Clinical Manifestations, Diagnosis, And Staging of Exocrine Pancreatic Cancer

12/4/2015 Clinicalmanifestations,diagnosis,andstagingofexocrinepancreaticcancer

http://www.uptodate.com/contents/clinicalmanifestationsdiagnosisandstagingofexocrinepancreaticcancer?topicKey=GAST%2F2501&elapsedTimeMs= 1/58

OfficialreprintfromUpToDate www.uptodate.com2015UpToDate

AuthorCarlosFernandezdelCastillo,MD

SectionEditorsKennethKTanabe,MDDouglasAHowell,MD,FASGE,FACG

DeputyEditorsDianeMFSavarese,MDAnneCTravis,MD,MSc,FACG,AGAF

Clinicalmanifestations,diagnosis,andstagingofexocrinepancreaticcancer

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Mar2015.|Thistopiclastupdated:Mar14,2014.

INTRODUCTIONCanceroftheexocrinepancreasisahighlylethalmalignancy.ItisthefourthleadingcauseofcancerrelateddeathintheUnitedStatesandsecondonlytocolorectalcancerasacauseofdigestivecancerrelateddeath.(See"Epidemiologyandriskfactorsforexocrinepancreaticcancer",sectionon'Epidemiology'.)

Surgicalresectionistheonlypotentiallycurativetreatment.Unfortunately,becauseofthelatepresentation,only15to20percentofpatientsarecandidatesforpancreatectomy.Furthermore,prognosisispoor,evenafteracompleteresection.Fiveyearsurvivalafterpancreaticoduodenectomyisabout25to30percentfornodenegativeand10percentfornodepositivedisease.(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis".)

Theclinicalpresentation,diagnosticevaluation,andstagingworkupforpancreaticexocrinecancerwillbereviewedhere.Epidemiologyandriskfactors,pathology,surgicalmanagement,adjuvantandneoadjuvanttherapy,andtreatmentofadvancedpancreaticexocrinecancer,includingpalliativelocalmanagement,arediscussedelsewhere.

PATHOLOGYThecommonlyusedterm"pancreaticcancer"usuallyreferstoaductaladenocarcinomaofthepancreas(includingitssubtypes),whichrepresentsabout85percentofallpancreaticneoplasms.Oftheseveralsubtypesofductaladenocarcinoma,mostshareasimilarpoorlongtermprognosis,withtheexceptionofcolloidcarcinomas,whichhaveasomewhatbetterprognosis.Themoreinclusiveterm"exocrinepancreaticneoplasms"includesalltumorsthatarerelatedtothepancreaticductalandacinarcellsandtheirstemcells(includingpancreatoblastoma),andispreferred.(See"Pathologyofexocrinepancreaticneoplasms".)

Morethan95percentofmalignantneoplasmsofthepancreasarisefromtheexocrineelements.Neoplasmsarisingfromtheendocrinepancreas(ie,pancreaticneuroendocrine[isletcell]tumors)comprisenomorethan5percentofpancreaticneoplasmstheirclinicalmanifestations,diagnosis,andstagingisaddressedelsewhere.(See"Classification,epidemiology,clinicalpresentation,localization,andstagingofpancreaticneuroendocrinetumors(isletcelltumors)".)

CLINICALPRESENTATIONThemostcommonpresentingsymptomsinpatientswithexocrinepancreaticcancerarepain,jaundice,andweightloss.Inamultiinstitutionalseriesof185patientswithexocrinepancreaticcancerdiagnosedoverathreeyearperiod(62percentinvolvingtheheadofthegland,10percentbody,6percenttail,andtheremaindernotdetermined),themostfrequentsymptomsatdiagnosiswere[1]:

(See"Epidemiologyandriskfactorsforexocrinepancreaticcancer".)(See"Pathologyofexocrinepancreaticneoplasms".)(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis".)(See"Adjuvanttherapyforresectedexocrinepancreaticcancer".)(See"Initialchemotherapyandradiationfornonmetastaticlocallyadvancedunresectable,borderlineresectable,andpotentiallyresectableexocrinepancreaticcancer".)

(See"Supportivecareofthepatientwithadvancedexocrinepancreaticcancer".)(See"Chemotherapyforadvancedexocrinepancreaticcancer".)

Asthenia86percent



Themostfrequentsignswere:

Theinitialpresentationofpancreaticcancervariesaccordingtotumorlocation.Approximately60to70percentofexocrinepancreaticcancersarelocalizedtotheheadofthepancreas,while20to25percentareinthebody/tailandtheremainderinvolvethewholeorgan[2].Comparedtotumorsinthebodyandtailofthegland,pancreaticheadtumorsmoreoftenpresentwithjaundice,steatorrhea,andweightloss[1,3,4].Asanexample,intheabovenotedseries,jaundicewaspresentin73percentofthe114patientswithatumorlocatedintheheadofthepancreas,comparedto11percentof19bodylesions,andnoneofthe11taillesions[1].Steatorrheawaspresentin28percentofthepatientswithpancreaticheadlesionsversus11percentofthosewithbody,andnoneofthosewithtaillesions.Steatorrheaisattributabletolossofthepancreasabilitytosecretefatdigestingenzymesortoblockageofthemainpancreaticduct.

Painisoneofthemostfrequentlyreportedsymptoms,evenwithsmall(



thecourseofthedisease,andmaybesecondarytolivermetastases.

Arecentonsetofatypicaldiabetesmellitus[911]maybenoted.Severalstudieshaveaddressedwhetherearlierdetectionofnonspecificsignsofanevolvingpancreaticneoplasm(particularlyinadultswithnewonsetdiabetesmellitus)mightimproveresectabilityandoveralloutcomes,buttheresultsareinconclusive.Screeningforpancreaticcancerinadultswithnewonsetdiabetesmellitusisdiscussedelsewhere.(See"Epidemiologyandriskfactorsforexocrinepancreaticcancer",sectionon'Diabetesmellitus,glucosemetabolism,andinsulinresistance'.)

Unexplainedsuperficialthrombophlebitis,whichmaybemigratory(classicTrousseaussyndrome)[12],issometimespresentandreflectsthehypercoagulablestatethatfrequentlyaccompaniespancreaticcancer.Thereisaparticularlyhighincidenceofthromboembolicevents(bothvenousandarterial),particularlyinthesettingofadvanceddisease,andcliniciansshouldmaintainahighindexofsuspicion.Multiplearterialemboliresultingfromnonbacterialthromboticendocarditismayoccasionallybethepresentingsignofapancreaticcancer[13].Thromboemboliccomplicationsoccurmorecommonlyinpatientswithtumorsarisinginthetailorbodyofthepancreas[14].(See"Riskandpreventionofvenousthromboembolisminadultswithcancer"and"Nonbacterialthromboticendocarditis".)

Skinmanifestationsoccurasparaneoplasticphenomenainsomepatients.Asanexample,bothcicatricialandbullouspemphigoidaredescribed,evenasafirstsignofdisease[15].(See"Cutaneousmanifestationsofinternalmalignancy",sectionon'Paraneoplasticpemphigus'.)

Rarely,erythematoussubcutaneousareasofnodularfatnecrosis,typicallylocatedonthelegs(pancreaticpanniculitis),maybeevident,particularlyinpatientswiththeacinarcellvariantofpancreaticcancer(figure1).Itishypothesizedthattheconditionisinitiatedbyautodigestionofsubcutaneousfatsecondarytosystemicspillageofexcessdigestivepancreaticenzymes.Thepresenceofthisconditionisnotpathognomonicforanexocrinepancreaticcancer,asithasbeendescribedwithpancreaticneuroendocrinetumors,intraductalpapillarymucinousneoplasms,andinchronicpancreatitis.(See"Cutaneousmanifestationsofinternalmalignancy",sectionunderconstructionand"Pathologyofexocrinepancreaticneoplasms",sectionon'Acinarcellcarcinoma'and"Panniculitis:Recognitionanddiagnosis".)

Signsofmetastaticdiseasemaybepresentatpresentation.Metastaticdiseasemostcommonlyaffectstheliver,peritoneum,lungs,andlessfrequently,bone.Signsofadvanced,incurablediseaseinclude:

Routinelaboratorytestsareoftenabnormal,butarenotspecificforpancreaticcancer.Commonabnormalitiesincludeanelevatedserumbilirubinandalkalinephosphataselevels,andthepresenceofmildanemia.

IncidentalfindingAsolidpancreaticlesionisuncommonlyfoundasanincidentalfindingonCTscansdoneforanotherreason.Inonereport,24ofthe321patientswithasolidpancreaticmasswhowereidentifiedoveraneightyearperiodhaditincidentallydiscovered(7percent)onehalfofthesewereadenocarcinomas,whiletheremainderwerepancreaticneuroendocrinetumors[17].Themajorityofpancreaticlesionsdiscoveredonradiographicstudiesperformedforanotherreasonarecystic,andmanyoftheserepresentintraductalpapillarymucinousneoplasms,whichrepresentaprecursorlesiontoexocrinepancreaticcancer.(See"Pathophysiologyandclinicalmanifestationsofintraductalpapillarymucinousneoplasmofthepancreas",sectionon'Clinicalpresentation'and"Pathophysiologyandclinicalmanifestationsofintraductalpapillarymucinousneoplasmofthepancreas",sectionon'Progressiontopancreaticcancer'.)

AnabdominalmassAscites(image1)Leftsupraclavicularlymphadenopathy(Virchow'snode)(image2)Apalpableperiumbilicalmass(SisterMaryJosephsnode)(image3)orapalpablerectalshelfarepresentinsomepatientswithwidespreaddisease.Pancreaticcanceristheoriginofacutaneousmetastasistotheumbilicusin7to9percentofcases[16].



DIFFERENTIALDIAGNOSISThesignsandsymptomsassociatedwithpancreaticcancerareoftennonspecific,sothedifferentialdiagnosisislarge.Threeofthemorecommonfindingsleadingtosuspicionforpancreaticcancerarejaundice,epigastricpain,andweightloss.

Thepositivepredictivevalue(PPV)ofthesesymptomsforthediagnosisofpancreaticcancerislow,withthepossibleexceptionofjaundiceinanolderpatient.Thiswasshowninacasecontrolstudythatexaminedtheriskofpancreaticcancerbaseduponsymptomsthatwereidentifiedintheyearbeforediagnosisin21,624patientsseeninaprimarycareclinic[18].ThePPVofjaundiceforpancreaticcancerinapatientaged60orolderwas22percentitwas



malignantdiseaseinothersites.

Cluessuggestingthepossibilityofaprimarypancreaticlymphomaincludealackofjaundice,constitutionalsymptoms(weightloss,fever,andnightsweats),anelevatedserumlactatedehydrogenase(LDH)orbeta2microglobulinlevel,andanormalserumCA199[19,20]. Primarypancreaticlymphomasaretypicallylargerthan6cm,andsurroundinglymphadenopathyiscommonaswithanylymphomahowever,neitherofthesefeatureswouldexcludeadenocarcinoma.

Anendoscopicultrasound(EUS)guidedbiopsymayberecommendedifadiagnosisofchronicorautoimmunepancreatitisissuspectedonthebasisofhistory(eg,extremeyoungage,prolongedethanolabuse,historyofotherautoimmunediseases),particularlyiffurtherimagingstudies(eitherEUS,endoscopicretrogradecholangiopancreatography,magneticresonancecholangiopancreatography)revealmultifocalbiliarystrictures(suggestiveofautoimmunepancreatitis)ordiffusepancreaticductalchanges(suggestiveofchronicpancreatitis).

Amongpatientswhohaveamassintheheadofthepancreasoramalignantbileductobstructioninthevicinityofthedistalcommonbileduct,differentiatingaprimaryexocrinepancreaticcarcinomafromotherlesscommonperiampullarymalignancies(arisingintheampulla,duodenum,orbileduct)canbechallenging(figure2).Althoughthediagnosismaybeevidentafterradiographicandendoscopicevaluation,itmaynotbepossibletodistinguishthetissueoriginofamalignantperiampullaryneoplasmuntilresectionandhistopathologicevaluationoftheentiresurgicalspecimeniscompleted.(See"Ampullarycarcinoma:Epidemiology,clinicalmanifestations,diagnosisandstaging",sectionon'Diagnosticevaluation'.)

