Health-related quality of life among patients cured by surgery for esophageal cancer

Health-relatedQualityofLifeAmongPatientsCuredbySurgeryforEsophagealCancer

PernillaLagergren,RN,PhD1,2,3KerryN.L.Avery,PhD1RachaelHughes,MSc1C.PaulBarham,MD,FRCS(GenSurg)4DerekAlderson,MD,FRCS3,4StephenJ.Falk,MD,MRCP5JaneM.Blazeby,MD,FRCS(GenSurg)1,3,4DepartmentofSocialMedicine,UniversityofBristol,Bristol,UnitedKingdom.

UnitofEsophagealandGastricResearch(ESOGAR),DepartmentofMolecularMedicineandSurgery,KarolinskaInstitute,Stockholm,Sweden.

ClinicalSciencesatSouthBristol,UniversityofBristol,Bristol,UnitedKingdom.

DivisionofSurgery,HeadandNeck,UnitedBristolHealthcareTrust,Bristol,UnitedKingdom.BristolHaematologyandOncologyCentre,UnitedBristolHealthcareTrust,Bristol,UnitedKingdom.

321BACKGROUND.Littleisknownregardingthelong-term,health-relatedqualityof

life(HRQL)ofsurvivorsofesophagectomyforcancer.

METHODS.ConsecutivepatientscompletedthevalidatedEuropeanOrganization

forResearchandTreatmentofCancergeneralquality-oflife-questionnaire(QLQ-C30)andtheesophageal-specificmodule(QLQ-OES18)beforesurgeryandregu-larlythereafterforatleast3years.Meanscoreswith95%confidenceintervalswerecalculated.TheStudentttestforpaireddatawasusedtodeterminediffer-encesbetweenbaselineand3-yearHRQLscoresinwhichscoresdifferedby!5points.

RESULTS.Of90patientswhounderwentsurgery,47patients(52%)survivedfor

!3years.Inthisgroup,mostaspectsofHRQLrecoveredtopreoperativelevelsbythe3-yearassessment,exceptthatscoresforphysicalfunction,breathlessness,diarrhea,andrefluxweresignificantlyworsethanatbaseline(P<.01).However,patientsreportedsignificantlybetteremotionalfunction3yearsaftersurgerythanbeforetreatment(P5.0008).

CONCLUSIONS.Evenafter3years,patientswhounderwentesophagectomysuf-feredpersistentproblemswithphysicalfunctionandspecificsymptoms.Thesefindingsmaybeusedtoinformpatientsofthelong-termconsequencesofsur-gery.Cancer2007;110:686–93.Ó2007AmericanCancerSociety.

KEYWORDS:esophagealneoplasm,esophagectomy,longitudinal,prospective,long-termsurvivors.

SupportedbytheMedicalResearchCouncil.Dr.BlazebywassupportedbyaUnitedKingdomMedicalResearchCouncilClinicianScientistFellowship.Dr.LagergrenwassupportedbytheKarolinskaInstitutet(CenterforHealthCareSciences)andtheSwedishCancerSociety.WethankJoannaNicklinforcollectinghealth-relatedquality-of-lifedata.

Addressforreprints:JaneM.Blazeby,MD,DepartmentofSocialMedicine,UniversityofBristol,CanyngeHall,WhiteladiesRoad,Clifton,Bristol,BS82PR,UnitedKingdom;Fax:(011)44(0)1179287292;E-mail:j.m.blazeby@bristol.ac.uk

ReceivedFebruary16,2007;revisionreceivedApril6,2007;acceptedApril13,2007.

urgicalresectionforesophagealcancerisassociatedwithhighmorbidityandapostoperativemortalityratefrom1%to5%,anditentailsatleastatemporarydetrimentalimpactonhealth-relatedqualityoflife(HRQL).1–4Duringthefirstpostoperativeyear,patientsreportdecreasedphysical,role,andsocialfunctionandsignificantlymoreproblemswithfatigue,breathlessness,andpain.RecoveryofHRQLseemstooccurwithin12to24months,althoughpatientswhoaredyingfromrecurrentdiseaseneverregainpreoperativeHRQL.5Nevertheless,surgeryisoftenthemaintreatmentamongpatientswithresectablecanceroftheesophagusbecauseofpoten-tialcureinupto40%.6,7Patientswhobecomelong-termsurvivorsofesophagealsurgerymayreportresidualHRQLdeficitsrelatedtothereconstructionortotheexperienceofacancerdiagnosis.Understandinghowesophagectomyimpactsonlong-termHRQL,therefore,isimportant,becauseitwillprovideinformationthatcanbeusedtoinformdecision-making.

