Ampullary Carcinoma_ Epidemiology, Clinical Manifestations, Diagnosis and Staging
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Official reprint from UpToDate www.uptodate.com ©2015 UpToDate Author John A Martin, MD Section Editor Douglas A Howell, MD, FASGE, FACG Deputy Editors Anne C Travis, MD, MSc, FACG, AGA Diane MF Savarese, MD Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2015. | This topic last updated: Jan 06, 2015. INTRODUCTION — Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater. They can originate from the pancreas, duodenum, distal common bile duct (CBD), or the structures of the ampullary (ampulla of Vater) complex. The ampulla of Vater is formed by the duodenal aspect of the sphincter of Oddi muscle, which surrounds the confluence of the distal CBD and main pancreatic duct as well as the papilla of Vater, a mucosal papillary mound at the distal insertion of these ducts on the medial wall of the duodenum ( figure 1 ). Ampullary carcinomas are defined as those that arise within the ampullary complex, distal to the bifurcation of the distal common bile duct and the pancreatic duct ( figure 2 ). The papilla is a nipplelike structure on the medial aspect of the second portion of the duodenum best visualized with a sideviewing endoscope. The distal bile and ventral pancreatic ducts traverse the duodenal wall in this location and open into the duodenal lumen through the small mucosal elevation of the papilla of Vater. The epidemiology, clinical features, diagnosis, and staging of ampullary carcinoma will be reviewed here. Treatment of ampullary cancers and the approach to the patient with ampullary adenoma is presented separately. (See "Ampullary carcinoma: Treatment and prognosis" and "Clinical manifestations and diagnosis of ampullary adenomas" and "Treatment of ampullary adenomas" .) EPIDEMIOLOGY AND BIOLOGIC BEHAVIOR — Neoplastic transformation of the intestinal mucosa occurs more commonly near the ampulla than at any other site in the small intestine. Despite this, primary ampullary tumors are rare, with an incidence of approximately four to six cases per million population [14 ]. They account for only 6 percent of lesions that arise in the periampullary region [5 ], but are responsible for 20 percent of all tumor related obstructions of the common bile duct [6 ]. There is some evidence that the incidence has increased over the last 30 years [3 ]. Both benign and malignant ampullary tumors can occur sporadically or in the setting of a genetic syndrome. The incidence of ampullary tumors is increased 200 to 300fold among patients with hereditary polyposis syndromes, such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) compared with the general population [79 ]. Surveillance endoscopy is particularly important to detect early ampullary lesions in patients with FAP given the high incidence of coexisting premalignant duodenal adenomatous polyps. Up to 90 percent of patients with FAP develop adenomas in the upper gastrointestinal tract [10 ]. (See "Familial adenomatous polyposis: Screening and management of patients and families" .) The average age at diagnosis of sporadic ampullary carcinomas is 60 to 70 years old [8,1113 ]. In contrast, patients whose ampullary carcinomas arise in the setting of an inherited polyposis syndrome usually present at an earlier age, due in part to endoscopic screening and surveillance programs. Biologic behavior — Several lines of evidence suggest that the biology of primary ampullary adenomas and carcinomas is more analogous to intestinal rather than pancreaticobiliary neoplasms: ® ® The histology of primary ampullary neoplasms more often resembles that of adenomas and adenocarcinomas of intestinal origin rather than pancreaticobiliary origin. In one study of 170 ampullary carcinomas, the most common histologic subtype was intestinal (47 percent), followed by pancreatobiliary (24 percent), poorly differentiated adenocarcinomas (13 percent), intestinalmucinous (8 percent), and invasive papillary (5 ●
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Transcript of Ampullary Carcinoma_ Epidemiology, Clinical Manifestations, Diagnosis and Staging
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OfficialreprintfromUpToDate www.uptodate.com2015UpToDate
AuthorJohnAMartin,MD
SectionEditorDouglasAHowell,MD,FASGE,FACG
DeputyEditorsAnneCTravis,MD,MSc,FACG,AGAFDianeMFSavarese,MD
Ampullarycarcinoma:Epidemiology,clinicalmanifestations,diagnosisandstaging
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Mar2015.|Thistopiclastupdated:Jan06,2015.
