英文课件难治性胃食管反流病

英文课件此ppt下载后可自行编辑难治性胃食管反流病英文课件此ppt下载后可自行编辑难治性胃食管反流病1英文课件难治性胃食管反流病2RefractoryGastroesophagealrefluxdiseaseRefractoryGastroesophagealre3DefinitionofRGERDRGERD:Patientswhoareunresponsiveto4-8weeks'treatmentwithPPIstwicedailyoresophagealinjurycausedbyREcan’ttobehealing.—RichterJENatlClinGastroenterol2007;4:658OtherssuggestthatlackofsatisfactorysymptomaticresponsetoPPIonceadayissufficienttoconsiderpatientsasPPIfailures.AnyattempttonarrowthedefinitionofrefractoryGERDmightexcludemanytruesufferers.——HershcoviciTetal.BestPractice&ResearchClinicalGastroenterology2010(24)923-936RemainsanareaofcontroversyDefinitionofRGERDRGERD:Patie4PPIfailedinEachoftheGastrooesophagealRefluxDisease(GERD)GroupsGERDNERD60-70%EE20-30%Barrett′soesophagus6-10%PPIfailurepatientsFailureonPPIqd40-50%FailureonPPIqd6-15%FailureonPPIqd20%——Fassetal.AlimentPharmacolTher2005;22(2):79-94.PPIfailedinEachoftheGast530%NERDfailtoPPItreatment30%NERDfailtoPPItreatment6NERD-acid,visceralsensitivityNERD-acid,visceralsensitivity7PotentialcausesofPPIrefractorinessinGERDNeurogastroenterolMotil(2012)24,697–704PotentialcausesofPPIrefrac8MechanismWeaklyacidrefluxNABDilatedintercellularspacesDGEREsophagealhypersensitivityGastroparesisPoorcompliancewithPPItreatmentPsychologicalMechanismWeaklyacidrefluxNAB9WeaklyAcidRefluxTheprevalenceofweaklyacidicrefluxinrefractoryGERDis30-40%.WhentheesophagealpHfallsby≥1unit,butremains＞4,itisconsidered“weaklyacidicreflux”.Gut,2004,53:1024-1031EsophagealdistensionPersistentimpairedmucosalintegrity

EsophagealhypersensitivityWeaklyAcidRefluxTheprevalen10EsophagealHypersensitivityAMJGastroenterol,2012,107,8-15.Esophagealreceptorupregulationand/orenhancedsignalingPhysiologicalstressors,sensitizationofspinalsensoryneurons.PotentialfactorscontributingtothespectrumofrefluxperceptioninpatientswithGERDEsophagealHypersensitivityAM11GastroparesisDelayedgastricemptying(gastroparesis)maybeafactorassociatedwithseverereflux,dyspepsia,orboth.Gastroparesis,concomitantin25%ofpatientswithgastroesophagealrefluxdisease(GERD),hasbeenshowntoimproveafterNissenfundoplication.SURGICALENDOSCOPYANDOTHERINTERVENTIONALTECHNIQUES

，2008，22

（11）:2440-2444GastroparesisSURGICALENDOSCOP12PoorCompliancewithPPITreatmentCompliancetotreatmentandproperdosingareimportant.Timingandfrequencyofdosingarecriticalformaximumefficacyofthemedication.Patients

dosedoptimallythePPIs(%)Properdosingtiming46%Patients

dosedsuboptimallythePPIs(%)>60min

beforemeals39%aftermeals30%atbedtime28%as-needed4%PPIdosingsituationin100patientswithpersistentGERDsymptomsAlimentPharmacolTher2006;23:1473–7PoorCompliancewithPPITreat13NocturnalAcidBreakthroughNAB:GastricpHbelow4over60consecutiveminutesatnight-timeinsubjectswhotakeprotonpumpinhibitorstwicedaily.AlimentPharmacolTher,2002,16()7:1309-1316.NocturnalAcidBreakthroughNAB14DilatedintercellularspacesThedilationofesophagealintercellularspaces(ICS)isconsideredanearlymorphologicmarkerofaciddamageinpatientswithGERD.ICSwillbedifficulttoeliminated

