12/6/2016

Pneumatic dilation and botulinum toxin injection for achalasia

OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

Pneumaticdilationandbotulinumtoxininjectionforachalasia
Authors
LindaNguyen,MD
PankajJPasricha,MD

SectionEditor
NicholasJTalley,MD,PhD

DeputyEditor
AnneCTravis,MD,MSc,FACG,
AGAF

Contributordisclosures
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:May2016.|Thistopiclastupdated:Apr12,2016.
INTRODUCTIONAchalasiaisanesophagealsmoothmusclemotilitydisorderinwhichtheloweresophageal
sphincter(LES)failstorelax.Itisthoughttoresultfromaselectivelossofinhibitorynitrinergicneurons(whichcontain
nitricoxidesynthase)inthemyentericplexus,resultinginrelativelyunopposedexcitationbythecholinergicsystem.
Clinicalsymptomsincludedysphagia,chestpain,regurgitation,heartburn,andweightloss.Thediagnosisisconfirmed
byesophagealmanometry.
Thereisnocureforachalasia.TreatmentisfocusedonpalliatingsymptomsbydecreasingLESpressuretofacilitate
emptyingofesophagealcontents.ThiscanbeaccomplishedbymechanicaldisruptionofthemusclefibersoftheLES
(eg,withpneumaticdilationorsurgicalmyotomy)orbybiochemicalreductioninLESpressure(eg,withinjectionof
botulinumtoxin).Forpatientsatlowsurgicalrisk,treatmentaimedatmechanicaldisruptionoftheLESisgenerally
recommended[1,2].
Thistopicwillreviewtheadvantagesanddisadvantagesofpneumaticdilatationandbotulinumtoxininjectionforthe
managementofachalasia.Thepathophysiology,etiology,clinicalmanifestations,diagnosis,andsurgicaltherapyof
achalasiaarediscussedseparately.(See"Pathophysiologyandetiologyofachalasia"and"Clinicalmanifestationsand
diagnosisofachalasia"and"Overviewofthetreatmentofachalasia"and"Surgicalmyotomyforachalasia".)
Therecommendationsthatfollowareconsistentwitha2013guideline[3]fromtheAmericanCollegeof
Gastroenterology.
PNEUMATICDILATIONPneumaticdilation(PD)weakenstheloweresophagealsphincter(LES)bytearingits
musclefibers.Anumberofdifferentballoondilatorshavebeenused(eg,Mosherbag,Sippydilators,BrownMcHardy
dilator,RiderMoellerdilator),butmostarenolongerbeingmanufactured.Atpresent,themostpopularpneumatic
dilatorintheUnitedStatesistheRigiflexballoon.
TheRigiflexballoonispassedoveraguidewireandpositionedusingfluoroscopyacrosstheLES.Theballoonis
availableinthreedifferentdiameters(3.0,3.5,and4.0cm).Thesmallestballoonistypicallyusedforthefirstdilation.If
symptomspersist,theprocedurecanberepeatedwithincrementallylargerballoons(thesocalled"gradedapproach").
Thestandardapproachtoballoondilationisonedilationpersession,withadditionaldilationsbeingperformedif
symptomspersistorreturn.Patientsareusuallyreferredtosurgeryifthreeconsecutivedilationsdonotprovide
symptomresolution.
Morerecently,dilationhasbeenperformedusingahydraulicballoondilationcatheter(EsoFlip)[4].TheEsoFlipisa7F,
230cmlongcatheterwithan8cmtaperednylonballoonwithamaximaldiameterof30mm.Thecathetercanbe
advancedalongsidetheendoscopeoveraguidewirefordirectvisualization.Inapilotstudywith10patients,dilation
wastechnicallyfeasiblewithoutcomplications.Theoneweekresponseratewas90percent,whilethethreemonth
responseratedroppedto70percent.Largerlongtermstudiesneedtobetterevaluatetheefficacyofhydraulicballoon
dilationinthetreatmentofachalasia.
TechniqueforPDThepatientisadvisedtofastforatleast12hourspriortotheprocedure.Aliquiddietshouldbe
prescribedforoneortwodaysprecedingthedilationinpatientswithclinicalorradiographicevidenceofseverefood
retentionwithintheesophagus.
ThereisnoconsensusontheoptimalmethodforperformingPD.Reportedprotocolshavevariedwidelywithregardto
thetypesofdilatorsused,themaximumdiameteroftheballoon(2.4to5.0cm),thepressuretowhichtheballoonis
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inflated(100to>1000mmHg),therateofballooninflation(rapidversusgradual),thedurationofballooninflation
(severalsecondstofiveminutes),andthenumberofballooninflationsperdilatingsession(onetofive)[57].Noneof
thevariationsintechniquehasledtosignificantchangesinoutcome.
WeusetheRigiflexballoonforPD[8].A3cmballoonisusedfortheinitialdilationinmostadults.Priortothe
procedure,theballoonisinflatedandcheckedforleaksordeformities.
Priortodilation,athoroughendoscopicexaminationisperformed,withparticularattentiongiventothecardia,where
malignancycansimulateachalasia(calledpseudoachalasia).Aguidewireisthenpassedthroughthebiopsychannelof
theendoscopeintothestomachandthescopeiswithdrawntothegastroesophagealjunction.Thedistancebetween
theincisorsandthegastroesophagealjunctionshouldbenotedusingthemarkingsalongthelengthofthescope.
Theendoscopeisthenremoved,takingcaretomaintainthepositionoftheguidewireinthestomach.Toaidwithinitial
balloonplacement,amarker(suchaspapertape)canbeplacedontheshaftofthedilatingcathetercorrespondingto
thepreviouslynoteddistancebetweentheincisorsandthegastroesophagealjunction.Thisdistanceshouldbe
measuredfromthemiddleoftheballoononthedilatingcathetersothat,wheninserted,themiddleoftheballoonwillbe
positionedacrosstheLES.