INTRODUCTIONPeriampullarytumorsareneoplasmsthatariseinthevicinityoftheampullaofVater.Theycanoriginatefromthepancreas,duodenum,distalcommonbileduct(CBD),orthestructuresoftheampullary(ampullaofVater)complex.TheampullaofVaterisformedbytheduodenalaspectofthesphincterofOddimuscle,whichsurroundstheconfluenceofthedistalCBDandmainpancreaticductaswellasthepapillaofVater,amucosalpapillarymoundatthedistalinsertionoftheseductsonthemedialwalloftheduodenum(figure1).Ampullarycarcinomasaredefinedasthosethatarisewithintheampullarycomplex,distaltothebifurcationofthedistalcommonbileductandthepancreaticduct(figure2).
Thepapillaisanipplelikestructureonthemedialaspectofthesecondportionoftheduodenumbestvisualizedwithasideviewingendoscope.ThedistalbileandventralpancreaticductstraversetheduodenalwallinthislocationandopenintotheduodenallumenthroughthesmallmucosalelevationofthepapillaofVater.
Theepidemiology,clinicalfeatures,diagnosis,andstagingofampullarycarcinomawillbereviewedhere.Treatmentofampullarycancersandtheapproachtothepatientwithampullaryadenomaispresentedseparately.(See"Ampullarycarcinoma:Treatmentandprognosis"and"Clinicalmanifestationsanddiagnosisofampullaryadenomas"and"Treatmentofampullaryadenomas".)
EPIDEMIOLOGYANDBIOLOGICBEHAVIORNeoplastictransformationoftheintestinalmucosaoccursmorecommonlyneartheampullathanatanyothersiteinthesmallintestine.Despitethis,primaryampullarytumorsarerare,withanincidenceofapproximatelyfourtosixcasespermillionpopulation[14].Theyaccountforonly6percentoflesionsthatariseintheperiampullaryregion[5],butareresponsiblefor20percentofalltumorrelatedobstructionsofthecommonbileduct[6].Thereissomeevidencethattheincidencehasincreasedoverthelast30years[3].
Bothbenignandmalignantampullarytumorscanoccursporadicallyorinthesettingofageneticsyndrome.Theincidenceofampullarytumorsisincreased200to300foldamongpatientswithhereditarypolyposissyndromes,suchasfamilialadenomatouspolyposis(FAP)andhereditarynonpolyposiscolorectalcancer(HNPCC)comparedwiththegeneralpopulation[79].SurveillanceendoscopyisparticularlyimportanttodetectearlyampullarylesionsinpatientswithFAPgiventhehighincidenceofcoexistingpremalignantduodenaladenomatouspolyps.Upto90percentofpatientswithFAPdevelopadenomasintheuppergastrointestinaltract[10].(See"Familialadenomatouspolyposis:Screeningandmanagementofpatientsandfamilies".)
Theaverageageatdiagnosisofsporadicampullarycarcinomasis60to70yearsold[8,1113].Incontrast,patientswhoseampullarycarcinomasariseinthesettingofaninheritedpolyposissyndromeusuallypresentatanearlierage,dueinparttoendoscopicscreeningandsurveillanceprograms.
BiologicbehaviorSeverallinesofevidencesuggestthatthebiologyofprimaryampullaryadenomasandcarcinomasismoreanalogoustointestinalratherthanpancreaticobiliaryneoplasms:
Thehistologyofprimaryampullaryneoplasmsmoreoftenresemblesthatofadenomasandadenocarcinomasofintestinaloriginratherthanpancreaticobiliaryorigin.Inonestudyof170ampullarycarcinomas,themostcommonhistologicsubtypewasintestinal(47percent),followedbypancreatobiliary(24percent),poorlydifferentiatedadenocarcinomas(13percent),intestinalmucinous(8percent),andinvasivepapillary(5
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SubdividingadenocarcinomasoftheampullaofVateraccordingtohistologicsubtypeandimmunohistochemicalstainingpatternintodistinctsubsetswithdifferingbiologicbehaviorhasprognosticimportance.Inaretrospectivestudyof208patientstreatedforampullaryadenocarcinomainSydney,Australia,thosewithahistomolecularpancreaticobiliaryphenotype(CDXnegative,MUC1positive)hadasignificantlyworseoutcomethandidthosewithanintestinalphenotype(CDXpositive,MUC1negative),withmediansurvivalof16versus116months[22].Whenhistomolecularphenotypewascombinedwiththelymphnodestatus,threesubsetsofampullaryadenocarcinomasemergedwithsignificantlydifferentsurvivaloutcomes:
Theresultswerecomparableintwoadditionalindependentcohortsof90patientsfromGlasgow,Scotland,and46fromVerona,Italy.