DIAGNOSTICAPPROACHItisnotpossibletoreliablydiagnoseapatientwithpancreaticcancerbasedonsymptomsandsignsalone.Thelackofspecificityforthediagnosisofpancreaticcancerwhenbasedonsymptomsthatarehighlysuggestiveandsensitiveforpancreaticcancerwasshowninalandmarkstudyinwhich57percentofsuchpatientshadotherdiagnoses,includingnonpancreaticintraabdominalcancers(13percent),pancreatitis(12percent),andnonpancreatic,noncancerousdisordersincludingirritablebowelsyndrome(23percent)andmiscellaneousotherconditions(10percent)[21].

Awarenessofriskfactors(geneticpredisposition,age,smoking,diabetes)mayleadtoanearlierandmoreaggressiveevaluationforpancreaticcancerinpatientswhopresentwithsymptomssuspiciousforthedisease.(See"Epidemiologyandriskfactorsforexocrinepancreaticcancer".)

Ingeneral,thediagnosticevaluationofapatientwithsuspectedpancreaticcancerincludesserologicevaluationandabdominalimaging.Additionaltestingisthendirectedbaseduponthefindingsoftheinitialtestingaswellasthepatientsclinicalpresentationandriskfactors.

InitialtestingAllpatientspresentingwithjaundiceorepigastricpainshouldhaveanassayofserumaminotransferases,alkalinephosphatase,andbilirubintodetermineifcholestasisispresent.Inaddition,patientswithepigastricpainshouldbeevaluatedforacutepancreatitiswithaserumlipase.(See"Diagnosticapproachtotheadultwithjaundiceorasymptomatichyperbilirubinemia",sectionon'Initiallaboratorytests'and"Diagnosticapproachtoabdominalpaininadults",sectionon'Epigastricpain'.)

Thenextstepinthepatientsevaluationisabdominalimaging,thoughthechoiceoftestvariesdependinguponthepatientspresentingsymptoms.

JaundiceForpatientswithjaundice,theinitialimagingstudyistypicallyatransabdominalultrasound(US).TransabdominalUShashighsensitivityfordetectingbiliarytractdilationandestablishingthelevelofobstruction.Italsohashighsensitivity(>95percent)fordetectingamassinthepancreas,althoughsensitivityislowerfortumors



withtheseprocedures,transabdominalUSispreferredastheinitialimagingstudyforpatientssuspectedofhavingpancreaticcancer.(See'ERCP'belowand"Endoscopicretrogradecholangiopancreatography:Indications,patientpreparation,andcomplications",sectionon'IndicationsforERCP'and"Magneticresonancecholangiopancreatography",sectionon'Clinicaluse'.)

EpigastricpainandweightlossAbdominalcomputedtomography(CT)isthepreferredinitialimagingtestinpatientspresentingwithepigastricpainandweightloss,butwithoutjaundice.(See'AbdominalCT'below.)

Inpractice,transabdominalUSiscommonlyutilizedasaninitialscreeningtechniqueforbiliarypancreaticdiseaseinsuchpatientsbecauseoftoitslowcostandwideavailability[22,23].However,whiletransabdominalultrasoundhashighsensitivityfordetectingtumors>3cm,itismuchlowerforsmallertumors.(See'Transabdominalultrasound'below.)

Furthermore,ifacutepancreatitisisinthedifferential,transabdominalUSisnotthepreferredinitialtest.Itisassociatedwithahighfrequencyofincompleteexaminationsowingtooverlyingbowelgasfromanileus,anditcannotclearlyidentifynecrosiswithinthepancreastheseimportantfindingsarebestseenbycontrastenhancedCTscan.

Forthesereasons,andbecauseofthegreateramountofstaginginformationthatcanbeobtained,CTispreferredinthissetting,particularlyforpatientswhohavesymptomsotherthanepigastricpainthatraisesuspicionforpancreaticcancer(eg,weightloss,recentdiagnosisofatypicaldiabetesmellitus)[2428].(See'Clinicalpresentation'above.)

SubsequenttestingifinitialimagingispositiveIfapancreaticmassisseenontransabdominalUS,anabdominalCTscanistypicallyobtainedtoconfirmthepresenceofthemassandtoassessdiseaseextent.IftheCTappearanceistypical,enoughinformationisprovidedtoassessresectability,andthepatientisfitforamajoroperation,additionaltesting(includingbiopsy)maybeunnecessarybeforesurgicalintervention.Ontheotherhand,ifthediagnosisisindoubt,resectabilityisuncertain,orifatherapeuticinterventionisneeded,additionalproceduresmaybeindicated.(See'Stagingsystemandthestagingworkup'belowand'Diagnosticalgorithmandneedforpreoperativebiopsy'below.)

ERCPisindicatedifcholedocholithiasisremainsinthedifferentialdiagnosisafterinitialevaluationorifbiliarydecompressionisrequired.However,notallpatientswithbiliaryobstructionfrompancreaticcancerrequiredecompression,andstentplacementshouldbeavoidedinpatientswhohavenotyetundergoneCTbecauseastentmaycauseartifactinthepancreaticheadthatcanmaskthelesion,andthetraumaofstentinsertionmayinduceinflammatorychangesthatmightbeindistinguishablefromtumor.(See'ERCP'belowand"Endoscopicstentingformalignantpancreaticobiliaryobstruction"and"Surgicalresectionoflesionsoftheheadofthepancreas",sectionon'Preoperativebiliarydrainage'and"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis",sectionon'Roleofpreoperativebiliarydrainage'.)

MRCPisanalternativeforpatientswhocannotundergoERCP(eg,thosewithagastricoutletobstruction),butitlackstherapeuticcapability.(See'MRCP'below.)

EUSguidedorpercutaneousbiopsiesofapancreaticmasscanbeobtainedifhistologicconfirmationisneeded,thoughthisisnotalwaysrequiredinpatientswhoappeartohavepotentiallyresectablediseaseandwhohavetypicalimagingfindings.EUSmayalsobeusedasanalternativetocontrastenhancedtriplephasehelicalCTforthestagingofpancreaticcancer.(See'EUS'belowand'Biopsyandestablishingthediagnosis'below.)

SubsequenttestingifinitialimagingisnegativeForpatientswhoarestronglysuspectedofhavingpancreaticcancerbutwhoseinitialimagingisnegative,furthertestingmaybeindicated.IfanabdominalCTscanhasnotyetbeendone,thatisthenextstep.

ForpatientswithcholestasiswhohaveonlyhadtransabdominalUS,ERCPisindicated.MRCPisanalternativeforpatientswhocannotundergoERCP(eg,thosewithagastricoutletobstruction).(See'Jaundice'aboveand'MRCP'below.)



Ifthesetestsarenegative,additionaltestingistypicallynotrequiredandanalternativecauseforthepatientssymptomsshouldbesought.However,ifthesuspicionforpancreaticcancerremainshigh(eg,inapatientwithprofoundweightlossorwhohasriskfactorsforpancreaticcancer,suchashereditarypancreatitisorchronicpancreatitis),anEUSisareasonablenextsteptoexcludeasmallpancreaticcancer(algorithm2).(See"Epidemiologyandriskfactorsforexocrinepancreaticcancer",sectionon'Riskfactors'.)

AnylesionsthatarevisibleonlyonEUSshouldbebiopsiedtoconfirmthediagnosispriortosurgicalexploration.EUSguidedfineneedleaspiration(FNA)biopsyisthebestmodalityforobtainingatissuediagnosis,evenifthetumorispoorlyvisualizedbyotherimagingmodalities.Inaseriesof116patientssuspectedofhavingpancreaticcancer,butwithinconclusivefindingsonCTscan,EUSwithFNAhadasensitivityandspecificityfordiagnosingapancreaticmalignancyof87and98percent,respectively[29].IndependentriskfactorsassociatedwithEUSdetectionofpancreaticductaladenocarcinomaincludedpancreaticductaldilationonCTscan(oddsratio[OR]4.1,95%confidenceinterval[CI]1.511)andtumorsizedetectedbyEUSof1.5cm(OR8.5,95%CI2.035).

Specifictestsusedintheinitialevaluation

TransabdominalultrasoundTheinitialstudyinpatientswhopresentwithobstructivejaundiceorepigastricpainandweightlossisoftentransabdominalultrasound(US).TransabdominalUShashighsensitivityfordetectingbiliarytractdilationandestablishingthelevelofobstruction.(See"Diagnosticapproachtotheadultwithjaundiceorasymptomatichyperbilirubinemia",sectionon'Suspectedbiliaryobstructionorintrahepaticcholestasis'.)

OnUS,apancreaticcarcinomatypicallyappearsasafocalhypoechoichypovascularsolidmasswithirregularmargins.Dilatedbileductsmayalsosuggestthepresenceofapancreatictumor.

SupportfortheutilityoffirstlineabdominalUSforthediagnosisofapancreatictumorinpatientswhopresentwithsymptomsofpancreaticcancercomesfromaprospectivecohortstudyof900patientswhounderwenttransabdominalUStoworkuppainlessjaundice,anorexia,orunexplainedweightloss[30].Thesensitivityfordetectionofalltumorsinthepancreaswas89percent(124of140),including90percentfordetectionofexocrinepancreaticcancer(79of88patients).Amongthe779patientswhowerefollowedovertimeandestablishednottohavedevelopedapancreatictumor,ninehadfalsepositiveUSfindings(specificity99percent).

WhilethereportedsensitivityforUSindiagnosingpancreaticcanceris95percentfortumors>3cm,itismuchlessforsmallertumors[22,30,31].Sensitivityisalsodependentupontheexpertiseoftheultrasonographerandthepresenceorabsenceofbileductobstruction.

AbdominalCTAmasswithinthepancreasisthemostcommonCTfindingofpancreaticcancer,althoughenlargementofthewholeglandissometimesseen[26,32].SensitivityofCTforpancreaticcancerdependsontechniqueandishighest(89to97percent)withtriplephase,helicalmultidetectorrowCT[33].Asexpected,sensitivityishigherforlargertumorsinonestudy,thesensitivitywas100percentfortumors>2cm,butonly77percentfortumors2cminsize[34].ThispancreaticprotocoltypeofCTisoftennottheinitialstudyforapatientwithoutaknowndiagnosisofpancreaticcancer.(See'Technique'belowand'Initialtesting'above.)

ThetypicalCTappearanceofanexocrinepancreaticcancerisanilldefinedhypoattenuatingmasswithinthepancreas(image12),althoughsmallerlesionsmaybeisoattenuating,makingtheiridentificationdifficult,particularlyonnoncontrastCT[35].

Secondarysignsofapancreaticcancer(whichareseenwithmanysmallisoattenuatingcancers)includeapancreaticductcutoff,dilatationofthepancreaticductorcommonbileduct,parenchymalatrophy,andcontourabnormalities(image13).Dilationofboththepancreaticductandthecommonbileduct,commonlyreferredtoasthedoubleductsignispresentinabout62to77percentofcasesofpancreaticcancer(picture1),butisnotdiagnosticforapancreaticheadmalignancy[36,37].Approximately50percentofampullarycarcinomashaveadoubleductsign[38],anditcanalsooccasionallybeseenwithbenignadenomas.

ERCPEndoscopicretrogradecholangiopancreatography(ERCP)isahighlysensitivetoolforvisualization



ofthebiliarytreeandpancreaticducts.(See"Endoscopicmethodsforthediagnosisofpancreatobiliaryneoplasms",sectionon'Endoscopicretrogradecholangiopancreatography'.)

Anearlymetaanalysisfoundasensitivityof92percentandspecificityof96percentfordiagnosingcancerofthepancreasbyERCP[39].Findingssuggestiveofamalignanttumorwithintheheadofthepancreasincludesuperimposablestricturesorobstructionofthecommonbileandpancreaticducts(the"doubleduct"sign),apancreaticductstrictureinexcessof1cminlength,pancreaticductobstruction,andtheabsenceofchangessuggestiveofchronicpancreatitis(picture1).

Furthermore,ERCPprovidesanopportunitytocollecttissuesamples(forcepsbiopsy,brushcytology)forhistologicdiagnosis.However,thesensitivityfordetectionofmalignancy(approximately50to60percent)islowerthanthatofendoscopicultrasound(EUS)guidedFNA(sensitivity92percent).(See"Endoscopicmethodsforthediagnosisofpancreatobiliaryneoplasms",sectionon'TissuesamplingduringERCP'and'EUSguidedbiopsy'below.)

OtherlimitationsofERCParethatparenchymalabnormalitiescanonlybedetectedbyinferencetumorscanbemissedintheuncinateprocess,accessoryduct,andtailandtheneedforintraductalcontrastadministration.DirectvisualizationofthepancreaticductispossibleduringERCPusingpancreatoscopy.Pancreatoscopyusesaminiatureendoscopethatispassedthroughtheduodenoscope(image14)tovisualizethepancreaticductandtoobtaintargetedbiopsiesofpancreaticductstrictures.However,theprocedureisnotwidelyavailable.(See"Cholangioscopyandpancreatoscopy".)