inRGERDpatientswhofailtoPPItreament.DilatedintercellularspacesT15BileRefluxGastroenterol2009January21;15(3):334-338230patientswithheartburnandregurgitationcontinuedtoreportsymptomsafter8wkofhigh-dosePPItherapy(40mgesomeprazolebid).BileRefluxGastroenterol200916PsychologicalComorbiditiesALIMENTARYPHARMACOLOGY&THERAPEUTICS

,2007,26

(3):443-452.AnxietyanddepressionhavebeenshowntoincreaseGERD-relatedsymptomsreportinpopulation-basedstudies.PsychologicalComorbiditiesALI17NewMechanismNewMechanism18Aninflammatoryresponseoccursinthesquamousepithelium,inducedbythereleaseofinflammatorymediatorsLeadstothesubsequentchemoattractionandinfiltrationofimmunecellsFollowedbytheproliferativeresponseoftheratepithelium.Immunity:MucosalInflammationGastroesophagealrefluxdisease-fromrefluxepisodestomucosalinflammation.

Nat.Rev.Gastroenterol.Hepatol.2012AninflammatoryresponseLeads19Proteaseactivatedreceptor2(PAR2)Gastroesophagealrefluxdisease-fromrefluxepisodestomucosalinflammation.

Nat.Rev.Gastroenterol.Hepatol.2012

ActivatedbyserineproteasesUpregulatedinpatientswithGERDandinducedbyacidconditionsincellculturemodelsPAR2activation:LeadstoepithelialIL-8releaseandcontributestothepathogenesisofGERDImplicatedininflammatoryandneuroinflammatoryeffectsthemodulationofvisceralhypersensitivityandpaingenerationandincreasingepithelialpermeability.

GERDisImmune-mediatedesophagealmucosaldamage(IL-8AnewtargetsforGERDdrugdevelopment.Proteaseactivatedreceptor2(20ProinflammatoryandNeuroinflammatoryAspectsGastroenterol.Hepatol.2012TRPV1(transientreceptorpotentialcationchannelsubfamilyVmember1)TRPV1isinvolvedintheinflammatoryepithelialresponse,thatissupposedtobeinvolvedinGERD-relatedsymptomgeneration.EEorNERDpatientswithhighexpressionlevelofTRPV１．NuroinflammatoryaspectsinGERDpatientsNGF↑GNDF↑ProinflammatoryandNeuroinfla21EsophagealEosinophiliaAmericanJournalofGastroenterology，2008，435-442Highintraepithelialeosinophilcountsinesophagealsquamousepitheliumarenotspecificforeosinophilicesophagitis.Eos＞20/HPFinGERDpatientssuggestitmaybeRGERD.＞20/HPFEsophagealEosinophiliaAmerica22ErosiveesophagitismayberelatedtosmallintestinalbacterialovergrowthScandinavianJournalofGastroenterology.2012GERDandSIBOOverlapofGERDandIBSLactulosehydrogenbreathtest（LHBT）InAbnormalLHBT,67%inEE,37%incontrol

（P=0.024）65%inEE,31%incontrol(withoutIBS)（P=0.032）SmallIntestinalBacterialOvergrowthErosiveesophagitismayberel23DiagnosistestsDiagnosistests24UpperGastrointestinalEndoscopyGastrointestEndosc2007;66:219–24CommonlyusedinclinicalpracticetoevaluatepatientswithGERDwhofailedPPItreatment.ThevalueofendoscopyinpatientswithrefractoryGERDisverylow—Eosinophilicoesophagitiswasfoundinonly0.9%ofRGERDpatients,andNERDandfunctionalheartburnpatientstakeabigpart.UpperGastrointestinalEndosco25Anewmethodinthediagnosisofrefluxesophagitis:confocallaserendomicroscopy.GIE.2012