Identificationofprognosticallyrelevantsubgroupshasalsobeenachievedbyuseofgeneexpressionprofilinginconjunctionwithimmunohistochemicalstainingforcytokeratins7and20[23].However,moleculartechniquessuchasthesearenotyetreadyforclinicalapplication.(See"Overviewofgeneexpressionprofiling,proteomics,andmicroRNAprofilinginclinicaloncology".)
Whetherandhowthisinformationcouldbeusedtoindividualizetreatmentdecisions,particularlyaboutadjuvanttherapy,isunclear.Theimpactofadjuvanttherapyonoutcomesaccordingtohistomolecularphenotypecouldnotbeaddressedinthestudydescribedabovesinceonlyaminorityofpatients(64of208)inallthreecohortsreceivedadjuvantchemotherapy,anditwasnotrandomlyassigned[22].Prospectivestudyoftreatmentselectionbaseduponhistomolecularphenotypeisneededbeforeconclusionscanbedrawn.Atpresent,adjuvanttherapyrecommendationsforpatientswithampullarycancerfollowguidelinesestablishedforpancreaticcancer,rather
percent)[14].
Ampullarycarcinomasarethoughttoarisefromampullaryadenomas,apremalignantprecursorlesiondisplayingtheadenomacarcinomasequenceobservedincolorectalneoplasia.Moreover,patientswithFAPhaveasignificantlyincreasedincidenceofbothampullaryandcolorectalcancersrelativetothegeneralpopulation,suggestingthatthemechanismofampullaryandcolorectalcarcinogenesismaybesimilar[15].
Krasmutationsareanearlyeventinampullarycarcinogenesis,withanincidence(37percent)thatissimilartothatincoloncancer(upto50percent)[16].(See"Moleculargeneticsofcolorectalcancer",sectionon'Oncogenes'.)
Expressionprofilingofcyclooxygenase2(COX2)byampullarycarcinomasismoreconsistentwithaneoplasmofintestinaloriginthanpancreaticobiliaryorigin.HighCOX2expressionhasbeendetectedin78percentofampullarycarcinomas[17].Ofampullarycarcinomasclassifiedashavinganintestinalorigin,95percenthadhighCOX2expression,whereasonly50percentoflesionswithapancreaticobiliaryorigindemonstratedhighCOX2expression.
Trueampullarycancershaveabetterprognosisthanperiampullarymalignanciesofpancreatic[1820]orextrahepaticbiliary[21]origin.Resectabilityratesarehigher(over90percentinsomecontemporaryseries),andfiveyearsurvivalratesareapproximately30to50percent,eveninpatientswithlymphnodeinvolvement.Incontrast,fewerthan10percentofpatientswithcompletelyresectednodepositivepancreaticcancerarealiveattwoyears.(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis"and"Ampullarycarcinoma:Treatmentandprognosis".)
Patientswithanodenegative,nonpancreaticobiliaryhistomolecularphenotypetumorhadanexcellentprognosis(fiveyearsurvival88percent).
Patientswithanodepositivepancreaticobiliaryphenotypehadapoorprognosis(fiveyearsurvival20percent).
Theremainingpatients(nodepositivenonpancreaticobiliaryphenotype,nodenegativepancreaticobiliaryphenotype)hadanintermediateprognosis(fiveyearsurvival47percent).
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thanintestinalcancer.(See"Ampullarycarcinoma:Treatmentandprognosis",sectionon'Adjuvanttherapy'.)
CLINICALMANIFESTATIONSAswithampullaryadenomas,themostcommonpresentingsymptomofampullarycarcinomaisobstructivejaundice(80percent)causedbycompressionofthedistalbileductbythetumor[11,24].(See"Clinicalmanifestationsanddiagnosisofampullaryadenomas".)
Ampullarycancersarenotusuallysuspectedasacauseofobstructivejaundicebecauseoftheirlowerincidencerelativetootherperiampullarymalignancies.Additionalsymptomsmayincludediarrheaduetofatmalabsorption(steatorrhea),mildweightloss,andfatigue.
