BILIARY TRACT BILIARY TRACT MALIGNANCIES:MALIGNANCIES:

Diagnosis and StagingDiagnosis and StagingRichard M. Gore, MD

SCBT/MR Summer Practicum Williamsburg, Virginia

August 10, 2009

OBJECTIVESOBJECTIVES

•• Review the imaging findings of cancer of Review the imaging findings of cancer of the gallbladder and the gallbladder and cholangiocarcinomacholangiocarcinoma

•• Applications of MDCT, MR, MRCP, PET/CT Applications of MDCT, MR, MRCP, PET/CT in the staging of these in the staging of these neoplasmsneoplasms

•• Suggest practice guidelines to promote Suggest practice guidelines to promote early detection in high risk individualsearly detection in high risk individuals

GALLBLADDER CARCINOMAGALLBLADDER CARCINOMAEPIDEMIOLOGYEPIDEMIOLOGY

•• 66thth most common GI malignancymost common GI malignancy•• F:M 2.5F:M 2.5--3 to 1 ratio3 to 1 ratio•• Peak incidence 7Peak incidence 7thth decade of lifedecade of life•• At autopsy, GB cancer accounts for 1At autopsy, GB cancer accounts for 1--5% of 5% of

malignancies with 20% being asymptomaticmalignancies with 20% being asymptomatic•• 5 year survival ~ 5%5 year survival ~ 5%

GALLBLADDER CARCINOMAGALLBLADDER CARCINOMAEPIDEMIOLOGYEPIDEMIOLOGY

•• Highly lethal cancer because anatomic Highly lethal cancer because anatomic factors promote early spread of tumorfactors promote early spread of tumor

•• Median survival is 6 months indicating that Median survival is 6 months indicating that most patients present with advanced tumormost patients present with advanced tumor

•• Early diagnosis is rare because there are Early diagnosis is rare because there are no specific S+S of GB cancerno specific S+S of GB cancer

GALLBLADDER CANCER:GALLBLADDER CANCER:RISK FACTORSRISK FACTORS

•• GallstonesGallstones•• Female genderFemale gender•• AgeAge•• SmokingSmoking•• CholedochalCholedochal cystscysts•• SclerosingSclerosing cholangitischolangitis

•• Ethnic origin: Native Ethnic origin: Native Americans, Israelis, Americans, Israelis, Chile, Northern JapanChile, Northern Japan

•• ObesityObesity•• Typhoid infectionTyphoid infection•• Chemical exposureChemical exposure

GALLBLADDER CANCERGALLBLADDER CANCERPATHOGENESISPATHOGENESIS

•• > 90% coexistent chronic > 90% coexistent chronic cholecystitischolecystitis and stonesand stones

•• More common with 1 large More common with 1 large stone rather than multiple stone rather than multiple smaller stonessmaller stones

•• Gallstones > 3cm in size Gallstones > 3cm in size have a 10X increased risk have a 10X increased risk of GB cancerof GB cancer

•• GB cancer found in 27% of GB cancer found in 27% of patients having surgery for patients having surgery for MirriziMirrizi syndrome syndrome compared to 1compared to 1--2% for 2% for other indicationsother indications

METAPLASIAMETAPLASIA

DYSPLASIADYSPLASIA

CARCINOMACARCINOMA

CHOLELITHIASISCHOLELITHIASIS

•• 48 million Americans with gallstones48 million Americans with gallstones•• 850,000 850,000 cholecystectomiescholecystectomies annuallyannually•• 2,000 GB cancers found in specimens2,000 GB cancers found in specimens•• ~ ~ CarcinoidCarcinoid in appendicitisin appendicitis

GALLBLADDER CANCER:GALLBLADDER CANCER:PORCELAIN GALLBLADDERPORCELAIN GALLBLADDER

Nearly 30% will have Nearly 30% will have gallbladder cancergallbladder cancer

Tend to have a poor Tend to have a poor prognosis because prognosis because of liver invasionof liver invasion

GALLBLADDER MASSGALLBLADDER MASSSEEN ON US: SEEN ON US: DDxDDx

•• StoneStone•• Cholesterol polypCholesterol polyp•• AdenomyomatosisAdenomyomatosis•• TumefactiveTumefactive sludgesludge•• Gallbladder cancerGallbladder cancer•• Congenital fold or Congenital fold or

septumseptum•• Mets, adenoma, Mets, adenoma,

ectopic ectopic pancpanc, , hematomahematoma

GALLBLADDER CANCERGALLBLADDER CANCERPATHOGENESISPATHOGENESIS

•• GB polyps > 1cm GB polyps > 1cm are most likely to are most likely to become malignant become malignant and are an and are an indication for indication for cholecystectomycholecystectomy

