Upload File

overview of the natural history and treatment of peptic ulcer disease

  • Home
  • Documents
  • Overview of the Natural History and Treatment of Peptic Ulcer Disease
14
2/19/2015 Overview of the natural history and treatment of peptic ulcer disease http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s… 1/14 Official reprint from UpToDate www.uptodate.com ©2015 UpToDate Authors Andrew H Soll, MD Nimish B Vakil, MD, AGAF, FACP, FACG, FASGE Section Editor Mark Feldman, MD, MACP, AGAF, FACG Deputy Editor Shilpa Grover, MD, MPH Overview of the natural history and treatment of peptic ulcer disease All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan 2015. | This topic last updated: Dec 02, 2013. INTRODUCTION — Peptic ulcer disease (PUD) is a common problem. The natural history and an overview of the treatment of peptic ulcer disease will be reviewed here. Issues related to the treatment of Helicobacter pylori infection, treatment of complications of peptic ulcer disease, and the role of surgery are discussed separately. (See "Management of duodenal ulcers in patients infected with Helicobacter pylori" and "Treatment regimens for Helicobacter pylori" and "Overview of the complications of peptic ulcer disease" and "Surgical management of peptic ulcer disease" .) NATURAL HISTORY — Data from the preH. pylori, preproton pump inhibitor (PPI) era provide important to insights into the natural history of PUD. Untreated, peptic ulcers have a widely variable natural history [17 ]. Some heal spontaneously, but recur within months or sometimes within a year or two. An illustrative report described patients who were followed for 12 months after documented healing of duodenal ulcers. Relapse occurred in 74 percent of cases; 33 percent had one recurrence, 24 percent two recurrences, and 17 percent experienced three or more recurrences [1 ]. Other reports have confirmed a 50 to 80 percent recurrence rate during the 6 to 12 months following initial ulcer healing, although relapses are not always symptomatic [2,3 ]. Other ulcers cause complications or remain refractory despite antisecretory therapy. The patient's prior ulcer history tends to predict future behavior; those with a history of complications have an increased risk of future complications. Ulcers that take longer to heal initially are more likely to recur rapidly and ulcers that have recurred frequently are likely to continue to do so, unless the underlying cause (eg, H. pylori or nonsteroidal anti inflammatory drugs [NSAIDs]) is removed. A long duration of symptoms prior to presentation is more likely to be associated with a poor response to medical therapy. (See "Refractory or recurrent peptic ulcer disease" .) Distal antral ulcers, especially prepyloric ulcers (within 2 to 3 cm of the pylorus), may have a different pattern of healing than ulcers at or proximal to the incisura because of different levels of acid secretion and the distribution of gastritis [8 ]. Many studies did not analyze gastric ulcers by location, and available data are conflicting. Nevertheless, prepyloric ulcers appear to heal more slowly and may be more likely to recur [9,10 ]. Treatment of H. pylori in infected individuals dramatically alters the incidence of ulcer relapse [11,12 ]. In a meta analysis that included 14 studies, duodenal ulcers recurred in fewer than 10 percent of patients successfully treated for H. pylori compared with 65 to 95 percent of those who remained infected [11 ]. However, newer data from the United States suggest that recurrences after successful H. pylori antibiotic treatment may be more frequent [13 ]. By contrast, relapse is the rule in the absence of successful antiH. pylori therapy. (See "Management of duodenal ulcers in patients infected with Helicobacter pylori" .) When the cause of the ulcer cannot be identified or removed (eg, continued NSAID use, or nonH. pylori, non NSAID ulcers), recurrences are frequent [14 ]. (See "Refractory or recurrent peptic ulcer disease" and "Unusual causes of peptic ulcer disease" .) TREATMENT General approach — The following points should be considered when treating peptic ulcer disease (PUD): ® ®

Upload: alex-sauzameda

Post on 28-Sep-2015

3 views

Category:

Documents


0 download

Report

DESCRIPTION

UP

TRANSCRIPT

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 1/14

    OfficialreprintfromUpToDate www.uptodate.com2015UpToDate

    AuthorsAndrewHSoll,MDNimishBVakil,MD,AGAF,FACP,FACG,FASGE

    SectionEditorMarkFeldman,MD,MACP,AGAF,FACG

    DeputyEditorShilpaGrover,MD,MPH

    Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Jan2015.|Thistopiclastupdated:Dec02,2013.

    INTRODUCTIONPepticulcerdisease(PUD)isacommonproblem.Thenaturalhistoryandanoverviewofthetreatmentofpepticulcerdiseasewillbereviewedhere.IssuesrelatedtothetreatmentofHelicobacterpyloriinfection,treatmentofcomplicationsofpepticulcerdisease,andtheroleofsurgeryarediscussedseparately.(See"ManagementofduodenalulcersinpatientsinfectedwithHelicobacterpylori"and"TreatmentregimensforHelicobacterpylori"and"Overviewofthecomplicationsofpepticulcerdisease"and"Surgicalmanagementofpepticulcerdisease".)