Uptoonethirdofpatientshavechronic,frequentlyoccultgastrointestinalbloodlosswithanassociatedmicrocyticanemiaorhemepositivestools.Patientsoccasionallypresentwithfrankbleedingduetosloughingofthetumor,aconditionexacerbatedbytheuseofantiplateletagentssuchasaspirinandclopidogrel.Inonereport,nonspecificsymptomsincludeabdominalpain(45percent),fever(45percent),mildnausea,anddyspepsia[25].Largelesionsmayproducegastricoutletobstructionassociatedwithseverenauseaandvomiting.
DIAGNOSISANDSTAGINGThediagnosisofanampullarycarcinomaisestablishedbyacombinationofendoscopic,radiologic,andhistologicfeatures.Accuratestagingisessentialforplanningsurgicaltreatment.
TNMstagingsystemThemostcommonlyusedstagingsystemisthetumornodemetastasis(TNM)systemofthecombinedAJCC(AmericanJointCommitteeonCancer)/UICC(InternationalUnionAgainstCancer)(table1)[26].
Intheabsenceofmetastases,theprognosisofanampullarycarcinomadependsprimarilyupontwofactors:thedegreeoflocaltumorinvasion,asreflectedbytheTstage,andthepresenceoflymphaticspread,asreflectedbytheNstage.
DiagnosticevaluationThediagnosticevaluationofajaundicedpatientwithasuspectedmalignantbileductobstructionisdesignedtoeliminatebenigntumorsorgallstonesfromthedifferential,andtoestablishtheextentoftumorinvasionandspread.Althoughadvancedendoscopictechniquescanhelptodifferentiateampullaryadenomasfromcarcinomas,itmaybedifficulttocompletelyexcludeacarcinomawithoutcompleteresectionofthelesion.Ampullaryadenomashavethepotentialtoundergomalignanttransformation,andanoccultfocusofcarcinomamaybepresentwithinapredominantlybenignadenoma.(See"Clinicalmanifestationsanddiagnosisofampullaryadenomas".)
Atransabdominalultrasound(US)isareasonablefirsttestinpatientspresentingwithobstructivejaundice,butitwillgenerallynotshowthetumor.Helicalcomputedtomography(CT)scanningshouldbeobtainedtovisualizethepancreasandsurroundingstructures.Althoughitsspatialresolutionisinadequatetodeterminethedegreeoflocaltumorinvasion,itisthemostusefultesttoexcludethepresenceofdistantmetastases.(See'Transabdominalultrasonography'belowand'AbdominalCT'below.)
Endoscopicretrogradecholangiopancreatography(ERCP)isthesinglemostusefulendoscopicstudyfordiagnosingampullarycarcinomabecauseitpermitsidentificationofthetumor,biopsy,anddecompression,ifneeded.Whileendoscopicultrasonography(EUS)isassensitiveasERCPandsuperiortoCTandtransabdominalUSfordetectingsmallampullarytumors,itistypicallynotrequiredfordiagnosis.Itmayhavearoleinpreoperativestagingbutmayresultinoverstaging.Asaresult,wedonotroutinelyemployEUSforthediagnosisandstagingofampullarycarcinoma.(See'ERCP(endoscopicretrogradecholangiopancreatography)'belowand'Endoscopicultrasonography(EUS)'below.)
Differentiatingaprimaryampullarycarcinomafromothermorecommonperiampullarymalignancies(arisinginthepancreas,duodenum,orbileduct)ischallenging.Althoughthedistinctionmaybeevidentafterradiographicandendoscopicevaluation,itmaynotbepossibletodeterminethetissueoriginofamalignantperiampullaryneoplasmuntilresectionandhistopathologicevaluationoftheentiresurgicalspecimeniscompleted[27].Thisisparticularlytrueifthelesionislargeandobstructstheduodenallumen.Fromasurgicalstandpoint,thedistinctionbetweenampullaryandperiampullarycancersisnotessentialpreoperativelysincethetreatmentisthesameforboth
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lesions.However,theoncologicimplicationsandprognosisoftheampullaryandperiampullarytumorsaresubstantiallydifferent.(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis"and"Diagnosisandstagingofsmallbowelneoplasms",sectionon'Adenocarcinoma'and"Treatmentoflocalizedcholangiocarcinoma:Adjuvantandneoadjuvanttherapyandprognosis",sectionon'Distalcholangiocarcinoma'.)
