Cholangiocarcinoma (CCA)

Cholangiocarcinoma is a relatively rare type of primary liver cancer that effects the biliary system, used to transport bile from the liver to the intestines. The malignancy originates in the bile duct epithelium and represents less than 10% of primary hepatic malignancies. Risk factor for the development of cholangiocarcinoma include ong standing inflammation and chronic injury of the biliary epithelium₃. The tumors are classified as either intrahepatic, occuring with the liver, or extrahepatic, located outside the liver. Intrahepatic cholangiocarcinomas are further classified as either peripheral or hilar. The hilar variety are located in the hepatic hilum region and appear as discrete masses. Peripheral cholangiocarcinoma is the most common and develops in the interlobular ducts of the liver, where the interlobular bile duct branches within the portal triads. They may be a single or multiple masses.

Peripheral cholangiocarcinoma₉

Hilar cholangiocarcinoma₉

Histology:

Many varieties of cholangiocarcinomas exist. The Japanese Society for Biliary Surgery classified the types of cholangiocarcinoma histologically as papillary, tubular, mucinous, signet ring cell, adenosquamous, squamous, anaplastic, undifferentiated miscellaneous, and unclassified.

The Atlas of Liver Pathology described the histology of cholangiocarcinoma:

"The histology of cholangiocarcinomas is that of small glandular structures which often appear deceptively bland. The nuclei are often quite oval and vesicular. There is characteristically a dense sparsely cellular fibrous stroma. There may be a papillary configuration. Mucin production is frequently demsonstrable, and, when present, clearly excludes hepatocellular carcinoma. Another variable clue to ductal origin is the presence of nuclear atypia in surrounding triads. There has been much recent interest centering on immunoperoxidase methods for identifying cholangio-carcinoma. Markers such as CA 19-9 and CA-50 are said to be consistently positive in cholangiocarcinoma and negative in hepatocellular carcinoma. A polyclonal CEA tends to strain canalculi; if present, this pattern is specific for hepatocellular carcinoma. Keratin straining with AE-1 is highly suggestive of bile duct rather than hepatocyte origin. Once hepatocellular carcinoma is excluded, the problem of excluding metastatic adenocarcinoma remains. This can be done in a rigorous fashion only after autopsy has been performed. However, the diagnosis of cholangiocarcinoma can usually be made reasonably reliably based on the clinical information and characteristic histology; it is virtually certain when one of the predisposing conditions listed earlier is present." ₉

 

Needle Biopsy of cholangiocarcinoma₉

Incidence and Symptoms:

- Symptoms include: clay colored stools, progressive jaundice, itching, right upper abdominal pain that may radiate to the back, loss of appetite, weight loss, fever, chills.

-Obstructive jaundice often signals hilar tumor localization

-Tumors usually grow and metastasize slowly.

-Occurs most commonly between 50 and 70 and affects 5 out of 100,000 people₁.

-Affects males and females equally.

Predisposing factors:

-primary sclerosing cholangitis

-ulcerative colitis

-parasitic infection (Clonorchis sinensis or Opistorchis viverrini)

-hepatobiliary fibropolycystic disease

-Thorotrast exposure

-intrahepatic calculi

Diagnostic Tests:

-ERCP (endoscopic retrograde cholagiopancreatography)

-percutaneous transhepatic cholangiogram (PTCA)

-abdominal CT scan

-abdominal ultrasound

-CT scan directed biopsy of the biliary tract

-biliary cytology (examination of the cells found in a sample of bile) that shows cholangiocarcinoma

-Abnormal blood tests: elevated liver function tests or elevated biliruben₁.

-Pathological levels of tumor markers carcinoembryonic antigen (CEA) and CA 19-9₈.

-MRIs are starting to be used for diagnosis₄.

Treatment Options:

1) Cholangiocarcinomas are surgically removed and/or irradiated, chemotherapy has generally not been successful.

2) Tumors are considered unresectable if they involve both liver lobes, bilateral IHDs, encase common hepatic artery or bil portal vein or branches, extrahepatic metastases, or the caudate lobe.

3) Palliative treatments include surgical bypass or drainage, percutaneous drainage, and internal stent₁₄.

3)Molecular chemotherapy combined with radiation has shown promising results. This involves using the gene therapy strategy of toxin gene conversion of nontoxic prodrug to chemotherapeutic drug in combination with radiation therapy. The chemotherapeutic agent of choice would be 5-FU₁₂.

4) Liver transplantation has generally not been effective₈.

Prognosis:

-Liver-fluke associated CCA generally has a poor prognosis, few survive more than six months after diagnosis.

-Often resistant to current surgical, chemotherapy, and radiotherapy interventions.

-Survival 2-3 years with biliary decompression.

-Survival for at least 5 years in 30-40% of patients with complete tumor ressection₁.

-Death usually results from biliary obstruction rather than tumor metastases.

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