Althoughseveralcross-sectionalstudieshaveusedgenericques-tionnairestoassesstheHRQLofsurvivorsofesophagealsurgery,8–12thereisaneedforprospectiveseriesusingvalidated,multidimen-sional,cancer-andsite-specifictoolsthataresufficientlysensitive

S

ª2007AmericanCancerSociety

DOI10.1002/cncr.22833

Publishedonline20June2007inWileyInterScience(www.interscience.wiley.com).

toassessdetailedaspectsofHRQL.Theobjectiveofthisstudy,therefore,wastoassessHRQLprospec-tivelyinalongitudinalcohortofsurgicallytreatedpatientswhosurvivedesophagealcancerfor!3postoperativeyears.

MATERIALSANDMETHODS

StudyDesign

Aprospective,longitudinalstudythataddressedHRQLrecruitedpatientsattheUnitedBristolHealthcareTrust,Bristol,U.K.betweenNovember2000andNovember2003.Patientswithadenocarci-noma,squamouscellcarcinoma,orhigh-gradedys-plasiaoftheesophagusorthegastroesophagealjunctionwhounderwentesophagectomyandsur-vivedpostoperativelyfor!3yearswereeligibleforthestudy.Patientswereexcludediftheywereunabletounderstandthelanguageorcontentofthequestionnaire,iftheyhadotherpreviousorconcurrentmalignancies,oriftheywereunabletoprovidewritteninformedconsent.TheCentralandSouthBristolResearchEthicsCommitteeapprovedthestudy.

Treatment

TreatmentdecisionsweremadewithinthecontextoftheuppergastrointestinalmultidisciplinaryteamattheUnitedBristolHealthcareTrust,whichmeetsweeklyandconsidersallpatientswithesophagealcancerwithintheAvonandSomersetandWiltshireCancerNetwork.Computedtomographyscansofthechestandabdomenandendoluminalultrasoundscanswereperformedtodefinetumorstage.13AlaparoscopywasundertakenforcancersoftumorstageT3extendingbelowthediaphragm.Duringthestudy,patientswithstageT3N1M0,T3N0M0,orT2N1M0wereofferedneoadjuvantchemotherapyand/orradiotherapybeforeesophagectomy,whereassurgeryalonewasofferedtopatientswithT1/T2N0M0disease.Standardsurgeryinvolveda2-phaseesophagectomy(abdomenandrightthoracot-omy)anda2-fieldlymphadenectomy(abdomenandmediastinum),althoughatranshiatalor3-phaseapproachwasusedifclinicallyindicated.

ClinicalandHRQLData

Datawerecollectedprospectivelyinastudy-specificdatabase,whichincludedbaselineclinical,sociode-mographic,andHRQLdata.Follow-upclinicaldetailsandHRQLalsowererecorded.Awidelyused,generic,quality-of-lifecancerquestionnaire,

QualityofLifeAfterEsophagectomy/Lagergrenetal.687

theEuropeanOrganizationforResearchandTreat-mentofCancer(EORTC)QLQ-C30,wasusedtoassesscoreaspectsofHRQL,andsite-specificissueswereaddressedwiththeesophageal-specificmod-ule,EORTCQLQ-OES18.14,15ThestructureoftheQLQ-C30hasbeenreportedindetailelsewhere,anditsvalidityandreliabilityhavebeenexaminedinseveraldiagnosticsettings,includingcanceroftheesophagus.16TheQLQ-OES18hasbeenvalidatedinpatientswhounderwentesophagectomy.15Itcon-tainsscalesthataddressdysphagia,eatingrestric-tions,reflux,andesophagealpainaswellassomerelevantsingleitems.Allquestionnaireresponsesweretransformedlinearlytoscoresfrom0to100.15–17Highscoresonthemulti-itemfunctionscalesandtheglobalquality-of-lifescaleindicatebetterlevelsoffunctionandqualityoflife,respectively;whereashighscoresonthesymptomscalesanditemsrepre-sentmoresymptoms.BaselineHRQLassessmentswereperformedwithin6weeksbeforesurgery,andfollow-updatawerecollectedat6weeks(Æ14days)andat3months,6months,9months(Æ30days),12months,18months,24months,and36months(Æ50days)postoperatively.BaselineHRQLdatawerecol-lectedinthehospital,andfollow-upassessmentswerearrangedbytelephoneandperformedbymail,with1telephonereminderifrequired.Allquestion-naireswerescrutinizedformissingindividualitems.Ifitemsweremissing,thenpatientsweretelephonedforadditionalresponsestominimizemissingdata.