Theballoonandtipofthecatheterarelubricatedandpassedoverthepreviouslyplacedguidewireuntilthemarker
reachestheincisors.Usingfluoroscopy,theballoonisthengraduallyinflatedwithair,notingthepositionofthe
developing"waist"intheballoon(image1).Smalladjustmentsusuallyhavetobemadeintheposition(deflatingthe
ballooneachtime)toensurethatthewaistoccursatthecenteroftheballoon(thisiscriticalforbothefficacyand
safety).Weofteninjectasmallvolumeofdilutecontrastintotheballoontoassistinradiographicvisualization.
Becausepatientsmaybeextremelyuncomfortableduringballooninflation,wefinditusefultoadministeradoseofan
opiateonetotwominutesbeforetheballoonisinflated.(See"Overviewofproceduralsedationforgastrointestinal
endoscopy".)
Afterasatisfactorypositionisobtained,theballoonisfullyinflatedsothatthewaistisobliterated,takingnoteofthe
pressurewithintheballoonusinganexternalgauge.Inourexperience,approximately7to15poundspersquareinch
(psi)ofpressureisrequiredforwaistobliteration,whichusuallyrequiresapproximately120mLofair.
Inflationismaintainedfor60seconds,afterwhich,theballoonisrapidlydeflated.Wethenperformasecondfullinflation
for60secondsandagainnotethepressurerequiredtoobliteratethewaist.Thisisusuallyatleast3psilessthanthe
initialpressure.
Afterthesecondinflation,thedeflatedballoonandguidewireareremovedandthepatientistransferredtotherecovery
area.Thepatientisobservedforfivetosixhourssinceseriouscomplications,suchasperforation,willusuallybecome
clinicallyapparentwithinthistimeperiod[912].Thepatientissubsequentlydischargediftherecoverywasuneventful.
EfficacyofPDApproximately71to90percentofpatientsrespondinitiallytoPD[1316],butmanypatients
subsequentlyrelapse.AlthoughretrospectiveanalysesofPDoutcomessuggestgoodtoexcellentsustainedresponses
inapproximatelytwothirdsofpatients,prospectivestudiessuggestalessfavorableprognosis,withmorethan50
percentofpatientsrelapsingoverafiveyearperiod[17,18].OnethirdtoonehalfofpatientstreatedwithPDwillrequire
atleastoneadditionaldilation,andasubsetofthesepatientswillrequiresurgery.
FiveyearfollowupresultsfromtheEuropeanachalasiastudyidentifiedthefollowingfactorsaspredictorsoffailure
followingpneumaticdilation:age<40years(hazardratio[HR]1.2,95%CI1.3to9.2,p=0.02),preexistingdailychest
pain(HR1.1,95%CI0.9to6.5,p=0.07),andawidthoftheesophagusof<4cmbeforetreatment(HR1.03,95%CI
0.9to8.6,p=0.07)[19].Inaddition,theinvestigatorsalsoidentifiedriskfactorsfortheneedforredilation:age<40
years,esophagealdiameterof4cm,andtypeIII(spasticachalasia)manometricpattern.Esophagealstasisafter
treatmentbycontrastwasnotariskfactor.(See"Clinicalmanifestationsanddiagnosisofachalasia".)
PDmaynotbeequallyeffectiveforrelievingallsymptomsofachalasia.Inonereport,forexample,PDhadlittleeffect
onchestpain,whichispresentinapproximately40to60percentofpatientswithachalasia[20].Inanotherstudy,chest
paincontinuedafterPDinapproximatelyhalfofthepatientswhoinitiallycomplainedofthissymptom[21].(See"Clinical
manifestationsanddiagnosisofachalasia",sectionon'Clinicalfeatures'.)
ShorttomediumtermresultsShorttomediumtermresultshavebeendescribedinbothretrospectiveand
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prospectivestudies.Retrospectivestudiesarelimitedbecausepatientsforwhomtreatmentwasunsuccessfulmayhave
beenlosttofollowuporreferredelsewhere.Inaddition,manypatientswhocontinuetobesymptomaticdonotseek
medicalattention(38percentinoneseries)[17].
Datafromprospectivereportsaregenerallymorereliable.Small(7to29patients)prospectivestudiesofPDusing
Rigiflexballoonsreportedsuccessratesof53to93percent,butmosthadlessthantwoyearsoffollowup[22,23].Two
largerprospectivestudiesofapproximately50patientseachwithlongerfollowuphadlessfavorableresultswitha
remissionrateof26to40percentafterfouryearsormore[17,18].However,aprospectivestudyof77patientshad
betterresults,with70percentofpatientsinremissionafteramedianof5.6yearsoffollowup(range3to10.7years)
[16],asdidtworandomizedtrialsinwhichpatientstreatedwithPDhadremissionratesof84to90percentafter3.5to5
yearsoffollowup(thoughinoneofthetrials,25percentofpatientsrequiredrepeatdilation)[24,25].
PDhasalsobeenstudiedinchildrenwithachalasia.Inaprospectivestudyof24childrenwithachalasiawhowere
followedforamedianofsixyears(rangetwotosevenyears),theoverallsuccessratefollowingPD(uptothree
sessions)was87percent[26].OlderchildrenweremorelikelytorespondtoPDthanyoungerchildren.
