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OBSTRUCTIVEJAUNDICE­Areviewarticle

1.Introduction/Definition

1.Introduction/Definition

2.SurgicalAnatomyoftheHepatobiliarysystem

3.Physiology/BiochemistryofBilirubinproductionandtransport

3.Physiology/BiochemistryofBilirubinproductionandtransport

4.Pathophysiology

5.Etiology

6.ClinicalFeatures

7.Investigations

8.ApproachtotheJaundicedpatient

9.Treatment

9.1.GeneralConsiderations

9.2.Specifictreatmentbasedoncauses

9.2.1.Choledocholithiasis

9.2.2.Cholangiocarcinoma

9.2.3.Ampullarytumours

9.2.4.PancreaticCancer

9.2.5.BiliaryStrictures

10.Complications

11.Conclusion

12.Recommendations

ReferenceList

1.Introduction/Definition

Jaundice(derivedfromFrenchword‘jaune’foryellow)oricterus(Latinwordforjaundice)isayellowishstainingoftheskin,sclera

andmucousmembranesbydepositionofbilirubin(ayelloworangebilepigment)inthesetissues.(1)Jaundicewasoncecalledthe

"morbusregius"(theregaldisease)inthebeliefthatonlythetouchofakingcouldcureit.

Jaundiceindicatesexcessivelevelsofconjugatedorunconjugatedbilirubininthebloodandisclinicallyapparentwhenthebilirubin

levelexceeds2mg/dl(34.2µmolperL).Itismostapparentinnaturalsunlight.Infact,itmaybeundetectableinartificialorpoorlight.

Infair­skinnedpatients,jaundiceismostnoticeableontheface,trunk,andsclerae;indark­skinnedpatients,it’snoticeableonthehard

palate,sclerae,andconjunctivae.Pseudojaundicemaybefoundinblackpatientswithpigmentedsclera,fromcarotinemia,uremia(a

sallowyellowishpallor),andquinacrine(ayellow­greencolor).

Causesofjaundicecanbeclassifiedintopre­hepatic,hepaticorposthepatic.Inthisreview,ourfocusisonposthepaticcausesof jaundice(obstructiveorsurgicalcholestasis)asthisismorerelevanttosurgeons.Obstructivejaundiceisnotadefinitivediagnosisand earlyevaluationtoestablishtheetiologyofthecholestasisiscrucialtoavoidsecondarypathologicalchanges(e.g.secondarybiliary

cirrhosis)ifobstructionisnotrelieved.(2)

2.SurgicalAnatomyoftheHepatobiliarysystem

Anaccurateknowledgeoftheanatomyoftheliverandbiliarytract,andtheirrelationshiptoassociatedbloodvesselsisessentialfor theperformanceofhepatobiliarysurgerybecausewideanatomicvariationsarecommon.Theclassicanatomicdescriptionofthe

biliarytractisonlypresentin58%ofthepopulation.(3)

Theliver,gallbladder,andbiliarytreeariseasaventralbud(hepaticdiverticulum)fromthemostcaudalpartoftheforegutearlyinthe fourthweek.Thisdividesintotwopartsasitgrowsbetweenthelayersoftheventralmesentery:thelargercranialpart(parshepatica) istheprimordiumoftheliver,andthesmallercaudalpart(parscystica)expandstoformthegallbladder,itsstalkbecomingthecystic duct.Theinitialconnectionbetweenthehepaticdiverticulumandtheforegutnarrows,thusformingthebileduct.Asaresultofthe

positionalchangesoftheduodenum,theentranceofthebileductiscarriedaroundtothedorsalaspectoftheduodenum.(4)

Thebiliarysystemcanbebroadlydividedintotwocomponents,theintra­hepaticandtheextra­hepatictracts.Thesecretoryunitsof theliver(hepatocytesandbiliaryepithelialcells,includingtheperibiliaryglands),thebilecanaliculi,bileductules(canalsofHering), andtheintrahepaticbileductsmakeuptheintra­hepatictractwhiletheextra­hepaticbileducts(rightandleft),thecommonhepatic

duct,thecysticduct,thegallbladder,andthecommonbileductconstitutetheextra­hepaticcomponentofthebiliarytree.(5;6)

Thecysticandcommonhepaticductsjointoformthecommonbileduct.Thecommonbileductisapproximately8to10cminlength

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and0.4to0.8cmindiameter.Thecommonbileductcanbedividedintothreeanatomicsegments:supraduodenal,retroduodenal,and

intrapancreatic.Thecommonbileductthenentersthemedialwalloftheduodenum,coursestangentiallythroughthesubmucosallayer

for1to2cm,andterminatesinthemajorpapillainthesecondportionoftheduodenum.Thedistalportionoftheductisencircledby

smoothmusclethatformsthesphincterofOddi.Thecommonbileductmayentertheduodenumdirectly(25%)orjointhepancreatic

duct(75%)toformacommonchannel,termedtheampullaofVater.

Thebiliarytractissuppliedbyacomplexvasculaturecalledtheperibiliaryvascularplexus.Afferentvesselsofthisplexusderivefrom

hepaticarterialbranches,andthisplexusdrainsintotheportalvenoussystemordirectlyintohepaticsinusoids.