ERCPissuperiortotransabdominalUSandCTforthedetectionofextrahepaticbiliaryobstruction,andistheprocedureofchoicewhenthereissuspicionforcholedocholithiasis.However,itisalsomoreexpensivethanultrasoundorCT,andasaninvasiveprocedure,itisassociatedwithafiniterateofmortality(0.2percent)andcomplicationssuchaspancreatitis,bleeding,andcholangitis.Asaresult,theroleofERCPinpatientswithsuspectedpancreaticcancerisevolvingintoamainlytherapeuticmodalityforpatientswhopresentwithcholestasisduetotumorobstructionofthebiliarysystemandrequireplacementofabiliarystent.(See"Endoscopicstentingformalignantpancreaticobiliaryobstruction"and"Diagnosticapproachtotheadultwithjaundiceorasymptomatichyperbilirubinemia",sectionon'Suspectedbiliaryobstructionorintrahepaticcholestasis'.)

However,preoperativestentingisnotalwaysnecessaryinapatientwithapotentiallyresectablepancreaticcancer,eveninthepresenceofcholangitis.Furthermore,ifitisundertaken,stentingshouldnotbeperformedbeforeCTscanningtoassessresectability,asthestentmaycauseartifactinthepancreaticheadthatcanmaskthelesion,andthetraumaofstentinsertionmayinduceinflammatorychangesthatmightbeindistinguishablefromtumor.Theindicationsandcontroversiessurroundingtherisksandbenefitsofpreoperativestentplacementarediscussedelsewhere.(See"Endoscopicstentingformalignantpancreaticobiliaryobstruction",sectionon'Indications'and"Surgicalresectionoflesionsoftheheadofthepancreas",sectionon'Preoperativebiliarydrainage'and"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis",sectionon'Roleofpreoperativebiliarydrainage'.)

MRCPAnalternativetodiagnosticERCPismagneticresonancecholangiopancreatography(MRCP).MRCPusesMRtechnologytocreateathreedimensionalimageofthepancreaticobiliarytree,liverparenchyma,andvascularstructures.MRCPisbetterthanCTfordefiningtheanatomyofthebiliarytreeandpancreaticduct,hasthecapabilitytoevaluatethebileductsbothaboveandbelowastricture,andcanalsoidentifyintrahepaticmasslesions.ItisatleastassensitiveasERCPindetectingpancreaticcancers[40,41],andunlikeconventionalERCP,itdoesnotrequirecontrastmaterialtobeadministeredintotheductalsystem.Thus,themorbidityassociatedwithendoscopicproceduresandcontrastadministrationisavoided.(See"Magneticresonancecholangiopancreatography".)

AlthoughMRCPhasnotyetreplacedERCPinthepatientssuspectedofhavingpancreaticcancerinmostcenters(algorithm2),itmaybepreferredinspecificsettings:



RoleoftumormarkersSeveralserummarkersforpancreaticcancerhavebeenevaluated,themostusefulofwhichiscancerassociatedantigen199(CA199).

CA199ThereportedsensitivityandspecificityratesofCA199forpancreaticcancerrangefrom70to92,and68to92percent,respectively[4347].However,sensitivityiscloselyrelatedtotumorsize.CA199levelsareoflimitedsensitivityforsmallcancers[43,4851].Furthermore,CA199requiresthepresenceoftheLewisbloodgroupantigen(aglycosyltransferase)tobeexpressed.AmongindividualswithaLewisnegativephenotype(anestimated5to10percentofthepopulation),CA199levelsarenotausefultumormarker[50,52].

CA199levelsalsohavelowspecificity.CA199isfrequentlyelevatedinpatientswithcancersotherthanpancreaticcancerandvariousbenignpancreaticobiliarydisorders(table2)[4850,53,54].Onestudyfoundthatserumconcentrationsabove37U/mLrepresentedthemostaccuratecutoffvaluefordiscriminatingpancreaticcancerfrombenignpancreaticdisease,butthesensitivityandspecificityforpancreaticcanceratthislevelwereonly77and87percent,respectively[53].Furthermore,thepositivepredictivevalue(PPV)islow,particularlyamongasymptomaticindividuals.Inalargeseriesofover70,000asymptomaticindividuals,thePPVofaserumCA199level>37U/mLwasonly0.9percent[55].Becauseofthis,expertguidelinesrecommendagainsttheuseofCA199asascreeningtestforpancreaticcancer[56].Evenamongsymptomaticindividuals(epigastricpain,weightloss,jaundice),thesensitivity,specificity,andpositivepredictivevalueofanelevatedCA199>37U/mLlevelareonlyapproximately80,85,and72percent[49,57].

ThespecificityandPPVforthediagnosisofpancreaticcancercanbeimprovedbyusinghighercutofflevels(100oreven1000U/mL),butattheexpenseofsensitivity[49].Importantly,thereisaverybroadrangeofCA199levelsthatcanbeseeninbenigndisease,andtherearenospecificcutoffvalues(evenbeyond10,000U/mL)thatareseenonlyinpatientswithmalignantdisease[46,53,58].

SerumlevelsofCA199dohavesomevalueasprognosticmarkersandalsoasanindicatorofdiseaseactivityinpatientswithinitiallyelevatedlevels:

Patientswhohavegastricoutletorduodenalstenosisorwhohavehadsurgicalrearrangement(eg,BillrothII)orductaldisruption,resultinginductswhicharedifficulttoassesssuccessfullybyERCP.

Todetectbileductobstructionoccurringinthesettingofchronicpancreatitis.(See"Complicationsofchronicpancreatitis".)

ForpatientsinwhomattemptedERCPiseithertotallyunsuccessfulorprovidesincompleteinformationbecauseofpancreaticductobstruction[42].

ThedegreeofelevationofCA199(bothatinitialpresentationandinthepostoperativesetting)isassociatedwithlongtermprognosis[5964].

Amongpatientswhoappeartohavepotentiallyresectablepancreaticcancer,themagnitudeofthepreoperativeCA199levelcanalsohelptopredictthepresenceofradiographicallyoccultmetastaticdisease,thelikelihoodofacomplete(R0)resection,andlongtermoutcomes[59,6568].Asexamples:

Inareportof491patientsundergoingstaginglaparoscopyforaradiographicallyresectablepancreaticadenocarcinoma,CA199valuesabove130units/mLwereasignificantpredictoroffindingradiographicallyoccultunresectabledisease[65].TheratesofunresectablediseaseamongallpatientswithaCA199level130units/mLversus


http://www.uptodate.com/contents/clinicalmanifestationsdiagnosisandstagingofexocrinepancreaticcancer?topicKey=GAST%2F2501&elapsedTimeMs 10/58

OthermarkersAlthoughseveralmarkercandidateshaveemergedfrompreclinicalstudies(andone,macrophageinhibitorycytokine1,appearsparticularlypromising[70]),nonehasreplacedCA199todate.

BiopsyandestablishingthediagnosisHistologicconfirmationisrequiredtoestablishadiagnosisofpancreaticcancer.(See"Pathologyofexocrinepancreaticneoplasms".)

Followingtheinitialevaluation,somepatientsmayhaveabiopsyprovendiagnosisofpancreaticcancer,typicallybecausetheypresentedwithjaundiceandunderwentanERCP.(See'ERCP'above.)

However,inmanycases,thediagnosiswillnotyetbehistologicallyconfirmed.Oncepancreaticcancerissuspectedoninitialimagingstudies,thenextstepintheworkupisgenerallyastagingevaluationtoestablishdiseaseextentandresectabilityratherthanbiopsy.Patientswhoarefitformajorsurgeryandwhoappeartohavepotentiallyresectablepancreaticcancerafterthestagingevaluationiscompletedonotnecessarilyneedapreoperativebiopsyconfirmingthediagnosisofapancreaticcancerbeforeproceedingdirectlytosurgery.However,theincreasedrecognitionofchronicorautoimmunepancreatitis,whichcancloselymimicpancreaticcancer,hasalteredthisparadigmincertainpopulations.Apreoperativebiopsymayberecommendedifadiagnosisofchronicorautoimmunepancreatitisissuspectedonthebasisofhistory(eg,extremeyoungage,prolongedethanolabuse,historyofotherautoimmunediseases),particularlyifimagingstudies(EUS,ERCPormagneticresonancecholangiopancreatography)revealmultifocalbiliarystrictures(suggestiveofautoimmunepancreatitis)ordiffusepancreaticductalchanges(suggestiveofchronicpancreatitis).Theseissuesarediscussedinmoredetailbelow.(See'Diagnosticalgorithmandneedforpreoperativebiopsy'below.)

Whenitisindicated,biopsyofapancreaticmasscanbeaccomplishedeitherpercutaneouslyorviaEUS.

PercutaneousbiopsyPercutaneousfineneedleaspiration(FNA)biopsyofapancreaticmasscanbeperformedusingeitherultrasoundorcomputedtomographic(CT)guidance(picture2).Thesensitivityandspecificityofthisprocedureforthediagnosisofpancreaticcancerdependsupontumorsizeandoperatorexpertisevaluesintherangeof80to90and98to100percent,respectively,arereported[71].

AtheoreticalconcernisthatpercutaneousFNAbiopsyofthepancreasmaydisseminatetumorcellsintraperitoneallyoralongtheneedlepathinpatientswhoarebelievedtobecandidatesforpotentiallycurativeresection.However,theriskappearstobequiteloworabsent.Inonestudyof41patientsundergoingresectionforprimarypancreaticadenocarcinoma,21of32patientswithoutpreoperativeopenbiopsieshadundergonepreoperativeCTorfluoroscopicallyguidedFNA[72].Therewasnoincreaseinpositiveperitonealwashings,peritonealfailurerate,ormediansurvivalinthesepatients.Nevertheless,concernpersistsand,inpractice,wetrytoavoidpercutaneousFNAinpatientswithresectablemasses.

AtransduodenalEUSguidedFNAbiopsyorERCPsamplingreducestheserisks[7375].(See'ERCP'above.)

EUSguidedbiopsyEUSguidedFNAisthebestmodalityforobtainingatissuediagnosis,evenifthetumorispoorlyvisualizedbyotherimagingmodalities.Thisprocedureislesslikelytocauseintraperitonealspreadofthetumorsincethebiopsyisobtainedthroughthebowelwallratherthanpercutaneously.EUSguidedFNAhasasensitivityofapproximately90percentandspecificityof96percentforthediagnosisofapancreaticcancer.(See"Endoscopicultrasoundinthestagingofexocrinepancreaticcancer",sectionon'AccuracyofEUSFNA'.)

Theadditionofmoleculargeneticanalysis(eg,assayforKrasorp53genemutationsbyRTPCR)tocytologic

expertpanelconvenedbytheAmericanSocietyofClinicalOncology(ASCO)recommendedagainsttheuseofCA199aloneasanindicatorofoperability[56].

SerialmonitoringofCA199levels(onceeveryonetothreemonths[56])isusefultofollowpatientsafterpotentiallycurativesurgeryandforthosewhoarereceivingchemotherapyforadvanceddisease.RisingCA199levelsusuallyprecedetheradiographicappearanceofrecurrentdisease,butconfirmationofdiseaseprogressionshouldbepursuedwithimagingstudiesand/orbiopsy[56].(See"Chemotherapyforadvancedexocrinepancreaticcancer",sectionon'CA199level'.)



examinationmayimprovesensitivity,especiallyinpatientswithsmallprimarytumors.Atpresent,however,molecularanalysisisnotaroutinecomponentofthediagnosticevaluationforpancreaticmasses.EUSguidedFNAisaddressedindetailelsewhere.(See"Endoscopicultrasoundinthestagingofexocrinepancreaticcancer",sectionon'EUSFNA'.)

IfFNAspecimensareinadequateornondiagnostic,EUSguidedtrucut(coreneedle)biopsymaybeconsidered,wherelocalexpertiseisavailable.Atsomeinstitutions,atrucutbiopsymaybepreferredoverFNAfortheevaluationofsolidpancreaticmasslesionsthatareaccessiblefromthestomach,intheabsenceofacontraindication(inaccessibletarget,presenceofinterveningstructuresprohibitingbiopsy,uncorrectablecoagulopathyorthrombocytopenia,uncooperativepatient).TheroleofEUSguidedtrucutbiopsyintheevaluationofpancreaticmassesisdiscussedseparately.(See"Endoscopicultrasoundguidedtrucutbiopsy".)