Longterm(>10year)resultsAchalasiaisachronicdiseaseandpatientsmayneedtobefollowedformorethan
adecadetojudgethesuccessoftreatment.However,fewstudieshaveaddressedtheoutcomeofPDafter10yearsor
more.Completesymptomresolutionhasbeendescribedinsomepatientsfollowedforaslongas10to25years
[9,27,28].However,dataareconflictingwithrespecttothelikelihoodofmaintenanceoflongtermremission:
Aretrospectivestudyof153patientsfoundthat,afterfiveyears,76percentofpatientsreportedgoodtoexcellent
symptomoutcomes[29].Ofthe35patientswith15ormoreyearsoffollowup,18(51percent)reportedgoodor
excellentoutcomesbytheendoffollowup.Themediantimetosymptomrecurrenceinthisstudywas11years.
Inaretrospectivereportof126patients,115(91percent)improvedafteronetothreesessionsofPD.Themedian
dysphagiafreedurationwas60months[13].
Inaprospectivestudy,54consecutivepatientswerefollowedeverytwoyearsforaperiodof10years,witha
meanfollowupof14years[18].TheremissionrateatfiveyearsafterasinglePDwas40percent.Amongthe21
patientsinremissionatfiveyears,18remainedinremissionforanadditional10years.Thus,patientswhose
symptomswerewellcontrolledforfiveyearswerelikelytocontinuetodowell.
Aretrospectivestudyincluded228patientswhohadaninitialresponsetoPD(definedasbeingsymptomfreeat
12monthsfollowingthefirstPD)[30].Duringfollowup,theestimatedrelapsefreesurvivalrateswere18percent
by2years,41percentby5years,and60percentby10years.Duringfollowup,additionaltreatments(PDs,
myotomy,botulinumtoxininjections)wereperformedin34percentof163patientsforwhomdatawereavailable.
Overall,afterameanfollowupof9.3years,thelongtermsuccessratewas71percent(68percentforthosewho
hadnoadditionaltreatment,79percentforthosewhohadintervalPD,and77percentforthosewhoreceived
otherintervaltreatments).
Thevalueofrepeateddilationsafterthefirstrelapsehasbeendifficulttoevaluateobjectively.Inaprospectivestudyof
54patientscitedabove,only35percentofpatientswhoreceivedthreedilationswereinremissionafterfiveyears[18].
However,aretrospectivestudyof150patientssuggestedthatrepeateddilationsmayhelpimprovelongtermremission
rates[14].Inthatstudy,137patients(91percent)wentintoremission.Amongthe25patientswhoattainedremission
afteronesessionofPDanddidnotundergorepeatPD,67percentwereinremissionatfiveyearsand50percentat10
years.Bycontrast,the112patientswhoreceivedrepeateddilationsasneededforrecurrentsymptoms(an"on
demand"approach)hadremissionratesofover90percentat10years.Apartfromtheretrospectivenatureofthisstudy,
thehigherresponseratemayalsohavebeenduetoanolderpatientpopulation.Studieshaveshownthatolderageis
predictiveofabetterresponsetopneumaticdilation.(See'Predictorsofoutcome'below.)
Theresultsdiscussedabovearefromstudiesinwhich"graded"or"ondemand"dilationswereperformed.Aless
popularregimen(the"progressive"method)practicedinEuropeconsistsofaseriesofprogressivelylargerdilationson
thesameorsuccessivedaysuntil"satisfactory"manometric(eg,loweresophagealsphincterpressure<15mmHg)
and/orradiographiccriteriaaremet.Aretrospectivestudyof209patientswhounderwentPDbythismethodfoundthat
theresponsetoasingleseriesofdilationswas66percentatsixyears.Fortyninepatientswithrecurrentsymptoms
underwentasecondseriesofdilations6.5yearslaterwitha65percentlongtermsuccessrate[21].Thesefigures
appearbetterthanthegradedmethod,butthesetwomethodshaveneverbeendirectlycompared.Atthistime,itisnot
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clearwhichmethodismoreeffectiveorsafer.
PredictorsofoutcomeThetwostrongestpredictorsofoutcomefollowingPDarepostdilationLESpressureand
age[13,18,28,31].Malesexandpatternsofesophagealcontractionseenonmanometrymayalsopredicttheresponse
toPD.
ApostdilationdecreaseinLESpressuretoapproximately10mmHghasbeensuggestedasareasonablegoalofPD
[28].Thevalueofachievingthisgoalwassupportedinaprospectivestudyof54patientswhowerefollowedfor10
years[18].Patientswhoachievedapostdilationpressureoflessthan10mmHgweremuchmorelikelytobein
remissionduringfollowupcomparedwiththosewithhigherLESpressures(100versus23percent).
ThesignificanceofpretreatmentLESpressurewithregardtolongtermresponseisunclear.Manystudieshavefound
thatpretreatmentLESpressuredoesnotinfluenceresponserates[13,32,33].However,onestudyof62patientsfound
thatapretreatmentLESpressure>50mmHgwasassociatedwithapoorresponse[15].
Higherpostdilationdistensibilityoftheesophagogastricjunctionisassociatedwithabettertreatmentresponse
comparedwiththosewithlowerdistensibility[34]
Youngage(<40years)predictsapoorresponsetopneumaticdilation[14,18,31,35,36].Asanexample,inthe
prospectiveseriesof54patientsdiscussedabove,theremissionrateinpatientsolderthan40wasmuchhigherthanin
youngerpatients(58versus16percentatfiveyears)[18].
Sexhasalsobeenimplicatedasapredictorofresponse[13,37].Inaretrospectivestudyof49menand16women,
youngmentreatedwitha3cmballoonrequiredrepeattreatmentmorefrequentlythanyoungwomen(hazardratio1.65)
[37].TheauthorsconcludedthatyoungmenmaybenefitfromaninitialPDwitha3.5cmballoon.
