARandomizedClinicalTrialonAnteriorApproachvsConventionalHepatectomy—ToTerminateorNottoTerminatetheStudy Comment&Response September1,2021 Divya Gupta, MD;J.Jack Lee, PhD;AlbertY. Lin, MD,MPH ErrorsinText,Table,andFigure Correction September1,2021 NonsuperiorityoftheAnteriorApproachtoConventionalHepatectomyforResectionofColorectalLiverMetastasis InvitedCommentary January1,2021 Iswanto Sucandy, MD;Allan Tsung, MD SeeMoreAbout HepatobiliarySurgeryOncologySurgicalOncologyGastrointestinalSurgeryColorectalCancerGastroenterologyGastroenterologyandHepatologyGastrointestinalCancerSurgery SelectYourInterests SelectYourInterests CustomizeyourJAMANetworkexperiencebyselectingoneormoretopicsfromthelistbelow. 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ViewCorrection ThisIssue Views 3,531 Citations 12 ViewMetrics DownloadPDF Twitter Facebook More LinkedIn CME&MOC Cite This Citation RahbariNN,BirginE,BorkU,MehrabiA,ReißfelderC,WeitzJ.AnteriorApproachvsConventionalHepatectomyforResectionofColorectalLiverMetastasis:ARandomizedClinicalTrial.JAMASurg.2021;156(1):31–40.doi:10.1001/jamasurg.2020.5050 Downloadcitationfile: Ris(Zotero) EndNote BibTex Medlars ProCite RefWorks ReferenceManager Mendeley ©2022 Permissions OriginalInvestigation November4,2020 AnteriorApproachvsConventionalHepatectomyforResectionofColorectalLiverMetastasis:ARandomizedClinicalTrial NuhN. Rahbari, MD1,2;Emrullah Birgin, MD3;Ulrich Bork, MD4;etal Arianeb Mehrabi, MD1;Christoph Reißfelder, MD1,2;Jürgen Weitz, MD4 AuthorAffiliations ArticleInformation 1DepartmentofGeneral,VisceralandTransplantationSurgery,UniversityofHeidelberg,Heidelberg,Germany 2nowaffiliatedwithDepartmentofSurgery,UniversitätsmedizinMannheim,MedicalFacultyMannheim,HeidelbergUniversity,Mannheim,Germany 3DepartmentofSurgery,UniversitätsmedizinMannheim,MedicalFacultyMannheim,HeidelbergUniversity,Mannheim,Germany 4DepartmentofGastrointestinal,ThoracicandVascularSurgery,UniversityHospitalCarlGustavCarusattheTechnischeUniversitätDresden,Dresden,Germany JAMASurg.2021;156(1):31-40.doi:10.1001/jamasurg.2020.5050 visualabstracticon VisualAbstract editorialcommenticon EditorialComment relatedarticlesicon RelatedArticles authorinterviewicon Interviews multimediaicon Multimedia InvitedCommentary NonsuperiorityoftheAnteriorApproachtoConventionalHepatectomyforResectionofColorectalLiverMetastasis Iswanto Sucandy, MD;Allan Tsung, MD Comment&Response ARandomizedClinicalTrialonAnteriorApproachvsConventionalHepatectomy—ToTerminateorNottoTerminatetheStudy Divya Gupta, MD;J.Jack Lee, PhD;AlbertY. Lin, MD,MPH Correction ErrorsinText,Table,andFigure KeyPointsQuestion  Doesanteriorapproachhepatectomyreducetumorcelldisseminationduringresectionofcolorectallivermetastasiscomparedwithconventionalhepatectomy?Findings  Inthisrandomizedclinicaltrialincluding80participants,nostatisticallysignificantdifferenceintumorcelldissemination(5of21[24%]vs6of22[27%])andoverall(median,73vs55months)anddisease-free(median,48vs40months)survivalwasfoundbetweenconventionalhepatectomyandtheanteriorapproach.Meaning  Thesefindingssuggestthatbothtechniquesoffersafeandcomparablepostoperativeandsurvivaloutcomesinpatientsundergoingright-sidedhepatectomyforcolorectalcancer. Abstract Importance  Tumorrelapseafterpartialhepatectomyforcolorectallivermetastasis(CRLM)remainsanunsolvedissue.Intraoperativemanipulationoftheliverduringconventionalhepatectomymightenhancehematogenoustumorcellspread.Theanteriorapproachisanalternativeapproachthatmayreduceintraoperativetumorcelldissemination.Objective  