STAGINGSYSTEMANDTHESTAGINGWORKUPThepreferredstagingsystemforallpancreaticcancers(exocrineandneuroendocrine)isthetumornodemetastasissystemofthecombinedAmericanJointCommitteeonCancer(AJCC)/InternationalUnionAgainstCancer(UICC)(table3)[76].Thegoalofthestagingworkupistodelineatetheextentofdiseasespreadandidentifypatientswhoareeligibleforresectionwithcurativeintent.

ImagingstudiesImagingstudiesplayanimportantroleinthestagingandmanagementofpancreaticcancer.

AbdominalCTAbdominalCTprovidesanassessmentoflocalandregionaldiseaseextent,whichdeterminesresectability,andalsoevaluatesthepossibilityofdistantmetastaticspread.

TechniqueThereliabilityofCTasastagingtoolforpancreaticcancerishighlydependentupontechnique.Triplephasecontrastenhancedthinslice(multidetectorrow)helicalcomputedtomography(MDCT)withthreedimensionalreconstructionisthepreferredmethodtodiagnoseandstagepancreaticcancer.HelicalCTscannerswithmultiplerowsofdetectorspermitimagingoflargervolumesoftissuewhileacquiringbotharterialandvenousphasesinshorterperiodsoftime(seebelow)[77,78].Thishasimprovedtheevaluationofthemainpancreaticductand,thus,thedetectionofsmalltumors[79].

Forcomprehensiveimagingofasuspectedpancreascancer,thepatientisusuallyscannedinseveraldynamicphasesofcontrastinjection(termedapancreasprotocol)[80]:

AssessingresectabilityCompletesurgicalresectionistheonlypotentiallycurativemodalityoftreatmentforpancreaticcancer.AninitialassessmentofresectabilitycanusuallybemadebaseduponthepreoperativetriplephasestagingcontrastenhancedCTscan.Localunresectabilityisusually(butnotalways)duetovascularinvasion,particularlyofthesuperiormesentericartery(SMA).

DefinitionsofunresectableandborderlineresectablediseaseAlthoughpracticeisvariableacrossinstitutions,manysurgeonswouldconsiderapancreaticcancertobecategoricallyunresectableifanyofthefollowingarepresent(see"Initialchemotherapyandradiationfornonmetastaticlocallyadvancedunresectable,borderlineresectable,andpotentiallyresectableexocrinepancreaticcancer",sectionon'Definitions'):

Thearterialphaseofenhancement,whichcorrespondstothefirst30secondsafterthestartofthecontrastinjection,providesexcellentopacificationoftheceliacaxis,superiormesentericartery(SMA),andperipancreaticarteries.

Anattenuationdifferencebetweentumorandnormalpancreas,whichincreaseslesionconspicuity,isbestachievedafterpeakenhancementoftheaortainthearterialphasebutbeforepeakenhancementoftheliver,whichoccursintheportalvenousphase.Thisissometimestermedthepancreaticphase[81,82].

Theportalvenousphase,whichisobtainedat60to70secondsafterthestartofthecontrastinjection,providesbetterenhancementofthesuperiormesentericvein,splenicandportalveins.Inaddition,peakhepaticenhancement,whichoptimizesthedetectionofhepaticmetastases,alsooccursintheportalvenousphase[83]

Extrapancreaticinvolvement,includingextensiveperipancreaticlymphaticinvolvement,nodalinvolvement



Thereislessconsensusonthedefinitionof"borderline"resectablepancreaticcancer[8486].Somereservetheterm"borderlineresectable"forcaseswherethereisfocal(lessthanonehalfofthecircumference)(image15)tumorabutmentofthevisceralarteriesorshortsegmentocclusionofthesuperiormesentericvein(SMV)orSMV/portalveinconfluenceorhepaticartery.(See"Initialchemotherapyandradiationfornonmetastaticlocallyadvancedunresectable,borderlineresectable,andpotentiallyresectableexocrinepancreaticcancer",sectionon'Borderlineresectable'.)

Encasement(morethanonehalfofthevesselcircumference)(image15)orocclusion/thrombusofthesuperiormesentericvein(SMV)ortheSMVportalveinconfluenceusedtobeuniversallyconsideredanindicatorofunresectability.However,manycentershavedemonstratedthefeasibilityofSMVreconstruction,andthisisnowconsideredbymanytoalsorepresentborderlineresectabledisease[87].Ifvenousocclusionispresent,asuitablesegmentofportalvein(above)andSMV(belowthesiteofvenousinvolvement)mustbepresenttoallowforvenousreconstruction.However,inmostcenters,surgerywillbeprecededbysomeformofneoadjuvanttreatmentforpatientswithvenousocclusion.(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis",sectionon'Vascularresection'and"Initialchemotherapyandradiationfornonmetastaticlocallyadvancedunresectable,borderlineresectable,andpotentiallyresectableexocrinepancreaticcancer",sectionon'Borderlineresectable'.)

TheNationalComprehensiveCancerNetwork(NCCN)considersthefollowingtorepresentcriteriaforborderlineresectabledisease:

Insomecases,patientswithborderlineresectablediseasearereferredforneoadjuvanttherapypriortosurgicalexploration.(See"Initialchemotherapyandradiationfornonmetastaticlocallyadvancedunresectable,borderlineresectable,andpotentiallyresectableexocrinepancreaticcancer".)

TheentireconceptofaborderlineresectablepancreaticcancerisproblematicforcenterstryingtoaccuratelystageandtreatpatientsaccordingtotheAJCCstagingsystem.TheAJCCusestheT4category(tumorinvolvestheceliacaxisorthesuperiormesentericartery)todesignateanunresectableprimarytumor,withT3designatingatumorthatextendsbeyondthepancreasbutwithoutinvolvementoftheceliacaxisormesentericartery.However,asnotedabove,involvementofafocalareaofthevisceralarteriesmaybeconsideredaborderlineresectablesituation.Onestudyof257patientswithstageIIIpancreaticcancer(allT4lesionsbaseduponinfiltrationoftheceliacaxisorSMA)foundthat30percentcouldundergoasuccessfulcomplete(R0)resectionafterchemoradiationorchemotherapyalone[88].RevisionstotheAJCCstagingsystemareanticipated.(See'Stagingsystemandthestagingworkup'above.)

AccuracyofCT

beyondtheperipancreatictissues,and/ordistantmetastases.

Directinvolvementofthesuperiormesentericartery(SMA),inferiorvenacava,aorta,celiacaxis,orhepaticartery,asdefinedbytheabsenceofafatplanebetweenthelowdensitytumorandthesestructuresonCTscan.

Fortumorsoftheheadorbody:

SevereunilateralorbilateralSMVorportalinfringement

Lessthanonehalfthecircumference(180degree)tumorabutmentontheSMA

Abutmentorencasementofthehepaticartery,ifreconstructible

ShortsegmentSMVocclusion,ifthereisanadequatesegmentofveinaboveandbelowthesiteoftumorinvolvementtoallowforvenousresectionandreconstruction

Fortumorsofthetail:

Lessthan180degreeencasementoftheSMAorceliacartery



PrimarytumorThesensitivityoftriplephasehelicalCTforpancreaticadenocarcinomaishigh,89to97percent[33].Asexpected,sensitivityishigherforlargertumorsinonestudy,thesensitivitywas100percentfortumors>2cm,butonly77percentfortumors2cminsize[34].However,mostsmallisoattenuatingpancreaticcancershavesecondarysignssuchasapancreaticductcutoffordilatedmainpancreaticduct[35].

MetastaticdiseaseContrastenhancedCTisthemodalityofchoicetodetectdistantmetastases(image16).Thesensitivityforhepaticmetastasesishigh,particularlyusingthepancreaticprotocoltechnique.Inonestudyof43patientswithpancreaticcancer,thesensitivity,specificity,positivepredictivevalue,andnegativepredictivevalueofcontrastenhancedmultidetectorrowhelicalCTfordetectionoflivermetastaseswere88,89,92and84percent,respectively[89].Lowersensitivityrates(53and69percent)arereportedbyothersandmayberelatedtothesizeofthehepaticmetastases[90,91].

Peritonealinvolvementmaybedetectedindirectlybythepresenceofascites,mesentericnodules,ormesentericlymphnodes.However,thesensitivityofCTforperitonealdisseminationispoorandnotsufficientlyhightoeliminatetheneedfordiagnosticlaparoscopyinequivocalcases[9294].(See'Staginglaparoscopy'below.)

Fortumorsoftheheadandneckofthepancreas,regionallymphatictumorspreadusuallyoccursaroundtheceliacaxisandtheperipancreaticandperiportalareas.Fortumorsarisinginthetail,regionalnodalbasinsarelocatedalongthecommonhepaticartery,celiacaxis,splenicarteryandsplenichilum.

ThesensitivityandspecificityofCTfordetectinginvolvementoflymphnodesislow,leadingsometosuggestthatinapatientwhohasapresumedpancreaticcancerthatisconsideredresectable,thefindingofperipancreaticnodesonCTshouldnotpreventexploration[95].However,thepresenceofextensiveperipancreaticlymphaticinvolvementandnodalinvolvementbeyondtheperipancreatictissuesisgenerallyconsideredtorepresentunresectabledisease.(See'Definitionsofunresectableandborderlineresectabledisease'above.)

VascularinvasionCTcriteriaforvascularinvasionincludearterialembedmentinthetumormassorvenousobliteration,tumorinvolvementexceedingonehalfthecircumferenceofthevessel,vesselwallirregularity,vesselcaliberstenosis,orateardropsignofthesuperiormesentericvein(SMV)[96].

Themostcommonlyusedsystemforpredictingvascularinvasionbyapancreaticcancerusesafivegradescale,whichisbaseduponthedegreeofcontactbetweenthetumorandthebloodvessel(table4)[97].Intheinitialreportof25patients,tumorcontiguitywith>50percentormoreoftheperimeterofthevesselwasfoundtobetheoptimalthresholdforpredictingvascularinvasion,withasensitivityof84percentandaspecificityof98percent.

However,thesecriteriawereappliedequallytovenousandarterialstructures.Asnotedabove,becauseofadvancesinvenousreconstruction,manyinstitutionsdonotconsiderinvolvementofmorethanonehalfofthecircumferenceofthesuperiormesentericvein(SMV)ortheSMVportalveinconfluencetorepresentunresectabledisease.(See'Definitionsofunresectableandborderlineresectabledisease'above.)

Modificationsofthisgradingsystemhavebeenproposed,toincreasethesensitivityfordetectingvenousinvasionandspecificityfordetectingarterialinvasion,butnoneisinwidespreaduse[96,98100].Highsensitivityforvenousinvasionisdesirablesothatpatientswithundiagnosedvenousinvasionwillnotbedeemedunresectableintraoperativelyifresectionisattemptedataninstitutionwherevenousreconstructionisnotperformed.Ontheotherhand,highspecificityforarterialinvasionisdesirabletominimizetheriskofoverstagingT3disease,whichmaydenysomepatientsachanceforpotentiallycurativesurgicalresection.



OtherstudiesAvarietyofotherimagingmodalities,includingendoscopicultrasound(EUS),MRI,FDGPETaswellasstaginglaparoscopy,mayberequiredtoassessresectabilityinsomecircumstances.

EUSDuetothesmalldistancebetweentheechoendoscopeandthepancreasthroughthegastricorduodenalwall,endoscopicultrasound(EUS)providesmuchhigherresolutionthantransabdominalultrasound.PancreaticcanceronEUSappearsasahypoechoicmass,typicallywithdilationoftheproximalpancreaticduct.Theborderofthelesionmayhaveanirregularcontour,andtheechopatternofthemassmaybehomogenousorinhomogeneous.(See"Endoscopicultrasound:Normalpancreaticobiliaryanatomy"and"Endoscopicultrasoundinthestagingofexocrinepancreaticcancer".)

MultiplestudiescomparingEUSwithotherimagingmodalitiesforinitialdiagnosisandstagingofpancreaticcancerconcludedthatEUSmaybemoreaccurateforsmallertumors,forlocalTandNstaging,andforpredictingvascularinvasion.EUSmaydetectmetastaticdiseaseintheliverormediastinallymphnodes,butisinferiortoCTforevaluationofdistantmetastases.Inaddition,thespecificityofEUSislimited,particularlywheninflammatorychangesarepresent.EUSisalsooperatordependentasaresult,itsvaluevarieswithlocallyavailableexpertise.ThedevelopmentofmodernmultidetectorrowCThasmarkedlyimprovedthesensitivityofCTforthedetectionofsmallertumorsandthepresenceofvascularinvasion,reachingvaluesthatarecomparabletothoseobtainedbyEUSbyanexperiencedendoscopist.However,headtoheadstudiescomparingthetwomodalitiesarelacking.(See"Endoscopicultrasoundinthestagingofexocrinepancreaticcancer",sectionon'ComparisonofEUSwithotherimagingtechniques'.)