    NATURALHISTORYDatafromthepreH.pylori,preprotonpumpinhibitor(PPI)eraprovideimportanttoinsightsintothenaturalhistoryofPUD.Untreated,pepticulcershaveawidelyvariablenaturalhistory[17].Somehealspontaneously,butrecurwithinmonthsorsometimeswithinayearortwo.Anillustrativereportdescribedpatientswhowerefollowedfor12monthsafterdocumentedhealingofduodenalulcers.Relapseoccurredin74percentofcases33percenthadonerecurrence,24percenttworecurrences,and17percentexperiencedthreeormorerecurrences[1].Otherreportshaveconfirmeda50to80percentrecurrencerateduringthe6to12monthsfollowinginitialulcerhealing,althoughrelapsesarenotalwayssymptomatic[2,3].

    Otherulcerscausecomplicationsorremainrefractorydespiteantisecretorytherapy.Thepatient'spriorulcerhistorytendstopredictfuturebehaviorthosewithahistoryofcomplicationshaveanincreasedriskoffuturecomplications.Ulcersthattakelongertohealinitiallyaremorelikelytorecurrapidlyandulcersthathaverecurredfrequentlyarelikelytocontinuetodoso,unlesstheunderlyingcause(eg,H.pyloriornonsteroidalantiinflammatorydrugs[NSAIDs])isremoved.Alongdurationofsymptomspriortopresentationismorelikelytobeassociatedwithapoorresponsetomedicaltherapy.(See"Refractoryorrecurrentpepticulcerdisease".)

    Distalantralulcers,especiallyprepyloriculcers(within2to3cmofthepylorus),mayhaveadifferentpatternofhealingthanulcersatorproximaltotheincisurabecauseofdifferentlevelsofacidsecretionandthedistributionofgastritis[8].Manystudiesdidnotanalyzegastriculcersbylocation,andavailabledataareconflicting.Nevertheless,prepyloriculcersappeartohealmoreslowlyandmaybemorelikelytorecur[9,10].

    TreatmentofH.pyloriininfectedindividualsdramaticallyalterstheincidenceofulcerrelapse[11,12].Inametaanalysisthatincluded14studies,duodenalulcersrecurredinfewerthan10percentofpatientssuccessfullytreatedforH.pyloricomparedwith65to95percentofthosewhoremainedinfected[11].However,newerdatafromtheUnitedStatessuggestthatrecurrencesaftersuccessfulH.pyloriantibiotictreatmentmaybemorefrequent[13].Bycontrast,relapseistheruleintheabsenceofsuccessfulantiH.pyloritherapy.(See"ManagementofduodenalulcersinpatientsinfectedwithHelicobacterpylori".)

    Whenthecauseoftheulcercannotbeidentifiedorremoved(eg,continuedNSAIDuse,ornonH.pylori,nonNSAIDulcers),recurrencesarefrequent[14].(See"Refractoryorrecurrentpepticulcerdisease"and"Unusualcausesofpepticulcerdisease".)

    TREATMENT

    GeneralapproachThefollowingpointsshouldbeconsideredwhentreatingpepticulcerdisease(PUD):

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 2/14

    EradicationofH.pyloriAllpatientswithpepticulcerswhoareinfectedwithH.pylorishouldundergotherapytoeradicatetheorganism[16,17].ThisrecommendationisbaseduponoverwhelmingdataindicatingthatH.pylorieradicationreducesulcerrecurrence[12,18].(See"TreatmentregimensforHelicobacterpylori"and"AssociationbetweenHelicobacterpyloriinfectionandduodenalulcer"and"ManagementofduodenalulcersinpatientsinfectedwithHelicobacterpylori".)

    InsettingswheretheprevalenceofH.pyloriinduodenalulcersisgreaterthan90percent[19,20],empirictherapyfortheinfectionisreasonableforuncomplicatedcasesintheabsenceofNSAIDuse[21].However,inmostareasinthewesternworldwheretheprevalenceofH.pyloriinduodenalulcersisconsiderablylessthan90percent[13,18],documentinginfectionisanessentialsteppriortoinitiatingantimicrobialtherapy.ThepresenceofH.pylorishouldalwaysbeconfirmedinpatientswithgastriculcerspriortoinitiatingantibacterialtherapyatleast30percentofsuchpatientswillnotbeinfected[22].(See"IndicationsanddiagnostictestsforHelicobacterpyloriinfection"and"Unusualcausesofpepticulcerdisease".)

    Inmostregions,thelargemajorityofcomplicatedulcersareduetoH.pyloriorNSAIDuse[23].TheprevalenceofH.pyloriinpatientswithcomplicatedpepticulceration(eg,bleedingandperforation)wasinitiallyreportedtobesomewhatlowerthanthatseeninpatientswithuncomplicateddisease[24,25].However,someoftheapparentdifferenceisduetoreducedsensitivityfordetectionofH.pyloriinthefaceofactivebleeding[26,27].(See"Overview

    AllpatientswithPUDshouldreceiveantisecretorytherapy.InpatientswithuncomplicatedH.pyloriulcers,theprotonpumpinhibitor(PPI)givenalongwiththeantibioticregimenisusuallyadequatetoinducehealing.(See'AntisecretorytherapyafterH.pylorieradication'below.)