TodeterminetheefficacyandsafetyoftheanteriorapproachcomparedwithconventionalhepatectomyinpatientsundergoingresectionforCRLM.Design,Setting,andParticipants  ThisrandomizedclinicalstudyevaluatedtheefficacyandsafetyoftheanteriorapproachcomparedwithconventionalhepatectomyinadultpatientswithCRLMwhowerescheduledforhepatectomyfromFebruary1,2003,toMarch31,2012,atatertiary-carehospital.Atotalof80patientswithCRLMwererandomizedtotheanteriorapproachandconventionalhepatectomygroupsina1:1ratio.Bonemarrowandbloodsampleswereanalyzedfordisseminatedtumorcellsandcirculatingtumorcells(CTC)usingcytokeratin20reversetranscriptase–polymerasechainreactionanalysis.DatawereanalyzedfromApril1toDecember1,2018,usingintentiontotreat.Interventions  Anteriorapproachvsconventionalhepatectomy.MainOutcomesandMeasures  TheprimaryendpointwasintraoperativeCTCdetectionincentralbloodsamplesafterliverresection.Secondaryendpointsincludedpostoperativemorbidity,mortality,andlong-termsurvival.Results  Amongthe80patientsincludedintheanalysis(48men[60%];mean[SD]age,61[10]years),baselinecharacteristics,includingpreoperativeCTCdetection,werecomparablebetweenbothgroups.TherewasnostatisticallysignificantdifferenceinintraoperativeCTCdetectionbetweenpatientsintheconventionalhepatectomy(5of21[24%])andanteriorapproach(6of22[27%])groups(P > .99).Exceptforalongeroperatingtimeintheanteriorapproachgroup(mean[SD],171[53]vs221[53]minutes;P  .65betweenbothgroups,indicatingfutilityoftheassessmentofwhethertheanteriorapproachissuperiortoconventionalhepatectomyinreducingintraoperativetumorcelldisseminationinpatientsundergoingresectionofCRLM. DatawereanalyzedfromApril1toDecember1,2018,usingtheintention-to-treatpopulation.TheprimaryendpointwasanalyzedusingtheFisherexacttest.Categoricalvariableswereexpressedbyabsoluteandrelativefrequencies(percentage)andcomparedusingthePearsonχ2ortheFisherexacttest.Continuousvariablesweresummarizedasmean(SD)ormedian(interquartilerange[IQR]or95%CI)andcomparedusingtheunpaired2-tailedttestortheWilcoxonranksumtest,dependingonthepatternofdistribution.Analysesforoverallsurvivalanddisease-freesurvivalwereperformedusingtheKaplan-Meiermethodandthelog-ranktestbetweenthegroups.Patientswhoreachedthefinalpointoffollow-uporwhowerelosttofollow-upwerecensored.TheprognosticrelevanceoftumorcelldetectioninbonemarrowandbloodsampleswasassessedusingtheCoxproportionalhazardsregressionmethod.Thefollowingexplanatoryvariableswereincluded:clinicalriskscore,operatingtechnique,anddetectionofCTC.TheCochranQtestwasperformedtocorrelatetheRT-PCRresultswithtimingofbloodsampling,andtheMcNemartestwasconductedtocomparetumorcelldetectionratesinbloodvsbonemarrowsamples.Allstatisticaltestswereevaluatedforsignificanceat2-sidedP  .99).Atotalof9of34patientsintheconventionalhepatectomygroup(26%)and12of38patientsintheanteriorapproachgroup(32%)haddisseminatedtumorcellsdetectedinthebonemarrowbeforesurgery(P = .80).Inlinewiththestudyprotocol,patientswithapositiveresectionmargin,excessiveintraoperativebloodloss,andpreoperativeCTCdetectionwereexcludedfromtheanalysisoftheprimaryendpoint.Afterexclusionofthesepatients,atotalof21patientsremainedintheconventionalhepatectomygroupand22remainedintheanteriorapproachgroupfortheanalysisoftheprimaryefficacyendpointofintraoperativedetectionofCK20-positiveCTC.QuizRefIDTheanalysisoftheprimaryendpointrevealednosignificantdifferenceinintraoperativeCTCdetectionbetweenbothgroups(5of21[24%]vs6of22[27%];P > .99)(Table3).Furtheranalysesshowednostatisticallysignificantdifferencesbetweenthetimingofbloodsamplinganddetectionoftumorcellsforallpatients(24of75[32%]forpreoperativevs21of73[29%]forintraoperative;P = .70)andforpatientsintheconventionalhepatectomy(12of37[32%]forpreoperativevs11of35[31%]forintraoperative;P > .99)oranteriorapproach(12of38[32%]forpreoperativevs10of38[26%]forintraoperative;P = .62)group(eTable1inSupplement2).Furthermore,therewasnostatisticallysignificantdifferenceinpreoperativedetectionofdisseminatedtumorcellsinbloodandbonemarrowsamplesoftherespectivepatients(13of21[62%]hadbothpositivetumorcellsdetectedinbloodandbonemarrowsamples,whereas8of21[38%]hadpositivetumorcellsdetectedinbloodbutnotumorcellsdetectedinbonemarrowsamples;P > .99)(eTable2inSupplement2). Long-termOutcomes Medianfollow-uptimewas46(IQR,0-116)monthsforthetotalcohort.Duringfollow-up,16patients(39%)intheconventionalhepatectomygroupand19patients(49%)intheanteriorapproachgroupdied.Therewasnosignificantdifferenceinmedianoverallsurvivalbetweenpatientsintheconventionalhepatectomygroup(73[95%CI,42-104]months)comparedwithpatientsintheanteriorapproachgroup(55[95%CI,35-75]months)(P = .43)(Figure2A). Onlastfollow-up,atotalof8patients(20%)intheconventionalhepatectomygroupand6patients(15%)intheanteriorapproachgroupshowednoevidenceofdisease(P = .47).Recurrenceofcolorectalcancerdevelopedin23patients(56%)intheconventionalhepatectomygroupandin17(44%)intheanteriorapproachgroup(P = .46).Themediandisease-freesurvivalwas48(95%CI,40-56)monthsintheconventionalhepatectomygroupand40(95%CI,28-52)monthsintheanteriorapproachgroup(P = .88)(Figure2B).Therewasnosignificantdifferenceinthepatternofdiseaserecurrencebetweenbothstudygroups.MostpatientswithrecurrentdiseasehadthefirstrecurrenceofCRLMwithintheliver(10[24%]intheconventionalhepatectomyvs8[21%]intheanteriorapproachgroups;P = .82).Althoughweobservedahigherincidenceofdiseaserecurrenceinthelungsinpatientsafterconventionalhepatectomy(n = 9)vsanteriorapproach(n = 5),thisdifferencedidnotreachstatisticalsignificance(P = .52).Fivepatientsintheconventionalhepatectomygroup(3 lung,1 liver,1 colon)and6patientsintheanteriorapproachgroup(2 liver,2 lung,1 bone,1 pelvis)underwentrepeatedmetastasectomyforrecurrentdisease.Chemotherapyforrecurrentdiseasewasadministeredinatotalof18patientsintheconventionalhepatectomyand12patientsintheanteriorapproachgroup.Overall,detectionofCTC(preoperativeandintraoperative)independentlyofthestudygroupwasassociatedwithsignificantlydecreasedoverallsurvival(median,46[95%CI,40-52]vs81[95%CI,54-107]months;P = .03)(Figure2C).Similarly,disease-freesurvivalwassignificantlyshorterinpatientswithpositiveCTCdetection(median,40[95%CI,34-46]vs60[95%CI,46-74]months;P = .04)(Figure2D).OnCoxproportionalhazardsregressionanalysis,detectionofpositiveCTCwasassociatedwithpoorsurvival(hazardratio,2.18;95%CI,1.09-4.37;P = .03)(eTable3inSupplement2). Discussion