Thepatternofesophagealcontractionsseenonhighresolutionesophagealmanometrymayalsopredicttreatment
response.(See'Influenceofachalasiasubtype'below.)
AnumberofotherfactorshavebeensuggestedtohavearoleinpredictingtheresponsetoPD,butnonehasprovento
beareliablepredictor.Theseincludedurationofsymptoms,theresultsofinitialmanometricstudies,findingsonnuclear
emptyingscintigraphy,thesizeoftheballoondilatorsused,andfindingsonpostdilationbariumesophagrams[5,28,37
39].
PDafterfailedmyotomyPDhasbeenstudiedasatreatmentoptioninpatientswhohavefailedsurgical
myotomyforachalasiaorwhohavehadsymptomaticrecurrencefollowingsurgicalmyotomy.Theresponsetodilationin
patientswhohavefailedmyotomyisnotasgoodastheresponseseeninpatientswhoaretreatmentnave.Inone
report,22of139patientsundergoingPDhadfailedpriorsurgicalmyotomy[40].Asymptomaticresponsewasseenin
50percentofthesepatientscomparedwith74percentofpreviouslyuntreatedpatients.
Asecondstudylookedat27patientswhounderwentpneumaticdilationforsymptomrecurrenceaftersurgicalmyotomy
[41].At12months,24patients(89percent)hadresponded.Relapseratesattwo,three,andfouryearswere16,25,
and42percent,respectively.
ConcernhadbeenraisedthatPDfollowingmyotomymayincreasetheriskofperforation.However,inthesetwo
studies,noneofthepatientswhohadundergonepriorsurgicalmyotomyhadaperforationfollowingPD.
PDafterBTinjectionPDappearstobesafeinpatientswhohavepreviouslyreceivedbotulinumtoxin(BT)
injection,andsomeauthoritieshaveadvocatedcombinationtherapywithPDandBTinjection.
Theefficacyofcombinedtherapywasevaluatedinarandomizedcontrolledtrialinwhich90patientswithachalasia
wereassignedtoBTinjection,PD,orbothBTinjectionandPD[42].Theresponserateattwoyearswassignificantly
higherwithcombinationtherapy(57percentversus14percentwithBTinjectionand36percentwithPD).
AsecondrandomizedtrialcomparingcombinationtherapywithPDalonefoundanonstatisticallysignificantdifference
inremissionratesatoneyear(77versus62percent,p=0.1)[43].Similarly,athirdrandomizedtrialcomparingPDplus
BTwithPDalonefoundanonstatisticallysignificanttrendtowardgreaterfiveyearremissionrateforthecombined
therapy(69versus50percentp=0.07)[44].
PDduringpregnancyInwomenwhoarepregnant,theshorttermefficacyofPDandsurgicalmyotomyare
similar,butPDisassociatedwithamuchlowerriskofcomplications.Asaresult,PDshouldbeattemptedbefore
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surgicalmyotomyduringpregnancy[45].
ComplicationsofPD
EsophagealperforationEsophagealperforationoccursinapproximately3to5percentofpatientsinmost
series,althoughtherangevariesfrom0to21percent[4649].Inoneseriesfromahighvolumecenterthatincluded272
pneumaticdilationsin198patients,only1patienthadaperforation[49].Perforationsusuallyoccurduringthefirst
dilationsession,tendtobesmall,andaretypicallylocatedabovethecardiaalongtheleftsideoftheesophagus,where
thereisananatomicareaofweakness.TheEuropeanachalasiatrialinitiallystarteddilationswiththe35mmballoon.
Amongtheinitial13patients,theperforationratewas31percent,promptingtheinvestigatorstoamendtheprotocolto
startdilationsusingthe30mmdilator[24].
Patientswithesophagealperforationusuallypresentwithinafewhoursafterdilation.Findingsthatraiseconcernabout
perforationincludetachycardiaandchestpainfollowingtheprocedurethatlastsformorethanfourhours[9].Some
authoritiesrecommendaroutinepostdilationesophagramhowever,manyexpertsdonotfollowthisapproach.Instead,
anesophagramisonlyorderedifthepatientexperiencessymptomsdiscussedabove.
Severalstudieshaveevaluatedriskfactorsforperforation.Theseincludehighamplitudeesophagealcontractionson
manometrybeforetheprocedure[50]andinstabilityoftheballoonduringinsufflation[51].Neitherofthesepredictors
hasbeenvalidated.
TheoptimalmanagementofesophagealperforationfollowingPDhasnotbeenestablished.Perforationscanoftenbe
managedwithconservativetreatmentsuchasantibioticsandparenteralnutrition[48,5153].Theroleofendoscopic
therapyintreatmentofesophagealperforationsisyettobedetermined.Esophagealstentingandclosurewithanover
thescopecliphavebeendescribed[54,55].However,itisdifficulttopredicthowagivenpatientwillrespond.Most
patientsdowellaftersurgicalrepair.Thus,manyauthoritiesadvocatesurgeryinlowriskpatientsassoonasthe
diagnosisisconfirmed,regardlessofthesizeoftheperforation.(See"Complicationsofendoscopicesophagealstricture
dilation".)
Clinicaldeteriorationorthepresenceoffreeflowingbariumintothemediastinumrequiresimmediatethoracotomyand
repair.Videothoracoscopicandendoscopicrepairhavealsobeenperformedinthissetting[56,57].(See"Complications
ofendoscopicesophagealstricturedilation".)
OtherOthercomplicationsofPDincludebleeding,intramuralhematomas,esophagealmucosaltears,and
diverticulaatthegastriccardia[9,14,51].Postproceduralfeverusuallyresolvesspontaneouslywithoutantibiotics.
