Post on 02-Apr-2018
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Cholangiocarcinoma
Rachel B. Wellner MD, MPH
Mount Sinai HospitalDepartment of Surgery
Team III Conference
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Definition of CholangiocarcinomaBile duct cancers arising from ductal
epithelial cells
Refers to cancers arising in the intrahepatic
(~5-15%), perihilar (~60-70%), or distal
(extrahepatic ~25%) biliary tree
Represents approx. 3% of all gastro-
intestinal malignancies
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Definition of CholangiocarcinomaBismuth-Corlette Classification subdivides
perihilar cholangiocarcinomas based on pattern
of involvement of hepatic ductsType I: tumors occurring below the confluence of theleft and right hepatic ducts
Type II : tumors reaching the confluenceTypes IIIA/IIIb: tumors occluding the common
hepatic duct and either the right or left hepatic ductType IV: tumors that are multicentric, or that involve
the confluence and both the right or left hepatic duct
Klatskin tumors occur at the bifurcation of the
proper hepatic duct
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Risk Factors
Primary Sclerosing Cholangitis 0.6-1.5% annual incidence of cholangioCA.
Choledocal Cysts and Carolis Disease 0.7 % risk for first 10 years, 6.8 % risk for
second ten years, and 14.3 % thereafter
Clonorchis and Opisthorchis
Cholelithiasis and hepatolithiasis Toxic exposure (Thorotrast)
Lynch syndrome II and multiple biliary
papillomatosis
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Pathology Adenocarcinoma (90%) Slow growing, locally invasive, mucin-producing Perineural spread, metastases uncommon
Three subtypes of adenocarcinoma Sclerosing
Majority of cholangiocarcinomas Characterized by an intense desmoplastic reaction Early ductal invasion leads to low resectability rates
Nodular Constricting annular lesion of the bile duct
Papillary Present as bulky masses occurring in the bile duct lumen Present early with biliary obstruction
Highest resectability rates
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Clinical
Triad Cholestasis
Abdominal pain (30-50 %)
Weight loss (30-50 %) Pruritus (66 %)
Clay-colored stools, dark urine.
Jaundice (~90 %)
Hepatomegaly
RUQ mass
Courvoisier's sign
Intrahepatic cholangioCA typically presents without
biliary obstruction
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Laboratory
Elevations in: Total bilirubin (>10 mg/dL)
Direct bilirubin Alkaline phosphatase (usually increased 2- to 10-
fold)
5'-nucleotidase
Gamma glutamyltransferase
Transaminase levels initially normalWith chronic biliary obstruction, liver
dysfunction may ensue with elevation in
ALT/AST and PT
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Differential Diagnosis
Choledocholithiasis
Benign bile duct strictures (usuallypostoperative),
Sclerosing cholangitis
Compression of the CBD (secondary to
chronic pancreatitis or pancreatic cancer)
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Diagnosis
Tumor markers Serum CEA >5.2 ng/mL(sensitivity 68%,
specificity 82%)
Biliary CEA
CA 19-9
Radiographic studies Transabdominal ultrasound- may reveal ductal
dilatation (intrahepatic >6mm)
CT/helical CT- can also detect vascular invasion
Helical CT (esp. portal venous phase)- can delinieatenodal basins
May be superior to MRI with respect to predicting
resectability
MRCP- may be coming the imaging modality of
choice (high PPV,NPV)
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Diagnosis
Cholangiography
ERCP or PTC Useful if suspected level of obstruction is distal Preoperative drainage of the biliary tree Obtain diagnostic bile samples or brush cytology
(low sensitivity) Endoscopic ultrasound Useful for visualizing distal tumors and regional
nodes Can be used for EUS-guided biopsy of tumors
and enlarged nodes
PET High glucose uptake of biliary duct epithelium
Angiography (rarely used) Staging laparoscopy
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Diagnosis
Role of Staging laparoscopy Tissue diagnosis important in the setting of:
Strictures of unknown origin (e.g. bile ductstones, PSC)
Family/patient request for a definitivediagnosis
