BILIARYBILIARY TRACTTRACT MALIGNANCIES:MALIGNANCIES: DiagnosisDiagnosis andand StagingStaging

Richard M. Gore, MD SCBT/MR Summer Practicum Williamsburg, Virginia August 10, 2009 OBJECTIVESOBJECTIVES

•• ReviewReview thethe imagingimaging findingsfindings ofof cancercancer ofof thethe gallbladdergallbladder andand cholangiocarcinomacholangiocarcinoma •• ApplicationsApplications ofof MDCT,MDCT, MR,MR, MRCP,MRCP, PET/CTPET/CT inin thethe stagingstaging ofof thesethese neoplasmsneoplasms •• SuggestSuggest practicepractice guidelinesguidelines toto promotepromote earlyearly detectiondetection inin highhigh riskrisk individualsindividuals GALLBLADDERGALLBLADDER CARCINOMACARCINOMA EPIDEMIOLOGYEPIDEMIOLOGY

•• 66th mostmost commoncommon GIGI malignancymalignancy •• F:MF:M 2.52.5--33 toto 11 ratioratio •• PeakPeak incidenceincidence 77th decadedecade ofof lifelife •• AtAt autopsy,autopsy, GBGB cancercancer accountsaccounts forfor 11--5%5% ofof malignanciesmalignancies withwith 20%20% beingbeing asymptomaticasymptomatic •• 55 yearyear survivalsurvival ~~ 5%5% GALLBLADDERGALLBLADDER CARCINOMACARCINOMA EPIDEMIOLOGYEPIDEMIOLOGY

•• HighlyHighly lethallethal cancercancer becausebecause anatomicanatomic factorsfactors promotepromote earlyearly spreadspread ofof tumortumor •• MedianMedian survivalsurvival isis 66 monthsmonths indicatingindicating thatthat mostmost patientspatients presentpresent withwith advancedadvanced tumortumor •• EarlyEarly diagnosisdiagnosis isis rarerare becausebecause therethere areare nono specificspecific S+SS+S ofof GBGB cancercancer GALLBLADDERGALLBLADDER CANCER:CANCER: RISKRISK FACTORSFACTORS

• • Ethnic origin: Native • Female gender Americans, Israelis, • Age Chile, Northern Japan • Smoking • Obesity • Choledochal cysts • Typhoid infection • Sclerosing cholangitis • Chemical exposure GALLBLADDERGALLBLADDER CANCERCANCER PATHOGENESISPATHOGENESIS

• > 90% coexistent chronic and stones • More common with 1 large METAPLASIAMETAPLASIA stone rather than multiple smaller stones • Gallstones > 3cm in size have a 10X increased risk DYSPLASIA of GB cancer DYSPLASIA • GB cancer found in 27% of patients having surgery for Mirrizi syndrome compared to 1-2% for CARCINOMACARCINOMA other indications CHOLELITHIASISCHOLELITHIASIS

•• 4848 millionmillion AmericansAmericans withwith gallstonesgallstones •• 850,000850,000 cholecystectomiescholecystectomies annuallyannually •• 2,0002,000 GBGB cancerscancers foundfound inin specimensspecimens •• ~~ CarcinoidCarcinoid inin appendicitisappendicitis GALLBLADDERGALLBLADDER CANCER:CANCER: PORCELAINPORCELAIN GALLBLADDERGALLBLADDER

NearlyNearly 30%30% willwill havehave gallbladdergallbladder cancercancer TendTend toto havehave aa poorpoor prognosisprognosis becausebecause ofof liverliver invasioninvasion GALLBLADDERGALLBLADDER MASSMASS SEENSEEN ONON US:US: DDxDDx

• Stone • Cholesterol • Adenomyomatosis • Tumefactive sludge • cancer • Congenital fold or septum • Mets, adenoma, ectopic panc, hematoma GALLBLADDERGALLBLADDER CANCERCANCER PATHOGENESISPATHOGENESIS

