2017525 Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagementUpToDate

OfficialreprintfromUpToDate
www.uptodate.com2017UpToDate

Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagement

Authors: MustafaAArain,MD,MartinLFreeman,MD
SectionEditor: DouglasAHowell,MD,FASGE,FACG
DeputyEditor: ShilpaGrover,MD,MPH,AGAF

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2017.|Thistopiclastupdated:Mar13,2015.

INTRODUCTIONCholedocholithiasisreferstothepresenceofgallstoneswithinthecommonbileduct.
AccordingtotheNationalHealthandNutritionExaminationSurvey(NHANESIII),over20millionAmericansare
estimatedtohavegallbladderdisease(definedasthepresenceofgallstonesontransabdominalultrasoundora
historyofcholecystectomy)[1].Amongthosewithgallbladderdisease,theexactincidenceandprevalenceof
choledocholithiasisarenotknown,butithasbeenestimatedthat5to20percentofpatientshave
choledocholithiasisatthetimeofcholecystectomy,withtheincidenceincreasingwithage[28].

InWesterncountries,mostcasesofcholedocholithiasisaresecondarytothepassageofgallstonesfromthe
gallbladderintothecommonbileduct.Primarycholedocholithiasis(ie,formationofstoneswithinthecommonbile
duct)islesscommon.Primarycholedocholithiasistypicallyoccursinthesettingofbilestasis(eg,patientswith
cysticfibrosis),resultinginahigherpropensityforintraductalstoneformation.Olderadultswithlargebileducts
andperiampullarydiverticularareatelevatedriskfortheformationofprimarybileductstones.Patientswith
recurrentorpersistentinfectioninvolvingthebiliarysystemarealsoatrisk,aphenomenonseenmostcommonly
inpopulationsfromEastAsia.(See"Recurrentpyogeniccholangitis".)

Thecausesofprimarycholedocholithiasisoftenaffectthebiliarytractdiffusely,sopatientsmayhaveboth
extrahepaticandintrahepaticbiliarystones.Intrahepaticstonesmaybecomplicatedbyrecurrentpyogenic
cholangitis.

Thistopicwillreviewtheclinicalmanifestationsanddiagnosisofcholedocholithiasis.Thetreatmentof
choledocholithiasis,aswellastheepidemiologyandthegeneralmanagementofpatientswithgallstones,are
discussedseparately:

(See"Endoscopicmanagementofbileductstones:Standardtechniquesandmechanicallithotripsy".)
(See"Epidemiologyofandriskfactorsforgallstones".)
(See"Approachtothepatientwithincidentalgallstones".)
(See"Uncomplicatedgallstonediseaseinadults".)
(See"Patientselectionforthenonsurgicaltreatmentofgallstonedisease".)
(See"Dissolutiontherapyforthetreatmentofgallstones".)

CLINICALMANIFESTATIONSPatientswithcholedocholithiasistypicallypresentwithbiliarytypepainand
laboratorytestingthatrevealsacholestaticpatternoflivertestabnormalities(ie,elevatedbilirubinandalkaline
phosphatase).Patientswithuncomplicatedcholedocholithiasisaretypicallyafebrileandhaveanormalcomplete
bloodcountandpancreaticenzymelevels.Occasionally,patientsareasymptomatic.Insuchpatients,the
diagnosismaybesuspectedbecauseofabnormalliverbloodtests,abnormalitiesseenonimagingstudies
obtainedforunrelatedreasons,orwhenanintraoperativecholangiogramobtainedduringcholecystectomy

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suggeststhepresenceofacommonbileductstone.(See"Approachtothepatientwithabnormalliver
biochemicalandfunctiontests",sectionon'Patternsoflivertestabnormalities'.)

Complicationsofcholedocholithiasisincludeacutepancreatitisandacutecholangitis.Patientswithacute
pancreatitistypicallyhaveelevatedserumpancreaticenzymelevels,andpatientswithacutecholangitisareoften
febrilewithaleukocytosis.Rarely,patientswithlongstandingbiliaryobstructiondevelopsecondarybiliary
cirrhosis.(See'Complicatedcholedocholithiasis'below.)

Uncomplicatedcholedocholithiasis

SymptomsMostpatientswithcholedocholithiasisaresymptomatic,althoughoccasionalpatientsare
asymptomatic.Symptomsassociatedwithcholedocholithiasisincluderightupperquadrantorepigastricpain,
nausea,andvomiting.Thepainisoftenmoreprolongedthanisseenwithtypicalbiliarycolic(whichtypically
resolveswithinsixhours).(See"Uncomplicatedgallstonediseaseinadults",sectionon'Biliarycolic'.)

Thepainfromcholedocholithiasisresolveswhenthestoneeitherpassesspontaneouslyorisremoved.Some
patientshaveintermittentpainduetotransientblockageofthecommonbileduct.Transientblockageoccurs
whenthereisretentionandfloatingofstonesordebriswithinthebileduct,aphenomenonreferredtoasa"ball
valve"effect.

PhysicalexaminationOnphysicalexamination,patientswithcholedocholithiasisoftenhaverightupper
quadrantorepigastrictenderness.Patientsmayalsoappearjaundiced.Courvoisier'ssign(apalpablegallbladder
onphysicalexamination)maybeseenwhengallbladderdilationdevelopsbecauseofanobstructionofthe
commonbileduct.Itismoreoftenassociatedwithmalignantcommonbileductobstruction,buthasbeen
reportedwithcholedocholithiasis[9].

LaboratorytestsSerumalanineaminotransferase(ALT)andaspartateaminotransferase(AST)
concentrationsaretypicallyelevatedearlyinthecourseofbiliaryobstruction.Later,livertestsaretypically
elevatedinacholestaticpattern,withincreasesinserumbilirubin,alkalinephosphatase,andgammaglutamyl
transpeptidase(GGT)exceedingtheelevationsinserumALTandAST.(See"Approachtothepatientwith
abnormalliverbiochemicalandfunctiontests",sectionon'Patternsoflivertestabnormalities'.)

