cholangiocarcinoma - rwellner

7/27/2019 Cholangiocarcinoma - RWellner

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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.

cholangiocarcinoma - rwellner

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