    PatientswithPUDshouldbetestedforH.pylori,keepinginmindthatPPIs,bismuth,manyantibiotics,aswellasupperGIbleeding,mayleadtofalsenegativetestresults.Inthefaceofaknownulcer(highpretestprevalence),H.pyloriisonlyconfidentlyexcludediftwoappropriatelyperformedtestsarenegative,withnoexposuretotheabovementionedfoursuppressivefactorsinthetwoweeksbeforetesting.(See"IndicationsanddiagnostictestsforHelicobacterpyloriinfection".)

    PatientswithH.pylorishouldbetreatedwithagoalofH.pylorieradication.(See"TreatmentregimensforHelicobacterpylori".)

    Antisecretorytherapyisthemainstayoftherapyinuninfectedpatients,andisappropriateformaintenancetherapyinselectedcases.

    Itisessentialtowithdrawpotentialoffendingorcontributingagentssuchasnonsteroidalantiinflammatorydrugs(NSAIDs),cigarettes,andexcessalcohol.(See"Pepticulcerdisease:Genetic,environmental,andpsychologicalriskfactorsandpathogenesis".)

    InnonH.pylori,nonNSAIDulcers,everyeffortshouldbemadetoaddressothercontributingfactorswheneverpossible,suchastreatingmedicalcomorbidities,poornutritionalstatus,ischemia,andacidhypersecretion(table1andtable2andtable3).(See"Unusualcausesofpepticulcerdisease".)

    Thereisnoevidencethataddressingstressfulpsychosocialsituationsandpsychologicalcomorbiditybenefitstreatmentoutcomesinfact,oneolderstudysuggestedthatcognitivepsychotherapyincreasedrelapserates[15].Ontheotherhand,itisimportanttokeepinmindthatpatientswithactivepsychosocialissuesmaybepredisposedtorecurrenceorpersistenceofsymptomsandulcers.Epidemiologicstudiesshowanincreaseintheincidenceofpepticulcerdiseaseaftereventsthatcausepsychologicaltrauma(eg,terroristattacks,naturaldisasters).Furthermore,psychosocialissuesshouldbeaddressedsincetheycanhaveotherdeleterioushealthconsequences.(See"Pepticulcerdisease:Genetic,environmental,andpsychologicalriskfactorsandpathogenesis".)

    Nofirmdietaryrecommendationsarenecessary,thoughpatientsshouldavoidanyfoodsthatprecipitatesymptoms.(See"Pepticulcerdisease:Genetic,environmental,andpsychologicalriskfactorsandpathogenesis".)

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 3/14

    ofthecomplicationsofpepticulcerdisease"and"NSAIDs(includingaspirin):Secondarypreventionofgastroduodenaltoxicity".)

    TreatmentofH.pyloriinpatientsonNSAIDsTherelationshipbetweenH.pyloriandNSAIDsiscontroversialandcomplexandmayberelatedtowhetherthepatientisanew("nave")orachronicuserofNSAIDs[28,29].InnaveNSAIDusers,H.pyloriappearstobeasignificantriskfactorforcomplicatedulcers[29,30].Furthermore,thereappearstobeabenefitfromscreeningnaveNSAIDusersatthestartoftherapyforH.pylorianderadicatingtheorganismbeforestartingNSAIDtreatment[28,29].Bycontrast,withestablishedNSAIDuserswhopresentwithulcercomplicationsandevidenceofH.pyloriinfection,eradicatingH.pyloriinfectiondoesnotappeartoreducethehighriskofulcercomplicationsifNSAIDsarecontinued[29].

    EradicatingH.pyloriinfectionmayalsolowertheriskofulcerrecurrenceinpatientsonlowdoseaspirin[31].However,treatmentofsuchpatientswithaPPIinadditiontotheeradicationofH.pyloricansignificantlyreducetheriskofrecurrentulcercomplications[32].

    Thus,theavailabledatasupportH.pyloritestingandtreatmentpriortostartingNSAIDs.ItisappropriatetolookforH.pylorianderadicateitfollowingpresentationofanyclinicalulcer.However,ifpatientsaregoingtocontinueNSAIDsoraspirin,theymustbetreatedwitharegimenthatreducestheriskoffurtherulcercomplications,suchasPPIs.(See"NSAIDs(includingaspirin):Secondarypreventionofgastroduodenaltoxicity".)

    AntisecretorytherapyafterH.pylorieradicationPatientswithuncomplicated,small(2cm,denselyfibrosedulcerbeds,oraprotractedpriorhistory)alsowarranttreatmentwithantisecretoryagents,atleastuntilbothcureofH.pyloriinfectionandulcerhealinghavebeenconfirmed.Prolongedantisecretorytherapycancertainlybejustifiedinpatientswhoareconsideredtobeathighrisk,sincenostudieshavehadthepowertodefinetheoptimalmanagementinthesepatients.Patientswithintermediatesizedulcers(1to2cm)areprobablyatsomeincreasedriskforslowhealing,asnotedpreviously.

    Someriskofrecurrenceorexacerbationmaybeduetothereboundacidhypersecretionthataccompaniesdiscontinuationofpotentantisecretoryagents,especiallyafteraprolongedcourseoftreatment[38,39].Althoughthemagnitudevariesandtheclinicalsignificancehasnotbeenfirmlyestablished,taperingthePPIandthensteppingdowntoanH2receptorantagonist(H2RA)fortwotothreemonthsdeservesconsiderationinhighriskpatients.