3.Physiology/BiochemistryofBilirubinproductionandtransport

Bileisasubstanceproducedintheliverandcontainsbilesalts,water,cholesterol,electrolytes,andbilirubin,whichisabreakdown

productofhemoglobin.

Theformationofbilirubinfromhemeisessentialformammalianlife,becauseitprovidesthebodywiththemainmeansofelimination ofheme.Eightypercentofthecirculatingbilirubinisderivedfromhemeofhemoglobinfromsenescentredbloodcellsdestroyedin thereticuloendotheliumofthebonemarrow,spleen,andliver.Tentotwentypercentofthebilirubincomesfromothersourcessuchas myoglobin,cytochromes,andotherheme­containingproteinsprocessedintheliver.Initially,hemeisoxidizedatthealphapositionto thegreenpigmentbiliverdin,whichisthenreducedatthegammapositiontobilirubin.

Bilirubinisvirtuallyinsolubleinaqueoussolutions.Inblooditisreversiblybuttightlyboundtoplasmaalbuminata1:1ratio.Newly

formedbilirubinisremovedfromthecirculationveryrapidlybytheliver.

Theprocessingoftheserumbilirubinloadbythehepatocytesoccursinfoursteps.Theseare:uptake,cytosolicbinding,conjugation,

andsecretion.Hepaticuptakeofbilirubinoccurswiththedissociationofthealbumin­bilirubincomplexfacilitatedbyplasma

membraneproteinswithsubsequenttranslocationofbilirubinintothehepatocytethroughasaturableproteincarrier,whichalsobinds

otherorganicanions,butnotbilesalts.

Inthehepatocytes,bilirubinbindstotwocytosolicproteins:ligandinandZprotein.Thebindinglimitstherefluxofbilirubinbackto

theplasmaanddeliversittotheendoplasmicreticulumforconjugation.Conjugationofbilirubininvolvesitsesterificationwith

glucuronicacidtoform,first,amonoglucuronide,thenadiglucuronide.Theprincipalenzymeinvolvedisuridinediphosphate(UDP)­

glucuronyltransferase.Conjugationrendersbilirubinwater­solubleandisessentialforitseliminationfromthebodyinbileandurine.

Mostoftheconjugatedbilirubinexcretedintobileinhumansisdiglucuronidewithalesseramountofmonoglucuronide.Secretionof

conjugatedbilirubinfromthehepatocytetothebilecanaliculiinvolvesaspecificcarrierandoccursagainstaconcentrationgradient.

Conjugatedbilirubinisexcretedinbile,asamicellarcomplexwithcholesterol,phospholipids,andbilesalts,throughthebiliaryand cysticductstoenterthegallbladder,whereitisstored;oritpassesthroughVater’sampullatoentertheduodenum.Insidethe intestines,somebilirubinisexcretedinthestool,whiletherestismetabolizedbythegutfloraintourobilinogensandthenreabsorbed. Themajorityoftheurobilinogensarefilteredfromthebloodbythekidneyandexcretedintheurine.Asmallpercentageofthe

urobilinogensarereabsorbedintheintestinesandre­excretedintothebilethroughtheenterohepaticcirculation(7;8)

Recentfindingsinthefieldofmolecularbiologyandthehumangenomeprojecthavehighlightedvariousproteinsandgenes

responsibleforthemetabolismofbilirubinandsomeofthesearebeingexploitedinthetreatmentofcholestasis.(9­11)

4.Pathophysiologyofobstructivejaundice

Bileisamultipurposesecretionwithanarrayoffunctions,includingintestinaldigestionandabsorptionoflipids,eliminationof environmentaltoxins,carcinogens,drugs,andtheirmetabolites(xenobiotics),andservingastheprimaryrouteofexcretionfora

varietyofendogenouscompoundsandmetabolicproducts,suchascholesterol,bilirubin,andmanyhormones.(12)

Inobstructivejaundice,thepathophysiologiceffectsreflecttheabsenceofbileconstituents(mostimportantly,bilirubin,bilesalts,and

lipids)intheintestines,andtheirbackup,whichcausesspillageintothesystemiccirculation.Stoolsareoftenpalebecauseless

bilirubinreachestheintestine.Absenceofbilesaltscanproducemalabsorption,leadingtosteatorrheaanddeficienciesoffat­soluble

vitamins(particularlyA,K,andD);vitaminKdeficiencycanreduceprothrombinlevels.Inlong­standingcholestasis,concomitant

vitaminDandCamalabsorptioncancauseosteoporosisorosteomalacia.

Bilirubinretentionproducesmixedhyperbilirubinemia.Someconjugatedbilirubinreachesanddarkenstheurine.Highlevelsof

circulatingbilesaltsareassociatedwith,butmaynotcause,pruritus.Cholesterolandphospholipidretentionproduceshyperlipidemia

despitefatmalabsorption(althoughincreasedliversynthesisanddecreasedplasmaesterificationofcholesterolalsocontribute);

triglyceridelevelsarelargelyunaffected.Thelipidscirculateasaunique,abnormal,low­densitylipoproteincalledlipoproteinX.