•• GBGB polypspolyps >> 1cm1cm areare mostmost likelylikely toto becomebecome malignantmalignant andand areare anan indicationindication forfor cholecystectomycholecystectomy GALLBLADDERGALLBLADDER CANCER:CANCER: SITESITE OFOF ORIGINORIGIN

•• 60%60% FUNDALFUNDAL •• 30%30% BODYBODY •• 10%10% NECKNECK UNIQUEUNIQUE ANATOMICANATOMIC FEATURESFEATURES OFOF THETHE GALLBLADDERGALLBLADDER

• Mucosa • Lamina propria • Smooth m layer • No musc mucosa • No submucosa • No serosa along hepatic surface • Perimusc CT of GB contiuous with interlobular CT of the liver GALLBLADDERGALLBLADDER CANCER:CANCER: PATTERNSPATTERNS OFOF PRESENTATIONPRESENTATION

•• FocalFocal oror diffusediffuse muralmural thickeningthickening •• IntraluminalIntraluminal polypoidpolypoid massmass >> 2cm2cm •• SubhepaticSubhepatic massmass replacingreplacing oror obscuringobscuring thethe gallbladdergallbladder CARCINOMACARCINOMA WITHWITH MURALMURAL THICKENING:THICKENING: USUS

•• EarlyEarly diagnosisdiagnosis isis difficultdifficult becausebecause ofof thethe smallsmall sizesize ofof earlyearly massesmasses andand subtlesubtle wallwall thickeningthickening withwith CACA cancan bebe obscuredobscured byby gallstonesgallstones •• WideWide DDxDDx ofof farfar moremore commoncommon disordersdisorders DIFFERENTIALDIFFERENTIAL DIAGNOSISDIAGNOSIS OFOF MURALMURAL THICKENINGTHICKENING

•• InadequateInadequate distentiondistention •• AcuteAcute andand chronicchronic cholecystitischolecystitis •• ,Hepatitis, pancreatitispancreatitis,, RR pyelonephritispyelonephritis •• HyperplasticHyperplastic cholecystosescholecystoses •• LowLow proteinprotein statesstates •• PortalPortal hypertensionhypertension GALLBLADDERGALLBLADDER CANCER:CANCER: PATTERNSPATTERNS OFOF PRESENTATIONPRESENTATION

• Focal or diffuse mural thickening • Intraluminal polypoid mass > 2cm • Subhepatic mass replacing or obscuring the gallbladder CARCINOMACARCINOMA ASAS AA GALLBLADDERGALLBLADDER FOSSAFOSSA MASSMASS

•• MostMost commoncommon presentationpresentation •• MayMay bebe difficultdifficult toto separateseparate massmass fromfrom liverliver onon imagingimaging •• AbsenceAbsence ofof aa clearlyclearly distinctdistinct gallbladdergallbladder andand thethe presencepresence ofof stonesstones areare cluesclues •• InhomogeneousInhomogeneous enhancementenhancement followingfollowing IVIV contrastcontrast onon CTCT andand MR.MR. •• InternalInternal necrosisnecrosis onon CTCT andand MRMR PATHWAYSPATHWAYS OFOF TUMORTUMOR SPREADSPREAD

•• DirectDirect invasioninvasion ofof thethe liver,liver, ,duodenum, coloncolon andand hepatoduodenalhepatoduodenal ligamentligament •• PeriportalPeriportal andand peripancreaticperipancreatic LADLAD •• IntraductalIntraductal tumortumor extensionextension •• MetastasesMetastases toto peritoneumperitoneum RESECTABILITYRESECTABILITY ASSESSMENT:ASSESSMENT: GALLBLADDERGALLBLADDER CANCERCANCER

TUMOR FACTORS PATIENT FACTORS • Liver invasion • Age • Colonic invasion • Medical condition • Duodenal invasion • Liver status • Vascular invasion • Renal function • Liver metastases • Nutrition • Peritoneal • Sepsis metastases • Distant metastases STAGINGSTAGING GALLBLADDERGALLBLADDER CANCER:CANCER: NEVINNEVIN’’SS CRITERIACRITERIA

