胃癌（英文版）課件

GastricCancer1EpidemiologyandEtiologyPreventionandEarlyDetectionPathologyClinicalPresentationDiagnosisStagingandAssessmentTreatmentFollow-up2EpidemiologyandEtiology

3Tremendousgeographicvariationexistsintheincidenceofthisdiseasearoundtheworld.RatesofthediseasearehighestinAsiaandpartsofSouthAmericaandlowestinNorthAmerica.4Stomachcancerin2002:incidenceandmortalityrates(age-standardised)inEurope.5AetiologyandriskfactorsAetiologicalfactors;Diet;Tobacco;Occuptionalrelationships;Precursorpathologicconditions;Gastricremnant;HelicobacterpyloriFamilyhistory……6Migrantpopulationsfromhigh-riskcountriesshowamarkeddiminutioninriskwhentheymovetoalowerriskarea.InJapanesemigrantstotheUSA,thereisquiteasubstantialfallintheriskbetweenthemigrantgenerationandUS-bornJapanese.Aetiologicalfactors7Foodandnutritionplayanimportantroleinpreventionandcausationofstomachcancer.Diet8Thereisstrongevidencethatnon-starchyvegetables,includingspecificallyalliumvegetables,aswellasfruitsprotectagainststomachcancer.Thereisalsostrongevidencethatsalt,andalsosalt-preservedfoods,arecausesofthiscancer.Thereislimitedevidencesuggestingthatlegumes,includingsoyaandsoyaproducts,andalsofoodscontainingseleniumprotectagainststomachcancer.Thereisalsolimitedevidencesuggestingthatchilli,processedmeat,smokedfoods,andgrilled(broiled)andbarbecued(charbroiled)animalfoodsarecausesofstomachcancer.theWorldCancerResearchFund(WCRF)andtheAmericanInstituteforCancerResearch(AICR)9Approximately18%ofgastriccancermaybeattributabletotobaccosmokingTobaccoDoyousmoke?10InfectionwiththebacteriumHelicobacterpylori(H.pylori)isestablishedasanecessarycauseofalmostallcasesofstomachcancer.Helicobacterpylori11PreventionandEarlyDetection

12Screeningprocedures(H.pylori/endoscopy/riskfactors…);Tumormarkers(CA19-9/CEA/CA242/CA724/AFP…);Genemutations(eg.CDH-1gene…);Microscopicevaluation…..13Pathology14GrosspathologicfeaturesMicroscopicpathologicfeaturesPathology15GrosspathologicfeaturesTypeIPolypoid:wellcircumscribedpolypoidtumours.TypeIIFungating:polypoidtumourswithmarkedcentralinfiltrationTypeIIIUlcerated:ulceratedtumourswithinfiltrativemargins.TypeIVInfiltrating:linitisplastica.Borrmann’stypes:16MicroscopicpathologicfeaturesAdenocarcinoma(90-95%)LymphomaLeiomyosarcomaCarcinoidAdenoacanthomaSquamouscellcarcinomas17Adenocarcinoma.Papillaryadenocarcinoma.Tubularadenocarcinoma.Mucinousadenocarcinoma(greaterthan50%mucinous).Signet-ringcellcarcinoma(greaterthan50%signet-ringcells).Adenosquamouscarcinoma.Squamouscellcarcinoma.Smallcellcarcinoma.Undifferentiatedcarcinoma.Other.ProposedbytheWorldHealthOrganizationisrecommended.18Gastriccancercanspreaddirectly,vialymphatic,orhematogenously.19N1:perigastricnodes(groups1-6)N2:nodesalongtheleftgastric,commonhepatic,celiac,andsplenicarteries(groups7-11)N3:portal,retropancreaticandmesentericroot(groups12-14)N4:middlecolicarteryandpara-aortic(groups15-16)202122Spreaddirectly,vialymphatic,orhematogenously.