DataAnalyses

MeanHRQLscoreswerecalculatedateachtimepointandwereplottedagainsttime.Meanscoresatbaselineand3yearspostsurgeryarepresentedwith95%confidenceintervals.TheStudentttestforpaireddatawasusedtotestfordifferencesbetweenbaselinescoresand3-yearscores.Toreducetheriskofmultipletesting,theStudentttestwasappliedonlywhenthemeandifferencebetweenthebaselinescoreandthe3-yearfollow-upscorewas!5(ie,clinicallyrelevant).18,19Thedataalsowereanalyzedusingnonparametricmethods.Onlytheresultsfromparametricanalysesarepresented,becausetheywerecomparabletothenonparametricresults.Plannedanalysescomparingmenandwomenwerenotconductedbecauseofthesmallnumberofwomen.AllanalysesandgraphswereconstructedusingthestatisticalsoftwarepackageStata9.2(StataCorporation,CollegeStation,TX).Missingitemswerehandledaccordingtotherecommendationsofthequestionnaire’sdevelopers.17688CANCERAugust1,2007/Volume110/Number3

TABLE1ClinicalandSociodemographicDataof47Long-termSurvivorsAfterSurgeryforEsophagealCancerVariableNo.ofpatients(%)Medianageattimeofsurgery[range],y63[44–79]Malegender31(66)CohabitationstatusLivingalone8(17)Livingwithfamily34(72)Unknown/missing5(11)MaritalstatusSingle3(6)Married32(68)Separated,divorced,widowed12(26)EducationLessthancompulsoryschooleducation3(6)Compulsoryschooleducation25(53)Postcompulsoryschooleducation18(38)Other/unknown1(2)EmploymentstatusEmployed16(34)Unemployed1(2)Retired26(55)Other/unknown4(9)MedianKPSattimeofsurgery[range]90[70–100]ASAgradeattimeofsurgeryGrade15(11)Grade238(81)Grade34(4)DysphagiagradeattimeofsurgeryAbletoeatanything20(43)Unabletoeatallsolids14(30)Onlyeatsoftfoods8(17)Onlydrinkliquids4(9)Completedysphagia1(2)HistologictumortypeAdenocarcinoma35(74)Squamouscellcarcinoma9(19)High-gradedysplasia3(6)TumorlocationEsophageal24(51)Gastroesophagealjunction23(49)KPSindicatesKarnofskyperformancestatus;ASA,AmericanSocietyofAnesthesiologists(seeVacantietal.,197021).RESULTS

Patients

Duringthestudyperiod,111patientswereconsid-eredforpotentiallycurativetreatmentthatinvolvedesophagectomy(84patientswereconsideredforneoadjuvanttherapyandsurgery,and27patientswereconsideredforesophagectomyalone).Intheneoadjuvantgroup,13patientsdidnotproceedtosurgerybecauseofdiseaseprogression(n511patients),myocardialinfarction(n51patient),andreluctancetoundergosurgery(n51patient).Amongthepatientswhounderwentesophagectomyalone,8patientsdidnotproceedtoesophagectomy,

TABLE2ClinicalDetailsFrom47Long-termSurvivorsAfterSurgeryforEsoph-agealCancerVariableNo.ofpatients(%)Neoadjuvanttherapy,yes29(62)Typeofsurgery2-Phaseesophagectomy42()3-Phaseesophagectomy2(4)Transhiatalesophagectomy3(6)In-hospitalcomplications!1Complication25(53)Pulmonaryproblems20(43)Anastomoticleak,gastricnecrosis4(8)UpperGIbleeding2(4)Cardiovascularproblems2(4)Chylothorax1(2)Woundinfection1(2)Other6(13)Reoperation3(6)Readmittedtointensivecareunit5(11)Medianin-hospitalstay[range],d17[9–77]pTNMstage0(pCR/HGD)6/2(13/4)I10(21)IIA17(36)IIB6(13)III6(13)GIindicatesgastrointestinal;pTNM,pathologictumor,lymphnode,metastasisstage;pCR,completepathologicresponse;HGD,high-gradedysplasia.becauseunsuspectedmetastaticdiseasewasdiscov-eredatsurgery.Thus,90patientsunderwentesopha-gectomy,including43patients(48%)whodiedwithin3yearsand47patientswhosurvivedfor!3yearsafteresophagectomyandremainedforthefinalanalyses.InTables1and2,clinicalandsociodemo-graphicdetailsarepresentedforthesestudypatients.