Cholestaticliverdiseasesarecharacterizedbyaccumulationofhepatotoxicsubstances,mitochondrialdysfunctionandimpairmentof liverantioxidantdefense.Thestorageofhydrophobicbileacidshasbeenindicatedasthemaincauseofhepatotoxicitywithalteration ofsomeimportantcellfunctions,suchasthemitochondrialenergyproduction.Bothmitochondrialmetabolismimpairmentand hydrophobicbileacidsaccumulationareassociatedwithincreasedproductionofoxygenfreeradicalspeciesanddevelopmentof

oxidativedamage.(13)

5.Etiology

Myriadofdiseasescanleadtoextrahepaticbiliaryobstruction(Table1)

Thecommononesinclude:

CholedocholithiasisTable1 ) Thecommononesinclude: Cholangiocarcinoma, Ampullarycancers, CancerofthePancreas

Cholangiocarcinoma,Table1 ) Thecommononesinclude: Choledocholithiasis Ampullarycancers, CancerofthePancreas

Ampullarycancers,Choledocholithiasis Cholangiocarcinoma, CancerofthePancreas

CancerofthePancreasCholedocholithiasis Cholangiocarcinoma, Ampullarycancers, http://www.ptolemy.ca/members/archives/2007/Jaundice/ 2/9

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3/31/2017 OBSTRUCTIVEJAUNDICE Biliarystrictures. 6.ClinicalFeatures

Biliarystrictures.

6.ClinicalFeatures

Agoodhistory,physicalexaminationanddiagnostictestsaretherequisitesfortheevaluationofthejaundicedpatient.Jaundice,dark

urine,palestoolsandgeneralizedpruritusarethehallmarkofobstructivejaundice.Historyoffever,biliarycolicandintermittent

jaundicemaybesuggestiveofcholangitis/choledocholithiasis.Weightloss,abdominalmass,painradiatingtothebackand

progressivelydeepeningjaundicemaybesuggestiveofpancreaticcancer.Deepjaundice(withagreenishhue)thatappearstofluctuate

inintensitymaybeduetoaperiampullarycancer.Apalpablyenlargedgallbladderinajaundicedpatientisalsosuggestiveofan

extrahepaticmalignancy(Couvoissier’sstatement).

7.Investigations

a)Biochemistry/Hematology

Elevatedserumbilirubinlevelwithapreponderanceoftheconjugatedfractionistherule.Theserumgammaglutamyltranspeptidase

(GGT)levelisalsoraisedincholestasis.

Ingeneral,patientswithgallstonediseasehavelesshyperbilirubinemiathanthosewithextra­hepaticmalignantobstruction.Theserum

bilirubinisusuallylessthan20mg/dL.Thealkalinephosphatasemaybeelevateduptotentimesnormal.Thetransaminasesmay

abruptlyriseabouttentimesnormalanddecreaserapidlyoncetheobstructionisrelieved.

ElevatedWBCmaybepresentincholangitis.Inpancreaticcancerandotherobstructivecancers,theserumbilirubinmayriseto35to

40mg/dL,thealkalinephosphatasemayriseuptotentimesnormal,butthetransaminasesmayremainnormal.

TumormarkerslikeCA19­9,CEAandCA­125areusuallyelevatedinpancreaticcancers,cholangiocarcinomaandperi­ampullary

cancers,buttheyarenonspecificandmaybeelevatedinotherbenigndiseasesofthehepatobiliarytree.(14)

b)Imaging

Thegoalsofimagingare:

(1)toconfirmthepresenceofanextrahepaticobstruction(i.e.,toverifythatthejaundiceisindeedpost­hepaticratherthanhepatic),

(2)todeterminetheleveloftheobstruction,(3)toidentifythespecificcauseoftheobstruction,and(4)toprovidecomplementary

informationrelatingtotheunderlyingdiagnosis(e.g.,staginginformationincasesofmalignancy).(15)Aplainabdominalxraymay

showcalcifiedgallstones,porcelaingallbladder,airinthebiliarytractorairinthegallbladderwall. Ultrasonographyshowsthesizeofthebileducts,maydefinetheleveloftheobstruction,mayidentifythecauseandgivesother

informationrelatedtothedisease(e.g.hepaticmetastases,gallstones,hepaticparenchymalchange).(2)

Itidentifiesbileductobstructionwith95%accuracythoughresultsarelargelyoperatordependent.Itwillalsoshowstonesinthe

gallbladderanddilatedbileduct,butitisunreliableforsmallstonesorstricturesinthebileducts.Itmayalsodemonstratetumors,

cysts,orabscessesinthepancreas,liver,andsurroundingstructures.InAfrica,thisisavailableinmostcentersandprobably

constitutesthemainimagingmodalityavailableapartfromX­ray.

Computedtomography(CT)oftheabdomenprovidesexcellentvisualizationoftheliver,gallbladder,pancreas,kidneys,and

retroperitoneum.Itcandifferentiatebetweenintra­andextra­hepaticobstructionwith95%accuracy.However,CTmaynotdefine

incompleteobstructioncausedbysmallgallstones,tumors,orstrictures.Contrast­enhancedmulti­sliceCTisveryusefulfor

assessmentofbiliarymalignancies.Contrastagentsgivenorallyorintravenouslyareusedandimagingdoneinunenhanced,arterial

andvenousphases.

ERCPandPTC(Percutaneoustranshepaticcholangiography)providedirectvisualizationofthelevelofobstruction.Howevertheyare

invasiveandassociatedwithcomplicationslikecholangitis,biliaryleakage,pancreatitisandbleeding.Thesefacilitiesaregenerallynot

availableinmostcentersinAfrica.