•• StageStage II MucosalMucosal involvementinvolvement onlyonly •• StageStage 22 ExtensionExtension intointo muscularismuscularis •• StageStage 33 ExtensionExtension intointo serosaserosa •• StageStage 44 InvolvementInvolvement ofof regionalregional LNLN •• StageStage 55 InvolvementInvolvement ofof liverliver SURVIVALSURVIVAL TIMESTIMES FORFOR GALLBLADDERGALLBLADDER CANCERCANCER

1 year survival 5 year survival

STAGE I 100% 96%

STAGE II 87 56

STAGE III 53 15

STAGE IV 58 16

STAGE V 10 6 CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• 1010--15%15% ofof hepatobiliaryhepatobiliary neoplasmsneoplasms •• 1/31/3 ICC,ICC, 2/32/3 ECC;ECC; 1.51.5--2:1,2:1, M:F;M:F; 66th decadedecade •• 0.320.32→→0.85/0.85/ 100,000100,000 ICCICC 70s70s--90s90s inin USUS •• 1.081.08→→0.82/0.82/ 100,000100,000 ECCECC 70s70s--90s90s inin USUS •• HighestHighest incidenceincidence inin ThailandThailand 96/100,00096/100,000 ♂♂ 36/100,00036/100,000 ♀♀ •• ICC:ICC: 55 yearyear survivalsurvival << 5%5% •• ECC:ECC: 55 yearyear survivalsurvival ~~ 15%15% CHOLANGIOCARCINOMA:CHOLANGIOCARCINOMA: RISKRISK FACTORSFACTORS

• Choledochal cysts • Age > 65 • BD adenoma and • PSC biliary papillomatosis • Liver flukes • Hepatolithiasis Opisthorchis viverrini • Clonorchis sinensis • Surgical biliary and • Caroli’s disease enteric drainage • Dioxin, vinyl chloride BENIGNBENIGN vsvs MALIGNANTMALIGNANT BILIARYBILIARY STRICTURESSTRICTURES

•• SmoothSmooth vsvs irregularirregular marginsmargins •• AsymmetricAsymmetric vsvs symmetricsymmetric narrowingnarrowing •• AbruptAbrupt vsvs gradualgradual taperingtapering •• PresencePresence oror absenceabsence ofof doubledouble ductduct signsign INTRAHEPATICINTRAHEPATIC CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• 1/31/3 -- 1/51/5 OFOF ALLALL PRIMARYPRIMARY HEPATICHEPATIC NEOPLASMSNEOPLASMS •• 22nd MOSTMOST COMMONCOMMON PRIMARYPRIMARY AFTERAFTER HCCHCC •• 10%10% OFOF ALLALL CHOLANGIOCARCINOMASCHOLANGIOCARCINOMAS •• 66th DECADE;DECADE; M>FM>F INTRAHEPATICINTRAHEPATIC CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• DelayedDelayed phasephase contrastcontrast enhancementenhancement correlatescorrelates withwith thethe amountamount ofof fibrousfibrous stromastroma andand frequencyfrequency oror perineuralperineural invasion.invasion. •• TumorsTumors withwith >> 2/32/3 delayeddelayed enhancementenhancement havehave aa poorerpoorer prognosisprognosis thanthan thosethose withwith << 2/32/3 delayeddelayed enhancement.enhancement.

AssayamaAssayama YY RadiologyRadiology 238:238: 150150--155,155, 20062006 INTRAHEPATICINTRAHEPATIC CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• 81.8%81.8% ofof patientspatients withwith severesevere stromalstromal fibrosisfibrosis showedshowed markedlymarkedly delayeddelayed hyperenhancementhyperenhancement •• NoneNone ofof patientspatients withoutwithout stromalstromal fibrosisfibrosis showedshowed hyperenhancementhyperenhancement..