HRQLCompliance

Baselinequestionnairecompliancewas98%.Oneassessmentwasmissedbecauseofanadministrativeerror.Duringfollow-up,complianceremainedabove85%.Thereasonsformissingquestionnaireswererelatedmostlytoadministrativeerrors.Atthe6-weekand3-yearfollow-upassessments,2patientsdidnotrespondtothequestionnairewithintheallowedtimewindow,and1patientdecidedtowithdrawfromthestudybefore2yearsoffollow-up;however,thatpatientwasincludedinthefinalanalyses.

HRQLFunctionalOutcomes

Meanscoresforthefunctionaloutcomesarepre-sentedinFigure1a–d.Atbaseline,levelsofHRQLgenerallyweregood([70ontheEORTCscales).Within6weeksofsurgery,allofthosefunctional

QualityofLifeAfterEsophagectomy/Lagergrenetal.6

FIGURE1.(a–d)Functionalaspectsofhealth-relatedqualityoflifeamong47long-termsurvivorsaftersurgeryforesophagealcancer(higherscoresindicate

betterfunction).

scoresdeterioratedexceptforemotionalfunction.Rolefunctionwasaffectedthemostseverely,withadecreaseof58points.Recoverythenoccurredandwassustainedby12monthsforrole,cognitive,andsocialfunction;however,scoresforphysicalfunctionandglobalqualityoflifeneverreturnedtobaselinelevels(Fig.1a–d)(Table3).Emotionalfunctioncon-tinuedtoimproveaftersurgeryandwasbetteratthe3-yearfollow-upassessmentthanatbaseline(Fig.1c)(Table3).

returnedtobaselinelevelswithin12monthsforfatigueandnauseaandvomiting.Problemswithdyspneaincreasedaftersurgeryandneverreturnedtopreoperativelevels(Table3)(Fig.2c).Halfofthepatients(50%)stillsufferedtosomedegreefromdyspneaafter3years.Diarrhearemainedproblem-aticduringtheentirefollow-upand,3yearsaftersurgery,wassignificantlyworsethanatbaseline(Table3)(Fig.2e).Threeyearsaftersurgery,40%ofthepatientswereexperiencingproblems(rangingfrom‘‘alittle’’to‘‘verymuch’’)withdiarrhea.

HRQLSymptomOutcomesGeneralsymptoms

MeanscoresforsymptomoutcomesarepresentedinFigure2a-e.Beforesurgery,patientsreportedpro-blemswithfatigue,pain,sleeplessness,andappetiteloss(Table3)(Fig.2a,d).Sixweeksaftersurgery,allsymptomscoreswerehigher(ie,worse),withmarkedincreasesinappetitelossanddyspnea.Recoverytobaselinelevelswasachievedforpain,sleeplessness,appetiteloss,andconstipation;andscoresalmost

Esophageal-specificsymptoms

Meanscoresofesophageal-specificsymptomsarepresentedinFigure3a–c.Atbaseline,manypatientsreportedproblemswithdysphagia,eatingrestric-tions,reflux,odynophagia,drymouth,taste,andcoughing,forwhichmeanscoresexceeded10points(Table3).Sixweeksaftersurgery,allofthesescoreshadincreased(wereworse).Recoveryofbaselinevalueswasobservedforallsymptomscalesanditemsexceptreflux,whichincreasedsubstantially