GALLBLADDER CANCER:GALLBLADDER CANCER:SITE OF ORIGINSITE OF ORIGIN

•• 60% FUNDAL60% FUNDAL•• 30% BODY30% BODY•• 10% NECK10% NECK

UNIQUE ANATOMIC FEATURES UNIQUE ANATOMIC FEATURES OF THE GALLBLADDEROF THE GALLBLADDER

•• MucosaMucosa•• Lamina Lamina propriapropria•• Smooth m layerSmooth m layer•• No No muscmusc mucosamucosa•• No No submucosasubmucosa•• No No serosaserosa along hepatic along hepatic

surfacesurface•• PerimuscPerimusc CT of GB CT of GB

contiuouscontiuous with interlobular with interlobular CT of the liverCT of the liver

GALLBLADDER CANCER:GALLBLADDER CANCER:PATTERNS OF PRESENTATIONPATTERNS OF PRESENTATION

•• Focal or diffuse mural thickeningFocal or diffuse mural thickening•• IntraluminalIntraluminal polypoidpolypoid mass > 2cmmass > 2cm•• SubhepaticSubhepatic mass replacing or obscuring mass replacing or obscuring

the gallbladderthe gallbladder

CARCINOMA WITH CARCINOMA WITH MURAL THICKENING: USMURAL THICKENING: US

•• Early diagnosis is difficult because of the Early diagnosis is difficult because of the small size of early masses and subtle wall small size of early masses and subtle wall thickening with CA can be obscured by thickening with CA can be obscured by gallstonesgallstones

•• Wide Wide DDxDDx of far more common disordersof far more common disorders

DIFFERENTIAL DIAGNOSIS OFDIFFERENTIAL DIAGNOSIS OFMURAL THICKENINGMURAL THICKENING

•• Inadequate distentionInadequate distention•• Acute and chronic Acute and chronic cholecystitischolecystitis•• Hepatitis, Hepatitis, pancreatitispancreatitis, R , R pyelonephritispyelonephritis•• HyperplasticHyperplastic cholecystosescholecystoses•• Low protein statesLow protein states•• Portal hypertensionPortal hypertension

GALLBLADDER CANCER:GALLBLADDER CANCER:PATTERNS OF PRESENTATIONPATTERNS OF PRESENTATION

•• Focal or diffuse mural Focal or diffuse mural thickeningthickening

•• IntraluminalIntraluminal polypoidpolypoidmass > 2cmmass > 2cm

•• SubhepaticSubhepatic mass mass replacing or obscuring replacing or obscuring the gallbladderthe gallbladder

CARCINOMA AS A CARCINOMA AS A GALLBLADDER FOSSA MASSGALLBLADDER FOSSA MASS

•• Most common presentationMost common presentation•• May be difficult to separate mass from liver May be difficult to separate mass from liver

on imagingon imaging•• Absence of a clearly distinct gallbladder Absence of a clearly distinct gallbladder

and the presence of stones are cluesand the presence of stones are clues•• Inhomogeneous enhancement following IV Inhomogeneous enhancement following IV

contrast on CT and MR.contrast on CT and MR.•• Internal necrosis on CT and MRInternal necrosis on CT and MR

PATHWAYS OF PATHWAYS OF TUMOR SPREADTUMOR SPREAD

•• Direct invasion of the liver, duodenum, Direct invasion of the liver, duodenum, colon and colon and hepatoduodenalhepatoduodenal ligamentligament

•• PeriportalPeriportal and and peripancreaticperipancreatic LADLAD•• IntraductalIntraductal tumor extensiontumor extension•• Metastases to peritoneumMetastases to peritoneum

RESECTABILITY ASSESSMENT: RESECTABILITY ASSESSMENT: GALLBLADDER CANCERGALLBLADDER CANCER

PATIENT FACTORSPATIENT FACTORS•• AgeAge•• Medical conditionMedical condition•• Liver statusLiver status•• Renal functionRenal function•• NutritionNutrition•• SepsisSepsis

TUMOR FACTORSTUMOR FACTORS•• Liver invasionLiver invasion•• Colonic invasionColonic invasion•• Duodenal invasionDuodenal invasion•• Vascular invasionVascular invasion•• Liver metastasesLiver metastases•• Peritoneal Peritoneal

metastasesmetastases•• Distant metastases Distant metastases

STAGING GALLBLADDER STAGING GALLBLADDER CANCER: NEVINCANCER: NEVIN’’S CRITERIAS CRITERIA

•• Stage IStage I Mucosal involvement onlyMucosal involvement only•• Stage 2Stage 2 Extension into Extension into muscularismuscularis•• Stage 3Stage 3 Extension into Extension into serosaserosa•• Stage 4Stage 4 Involvement of regional LNInvolvement of regional LN•• Stage 5Stage 5 Involvement of liverInvolvement of liver