    InitialapproachtoulcersnotduetoH.pyloriCommoncausesofH.pylorinegativeulcersarefalsenegativetestingforH.pyloriandundiscoveredconsumptionofNSAIDs.However,somepatientswillhaveulcersthatarenot

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 4/14

    relatedtoH.pyloriorNSAIDS(table1andtable2andtable3).(See"Unusualcausesofpepticulcerdisease".)

    ConfirmH.pylorinegativityInthefaceofaknownpepticulcer,asinglepositivetest(invasiveornoninvasive)issufficienttodiagnoseH.pyloriinfection.However,withaknownulcerasinglenegativetestisnotsufficienttoexcludeit,soadditionalH.pyloritestingisnecessaryinpatientswithPUDandnegativeH.pyloritesting.(See"IndicationsanddiagnostictestsforHelicobacterpyloriinfection".)

    Forexample,intheUnitedStatesandpartsofEurope,theprevalenceofH.pyloriinpatientswithduodenalulcersisintherangeof50to75percent.Assumingaprevalenceof75percent,anH.pyloritestwithsensitivityandspecificityof90percentwouldhaveanegativepredictivevalue(NPV)of75percent(ie,25percentofnegativeresultswouldbefalsenegatives).(See"AssociationbetweenHelicobacterpyloriinfectionandduodenalulcer",sectionon'IncidenceofH.pyloriinpatientswithduodenalulcer'.)

    ThepretestprobabilityofH.pyloriinpatientswithgastriculcersis60to80percent,soasinglenegativetestforH.pylorihasaboutan80percentNPV(ie,20percentofnegativeresultswouldbefalsenegatives).Inpatientswithgastriculcers,multiplebiopsiesoftheulcermarginaregenerallyindicatedtoexcludemalignancy.Inaddition,atleastthreebiopsiesoftheantrumarejustifiedforureasetestingforH.pylori,and,ifnegative,histology.TheabsenceofinflammationprovidessolidevidenceforthetrueabsenceofH.pylori.

    IfagastriculcerwerediscoveredonradiographyorfoundatendoscopybutH.pyloristatuswasnotdetermined,noninvasivetestingforH.pyloriisappropriate.However,ifadequatebiopsiesofagastriculcerwerenotobtained,endoscopyisindicatedtoexcludemalignancy.(See'Antisecretorytherapy'below.)

    AntisecretorytherapyAntisecretorytherapyiswarrantedinpatientswithPUDwhoaretrulynotinfectedwithH.pylori.ProtonpumpinhibitorsaremoreeffectivethanH2RAs.

    Althoughtherearedifferencesbetweentherapies,theyareoflittleclinicalimportanceinuncomplicatedulcerscosthasbecomeanimportantfactorinchoosingatherapeuticregimen.Combiningconventionalantiulceragents(eg,PPIsandH2RAs)addstocostwithoutenhancinghealingandisnotrecommendedtakingtheseclassesofagentsatthesametimemayactuallyattenuatePPIaction.(See"Pharmacologyofantiulcermedications".)

    Studiesofthevariousagentsusedtotreatulcershaveshownthefollowing:

    AllfourH2receptorantagonists(cimetidine,ranitidine,famotidine,andnizatidine)areassociatedwithhealingratesof70to80percentforduodenalulcersafterfourweeks,and87to94percentaftereightweeksoftherapy[6].Splitdose,evening,andnighttimetherapyarealleffective.Cimetidine,ranitidine,andfamotidineareapprovedforgastriculcerhealingintheUnitedStates[5].

    Protonpumpinhibitors,includingomeprazole,esomeprazole,lansoprazole,dexlansoprazole,pantoprazole,andrabeprazole,areeffectiveininducingulcerhealing[4043].Dailydosesofomeprazolefrom20to40mgproducedduodenalulcerhealingratesof63to93percentattwoweeks,andof80to100percentatfourweeks.Omeprazole(20mgdaily)producesmorerapidhealingthanstandarddosesofH2RAsinmost,butnotallstudies.Combiningdatafromeighttrialscomparing20mgofomeprazoleto300mgofranitidine,omeprazolehada14percentadvantageattwoweeksanda9percentadvantageatfourweeks[41].Thus,omeprazolehealsduodenalulcersmorerapidlythanstandarddosesofH2RAs,buttheadvantageafterfourweeksoftherapyissmall.

    Omeprazoleatdosesof20to40mgdailyproducesnumericallygreatergastriculcerhealingthanH2RAs,buttherateofearlyhealingofgastriculcersisnotacceleratedbyomeprazoletothesameextentasthatfoundwithduodenalulcers[41].

    Althoughantacids[44]andsucralfate[45]areingeneralsuperiortoplaceboinhealingduodenalulcers,efficacyhasnotbeenestablishedforgastriculcersorforeitherNSAIDulcersornonH.pylori,nonNSAIDulcers.