690CANCERAugust1,2007/Volume110/Number3

TABLE3MeanHealth-relatedQuality-of-LifeScoreswith95%ConfidenceIntervalsatBaselineandat3-YearFollow-upAmong47Long-termSurvivorsAfterSurgeryforEsophagealCancer*MeanScore(95%CI)Baseline3-yearfollow-upMeandifferencePyQLQ-C30{Physicalfunction88(83–93)81(75–88)27(211À22).007Rolefunction79(70–87)76(68–84)——Emotionalfunction69(61–77)80(73–87)11(5–18).0008Cognitivefunction82(75–)84(78–90)——Socialfunction78(67–88)74(–85)——Globalqualityoflife72(65–79)66(58–75)26(213À2).16Fatigue26(19–33)30(22–38)——Nauseaandvomiting10(3–17)14(8–20)——Pain16(8–23)18(10–27)——Dyspnea8(3–14)21(13–29)13(4À22).007Problemssleeping26(16–37)23(14–32)——Appetiteloss13(4–22)20(10–29)7(24À18).21Constipation11(3–19)5(0–10)26(216À4).21Diarrhea6(0–13)22(12–32)16(6–26).003Financialproblems11(4–18)13(5–21)——QLQ-OES18§Dysphagia17(9–26)10(3–17)27(218À4).18Eatingrestriction24(15–33)23(16–30)——Reflux12(5–18)32(22–43)20(11À30).0001Esophagealpain16(9–22)17(9–25)——Saliva5(0–12)12(3–22)7(25À19).27Choking4(0–8)3(0–6)——Drymouth29(17–40)33(21–45)——Tasteproblems18(8–29)12(5–20)26(217À5).30Cough15(6–24)13(5–22)——Speechproblems2(0–5)3(0–7)——95%CIindicates95%confidenceinterval;QLQ-C30,EuropeanOrganizationforResearchandTreat-mentofCancer(EORTC)generalquality-of-lifequestionnaire;QLQ-OES18,EORTCesophageal-speci-ficquality-of-life-questionnairemodule.*Scoresrangefrom0to100.Ahighscoreinthefunctionscalesandtheglobalquality-of-lifescalerepresentsbetterqualityoflifeorahigherleveloffunctioning,whereasahigherscoreforthesymp-tomscalesanditemsrepresentsmoreseveresymptoms.y

Ifmeanscoresdifferedby!5points,thentheStudentttestforpaireddatawasusedtodeterminewhethersuchdifferenceswerestatisticallysignificantatthe5%level.{Among39patientswithbaselineand3-yearfollow-upscoresexceptfordiarrhea(38).§Among35patientswithbaselineand3-yearfollow-upscores.shortlyaftersurgeryandworsenedovertime(Table3)(Fig.3c).Overall,75%ofthepatientsstillreportedproblems(‘‘alittle’’to‘‘verymuch’’)withpersistentreflux3yearsaftersurgery.Odynophagiawasvir-tuallyconstantwithtimebeforeandaftertheeso-phagectomy(Table3).

DISCUSSION

Inthisreport,wedescribethelongitudinalHRQLofsurvivorsaftersurgeryforesophagealcancer.Theobservedpostoperativeincreaseinsymptomsanddeteriorationinfunctionmostlyimprovedwithin6to12monthsaftersurgery.Scoresforphysicalfunc-

tion,breathlessness,reflux,anddiarrhea,however,weresignificantlyworse3yearsaftersurgerythanatbaseline,althoughitisnoteworthythatpatientsreportedsignificantlybetteremotionalfunctionatthistimepoint.Therefore,thesedataindicatethatpatientswhosurvivefor!3yearsafteresophagect-omycanexpectagenerallygoodqualityoflife.

TheliteratureaddressingHRQLamonglong-termsurvivorsaftersurgeryforesophagealcancerislimited.Somecross-sectionalstudies,usingvalidatedHRQLmeasures,haveindicatedthatpatientswhosurvivebetween2yearsand5yearsafteresopha-gectomyreportHRQLsimilartothatreportedinthegeneralpopulation.8–12Thosestudieswerelimitedbyalackofbaselinedata,althoughpersistentproblemswithreflux,dyspnea,pain,andappetitelosswereidentified.Thosefindingsareinaccordancewithourcurrentresults.AlongitudinalstudycomparingtranshiatalesophagectomywithatransthoracicapproachindicatedthatgenericaspectsofHRQLweresimilartobaselinelevelsatthe3yearfollow-upassessment.20Inthecurrentstudy,theobservedreductioninphysicalfunctionaftersurgerymayhavebeenbecauseofadvancingageduringthefollow-upperiod,althoughthemagnitudeofthisdeteriorationimprovedduringthefirstpostoperativeyearandremainedstablethereafter.Theimprove-mentinemotionalfunctionmaybeexplainedbypatientsfeelingdepressedatbaseline(diagnosis)or,overtime,becomingconfident(and,thus,happier)thattheyarecured.Withregardtosymptoms,persis-tentdyspneamayberelatedtoreducedlungvolumebecauseofthepresenceofanintrathoracicstomach,anddiarrheamostlikelyisrelatedtosurgicalvagot-omy.Refluxafteresophagectomyhasbeenreportedelsewhereandmostlikelyoccursbecauseofexcisionoftheloweresophagealsphinctermechanism.