TransabdominalultrasonographyTransabdominalultrasonography(US)shouldbethefirstimagingstudyorderedforpatientswithjaundice,sinceUScanidentifyintrahepaticandextrahepaticbileductdilatationandgallstones.However,overlyingbowelgasfrequentlyobscuresthedistalbileduct,ampulla,andpancreas.Inonestudy,only10of127ampullarymassesweredetectedbyultrasound[28].Theoverallaccuracywas15percent,accordingtoonestudy[29].Asaresult,abdominalCTshouldbeorderedasthenextdiagnosticprocedureifUSdoesnotdemonstrategallstonesoranobviouspancreaticheadmassinajaundicedpatient.
AbdominalCTCTismoresensitivethanUSforevaluatingtheperiampullaryregion(image1).A"pancreaticmassprotocol"CTshouldbeordered.Specifically,patientsshouldreceivewaterastheoral"contrastagent"(todistendtheduodenumandimprovevisualizationoftheduodenallumenandadjacentpancreas),andIVcontrastisinjectedasabolustopermitbotharterialandvenousphaseimaging.Imagesareacquiredat1.0to2.5mmintervalstoimprovethesensitivityofpancreaticimaging.(See"Clinicalmanifestations,diagnosis,andstagingofexocrinepancreaticcancer",sectionon'Imagingstudies'.)
AlthoughhelicalCTcandetectmassesobstructingthedistalcommonbileduct(CBD),itssensitivityusuallydoesnotpermitthevisualizationofsmallampullaryneoplasmswithintheduodenallumen[30].Inonereport,theoverallaccuracywasonly20percent[29].Furthermore,CTbyitselfisinadequateforstagingampullarycancersbecauseitlacksthespatialresolutiontodeterminethedegreeoflocaltumorinvasionintotheduodenalwall,adjacentpancreas,orthepresenceofmajorvascularinvolvement[31].Ontheotherhand,CTisgenerallythemostusefulstudytoevaluateforthepresenceofdistantmetastaticdiseasewhichmostfrequentlyinvolvestheregionallymphnodes,liver,peritoneum,lungs,andbone.
ERCP(endoscopicretrogradecholangiopancreatography)Inajaundicedpatientwithsuspectedmalignantbileductobstruction,ERCPisthepreferredinitialendoscopicstudysinceitpermitssimultaneousendoscopicvisualizationoftheampulla,cholangiographyofthepancreaticandbileducts,biopsyfromthepapillaandampullarysegmentoftheCBDorpancreaticduct,andplacementofastentforbiliarydecompression,ifnecessaryandtechnicallyfeasible.However,ERCPcannotdeterminetheextentoflocaltumorinvasionofanampullarycarcinomaintotheadjacentduodenumorpancreaticparenchyma,informationthatisessentialforpreoperativestagingandsurgicalplanning.
Mostampullarycancersareobviousendoscopically(image2).Ifanexophyticampullarytumorisidentifiedthathastheappearanceofanadenoma,malignancyshouldbestronglysuspectedifthemassisulceratedorover3cminsize.However,becausethefalsenegativerateofendoscopicbiopsyisashighas50percent,anegativeresultisinsufficienttoexcludethepresenceofmalignancyinanampullarylesion[3237].TheoverallaccuracyofdiagnosiswithERCPinonereportwas88percent(p>0.05)[38].
Attemptstoenhancetheaccuracyofendoscopicbiopsyincludetheacquisitionoftissueatleast48hoursfollowingsphincterotomy[39,40],theperformanceofmultiplebiopsies[41],andtheuseofpolymerasechainreaction(PCR)orimmunohistochemicalstainingtodetectp53(atumorsuppressorgenethatisfrequentlylostinperiampullaryneoplasms)orKrasgenemutations[16,4246].Noneofthesemethodsareusedroutinelyincurrentclinicalpractice.
MRCPandpercutaneoustranshepaticcholangiographyAmpullaryobstructioncanalsobeevaluatedbymagneticresonancecholangiopancreatography(MRCP)orpercutaneoustranshepaticcholangiography(PTC)inpatientswithcontraindicationstoERCP(eg,thosewhohaveundergonegastricsurgery,suchasaRouxenYgastrojejunostomy,withresultantanatomythatmaymakeendoscopicaccessoftheduodenumtechnicallychallengingorimpossible,evenwithdeepenteroscopytechniques).However,neitheroftheseimagingmodalitiespermitsdirectluminalvisualizationofthepapillaryaspectoftheampulla,nordotheyprovideaccessfortissueacquisitionviadirectforcepsbiopsy.