Confocallaserendomicroscopy，CLEAnewmethodtotestGERD—Thedistancebetweenthesurfacetopapillary(S-P)tipcanbemeasuredbyusingCLE.S-Pdistance:0.19um/cminRE,0.44um/cmincontrol.黏膜表面毛细血管袢Anewmethodinthediagnosis26共聚焦激光显微内镜诊断NERDNERDpatientshadmoreintrapapillarycapillaryloops(IPCLs)thancontrol.IPCLsnumberincreased;IPCLsdiameterbecomebigger;IPCLsextendedtomucosalsurface;Theintercellularspacesofsquamouscellswasenlarged.AmJGastroenterol.2012Mar13.

共聚焦激光显微内镜诊断NERDNERDpatientsh27NERDdiagnosedbyCLE-DilatedDICAmJGastroenterol.2012Mar13.

;Control:figuera,b,e;NERD:figurec,d,f（DIS）NERDdiagnosedbyCLE-Dilated28EsophagealpHmonitoringallowthequantificationofesophagealacidexposureandtheassessmentofthetemporalrelationshipbetweensymptomsandacidrefluxevents.PHmonitoringcanbeperformedoffPPItotestiftheinitialdiagnosiswascorrect(i.e.,heartburnwasduetoacidreflux)oronPPItotestwhetherthesymptomsareduetoresidualacidreflux.Remote

proximalacidrefluxRemote

proximalacidrefluxAmbulatory24hEsophagealpHMonitoringRemote proximalRemote 29Ambulatory24hEsophagealpHMonitoring-GraphsAmbulatory24hEsophagealpHM30EsophagealBilitec

Bilitecdetectsbilirubinintherefluxatethatisusedasasurrogatemarkerforbilereflux.Onehastorecallthatnon-acidicandbilerefluxaretwodistinctphenomena.Esophagealexposuretobileacidscanresultinheartburnsymptoms.DigDisSci2005;50:81–5.EsophagealBilitecDigDis31TreamentofRGERDTreamentofRGERD32TherapeuticoptionsforRGERDpatients

GastroenterologyandHepatology27(2012)Suppl.3;3–7TherapeuticoptionsforRGERD33GERDandPPIPaulMoayyedietal,Lancet,2006,June24(367):2086-2100GERDandPPIPaulMoayyedieta34NewPPIsDis.Esophagus2005;18:370–3.Gastroenterol，2010;105:2341–6InProcess

NewPPIsDis.Esophagus2005;135Histamine2receptorantagonist(H2RA)Histamine2receptorantagonistgivenindivideddosesmayalsobeusedandareeffectivetreatmentinmanypatientswithlesssevereGERD.AmericanguidelinesfordiagnosisandtreatmentofGERDHistamine2receptorantagonis36PromotilitytherapyRegurgitationmaybethemainsymtomofrefractoryGERD,comparewiththosewhoarewithouttreatment.GERDisadisorderofgastrointestinalmotilityDefectsinesophagogastricmotility(LESincompetence,pooresophagealclearance,anddelayedgastricemptying)arecentraltothepathogenesisofGERD.Ifthesedefectscouldbecorrected,thenGERDwouldbecontrolled,makingsuppressionofnormalamountsofgastricacidunnecessary.AmericanguidelinesfordiagnosisandtreatmentofGERDPromotilitytherapyRegurgitati37Transientloweresophagealsphincter

relaxation(TLESR)reducersGamma-aminobutyricacidB(GABAB)receptoragonists(Baclofen)Metabotropicglutamatereceptor5(mGluR5)antagonists(ADX10059)AmJPhysiol2001;281:G311–5.Gastroenterology2005;129:995–1004.Transientloweresophagealsph38Gastroesophagealrefluxdisease-fromrefluxepisodestomucosalinflammation.Nat.Rev.Gastroenterol.Hepatol.2012Cannabinoids(CB1)antagonist