Prior to chemotherapy or radiation therapy
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Management
Poor prognosis- avg. 5-year survival ~5-10%
Resectability rate superior for distal tumors
resectability rates for intrahepatic 60%, perihilar56%, and distal lesions 91% (Nakeeb A; Pitt HA,
JHU 1996)
Negative margins achieved in 20-40% of
proximal tumors cases, 50% of distal tumor cases
Current data in evolution
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Management
Accepted guidelines for resectability
(accurately determined at operative
exploration) Absence of N2 nodal metastases or distant liver
metastases
Absence of vascular (portal vein, hepatic artery)
invasion Absence of extrahepatic adjacent organ invasion
Absence of disseminated disease
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Management
Pre-operative biliary decompression Liver dysfunction increases postoperative
morbidity and mortality Arch Surg 2000 (Cherqui et. al.)Study demonstrated increased post-op morbidity
in jaundiced patients not undergoing pre-operative drainage (vs. nonjaundiced patients)
Pre-operative portal vein embolizationInduce liver hypertrophy to increase limits of
safe resection No demonstrated improvement in clincial
outcome
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Management
Surgical ProceduresDistal lesions: pancreaticoduodenectomy (5-yr survival
rates 15-25%)
Intrahepatic cholangiocarcinoma: hepatic resection (3-yr
survival rates 22- 66%)
Perihilar cholangiocarcinoma (5-yr survival rates 10-
45%; outcomes in PSC patients dismal)
Type I and II lesions: en bloc resection ofextrahepatic bile ducts and gallbladder with 5 to 10
mm bile duct margins, regional lymphadenectomy
with Roux-en-Y hepaticojejunostomy.
Type III and Type IV lesions: hepatectomy and portal
vein resection
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Management
Adjuvant radiation therapy
Adjuvant radiation aimed at achieving local contral,decreased recurrence (no RCTs) Retrospective series demonstrate a benefit in patients
with incompletely resectable lesions Unclear benefit in patients with completely resected
tumors Adjuvant chemotherapy (mitomycin, 5-FU)Benefit of adjuvant chemoradiotherapy for completely
resected patients unclear Some benefit seen when combined with radiation inpatients with incomplete resection Single multi-center prospective randomized trial
(Japan, Takada et. al. in Cancer, 2002) showed nobenefit with chemotherapy in patients with both curativeand non-curative resections
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Management
Neoadjuvant therapyTypically not offered to patients with
cholangiocarcinoma due to poor functional status atpresentationUsed in selected patients (McMasters, Am J Surg
1997)3/9 patients had a pathologic complete response
(6/9 showed different degrees of histologicresponse)Margin-negative resections were possible in all
nine patients receiving neoadjuvant therapy. Palliative treatment aimed at relieving biliary
obstruction, pain50-90% of patients with cholangiocarcinoma present
with unresectable disease
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References Bismuth, H, Nakache, R, Diamond, T. Management strategies in
resection for hilar cholangiocarcinoma. Ann Surg 1992; 215:31.
Cherqui, D, Benoist, S, Malassagne, B, et al. Major liver resection for
carcinoma in jaundiced patients without preoperative biliary drainage.
Arch Surg 2000; 135:302.
McMasters, KM, Tuttle, TM, Leach, SD, et al. Neoadjuvant
chemoradiation for extrahepatic cholangiocarcinoma. Am J Surg 1997;174:605.
Nakeeb, A, Pitt, HA, Sohn, TA, et al. Cholangiocarcinoma. A spectrum
of intrahepatic, perihilar, and distal tumors. Ann Surg 1996; 224:463.
Roayaie, S, Guarrera, JV, Ye, MQ, et al. Aggressive surgical treatment
of intrahepatic cholangiocarcinoma: predictors of outcomes. J Am CollSurg 1998; 187:365.
Takada, T, Amano, H, Yasuda, H, et al. Is postoperative adjuvant
chemotherapy useful for gallbladder carcinoma?. A phase III
multicenter prospective randomized controlled trial in patients with
resected pancreaticobiliary carcinoma. Cancer 2002; 95:1685.