VallsValls AbdomAbdom ImagImag 25:25: 490490--496,496, 20002000 BISMUTHBISMUTH CLASSIFICATIONCLASSIFICATION OFOF HILARHILAR CHOLANGIOCARCINOMASCHOLANGIOCARCINOMAS

•• TypeType II WithinWithin CHDCHD •• TypeType IIII RR andand LL HDHD •• TypeType IIIaIIIa RR 22nd intraintra--hepatichepatic ductduct •• TypeType IIIbIIIb LL 22nd intraintra--hepatichepatic ductduct •• TypeType IVIV BilateralBilateral 22nd intrahepaticintrahepatic BDBD PERIAMPULLARYPERIAMPULLARY CANCERSCANCERS ARISE WITHIN 2 CM FROM MAJOR PAPILLA

•• AmpullaryAmpullary cancercancer •• CholangiocarcinomaCholangiocarcinoma •• PancreaticPancreatic cancercancer •• DuodenalDuodenal cancercancer CHOLANGIOCARCINOMACHOLANGIOCARCINOMA STAGINGSTAGING

•• 74.5%74.5% accuracyaccuracy forfor predictionprediction ofof resectabilityresectability forfor hilarhilar cholangiocarcinomacholangiocarcinoma •• ArterialArterial invasioninvasion 92.7%92.7% •• PortalPortal veinvein invasioninvasion 85.5%85.5% •• ExtentExtent ductalductal involveinvolve 84.0%84.0% •• LNLN involvementinvolvement 27.0%27.0%

LeeLee RadiologyRadiology 239:239: 113113--121,121, 20062006 THERAPYTHERAPY FORFOR CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

• Efficacy of chemotherapy and external beam radiation therapy is dubious • Surgery or liver transplantation offer the only opportunity for cure • Most patients have either unresectable tumor or have other comorbidities that mitigate against surgery • Palliative therapy: stenting and photo-dynamic treatment (laser therapy after a photsensitizer) CHOLANGIOCARCINOMA:CHOLANGIOCARCINOMA: PET/CTPET/CT

•• PET/CTPET/CT valuablevaluable forfor detectingdetecting unsuspectedunsuspected metastasesmetastases •• PET/CTPET/CT foundfound 12/1212/12 metsmets vsvs CTCT whichwhich foundfound onlyonly 3/123/12

AndersonAnderson JJ GastrointestGastrointest SurgSurg 8:8: 9090--97,97, 20042004 CHOLANGIOCARCINOMA:CHOLANGIOCARCINOMA: UNRESECTABILITYUNRESECTABILITY CRITERIACRITERIA

• Bilobar involvement • Both hepatic ducts involved • Adenopathy • Perivascular fat plane invasion • Encasement or occlusion of major vessel • Invasion of adjacent organs • Ascites • Peritoneal metastases • Unilateral vascular involvement and extensive contralateral tumor spread CHOLANGIOCARCINOMA:CHOLANGIOCARCINOMA: SURVIVALSURVIVAL

Resectability Resectable Unresectable Rate Med survival Med survival

Intrahepatic 15-20% 18-30 mo 7 months

Perihilar -- 8 months 5 months

Distal 50% 24 months 8 months CONCLUSIONSCONCLUSIONS

•• BiliaryBiliary tracttract neoplasmsneoplasms areare uncommonuncommon butbut lethallethal neoplasmsneoplasms •• SurgerySurgery oror transplantationtransplantation offeroffer thethe onlyonly chancechance forfor survivalsurvival •• ImprovedImproved survivalsurvival willwill onlyonly comecome withwith earlierearlier detectiondetection oror breakthroughsbreakthroughs inin chemotherapychemotherapy WHATWHAT CANCAN WEWE DO?DO?

•• BeBe lessless dismissivedismissive ofof GBGB polypspolyps •• InvestigateInvestigate patientspatients withwith WESWES signsign •• WarningWarning aboutabout stonesstones >> 3cm3cm •• AlertAlert surgeonssurgeons aboutabout CACA riskrisk inin MirriziMirrizi’’ss •• SerialSerial imagingimaging inin PSCPSC andand choledochalcholedochal cysts:cysts: baselinebaseline PET?PET?