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MRCPisanoninvasivemethodofimagingthepancreaticobiliarytreeviamagneticresonanceimaging.SomeauthorsrecommendthisapproachinplaceofERCPinpatientswhowillnottolerateinvasiveproceduresorinwhomalargetumoroccludestheorificeofthepancreaticobiliaryducts,thuspreventingcannulationandductopacificationatthetimeofERCP.Ampullarycarcinomasappearasmasses(fillingdefects)protrudingintotheduodenallumen,withcharacteristicdelayedenhancementandhyperintensityondiffusionweightedimaging[47,48].InonereporttheoverallaccuracyofdiagnosiswithMRCPwas76percent[38].(See"Magneticresonancecholangiopancreatography".)
Incontrast,PTCisaninvasiveprocedureduringwhichthebiliarytreeisaccessedpercutaneouslyusinganeedleinsertedthroughtheparenchymaoftheliverintoanintrahepaticbileduct,thencontrastopacifiedunderfluoroscopy.PTCismostcommonlyperformedwhenthebiliarytreeisdilatedandERCPhasfailedtocannulateoradequatelydemonstratethebiliaryanatomy.PTCprovidesnotonlycholangiographybutalsotheopportunityforbrushcytology(althoughnotforcepsbiopsyforhistology)ofradiographicstrictures,althoughampullarylesionsthatdonotextendintothedistalCBDmaynotbeamenabletotissueacquisitionviathisroute.AnotherlimitationofPTCisthatitcannotdirectlyvisualizeampullarylesions,duodenaltumoringrowth,orinvolvementofthepancreaticduct.(See"Percutaneoustranshepaticcholangiography".)
Endoscopicultrasonography(EUS)Endoscopicultrasonography(EUS)isassensitiveasERCPandsuperiortoCTandtransabdominalUSfordetectingsmallampullarytumors,thoughitistypicallynotrequiredfordiagnosis[29,47,4957].Itmayhavearoleinpreoperativestagingtolookfortumorextensionandtodeterminethedepthoftumorinvasion,butitmayresultinoverstaging.Asaresult,wedonotroutinelyemployEUSforthediagnosisandstagingofampullarycarcinoma.
BecausebiliaryandpancreaticsphincterotomyandstentplacementcannotbeperformedusingEUSequipment,patientswhorequiretherapeuticinterventionmustalsoundergoanERCP,whichcanoftenbeperformedconcomitantly.
RoleindiagnosisMostcancersareclearlyseenendoscopically,andampullectomywillprovidetissueforhistologicdiagnosis,soEUSisgenerallynotrequiredfordiagnosis.Inaddition,EUSwillnotbehelpfulforidentifyingfociofcarcinomawithinotherwisebenignlesions.EUSmaybeindicatedfortheoccasionalbiopsynegativeampullarylesionthathasequivocalendoscopicfeaturesofmalignancy.(See"Treatmentofampullaryadenomas",sectionon'Endoscopicampullectomy'.)
IfmalignancyissuspectedinapatientundergoingEUS,fineneedleaspiration(FNA)oftheampulla,papilla,andsurroundingdeeperstructuresincludinglocallymphnodescanbeobtainedduringtheprocedure.However,anegativeresultdoesnotexcludethepresenceofamalignantfocuswithinanadenoma.(See"Endoscopicultrasoundguidedfineneedleaspirationbiopsyinthegastrointestinaltract".)
Inonereport,theoverallaccuracyofEUSguidedfineneedleaspirationbiopsy(FNAB)forprimarymassesoftheampullaryregionwas89percent,withasensitivityof82percentandaspecificityof100percent[58].
RoleinstagingEUSisthemostaccuratemodalityavailabletoassessthetumor(T)stageofampullarytumors,whichiscriticalforplanningsurgicalintervention.MultipleseriesconsistentlydocumentprimaryTstagingaccuraciesof70to90percent[7,49,51,54,5965].However,EUSstagingmethodstendtooverestimatethedepthoftumorinvasionandresultingTstage,whichcouldleadtoinappropriatetreatment[6].Accuracymaybedecreasedinthepresenceofanendobiliarystent[53].EUSislesshelpfulfornodal(N)staging.
EUSiscapableofobtainingimagesofthedistalbiliaryandpancreaticducts,permittingassessmentoflocalintraductaltumorextension.EUSalsoaccuratelydemonstratesthedepthoftumorpenetrationintotheduodenumbydemonstratingobliterationoftheinterfacebetweenthetumorandthemuscularispropriaoftheduodenum(afeaturethatupstagesthetumortoT2).Tumorextensionintothepancreasisassessedbythedepthofinvasion(2cmorcontiguousspreadtoadjacentorganssignifyingT4disease)(image3).