Studieshaveattemptedtoestimatethepredictivevalueofliverchemistrytestsforcholedocholithiasis[8,1012]:

Ametaanalysisof22studiesevaluatedthepredictiveroleofmultipleexaminationfindingsandtestsusedin
thediagnosisofcholedocholithiasis,includingserumbilirubinandalkalinephosphatase[10].Anelevationin
serumbilirubinhadasensitivityof69percentandaspecificityof88percentfordiagnosingacommonbile
ductstone.Forelevationsinserumalkalinephosphatase,thevalueswere57and86percent,respectively.

Astudyof1002patientswhounderwentlaparoscopiccholecystectomyforcholelithiasisevaluatedfiveliver
relatedbiochemicaltestsforpredictingcholedocholithiasis:serumGGT,alkalinephosphatase,totalbilirubin,
ALT,andAST[11].Thesensitivitiesrangedfrom64percentforASTto84percentforGGT,andthe
specificitiesrangedfrom68percentforALTto88percentforbilirubin.ElevatedserumGGT,alkaline
phosphatase,andbilirubinlevelswereindependentpredictorsofacommonbileductstoneonmultivariable
analysis(oddsratiosof3.2,2.0,and1.4,respectively).

Sincelivertestsmaybeelevatedduetoawidevarietyofetiologies,thepositivepredictivevalueofelevatedliver
testsispoor.Ontheotherhand,thenegativepredictivevalueofnormallivertestsishigh.Thus,normallivertests
playagreaterroleinexcludingcholedocholithiasisthanelevatedlivertestsplayindiagnosingstones.

Improvingliverbloodtestscombinedwithsymptomresolutionsuggeststhatapatientwithcholedocholithiasishas
spontaneouslypassedthegallstone.

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ComplicatedcholedocholithiasisThetwomajorcomplicationsassociatedwithcholedocholithiasisare
pancreatitisandacutecholangitis.Inadditiontothefindingsassociatedwithuncomplicatedcholedocholithiasis,
patientswithbiliarypancreatitistypicallypresentwithnausea,vomiting,elevationsinserumamylaseandlipase
(bydefinitiongreaterthanthreetimestheupperlimitofnormal),and/orimagingfindingssuggestiveofacute
pancreatitis.(See"Clinicalmanifestationsanddiagnosisofacutepancreatitis".)

PatientswithacutecholangitisoftenpresentwithCharcot'striad(fever,rightupperquadrantpain,andjaundice)
andleukocytosis.Inseverecases,bacteremiaandsepsismayleadtohypotensionandalteredmentalstatus
(Reynolds'pentad).(See"Acutecholangitis",sectionon'Clinicalmanifestations'.)

Longstandingbiliaryobstructionfromvariouscauses,includingcommonbileductstones,mayresultinliver
diseasethatmayprogresstocirrhosis,aphenomenonreferredtoassecondarybiliarycirrhosis[1,2].Although
rareinthesettingofbileductstones,secondarybiliarycirrhosismayeventuallyresultinthesamecirrhosis
relatedcomplicationsthatoccurwithotheretiologies.Reliefofbiliaryobstructionhasbeenshowntoresultin
regressionofliverfibrosisinpatientswithsecondarybiliarycirrhosisinthesettingofchronicpancreatitisand
choledochalcysts[3,4].Itislikely,butnotknown,whetherstoneremovalresultsinsimilarimprovementinliver
diseaseinpatientswithcholedocholithiasisinducedsecondarybiliarycirrhosis.

DIAGNOSISPatientssuspectedofhavingcholedocholithiasisarediagnosedwithacombinationoflaboratory
testsandimagingstudies.Thefirstimagingstudyobtainedistypicallyatransabdominalultrasound.Additional
testingmayincludemagneticresonancecholangiopancreatography(MRCP),endoscopicultrasound(EUS),
and/orendoscopicretrogradecholangiopancreatography(ERCP).

Theaimofthediagnosticevaluationistoconfirmorexcludethepresenceofcommonbileductstonesusingthe
leastinvasive,mostaccurate,andmostcosteffectiveimagingmodality[13].Thespecificapproachisdetermined
bythelevelofclinicalsuspicion,availabilityofimagingmodalities,andpatientfactors(eg,contraindicationstoa
particulartest)(algorithm1).(See'Diagnosticapproach'below.)

DiagnosticapproachPatientsareoftensuspectedofhavingcholedocholithiasiswhentheypresentwithright
upperquadrantpainwithelevatedliverenzymesinaprimarilycholestaticpattern(disproportionateelevationof
thealkalinephosphatase,gammaglutamyltransferase,andbilirubin).Inapatientsuspectedofhaving
choledocholithiasisbasedonthehistory,physicalexam,andlaboratorytesting,westartbyobtaininga
transabdominalultrasound.Ifnotalreadydone,wealsoobtainacompletebloodcounttolookforleukocytosis
(whichmaysuggestacutecholangitishasdeveloped)andpancreaticenzymelevels.(See'Transabdominal
ultrasound'below.)

Wethenusetheresultsoflaboratorytestsandtransabdominalultrasoundtostratifyapatientashighrisk,
intermediaterisk,orlowriskforhavingcholedocholithiasis.Subsequentmanagementvariesdependingonthe
patient'slevelofrisk(algorithm1)(see'Riskassessment'below):

PatientsathighriskproceedtoERCPwithstoneremoval,followedbyelectivecholecystectomy.