Approximately15percentofpatientscomplainofseverepostproceduralchestpainthatisselflimited.Chestpain
followingtheprocedurethatlastsformorethanfourhoursissuggestiveofpossibleesophagealperforation[9,14].
DespitePDinduceddisruptionoftheLES,whichistheprincipalbarriertogastroesophagealreflux,gastroesophageal
refluxdiseaseisuncommonafterpneumaticdilation.Areviewof1902patientsfoundanoverallincidenceof2percent
[46].
BOTULINUMTOXININJECTIONBotulinumneurotoxintypeAisapotentinhibitorofthereleaseofacetylcholine
fromnerveendingsandhasbeenusedsuccessfullytotreatcertainspasticdisordersofskeletalmusclesuchas
blepharospasmandtorticollis.Itisalsousedinthetreatmentofspasticdisordersofsmoothmuscle,includingachalasia.
Theideaofusingbotulinumtoxin(BT)inachalasiastemsfromanunderstandingofthepathophysiologyofachalasia.
Achalasiaiscausedbytheselectivelossofinhibitoryneurons,whichresultsinunopposedexcitationofthelower
esophagealsphincter(LES)bycholinergicneurons[5860].BTcanreducetheLESpressurebyselectivelyblockingthe
releaseofacetylcholinefrompresynapticcholinergicnerveterminalsinthemyentericplexus,therebyrestoringthe
balancebetweeninhibitoryandexcitatoryneurotransmitters[61].(See"Pathophysiologyandetiologyofachalasia".)
Inadditiontobeingusedasatreatmentforachalasia,aresponsetoBTinjectionhasbeenusedtosupportthe
diagnosisofachalasiainpatientsinwhomthediagnosisisuncertainbaseduponmanometry[62].(See"Clinical
manifestationsanddiagnosisofachalasia".)
TechniqueforBTinjectionBTisinjectedduringaroutineupperendoscopyusingastandardsclerotherapyneedle
thatispassedthroughtheaccessorychanneloftheendoscope.Aswithpneumaticdilation,athoroughendoscopic
examinationisperformed,withparticularattentiongiventothecardia,wheremalignancycansimulateachalasia(called
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pseudoachalasia).(See"Clinicalmanifestationsanddiagnosisofachalasia".)
ThemostcommonmethodfordeliveringBTinvolvesvisualestimationofthelocationofLESandinjectionof1mL
aliquots(20to25unitsBT/mL)intoeachoffourquadrantsapproximately1cmabovetheZline.TheZlineisthe
squamocolumnarjunction,whichcorrespondstothegastroesophagealjunctionintheabsenceofBarrett'sesophagus.
TheuseofendoscopicultrasoundtoidentifytheLEShasbeensuggestedasanaidforguidinginjection,butthereisno
evidencethatthisimprovesefficacy.ManometricallyguidedBTinjectionbymeansofadoublechannelendoscopehas
alsobeendescribed[63].ThismaytheoreticallypermitmoreprecisetargetingoftheLES.However,absoluteprecision
isprobablynotnecessarysinceBTdiffusesforalimiteddistanceintissue[64].
Patientsaredischargedfromtheendoscopyunitafterroutinepostsedationrequirementshavebeenmetandare
allowedtoeatlaterintheday.Animprovementinsymptomsisusuallyobservedafter24hours,althoughpeakeffects
occurlaterinsomepatients.
SeveralformulationsofBTareavailable.AcomparisonbetweenBotox100unitsandDysport250unitsshowedsimilar
efficacyatuptosixmonthsoffollowup[65].
EfficacyofBTinjectionInitialresponseratestoBTinjectionrangefrom70to90percent,butmanypatientsrelapse
withinseveralmonths[6676].Thedurabilityoftheresponsemaybeimprovedbymultipletreatmentsessions,asis
seenwiththeuseofBTforotherindications(eg,dystonia).(See"Treatmentofdystonia",sectionon'Botulinumtoxin
injections'.)
Thevastmajorityofstudiesalsoreportanassociatedimprovementinobjectiveparameters,withthemostcommonly
reportedbeingareductioninrestingLESpressure,generallyaveragingaround40percent[22,66,70,77,78].Although
lesscommonlyreported,radiographicorscintigraphicmeasuresalsoimprove[66,79,80].
Shorttermresults(<5years)Inasystematicreview,relapseratesofgreaterthan50percentwereseenin
manystudieswithin6to12monthsfollowingasingletreatmentsession[81].Betterresultswereobtainedinstudiesthat
usedmultipletreatmentsessions,withclinicalbenefitseenin60to85percentofpatientsattwoyears.
Thefollowingstudiesillustratetherangeoffindings:
Inastudyof60patientswithidiopathicachalasiawhoweretreatedwithBTinjection,70percenthadsignificant
symptomimprovementatonemonthfollowingasingletreatment[69].Amongthe33patientswithoneyearfollow
up,36percentcontinuedtohaveagoodorexcellentresponse,whereas39percenthadundergoneasubsequent
treatment(repeatinjection,pneumaticdilation,ormyotomy).Aresponsewasseeninsixofsevenpatientswho
receivedasecondinjectionofBT.
ArandomizedtrialsuggestedthatthedoseofBTandthedosingschedulemaypredictaresponsetotreatment
[76].Thetrialincluded118patientswhowererandomlyassignedtoreceiveoneofthreedosesofBT(50,100,or
200units).Patientsassignedtothe100unitdosewerereinjectedwithanadditional100unitsafter30days.At12
months,patientswhoreceivedthetwodosescheduleof100unitsweresignificantlymorelikelytobeinremission
(80versusapproximately55percentfortheothertwogroups).Onmultivariateanalysis,independentpredictorsof
responseincludedvigorousachalasia(oddsratio3.3)andthetwodoseregimen(oddsratio3.2).(See"Clinical
manifestationsanddiagnosisofachalasia".)