TheroleofEUSinthepreoperativestagingofpancreaticcancerisevolving,andthereareseveralpointsinthediagnosticevaluationwherethismodalitymaybeofbenefit,particularlyforpatientswhoseCTevaluationdoesnotdemonstrateadefinedmasslesion(algorithm2).(See'Subsequenttestingifinitialimagingisnegative'above.)

Inaddition,EUSguidedfineneedleaspirationbiopsy(FNA)isthebestmodalityforobtainingatissuediagnosis,evenifthetumorispoorlyvisualizedbyotherimagingmodalities.(See'EUSguidedbiopsy'above.)

MRIAlthoughpancreaticadenocarcinomasareeasilyvisualizedonMRI(image17),thereisnoevidencethatMRIoffersasignificantdiagnosticadvantageovertriplephaseMDCTforthelocalstagingevaluation[106110].OnepotentialbenefitofMRIisitsincreasedsensitivityforthedetectionofsmalllivermetastasescomparedwithCT[90,91,111,112].CombiningCTandMRIofferslittlethatcannotbeachievedwithonealone.Thus,thechoiceofMRIorCTdependsupontheleveloflocallyavailableexpertiseandtheclinician'scomfortwithoneortheotherradioimagingtechnique.WepreferMDCT.

ChestCTCTofthechestmaybeusedasastagingtooltodetectlungmetastases.However,mostcenterstonotperformaroutinestagingchestCTforpatientssuspectedofhavingpancreaticcancerbecauseinthepresenceoflungmetastases,theprimarytumorisusuallyunresectableforanotherreason[113].

PETscanningPETscanningwiththetracer18fluorodeoxyglucose(FDG)reliesuponfunctionalactivitytodifferentiatemetabolicallyactiveproliferativelesionssuchascancers,mostofwhichareFDGavid,frombenignmasses.MostbenignlesionsdonotaccumulateFDG,withtheexceptionofinflammatorylesionssuchaschronicpancreatitis[114].

TheutilityofPETscansinthediagnosticandstagingevaluationofsuspectedpancreaticcancer,particularlywhetherPETprovidesinformationbeyondthatobtainedbycontrastenhancedMDCT,remainsuncertain,as

Ingeneral,helicalCThasahighpredictivevalueforunresectability(90to100percent)[98,101103],butthepredictivevalueforresectabilityisslightlylower(range64to90percent)[97,98,104].TheaccuracyofMDCTforassessingvascularinvasionwasaddressedinasystematicreviewandmetaanalysisof18studies[105].Thepooledsensitivityandspecificityfordiagnosingvascularinvasionwere77and81percent,respectively,butwhentheanalysiswaslimitedtothefivemostrecentstudiesconductedsince2004,andpresumablyusingthemostadvancedCTtechnology,sensitivityandspecificityrateswere85and82percent,respectively.



illustratedbythefollowingdata:

Takentogether,thedataareinsufficienttoconcludethatPETorintegratedPET/CTprovidesusefulinformationabovethatprovidedbycontrastenhancedCT.ConsensusbasedguidelinesforstagingofpancreaticcancerfromtheNCCNstatethattheroleofPET/CTremainsunclear.DefinitiveassessmentoftheroleofPETasacomponentofthediagnosticand/orstagingevaluationawaitsalargeprospectivestudydesignedtoassessthebenefitofPET(preferablyintegratedPETwithacontrastenhancedCT)inpatientswithanegativeorindeterminateCTscan,withaprospectivelydesignedcosteffectivenessanalysis.

StaginglaparoscopyAccuratestagingdrivespropertreatmentofpatientswithpancreaticcancer,particularlywhenselectingpatientsforsurgicalresection.Becausemosthaveunresectablediseaseatpresentation,akeygoalistoavoidafutilelaparotomywheneverpossible.

Currentlyavailableimagingtechniquesarehighlyaccurateatpredictingunresectabledisease,buttheyfallshortinpredictingresectabledisease,mainlybecauseoflimitedsensitivityforsmallvolumemetastaticdisease.Radiographicallyoccultsubcentimetermetastasesonthesurfaceoftheliverorperitoneumthatarerarelyvisible

ThesensitivityofintegratedPET/CT(whichhasbetterspatialresolutionascomparedtoPETalone)intheinitialdiagnosisofpancreaticcancerrangesfrom73to94percent,whilespecificityrangesfrom60to89percent[115120].FalsenegativePETresultscanoccurinhyperglycemicpatientsorinsubcentimeterlesions,whilefalsepositiveresultscanbeseeninvariousinflammatorystatessuchaspancreatitis,infectedpseudocyst,orlocalinflammationcausedbyplacementofabiliarystent.Instudiesinwhichthetwomodalitieshavebeencompared,PETdoesnotappeartoprovideadditionalinformationtothatderivedfromMDCTorMRI[119121].

AmajorissueisthattheCTcomponentofintegratedPET/CTimagingisperformedinmanyinstitutionswithouttheuseofIVcontrastmaterial,atechniquethatprecludestheoptimaldetectionofsmalltumorsandmetastases.Increasingly,PET/CTisbeingcarriedoutwithIVcontrast,butthispracticeisnotwidespread.EarlyresultsarepromisingusingintegratedPETwithacontrastenhancedCT,butfurtherstudiesareneededtoestablishclinicalvaluecomparedwithMDCTaloneinpatientswithpancreaticcancer[122124].

OnepossiblebenefitofPETisenhanceddetectionofsmallvolumemetastaticdisease,whichisoftenmissedbyCT.Unfortunately,theavailabledataareconflicting,withsomestudiessuggestingthatPETisusefulforidentifyingmetastaticdiseasethatismissedbyCT(image18)[117,119,125127]andothersnotingthatPEToftenmissessmallvolumemetastaseswithintheperitoneumandelsewhere,includingtheliver[114,115,128].

However,theclinicalimpactremainsuncertain,asillustratedbythefollowingreports:

OneseriescomparedintegratedFDG/PET,MDCT,andMRIin38consecutivepatientssuspectedofhavingpancreaticcancer,withfindingsconfirmedbyoperationand/orhistopathologicanalysisorfollowup[119].Amongthe17patientswithadvancedpancreaticadenocarcinoma,FDGPET/CThadahighersensitivitythaneitherMDCTorMRI(88versus30and30percent,respectively),andtheclinicalmanagementof10patients(26percent)wasalteredbythefindingsonPET/CT.

Inanotherreport,82patientswithapancreaticmassthatwassuspiciousforcancerunderwentstagingwithintegratedPET/CTandcontrastenhancedCTofthechest,abdomen,andpelvis[117].ThesensitivityfordetectingmetastaticdiseaseforPET/CTalone,CTalone,andcombinedCTplusintegratedPET/CTwas61,57,and87percent,respectively.However,thefindingsonPET/CTchangedmanagementinonlysevenpatients(11percent),twobecauseofanoccultsupraclavicularlymphnode,twowithoccultliverlesions,twoperitonealimplants,andoneperiesophageallymphnode.Twoofthesepatientshadlocallyadvanceddiseaseandwouldnothavebeenconsideredforresection,evenifaPET/CThadnotbeendone.



byCT,MRI,PET,ortransabdominalUSmaybevisualizedlaparoscopically.Studieshaveconsistentlyshownthatuptoonethirdofpatientsthoughttoberesectablebystateoftheartimagingwillbefoundtobeunresectablebaseduponlaparoscopicfindings[92,129131].ACochranereviewconcludedthatpatientswithpancreaticandperiampullarymalignancieswhowereconsideredtohaveresectablediseaseafterdiagnosticlaparoscopyandCTscanhada17percentprobabilitythattheircancerwouldbeunresectablecomparedtoa40percentprobabilityforthoseundergoingCTalone[132].Onaverage,theuseofdiagnosticlaparoscopywithbiopsyconfirmationofsuspiciouslesionwouldavoid23unnecessarylaparotomiesperevery100patientsplannedforcurativeintentresection.

However,thevalueofstaginglaparoscopyisnotuniversallyaccepted.Whilehospitalstay,cost,andmorbidityarereducedwhenanunnecessaryopenlaparotomyisavoidedforunresectableormetastaticdisease,therearenocontrolledstudiesdemonstratingabenefitforthisprocedureinpatientswhohaveundergoneradiographicstagingevaluationusingmodernhighqualityimagingsuchasMDCT[133].Thisissuewasnotaddressedinthe2013Cochranereview,andgiventhat7ofthe15trialswereundertakeninthe1980sand1990s,itisunlikelythatmodernCTtechniqueswereused.(See'Technique'above.)

Otherssuggestaselectiveapproachtostaginglaparoscopytomaximizeyieldbylimitingtheproceduretothosewiththehighestlikelihoodofoccultmetastaticdisease[134].Thisincludespatientswithatumorofthebodyortailofthepancreaswhoappeartohavepotentiallyresectablediseasebycomputedtomographyscan(onehalfofwhomwillhaveoccultperitonealmetastases[135,136]),large(>3cm)primarytumors,anypatientforwhomhighqualityimagingisinanywaysuggestiveofoccultmetastaticdisease,andthosewithahighinitialCA199level(>100units/mL)[66].(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis",sectionon'Tumorsinthebodyortail'and'CA199'above.)

Weselectivelyusestaginglaparoscopyinpatientswithadvancedvascularinvolvement(butnotyetcompleteencasementorocclusionofthemajorvessels)andthosewithpancreaticbodyortaillesionswhoarenotjaundiced.OtherindicationsforastaginglaparoscopypriortoopenlaparotomyincludeahighpreoperativeCA199level(>1000units/mL)andanypatientforwhomhighqualityimagingisinanywaysuggestiveofoccultmetastaticdisease.Atsomeinstitutions,diagnosticlaparoscopyisperformedifneoadjuvanttherapyistoberecommended.

ImportanceofperitonealcytologyPeritonealwashingsareoftenobtainedatthetimeoflaparoscopy.Whileitwouldseemintuitivethatpatientswhohavepositiveperitonealwashingswouldbeunlikelytobenefitfromradicalresectionofthepancreaticprimarytumor,ithasnotbeenconclusivelydemonstratedthatpositiveperitonealcytologyasanisolatedfindingisanindependentadverseprognosticfactor[137139].Ingeneral,mostpatientswhohavecytologicallypositivewashingshaveotherfindingsthatsuggestadvanceddiseaseandunresectabilitysuchasascitesand/orthepresenceofmetastasesintheliver,pelvis,oromentum[137,140,141].Iftheseareabsent,mostpancreaticsurgeonsdonotrelyupontheresultsofperitonealwashingsobtainedatthetimeoflaparoscopytoguidedecisionmakingregardingresectability.However,theAJCCstagingsystemconsiderspositiveperitonealwashingstorepresentdistantmetastatic(M1)disease(table3)[76].

DIAGNOSTICALGORITHMANDNEEDFORPREOPERATIVEBIOPSYOursuggesteddiagnosticapproachtothepatientwithsuspectedpancreaticcancerisoutlinedinthealgorithm(algorithm2).(See'Biopsyandestablishingthediagnosis'above.)

Adiagnosticbiopsyofasuspectedpancreaticmalignancymaybeindicatedifthereisevidenceofsystemicspreadofdisease,ifthereislocalevidenceofunresectabilityonstagingstudies,ifthepatientisunfitformajorsurgery,ifneoadjuvanttreatmentisbeingcontemplated(eg,foraborderlineresectablelesion),orifalternativediagnosesneedtobeexcluded(eg,metastaticdiseasetothepancreas).(See"Initialchemotherapyandradiationfornonmetastaticlocallyadvancedunresectable,borderlineresectable,andpotentiallyresectableexocrinepancreaticcancer",sectionon'Roleofsurgery'.)

However,apreoperativediagnosticbiopsymaynotbeneededinafitpatientwithapotentiallyresectablepancreaticlesionthatishighlysuspectedofmalignancy.Whileapositivebiopsycanconfirmthesuspecteddiagnosis,abenignsamplewillnotexcludethepresenceofmalignancy.Inonesystematicreviewof53studies



addressingthisissue,thenegativepredictivevalueofpercutaneousandEUSguidedbiopsieswasonly60to70percent[142].Attemptstomakeapreoperativetissuediagnosismayinfactbedetrimentaliftumorcellsaredisseminatedduringpercutaneousbiopsy.