PatientsatintermediateriskeitherundergopreoperativeEUSorMRCP,ortheyproceedtolaparoscopic
cholecystectomywithintraoperativecholangiographyorultrasonography.Ifastoneisfoundpreoperatively,
patientsshouldproceedtoERCPwithstoneremoval,followedbyelectivecholecystectomy,provided
gallstonesorsludgewereseenonpreoperativeimaging.

Patientsatlowriskcanproceeddirectlytocholecystectomywithoutadditionaltesting,providedgallstonesor
sludgewereseenonpreoperativeimaging.

RiskassessmentIna2010guideline,theAmericanSocietyforGastrointestinalEndoscopy(ASGE)
proposedthefollowingapproachtostratifypatientsbasedontheirprobabilityofhavingcholedocholithiasis.
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Patientswerestratifiedusingthefollowingpredictors[14]:

"Verystrong"predictors

Thepresenceofacommonbileductstoneontransabdominalultrasound
Clinicalacutecholangitis
Aserumbilirubingreaterthan4mg/dL(68micromol/L)

"Strong"predictors

Adilatedcommonbileductonultrasound(morethan6mminapatientwithagallbladderinsitu)
Aserumbilirubinof1.8to4mg/dL(31to68micromol/L)

"Moderate"predictors

Abnormalliverbiochemicaltestotherthanbilirubin
Ageolderthan55years
Clinicalgallstonepancreatitis

Usingtheabovepredictors,patientsarestratifiedas:

Highrisk

Atleastoneverystrongpredictorand/or
Bothstrongpredictors

Intermediaterisk

Onestrongpredictorand/or
Atleastonemoderatepredictor

Lowrisk

Nopredictors

HighriskpatientsPatientscategorizedasbeinghighriskforcholedocholithiasishaveanestimated
probabilityofhavingacommonbileductstoneof>50percent[14].Insuchpatients,theappropriatefirststepin
treatmentisERCPwithremovalofanycommonbileductstones,followedbyelectivecholecystectomy.(See
'Endoscopicretrogradecholangiopancreatography'belowand"Endoscopicmanagementofbileductstones:
Standardtechniquesandmechanicallithotripsy".)

IntermediateriskpatientsIntermediateriskpatientshaveanestimated10to50percentprobabilityof
havingacommonbileductstone.Suchpatientsrequireevaluationtoruleoutcholedocholithiasis,buttheriskis
nothighenoughtowarrantgoingdirectlytoERCP[14].Lessinvasiveoptionsfordetectingcholedocholithiasis
includeEUSandMRCP.Decidingwhichtestshouldbeperformedfirstdependsonvariousfactorssuchasease
ofavailability,cost,patientrelatedfactors,andthesuspicionforasmallstone(table1).(See'EUSandMRCP'
below.)

Becauseitisnoninvasive,MRCPisoftenthefirsttestperformedtolookforstones.Ifpositive,patientsshould
undergoERCP.Inmostcases,iftheMRCPisnegativethepatientcanproceedtoelectivecholecystectomy
(providedgallstonesorbiliarysludgeweredemonstratedonpreoperativeimaging).However,iftheMRCPis
negative,butthesuspicionforacommonbileductstoneremainsmoderatetohigh(eg,inapatientwhose

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laboratorytestsarenotimproving),EUSisanappropriatenextstep.Inmanycenters,theendoscopist
performingtheEUScanperformanERCPduringthesamesessionifastoneisfound.

Analternativetopreoperativeimagingistoproceedtolaparoscopiccholecystectomywithintraoperative
cholangiographyorultrasonography,providedasurgeonwhoisexperiencedwiththetechniquesisavailable.
Thisapproachwasexaminedinarandomizedtrialwith100patientsatintermediateriskofhavingacommonbile
ductstone[15].Patientswereassignedtoeitherproceeddirectlytolaparoscopiccholecystectomywith
intraoperativecholangiographyortoinitialEUSfollowedbyERCPifpositive,andsubsequentlaparoscopic
cholecystectomy.Patientswhoproceededdirectlytosurgeryhadashortermedianlengthofstaythanthosewho
underwentEUSfirst(5versus8days)andoverallhadfewerEUSs,MRCPs,andERCPs(25versus71).There
werenodifferencesbetweenthegroupswithregardtoconversiontolaparotomy,timeintheoperatingroom,
complications,ordeath.(See'Intraoperativecholangiography'belowand'Intraoperativeultrasonography'below.)

LowriskpatientsLowriskpatientsareestimatedtohavea<10percentprobabilityofhavingacommon
bileductstone[14].Ifgallstonesorsludgearepresentwithinthegallbladderontransabdominalultrasoundand
thepatientisagoodsurgicalcandidate,thepatientshouldproceedtocholecystectomywithoutimagingofthe
commonbileductpreoperativelyorintraoperatively.Alternativetherapies,suchasmedicalgallstonedissolution,
maybeconsideredforpatientswhoarenotsurgicalcandidates.(See"Dissolutiontherapyforthetreatmentof
gallstones".)

Ifthereisnoevidenceofgallstonesonimaging,alternativeexplanationsforthepatient'spainshouldbesought.
(See"Evaluationoftheadultwithabdominalpain".)

Specialcircumstances

ConcomitantacutepancreatitisWhethertoproceeddirectlytoERCPinpatientswithacute
pancreatitisdependsonwhetherthepatientalsohasacutecholangitis.Patientswithbothacutepancreatitisand
acutecholangitisshouldundergoearlyERCP[14].However,itislessclearifpatientswithacutepancreatitis
withoutcholangitisbenefitfromearlyERCP[16].CurrentevidencesupportsearlyERCPinpatientswithongoing
evidenceofbiliaryobstruction,butitnolongersupportsearlyERCPinpatientswithseverepancreatitisalone
[17].