Anecdotally,itappearsthattheresponsetoBTinjectionsisoftenlessrobustwithsubsequentinjections.Antibodiesto
BThavebeendetectedinpatientswhoweresecondarytreatmentfailuresforvariousindications.Inonestudy,
antibodieswerefoundin45percentofpatientswhoweresecondarynonresponders[82].Despiteconcernsabout
neutralizingantibodies,onegroupwasablemaintainclinicalremissionwithrepeatBTinjectionsevery10monthsin43
of57patients(75percent)forfouryears[73].
PredictorsofresponseThemainpredictorsofafavorableoutcomeareolderageandthepresenceofvigorous
achalasia.Thiswasillustratedinastudyof31patientswhoweretreatedwithBTandwerefollowedprospectivelyfora
medianof2.4years[75].Aresponsebeyondthreemonthswassignificantlymorelikelyinpatientsolderthanage50(82
versus43percent)andinpatientswithvigorouscomparedwithclassicachalasia(100versus52percent).(See"Clinical
manifestationsanddiagnosisofachalasia".)
FactorsthatarenotreliablepredictorsofaresponsetoBTinjectionincludegender,durationofillness,meannumberof
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previousdilations,initialcharacteristicsonstandardmanometry(exceptforvigorousachalasia),andinitialsymptom
scores[67,69,75].
Thepatternofesophagealcontractionsseenonhighresolutionesophagealmanometrymayalsopredicttreatment
response(See'Influenceofachalasiasubtype'below.)
ComplicationsofBTThelowdoseofBTusedfortreatmentofachalasiahasvirtuallynoriskofcausinggeneralized
neuromuscularblockade.(See"Botulism".)
Reportedcomplicationsincludepostproceduraltransientchestpain(25percent)andheartburn(5percent).Esophageal
wallinjuryandparaesophagealtissueinflammationarerare[83].Otherreportedcomplicationshaveprimarilybeen
describedincasereports:
NonfatalmediastinitisfollowingBTinjection[84,85]
Esophagealmucosalulcerationandsinustractformation[86]
Pneumothoraxrequiringdrainage[87]
LongtermexperiencewithBTinjectioninthegastrointestinaltractislimited,butitappearssafe.Supportforthis
conclusioncomesfromtheobservationthatnosignificantmucosalorsubmucosalchangeswereseenduring
endoscopicultrasoundfollowingtreatmentinastudyof18patients[88].
COMPARATIVESTUDIESAnumberofstudiesandmetaanalyseshavecomparedtheefficacyofpneumaticdilation
(PD),botulinumtoxininjection(BT),andsurgicalmyotomy[24,70,77,79,8993].Ametaanalysisfrom2009compared
varioustreatmentsforachalasiain17randomizedtrialswith761patients[89].Withrespecttolongertermsymptom
control,surgicalmyotomywassuperiortobothPDandBTinjection,andPDwassuperiortoBTinjection.Theauthors
notedthatwhileBTinjectionistheleasteffectivetreatment,itisalsotheleastexpensive,lowrisk,andeasilyperformed.
PDversusBTinjectionFivetrialsinthemetaanalysiscomparedPDwithBTinjectioninpatientsfollowedforat
least12months[89].PDwasassociatedwithasignificantlyhigherremissionratethanBTinjection(66versus38
percent),asignificantlylowerrelapserate(17versus50percent),andalongertimetorelapse.
BTinjectionorPDversuslaparoscopicmyotomyTwotrialsinthemetaanalysiscomparedBTinjectionwith
laparoscopicmyotomy[89].Duringthefirstsixmonthsaftertreatment,therewasnodifferencebetweenthegroupswith
regardtosymptomrecurrence.However,afteroneyear,laparoscopicmyotomywasassociatedwithasignificantly
higherrateofpersistentefficacy(83versus65percent).PatientstreatedwithBThadmorefrequentrelapsesanda
shortertimetorelapse.
TwotrialswithatleastoneyearoffollowupinthemetaanalysiscomparedPDwithlaparoscopicmyotomy[89].
LaparoscopicmyotomyhadasignificantlyhigherremissionratethanPD(95versus78percent)andasignificantlylower
relapserate(5versus36percent).[94]
AmorerecentmetaanalysisthatcomparedgradedPDwithlaparoscopicsurgicalmyotomyincludedthreerandomized
trialswith346patientspublishedbetween2007and2011[94].Afteruptooneyearoffollowup,surgicalmyotomywas
moreeffectivethanPD(86versus77percent)andwasassociatedwithfeweradverseevents(0.6versus5percent).
However,therewerenodifferencesinpostprocedureloweresophagealsphincterpressure,rateofgastroesophageal
reflux,andqualityoflife.
Thelargesttrialinthemetaanalysisincluded201patientswhowereassignedtoeitherpneumaticdilationor
laparoscopicHellermyotomy[24].Patientswerefollowedforameanof43months.Inanintentiontotreatanalysis,
therewasnosignificantdifferencebetweenthegroupswithregardtotherapeuticsuccess.Atoneyearfollowup,the
successrateforpneumaticdilationwas90percent,andforlaparoscopicmyotomyitwas93percent.Aftertwoyears,
thesuccessrateswere86and90percent,respectively.Inaddition,aftertwoyearsoffollowuptherewasnosignificant
differencebetweenthegroupswithregardtoloweresophagealsphincterpressure,esophagealemptying,qualityoflife,
oresophagealacidexposure.Subgroupanalysesfoundthatpatientsyoungerthan40yearswereatincreasedriskof
requiringredilationafterpneumaticdilation.
