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DoesAppendicitisHavetoBeTreatedWithSurgery?
LaraC.Pullen,PhD June18,2015
Antibiotictreatmentofpatientswithcomputedtomography(CT)proven,uncomplicatedappendicitismaybeas
effectiveasappendectomy,accordingtoanewstudy.Themajorityofpatientsrandomlyassignedtoreceiveantibiotic
treatmentdidnotrequireanappendectomyduring1yearoffollowup,andthosewhodidreceiveanappendectomy
didnothavesignificantcomplications.Despitethis,whenthetwotreatmentswerecomparedinanoninferioritytrial,
theinvestigatorsfoundthatantibiotictreatmentdidnotmeettheprespecifiedcriterionfornoninferiority.

PaulinaSalminen,MD,PhD,fromtheTurkuUniversityHospitalinFinland,andcolleaguespublishedtheresultsof
theAppendicitisAcuta(APPAC)multicentertrialintheJune16issueofJAMA.

Theresearchersrandomlyassignedpatientstoeitherasurgerygrouptoreceiveanappendectomyperformedusing
thestandardopentechniqueortoanantibioticgrouptoreceivebroadspectrumantibiotics(ertapenem,levofloxin,
andmetronidazole).Theinvestigatorsnotethatmanypatientselectedtoreceivesurgery,andtheinvestigatorshad
difficultyrecruitingpatientswillingtobeassignedtotheantibioticgroup.Ofthosewhounderwentappendectomy,15
(5.5%)patientsunderwentlaparoscopicappendectomy.

"Toourknowledge,theAPPACtrialisthelargestmulticenter,openlabel,noninferiority[randomizedcontrolledtrial]
ofantibiotictreatmentforappendicitisconductedtodate.Whenthetrialwasdesigned,weassumedthattherewould
besufficientbenefitsfromavoidingsurgeryandthata24%failurerateintheantibioticgroupwouldbeacceptable.
Instead,wefoundafailurerateof27.3%(95%confidenceinterval,22.0%33.2%)andwerenotabletoestablishthe
noninferiorityofantibiotictreatmentforappendicitis,"theauthorswrite.

Theinvestigatorsdidfindthat72.7%(95%confidenceinterval,66.8%78.0%)ofpatientswithuncomplicatedacute
appendicitisrecoveredafterreceivingonlyantibiotictherapy.Eightpatientsrandomlyassignedtotheantibioticgroup
weremistakenlyidentifiedashavingcomplicatedappendicitisandreceivedanappendectomythatmaynothavebeen
required.Theseeightpatientsmayhaveconfoundedtheresultsofthestudy.

Patientsintheantibioticgrouphadalongermedianlengthofhospitalstaythanpatientsinthesurgerygroup.The
investigatorsnote,however,thattheminimallengthofhospitalstayforpatientsintheantibioticgroupwasspecified
inthetreatmentprotocolandcouldlikelybeshortenedinthefuture.

Previoustrialshaveaddressedtheroleofantibiotictherapyasatreatmentforappendicitis.Thesetrialswerelimited,
however,bytheirrelianceonclinicaldiagnosisofacuteappendicitis,durationofantibiotictreatment,andpoor
determinationoftheprimaryendpoint.Notsurprisingly,theresultsfromtheseprevioustrialshavebeenmixed.

Appendicitismaypresentasuncomplicatedandacute,oritmaybecomplicatedbyaperforation,intraabdominal
abscess,and/orappendicoliths.Apreviousstudy,forexample,foundthatpatientswithappendicolithsweremore
likelytohavecomplicatedacuteappendicitisandtofailantibiotictreatment.

ThecurrentstudyattemptedtoavoidthisproblembyenrollingonlypatientswithaCTconfirmeddiagnosisof
uncomplicatedacuteappendicitis.Theyexcluded,forexample,patientswithappendicoliths.

CTimagingmadesuchpatientselectionfeasible.TheauthorsexplainedthebenefitsofCTimaging:"Anotherfeature
ofourstudywasthelownegativeappendectomyrateattributabletoCTimaging.UseofCTalsoenabledusto
identifyuncomplicatedacuteappendicitisthatwassuccessfullytreatedwithantibioticsaloneinthemajorityof
patientsenrolledinourstudy,"theauthorswrite.

Anotherstrengthofthecurrentstudywastheinvestigators'choiceofantibiotics.Theyemphasizedintheirarticlethat

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successfulantibiotictreatmentofappendicitisrequirestheselectionofanantibioticthatprovidesbroadspectrum
coverageofthemanypathogensthatmightcauseappendicitis.

TheauthorssuggestthatpatientsdiagnosedwithCTprovenuncomplicatedacuteappendicitisbegiventhe
opportunitytomakeaninformeddecisionbetweenantibiotictreatmentandappendectomy.

EdwardLivingston,MD,fromNorthwesternUniversityFeinbergSchoolofMedicineinChicago,Illinois,andCorrine
Vons,MD,PhD,fromJohnsHopkinsSchoolofMedicineinBaltimore,Maryland,agreeandpennedan
accompanyingeditorialtothateffect.Theywritethat,"[t]hetimehascometoconsiderabandoningroutine
appendectomyforpatientswithuncomplicatedappendicitis.Theoperationservedpatientswellformorethan100
years.WithdevelopmentofmoreprecisediagnosticcapabilitieslikeCTandeffectivebroadspectrumantibiotics,
appendectomymaybeunnecessaryforuncomplicatedappendicitis,whichnowoccursinthemajorityofacute
appendicitiscases."

MonicaE.Lopez,MD,asurgeonatBaylorCollegeofMedicineinHouston,Texas,whowasnotinvolvedinthestudy,
remains,however,unconvinced:"Overall,Idon'tthinkthefindingsofthestudywarrantachangeinpractice,"she
explainedinanemailtoMedscapeMedicalNews.

DrSalminenreportedreceivingpersonalfeesforlecturesfromMerck andRoche.Theotherauthors,theeditorialists,
andDrLopezhavedisclosednorelevantfinancialrelationships.

JAMA.2015313:23402348.Articleabstract,Editorialextract

MedscapeMedicalNews2015WebMD,LLC

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Citethisarticle:DoesAppendicitisHavetoBeTreatedWithSurgery?Medscape.Jun18,2015.

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