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 5/14

    Antisecretorydrugscanbediscontinuedafterfourtosixweeksinpatientswithuncomplicatedulcerswhoareasymptomatic.Althoughsomeprogressivehealingoccurswithlongertreatmentperiods,theadvantagesrelativetofurtherincreasingtreatmentcostsinpatientswhoareasymptomaticanduncomplicatedaredebatable.Somepatientsareatincreasedriskforrecurrence,especiallythoseinwhomtheunderlyingcauseoftheulcercannotbereversed.Suchpatientsmaybenefitfrommaintenancetherapywithanantisecretorydrug.(See'Maintenancetherapy'below.)

    GiantulcersMedicalmanagementofgiantulcersismoredifficultthanordinaryulcers,althoughnocontrolledtrialshaveaddressedthetreatmentofgiantulcersorcomparedoptions.Aswithotherpepticulcers,theroleofNSAIDsandH.pylorimustbeassessed.TherapeuticresponsestoH2RAsoccur,butslowhealingandrecurrences,evenonmaintenanceorfulldosetherapy,arecommon[4749].

    Protonpumpinhibitorsarethedrugsofchoiceforgiantpepticulcers.Twelveweeksoftherapyiseffectiveinthemajorityofcases.Patientsshouldbereevaluatedendoscopicallyafteracourseofmedicaltherapytoensurehealingandbecausethereisa10percentincidenceofmalignancywithgiantgastriculcers.

    FOLLOWUPAFTERINITIALTHERAPYFORPEPTICULCER

    DuodenalulcersPatientswithuncomplicatedduodenalulcerswhohavebeentreateddonotneedfurtherendoscopyorradiographyunlesssymptomspersistorrecur.However,patientswithgiantduodenalulcersshouldundergorepeatendoscopytoconfirmhealing.ThenecessityforfollowuptestingofH.pyloriisdiscussedseparately.(See"IndicationsanddiagnostictestsforHelicobacterpyloriinfection".)

    GastriculcersTherearenoprospectiveoutcomedataandnoclearconsensustoguidemanagementwithrespecttoappropriatefollowupinpatientswithgastriculcersandtheliteratureisfilledwithdivergentviewsandrecommendations.Repeatendoscopywithbiopsyhasbeenadvocatedtoconfirmgastriculcerhealingasameansofensuringthatthelesionsarebenign.However,withthedecreasingincidenceofgastriccancerindevelopedcountries,theincreaseduseofnonsteroidalantiinflammatorydrugs(NSAIDs),andtheconcernoverthecostsofcare,thispracticestandardhasbeenquestioned.

    Overall,theriskoffindinggastriccanceronfollowupendoscopyofanapparentlybenigngastriculcervariesfromabout0.8to4.3percent.However,ifanexperiencedendoscopistjudgesthegastriculcertobebenignandifinitialbiopsiesareadequateandnegativeformalignancyanddysplasia,theyieldoffollowupstudiesislowandthecostofeverycancerdiscoveredwillbehigh.Manycasesofcarcinomamasqueradingasbenignulcersoccurbecausebiopsieswereinadequateordysplasiaorneoplasiawasmissedintheinitialbiopsy[50,51].(See"Diagnosisofpepticulcerdisease".)

    Itmustbeemphasizedthatan"adequate"approachistoobtainatleastfourjumbobiopsiesfromtheulcermarginorsevenregularbiopsiesandonefromthebase,iftheulcerisnottoodeep.Thesebiopsiesmustcontainadequatetissueforthepathologistmanybiopsiestakenevenbyexperiencedendoscopistscontainonlymucusorblood,whichofcoursedonotruleoutmalignancy.

    Intheabsenceofguidingdataorconsensus,thereisawiderangeofstandardpractice.Ourapproachistonotrepeatanupperendoscopyonpatientswithbenignappearinggastriculcersthathavebeenadequatelybiopsiedwithnoevidenceofmalignancyordysplasiaonbiopsies.Inpatientsathighriskformalignancyweperformafollowupendoscopy(withbiopsiesoftheulcerifstillpresent)aftersixweeksoftherapy.Highriskgastriculcersincludethefollowing:

    Misoprostolenhancesduodenalulcerhealingcomparedwithplaceboatdosesof400to800mcgdaily[45,46].However,prostaglandinanalogshavenoadvantageoverantisecretoryagentsforulcerhealingandarenotindicatedforthispurpose.

    Occurrenceinethnicgroupsraisedinendemicareas(eg,Asians,Latinos),orafamilyhistoryofgastriccancer

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 6/14

    MAINTENANCETHERAPYMaintenancetherapyshouldbeconsideredtopreventrecurrenceinhighrisksubgroups,definedbyahistoryofcomplications,frequentrecurrences,orrefractory,giant,orseverelyfibrosedulcers.InsuchpatientswhoarealsoinfectedwithH.pylori,maintenancetherapyshouldbecontinuedatleastuntilcureoftheinfectionhasbeenconfirmed,andpossiblylonger.LongtermmaintenancetherapyisindicatedinhighriskpatientswhofailH.pylorieradicationorwhohaveH.pylorinegativeulcers.

    DuodenalulcersMaintenanceantisecretorytherapyiseffectiveinreducingduodenalulcerrecurrencesandcomplications[52].Typicalrecurrenceratesare20to25percentovera12monthperiodinpatientswhotakeH2receptorantagonists(H2RAs)versus60to90percentforplacebo.