:(rimonabant)Decreasedmeal-inducedTLESR;ThetotalnumberofpostprandialTLESRepisodesacidrefluxepisodeswasmarkedlyreducedinhealthyvolunteersaftertreatmentwithrimonabant.DrugTherapy-InProcess

Gastroesophagealrefluxdiseas39Gastroesophagealrefluxdisease-fromrefluxepisodestomucosalinflammation.

Nat.Rev.Gastroenterol.Hepatol.2012mGluR5antagonist

（

ADX10059）

ADX10059hasadifferentpharmacodynamicapproachtoTLESRreductionthantheabovemedications,andhasbeenshowntoreducebothacidicandnonacidicrefluxevents.

Afteranincreaseinabnormallaboratorytestresults(liverenzymes)andafewcasesofhepaticfailure,thefurtherdevelopmentofADX10059wasalsodiscontinued.DrugTherapy-InProcess

Gastroesophagealrefluxdiseas40

Aliment.Pharmacol.Ther.33,1113–1122(2011).TRPV1

antagonist

（

AZD1386)：TRPV1channelisresponsivetonoxiousheatandacid.TRPV1antagonist(AZD1386)increasedoesophagealandskinheatpainthresholds.ItisapotentialdrugclassforGERDtreatment.DrugTherapy-InProcess

Aliment.Pharmacol.Ther.33,41VisceralpainmodulatorsMostofthepatientswhofailPPItreatmentoriginatefromtheNERDgroupmorethan50%ofthePPIfailure(twicedaily)subjectsdemonstratelackofeitherweaklyoracidicreflux,theusageoftheseagentsishighlyattractive.TricyclicantidepressantsTrazodone(atetracyclicantidepressants)

Selectiveserotoninreuptakeinhibitors(SSRIs)Gut，2006，55:1398–402VisceralpainmodulatorsMosto42AntirefluxSurgeryGastrointestSurg(2010)14:1434–1441Gut

2011;60:435e441.RefractoryGERDwasthemostcommon(88%)indicationforantirefluxsurgeryandthemostcommonpreoperativesymptomreportedunderfailureofmedicalantirefluxtreatmentwasregurgitation(54%).AntirefluxSurgeryGastrointest43EndoscopictherapyRadiofrequencytherapy:Strettaprocedure;Injectiontherapy:Enteryx,GK,Stemcellinjection;Suturing/plicationtherapyLINXrefluxmanagementsystemEndoscopictherapyRadiofrequen44LINXrefluxmanagementsystemSurgEndosc，2012AprilJGastrointestSurg(2008)

Thedeviceconsistsofaseriesofinterlinkedtitaniumbeadscontainingamagneticcore,isplacedlaparoscopicallyaroundtheexternalesophagusatthegastroesophagealjunction(EGJ)