TheanteriorapproachtechniquewasfirstdescribedbyOzawa15in1992.Severalliversurgeonsadoptedthisapproachasano-touchtechniquewithouttumormanipulation,andrefinementsweremadebythehanginglivermaneuver.16Althoughthisapproachwasshowntobesafeandpotentiallysuperiortotheconventionalapproachintermsofmorbidity,survival,andCTCdisseminationinHCC,itsefficacyandsafetyforresectionofCRLMhasremainedunclear.11,12,17ThisrandomizedclinicaltrialaddressedthislackofevidenceusingintraoperativeCTCdetectionastheprimaryefficacyendpoint.Basedonanaprioriinterimanalysis,thetrialwasstoppedprematurely,andthenullhypothesiswasnotrejected.Intheentirecohort,however,CTCdetectionwasassociatedwithpooreroverallanddisease-freesurvival,whereasCTCdetectioninthestudygroupswascomparableandreflectedasimilaroncologicaloutcome.Perioperativeresultsrevealednosignificantdifferencesbetweenbothsurgicaltechniquesexceptforalongeroperatingtimeintheanteriorapproachgroup. DetectionofCTCisassociatedwithpooroutcomeinpatientswithprimaryaswellasmetastaticcolorectalcancer.6,7,18,19UsingtheUSFoodandDrugAdministration–approvedCellSearchdeviceforCTCdetectioninpatientswithcolorectalcancer,moreover,Rahbarietal8demonstratedtheabilityoflivermetastasestoshedintacttumorcellsintocirculation.Measurestolimitdetachmentoftumorcellsfrommetastaticlesionsarethereforeurgentlyneededtodecreasepotentialfurtherspreadoftumorcells.However,increasingdatasuggestthatCTCspontaneouslyleavingthecellularunionofatumormassarephenotypicallyandgenotypicallydifferentfromtumorcellsthataredetachedfromtheoriginalmasssecondarytomechanicalmanipulation.20-22AlthoughtheanteriorapproachfailedtoreducetheintraoperativeCTCdetectionrates,thesedatadonotsupportfurthereffortstoreducetumorcelldisseminationandsubsequentdiseaserecurrencebyminimizingintraoperativemanipulation.Theyshouldratherpromptstrategiestopreventspontaneoustumorcelldisseminationandtotargetminimalresidualdiseaseafterpotentiallycurativeresection. MostdataontheoncologicaleffectoftheanteriorapproachareavailableforpatientsundergoingresectionforHCC.ThefirstrandomizedclinicalstudyonthistopicbyLiuetal12analyzedpatientswithlargeHCC(>5cm)andrevealedasignificantoverallsurvivalbenefitaftertheanteriorapproach,whereasdisease-freesurvivalandperioperativeoutcomewerecomparablebetweenthestudygroups.Althoughtherecurrenceratewas56%inbothstudygroups,recurrentdiseasewasamenabletolocalablativeorsurgicaltherapyin80%ofpatientsaftertheanteriorapproachcomparedwith17%afterconventionalhepatectomy.Furthermore,theanteriorapproachwasassociatedwithintraoperativelowerplasmalevelsofalbuminmessengerRNA,supportingtheevidenceoflowerlevelsofcirculatinglivercellsduringtheanteriorapproach;however,CTCwerenotevaluated.AnotherrecentrandomizedclinicaltrialbyHaoetal11assessedpatientswithaheterogenoussizeofHCCanddetectedlessmeanandmedianepithelialcelladhesionmolecule–positiveCTCaftertheanteriorapproachcomparedwithconventionalhepatectomyinthefirst10postoperativedays.Unfortunately,long-termoutcomewasnotreported,but2-yearoverallandrecurrence-freesurvivalwassignificantlyreducedaftertheconventionalapproach.Thusfar,perioperativeoutcomeandlong-termsurvivalofpatientswithCRLMwhounderwentanteriorapproachandconventionalhepatectomywereonlyassessedin2nonrandomizedcohortstudies.23,24Finally,thesestudiesrevealednosignificantdifferencesbetweenthestudygroups,whichisconsistentwiththeresultsofthepresentstudy. Morbidityaftermajorhepatectomyremainshighandrangesfrom35%to69%dependingonthepatientpopulation,preexistingliverdisease,andvolumeofthefutureliverremnant.25-27Althoughtheanteriorapproachfailedtoprovideabenefitwithrespecttopatients’oncologicaloutcome,advantagesinperioperativeoutcomesmightstilljustifyitsuseinclinicalroutine.Ourresultsshowedasignificantlyprolongedoperatingtimeanddurationofportaltriadclampingforpatientsintheanteriorapproachgroupwithnostatisticallysignificantdifferenceinanyfurtherperioperativeparameters,includingbloodloss,morbidity,andlengthofhospitalstay.Thesedataareinlinewithpreviousdatafromrandomizedtrialsthatreportedsimilarperioperativeoutcomesforpatientswhounderwentaright-sidedhepatectomywiththeanteriorapproachandtheconventionalhepatectomyapproach.11,12,28Owingtothelackofbenefitsinperioperativeoutcomes,theanteriorapproachdoesnotappearsuperiortoconventionalhepatectomy.However,itisusefulinpatientswithlargemassesthatrenderprimarymobilizationoftherightlobedifficult.29PreviousstudiesonCTCdetectionusingCK20RT-PCRreportedhigherratesofCTC-positivefindings.30 WeusedahighlysensitiveandspecificRT-PCRassaytoidentifyCTCasdescribedandstandardizedpreviously.14,31Thenumberofpatientswithintraoperativepositivetumorcellswerecomparableinbothgroups.Intotal,wefoundaconsiderablylowerrateofCTCasdescribedintheliterature31,32;however,thiscouldbeowingtomodernchemotherapyprotocolswithsubsequentreductionoftumorcells. Limitations Ourstudyhassomelimitations.First,oursamplesizeisrelativelysmall,whichisprimarilyowingtoaprematureterminationofthestudy.Becausetherewerenostatisticallysignificantdifferencesfortheprimaryendpointoninterimanalysis,thestudywasdiscontinuedinlinewiththestudyprotocol.Second,8patientshadnobonemarrowsamplesbecauseofpatient’spreferencetoavoidanadditionalprocedure.Third,evaluationoftheprimaryendpointwaslimitedtoarelativelysmallgroupofpatientsowingtoahighnumberofpatientswithpreoperativepositivetumorcellsinbloodaswellasintraoperativebloodlossofmorethan2000mL,resultinginlossofstatisticalpowerandinconclusiveresults.Fourth,tominimizereportingbias,allpatientswereevaluatedforsecondaryoutcomes. Conclusions Inthisrandomizedclinicaltrial,patientsundergoingrighthepatectomyforcolorectalcancerbyanteriororconventionalresectionboreasimilarriskoftumorcelldissemination.Findingssuggestthatbothtechniquesaresafeandindicatenostatisticallysignificantdifferenceinpostoperativeoutcomeorlong-termsurvival. Backtotop ArticleInformation AcceptedforPublication:July30,2020.PublishedOnline:November4,2020.doi:10.1001/jamasurg.2020.5050Correction:ThisarticlewascorrectedonMay26,2021,tofixthePvalueforthedetectionofpreoperativeandintraoperativetumorcellsintheAbstract,maintext,andTable3,andtofixanerrorinthenumbersatriskinFigure2A.CorrespondingAuthor:JürgenWeitz,MD,DepartmentofGastrointestinal,ThoracicandVascularSurgery,UniversityHospitalCarlGustavCarusattheTechnischeUniversitätDresden,Fetscherstraße74,01307Dresden,Germany([email protected]).AuthorContributions:DrsRahbariandBirgincontributedequallytothisstudy.DrsRahbariandBirginhadfullaccesstoallthedatainthestudyandtakeresponsibilityfortheintegrityofthedataandtheaccuracyofthedataanalysis.Conceptanddesign:Weitz.Acquisition,analysis,orinterpretationofdata:Allauthors.Draftingofthemanuscript:Rahbari,Birgin.Criticalrevisionofthemanuscriptforimportantintellectualcontent:Allauthors.Statisticalanalysis:Rahbari,Birgin.Administrative,technical,ormaterialsupport:Bork,Mehrabi,Weitz.Supervision:Rahbari,Bork,Reißfelder.ConflictofInterestDisclosures:Nonereported.Funding/Support:ThisstudywassupportedbytheDepartmentofSurgery,UniversityofHeidelberg.RoleoftheFunder/Sponsor:Thesponsorhadnoroleinthedesignandconductofthestudy;interpretationofthedata;andpreparation,review,orapprovalofthemanuscript.Thesponsorwasinvolvedinthecollection,management,andanalysisofthedataandgrantedapprovaltosubmitthemanuscriptforpublication.DataSharingStatement:SeeSupplement3. 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