Endoscopicultrasound:Endoscopicultrasonographyhasvariousapplications,suchasstagingofgastrointestinalmalignancy, evaluationofsubmucosaltumors,andhasgrowntobeanimportantmodalityinevaluatingthepancreaticobiliarysystem.Withregard tothebiliarysystem,EUSisusefulforthedetectionandstagingofampullarytumors,detectionofmicrolithiasis,choledocholithiasis andevaluationofbenignandmalignantbile­ductstrictures.Itcanfurtherevaluaterelationshipstovascularstructures.Itmayhelp definebenignlesionsmimickingcancer(e.g.sclerosingpancreatitis)ifthereisdiagnosticdoubt.Endoscopicultrasoundenablesthe

aspirationofcystsandbiopsyofsolidlesions,butisoperator­dependent.(16)Unfortunately,thisisnotreadilyavailableinmost

centersinAfrica.

Magneticresonancecholangiopancreatography(MRCP)isanewer,noninvasivetechniqueforvisualizationofthebiliaryand

pancreaticductalsystem.Itisespeciallyusefulinpatientswhohavecontraindicationsforendoscopicretrograde

cholangiopancreatography(ERCP).ExcellentvisualizationofbiliaryanatomyispossiblewithouttheinvasivenessofERCP.Unlike

ERCP,itispurelydiagnostic.

OtherimagingtestsincludeCholescintigraphy,radionuclidescanning(Tc99)angiographyandstaginglaparoscopy.

TheseimagingfacilitiesarehardtofindinAfricaandultrasonographyremainstheonlydiagnostictestavailableinmostcenters.

8.ApproachtotheJaundicedPatient

Barkunetalhavewrittenanexcellentreviewonanapproachtothejaundicedpatient.(15)Ihavesummarizedtheapproachwiththe

followingquestions:

Question1:IsJaundicepresent?Askindiscolorationsuggestiveofjaundicecanbemimickedbyavarietyofconditionswhich

include:

a)consumptionoflargequantitiesoffoodcontaininglycopeneorcarotene

b)useofdrugslikerifampicinorquinacrine

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Itisthereforenecessarytoinspectnotonlytheskin,butthemucousmembranesofthemouth,palm,solesandthesclera.

Q2:IsitDirectorIndirectHyperbilirubinemia?Darkurine,palestoolsandotherfeaturesofcholestasis,likepruritus,aresuggestiveof

directhyperbilirubinemia,whilenormalcoloredurineandstoolreflectunconjugatedhyperbilirubinemia.Inmajorityofcases,clinical

findingsalonewillbesufficienttodifferentiateconjugatedfromunconjugatedhyperbilirubinemia.

Q3:IsitHepaticorPosthepatic?Oncedirecthyperbilirubinemiahasbeenconfirmed,thenextquestiontoansweriswhetherthe

jaundiceisfromhepaticorpost­hepaticlesions.Clinicalfeaturesofhepaticjaundiceincludehistoryofalcoholabuse,acutehepatitis, andstigmataofchronicliverdiseaselikepalmarerythema,caputmedusae,ascitesandDupuytren’scontracture.

Post­hepaticjaundiceusuallypresentwithabdominalpain,rigors,itchingandpalpablelivermorethan2cmbelowthecostalmargin.

Usingclinicalapproachandsimplebiochemicaltests(totalserumbilirubin,alkalinephosphataseandgammaglutamyltransferrase

levels)willusuallygiveagoodjudgmentonwhetherthejaundiceishepaticorpost­hepatic.However,thisapproachwillnotbeableto

identifytheleveloftheobstruction.

Q4:Whatistheleveloftheobstruction?Imagingisthekeytoidentifyingthelevelofobstruction.Ultrasonographywillbeableto

identifythelevelofobstructioninabout90%ofcases.OtherimagingfacilitieslikeMRCP,ERCP,PTC,andCTscanmaybeused

whereUltrasonographycannotdeterminetheleveloftheobstruction.

Q5:Whatisthecauseoftheobstruction?ThecommonestcauseofobstructionintheWestisusuallycholedocholithiasis.However,if

choledocholithiasisisexcluded,pancreaticandperiampullarycancersarethenextcommoncauses.

Q6.Whatistheextentofthedisease(staging)/complications(cholangitis)?Whileobviousmetastasesmaybepresentbyapalpationof

anodularenlargedliverorotherevidenceofwidespreaddisease,sophisticatedimagingisrequiredformoreprecisestaging.Feverand

elevatedWBCareindicativeofcholangitis.

Q7.Ifitismalignant,isitrespectable?Assessmentoftheresectabilityofatumorusuallyhingesonwhetherthesuperiormesenteric

vein,theportalvein,thesuperiormesentericartery,andtheportahepatisarefreeoftumorandonwhetherthereisevidenceof

significantlocaladenopathyorextrapancreaticextensionoftumor.MultislicespiralCTistheimagingofchoiceforassessmentof

respectabilityofpancreaticcancers.Optimalevaluationisachievedwithafine­cutdual­phase(arterialphaseandportalvenousphase).