Improvetherefluxbarrier(reducedesophagealacidexposure),improvedGERD-relatedqualityoflife,andcessationofdependenceonPPIsLINXrefluxmanagementsystemSu45ManagementalgorithmofGERDpatientwhofailedPPIoncedailyBestPractice&ResearchClinicalGastroenterology24(2010)923–936ManagementalgorithmofGERDp46此ppt下载后可自行编辑谢谢大家此ppt下载后可自行编辑谢谢大家47英文课件难治性胃食管反流病48英文课件此ppt下载后可自行编辑难治性胃食管反流病英文课件此ppt下载后可自行编辑难治性胃食管反流病49英文课件难治性胃食管反流病50RefractoryGastroesophagealrefluxdiseaseRefractoryGastroesophagealre51DefinitionofRGERDRGERD:Patientswhoareunresponsiveto4-8weeks'treatmentwithPPIstwicedailyoresophagealinjurycausedbyREcan’ttobehealing.—RichterJENatlClinGastroenterol2007;4:658OtherssuggestthatlackofsatisfactorysymptomaticresponsetoPPIonceadayissufficienttoconsiderpatientsasPPIfailures.AnyattempttonarrowthedefinitionofrefractoryGERDmightexcludemanytruesufferers.——HershcoviciTetal.BestPractice&ResearchClinicalGastroenterology2010(24)923-936RemainsanareaofcontroversyDefinitionofRGERDRGERD:Patie52PPIfailedinEachoftheGastrooesophagealRefluxDisease(GERD)GroupsGERDNERD60-70%EE20-30%Barrett′soesophagus6-10%PPIfailurepatientsFailureonPPIqd40-50%FailureonPPIqd6-15%FailureonPPIqd20%——Fassetal.AlimentPharmacolTher2005;22(2):79-94.PPIfailedinEachoftheGast5330%NERDfailtoPPItreatment30%NERDfailtoPPItreatment54NERD-acid,visceralsensitivityNERD-acid,visceralsensitivity55PotentialcausesofPPIrefractorinessinGERDNeurogastroenterolMotil(2012)24,697–704PotentialcausesofPPIrefrac56MechanismWeaklyacidrefluxNABDilatedintercellularspacesDGEREsophagealhypersensitivityGastroparesisPoorcompliancewithPPItreatmentPsychologicalMechanismWeaklyacidrefluxNAB57WeaklyAcidRefluxTheprevalenceofweaklyacidicrefluxinrefractoryGERDis30-40%.WhentheesophagealpHfallsby≥1unit,butremains＞4,itisconsidered“weaklyacidicreflux”.Gut,2004,53:1024-1031EsophagealdistensionPersistentimpairedmucosalintegrity

EsophagealhypersensitivityWeaklyAcidRefluxTheprevalen58EsophagealHypersensitivityAMJGastroenterol,2012,107,8-15.Esophagealreceptorupregulationand/orenhancedsignalingPhysiologicalstressors,sensitizationofspinalsensoryneurons.PotentialfactorscontributingtothespectrumofrefluxperceptioninpatientswithGERDEsophagealHypersensitivityAM59GastroparesisDelayedgastricemptying(gastroparesis)maybeafactorassociatedwithseverereflux,dyspepsia,orboth.Gastroparesis,concomitantin25%ofpatientswithgastroesophagealrefluxdisease(GERD),hasbeenshowntoimproveafterNissenfundoplication.SURGICALENDOSCOPYANDOTHERINTERVENTIONALTECHNIQUES

，2008，22

（11）:2440-2444GastroparesisSURGICALENDOSCOP60PoorCompliancewithPPITreatmentCompliancetotreatmentandproperdosingareimportant.Timingandfrequencyofdosingarecriticalformaximumefficacyofthemedication.Patients

dosedoptimallythePPIs(%)Properdosingtiming46%Patients

dosedsuboptimallythePPIs(%)>60min

beforemeals39%aftermeals30%atbedtime28%as-needed4%PPIdosingsituationin100patientswithpersistentGERDsymptomsAlimentPharmacolTher2006;23:1473–7PoorCompliancewithPPITreat61NocturnalAcidBreakthroughNAB:GastricpHbelow4over60consecutiveminutesatnight-timeinsubjectswhotakeprotonpumpinhibitorstwicedaily.AlimentPharmacolTher,2002,16()7:1309-1316.NocturnalAcidBreakthroughNAB62DilatedintercellularspacesThedilationofesophagealintercellularspaces(ICS)isconsideredanearlymorphologicmarkerofaciddamageinpatientswithGERD.ICSwillbedifficulttoeliminated

inRGERDpatientswhofailtoPPItreament.DilatedintercellularspacesT63BileRefluxGastroenterol2009January21;15(3):334-338230patientswithheartburnandregurgitationcontinuedtoreportsymptomsafter8wkofhigh-dosePPItherapy(40mgesomeprazolebid).BileRefluxGastroenterol200964PsychologicalComorbiditiesALIMENTARYPHARMACOLOGY&THERAPEUTICS

