Diagnosis and management of cholangiocarcinomas: a comprehensive review.

First described by Maximilian deStoll in 1777, cholangiocarcinoma remains to be a diagnostic and therapeutic challenge. The incidence of cholangiocarcinoma is of 2000-3000 cases a year in the US but much higher in Southeast Asia and Eastern Europe. Sclerosing cholangitis, ulcerative colitis, liver fluke infestations, hepatolithiasis, thorotrast exposure, choledochal cysts are associated with an increased risk. Recently, substantial progress has been achieved in the understanding of the cellular and molecular mechanisms playing a role in biliary carcinogenesis including oncogenes and tumor suppressor genes. Surgery alone can be a curative treatment in only a fraction of patients with a 5-year survival rate of 0-39%. The role of radiotherapy including intensification with intraoperative radiation therapy, brachytherapy or conformal external beam radiation therapy has not been proven. Experience with chemotherapy is not widespread in cholangiocarcinoma. Chemotherapy trials have mostly included small numbers of patients and there have been no large prospective randomized trials. Observed objective response rates have been between 0% and 40% with no complete remissions. Further studies are required to find out the impact of chemotherapy in the management of cholangiocarcinoma and search for newer agents with novel mechanisms of action that can be more active in cholangiocarcinoma should continue. Meanwhile prevention and early diagnosis of cholangiocarcinoma is essential. Efforts should also continue to discover means to detect high-risk patients with less invasive methods.