Somemethodologicaspectsdeserveattention.Thisstudybenefitsfromaprospectiveandlongitudi-naldesigncomparedwiththecross-sectionalstudiespreviouslypublishedinthisarea.Thehighcompli-ancerateandtheuseofvalidated,multidimensional,disease-specificquestionnaires,includinganesopha-geal-specificmodule,shouldminimizebothselectionbiasandinformationbias.Wecouldnotevaluatewhetherourpatientshadanyrecurrentdiseaseatthe3-yearfollow-upassessment;however,noneofthepatientsrefusedtorespondtothequestionnairebecauseofillness.Despitearelativelysmallsamplesize,theclinicallyrelevantchangesinscoresdetectedbetweenbaselineandthe3-yearfollow-upappeartohavethepowertodemonstratestatisticalsignificance.Toreducetheriskofmultipletesting,weonlytestedforstatisticalsignificancewhenthe

QualityofLifeAfterEsophagectomy/Lagergrenetal.691

FIGURE2.(a–e)Health-relatedquality-of-lifesymptomscoresamong47long-termsurvivorsaftersurgeryforesophagealcancer(higherscoresindicate

moresymptoms).

meandifferencebetweenthebaselinescoreandthe3-yearfollow-upscorewas!5(ie,clinicallyrele-vant).18,19Althoughthestudy’shospital-baseddesignmayincreasetheriskofselectionbias,itisnotanticipatedthatthiswouldseverelyaffecttheHRQLfindings.Itisimportanttonotethat,atbaseline,patientsalreadyhavetheirtumor,andtheirHRQLmaybeaffectedsubsequently,whichwoulddiffercomparedwithwhatwouldbeobservedifatruebaselineHRQLscorehadbeenobtained(ie,beforethediseasehasoccurred).Mostpatients,forexam-ple,reporteddysphagiaatbaselinebecauseoftheobstructingcancer,yetpostoperativedysphagiascoresdidnotimprovebeyondbaselinevalues,indi-catingpersistentproblems.However,suchtruebase-lineassessmentisnotfeasible.

692CANCERAugust1,2007/Volume110/Number3

FIGURE3.(aÀc)Esophageal-specificsymptomscoresamong47long-term

survivorsafteresophagealcancersurgery(higherscoresindicatedmoresymptoms).

Inconclusion,theresultsfromthisprospective,longitudinalstudyindicatedthatesophagectomyforcancerhadatemporary,negativeimpactonmostaspectsofself-reportedHRQLthattypicallyrecov-eredwithinthefirstpostoperativeyear.Persistingdeteriorationinphysicalfunctionandincreasedbreathlessness,diarrhea,andrefluxwereobserved.

Thesefindingsmaybeusedtoinformpatientsregardingwhattoexpectaftersurgeryandtoguidetimely,supportiveinterventions.MethodstoinformpatientsofthelikelyHRQLimpactofsurgerycur-rentlydonotexist.FuturestudiesthatdevelopaidstocommunicateHRQLresultstopatientsandclini-cianswithinaclinicalcontextarewarranted.

REFERENCES

1.

JamiesonGG,MathewG,LudemannR,WaymanJ,MyersJC,DevittPG.Postoperativemortalityfollowingoesopha-gectomyandproblemsinreportingitsrate.BrJSurg.2004;91:943–947.

2.

BlazebyJM,SanfordE,FalkSJ,AldersonD,DonovanJL.Health-relatedqualityoflifeduringneoadjuvanttreatmentandsurgeryforlocalizedesophagealcarcinoma.Cancer.2005;103:1791–1799.

3.

ReynoldsJV,McLaughlinR,MooreJ,RowleyS,RaviN,ByrnePJ.Prospectiveevaluationofqualityoflifeinpatientswithlocalizedoesophagealcancertreatedbymul-timodalitytherapyorsurgeryalone.BrJSurg.2006;93:1084–1090.