MRCP,EUS,CTangiographyorduplexDopplerUltrasonographyareotherimagingfacilitiesthatcanbeusedinassessmentof

hepatobiliarymalignanciesincenterswheretheyareavailable.Forunresectablemalignancies,thechoiceisbetweensurgical

palliation/bypassandERCP/PTCwithdrainage.Insomecases,neitheroptionmaybefeasiblebecauseofadvanceddisease;insucha

casesupportivecarealonewillsuffice.

Forlesionsthatarerespectableoramenabletosurgicalpalliation,thechoiceoftreatmentwilldependonthelevelofobstructionand

thepreciseetiology.

Forthispurpose,thelesionscanbeclassifiedintothree:(Table2)

a)Upperthirdobstruction:Surgicalpalliationisbestachievedwithaleft(segment3)hepaticojejunostomy(Thelongextrahepatic

courseofthelefthepaticductmakesitmoreaccessible).Forrespectablelesions,thetumorisresectedwithapossiblehepatectomyor

segmentectomyandreconstructionachievedbyhepaticojejunostomyorcholangiojejunostomy.

b)Middlethirdobstruction:Surgicalpalliationiseasierandhepaticojejunostomyafterthebifurcationisdone.Iftumorisresectable,

reconstructionisachievedwithhepaticojejunostomy.

c)Lowerthirdobstruction:SurgicalpalliationdoneusingaRouxenYcholedochojejunostomy.Cholecystojejunostomycarriesahigh

riskofcomplicationsandsubsequentjaundice.Iftumorisrespectable,apancreatiduodenectomy(Whipple’sprocedure)orlocal

ampullaryresectionshouldbedone.

9.Treatment

Extrahepaticbiliaryobstructionrequiresmechanicaldecompression.Othergoalsincludetreatmentoftheunderlyingcause,symptoms, andcomplications(e.g.,vitaminmalabsorption).Decompressionofextrahepaticbiliaryobstructioncanbeachievedbyanyofthese threemethods:surgicalbypass,resectionofobstructinglesions,percutaneousinsertionofstents,andendoscopicinsertionofstents.

(17)

9.1.GeneralConsiderations

Pruritususuallysubsideswithcorrectionoftheunderlyingdisorderorwith2to8gm.orallyofcholestyraminebid,whichbindsbile

saltsintheintestine.However,thisisineffectiveincompletebiliaryobstruction.Unlessseverehepatocellulardamageispresent,

hypoprothrombinemiausuallysubsidesafteruseof(vitaminK1)5to10mgsconce/dayfor2to3days.CaandvitaminD

supplements,withorwithoutabisphosphonate,slowtheprogressionofosteoporosisonlyslightlyinlong­standingirreversible

cholestasis.VitaminAsupplementspreventdeficiencyandseveresteatorrheacanbeminimizedbyreplacingsomedietaryfatwith

medium­chaintriglycerides.

Jaundicedpatientsundergoingsurgeryforlargebileductobstruction(fromanycause)aresubjecttospecificrisksthatrequire

prophylacticmeasures.Theseinclude:

infections(cholangitis,septicaemia,woundinfections)

bleeding(non­coagulantacarboxylderivativesofvitaminKdependentfactors)

renalfailureliverfailure fluidandelectrolyteabnormalities

liverfailurerenalfailure fluidandelectrolyteabnormalities

fluidandelectrolyteabnormalities

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Preparationforsurgeryisimportantbecauseoftheassociatedperioperativemorbiditypreviouslydiscussed.Thespecificmeasures

requiredinallpatientsare:

parenteraladministrationofvitaminKanalogues–tonormaliseprothrombintime

intravenoushydrationandcatheterizationoftheurinarybladder

forcednatriuresisbymannitolwithinductionofanaesthesia

antibioticprophylaxisagainstgramnegativeaerobes–usingathree­doseregimen

frozensectionshouldbebookedforallpatientsundergoingresectionforcancer

9.2.SpecificTreatmentbasedoncauses

9.2.1.Choledocholithiasis(bileductstones)

Therearevariousoptionsavailable.Thebestoptionshouldbeindividualizedandbasedonthefollowingfactors:

Physicalconditionofthepatientincludingcomorbidityandmedicalhistory

Previousattemptsatinterventionorpreviouscholecystectomy

Availabilityofequipment/theatre/anesthetist/expertiseofInterventionist

Patientpreference.Openexplorationofthecommonbileduct:involves:

Openexplorationofthecommonbileduct:involves:

Cholecystectomy,ifpresent.

supraduodenallongitudinalcholedochotomy

ExtractionofcalculibyFogartyballoontrawl,DesjardinsforcepsorDormiabasketandirrigationwithsaline.

Confirmationofductclearancesuperiorlyandinferiorlybycholedochoscopyand/orcholangiography.

Wherefacilitiesforcholedochoscopyandintraoperativecholangiogramarenotavailable,toavoidtheriskofleavingretainedduct stones,aTtubeisusuallyinsertedtoconfirmclearanceoftheductbyapostoperativecholangiogramafteratleastfivedays.TheT tubeisremovedaftertwoweeks,whenanepithelialzedtracthasformedtoavoidbileleakintotheperitonealcavity. SeveraltrialshoweverhaveshownthatprimaryclosureofthebileductwithoutTtubeisassafeasusingTtubeandisassociatedwith

lesscomplicationslikesepsis,tubemigrationsandbileperitonitis.(18;19).InAfricaandotherdevelopingcountrieswheretheremay

benofacilitiesforintraoperativecholangiogramorintraoperativeUltrasonography,Ttubeplacementwillbeapragmaticapproach.