    Protonpumpinhibitors(PPIs)alsopreventduodenalulcerrecurrencesifusedinadequatedoses.Theantisecretoryresponsetolowdosesofomeprazole(5to20mg)isvariablesomepatientsshowminimalresponse,whileothersexperiencemarkedsecretoryinhibition.Onestudyfoundthata20mgdosetakenthreedaysperweekreducedrecurrencesto23percentatsixmonthscomparedwith67percentforplacebo[53].WegenerallysuggestthatPPIsbeusedformaintenanceonlywhenH2RAshavefailedorwhendealingwithalarge,severelyfibrosedorrefractoryulcerorahistoryofulcercomplications.ThereasonforstilladvisinguseofH2RAs,ifeffective,isthatcostswillbelowerandH2RAswillhavefewerconsequencesrelatedtoprolongedacidinhibitionthanPPIs.IfaPPIisnecessary,thelowesteffectivedoseofPPIshouldbeused,suchas20mgdailyofomeprazole(oranequivalentdoseofanotherPPI).Althoughthesupportingdataremainlimited,adverseeffectsofprolongedPPIuse,suchasdecreasedcalciumabsorptionandincreasedriskofbonefracturesandcertaininfections(eg,C.difficile),andhypomagnesemiaareaconsideration[54].(See"Overviewandcomparisonoftheprotonpumpinhibitorsforthetreatmentofacidrelateddisorders",sectionon'Safety'.)

    GastriculcersThelargemajorityofdataforrecurrenceareavailableforduodenalulcers.However,thepatternwithgastriculcersappearscomparable.Thehighestriskofrecurrenceoccursinthefirstthreetosixmonthsofmaintenancetherapy[52,55].Antisecretorytherapyappearstoremaineffectiveformorethanfiveyearsrecurrenceratesafterthistimeperiodarelowerthaninthefirstyearoftherapy[47,49].PatientsfollowedfortheseprolongedperiodsonH2receptorantagonistsincludemanyindividualswithahistoryofcomplicationsorthoseinitiallyreferredforulcersurgery.Approximatelythreequartersofthesepatientsdidwellclinicallyonmaintenancedosesinonereport:onequarterremainedasymptomaticandulcerfree,andonehalfhadoneormorerelapsesthatrespondedtofulldoseH2receptorantagonisttherapy[56].

    Ifmaintenancetherapyisstoppedafteroneyear,ulcerrecurrenceissimilartothatforpatientsplacedonplaceboafterinitialulcerhealing[57].Thereisdebateastowhetherrecurrenceratessubsequentlydropafterprolongedmedicaltherapy[52,56].However,thesedataaredrawnfromalargelyH.pyloripositivepatientpopulation,whichmaynotbepredictiveoftreatmentofnonH.pylori,nonNSAIDulcers.

    Therearenodatafromcontrolledtrialsregardingtheappropriatedurationofmaintenancetherapy.Wesuggestthatthelengthoftherapyvarywiththeindication.Foruncomplicatedrecurrentdisease,stoppingtherapyaftertwoyearsisreasonable,whileafiveyearcoursemaybemoreappropriateforcomplicateddisease.Ifthecausalfactorcanbe

    TheabsenceofrecentNSAIDuse

    ThepresenceofH.pylori,particularlyifassociatedwithgastricatrophy

    Agegreaterthan50years

    Theabsenceofeitheraconcomitantduodenalulcerorapriorhistoryofduodenalulcer(duodenalulcersrequirehigheracidsecretion,whichisincompatiblewiththepangastritistypicalofmostgastriccancers)

    Giantulcers(>2to3cm)

    Theabsenceofaprotractedulcerhistory.Althoughtherewillbeexceptions,thelongertheulcerhistory,thelowertheriskthatagastriculceriscancer.Gastriculcersrequireacidandgastriccancerusuallydevelopsinthesettingofatrophicpangastritis.

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 7/14

    confidentlyreversed(eg,H.pyloriinfectioneradicatedorNSAIDsdiscontinued),thenrequirementsformaintenancearemarkedlyreduced[35].

    DISCONTINUINGPPIsReboundacidhypersecretionisanimportantconsiderationfollowingabruptcessationofprolongedtreatmentwithprotonpumpinhibitors(PPIs).Asaresult,treatmentshouldbetaperedfollowingprolongedorhigherdosetreatmentwithaPPI.(See"Overviewandcomparisonoftheprotonpumpinhibitorsforthetreatmentofacidrelateddisorders",sectionon'Discontinuingprotonpumpinhibitors'.)

    TREATMENTDURINGPREGNANCYANDLACTATIONWhenpepticulcerdiseaseisdiagnosedinawomanwhoispregnant,thefocusoftreatmentistypicallyacidsuppression[58].AllofthePPIsareconsideredlowriskinpregnancy,whereasmisoprostoliscontraindicatedinpregnancyasitcanprecipitateabortion.Althoughconfirmationisrequired,alargeSwedishstudyassociatedgastricacidsuppressors(H2receptorantagonists,PPIs,prostaglandins,combinationsforH.pylorieradication,anddrugsforpepticulcerandgastroesophagealrefluxdisease[GERD])withasignificant,butlow,absoluteriskofallergicdiseaseandasthmainchildrenexposedinutero[59].Theoddsratiosforallergyandasthmawere1.43and1.51,respectively.