Inpatientswithacutepancreatitisbutequivocalevidenceofbileductstones(eg,improvingliverenzymetests
and/orimprovementorresolutionofpain),MRCPorEUSfollowedbyERCPonlyiftheEUS/MRCPrevealsa
commonbileductstoneisanattractiveoptionbecauseitcandetectcommonbileductstones,butisnot
associatedwithpancreatitis.

IssuesrelatedtoERCPinpatientswithacutebiliarypancreatitisarediscussedelsewhere.(See"Managementof
acutepancreatitis",sectionon'Endoscopicretrogradecholangiopancreatography'.)

PriorcholecystectomyCholedocholithiasiswillsometimesbesuspectedinapatientwhohas
previouslyundergonecholecystectomy.Choledocholithiasiscanoccurinthissettingifagallstoneescapesfrom
thegallbladderduringcholecystectomyorifthereisdenovostoneformationwithinthecommonbileduct.(See
'Introduction'aboveand"Laparoscopiccholecystectomy",sectionon'Postcholecystectomysyndrome'.)

Insuchpatients,transabdominalultrasoundislesshelpfulbecauseadilatedcommonbileductseenon
ultrasoundmaybetheresultofacommonbileductstone,oritmaybetheresultofthecholecystectomy.
Followingcholecystectomy,thecommonbileductmaydilateto10mm.(See"Ultrasonographyofthe
hepatobiliarytract",sectionon'Normalmeasurementsonultrasound'.)

Oneapproachtopatientswhohaveundergoneapriorcholecystectomyandwhopresentwithbiliarytypepain
andlivertestabnormalities,butinwhomthereisuncertaintyastopresenceofabileductstone,istoproceed
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withanMRCPorEUStoconfirmthepresenceofastone.Ifastoneisseen,proceedingwithERCPforstone
removalisthenextstep.Ifastoneisabsent,thenthepatientmayhavesphincterofOddidysfunction,andthe
approachtopossibleERCPshouldbemodifiedtoincludespecificinformedconsentregardinghigherriskof
ERCPinthissettingandthedecreasedbenefitfromsphincterotomy.Inaddition,theERCPtechniquesused
shouldfocusonriskreduction,withliberaluseofprotectivepancreaticstents[18]andconsiderationofrectal
indomethacin[19].(See"TreatmentofsphincterofOddidysfunction",sectionon'Endoscopicsphincterotomy'
and"ProphylacticpancreaticstentstopreventERCPinducedpancreatitis:Whendoyouusethem?",sectionon
'SphincterofOddidysfunctionorasmallbileduct'and"Postendoscopicretrogradecholangiopancreatography
(ERCP)pancreatitis",sectionon'Nonsteroidalantiinflammatorydrugs'.)

ImagingtestcharacteristicsSeveralimagingmodalitiescanbeusedfortheevaluationofpatientswith
suspectedcholedocholithiasis,including:

Transabdominalultrasound
ERCP
EUS
MRCP
Intraoperativecholangiographyorultrasonography

TransabdominalultrasoundTheinitialimagingstudyofchoiceinpatientswithsuspectedcommonbile
ductstonesisatransabdominalultrasoundoftherightupperquadrant.Transabdominalultrasoundcanevaluate
forcholelithiasis,choledocholithiasis,andcommonbileductdilation.Itisreadilyavailable,noninvasive,permits
bedsideevaluation,andprovidesalowcostmeansofevaluatingthecommonbileductforstones.(See
"Ultrasonographyofthehepatobiliarytract".)

Thesensitivityoftransabdominalultrasoundforcholedocholithiasisrangesfrom20to90percent[14].Inameta
analysisoffivestudies,thepooledsensitivityofultrasoundfordetectingacommonbileductstonewas73
percent,withaspecificityof91percent[20].Transabdominalultrasoundhaspoorsensitivityforstonesinthe
distalcommonbileductbecausethedistalcommonbileductisoftenobscuredbybowelgasintheimagingfield
[2125].Occasionally,adefinitecommonbileductstone(onethatcastsashadow)canbeimagedby
transabdominalultrasound(image1).

Adilatedcommonbileductontransabdominalultrasoundissuggestiveof,butnotspecificfor,choledocholithiasis
[6,8,10].Acutoffof6mmisoftenusedtoclassifyaductasbeingdilated[14].However,usingacutoffof6mm
maymissstones[26].Onestudyof870patientsundergoingcholecystectomyfoundthatstoneswereoften
detectedinpatientswhoseductswouldhavebeenclassifiedas"nondilated"usingthe6mmcutoff[27].In
addition,theprobabilityofastoneinthecommonbileductincreasedwithincreasingcommonbileductdiameter:

0to4mm:3.9percent
4.1to6mm:9.4percent
6.1to8mm:28percent
8.1to10mm:32percent
>10mm:50percent

Conversely,becausethediameterofthecommonbileductincreaseswithage,olderadultsmayhaveanormal
ductwithadiameterthatis>6mm.(See"Ultrasonographyofthehepatobiliarytract",sectionon'Normal
measurementsonultrasound'.)

EndoscopicretrogradecholangiopancreatographyTraditionally,ERCP(image2)wasusedbothasa
diagnosticandtherapeuticprocedureinpatientswithsuspectedcholedocholithiasis.ThesensitivityofERCPfor

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choledocholithiasisisestimatedtobe80to93percent,withaspecificityof99to100percent[28,29].However,
ERCPisinvasive,requirestechnicalexpertise,andisassociatedwithcomplicationssuchaspancreatitis,
bleeding,andperforation.Asaresult,ERCPisnowreservedforpatientswhoareathighriskforhavinga
commonbileductstone,particularlyifthereifevidenceofcholangitis,orwhohavehadastonedemonstratedon
otherimagingmodalities.(See'Highriskpatients'aboveand"Endoscopicretrogradecholangiopancreatography:
Indications,patientpreparation,andcomplications".)