Thus,ifapatientisareasonablesurgicalcandidate,andiftheclinicalpresentationandimagingaretypicalforaresectableadenocarcinomaafterthestagingevaluationhasbeencompleted,itisreasonabletoproceedtosurgerywithoutatissuediagnosis.(See'Stagingsystemandthestagingworkup'above.)

However,itmustberecognizedbyboththeclinicianandthepatientthatuncertaintyregardingthediagnosisintheseinstancespersistsandthatsomepatientswithbenignlesionsmaybesubjectedtotheradicalresectionsusedformalignantlesions.Thesecasescomprisebetween5and11percentofpatientsresectedforapresumedcancer[143146].Thefrequencyofradicalresectionforbenigndiseasemaybereducedwhenthisapproachiscombinedwithadditionalimaging,EUSguidedtransduodenalbiopsy.(See'EUSguidedbiopsy'above.)

FocalchronicpancreatitisandautoimmunepancreatitisarethetwobenignprocessesthataremostcommonlymistakenforpancreaticmalignancyonCTorUS.EUSguidedbiopsymayberecommendedifadiagnosisofchronicorautoimmunepancreatitisissuspectedonthebasisofhistory(eg,extremeyoungage,prolongedethanolabuse,historyofotherautoimmunediseases),particularlyiffurtherimagingstudies(eitherEUS,ERCPormagneticresonancecholangiopancreatography)revealmultifocalbiliarystrictures(suggestiveofautoimmunepancreatitis)ordiffusepancreaticductalchanges(suggestiveofchronicpancreatitis).Inaddition,serologictestingcanaidinthediagnosisofautoimmunepancreatitis.(See"Clinicalmanifestationsanddiagnosisofchronicpancreatitisinadults"and"Autoimmunepancreatitis".)

ForjaundicedpatientswhohavenoinvolvementorminimalinvolvementofthemajorvesselsaccordingtoCTorEUSandnoevidenceofdistantmetastasesonhelicalCTorEUS,weproceeddirectlytoanattemptatsurgicalresection.Fornonjaundicedpatients(particularlywithbodyortailtumors),orthosewithmajorbutincompleteinvolvementofthevascularstructures(tumorcontiguoustolessthanonehalfofthevesselcircumference[97,98]),weperformpreoperativelaparoscopytoexcludetinymetastasesthatmighthavebeenoverlookedbyCT.Ifthelaparoscopyisnegative,wethenembarkonaradicalsurgicalresection.(See'Staginglaparoscopy'above.)

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5 to6 gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10 to12 gradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon"patientinfo"andthekeyword(s)ofinterest.)

SUMMARYANDRECOMMENDATIONS

th th

th th

Basicstopics(see"Patientinformation:Pancreaticcancer(TheBasics)")

BeyondtheBasicstopics(see"Patientinformation:Pancreaticcancer(BeyondtheBasics)")

Thecommonlyusedterm"pancreaticcancer"usuallyreferstoaductaladenocarcinomaofthepancreas(includingitssubtypes).Morethan95percentofmalignantneoplasmsofthepancreasarisefromtheexocrineelementsandarereferredtoasexocrinepancreaticcancers.(See'Pathology'above.)

Themostcommonpresentingsymptomsinpatientswithexocrinepancreaticcancerarepain,jaundice,andweightloss.Comparedtotumorsinthebodyandtailofthegland,pancreaticheadtumorsmoreoftenpresentwithjaundice,steatorrhea,andweightloss.(See'Clinicalpresentation'above.)



Patientswhopresentwithjaundiceorepigastricpainandweightlossoftenundergorightupperquadranttransabdominalultrasoundinitiallytoevaluatefordilatedbileductsorapancreaticmass.(See'Initialtesting'aboveand'Transabdominalultrasound'above.)

Inthejaundicedpatient,ultrasoundishighlysensitivefordetectingbiliarytractdilationandestablishingthelevelofobstructionitishighlysensitiveforpancreaticmasses>3cm.(See'Jaundice'above.)

Endoscopicretrogradecholangiopancreatography(ERCP)isahighlysensitivetoolforvisualizationofthebiliarytreeandpancreaticductsinpatientswithjaundice.However,theroleofERCPinpatientswithsuspectedpancreaticcancerisevolvingintoamainlytherapeuticratherthandiagnosticmodalityinpatientswhopresentwithcholestasisduetotumorobstructionofthebiliarysystem.(See'ERCP'above.)

Analternativeapproachismagneticresonancecholangiopancreatography(MRCP).MRCPisgenerallyreservedforpatientswithgastricoutletorduodenalstenosis,orwhohavehadsurgicalrearrangement(eg,BillrothII)orductaldisruption,resultinginductsthataredifficulttoassesssuccessfullybyERCP,inthesettingofchronicpancreatitis,orforpatientsinwhomattemptedERCPiseithertotallyunsuccessfulorprovidesincompleteinformationbecauseofpancreaticductobstruction.(See'MRCP'above.).

Forpatientswithepigastricpainandweightlosswithoutjaundice,inwhomthedifferentialdiagnosisincludespancreatitis,transabdominalultrasoundisnotthepreferredinitialtestbecauseitisassociatedwithahighfrequencyofincompleteexaminationsowingtooverlyingbowelgasduetoileus,anditcannotclearlyidentifynecrosiswithinthepancreastheseimportantfindingsarebestseenbycontrastenhancedCTscan.(See'Epigastricpainandweightloss'above.)

Endoscopicultrasound(EUS)maybeofuseinapatientwhoissuspectedofhavingpancreaticcancerbasedupontheclinicalpresentationofjaundice,unexplainedupperabdominalpain/weightloss,oranunexplainedepisodeofpancreatitis,butwhohasnoevidenceofamasslesiononinitialtransabdominalultrasoundorCT.(See'Subsequenttestingifinitialimagingisnegative'above.)

Giventhelimitedsensitivityandspecificity,theserumtumormarkerCA199shouldnotbeusedasadiagnostictestforpancreaticcancer.(See'CA199'above.)

Histologicconfirmationisrequiredtoestablishadiagnosisofpancreaticcancer.Biopsyofapancreaticmasscanbeaccomplishedthroughpercutaneousorendoscopicapproaches.However,notallpatientsrequireapreoperativebiopsy,andthenextstepintheworkupofapatientwithsuspectedpancreaticcancerisoftenastagingevaluationtoestablishdiseaseextentandresectabilityratherthanbiopsy.(See'Biopsyandestablishingthediagnosis'above.)

WhenamasslesionofthepancreasisdetectedonCTorultrasound,itisreasonabletoconcludethataneoplasm(mostlikelymalignant)ispresent,andtriplephase,contrastenhancedhelical(preferablymultidetectorrow)CTisanappropriatenextsteptoassessdiseaseextentandresectability.Localunresectabilityisusually(butnotalways)duetovascularinvasion,particularlyofthesuperiormesentericartery(SMA).(See'AbdominalCT'above.)

Endoscopicultrasound(EUS)isanothereffectivemethodtoassesstumorextentandvascularinvasion,butwegenerallypreferCTgivenitsgreaterutilityinassessingfordistantmetastases.(See'EUS'above.)

Althoughpracticeisvariable,mostsurgeonswouldconsiderapancreaticcancertobecategoricallyunresectableifanyofthefollowingarepresent(see'Definitionsofunresectableandborderlineresectabledisease'above):

Extensiveperipancreaticlymphaticinvolvement,nodalinvolvementbeyondtheperipancreatictissues,



UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

REFERENCES

1. PortaM,FabregatX,MalatsN,etal.Exocrinepancreaticcancer:symptomsatpresentationandtheirrelationtotumoursiteandstage.ClinTranslOncol20057:189.

2. ModolellI,GuarnerL,MalageladaJR.Vagariesofclinicalpresentationofpancreaticandbiliarytractcancer.

and/ordistantmetastases.

Directinvolvementofthesuperiormesentericartery(SMA),inferiorvenacava,aorta,celiacaxis,orhepaticartery,asdefinedbytheabsenceofafatplanebetweenthelowdensitytumorandthesestructuresonCTscan.

Encasement(morethanonehalfofthevesselcircumference)orocclusion/thrombusofthesuperiormesentericvein(SMV)ortheSMVportalveinconfluenceusedtobeuniversallyconsideredanindicatorofunresectability.However,manycentershavedemonstratedthefeasibilityofSMVreconstruction,andthisisnowconsideredbymanytorepresentborderlineresectablediseaseinpractice,mostofthesepatientsarereferredforneoadjuvanttherapypriortosurgery.

TheutilityofPETscans,chestCT,andMRIinthestagingworkupofsuspectedpancreaticcancer,particularlywhetheranyoftheseimagingstudiesprovidesinformationbeyondthatobtainedbytriplephase,contrastenhancedhelicalmultidetectorrowCTremainsuncertain,andwedonotroutinelyorderthesetests.(See'PETscanning'aboveand'ChestCT'aboveand'MRI'above.)

AssessmentofserumlevelsofthetumormarkerCA199priortosurgeryandfollowingresection,ifelevated,isvaluabletoassistinprognostication.Inaddition,serialmonitoringofCA199levels,ifinitiallyelevated,isusefultofollowpatientsafterpotentiallycurativesurgeryandforthosewhoarereceivingchemotherapyforadvanceddisease.(See'CA199'above.)

Ourgeneraldiagnosticapproach,asdetailedinthefollowingsections,issummarizedinthealgorithm(algorithm2).Ingeneral(see'Diagnosticalgorithmandneedforpreoperativebiopsy'above):

Tissuediagnosisismandatoryforpatientswhoareunfittoundergoamajorresection,forthosewithahighsuspicionofmetastaticdisease,andforanypatientbeingconsideredforneoadjuvanttherapybecauseoflocallyadvancednonmetastaticdisease.EUSguidedFNAisthebestmodalityforobtainingatissuediagnosis,evenifthetumorispoorlyvisualizedbyotherimagingmodalities.

Ifapatientisareasonablesurgicalcandidate,andiftheclinicalpresentationandimagingaretypicalforaresectableadenocarcinoma,itisreasonabletoproceedtosurgerywithoutatissuediagnosis.

Forjaundicedpatientswithnoinvolvementorminimalinvolvementofthemajorvesselsandnoevidenceofdistantmetastasesonradiographicimaging,weproceeddirectlytoopenlaparotomy.(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis".)

Fornonjaundicedpatients(includingallthosewithbodyortailtumors),aswellasthosewithmajorbutincompleteinvolvementofthevascularstructures(eg,tumorcontiguoustolessthanonehalfofthevesselcircumference),weperformpreoperativelaparoscopytoexcludetinymetastasesthatmighthavebeenoverlookedbyCT.Ifthelaparoscopyisnegative,wethenproceedtoopenlaparotomytoassessresectability.OtherindicationsforastaginglaparoscopypriortoopenlaparotomyincludeahighpreoperativeCA199level(>1000units/mL),anypatientforwhomhighqualityimagingisinanywaysuggestiveofoccultmetastaticdisease,andatsomeinstitutions,forpatientsinwhomaneoadjuvantapproachtotherapyisbeingconsidered.(See'Staginglaparoscopy'above.)



AnnOncol199910Suppl4:82.3. KalserMH,BarkinJ,MacIntyreJM.Pancreaticcancer.Assessmentofprognosisbyclinicalpresentation.

Cancer198556:397.4. BakkevoldKE,ArnesjB,KambestadB.CarcinomaofthepancreasandpapillaofVater:presenting

symptoms,signs,anddiagnosisrelatedtostageandtumoursite.Aprospectivemulticentretrialin472patients.NorwegianPancreaticCancerTrial.ScandJGastroenterol199227:317.

5. FurukawaH,OkadaS,SaishoH,etal.Clinicopathologicfeaturesofsmallpancreaticadenocarcinoma.Acollectivestudy.Cancer199678:986.

6. TsuchiyaR,NodaT,HaradaN,etal.Collectivereviewofsmallcarcinomasofthepancreas.AnnSurg1986203:77.

7. MujicaVR,BarkinJS,GoVL.Acutepancreatitissecondarytopancreaticcarcinoma.StudyGroupParticipants.Pancreas200021:329.

8. ManabeT,MiyashitaT,OhshioG,etal.Smallcarcinomaofthepancreas.Clinicalandpathologicevaluationof17patients.Cancer198862:135.

9. HollyEA,ChalihaI,BracciPM,GautamM.Signsandsymptomsofpancreaticcancer:apopulationbasedcasecontrolstudyintheSanFranciscoBayarea.ClinGastroenterolHepatol20042:510.