    IfH.pyloriispresent,treatmentistypicallydeferreduntilafterdelivery.However,withtheexceptionofbismuthandtetracycline,theothermedicationsusedforH.pylorieradicationarelowriskinpregnancy,especiallyafter14weeks.Thisincludesclarithromycin,amoxicillin,andprobablymetronidazole.Moreover,thereissomeevidencethatH.pyloricancauseseverenausea/vomitinginpregnancy,includinghyperemesisgravidarum[60,61].Thus,ifindicated,H.pyloritreatmentshouldbeconsideredinpregnancy.Inaddition,someofthemedicationstypicallyusedforthetreatmentofH.pyloriareconsideredpossiblyunsafefornursinginfants(eg,bismuth,metronidazole).(See"Medicalmanagementofgastroesophagealrefluxdiseaseinadults",sectionon'Pregnancyandlactation'and"Initialprenatalassessmentandfirsttrimesterprenatalcare",sectionon'Antibiotictherapy'.)

    REFRACTORYULCERSThetreatmentofrefractoryulcersisdiscussedelsewhere.(See"Refractoryorrecurrentpepticulcerdisease".)

    INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5 to6 gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10 to12 gradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.

    Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon"patientinfo"andthekeyword(s)ofinterest.)

    SUMMARYANDRECOMMENDATIONSThemanagementofpatientswithpepticulcerdisease(PUD)needstobeadaptedtothespecificclinicalsituation,etiology,andanticipatednaturalhistory.ThefollowingpointsshouldbeconsideredwhentreatingPUD:

    th th

    th th

    Basicstopics(see"Patientinformation:Pepticulcers(TheBasics)"and"Patientinformation:H.pyloriinfection(TheBasics)"and"Patientinformation:Gastritis(TheBasics)")

    BeyondtheBasicstopics(see"Patientinformation:Pepticulcerdisease(BeyondtheBasics)"and"Patientinformation:Helicobacterpyloriinfectionandtreatment(BeyondtheBasics)")

    AllpatientswithPUDshouldreceiveantisecretorytherapy.InpatientswithuncomplicatedH.pyloriulcers,theprotonpumpinhibitorgivenalongwiththeantibioticregimenisusuallyadequatetoinducehealing.(See"TreatmentregimensforHelicobacterpylori"and'InitialapproachtoulcersnotduetoH.pylori'above.)

    PatientswithPUDshouldbetestedforH.pylori,keepinginmindthatupperGIbleedingandmedications

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 8/14

    UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

    Topic25Version14.0

    usedforthetreatmentofmayleadtofalsenegativetestresults.(See"IndicationsanddiagnostictestsforHelicobacterpyloriinfection".)

    PatientswithH.pylorishouldbetreatedwithagoalofH.pylorieradication.(See'TreatmentofH.pyloriinpatientsonNSAIDs'aboveand"TreatmentregimensforHelicobacterpylori"and"IndicationsanddiagnostictestsforHelicobacterpyloriinfection",sectionon'Confirmationoferadication'.)

    ThemanagementofH.pyloripositiveulcersafterantibiotictreatmentdependsupontheclinicalsituationandthepresenceofriskfactors.Forsmall(

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source=s 9/14

    GRAPHICS

    WorkupforapparentlyH.pylorinegative,NSAIDnegativeulcers

    Etiologicfactor Action

    Smoking Carefulhistory

    Comorbiddisease Clinicalevaluation

    H.pylorithathasescapeddetection

    PerformatleasttwotestsforH.pyloriEnsuretestingisperformedwhilethepatientisoffofPPIs,antibiotics,bismuthConsiderfourduodenalmucosalbiopsiestodetectisolatedduodenalcolonization

    NSAIDs,aspirin,otherpotentiallyulcerogenicdrugs

    CarefulhistoryConsiderobtainingurinesalicylatelevelsorplateletfunctionteststoexcludesurreptitiousNSAIDuse

    Neoplasia,infection,infiltrativedisease

    Biopsyulcersandsurroundingmucosa,includingintheduodenum

    Acidhypersecretion MeasureserumgastrinlevelsoffofPPIsMeasurebasalacidoutputConsidersecretinstimulationinpatientswithnormalserumgastrinlevels

    Ischemicmechanisms Excludeuseofcrackcocaineandmethamphetamine

    H.pylori:HelicobacterpyloriNSAID:nonsteroidalantiinflammatorydrugPPI:protonpumpinhibitor.

    Adaptedfrom:GisbertJP,CalvetX.Reviewarticle:Helicobacterpylorinegativeduodenalulcerdisease.AlimentPharmacolTher200930:791.