However,anumberoffactorsshouldbeconsideredwheninterpretingtheresultsofthistrial[95].First,theprotocolfor
pneumaticdilationusedinthistrialwasrigorous,involvinguptothreesetsofballoondilationsoveraperiodof>2years,
withindividualsetsincludingasmanyasthreeseparatedilationsessions.Eachdilationsessiongenerallymeansaday
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lostfromwork.Bycontrast,theinconvenienceofHellermyotomyisprimarily"upfront,"involvingtheoperationitselfand
thepostoperativerecovery.Furthermore,esophagealperforationsoccurredinapproximately4percentofpatients
treatedwiththisrigorouspneumaticdilationprotocol,requiringhospitalization,andinsomecases,emergencysurgical
repairwithanopen(ratherthanlaparoscopic)procedure.Inaddition,theballoondilationsandoperationsinthistrial
wereperformedbyveryexperiencedgastroenterologistsandsurgeons.Itisnotclearthattheirexcellentresultscanbe
reproducedincommunitypractices.Finally,themeanfollowupforthistrialwasonly43months,andthelongterm
outcomesremaintobedetermined.
Inalongertermfollowupstudyof201patientsintheEuropeanachalasiatrialthatcomparedlaparoscopicmyotomyto
pneumaticdilation,thefiveyearsuccessrateshowedatrendinfavorofmyotomyintheperprotocolanalysis(91
versus82percentp=0.08)[19].PDresultedinanoverallrateofperforationof5percent(2.1percentperprocedure).
Furthermore,25percentofpatientstreatedwithPDrequiredredilationoverthisperiod.Thirtyfourpercentofpatientsin
themyotomygroupand12percentofpatientsinthePDgrouphadacidrefluxbasedonfollowuppHtesting(p=0.14).
INFLUENCEOFACHALASIASUBTYPEUsinghighresolutionmanometry,achalasiahasbeensubdividedinto
subtypesthatmayinfluencethetreatmentresponse[96].Thesubtypesaredefinedbythepatternofcontractilityofthe
esophagealbody,whichmanometricallyappearsasesophagealpressurization.
TypeI(classicachalasia)patientsarethosewithclassicachalasiawhodisplaynopressuregenerationinthe
esophagus.TypeII(withpressurization)patientshaveatleasttwoswallowsthatareassociatedwithpanesophageal
pressurization.TypeIII(spasticachalasia)patientsmayalsohavesignificantintraesophagealpressure,butintypeIII
patientsitisduetolumenobliteratingcontractionsinthedistalesophagus,causingafunctionalobstruction(patients
withsocalledvigorousachalasiafallintothiscategory).
Inonestudy,comparedwithtypeIandtypeIIIpatients,typeIIpatientsweremuchmorelikelytorespondtoanykindof
therapy(oddsratio[OR]11.2),whereaspatientswithtypeIIIweremuchlesslikelytorespondtoanytherapy(OR0.24)
[96].Severeesophagealdilationalsosignificantlyreducedtheresponsetotreatment(OR0.2comparedwithno
dilation).TheprospectiveEuropeanachalasiastudyhasofferedmoreinsightintothis[19].Althoughtheinvestigators
didnotusehighresolutionmanometry,theywereneverthelessabletoclassifypatientsintothesamethreesubtypes.
Posthocanalysisofperprotocoldatarevealedthat,comparedwithmyotomy,pneumaticdilationhadahighersuccess
ratefortypeII(100versus88percentp=0.003)butapossiblylowersuccessratefortypeIII(57versus86percentp
=0.2).ThetreatmentswerecomparableintypeIpatients(82versus75percentp=0.6).
IMPACTOFENDOSCOPICTREATMENTONSUBSEQUENTMYOTOMYInanimalmodels,bothpneumaticdilation
(PD)andbotulinumtoxin(BT)injectioninduceacuteandchronicesophagealinflammation,withareasofincreased
fibrosisinthemuscle[97].ThishasledtoconcernregardingtheeffectsofpriorPDorBTtreatmentonthesuccessof
subsequentsurgery.
Theavailabledatainhumansareconflicting.Somestudiessuggestthatpriorendoscopictherapydecreasesthe
efficacyofsubsequentmyotomyandmayincreasecomplicationrates[98101].However,becausethestudieswerenot
randomized,itisnotpossibletodeterminewhetherthelowerefficacywasduetoatrueeffectortotheinclusionof
patientsinthemyotomyfollowingendoscopictreatmentwhowererefractorytoanyformoftreatment.
Othernonrandomizedstudieshaveshownsimilarsurgicaloutcomeswithregardtoefficacyand/orcomplicationsfor
patientswhohadpreviouslyreceivedendoscopictherapycomparedwithpatientsundergoinglaparoscopicmyotomyor
peroralendoscopicmyotomyasinitialtherapy[102106].(See"Overviewofthetreatmentofachalasia",sectionon
'Peroralendoscopicmyotomy'.)
APPROACHTOTHEPATIENTEndoscopictherapywithpneumaticdilation(PD)orbotulinumtoxin(BT)injectionfor
thetreatmentofachalasiahastheadvantageofbeinglessinvasivecomparedwithsurgery.Inaddition,BTinjection
doesnotrequirespecializedtrainingandcanbeeasilyperformedduringroutineendoscopy.Priorstudiessuggestthat
symptomrecurrencewithbothofthesetechniquesiscommon,anditisnotclearifpriorendoscopictherapyadversely
affectsfuturesurgicalmyotomy.However,morerecentdatasuggestthatinexperiencedhands,PDmayhavesuccess
ratessimilartosurgicalmyotomy.(See'EfficacyofPD'aboveand'EfficacyofBTinjection'aboveand'Impactof
endoscopictreatmentonsubsequentmyotomy'above.)