SURVIVAL TIMES FORSURVIVAL TIMES FORGALLBLADDER CANCERGALLBLADDER CANCER

1 year survival1 year survival 5 year survival5 year survival

STAGE ISTAGE I 100%100% 96%96%

STAGE IISTAGE II 8787 5656

STAGE IIISTAGE III 5353 1515

STAGE IVSTAGE IV 5858 1616

STAGE VSTAGE V 1010 66

CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• 1010--15% of 15% of hepatobiliaryhepatobiliary neoplasmsneoplasms•• 1/3 ICC, 2/3 ECC; 1.51/3 ICC, 2/3 ECC; 1.5--2:1, M:F; 62:1, M:F; 6thth decadedecade•• 0.320.32→→0.85/ 100,000 ICC 70s0.85/ 100,000 ICC 70s--90s in US90s in US•• 1.081.08→→0.82/ 100,000 ECC 70s0.82/ 100,000 ECC 70s--90s in US90s in US•• Highest incidence in Thailand 96/100,000 Highest incidence in Thailand 96/100,000 ♂♂

36/100,000 36/100,000 ♀♀•• ICC: 5 year survival < 5%ICC: 5 year survival < 5%•• ECC: 5 year survival ~ 15%ECC: 5 year survival ~ 15%

CHOLANGIOCARCINOMA:CHOLANGIOCARCINOMA:RISK FACTORSRISK FACTORS

•• Age > 65Age > 65•• PSCPSC•• Liver flukes Liver flukes

OpisthorchisOpisthorchis viverriniviverriniClonorchisClonorchis sinensissinensis

•• CaroliCaroli’’ss diseasedisease

•• CholedochalCholedochal cystscysts•• BD adenoma and BD adenoma and

biliarybiliary papillomatosispapillomatosis•• HepatolithiasisHepatolithiasis•• CirrhosisCirrhosis•• Surgical Surgical biliarybiliary and and

enteric drainageenteric drainage•• Dioxin, vinyl chlorideDioxin, vinyl chloride

BENIGN BENIGN vsvs MALIGNANTMALIGNANTBILIARY STRICTURESBILIARY STRICTURES

•• Smooth Smooth vsvs irregular marginsirregular margins•• Asymmetric Asymmetric vsvs symmetric narrowingsymmetric narrowing•• Abrupt Abrupt vsvs gradual taperinggradual tapering•• Presence or absence of double duct signPresence or absence of double duct sign

INTRAHEPATIC INTRAHEPATIC CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• 1/3 1/3 -- 1/5 OF ALL PRIMARY HEPATIC 1/5 OF ALL PRIMARY HEPATIC NEOPLASMSNEOPLASMS

•• 22ndnd MOST COMMON PRIMARY AFTER MOST COMMON PRIMARY AFTER HCCHCC

•• 10% OF ALL CHOLANGIOCARCINOMAS10% OF ALL CHOLANGIOCARCINOMAS•• 66thth DECADE; M>FDECADE; M>F

INTRAHEPATICINTRAHEPATICCHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• Delayed phase contrast enhancement Delayed phase contrast enhancement correlates with the amount of fibrous correlates with the amount of fibrous stromastromaand frequency or and frequency or perineuralperineural invasion.invasion.

•• Tumors with > 2/3 delayed enhancement Tumors with > 2/3 delayed enhancement have a poorer prognosis than those with have a poorer prognosis than those with < 2/3 delayed enhancement.< 2/3 delayed enhancement.

AssayamaAssayama Y Radiology 238: 150Y Radiology 238: 150--155, 2006155, 2006

INTRAHEPATICINTRAHEPATICCHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• 81.8% of patients with severe 81.8% of patients with severe stromalstromalfibrosis showed markedly delayed fibrosis showed markedly delayed hyperenhancementhyperenhancement

•• None of patients without None of patients without stromalstromal fibrosis fibrosis showed showed hyperenhancementhyperenhancement. .

