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CHOLANGIOCARCINOMA

Cholangiocarcinoma is an intrahepatic malignant tumor made up of cells that resemble biliary epithelium. To achieve a precise definition, it is necessary to note that the distinction between intrahepatic and extrahepatic bile ducts is defined as the point at which the second-order bile ducts join to become the first-order ducts (right and left hepatic) bile duct cancer.

Epidemiology

Cholangiocarcinoma has less of a geographic variation than does hepatocellular carcinoma, except for areas such as Hong Kong and Thailand, where liver fluke infestation is endemic. Its frequency in Western countries is approximately 20%, whereas it is less than 10% in African and Asian nations that are endemic for hepatocellular carcinoma.

Sex and Age

The age of occurrence is considerably older than hepatocellular carcinoma. The mean age is approximately 65 years, with most patients ranging from 50 to 70 years of age. Male preponderance is modest and varies.

Etiology

Correlation has been shown between liver fluke infection and cholangiocarcinoma. Studies have found an incidence of liver cancer of 56.6% in patients with opistorchiasis; 77% of these malignancies were cholangiocarcinomas.

Intrahepatic stones have been implicated as causing persistent irritation of the biliary epithelium that may eventually degenerate into cholangiocarcinoma.

Ulcerative colitis and primary sclerosing cholangitis have a well-established association with bile duct carcinoma. Cholangiocarcinoma occurs in approximately 1 in 256 patients with ulcerative colitis; one third of these tumors are within the liver. The colitis precedes cholangiocarcinoma, when present, by an average of 5 years (range, 0-30 years). In patients with primary sclerosing cholangitis, the incidence of cholangiocarcinoma ranges from 4% to 20%; the cumulative risk for cholangiocarcinoma in these patients has been reported to be 11.2% at 10 years.

Caroli's disease, choledochal cysts, hepatic cysts, Meyenburg's complexes, and congenital hepatic fibrosis, among others, have been implicated in the pathogenesis of cholangiocarcinoma.

Pathology

Peripheral cholangiocarcinomas represent 50% to 70% of the total, whereas hilar types account for the remainder.

Grossly, cholangiocarcinoma appears as a firm, gray-white infiltrative mass, ranging from 2 cm to 15 cm in diameter. Central necrosis and venous invasion (portal or hepatic) may be observed. Hemorrhage and tumor rupture are rare. Peripheral tumors tend to present as solitary masses, although multiple or diffusely nodular varieties.

Hilar cholangiocarcinomas (Klatskin tumors) may present as an infiltrative mass that extends from the hilum into the parenchyma, as a sclerotic mass encircling a large bile duct, or as a polypoid tumor invading the lumen of a large bile duct. Extrahepatic metastases occur more frequently through the lymphatic system than through the hematogenous route. Peripancreatic and hilar nodes are involved in approximately half of cases. Autopsy cases report an incidence of extrahepatic metastases.

Clinical Features

Signs and symptoms are similar to those of hepatocellular carcinoma, except that biliary obstruction is more common. Affected individuals tend to present with jaundice, abdominal pain, fever, general malaise, abdominal distension, fullness, anorexia, pruritus.

Diagnosis

Biochemistry.

Biochemical tests are not specific. ALP is almost always elevated, and hypercalcemia may be encountered in some cases. Hepatic function in the absence of severe jaundice.

Tumor Markers.

Carcinoembryonic antigen and CA 19-9, although not specific, are of diagnostic value. Some have found CEA to be positive in more than 40% of cases. CEA in combination with CA 19-9 is a factor used to differentiate cholangiocarcinoma from hepatocellular carcinoma. This combination, however, cannot help differentiate cholangiocarcinoma from metastatic tumors. AFP may be increased in some cases of cholangiocarcinoma, although the increase is less significant than for hepatocellular carcinoma.

Cholangiography.

Cholangiography may prove diagnostic in hilar tumors, but it is not as effective for peripheral lesions.

Sonography.

Cholangiocarcinoma may be either hypoechoic or hyperechoic.

Computed Tomography.

On plain scans, cholangiocarcinomas are low-density lesions usually associated with dilated bile ducts. Because of their hypovascularity, they usually enhance only mildly on dynamic CT and are either faintly hypodense or isodense to liver parenchyma during the portal venous phase. If a major portal vein branch is compromised, the corresponding lobe atrophies. Hilar cholangiocarcinomas are hypodense or isodense and may not be readily detected. They may appear, however, on late-phase enhanced CT because of the presence of fibrous tissue.

Magnetic Resonance Imaging.

Well-differentiated cholangiocarcinoma has a high signal intensity on T2-weighted spin-echo imaging. Scirrhous cholangiocarcinoma, on the other hand, demonstrates a signal only slightly more intense than the liver parenchyma. Biliary dilatation and metastases to lymph nodes may be detected.

Angiography.

Cholangiocarcinoma is usually hypovascular or avascular; however, the presence of thin, neoplastic vessels may give an appearance of hypervascularity. Venous obstruction, vascular encasement, and arterial collaterals.

Treatment and Prognosis

Early diagnosis is seldom achieved.

Surgical Resection and Liver Transplantation for Cholangiocarcinoma--University of Pittsburgh Experience.

Although numerous cases of surgical treatment of hilar cholangiocarcinoma have been reported, with few exceptions, long-term survival has been poor. For hilar and peripheral cholangiocarcinoma, bile duct resection with or without partial hepatectomy is the procedure of choice for patients with anatomically resectable tumors without advanced cirrhosis or sclerosing cholangitis. Total hepatectomy with liver replacement is the procedure of choice when tumor extension, underlying cirrhosis, or sclerosing cholangitis prevents resection. As will be shown later, subsets of patients with favorable tumor characteristics that justify transplantation.

Hilar Cholangiocarcinoma (Klatskin Tumor).

Between 1981 and 2006, 34 patients underwent Hx, and 38 underwent transplantation (total 72), all with curative intent. Of the 38 patients who underwent transplantation, 27 had OLTx alone, and 11 had upper abdominal exenteration and organ cluster transplantation. Despite the curative intent, 41% of patients in the Hx group, 22% in the OLTx group, and 9% in the organ cluster transplant group had positive margins.

Peripheral Cholangiocarcinoma.

Between 1981 and 1994, 34 patients underwent Hx and 20 underwent transplantation (total 54). Of the 38 patients who underwent transplantation, 11 had OLTx alone, and 9 had upper abdominal exenteration and organ cluster transplantation. Of the patients in the Hx group, 29.4% had positive margins compared with 20% in the OLTx group. Perioperative mortality was 7.4% for the entire group.