,2007,26

(3):443-452.AnxietyanddepressionhavebeenshowntoincreaseGERD-relatedsymptomsreportinpopulation-basedstudies.PsychologicalComorbiditiesALI65NewMechanismNewMechanism66Aninflammatoryresponseoccursinthesquamousepithelium,inducedbythereleaseofinflammatorymediatorsLeadstothesubsequentchemoattractionandinfiltrationofimmunecellsFollowedbytheproliferativeresponseoftheratepithelium.Immunity:MucosalInflammationGastroesophagealrefluxdisease-fromrefluxepisodestomucosalinflammation.

Nat.Rev.Gastroenterol.Hepatol.2012AninflammatoryresponseLeads67Proteaseactivatedreceptor2(PAR2)Gastroesophagealrefluxdisease-fromrefluxepisodestomucosalinflammation.

Nat.Rev.Gastroenterol.Hepatol.2012

ActivatedbyserineproteasesUpregulatedinpatientswithGERDandinducedbyacidconditionsincellculturemodelsPAR2activation:LeadstoepithelialIL-8releaseandcontributestothepathogenesisofGERDImplicatedininflammatoryandneuroinflammatoryeffectsthemodulationofvisceralhypersensitivityandpaingenerationandincreasingepithelialpermeability.

GERDisImmune-mediatedesophagealmucosaldamage(IL-8AnewtargetsforGERDdrugdevelopment.Proteaseactivatedreceptor2(68ProinflammatoryandNeuroinflammatoryAspectsGastroenterol.Hepatol.2012TRPV1(transientreceptorpotentialcationchannelsubfamilyVmember1)TRPV1isinvolvedintheinflammatoryepithelialresponse,thatissupposedtobeinvolvedinGERD-relatedsymptomgeneration.EEorNERDpatientswithhighexpressionlevelofTRPV１．NuroinflammatoryaspectsinGERDpatientsNGF↑GNDF↑ProinflammatoryandNeuroinfla69EsophagealEosinophiliaAmericanJournalofGastroenterology，2008，435-442Highintraepithelialeosinophilcountsinesophagealsquamousepitheliumarenotspecificforeosinophilicesophagitis.Eos＞20/HPFinGERDpatientssuggestitmaybeRGERD.＞20/HPFEsophagealEosinophiliaAmerica70ErosiveesophagitismayberelatedtosmallintestinalbacterialovergrowthScandinavianJournalofGastroenterology.2012GERDandSIBOOverlapofGERDandIBSLactulosehydrogenbreathtest（LHBT）InAbnormalLHBT,67%inEE,37%incontrol

（P=0.024）65%inEE,31%incontrol(withoutIBS)（P=0.032）SmallIntestinalBacterialOvergrowthErosiveesophagitismayberel71DiagnosistestsDiagnosistests72UpperGastrointestinalEndoscopyGastrointestEndosc2007;66:219–24CommonlyusedinclinicalpracticetoevaluatepatientswithGERDwhofailedPPItreatment.ThevalueofendoscopyinpatientswithrefractoryGERDisverylow—Eosinophilicoesophagitiswasfoundinonly0.9%ofRGERDpatients,andNERDandfunctionalheartburnpatientstakeabigpart.UpperGastrointestinalEndosco73Anewmethodinthediagnosisofrefluxesophagitis:confocallaserendomicroscopy.GIE.2012

Confocallaserendomicroscopy，CLEAnewmethodtotestGERD—Thedistancebetweenthesurfacetopapillary(S-P)tipcanbemeasuredbyusingCLE.S-Pdistance:0.19um/cminRE,0.44um/cmincontrol.黏膜表面毛细血管袢Anewmethodinthediagnosis74共聚焦激光显微内镜诊断NERDNERDpatientshadmoreintrapapillarycapillaryloops(IPCLs)thancontrol.IPCLsnumberincreased;IPCLsdiameterbecomebigger;IPCLsextendedtomucosalsurface;Theintercellularspacesofsquamouscellswasenlarged.AmJGastroenterol.2012Mar13.