4.

ViklundP,LindbladM,LuM,YeW,JohanssonJ,LagergrenJ.Riskfactorsforcomplicationsafteresophagealcancerresection:aprospectivepopulation-basedstudyinSweden.AnnSurg.2006;243:204–211.

5.

BlazebyJM,FarndonJR,DonovanJ,AldersonD.Apro-spectivelongitudinalstudyexaminingthequalityoflifeofpatientswithesophagealcarcinoma.Cancer.2000;88:1781–1787.

6.EnzingerPC,MayerRJ.Esophagealcancer.NEnglJMed.2003;349:2241–2252.

7.WuPC,PosnerMC.Theroleofsurgeryinthemanagementofoesophagealcancer.LancetOncol.2003;4:481–488.

8.

McLartyAJ,DeschampsC,TrastekVF,AllenMS,PairoleroPC,HarmsenWS.Esophagealresectionforcanceroftheesophagus:long-termfunctionandqualityoflife.AnnThoracSurg.1997;63:1568–1572.

9.

DeBoerAG,GenovesiPI,SprangersMA,VanSandickJW,ObertopH,VanLanschotJJ.Qualityoflifeinlong-termsurvivorsaftercurativetranshiataloesophagectomyforoesophagealcarcinoma.BrJSurg.2000;87:1716–1721.

10.

HallasCN,PatelN,OoA,etal.Five-yearsurvivalfol-lowingoesophagealcancerresection:psychosocialfunc-tioningandqualityoflife.PsycholHealthMed.2001;6:85–94.

11.

DeschampsC,NicholsFC3rd,CassiviSD,AllenMS,Pairo-leroPC.Long-termfunctionandqualityoflifeafteresoph-agealresectionforcancerandBarrett’s.SurgClinNorthAm.2005;85:9–656,xi.

12.

MoracaRJ,LowDE.Outcomesandhealth-relatedqualityoflifeafteresophagectomyforhigh-gradedysplasiaandintramucosalcancer.ArchSurg.2006;141:5–9;discussion9–551.

13.

SobinLH,WittekindC,eds.TNMClassificationofMalig-nantTumors.6thed.NewYork,NY:JohnWiley&Sons;2002.

14.

AaronsonNK,AhmedzaiS,BergmanB,etal.TheEuropeanOrganizationforResearchandTreatmentofCancerQLQ-C30:aquality-of-lifeinstrumentforuseininternationalclinicaltrialsinoncology.JNatlCancerInst.1993;85:365–376.

QualityofLifeAfterEsophagectomy/Lagergrenetal.

15.BlazebyJM,ConroyT,HammerlidE,etal.Clinicaland

psychometricvalidationofanEORTCquestionnairemod-ule,theEORTCQLQ-OES18,toassessqualityoflifeinpatientswithoesophagealcancer.EurJCancer.2003;39:1384–1394.

16.BlazebyJM,WilliamsMH,BrookesST,AldersonD,FarndonJR.

Qualityoflifemeasurementinpatientswithoesophagealcancer.Gut.1995;37:505–508.

17.FayersPM,AaronsonNK,BjordalK,GroenvoldM,Curran

D,BottomleyA,onbehalfoftheEORTCQualityofLifeStudyGroup.TheEORTCQLQ-C30ScoringManual.3rded.Brussels,Belgium:EuropeanOrganizationforResearch693

18.OsobaD,RodriguesG,MylesJ,ZeeB,PaterJ.Interpreting

thesignificanceofchangesinhealth-relatedquality-of-lifescores.JClinOncol.1998;16:139–144.

19.KingMT.TheinterpretationofscoresfromtheEORTC

qualityoflifequestionnaireQLQ-C30.QualLifeRes.1996;5:555–567.

20.deBoerAG,vanLanschotJJ,vanSandickJW,etal.Quality

oflifeaftertranshiatalcomparedwithextendedtranstho-racicresectionforadenocarcinomaoftheesophagus.JClinOncol.2004;22:4202–4208.

21.VacantiCJ,VanHoutenRJ,HillRC.Astatisticalanalysisof

therelationshipofphysicalstatustopostoperativemortal-andTreatmentofCancer;2001.

ityin68,388cases.AnesthAnalg.1970;49:5–566.