Valls Valls AbdomAbdom ImagImag 25: 49025: 490--496, 2000496, 2000

BISMUTH CLASSIFICATION OF HILARBISMUTH CLASSIFICATION OF HILARCHOLANGIOCARCINOMASCHOLANGIOCARCINOMAS

•• Type I Within CHDType I Within CHD•• Type II R and L HDType II R and L HD•• Type Type IIIaIIIa R 2R 2ndnd intraintra--hepatic ducthepatic duct•• Type Type IIIbIIIb L 2L 2nd nd intraintra--hepatic ducthepatic duct•• Type IVType IV Bilateral 2Bilateral 2ndnd intrahepaticintrahepatic BDBD

PERIAMPULLARY CANCERSPERIAMPULLARY CANCERSARISE WITHIN 2 CM FROM MAJOR PAPILLAARISE WITHIN 2 CM FROM MAJOR PAPILLA

•• AmpullaryAmpullary cancercancer•• CholangiocarcinomaCholangiocarcinoma•• Pancreatic cancerPancreatic cancer•• Duodenal cancerDuodenal cancer

CHOLANGIOCARCINOMACHOLANGIOCARCINOMASTAGINGSTAGING

•• 74.5% accuracy for prediction of 74.5% accuracy for prediction of resectabilityresectability for for hilarhilar cholangiocarcinomacholangiocarcinoma

•• Arterial invasionArterial invasion 92.7%92.7%•• Portal vein invasionPortal vein invasion 85.5%85.5%•• Extent Extent ductalductal involveinvolve 84.0%84.0%•• LN involvementLN involvement 27.0%27.0%

Lee Radiology 239: 113Lee Radiology 239: 113--121, 2006121, 2006

THERAPY FOR THERAPY FOR CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

•• Efficacy of chemotherapy and external beam Efficacy of chemotherapy and external beam radiation therapy is dubiousradiation therapy is dubious

•• Surgery or liver transplantation offer the only Surgery or liver transplantation offer the only opportunity for cureopportunity for cure

•• Most patients have either Most patients have either unresectableunresectable tumor or tumor or have other have other comorbiditiescomorbidities that mitigate against that mitigate against surgerysurgery

•• Palliative therapy: Palliative therapy: stentingstenting and photoand photo--dynamic dynamic treatment (laser therapy after a treatment (laser therapy after a photsensitizerphotsensitizer) )

CHOLANGIOCARCINOMA: PET/CTCHOLANGIOCARCINOMA: PET/CT

•• PET/CT valuable for detecting unsuspected PET/CT valuable for detecting unsuspected metastasesmetastases

•• PET/CT found 12/12 PET/CT found 12/12 metsmets vsvs CT which CT which found only 3/12found only 3/12

Anderson J Anderson J GastrointestGastrointest SurgSurg 8: 908: 90--97, 200497, 2004

CHOLANGIOCARCINOMA:CHOLANGIOCARCINOMA:UNRESECTABILITY CRITERIAUNRESECTABILITY CRITERIA

•• BilobarBilobar involvementinvolvement•• Both hepatic ducts involvedBoth hepatic ducts involved•• AdenopathyAdenopathy•• PerivascularPerivascular fat plane invasionfat plane invasion•• Encasement or occlusion of major vesselEncasement or occlusion of major vessel•• Invasion of adjacent organsInvasion of adjacent organs•• AscitesAscites•• Peritoneal metastasesPeritoneal metastases•• Unilateral vascular involvement and extensive Unilateral vascular involvement and extensive

contralateralcontralateral tumor spreadtumor spread

CHOLANGIOCARCINOMA:CHOLANGIOCARCINOMA:SURVIVALSURVIVAL

ResectabilityResectabilityRateRate

ResectableResectableMed survivalMed survival

UnresectableUnresectableMed survivalMed survival

IntrahepaticIntrahepatic 1515--20%20% 1818--30 mo30 mo 7 months7 months

PerihilarPerihilar ---- 8 months8 months 5 months5 months

DistalDistal 50%50% 24 months24 months 8 months8 months

CONCLUSIONSCONCLUSIONS

•• BiliaryBiliary tract tract neoplasmsneoplasms are uncommon but are uncommon but lethal lethal neoplasmsneoplasms

•• Surgery or transplantation offer the only Surgery or transplantation offer the only chance for survivalchance for survival

•• Improved survival will only come with earlier Improved survival will only come with earlier detection or breakthroughs in detection or breakthroughs in chemotherapychemotherapy

•• Be less dismissive of GB polypsBe less dismissive of GB polyps•• Investigate patients with WES signInvestigate patients with WES sign•• Warning about stones > 3cmWarning about stones > 3cm•• Alert surgeons about CA risk in Alert surgeons about CA risk in MirriziMirrizi’’ss•• Serial imaging in PSC and Serial imaging in PSC and choledochalcholedochal

cysts: baseline PET?cysts: baseline PET?

WHAT CAN WE DO?WHAT CAN WE DO?