EUSislessaccurateforNstagingthanitisforTstaging.Ampullarycancersdrainintotwolymphnodebasins:
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theretroduodenopancreaticchainandthesuperiormesentericchain.Onestudyreportedasensitivityandspecificityof67and96percent,respectively,forEUSdetectionofnodalmetastaseswhenabnormalnodeswereseen(definedasthoseoveronecentimeterindiameterandlocatedintheabovetwopositions)[65].Anotherseriesfoundsensitivityandspecificityratesof69and38percent,respectively,whenallvisualizedlymphnodespresentaroundtheduodenopancreaticblockwerepresumedtobemetastatic,regardlessofsizeorposition[64].However,othershavereportedsensitivityratesaslowas21percentfordetectionofnodalmetastasesbyEUS[66].
EUSguidedFNAofsuspiciouslymphnodesmayfurtherincreasetheaccuracyofnodalstaging.Thistopicisdiscussedindetailelsewhere.(See"Endoscopicultrasoundguidedfineneedleaspirationbiopsyinthegastrointestinaltract",sectionon'Pancreaticmasses'.)
IntraductalultrasonographyThetechnicalevolutionofEUShasledtothedevelopmentofsmallcaliberintraductalultrasound(IDUS)miniprobes(approximately2mm),whichcanbepassedthroughstandardendoscopesdirectlyintothebileorpancreaticduct.Thesmallcaliber,flexibility,andexcellentimagequalityproducedbythesecathetersmakesthemusefulforevaluatingavarietyofbiliaryandpancreaticdisorders.IDUSaccuratelyvisualizestheanatomyofthepapillaandistheonlyprocedurethatreliablydifferentiatesthesphincterofOddimusclefromtheremainderofthepapilla.Asaresult,IDUScanbeusefulfordiagnosingandassessingthesizeandextentofpapillarytumors.Inastudyof40patientswithampullarycarcinoma,IDUSwasmoreaccuratethanEUSforTstagingandevaluatingductalinvasion[67].(See"Intraductalultrasoundofthepancreaticobiliaryductalsystem".)
MagnificationendoscopywithnarrowbandimagingNarrowbandimagingusesopticalfilterstoenhancevisualizationofmicrovesselsandmucosalsurfacearchitectureingastrointestinaldiseases.Thetechniquedemonstratesabnormalvesselsassociatedwithhighgradedysplasiaonthesurfaceofhighgradeadenomasandadenocarcinomas.Abnormalvesselshavenotbeenidentifiedonthesurfaceofbenignampullaryadenomaswithhyperplasticorinflammatoryhistology.Preliminarystudieshavesuggestedapotentialroleforevaluationofampullarylesions[68].
LiverbiochemicaltestsBloodchemistriescannotestablishthediagnosisofampullarycarcinoma,butmayreflectthepresenceofcholestasiswhenanampullaryneoplasmresultsinpartialorcompletebiliaryobstruction.Patientsgenerallyhaveacholestaticpatternofliverbiochemicaltestabnormalities,althoughaminotransferasesmayalsobeelevated[25].TheprothrombintimemaybeelevatedduetoimpairedabsorptionoffatsolublevitaminsincludingvitaminK[69].
SerumtumormarkersSerumtumormarkersarenotspecificforampullarycarcinomasandhavelimiteddiagnosticapplication.Nevertheless,someampullarycancersareassociatedwithincreasedserumlevelsofcarbohydrateantigenCA199and/orcarcinoembryonicantigen[19,70],andserialassayofthesetumormarkersmaybeusefulforposttreatmentfollowup.(See"Ampullarycarcinoma:Treatmentandprognosis",sectionon'Posttreatmentsurveillance'.)
SUMMARYANDRECOMMENDATIONSPatientswithampullarycancermostcommonlypresentwithjaundice(80percent)causedbyobstructionofthedistalbileductbytumor.Diagnosisandstagingareachievedbyacombinationofendoscopic,radiologic,andhistologicfeatures(algorithm1).Therearetwomajorconsiderations:identificationofthetumor,anddistinctionfromanampullaryadenomaortumorarisingfromoutsideoftheampulla(mainlypancreaticcarcinomaoradistalcholangiocarcinoma).