EUSandMRCPEUS(image3)andMRCP(picture1)havelargelyreplacedERCPforthediagnosisof
choledocholithiasisinpatientsatintermediateriskforcholedocholithiasis.EUSislessinvasivethanERCP,and
MRCPisnoninvasive.Bothtestsarehighlysensitiveandspecificforcholedocholithiasis[30].Decidingwhichtest
shouldbeperformedfirstdependsonvariousfactorssuchaseaseofavailability,cost,patientrelatedfactors,
andthesuspicionforasmallstone(table1).(See'Intermediateriskpatients'aboveand"Magneticresonance
cholangiopancreatography"and"Endoscopicultrasoundinpatientswithsuspectedcholedocholithiasis".)

EUSandMRCPforthediagnosisofcholedocholithiasishavebeenevaluatedusingERCPasthereference
standard:

Ametaanalysisof27studieswith2673patientsfoundthatEUShadasensitivityof94percentanda
specificityof95percent[31].

Areviewof13studiesfoundthatMRCPhadamediansensitivityof93percentandamedianspecificityof94
percent[32].

StudieshaveprospectivelycomparedtheaccuracyofEUSwithMRCPinthediagnosisofcholedocholithiasis.
Thesehavebeenreviewedintwosystemicreviews,bothofwhichshowednosignificantdifferencesbetweenthe
twomodalities[33,34].Inapooledanalysisof301patientsfromfiverandomizedtrialsthatcomparedEUSwith
MRCP,therewasnostatisticallysignificantdifferenceinaggregatedsensitivity(93versus85percent)or
specificity(96versus93percent).

MRCPispreferredformanypatientsbecauseitisnoninvasive.However,thesensitivityofMRCPmaybelower
forsmallstones(<6mm,(image3))[35],andbiliarysludgecanbedetectedbyEUS,butgenerallynotbyMRCP.
Asaresult,EUSshouldbeconsideredinpatientsinwhomthesuspicionforcholedocholithiasisremains
moderatetohighdespiteanegativeMRCP.(See'Intermediateriskpatients'above.)

IntraoperativecholangiographyIntraoperativecholangiographyhasanestimatedsensitivityof59to100
percentfordiagnosingcholedocholithiasis,withaspecificityof93to100percent[29,36,37].However,itishighly
operatordependentandisnotroutinelyperformedbymanysurgeons[38].

Intheerapriortolaparoscopicsurgery,patientswithgallstonediseaseandsuspectedcholedocholithiasis
underwentopencholecystectomyincludingcholangiographyandpalpationofthecommonbileductand/oropen
explorationofthecommonbileducttodiagnoseandtreatcholedocholithiasis.Aslaparoscopicsurgeryreplaced
opensurgeryasthepreferredmethodforcholecystectomy,explorationofthecommonbileductforremovalof
intraductalstonesbecametechnicallymorechallenging.(See"Laparoscopiccholecystectomy",sectionon
'Evaluationforcholedocholithiasis'and"Commonbileductexploration",sectionon'Intraoperative
cholangiography'.)

Withimprovementsincholangiographytechniquesandtheuseoffluoroscopicratherthanstaticcholangiography,
thesuccessfulcompletionrateandaccuracyofintraoperativecholangiographyhaveimprovedovertime[39].In
practice,theuseofintraoperativecholangiographyishighlyoperatordependentandmaybetechnically
unfeasibleinpatientswithaseverelyinflamedgallbladderorwithatinyorinflamedcysticduct.

Studiesofintraoperativecholangiographyduringlaparoscopiccholecystectomyhaveshownthefollowing:
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Inareviewof13studieswith1980patientsundergoinglaparoscopiccholecystectomy,9percenthad
choledocholithiasis[36].Thesuccessratefortechnicalcompletionofintraoperativecholangiographyranged
from88to100percent.Intraoperativecholangiographyhadasensitivityof68to100percentanda
specificityof92to100percentfordiagnosingcholedocholithiasis.

Inamorerecentprospectivepopulationbasedstudy,intraoperativecholangiographywasroutinely
attemptedin1171patientsundergoingcholecystectomy[37].Thecholecystectomywascarriedout
laparoscopicallyin79percent.Intraoperativecholangiographywassuccessfulin95percent,and
choledocholithiasiswasidentifiedin134patients(11percent).Thesensitivityandspecificityofintraoperative
cholangiographywere97and99percent,respectively.

Thereisongoingdebateabouttheroutineuseofintraoperativecholangiographyinallpatientsundergoing
laparoscopiccholecystectomyversusselectiveuseinpatientsatincreasedriskforintraductalstones,and
practicesvarywidelyamongsurgeons.Proponentsofroutineintraoperativecholangiographyarguethatitpermits
delineationofbiliaryanatomy,reducesandidentifiesbileductinjuries,andidentifiesasymptomatic
choledocholithiasis.Opponentsarguethatintraoperativecholangiographyaddstoproceduretimeandexpense.
Inaddition,theyarguethatasymptomaticcommonbileductstonesmaypassspontaneouslyand/orhavealow
potentialforcausingcomplications,suchthattheiridentificationmayleadtounnecessarycommonbileduct
explorationand/orconversiontoopensurgery[4050].

A2008studyexaminedthefrequencywithwhichsurgeonsemployintraoperativecholangiography.Inthesurvey
of1417surgeons,27percentdefinedthemselvesasroutineintraoperativecholangiographyusers[38].Among
theroutineusers,91percentreportedusingintraoperativecholangiographyinmorethan75percentof
laparoscopiccholecystectomies.Academicsurgeonswerelessoftenroutineuserscomparedwithnonacademic
surgeons(15versus30percent).

