A Review and Update on Cholangiocarcinoma

Abstract

Cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium that was first described by Durand-Fardel in 1840. Today, it continues to defy diagnosis and treatment. It is difficult to diagnose in part because of its relative rarity, and because it is clinically silent until it becomes advanced disease with obstructive symptoms. The worldwide incidence of cholangiocarcinoma has risen over the past three decades. There is marked geographic variability in the prevalence of this disease, due in large part to regional environmental risk factors. Surgical resection remains the only curative treatment, and high priorities are improving diagnostic methods, and clinical staging for resection once the disease is suspected. A recent trend towards aggressive surgical management has improved outcomes. Chemotherapy, palliative stenting, and radiation are reserved for patients who are not resectable, those with recurrence after surgery, and those who decline surgical intervention. Recent trials using combination systemic chemotherapy and neoadjuvant chemoradiation are promising, but require further study. Over the past five years, several important studies have yielded new insights into the molecular mechanisms of cholangiocarcinoma tumorigenesis. In this review we discuss epidemiology, etiologic factors, molecular pathogenesis, diagnosis, staging, and treatment of cholangiocarcinoma. Particular focus is on recent studies into the cellular and molecular pathogenesis of the disease, recent chemotherapy trials, and newer methods of staging and screening for this devastating malignancy.

Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

“…[26][27][28][29][30] For most of the patients, palliative therapeutic options exist and are based on multimodal promising combinations including systemic chemotherapy, endoscopic biliary stenting, radiation therapy and photodynamic treatment. 26,[31][32][33][34][35][36] Those palliative treatment options can help to improve survival, relieve symptoms and enhance the patient's quality of life. 37,38 The role of image-guided locoregional therapies in the management of patients with cancer has grown.…”

CEACAM6 gene expression in intrahepatic cholangiocarcinoma

“…One reason is that most patients have advanced disease far beyond surgical treatment. The other is that the effects of chemotherapy for cholangiocarcinoma are largely disappointing (Kelley et al, 2004;Olnes and Erlich, 2004;Khan et al, 2005). 5-Fluorouracil (5-FU) as a single therapy or in combination with other drugs has been studied extensively for cholangiocarcinoma.…”

“…Although it is a relatively rare malignancy, the worldwide incidence of intrahepatic cholangiocarcinoma is steadily increasing (Olnes and Erlich, 2004;Khan et al, 2005;Lazaridis and Gores, 2005). The overall survival rate is poor; o5% of patients survive more than 5 years, and the rate has not changed significantly over the past 30 years (Shaib and El-Serag, 2004).…”

“…More than two-thirds of patients with cholangiocarcinoma are not resectable at the time of initial diagnosis (Khan et al, 2002), because it is clinically silent until it has become an advanced disease with obstructive symptoms. Chemotherapy for cholangiocarcinoma is carried out for those patients who are inoperable or who have recurrent disease, but the results tend to be disappointing (Olnes and Erlich, 2004;Khan et al, 2005). Several different new anticancer drugs are under investigation for the treatment of advanced cholangiocarcinoma (Thongprasert, 2005).…”

The Tyrosine Kinase c-Met Contributes to the Pro-tumorigenic Function of the p38 Kinase in Human Bile Duct Cholangiocarcinoma Cells

“…Cholangiocarcinoma is highly aggressive malignancy of the bile ducts with poor prognosis (1,2). Cholangiocarcinoma often arises from background conditions that cause long term inflammation, injury, and reparative biliary epithelial cell proliferation (3)(4)(5)(6)(7).…”