Atransabdominalultrasound(US)isareasonablefirsttestinpatientspresentingwithobstructivejaundice,butitwillgenerallynotshowthetumor.Helicalcomputedtomography(CT)scanningshouldbeobtainedtovisualizethepancreasandsurroundingstructures.Althoughitsspatialresolutionisinadequatetodeterminethedegreeoflocaltumorinvasion,itisthemostusefultesttoexcludethepresenceofdistantmetastases.(See'Transabdominalultrasonography'aboveand'AbdominalCT'above.)
Endoscopicretrogradecholangiopancreatography(ERCP)isthesinglemostusefulendoscopicstudysinceit
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ACKNOWLEDGMENTTheauthorsandUpToDatewouldliketothankDr.A.JamesMoser,whocontributedtoearlierversionsofthistopicreview.
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Topic655Version11.0
permitsidentificationofthetumor,biopsy,anddecompression,ifneeded.Whileendoscopicultrasonography(EUS)isassensitiveasERCPandsuperiortoCTandtransabdominalUSfordetectingsmallampullarytumors,itistypicallynotrequiredfordiagnosis.Itmayhavearoleinpreoperativestagingbutmayresultinoverstaging.Asaresult,wedonotroutinelyemployEUSforthediagnosisandstagingofampullarycarcinoma.(See'ERCP(endoscopicretrogradecholangiopancreatography)'aboveand'Endoscopicultrasonography(EUS)'above.)
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GRAPHICS
SphincterofOddiinrelationtotheampullaofVater
DiagramoftheanatomyofthesphincterofOddiandampullaofVater.ThemusclefibersofthesphincterofOddisurroundtheintraduodenalsegmentofthecommonbileductandtheampullaofVater.Acircularaggregateofmusclefibers,knownasthesphinctercholedochus(orsphincterofBoyden),keepsresistancetobileflowhigh,andtherebypermitsfillingofthegallbladderduringfastingandpreventsretrograderefluxofduodenalcontentsintothebiliarytree.Aseparatestructure,calledthesphincterpancreaticus,encirclesthedistalpancreaticduct.Themusclefibersofthesphincterpancreaticusareinterlockedwiththoseofthesphinctercholedochusinafigureeightpattern.
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Locationsampullarytumors
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TNMstagingforampullarycarcinoma
Primarytumor(T)
TX Primarytumorcannotbeassessed
T0 Noevidenceofprimarytumor
Tis Carcinomainsitu
T1 TumorlimitedtotheampullaofVaterorsphincterofOddi
T2 Tumorinvadesduodenalwall
T3 Tumorinvadespancreas
T4 Tumorinvadesperipancreaticsofttissuesorotheradjacentorgansorstructuresotherthanpancreas
Regionallymphnodes(N)
NX Regionallymphnodescannotbeassessed
N0 Noregionallymphnodemetastasis
N1 Regionallymphnodemetastasis
Distantmetastasis(M)
M0 Nodistantmetastasis
M1 Distantmetastasis
Anatomicstage/prognosticgroups
Stage0 Tis N0 M0
StageIA
T1 N0 M0
StageIB
T2 N0 M0
StageIIA
T3 N0 M0
StageIIB
T1 N1 M0
T2 N1 M0
T3 N1 M0
StageIII
T4 AnyN M0
StageIV
AnyT AnyN M1
Note:cTNMistheclinicalclassification,pTNMisthepathologicclassification.
UsedwiththepermissionoftheAmericanJointCommitteeonCancer(AJCC),Chicago,Illinois.TheoriginalsourceforthismaterialistheAJCCCancerStagingManual,SeventhEdition(2010)publishedbySpringerNewYork,Inc.
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Ampullarycarcinoma
SpiralabdominalCTscanshowingasmallampullarymass(arrow)ina74yearoldwomanwithoccultgastrointestinalbloodloss.Notethatthepancreaticheadappearsuninvolved.
CourtesyofAJamesMoser,MD.
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Ampullarycancerendoscopy
Endoscopicviewofanampullarycarcinoma.Notethenodularappearanceofthetumor.
CourtesyofDavidCarrLocke,MD.
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Ampullarycarcinoma
EndoonographicimageobtainedduringEUSshowinginvasionofanampullarylesionintothepancreatichead(T3).Thetumorclearlypenetratesthemuscularispropria.
CourtesyofAJamesMoser,MD.
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Ampullarycarcinomaalgorithm
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