IntraoperativeultrasonographyAnotherintraoperativeapproachfordetectingcholedocholithiasisis
intraoperativeultrasonography.Duringlaparoscopy,anultrasoundprobeisinsertedintotheperitonealcavity
thougha10mmtrocharandisusedtoscanthebileducts.Thereportedsensitivityandspecificityareover90
percent,andithasbeensuggestedthattheroutineuseofintraoperativeultrasoundfollowedbyselective
intraoperativecholangiographyleadstotheaccuratediagnosisofcholedocholithiasis,whilereducingtheneedfor
intraoperativecholangiography[51].

Theuseofintraoperativeultrasoundmayalsodecreasetherateofbileductinjury[52].Comparedwith
intraoperativecholangiography,intraoperativeultrasounddoesnotrequireentryintothebileduct.However,itis
associatedwithalongerlearningcurveandiscurrentlynotaswidelyavailable[36].Thedecisionregarding
intraoperativecholangiographyorintraoperativeultrasonographydependsuponpatientselectionandthe
surgeon'sexpertiseandcomfortwiththetechniques.

OtherimagingmodalitiesAbdominalcomputedtomography(CT)andpercutaneous
cholangiopancreatographyarealternativemethodsfordiagnosingcholedocholithiasis.Unenhancedabdominal
CTisneithersensitivenorspecificforcholedocholithiasis.However,bothsensitivityandspecificitycanbe
improvedwiththeuseofintravenouscontrastmediacombinedwithahelicalcholangiographyprotocol,increasing
from65to93percentandfrom84to100percent,respectively[5358].Ifacommonbileductstoneisclearly
visualizedonCT(image4),thefindingishighlyspecific.(See"Computedtomographyofthehepatobiliarytract".)

PercutaneoustranshepaticcholangiographyistypicallyperformedinpatientswhoarenotcandidatesforERCP,
whohavefailedERCP,whohavesurgicallyalteredanatomypreventingendoscopicaccesstothebiliarytree,or
whohaveintrahepaticstones.Duetoitsinvasivenature,itshouldgenerallybeconsideredatherapeutic
procedure,ratherthanadiagnosticone.(See"Percutaneoustranshepaticcholangiography".)

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DIFFERENTIALDIAGNOSISPatientswithuncomplicatedgallstonedisease,acutecholecystitis,sphincterof
Oddidysfunction,orfunctionalgallbladderdisordermayallpresentwithbiliarycolic,andpatientswithliver
disease,hematologicdisorders,orbiliaryobstructionfromanycausemaypresentwithjaundice(table2).
Choledocholithiasiscantypicallybedifferentiatedfromtheseotherentitiesbasedonthepatient'shistory,
laboratorytests,andabdominalimaging.

Patientswithcholedocholithiasistypicallypresentacutelywithprolongedepisodesofpain.Ontheotherhand,the
episodesofpaininpatientswithuncomplicatedgallstonedisease,sphincterofOddidysfunction,orfunctional
gallbladderdisordertypicallylastlessthansixhoursandoftenoccurintermittently.Inaddition,patientswith
uncomplicatedgallstonediseaseorfunctionalgallbladderdisordershouldhavenormallaboratorytestsand
imaging(thoughpatientswithsphincterofOddidysfunctionmayhavebileductdilationandelevationsinthe
alanineaminotransferase,aspartateaminotransferase,andalkalinephosphatasethatnormalizebetween
attacks).Endoscopicultrasoundormagneticresonancecholangiopancreatographymayberequiredto
differentiatebetweensphincterofOddidysfunctionandcholedocholithiasis.(See"Uncomplicatedgallstone
diseaseinadults"and"ClinicalmanifestationsanddiagnosisofsphincterofOddidysfunction"and"Functional
gallbladderdisorderinadults".)

Likepatientswithcholedocholithiasis,patientswithacutecholecystitismayhaveprolongedepisodesofpainthat
startsuddenly.However,patientswithacutecholecystitisshouldnothaveasignificantlyelevatedbilirubinor
alkalinephosphataseunlessthereisasecondaryprocesscausingcholestasis.Inaddition,abdominalimagingin
acutecholecystitistypicallyrevealsanormalcommonbileduct,gallbladderwallthickening,andasonographic
Murphy'ssign.(See"Acutecholecystitis:Pathogenesis,clinicalfeatures,anddiagnosis".)

Therearenumerouscausesofjaundiceinadditiontocholedocholithiasis(table2).Choledocholithiasisis
differentiatedfromtheseotherconditionsbythepresenceofbiliarytypepainandsometimesbyadilated
commonbileductonabdominalimaging.(See"Diagnosticapproachtotheadultwithjaundiceorasymptomatic
hyperbilirubinemia",sectionon'Causesofhyperbilirubinemia'.)

MANAGEMENTThemainstayofthemanagementofcholedocholithiasisisremovalofthecommonbileduct
stoneeitherendoscopicallyorsurgically.Itisalsoimportanttoidentifyandtreatthecomplicationsof
choledocholithiasis,suchasacutepancreatitisandacutecholangitis.(See"Managementofacutepancreatitis"
and"Acutecholangitis",sectionon'Management'.)

Theapproachtostoneremovaldependsonwhenthestoneisdiscovered.Ifthestoneisdetectedbeforeorafter
cholecystectomy,thestoneshouldberemovedwithendoscopicretrogradecholangiopancreatography(ERCP).
(See"Endoscopicmanagementofbileductstones:Standardtechniquesandmechanicallithotripsy".)

ThechoiceoftreatmentforpatientswithcholedocholithiasisfoundduringsurgeryincludesintraoperativeERCP,
intraoperativecommonbileductexploration(laparoscopicoropen),andpostoperativeERCP.Atourcenter,
intraoperativeERCPisperformedifconsentwasobtainedpreoperatively.Otherwise,ERCPisperformedata
latertimeduringthesamehospitalization,asisstandardinmostpracticesettings.(See'Intraoperative
cholangiography'aboveand'Intraoperativeultrasonography'above.)