共聚焦激光显微内镜诊断NERDNERDpatientsh75NERDdiagnosedbyCLE-DilatedDICAmJGastroenterol.2012Mar13.

;Control:figuera,b,e;NERD:figurec,d,f（DIS）NERDdiagnosedbyCLE-Dilated76EsophagealpHmonitoringallowthequantificationofesophagealacidexposureandtheassessmentofthetemporalrelationshipbetweensymptomsandacidrefluxevents.PHmonitoringcanbeperformedoffPPItotestiftheinitialdiagnosiswascorrect(i.e.,heartburnwasduetoacidreflux)oronPPItotestwhetherthesymptomsareduetoresidualacidreflux.Remote

proximalacidrefluxRemote

proximalacidrefluxAmbulatory24hEsophagealpHMonitoringRemote proximalRemote 77Ambulatory24hEsophagealpHMonitoring-GraphsAmbulatory24hEsophagealpHM78EsophagealBilitec

Bilitecdetectsbilirubinintherefluxatethatisusedasasurrogatemarkerforbilereflux.Onehastorecallthatnon-acidicandbilerefluxaretwodistinctphenomena.Esophagealexposuretobileacidscanresultinheartburnsymptoms.DigDisSci2005;50:81–5.EsophagealBilitecDigDis79TreamentofRGERDTreamentofRGERD80TherapeuticoptionsforRGERDpatients

GastroenterologyandHepatology27(2012)Suppl.3;3–7TherapeuticoptionsforRGERD81GERDandPPIPaulMoayyedietal,Lancet,2006,June24(367):2086-2100GERDandPPIPaulMoayyedieta82NewPPIsDis.Esophagus2005;18:370–3.Gastroenterol，2010;105:2341–6InProcess

NewPPIsDis.Esophagus2005;183Histamine2receptorantagonist(H2RA)Histamine2receptorantagonistgivenindivideddosesmayalsobeusedandareeffectivetreatmentinmanypatientswithlesssevereGERD.AmericanguidelinesfordiagnosisandtreatmentofGERDHistamine2receptorantagonis84PromotilitytherapyRegurgitationmaybethemainsymtomofrefractoryGERD,comparewiththosewhoarewithouttreatment.GERDisadisorderofgastrointestinalmotilityDefectsinesophagogastricmotility(LESincompetence,pooresophagealclearance,anddelayedgastricemptying)arecentraltothepathogenesisofGERD.Ifthesedefectscouldbecorrected,thenGERDwouldbecontrolled,makingsuppressionofnormalamountsofgastricacidunnecessary.AmericanguidelinesfordiagnosisandtreatmentofGERDPromotilitytherapyRegurgitati85Transientloweresophagealsphincter

relaxation(TLESR)reducersGamma-aminobutyricacidB(GABAB)receptoragonists(Baclofen)Metabotropicglutamatereceptor5(mGluR5)antagonists(ADX10059)AmJPhysiol2001;281:G311–5.Gastroenterology2005;129:995–1004.Transientloweresophagealsph86Gastroesophagealrefluxdisease-fromrefluxepisodestomucosalinflammation.Nat.Rev.Gastroenterol.Hepatol.2012Cannabinoids(CB1)antagonist

:(rimonabant)Decreasedmeal-inducedTLESR;ThetotalnumberofpostprandialTLESRepisodesacidrefluxepisodeswasmarkedlyreducedinhealthyvolunteersaftertreatmentwithrimonabant.Drug