Surgeryhastheadvantageofofferingamorepermanentsolutionformanagingthesymptomsofachalasia,withthe
disadvantagesofbeingamoreinvasiveprocedureandofputtingpatientsatincreasedriskforrefluxandothersurgical
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complications.(See'Comparativestudies'aboveand'Impactofendoscopictreatmentonsubsequentmyotomy'above
and"Overviewofthetreatmentofachalasia".)
Theapproachtochoosingamongthevarioustreatmentsforagivenpatientisdiscussedelsewhere.(See"Overviewof
thetreatmentofachalasia",sectionon'Choiceoftreatment'.)
FOLLOWUPBecausethereisnocureforachalasia,regularfollowupisrequired.Weevaluatepatientswithinone
monthfollowingendoscopictherapy.Patientswhoremainsymptomaticareofferedrepeatdilation.
Patientsareusuallyreferredtosurgeryifthreeconsecutivedilatationsdonotprovidesymptomresolution.Consideration
forsurgicalreferralshouldalsobemadeinpatientswithearlysymptomrecurrencefollowingpneumaticdilation(PD).
(See'EfficacyofPD'above.)
Thefollowupofpatientstreatedwithbotulinumtoxin(BT)dependsupontheindicationforBT.Asnotedabove,we
typicallyreserveBTinjectionsforpatientswhoare(1)notsurgicalorPDcandidates,(2)thosereluctanttoundergo
surgeryorPD,or(3)patientswithatypicalpresentationsofachalasiatohelpguidetherapy.Inthefirstscenario,we
monitorpatientscloselyforrecurrenceofsymptomsandofferrepeatBTinjectionsuntiltheybecomesurgicalcandidates
oruntilBTlosesefficacyiftheyremainpoorsurgicalcandidates.Inthesecondscenario,wemonitorthepatientclosely
atoneandfourmonthsaftertherapy.IfthereisnoresponseaftertwoBTinjections,weencourageproceedingtoeither
PDorsurgery.Inthethirdscenario,patientswhorespondtoBTinjectionarereferredforsurgeryorPDifthepatientis
reluctanttohavesurgery.
Patientswhodowellwiththeabovetherapies,especiallyBTinjection,requireclosefollowuptomonitorforsymptom
recurrence.BTinjectionpatientsarefollowedonemonthaftertherapyandsubsequentlyeverythreemonthsuntil
symptomrecurrence.PDpatientsarefollowedupat1,3,6,and12monthsaftertherapyandeveryfourtosixmonths
thereafter.Inadditiontorecurrenceofdysphagia,particularattentionispaidtothedevelopmentofrefluxsymptomsand
protonpumpinhibitortherapyisoftenprescribedempirically.
SomeexpertssuggestthatpatientstreatedwithBTorPDbeassessedradiographically,withthegoalofrecognizing
andtreatingearlyrecurrenceofobstruction,butthispracticeisdifficulttojustifyifthepatientistrulyasymptomatic.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereading
level,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesare
bestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatient
educationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10thto12thgrade
readinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicsto
yourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon"patientinfo"and
thekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Achalasia(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Achalasia(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Thetherapeuticoptionsforachalasiaincludepneumaticdilation(PD),botulinumtoxin(BT)injection,peroral
endoscopicmyotomy,andsurgicalmyotomy.(See"Overviewofthetreatmentofachalasia".)
EndoscopictherapywithPDorBTinjectionforthetreatmentofachalasiahastheadvantageofbeinglessinvasive
comparedwithsurgery.WhilesymptomrecurrenceiscommonwithBT,inexperiencedhands,PDmayhave
successratessimilartosurgicalmyotomy,butmayrequirerepeatdilationsinasignificantnumberofpatients(25
to50percent)alongwithanontrivialriskofperforation.(See'EfficacyofBTinjection'aboveand'EfficacyofPD'
above.)
Initialresponseratesof70to90percentareseenwithBTinjection,butmanypatientsrelapsewithinseveral
months.Betterresultshavebeenseeninstudiesthatusedmultipletreatmentsessions,withclinicalbenefit
seenin60to85percentofpatientsattwoyears.(See'EfficacyofBTinjection'above.)
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ThemostcommoncomplicationsofBTinjectionarepostproceduraltransientchestpain(25percent)and
heartburn(5percent).(See'ComplicationsofBT'above.)
Approximately71to90percentofpatientsrespondinitiallytoPD,butmanypatientssubsequentlyrelapse.
OnethirdtoonehalfofpatientstreatedwithPDwillrequireatleastoneadditionaldilation,andasubsetof
thesepatientswillrequiresurgery.(See'EfficacyofPD'above.)
ComplicationsofPDincludeesophagealperforation,developmentofbleeding,intramuralhematomas,
esophagealmucosaltears,diverticulaofthegastriccardia,andgastroesophagealreflux.(See'Complications
ofPD'above.)
Surgeryhastheadvantageofofferingamorepermanentsolutionformanagingthesymptomsofachalasia,butis
moreinvasivethanendoscopictherapyandputspatientsatincreasedriskforrefluxandothersurgical
complications.(See"Overviewofthetreatmentofachalasia",sectionon'Surgicalmyotomy'.)
Theapproachtochoosingamongthedifferenttreatmentoptionsisdiscussedindetailelsewhere.(See"Overview
ofthetreatmentofachalasia",sectionon'Choiceoftreatment'.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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