Intraoperativecommonbileductexplorationisperformedselectively,basedonsurgeonpreferenceandlocal
expertise.Opencommonbileductexplorationismorewidelyavailablethanlaparoscopiccommonbileduct
explorationbutisassociatedwithsignificantlymorecomplications[59].Inselectedcenters,laparoscopiccommon
bileductexplorationandstoneremovalisroutinelyperformed.Therearerelativelyfewindicationsforopen
commonbileductexploration,butcholecystectomyinpatientswithsurgicallyalteredanatomy(eg,RouxenY
gastricbypass)maybeanexampleofanappropriatesetting.(See"Commonbileductexploration"and"Open
cholecystectomy",sectionon'Commonbileductexploration'.)

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2017525 Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagementUpToDate

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandare
comfortablewithsomemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)

BeyondtheBasicstopics(see"Patienteducation:ERCP(endoscopicretrogradecholangiopancreatography)
(BeyondtheBasics)")

SUMMARYANDRECOMMENDATIONS

Choledocholithiasisreferstothepresenceofgallstoneswithinthecommonbileduct.Ithasbeenestimated
that5to20percentofpatientswithgallstoneswillhavecholedocholithiasisatthetimeofcholecystectomy,
withtheincidenceincreasingwithage.(See'Introduction'above.)

Mostpatientswithcholedocholithiasisaresymptomatic,althoughoccasionalpatientsareasymptomatic.
Symptomsassociatedwithcholedocholithiasisincluderightupperquadrantorepigastricpain,nausea,and
vomiting.Thepainisoftenmoreprolongedthanisseenwithtypicalbiliarycolic(whichtypicallyresolves
withinsixhours).(See'Symptoms'above.)

Onphysicalexamination,patientswithcholedocholithiasisoftenhaverightupperquadrantorepigastric
tenderness.Patientsmayalsoappearjaundiced.(See'Physicalexamination'above.)

Serumalanineaminotransferase(ALT)andaspartateaminotransferase(AST)aretypicallyelevatedearlyin
thecourseofbiliaryobstruction.Later,livertestsaretypicallyelevatedinacholestaticpattern,with
elevationsinserumbilirubin,alkalinephosphatase,andgammaglutamyltranspeptidase(GGT)beingmore
pronouncedthanthoseinALTandAST.(See'Laboratorytests'above.)

Complicationsofcholedocholithiasisincludeacutepancreatitisandacutecholangitis.Patientswithacute
pancreatitistypicallyhaveelevatedserumpancreaticenzymelevels,andpatientswithacutecholangitisare
oftenfebrilewithaleukocytosis.(See'Complicatedcholedocholithiasis'above.)

Patientssuspectedofhavingcholedocholithiasisarediagnosedwithacombinationoflaboratorytestsand
imagingstudies.Thefirstimagingstudyobtainedistypicallyatransabdominalultrasound.Theresultsof
laboratorytestingandtransabdominalultrasoundarethenusedtostratifyapatientashighrisk,intermediate
risk,orlowriskforhavingcholedocholithiasis(algorithm1)(See'Diagnosis'aboveand'Riskassessment'
above.)

Patientsathighriskforhavingcommonbileductstonesandwithintactgallbladdergenerallyproceedto
endoscopicretrogradecholangiopancreatography(ERCP)withstoneremoval,followedbyelective
cholecystectomy,ortheyundergocholecystectomywithintraoperativecholangiography,followedby
intraoperativeorpostoperativeERCPwhereavailable,laparoscopiccommonductexplorationcanbe
performed.PrecholecystectomyERCPwithpostponedcholecystectomyisappropriateinpatientswith
acutecholangitis,inthosewithongoingevidenceofbiliaryobstructionandacutepancreatitis,andin
patientswhoarepoorsurgicalcandidates.

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Patientsatintermediateriskeitherundergopreoperativeendoscopicultrasoundormagneticresonance
cholangiopancreatography,ortheyproceedtolaparoscopiccholecystectomywithintraoperative
cholangiographyorultrasonography.Subsequentmanagementchoicesareasabove.

Patientsatlowriskcanproceeddirectlytocholecystectomywithoutadditionaltesting,provided
gallstonesorsludgewereseenonpreoperativeimaging.

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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Topic13922Version25.0

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GRAPHICS

Flowchartfortheevaluationandmanagementof
choledocholithiasis

CBD:commonbileductERCP:endoscopicretrogradecholangiopancreatographyEUS:
endoscopicultrasoundIOC:intraoperativecholangiogramMRCP:magneticresonance
cholangiopancreatography.

Reproducedfrom:ASGEStandardsofPracticeCommittee.Theroleofendoscopyintheevaluation
ofsuspectedcholedocholithiasis.GastrointestEndosc201071:1.Copyright2010.Illustration
usedwiththepermissionofElsevierInc.Allrightsreserved.

Graphic66945Version2.0

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AdvantagesanddisadvantagesassociatedwithMRCPandEUSfortheevaluationof
choledocholithiasis

MRCP
Advantages

Noninvasive

Intravenouscontrastusuallygivenbutnotrequired

Establishedtechnique,widelyavailable

Disadvantages

Timeconsuming

Contraindicationssuchascardiacpacemaker/defibrillator,intracranialmetalclips

Falsepositivestudies(eg,intraductalartifactssuchasairorblood,imagereconstructionartifacts,motionartifacts)

Falsenegativestudies(eg,stonesindilatedCBDorstones<5mminthedistalductmaynotbevisualizedwell)

EUS
Advantages

Veryhighresolution(0.1mm)comparedwithMRCP(1.5mm)

Dynamicimagingallowingmanipulationandmagnificationofimageforbettervisualization

ERCPcanpotentiallybeperformedinthesamesettingforstoneremoval

Canbeperformedatthebedsideincriticallyillpatients

Disadvantages

MoreinvasivethanMRCP

Needforsedation

Risksassociatedwithsedation(eg,cardiopulmonarycompromise)andendoscopy(eg,bleedingandperforation)

Limitedavailabilityofequipmentandtrainedendosonographers

Notpossibleorlimitedroleinalteredanatomy(eg,pyloricstenosis,RouxenYbypass)

CBD:commonbileductERCP:endoscopicretrogradecholangiopancreatographyEUS:endoscopicultrasoundMRCP:
magneticendoscopicretrogradecholangiopancreatography.

