Esophageal Carcinoma

Thenewenglandjournalofmedicinenengljmed371;26nejm.orgDecember25,20142499ReviewArticleEsophagealadenocarcinomahasbecomethepredominanttypeofesophagealcancerinNorthAmericaandEurope,andgastroesophagealrefluxdisease(GERD)andobesityarethemainriskfactors.Barrett’sesopha-gus,therecognizedprecursorlesion,canbedetectedbymeansofendoscopicscreening,whichisfollowedbytreatmentofprecancerouslesionsandmonitoringforthedevelopmentofneoplasticprogression.Esophagealsquamous-cellcarcinomaremainsthepredominantesophagealcancerinAsia,Africa,andSouthAmericaandamongAfricanAmericansinNorthAmerica.Alcoholandtobaccousearethemainriskfactors,andesophagealsquamousdysplasiaistheprecursorlesion.The5-yearsurvivalrateforpatientswithesophagealcancer,althoughgenerallypoor,hasimprovedduringthepastdecade,andlong-termsurvivalisincreasinglypos-sibleforpatientswithearlyorlocallyadvanceddisease.Thisreviewdiscussestheepidemiologicaspectsandpathogenesisofthesetwoesophagealcancers,aswellaspreventionandtherapy,focusingonrecentadvances.EpidemiologicAspectsofAdenocarcinomaandSquamous-CellCarcinomaEsophagealcancerhastwomainsubtypes—esophagealsquamous-cellcarcino-maandesophagealadenocarcinoma.Althoughsquamous-cellcarcinomaaccountsforabout90%ofcasesofesophagealcancerworldwide,theincidenceofandmortalityratesassociatedwithesophagealadenocarcinomaarerisingandhavesurpassedthoseofesophagealsquamous-cellcarcinomainseveralregionsinNorthAmericaandEurope.Esophagealcarcinomaisrareinyoungpeopleandincreasesinincidencewithage,peakingintheseventhandeighthdecadesoflife.Adenocarcinomaisthreetofourtimesascommoninmenasitisinwomen,whereasthesexdistributionismoreequalforsquamous-cellcarcinoma.IntheUnitedStates,morethan18,000newcasesofesophagealcancerandmorethan15,000deathsfromesophagealcancerwereexpectedin2014.Overthepastthreedecades,theratesofesophagealsquamous-cellcarcinomahavede-clined,whilethoseofesophagealadenocarcinomahavebeenprogressivelyincreas-ing(Fig.1).1EnvironmentalRiskFactorsPopulation-basedcase–controlandcohortstudiesindicatethatGERD,cigarettesmoking,andobesityarethemainriskfactorsforesophagealcancer.TheoddsthatesophagealadenocarcinomawilldevelopincreasebyafactoroffiveforpersonswithweeklyGERDsymptomsandbyafactorofsevenforpersonswithdailyGERDsymptoms,ascomparedwiththosewithlessfrequentepisodes.2Theabsoluteriskofesophagealadenocarcinomadevelopinginaperson50yearsofageorolderisFromtheDivisionofGastroenterology,DepartmentsofMedicineandGenetics,AbramsonCancerCenter,UniversityofPennsylvaniaPerelmanSchoolofMedi-cine,Philadelphia(A.K.R.);andtheSec-tionofGastroenterologyandHepatolo-gy,MichaelE.DeBakeyVeteransAffairsMedicalCenter,BaylorCollegeofMedi-cine,Houston(H.B.E.-S.).Addressre-printrequeststoDr.El-SeragattheMi-chaelE.DeBakeyVAMedicalCenter,2002HolcombeBlvd.(152),Houston,TX77030,[e-mail]2014;371:2499-509.DOI:10.1056/NEJMra1314530Copyright©2014MassachusettsMedicalSociety.JulieR.Ingelfinger,M.D.,EditorEsophagealCarcinomaAnilK.Rustgi,M.D.,andHashemB.El-Serag,M.D.,M.P.H.TheNewEnglandJournalofMedicineDownloadedfromnejm.orgatUNIVMIAMIMILLERSCHMEDonDecember24,2014.Forpersonaluseonly.Nootheruseswithoutpermission.Copyright©2014MassachusettsMedicalSociety.Allrightsreserved.nengljmed371;26nejm.orgDecember25,20142500Thenewenglandjournalofmedicineapproximately0.04%peryear.3However,upto40%ofallpatientswithesophagealcancerdonotreportGERDsymptoms.Theriskofesophagealadenocarcinomaisap-proximatelytwiceashighamongcurrentsmok-ersasitisamongpeoplewhohaveneversmoked,butsmokingisaconsiderablystrongerriskfac-torforesophagealsquamous-cellcarcinomathanforesophagealadenocarcinoma.4,5Incontrast,population-basedstudieshavenotshownanas-sociationbetweenalcoholconsumptionandesoph-agealadenocarcinoma.6Unlikeadenocarcinoma,esophagealsquamous-cellcarcinomaisthreetofivetimesaslikelyamongpeoplewhoconsumealcohol(threeormoredrinksdaily),andtheriskincreasessynergisticallywithtobaccosmoking.Highintakeofredmeats,fats,andprocessedfoodsisassociatedwithanincreasedriskofbothtypesofesophagealcancer,whereashighintakeoffiber,freshfruit,andvegetablesisassociatedwithalowerrisk.7,8Therisingincidenceofesophagealadenocar-cinomahasbeenhypothesizedtoberelatedtotheincreasingprevalenceofGERDaloneandobesityplusGERD,combinedwiththedecliningpreva-lenceofHelicobacterpyloriinfection.Obesityisas-sociatedwithariskofesophagealadenocarcino-mathatisincreasedbyafactorof2.4to2.8.9,10AbdominalobesityinparticularisassociatedwithanincreasedriskofBarrett’sesophagusandcan-cer,11possiblybecauseincreasingintragastricpres-surerelaxestheloweresophagealsphincterandleadstohiatalhernia,andthesefactorstogethermaypromoteandexacerbateGERD.12Abdominaladiposityismorecommoninmen,whichhasledtospeculationthatsuchadiposityexplainssomesex-relateddifferencesincancerrisk.PopulationsinwhichH.pyloriinfectionispreva-lenthaveareducedriskofesophagealadenocar-cinoma.Ameta-analysisof15observationalstudiesshowedthattheriskofadenocarcinomadecreasedby41%amongpersonswithH.pyloriinfection.13H.pyloriinfection,whichleadstogas-tritis,mayultimatelyreduceacid