10. ChariST,LeibsonCL,RabeKG,etal.Probabilityofpancreaticcancerfollowingdiabetes:apopulationbasedstudy.Gastroenterology2005129:504.

11. AggarwalG,KamadaP,ChariST.Prevalenceofdiabetesmellitusinpancreaticcancercomparedtocommoncancers.Pancreas201342:198.

12. KhoranaAA,FineRL.Pancreaticcancerandthromboembolicdisease.LancetOncol20045:655.13. ChenL,LiY,GebreW,LinJH.Myocardialandcerebralinfarctionduetononbacterialthrombotic

endocarditisasaninitialpresentationofpancreaticadenocarcinoma.ArchPatholLabMed2004128:1307.14. PinzonR,DrewinkoB,TrujilloJM,etal.PancreaticcarcinomaandTrousseau'ssyndrome:experienceata

largecancercenter.JClinOncol19864:509.15. OstlereLS,BranfootAC,StaughtonRC.Cicatricialpemphigoidandcarcinomaofthepancreas.ClinExp

Dermatol199217:67.16. GalvaVG.SisterMaryJoseph'snodule.AnnInternMed1998128:410.17. GoodmanM,WillmannJK,JeffreyRB.Incidentallydiscoveredsolidpancreaticmasses:imagingand

clinicalobservations.AbdomImaging201237:91.18. StapleyS,PetersTJ,NealRD,etal.Theriskofpancreaticcancerinsymptomaticpatientsinprimarycare:

alargecasecontrolstudyusingelectronicrecords.BrJCancer2012106:1940.19. RoseJF,JieT,UseraP,OngES.Pancreaticoduodenectomyforprimarypancreaticlymphoma.

GastrointestCancerRes20125:32.20. RockJ,BloomstonM,LozanskiG,FrankelWL.Thespectrumofhematologicmalignanciesinvolvingthe

pancreas:potentialclinicalmimicsofpancreaticadenocarcinoma.AmJClinPathol2012137:414.21. DiMagnoEP,MalageladaJR,TaylorWF,GoVL.Aprospectivecomparisonofcurrentdiagnostictestsfor

pancreaticcancer.NEnglJMed1977297:737.22. BrambsHJ,ClaussenCD.Pancreaticandampullarycarcinoma.Ultrasound,computedtomography,

magneticresonanceimagingandangiography.Endoscopy199325:58.23. TanakaS,KitamraT,YamamotoK,etal.Evaluationofroutinesonographyforearlydetectionofpancreatic

cancer.JpnJClinOncol199626:422.24. PasanenPA,EskelinenM,PartanenK,etal.Aprospectivestudyofthevalueofimaging,serummarkers

andtheircombinationinthediagnosisofpancreaticcarcinomainsymptomaticpatients.AnticancerRes199212:2309.

25. PasanenPA,PartanenKP,PikkarainenPH,etal.Acomparisonofultrasound,computedtomographyandendoscopicretrogradecholangiopancreatographyinthedifferentialdiagnosisofbenignandmalignantjaundiceandcholestasis.EurJSurg1993159:23.

26. HesselSJ,SiegelmanSS,McNeilBJ,etal.Aprospectiveevaluationofcomputedtomographyandultrasoundofthepancreas.Radiology1982143:129.

27. BluemkeDA,CameronJL,HrubanRH,etal.Potentiallyresectablepancreaticadenocarcinoma:spiralCT



assessmentwithsurgicalandpathologiccorrelation.Radiology1995197:381.28. BrandR.Thediagnosisofpancreaticcancer.CancerJ20017:287.29. WangW,ShpanerA,KrishnaSG,etal.UseofEUSFNAindiagnosingpancreaticneoplasmwithouta

definitivemassonCT.GastrointestEndosc201378:73.30. KarlsonBM,EkbomA,LindgrenPG,etal.AbdominalUSfordiagnosisofpancreatictumor:prospective

cohortanalysis.Radiology1999213:107.31. MaringhiniA,CiambraM,RaimondoM,etal.Clinicalpresentationandultrasonographyinthediagnosisof

pancreaticcancer.Pancreas19938:146.32. FreenyPC,MarksWM,RyanJA,TraversoLW.Pancreaticductaladenocarcinoma:diagnosisandstaging

withdynamicCT.Radiology1988166:125.33. VallsC,AndaE,SanchezA,etal.DualphasehelicalCTofpancreaticadenocarcinoma:assessmentof

resectabilitybeforesurgery.AJRAmJRoentgenol2002178:821.34. BronsteinYL,LoyerEM,KaurH,etal.DetectionofsmallpancreatictumorswithmultiphasichelicalCT.

AJRAmJRoentgenol2004182:619.35. YoonSH,LeeJM,ChoJY,etal.Small(20mm)pancreaticadenocarcinomas:analysisofenhancement

patternsandsecondarysignswithmultiphasicmultidetectorCT.Radiology2011259:442.36. NinoMurciaM,JeffreyRBJr,BeaulieuCF,etal.MultidetectorCTofthepancreasandbileductsystem:

valueofcurvedplanarreformations.AJRAmJRoentgenol2001176:689.37. FulcherAS,TurnerMA.MRpancreatography:ausefultoolforevaluatingpancreaticdisorders.

Radiographics199919:5.38. KimJH,KimMJ,ChungJJ,etal.DifferentialdiagnosisofperiampullarycarcinomasatMRimaging.

Radiographics200222:1335.39. NiederauC,GrendellJH.Diagnosisofpancreaticcarcinoma.Imagingtechniquesandtumormarkers.

Pancreas19927:66.40. VargheseJC,FarrellMA,CourtneyG,etal.RoleofMRcholangiopancreatographyinpatientswithfailedor

inadequateERCP.AJRAmJRoentgenol1999173:1527.41. AdamekHE,AlbertJ,BreerH,etal.Pancreaticcancerdetectionwithmagneticresonance

cholangiopancreatographyandendoscopicretrogradecholangiopancreatography:aprospectivecontrolledstudy.Lancet2000356:190.

42. LopezHnninenE,AmthauerH,HostenN,etal.Prospectiveevaluationofpancreatictumors:accuracyofMRimagingwithMRcholangiopancreatographyandMRangiography.Radiology2002224:34.

43. PleskowDK,BergerHJ,GyvesJ,etal.Evaluationofaserologicmarker,CA199,inthediagnosisofpancreaticcancer.AnnInternMed1989110:704.

44. CwikG,WallnerG,SkoczylasT,etal.Cancerantigens199and125inthedifferentialdiagnosisofpancreaticmasslesions.ArchSurg2006141:968.

45. vandenBoschRP,vanEijckCH,MulderPG,JeekelJ.SerumCA199determinationinthemanagementofpancreaticcancer.Hepatogastroenterology199643:710.

46. PaganuzziM,OnettoM,MarroniP,etal.CA199andCA50inbenignandmalignantpancreaticandbiliarydiseases.Cancer198861:2100.

47. MalesciA,TommasiniMA,BonatoC,etal.DeterminationofCA199antigeninserumandpancreaticjuicefordifferentialdiagnosisofpancreaticadenocarcinomafromchronicpancreatitis.Gastroenterology198792:60.

48. DiMagnoEP,ReberHA,TemperoMA.AGAtechnicalreviewontheepidemiology,diagnosis,andtreatmentofpancreaticductaladenocarcinoma.AmericanGastroenterologicalAssociation.Gastroenterology1999117:1464.

49. SteinbergW.TheclinicalutilityoftheCA199tumorassociatedantigen.AmJGastroenterol199085:350.50. LamerzR.Roleoftumourmarkers,cytogenetics.AnnOncol199910Suppl4:145.51. GogginsM.Molecularmarkersofearlypancreaticcancer.JClinOncol200523:4524.52. TemperoMA,UchidaE,TakasakiH,etal.Relationshipofcarbohydrateantigen199andLewisantigensin

pancreaticcancer.CancerRes198747:5501.



53. KimHJ,KimMH,MyungSJ,etal.AnewstrategyfortheapplicationofCA199inthedifferentiationofpancreaticobiliarycancer:analysisusingareceiveroperatingcharacteristiccurve.AmJGastroenterol199994:1941.

54. MolinaV,VisaL,ConillC,etal.CA199inpancreaticcancer:retrospectiveevaluationofpatientswithsuspicionofpancreaticcancer.TumourBiol201233:799.

55. KimJE,LeeKT,LeeJK,etal.Clinicalusefulnessofcarbohydrateantigen199asascreeningtestforpancreaticcancerinanasymptomaticpopulation.JGastroenterolHepatol200419:182.

56. LockerGY,HamiltonS,HarrisJ,etal.ASCO2006updateofrecommendationsfortheuseoftumormarkersingastrointestinalcancer.JClinOncol200624:5313.

57. GoonetillekeKS,SiriwardenaAK.Systematicreviewofcarbohydrateantigen(CA199)asabiochemicalmarkerinthediagnosisofpancreaticcancer.EurJSurgOncol200733:266.

58. MarcouizosG,IgnatiadouE,PapanikolaouGE,etal.HighlyelevatedserumlevelsofCA199incholedocholithiasis:acasereport.CasesJ20092:6662.

59. MaiseyNR,NormanAR,HillA,etal.CA199asaprognosticfactorininoperablepancreaticcancer:theimplicationforclinicaltrials.BrJCancer200593:740.

60. BergerAC,GarciaMJr,HoffmanJP,etal.PostresectionCA199predictsoverallsurvivalinpatientswithpancreaticcancertreatedwithadjuvantchemoradiation:aprospectivevalidationbyRTOG9704.JClinOncol200826:5918.

61. KoomWS,SeongJ,KimYB,etal.CA199asapredictorforresponseandsurvivalinadvancedpancreaticcancerpatientstreatedwithchemoradiotherapy.IntJRadiatOncolBiolPhys200973:1148.

62. KondoN,MurakamiY,UemuraK,etal.PrognosticimpactofperioperativeserumCA199levelsinpatientswithresectablepancreaticcancer.AnnSurgOncol201017:2321.

63. AbdelMisihSR,HatzarasI,SchmidtC,etal.FailureofnormalizationofCA199followingresectionforpancreaticcanceristantamounttometastaticdisease.AnnSurgOncol201118:1116.

64. HumphrisJL,ChangDK,JohnsAL,etal.TheprognosticandpredictivevalueofserumCA19.9inpancreaticcancer.AnnOncol201223:1713.

65. MaithelSK,MaloneyS,WinstonC,etal.PreoperativeCA199andtheyieldofstaginglaparoscopyinpatientswithradiographicallyresectablepancreaticadenocarcinoma.AnnSurgOncol200815:3512.

66. KarachristosA,ScarmeasN,HoffmanJP.CA199levelspredictresultsofstaginglaparoscopyinpancreaticcancer.JGastrointestSurg20059:1286.

67. FujiokaS,MisawaT,OkamotoT,etal.Preoperativeserumcarcinoembryonicantigenandcarbohydrateantigen199levelsfortheevaluationofcurabilityandresectabilityinpatientswithpancreaticadenocarcinoma.JHepatobiliaryPancreatSurg200714:539.

68. KiliM,GmenE,TezM,etal.ValueofpreoperativeserumCA199levelsinpredictingresectabilityforpancreaticcancer.CanJSurg200649:241.

69. HartwigW,StrobelO,HinzU,etal.CA199inpotentiallyresectablepancreaticcancer:perspectivetoadjustsurgicalandperioperativetherapy.AnnSurgOncol201320:2188.

70. KoopmannJ,RosenzweigCN,ZhangZ,etal.Serummarkersinpatientswithresectablepancreaticadenocarcinoma:macrophageinhibitorycytokine1versusCA199.ClinCancerRes200612:442.

71. DelMaschioA,VanzulliA,SironiS,etal.Pancreaticcancerversuschronicpancreatitis:diagnosiswithCA199assessment,US,CT,andCTguidedfineneedlebiopsy.Radiology1991178:95.

72. JohnsonDE,PendurthiTK,BalshemAM,etal.Implicationsoffineneedleaspirationinpatientswithresectablepancreaticcancer.AmSurg199763:675.

73. MicamesC,JowellPS,WhiteR,etal.LowerfrequencyofperitonealcarcinomatosisinpatientswithpancreaticcancerdiagnosedbyEUSguidedFNAvs.percutaneousFNA.GastrointestEndosc200358:690.

74. ChongA,VenugopalK,SegarajasingamD,LisewskiD.TumorseedingafterEUSguidedFNAofpancreatictailneoplasia.GastrointestEndosc201174:933.