CourtesyofMLFreeman,MD.

Graphic73388Version1.0

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Transabdominalultrasoundshowingcommonbileduct
stones

Atransverseultrasoundintheregionoftheportahepatisshowsmultiple
shadowingstones(arrows)withinadilateddistalcommonbileduct.

CourtesyofMLFreeman,MD.

Graphic62309Version5.0

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Commonbileductstoneonendoscopicretrograde
cholangiopancreatography(ERCP)

Cholangiogramshowinglarge(2cm)commonbileductstone(arrow).

CourtesyofMartinL.Freeman,MD.

Graphic59987Version5.0

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2017525 Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagementUpToDate

ComparisonofMRCP/ERCPandEUSforthedetectionof
commonbileductstones

Smallbileductstonemissedbymagneticresonancecholangiopancreatography(MRCP)
andendoscopicretrogradecholangiopancreatography(ERCP),butshownbyendoscopic
ultrasound(EUS).ThisdemonstratesthesuperiorsensitivityofEUSforsmallbileduct
stones.A)MRCPshowingdilatedbileductwithnoapparentstone,incidentalpancreas
divisum.B)EUSinsamepatientshowingverysmallbileductstone(<5mm)(arrow).C)
ERCPinsamepatientshowingdilatedcommonbileductwithoutapparentstone.D)
Endoscopicviewofextractedstoneafterbiliarysphincterotomy(arrow).

CourtesyofMLFreeman,MD.

Graphic60410Version3.0

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2017525 Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagementUpToDate

CholedocholithiasisafterRouxenYgastricbypass

Magneticresonancecholangiopancreatography(MRCP)showinglargedistally
impactedbileductstoneinapatientpostRouxenYgastricbypasswith
jaundice.

CourtesyofMLFreeman,MD.

Graphic70857Version3.0

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2017525 Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagementUpToDate

Computedtomographyscanshowingadistalbileduct
stone

CourtesyofMLFreeman,MD.

Graphic64701Version3.0

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2017525 Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagementUpToDate

Classificationofjaundiceaccordingtotypeofbilepigmentandmechanism

Unconjugatedhyperbilirubinemia Conjugatedhyperbilirubinemia(continued)
Increasedbilirubinproduction* Extrahepaticcholestasis(biliaryobstruction)

Extravascularhemolysis Choledocholithiasis

Extravasationofbloodintotissues Intrinsicandextrinsictumors(eg,
cholangiocarcinoma)
Intravascularhemolysis
Primarysclerosingcholangitis
Dyserythropoiesis
AIDScholangiopathy
Wilsondisease
Acuteandchronicpancreatitis
Impairedhepaticbilirubinuptake
Stricturesafterinvasiveprocedures
Heartfailure
Certainparasiticinfections(eg,Ascaris
Portosystemicshunts
lumbricoides,liverflukes)
SomepatientswithGilbertsyndrome
Intrahepaticcholestasis
Certaindrugs rifampin,probenecid,flavaspadic
Viralhepatitis
acid,bunamiodyl
Alcoholichepatitis
Impairedbilirubinconjugation
Nonalcoholicsteatohepatitis
CriglerNajjarsyndrometypesIandII
Chronichepatitis
Gilbertsyndrome
Primarybiliarycholangitis
Neonates
Drugsandtoxins(eg,alkylatedsteroids,
Hyperthyroidism
chlorpromazine,herbalmedications[eg,Jamaican
Ethinylestradiol bushtea],arsenic)
Liverdiseaseschronichepatitis,advanced Sepsisandhypoperfusionstates
cirrhosis
Infiltrativediseases(eg,amyloidosis,lymphoma,
Conjugatedhyperbilirubinemia sarcoidosis,tuberculosis)

Defectofcanalicularorganicaniontransport Totalparenteralnutrition

DubinJohnsonsyndrome Postoperativecholestasis

Defectofsinusoidalreuptakeofconjugated Followingorgantransplantation
bilirubin Hepaticcrisisinsicklecelldisease
Rotorsyndrome Pregnancy

Endstageliverdisease

AIDS:acquiredimmunodeficiencysyndrome.
*Serumbilirubinconcentrationusuallylessthan4mg/dL(68mmol/L)intheabsenceofunderlyingliverdisease.
Thehyperbilirubinemiainducedbydrugsusuallyresolveswithin48hoursafterthedrugisdiscontinued.

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ContributorDisclosures
MustafaAArain,MD Nothingtodisclose MartinLFreeman,MD Consultant/AdvisoryBoards:Boston
ScientificXlumenaCorporationCookEndoscopy[Endoscopicaccessories(Endoscopicaccessories)]. Douglas
AHowell,MD,FASGE,FACG Grant/Research/ClinicalTrialSupport:CookEndoscopy(Researchsupport).
Consultant/AdvisoryBoards:CookEndoscopyConsultant[AdvancedEndoscopy]OlympusAmerica[Endoscopy
(GeneralandAdvanced).PatentHolder:CookEndoscopy[advancedinterventionalendoscopy(ERCP
devices/stents)]. ShilpaGrover,MD,MPH,AGAF Nothingtodisclose

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