23ClinicalPresentation2425Patientsmaypresentwithawidevarietyofsymptoms,ortheymayremaincompletelyasymptomatic.26Diagnosis27SignsandsymptomsRadiologicaltechniquesEndoscopyandpathologicassessmentBiologicalmarkers28Positivefindingonphysicalexaminationarethoseofadvanceddisease.Signsandsymptoms29Radiologicaltechniques30EndoscopyGastroscopyEGDEUS31PETscan32CA19-9CEACA242CA724AFP………BiologicalmarkersGenemutation----CDH-1geneCarriersofthesemutationhavea70%lifetimeriskofdevelopinggastriccancer.33BiopsyforcytologicandhistologictestingPathologicassessment34StagingandAssessment35TreatmentdecisionsareusuallymadeinreferencetotheAmericanJointCommitteeonCancer(AJCC)andtheInternationalUnionAgainstCancer(UICC)Stageclassifications36TXPrimarytumourcannotbeassessed.T0Noevidenceofprimarytumour.TisCarcinomainsitu:intraepithelialtumourwithoutinvasionofthelaminapropria.T1Tumourinvadeslaminapropriaorsubmucosa.T2Tumourinvadesmuscularispropriaorsubserosa.T2aTumourinvadesmuscularispropria.T2bTumourinvadessubserosa.T3Tumourinvadestheserosa(visceralperitoneum)withoutinvasionofadjacentstructures.T4Tumourdirectlyinvadesadjacentstructures.TNMclassificationPrimarytumour(T)37NXRegionallymphnode(s)cannotbeassessed.N0Noregionallymphnodemetastasis.N1Metastasisin1–6regionallymphnodes.N2Metastasisin7–15regionallymphnodes.N3Metastasisinmorethan15regionallymphnodes.TNMclassificationRegionallymphnodes(N)38MXPresenceofdistantmetastasiscannotbeassessed.M0Nodistantmetastasis.M1Distantmetastasis.TNMclassificationDistantmetastasis(M):39Stage0isdefinedasfollows:TisN0M0(carcinomainsitu).StageIisdefinedasfollows:T1N0M0(IA),T1N1M0(IB),T2a/bN0M0(IB).StageIIisdefinedasfollows:T1N2M0,T2a/bN1M0,T3N0M0.StageIIIisdefinedasfollows:T2a/bN2M0(IIIA),T3N1M0(IIIA),T4N0M0(IIIA),T3N2M0(IIIB).StageIVisdefinedasfollows:T4N1M0,T4N2M0,anyTN3M0,anyTanyNM1.StagegroupingaccordingtotheAJCCUICC40Japaneseclassification

Themajordifferencesbetweenthetwoclassifications,theInternationalUnionAgainstCancer(UICC)TNMclassificationandtheJRSGCJapaneseclassification,inthemultiplecategoriesusedintheJapanesesystem(clinical,surgical,pathological,finaldiagnosis),theseparatedescriptionofPandHindicatingpoorprognosis,andintheNclassification.

Differences4142Treatment43Overalltreatmentstrategy？44AdjuvantTherapyBiologicalTherapyPrimaryTherapy45Surgicaltreatment4647Anatomyofstomach48GastrectomywithremovalofperigastriclymphnodesTreatmentofcancerofthestomachdependsonthestageofthedisease,thepartofthestomachwherethecanceris,andthepatient’sgeneralhealth.49ExtentofgastricresectionExtentlymphnodedissectionRoleofsplenectomyRoleofdistalpancreatectomyConcernsofthesurgicaltreatment50ExtentofgastricresectionTotalgastrectomyshouldberecommendedforpatientswithlesionslocatedintheproximalormiddlethirdofthestomach,orwhenadiffusetypegastriccancerisfound,whichiscommonlyseeninpatientsinwhomthewholestomachisinvolved.patientswithdistalgastriccancersubtotalgastrectomyshouldberecommended.A5?cmfreeproximalmarginisrequiredforgastriccanceroftheinfiltrativetype.Whenthetumourinvadestheoesophagus,distalesophagectomyshouldbeperformed.51ExtentlymphnodedissectionTheextentofthelymphnodedissectionalsodependsonthelocationofthetumor.Whenperformingaradicalsubtotalgastrectomyandomentectomy,allN1andN2nodesshouldberemoved(D2dissection).SomeJapansurgeonsroutinelyremoveN3lymphnodes(D3dissection,usuallyportalandretropancreatic)N1:perigastricnodes(groups1-6)N2:nodesalongtheleftgastric,commonhepatic,celiac,andsplenicarteries(groups7-11)N3:portal,retropancreaticandmesentericroot(groups12-14)N4:middlecolicarteryandpara-aortic(groups15-16)52atleast,aD1lymphadenectomyisrecommended.InpatientswherethereisasuspicionofN2nodes,aD2resectionshouldbeadvisedandshouldperformedbysurgeonsexperiencedwiththistechnique.IncaseswhereD1dissectionisperformed,atleast15nodesshouldberemovedinpatientswithresectablecancer.53Roleofsplenectomy54TheRoleofsplenectomy,BecausetheremovalofStation10lymphnodesisgreatlyfacilitatedbyperformingsplenectomy,anothermuch-debatedissuehasarisen:whetherornottoperformsplenectomyintheradicalresectionoftheproximalstomach.Theincidenceofmetastasisatsplenichilumlymphnodesishighlyrelatedtothedepthofinvasionandthetumourlocation.Roleofdistalpancreatectomy55Inadditiontosplenectomy,distalpancreatectomyensurescompleteremovaloflymphnodesalongthesplenicartery(station11).InaBritishtrial,pancreaticosplenectomycarriedamarkedadverseeffectonmorbidity,mortality,andoverallsurvival.Splenectomyandpancreaticosplenectomy,butnottheextendedlymphadenectomy,hadbeenresponsiblefortheincreasedmorbidityandmortalityintheD2groupofoneoftheEuropeantrials.Thedistalpancreatectomyshouldberecommendedonatype1levelofevidenceonlywhenthereisdirectinvasionofthepancreasbythetumourthroughthegastricserosa.5657Severalkeypointsofthegastrectomyshowedinfollowingvideos.Neoadjuvanttreatment58NeoadjuvantchemotherapyNeoadjuvantradiotherapy59NeoadjuvantchemotherapyInWesterncountries,themajorityofpatientsarediagnosedwithlocallyadvancedgastriccancer,namelyT3-4N0-2M0disease.Acurativeresectionmaybeperformedinabouthalfofthesepatients,andevenafteranR0resectiontwothirdofthepatientswillshowrecurrencewithin2–3years.60Preoperativeassessmentofresectabilityofgastriccanceriscritical.CTscanisusefulfordetectingofbothtumourinvasionofadjacentorgansandlivermetastases.EUSisquiteaccuratefortheassessmentoftheexactT-category,andlaparoscopymayexcludeperitonealtumourspreadandallowanassessmentofthepresenceoftumourcellsbyperitoneallavage.TheaccuracyofpredictionoflymphnodestatusmaybeincreasedbyaddingEUStoCTscan.61Newactiveagentsforgastriccancer,suchasdocetaxel,paclitaxel,andirinotecanhavebeenintroducedintoneoadjuvantregimens.Basedonthepublisheddata,perioperativeECFor5-FU/CisplatinbasedregimenschemotherapyshouldbeconsideredtofitpatientswithstageII/IVM0gastriccancer.62NeoadjuvantradiotherapyPreoperativeradiationtherapyimprovedlocalcontrol,whereasnodifferenceindistantfailurewasobserved.Neoadjuvantradiotherapyisdescribedassafeandwelltolerated,butfurtherrandomisedtrialsarerequiredtoassessthebenefitintermsofoverallsurvivalofradiotherapygivenpreoperatively.Adjuvanttreatment63AdjuvantchemotherapyAdjuvantradiotherapyAdjuvantchemoradiotherapy

Adjuvantintraperitonealchemotherapy64AdjuvantchemotherapyTheprognosisforpatientswithgastriccancerislargelydependentonthestageofthediseaseatthetimeofdiagnosis.PatientswithEGChaveacurerateexceeding70–80%afteroperationalone,whereaspatientswithstageT3N0gastriccancershaveatleasta50%chanceofdyingwithin5years,andthepercentagecureratesaredismalforpatientswithlymphnodemetastases.Theneedforadditivetreatmentaftersurgeryforpatientswithhigh-riskgastriccancerisobvious.Inthepastdecadesnumerousrandomisedtrialsofadjuvantchemotherapyhavebeenconducted,byusingdifferentdrugsandregimens.JapaneseAuthorsrecommendedS-1adjuvantchemotherapyforstageII/IIIgastriccancerpatientsaftercurativeD2dissection.65Abenefitfromchemotherapywassuggestedforpatientswithsixormoreinvolvedlymphnodes.S-1isafourth-generationoralfluoropyrimidinederivative,thathasbeendevelopedmainlyinJapan.66

AdjuvantintraperitonealchemotherapyAsignificantproportion–upto50%–ofpatientscurativelyresectedforgastriccancerdevelopclinicallyevidentperitonealcarcinomatosisatasiteoffailure.Thisfrequenteventsupportedtheuseofintraperitonealtherapyafterresectionoftheprimarygastriccancer.Inthepast,cisplatin,mitomycin,or5FUwerecommonlyusedforthispurpose67Onlyhyperthermicintraoperativeintraperitonealchemotherapywithorwithoutpostoperativeintraperitonealchemotherapyafterresectionofadvancedgastriccancerwasassociatedwithanimprovedoverallsurvival.However,intraperitonealchemotherapywasalsofoundtobeassociatedwithincreasedrisksofintra-abdominalabscessandneutropenia.68AdjuvantradiotherapyTherewasnoevidenceofabenefitforadjuvantradiotherapy.69AdjuvantchemoradiotherapyAsresultswithadjuvantradiotherapyalonehavebeendisappointing,investigatorshavetriedtoimprovetheefficacyofradiationtherapybyusingconcomitant5FUchemotherapy.Postoperativechemoradiotherapyprolongedsignificantlysurvivalanddisease-freesurvival.Follow-up7071Inageneralpopulationofpatientstreatedcurativelyforgastriccancerapproximately40–60%ofthemwilldeveloparecurrence.About75–80%ofthesewilloccurwithin2years,andinnearly98%ofpatientswithin5yearsfromsurgery.Local-regionaldiseaseastheonlysiteoffailureoccursin23–56%ofpatients;bycontrast,distantorganmetastasesassinglesiteofrelapseisquiterare(6%),andaregenerallyfoundinthesettingofadvancedlocoregionalorperitonealdisease.72Themajoraimsinthefollow-upstrategyaretheearlydetectionoflocalrelapse(generally,thestump)amenabletotreatmentwithcurativeintent,andtheassessmentandtreatmentofdisordersrelatedtothenutritionalstatusofpatientsaftergastrectomy(e.g.,dumpingsyndrome),orotherfunctionaldisordersrelatedtorecurrence.73SuggestedprotocolsThereis