Unfortunately,inmostcenters,Ttubesarehardtofind.

Otherproceduresindifficultcases:

Removalofcommonbileductcalculimayprovedifficultbyanyoftheabovemethods,forexample:

impactedstonewhenalleffortstoremoveithavefailed

multiplelargestonesimpactedstonewhenalleffortstoremoveithavefailed inaccessibleduct(e.g.previoussurgery,unfitpatient).

inaccessibleduct(e.g.previoussurgery,unfitpatient).

Surgicalorpercutaneousdrainageproceduresmaybeuseful.Choledochoduodenostomymaybedonebyanastomosisofadilated

commonbileducttotheduodenum.Alternatively,particularlyinanon­dilatedduct,atransduodenalsphincteroplasty

isundertakenbyfirstcarryingoutanopensphincterotomyandstoneextraction,thensuturingthemucosaoftheductandduodenum

togethertokeepthelowerendpatent;theseproceduresarerarelyundertaken.Percutaneousstentingornaso­biliarydrainagemaybe

doneinanunfitpatientwithcommonbileductstonesthatcannotberemovedbyERCP

ERCP±sphincterotomy:AcholangiogramisdoneaftertheampullaofVaterhasbeenidentifiedandcannulatedtoconfirmanatomy

andthepresenceofstones.AnadequatesphincterotomyisundertakenandtheductclearedusingaballooncatheterorDormiabasket.

Confirmationofductclearanceshouldbeestablishedwitharadiograph.

Ifthestonesaretoolarge,theycanbecrushedinsituusingamechanicallithotripter;howevercareshouldbeexercisedtoavoid

damagetotheductlining.Othertechniquesdescribedintheliteratureincludeextracorporealshockwavelithotripsy,contactlithotripsy,

laserunderdirectvision.Thesearehowevertimeconsuming,resourceintensiveandarelimitedtofewspecializedcenters.

Endoscopicplacementofastent,ortemporarynaso­biliarydrainagecanbeagoodoptionifthestonesaremultipleortoolargefor extraction.ThisrelievesobstructionandpreventsimpactionofstonesattheampullaofVater.SuccessrateafterERCP±sphincterotomy

isabout90%withlowcomplicationsinexperiencedhands.Complicationsincludeperforation,acutepancreatitis,andbleedingfrom

damagetoabranchofthesuperiorpancreatico­duodenalartery.Difficultiesmayariseasaresultoftechnicalproblemsincannulating theampullaofVateroranatomicalanomalieslikeduodenaldiverticulumERCPmaybeconsideredthedefinitivetreatmentforsome

unfitpatients,butmostwillproceedtocholecystectomytoremoveremaininggallstonesandpreventfurthercomplications.(2;20;21)

Endoscopicballoondilationwasintroducedaboutthreedecadesagoforelderlyandfrailpatientsasanalternativetosphincterotomy,

becauseoftheadvantagesofpreservingthesphincterofOddi.ThishasbeenabandonedinNorthAmericabecauseoftheriskof

pancreatitis.ItisstillpracticedinpartsofAsiaandEurope.

ArecentCochranereviewconcludedthatitisslightlylesssuccessfulthanendoscopicsphincterotomyinstoneextractionandmore riskyregardingpancreatitisandprobablyhasaclinicalroleinpatientswhohavecoagulopathy,whoareatriskforinfection,and

possiblyinthosewhoareolder.(22)

Laparoscopicexplorationofthecommonbileductmaybedonethroughthecysticduct(ifthegallbladderhasnotbeenpreviously

removed)orcommonductviaacholedochotomy.StonesareextractedunderfluoroscopicguidanceusingballooncathetersorDormia

basket.Choledochoscopyandlithotripsycanalsobedoneforlargerstones.Thistechniquerequiresconsiderablelaparoscopic

expertiseandistimeconsuming,soitisrarelythefirst­linetreatmentforcommonbileductstones;theseareusuallyremovedatERCP

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preoperativelyandalaparoscopiccholecystectomydoneelectively.Singlestagelaparoscopiccholecystectomyandductalstone clearancehasbeenshowninseveralstudiestohavethesameefficacyandmorbiditywiththestagedapproachwiththeaddedbenefit

ofreducedcosts.(15;23;24)

Nevertheless,mostcentersstillfavorpreoperativeendoscopicductalclearancebecauseLECBDistechnicallydemandingand

sophisticatedlaparoscopicequipmentmaynotbeavailableineverysurgicalunit.

Medicaldissolutionofcommonbileductstones:

Flushingwithnormalsaline;infusionofbilesalts,monooctanoin,methyltert­butylether,orothersolventsintotheCBDthrougha

Ttubearemedicalremediesforcholedocholithiasisthathavebeendescribedintheliterature.