    Graphic75002Version5.0

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source= 10/14

    Etiologiesanddiseaseassociationsforpepticulcer

    Ulcersduetodefinedmechanisms

    Infection

    Helicobacterpylori

    HSV

    CMV

    Helicobacterheilmannii

    Otherrareinfections:TB,syphilis,mucormycosis,etc

    Drugexposure(allprobablyworsewhencombinedwithNSAIDsorinhighrisksubjects)

    NSAIDsandaspirinincludinglowdoseaspirin

    Bisphosphonates(probablywhencombinedwithNSAIDs)

    C lopidogrel(whencombinedwithNSAIDsorinhighrisksubjects)

    Corticosteroids(whencombinedwithNSAIDs)

    Sirolimus

    Spironolactone(probable,nodatawithNSAIDcotherapy)

    Mycophenolatemofetil

    Potassiumchloride

    Chemotherapy(eg,hepaticinfusionwith5fluorouracil)

    Hormonalormediatorinduced,includingacidhypersecretorystates

    Gastrinoma(ZollingerEllisonsyndrome)

    Systemicmastocytosis

    Basophiliainmyeloproliferativedisease

    AntralGcellhyperfunction(existenceindependentofH.pyloriisdebatable)

    Postsurgical

    Antralexclusion

    Postgastricbypass

    Vascularinsufficiencyincludingcrackcocaineuse

    Mechanical:Duodenalobstruction(eg,annularpancreas)

    Radiationtherapy

    Infiltratingdisease

    Sarcoidosis

    Crohndisease

    Idiopathicpepticulcer

    NonHelicobacterpylori,nonNSAIDpepticulcer

    Comorbidulcersassociatedwithdecompensatedchronicdiseaseoracutemultisystemfailure

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source= 11/14

    Stressintensivecareunitulcers

    Cirrhosis

    Organtransplantation

    Renalfailure

    Chronicobstructivepulmonarydisease(secondarytosmoking)

    HSV:herpessimplexvirusCMV:cytomegalovirusNSAID:nonsteroidalantiinflammatorydrugTB:tuberculosis.

    CourtesyofAndrewHSoll,MD.

    Graphic79691Version4.0

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source= 12/14

    Causesofrefractoryorrecurrentpepticulcerdisease

    PersistingH.pyloriinfection

    Poorcompliancewithtreatment

    Resistantorganism

    InadequateH.pyloriregimen

    UnrecognizedH.pyloriinfection:

    FalsenegativeH.pyloritesting

    Skippedorinadequatetesting

    Ulcersrelatedtononsteroidalantiinflammatorydrugs(NSAIDs)

    ContinuedNSAIDuse

    UndiscoveredNSAIDuse

    PoorresponsetoPPIcotherapy

    Othermechanisms

    Impairedhealing:

    Densefibrosis

    C igarettesmoking,especiallyheavy

    Giantulcer

    Inadequateinhibitionofacidsecretion:

    Noncompliance

    Pharmacologicresistancetohistaminetype2receptorantagonists(H2RAs)orPPIs

    RapidPPImetabolizers

    TolerancetoH2RAs

    Hypersecretorystates:

    Gastrinoma

    AntralGcellhyperfunction

    Idiopathichypersecretoryduodenalulcer

    Comorbidconditions:

    Uremia

    Cirrhosis

    Catabolicstate

    Pulmonaryormultisystemfailure

    Cotherapies:

    Glucocorticoids

    Cytotoxicdrugs

    Otherdrugs,suchasmethamphetamineorcocaineuse

    Uncommoncauses:

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source= 13/14

    Cancer

    Crohndisease

    InfectionsotherthanH.pylori

    Eosinophilicandotherinflammatoryconditions

    H.pylori:HelicobacterpyloriPPI:protonpumpinhibitor.

    Graphic76314Version7.0

  • 2/19/2015 Overviewofthenaturalhistoryandtreatmentofpepticulcerdisease

    http://www.uptodate.com/contents/overviewofthenaturalhistoryandtreatmentofpepticulcerdisease?topicKey=GAST%2F25&elapsedTimeMs=0&source= 14/14

    Disclosures:AndrewHSoll,MDNothingtodisclose.NimishBVakil,MD,AGAF,FACP,FACG,FASGEConsultant/AdvisoryBoards:AstraZeneca[GERD(Esomeprazole)]Baxter[Probiotics].OtherFinancialInterest:Salix[GERD(w ebbasedreview article)].MarkFeldman,MD,MACP,AGAF,FACGNothingtodisclose.ShilpaGrover,MD,MPHEmployeeofUpToDate,Inc.Contributordisclosuresarereview edforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreview process,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.Conflictofinterestpolicy

    Disclosures


PEPTIC ULCER DISEASE - pharmacytechtopics.com · 10/31/2012 · Describe the pathophysiology of peptic ulcer disease. 2. List the risk factors for developing peptic ulcer disease

Peptic ulcer disease Disorders of the esophagussemmelweis.hu/belgyogyaszat3/files/2018/02/Peptic-ulcer-disease_Disorders-of-the...Peptic ulcer disease Disorders of the esophagus. Peptic

38622470 Peptic Ulcer Disease

Pharmacology of Peptic Ulcer Disease - GBV · Pharmacology of Peptic Ulcer Disease ... D. Eradication oi Helicobacter pylori and Peptic Ulcer Disease ... B. Etiology and Pathophysiology

PEPTIC ULCER disease (PUD)

Peptic Ulcer Disease( PUD):

Peptic ulcer disease final

Peptic Ulcer Disease (Pud)

Peptic Ulcer Disease

Gastritis & Peptic Ulcer Disease