75. PaquinSC,GaripyG,LepantoL,etal.AfirstreportoftumorseedingbecauseofEUSguidedFNAofapancreaticadenocarcinoma.GastrointestEndosc200561:610.

76. AJCC(AmericanJointCommitteeonCancer)CancerStagingManual,7thed,EdgeSB,ByrdDR,Compton



CC,etal(Eds),Springer,NewYorkVol2010,p.241.77. HortonKM,FishmanEK.MultidetectorrowCTwithdualphaseCTangiographyinthepreoperative

evaluationofpancreaticcancer.CritRevComputTomogr200243:323.78. DeWittJ,DevereauxB,ChriswellM,etal.Comparisonofendoscopicultrasonographyandmultidetector

computedtomographyfordetectingandstagingpancreaticcancer.AnnInternMed2004141:753.79. SmithSL,RajanPS.ImagingofpancreaticadenocarcinomawithemphasisonmultidetectorCT.ClinRadiol

200459:26.80. WongJC,RamanS.Surgicalresectabilityofpancreaticadenocarcinoma:CTA.AbdomImaging2010

35:471.81. LuDS,VedanthamS,KrasnyRM,etal.TwophasehelicalCTforpancreatictumors:pancreaticversus

hepaticphaseenhancementoftumor,pancreas,andvascularstructures.Radiology1996199:697.82. FletcherJG,WiersemaMJ,FarrellMA,etal.Pancreaticmalignancy:valueofarterial,pancreatic,and

hepaticphaseimagingwithmultidetectorrowCT.Radiology2003229:81.83. FrancisIR,CohanRH,McNultyNJ,etal.MultidetectorCToftheliverandhepaticneoplasms:effectof

multiphasicimagingontumorconspicuityandvascularenhancement.AJRAmJRoentgenol2003180:1217.

84. KatzMH,PistersPW,EvansDB,etal.Borderlineresectablepancreaticcancer:theimportanceofthisemergingstageofdisease.JAmCollSurg2008206:833.

85. NationalComprehensiveCancerNetwork(NCCN).NCCNClinicalpracticeguidelinesinoncology.http://www.nccn.org/professionals/physician_gls/f_guidelines.asp(AccessedonApril01,2014).

86. CalleryMP,ChangKJ,FishmanEK,etal.Pretreatmentassessmentofresectableandborderlineresectablepancreaticcancer:expertconsensusstatement.AnnSurgOncol200916:1727.

87. BoldRJ,CharnsangavejC,ClearyKR,etal.Majorvascularresectionaspartofpancreaticoduodenectomyforcancer:radiologic,intraoperative,andpathologicanalysis.JGastrointestSurg19993:233.

88. StrobelO,BerensV,HinzU,etal.Resectionafterneoadjuvanttherapyforlocallyadvanced,"unresectable"pancreaticcancer.Surgery2012152:S33.

89. SatoiS,YamamotoH,TakaiS,etal.Clinicalimpactofmultidetectorrowcomputedtomographyonpatientswithpancreaticcancer.Pancreas200734:175.

90. HolzapfelK,ReiserErkanC,FingerleAA,etal.ComparisonofdiffusionweightedMRimagingandmultidetectorrowCTinthedetectionoflivermetastasesinpatientsoperatedforpancreaticcancer.AbdomImaging201136:179.

91. MotosugiU,IchikawaT,MorisakaH,etal.DetectionofpancreaticcarcinomaandlivermetastaseswithgadoxeticacidenhancedMRimaging:comparisonwithcontrastenhancedmultidetectorrowCT.Radiology2011260:446.

92. JohnTG,GreigJD,CarterDC,GardenOJ.Carcinomaofthepancreaticheadandperiampullaryregion.Tumorstagingwithlaparoscopyandlaparoscopicultrasonography.AnnSurg1995221:156.

93. GullN,PatritiA,CirocchiR,etal.[Theroleoflaparoscopyintheidentificationofperitonealcarcinosisfromabdominalneoplasms.Analysisofourinitialexperience].MinervaChir200055:737.

94. ReddyKR,LeviJ,LivingstoneA,etal.Experiencewithstaginglaparoscopyinpancreaticmalignancy.GastrointestEndosc199949:498.

95. RocheCJ,HughesML,GarveyCJ,etal.CTandpathologicassessmentofprospectivenodalstaginginpatientswithductaladenocarcinomaoftheheadofthepancreas.AJRAmJRoentgenol2003180:475.

96. LiH,ZengMS,ZhouKR,etal.Pancreaticadenocarcinoma:thedifferentCTcriteriaforperipancreaticmajorarterialandvenousinvasion.JComputAssistTomogr200529:170.

97. LuDS,ReberHA,KrasnyRM,etal.Localstagingofpancreaticcancer:criteriaforunresectabilityofmajorvesselsasrevealedbypancreaticphase,thinsectionhelicalCT.AJRAmJRoentgenol1997168:1439.

98. O'MalleyME,BolandGW,WoodBJ,etal.Adenocarcinomaoftheheadofthepancreas:determinationofsurgicalunresectabilitywiththinsectionpancreaticphasehelicalCT.AJRAmJRoentgenol1999173:1513.

99. LoyerEM,DavidCL,DubrowRA,etal.Vascularinvolvementinpancreaticadenocarcinoma:reassessmentbythinsectionCT.AbdomImaging199621:202.



100. NakayamaY,YamashitaY,KadotaM,etal.Vascularencasementbypancreaticcancer:correlationofCTfindingswithsurgicalandpathologicresults.JComputAssistTomogr200125:337.

101. SaldingerPF,ReillyM,ReynoldsK,etal.IsCTangiographysufficientforpredictionofresectabilityofperiampullaryneoplasms?JGastrointestSurg20004:233.

102. ColeySC,StricklandNH,WalkerJD,WilliamsonRC.SpiralCTandthepreoperativeassessmentofpancreaticadenocarcinoma.ClinRadiol199752:24.

103. KanekoOF,LeeDM,WongJ,etal.Performanceofmultidetectorcomputedtomographicangiographyindeterminingsurgicalresectabilityofpancreaticheadadenocarcinoma.JComputAssistTomogr201034:732.

104. VedanthamS,LuDS,ReberHA,KadellB.Smallperipancreaticveins:improvedassessmentinpancreaticcancerpatientsusingthinsectionpancreaticphasehelicalCT.AJRAmJRoentgenol1998170:377.

105. ZhaoWY,LuoM,SunYW,etal.Computedtomographyindiagnosingvascularinvasioninpancreaticandperiampullarycancers:asystematicreviewandmetaanalysis.HepatobiliaryPancreatDisInt20098:457.

106. LiKC,HopkinsKL,DalmanRL,SongCK.SimultaneousmeasurementofflowinthesuperiormesentericveinandarterywithcinephasecontrastMRimaging:valueindiagnosisofchronicmesentericischemia.Workinprogress.Radiology1995194:327.

107. MegibowAJ,ZhouXH,RotterdamH,etal.Pancreaticadenocarcinoma:CTversusMRimagingintheevaluationofresectabilityreportoftheRadiologyDiagnosticOncologyGroup.Radiology1995195:327.

108. IrieH,HondaH,KanekoK,etal.ComparisonofhelicalCTandMRimagingindetectingandstagingsmallpancreaticadenocarcinoma.AbdomImaging199722:429.

109. SheridanMB,WardJ,GuthrieJA,etal.DynamiccontrastenhancedMRimaginganddualphasehelicalCTinthepreoperativeassessmentofsuspectedpancreaticcancer:acomparativestudywithreceiveroperatingcharacteristicanalysis.AJRAmJRoentgenol1999173:583.

110. BuchsNC,ChilcottM,PolettiPA,etal.Vascularinvasioninpancreaticcancer:Imagingmodalities,preoperativediagnosisandsurgicalmanagement.WorldJGastroenterol201016:818.

111. TredeM,RumstadtB,WendlK,etal.Ultrafastmagneticresonanceimagingimprovesthestagingofpancreatictumors.AnnSurg1997226:393.

112. BalciNC,SemelkaRC.Radiologicdiagnosisandstagingofpancreaticductaladenocarcinoma.EurJRadiol200138:105.

113. NordbackI,SaaristoR,PiironenA,SandJ.Chestcomputedtomographyinthestagingofpancreaticandperiampullarycarcinoma.ScandJGastroenterol200439:81.

114. SingerE,GschwantlerM,PlattnerD,etal.Differentialdiagnosisofbenignandmalignpancreaticmasseswith18Ffluordeoxyglucosepositronemissiontomographyrecordedwithadualheadcoincidencegammacamera.EurJGastroenterolHepatol200719:471.

115. IzuishiK,YamamotoY,SanoT,etal.Impactof18fluorodeoxyglucosepositronemissiontomographyonthemanagementofpancreaticcancer.JGastrointestSurg201014:1151.

116. HeinrichS,GoerresGW,SchferM,etal.Positronemissiontomography/computedtomographyinfluencesonthemanagementofresectablepancreaticcanceranditscosteffectiveness.AnnSurg2005242:235.

117. FarmaJM,SantillanAA,MelisM,etal.PET/CTfusionscanenhancesCTstaginginpatientswithpancreaticneoplasms.AnnSurgOncol200815:2465.

118. SchickV,FranziusC,BeynaT,etal.Diagnosticimpactof18FFDGPETCTevaluatingsolidpancreaticlesionsversusendosonography,endoscopicretrogradecholangiopancreatographywithintraductalultrasonographyandabdominalultrasound.EurJNuclMedMolImaging200835:1775.

119. KauhanenSP,KomarG,SeppnenMP,etal.Aprospectivediagnosticaccuracystudyof18Ffluorodeoxyglucosepositronemissiontomography/computedtomography,multidetectorrowcomputedtomography,andmagneticresonanceimaginginprimarydiagnosisandstagingofpancreaticcancer.AnnSurg2009250:957.

120. LytrasD,ConnorS,BosonnetL,etal.Positronemissiontomographydoesnotaddtocomputedtomographyforthediagnosisandstagingofpancreaticcancer.DigSurg200522:55.

121. NguyenNQ,BartholomeuszDF.18FFDGPET/CTintheassessmentofpancreaticcancer:isthecontrastorabetterdesignedtrialneeded?JGastroenterolHepatol201126:613.

122. StrobelK,HeinrichS,BhureU,etal.Contrastenhanced18FFDGPET/CT:1stopshopimagingfor



assessingtheresectabilityofpancreaticcancer.JNuclMed200849:1408.123. BuchsNC,BhlerL,BucherP,etal.Valueofcontrastenhanced18Ffluorodeoxyglucosepositronemission

tomography/computedtomographyindetectionandpresurgicalassessmentofpancreaticcancer:aprospectivestudy.JGastroenterolHepatol201126:657.

124. KitajimaK,MurakamiK,YamasakiE,etal.PerformanceofintegratedFDGPET/contrastenhancedCTinthediagnosisofrecurrentpancreaticcancer:comparisonwithintegratedFDGPET/noncontrastenhancedCTandenhancedCT.MolImagingBiol201012:452.

125. MertzHR,SechopoulosP,DelbekeD,LeachSD.EUS,PET,andCTscanningforevaluationofpancreaticadenocarcinoma.GastrointestEndosc200052:367.

126. NishiyamaY,YamamotoY,YokoeK,etal.ContributionofwholebodyFDGPETtothedetectionofdistantmetastasisinpancreaticcancer.AnnNuclMed200519:491.

127. ZafraM,AyalaF,GonzalezBillalabeitiaE,etal.Impactofwholebody18FFDGPETondiagnosticandtherapeuticmanagementofMedicalOncologypatients.EurJCancer200844:1678.

128. DiederichsCG,StaibL,VogelJ,etal.Valuesandlimitationsof18Ffluorodeoxyglucosepositronemissiontomographywithpreoperativeevaluationofpatientswithpancreaticmasses.Pancreas200020:109.

129. LiuRC,TraversoLW.Diagnosticlaparoscopyimprovesstagingofpancreaticcancerdeemedlocallyunresectablebycomputedtomography.SurgEndosc200519:638.

130. ThomsonBN,ParksRW,RedheadDN,etal.Refiningtheroleoflaparoscopyandlaparoscopicultrasoundinthestagingofpresumedpancreaticheadandampullarytumours.BrJCancer200694:213.

131. MayoSC,AustinDF,SheppardBC,etal.Evolvingpreoperativeevaluationofpatientswithpancreaticcancer:doeslaparoscopyhavearoleinthecurrentera?JAmCollSurg2009208:87.

132. AllenVB,GurusamyKS

Clinical Manifestations, Diagnosis, And Staging of Exocrine Pancreatic Cancer

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