Theefficacyofthesurgical/endoscopicapproachestobileductstoneshavemademedicalapproachesunattractive.Theprincipal disadvantagesofbileacidinfusionaretheprolongedperiodofhospitalizationrequiredtocarryoutthetreatment,theunsatisfactory handlingofdistaloccludingstonesandthoseonthehepaticsideoftheT­tube,thehighincidenceofsideeffects,andtherather

unpredictableoutcome.(25­29)

9.2.2.Cholangiocarcinoma

Cholangiocarcinomasareepithelialcancersofthecholangiocytesandtheycanoccuratanylevelofthebiliarytree.Theyarebroadly classifiedintointra­hepatictumours,(extra­hepatic)hilartumoursand(extra­hepatic)distalbileducttumours. Majorityariseintheabsenceofriskfactors,howeveridentifiedriskfactorsincludeage,primarysclerosingcholangitis,chronic choledocholithiasis,bileductadenoma,biliarypapillomatosis,Caroli’sdisease,choledochalcyst,thorotrast,smoking,parasiticbiliary

infestationandchronictyphoidcarrierstate.(30)Hilarcholangiocarcinomaaccountsfortwothirdsofallcasesofextra­hepatic

cholangiocarcinoma.

Intra­hepaticanddistalextra­hepaticcholangiocarcinomasarelesscommon,butsurgicalresectionremainstheonlychanceofcure

consistingofliverresectionandpancreaticoduodenectomy,respectively.Unfortunately,themajorityofthesetumorsareunresectable,

Surgeryistheonlycurativeoptionforcholangiocarcinoma.Theextentofspread,availablesurgicalexpertiseandassociatedco­

morbiditiesareimportantfactorsthatwilldeterminethetreatmentapproach.Althoughseveralsurgicalserieshavebeenreported,

recenttrendsaretoadvocateaccuratepreoperativestagingwithanaggressiveonco­surgicalapproachinvolvingen­blochilaror

hepaticresections.

Currently,cholecystectomy,lobarorextendedlobarhepaticandbileductresection,regionallymphadenectomy,andRoux­en­Y hepaticojejunostomyarethetreatmentsofchoiceforhilarcholangiocarcinoma.Encouragingreportswiththeuseofphotofrinbased

photodynamictherapyhavebeenreportedintheliterature.(31­34)

Systemictherapy/Palliativetherapy:Themajorityofpatientswithcholangiocarcinomapresentatanadvancedstageorhaveassociated

co­morbiditythatprecludesurgery.Forthesepatients,thegoaloftreatmentistoobtainadequatepalliation.Biliaryendoprosthesis

(stent)placementisausefuloptionforpalliationofjaundice.TheapproachisusuallybyERCPbutforproximallesionsthe

transhepaticroutemaybeused.

Photodynamictherapy,radiationandchemotherapyareallavailableaspalliativeoptions.Severalchemotherapeuticagentshavebeen

evaluatedwithlimitedresults.Gemcitabineor5­Fluorouracilarethetwocommonagentsusedasasingleagentorincombinationwith

otherdrugs.(35;36)

9.2.3.Ampullarytumours

Peri­ampullarycancerscanbebroadlyconsideredastumorsarisingwithin1cmoftheampullaofVaterandincludeampullary,distal

bileduct,pancreatic,andduodenalcancers.However,withoutcarefulhistologicalanalysis,itisdifficultifnotimpossibleto

differentiatethetumortype.

Surgicalexcisionisthemainstayoftreatmentforperi­ampullarycancers.Carefulpreoperativestagingandassessmentofrespectability iscrucial.Ifthetumorisresectable,theprocedureofchoiceisapancreaticoduodenectomy.Theclassicalapproach(Whipple’s procedureorcWhipple)describedbyKauschandWhippleremainsthemostpopulartechniqueinNorthAmericaandEurope.The

moreconservativeapproach(pyloruspreservingWhippleresectionorppWhipple)describedbyWatsonin1943andlaterpopularized

byTraversoandLongmireisanothertechniquethatisgraduallygainingmoreconverts.Pylorus­preservingpancreaticoduodenectomy isreportedtobeaneasierandlesstime­consumingoperationwithlessbloodloss,ashorterhospitalstay,andbetterweightgainduring follow­upcare.Also,nodifferencesintherecurrencerateandpatientsurvivalexistbetweenpylorus­preserving

pancreaticoduodenectomyandthestandardWhippleprocedure.(37;38)

Forunresectabletumors,palliativetreatmentwilldependoncomorbidityfactors,andavailabilityofresourcesandexpertisefor endoscopictreatment.Biliarybypassprocedurescanbedoneoperatively,laparoscopically,endoscopicstentingorbypercutaneous

transhepaticapproaches.(39)

Gastricbypassproceduresmayalsobeindicatedinpatientswithgastricoutletobstruction.Theroleofprophylacticgastricbypass proceduresiscontroversial,howeveraprospectiverandomizedclinicaltrialconcludedthataprophylacticgastrojejunostomy significantlydecreasestheincidenceoflategastricoutletobstructionanddidnotincreasetheincidenceofpostoperativecomplications

orextendthelengthofstay.(40)

9.2.4.PancreaticCancer

PancreaticductaladenocarcinomaisonethemostlethalGImalignancywithanoverall5­yearsurvivalrateoflessthan4%.Factors

influencingthisgrimprognosisare1)clinicalsymptomsintheearlystageareusuallyabsentornonspecificresultinginlatediagnosis,

withonly15–20%oftumorsbeingrespectableatpresentation.2)Clinically,aggressivegrowth,withretroperitonealandperineural

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OBSTRUCTIVEJAUNDICE

infiltration,angioinvasion,highratesoflocalrelapse,formationofmetastases,and3)resistancetomostoftheavailabletreatment

regimens,makespatientmanagementacomplexandchallengingtask.(41)

Theonlyhopeforcureissurgery,butunfortunatelylessthan20%arerespectable.

Thereisnowanacceptableoperativemortalityrateoflessthanorequalto5%forresectedpatientswhenperformedatexperiencedor

dedicatedcenterswithhighvolumeofpatientsinthewesternworld.Thetreatmentoptionsaresimilartoperi­ampullarycancers.The

roleofadjuvanttherapyinadvancedpancreaticcanceriscontroversialasmostofthetrialsshowlimitedbenefits.Gemcitabine,5FU

areagentsthatshowsomepromise.

PainPalliation:Patientswhopresentwithseverepainmustreceiveopioids.Morphineisgenerallythedrugofchoice.Usually,theoral routeispreferredinroutinepractice.Parenteralroutesofadministrationshouldbeconsideredforpatientswhohave impairedswallowingorgastrointestinalobstruction.Percutaneousceliacplexusblockadecanbeconsidered,especiallyforpatients whoexperiencepoortoleranceofopiate

analgesics.(42)

9.2.5.BiliaryStrictures

Biliarystricturescanbebenignormalignant.Inthissectionofthereview,ourfocuswillbeonbenignbiliarystricturesasthecommon

causesofmalignantstrictureshavebeentreatedearlier.

Themajorityofbenignstricturesareiatrogenic­asaresultofoperationsonthegallbladderandthebiliarytree.Theintroductionof

laparoscopiccholecystectomyinitiallyledtoanincreaseinoperativetraumatothebileductsfrom0.1­0.2%to2%.Thiswasnot

surprisingconsideringthesteeplearningcurveoflaparoscopicprocedures.However,afterwidespreadadoptionoflap

cholecystectomy,theincidenceofoperativetraumastillremainshigherthanwhatobtainedintheeraofopencholecystectomyat0.2­

0.7%.(43)

Noniatrogeniccausesofbenignstricturesincludeinflammatoryconditionsandsubsequentfibrosisrelatedtochronicpancreatitis, cholelithiasis,choledocholithiasis,sclerosingcholangitis,stenosisofthesphincterofOddi,orinfectionsofthebiliarytract. Threeoptionsforthemanagementofbenignbiliarystricturesarecurrentlyavailable:percutaneousdilationandstenting,endoscopic dilationandstenting,andsurgicalbiliarydrainage,mostcommonlybyaRoux­en­Yhepaticojejunostomy.

Alltheoptionshavecomparableresults,withstricturerelapseratesreportedbetween15%–45%andmeanfollow­uptimesof4–9

years.(43)

Thechoiceoftreatmentmodalitymustbeindividualizedandshouldbebasedonthefollowingconsiderations:thelocationand

severityofthestricture,thepresenceofbiliary­entericcontinuity,thedegreeofinfection,over­allhealthoftheindividualpatient,the

lengthoftimeanticipatedforstenting,andtheneedforrepeateddilationandstentexchange.Itcallsforaclosecollaborationbetween

thesurgeonandtheinterventionalradiologist.

10.Complications

Complicationsofobstructivejaundiceincludesepsisespeciallycholangitis,biliarycirrhosis,pancreatitis,coagulopathy,renalandliver

failure.Othercomplicationsarerelatedtotheunderlyingdiseaseandtheproceduresemployedinthediagnosisandmanagementof

individualdiseases.Cholangitisespeciallythesuppurativetype(Charcot’striadorRaynaud’spentad)isusuallysecondaryto

choledocholithiasis.ItmayalsocomplicateprocedureslikeERCP.Treatmentshouldincludecorrectionofcoagulopathy,

fluid/electrolyteanomaly,antibioticsandbiliarydrainagewithERCPwhereavailableortrans­hepaticdrainageorsurgery.

11.Conclusion

Obstructivejaundiceisaclinicaldiagnosisthatrequiresbothclinicalanddiagnosticworkuptoelucidatethepreciseetiology.Amulti

disciplinaryapproachthatrequirestheclinician,radiologist,endoscopistandinterventionalradiologistwillleadtoabetteroutcome.

12.Recommendations

1.Treatmentshouldbeindividualized­basedonpatientfactorsandavailabilityofresourcesandpersonnel.

2.Tooptimizetreatmentforpancreaticcancers,dedicatedcentersshouldbeestablished.

3.PyloruspreservingresectionisrecommendedinsteadoftheClassicalWhipple’sresection.

4.Extensivepalliativeprocedurescarryasignificantdegreeofmorbidityandmortalityinadvancedhepatobiliarymalignanciesand

shouldbediscouraged.

5.NeedfortraininginendoscopicproceduresforAfricansurgeons.

6.ERCPispreferredtotrans­hepaticdrainageforbiliarydecompressionexceptforobstructionsnearthehepaticbifurcation.

7.PrimaryclosureofthecommonbileductafterexplorationforstonesisassafeasleavingaTtubeinsituandassociatedwith

fewercomplicationsifconfirmationofbiliaryclearancecanbeobtained.

AdisaAdeyinkaCharlesMD,FWACS,FICS

AssociateProfessorofSurgery

AbiaStateUniversityTeachingHospital

Aba,Nigeria

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