Risk factors:

• Smoking (1)
• Presence of ulcerative colitis (2)
• Alcohol consumption (4)
• Presence of dysplasia on liver biopsy (12)

Diagnosis:
Abdominal pain is more frequent in the presence of cholangiocarcinoma (1); other clinical and biochemical parameters do not discriminate (1;4). Rapidly increasing bilirubin and weight loss predict cholangiocarcinoma (7).
In a retrospective study, 83 % of cholangiocarcinomas could be demonstrated by an imaging procedure (US, CT, cholangiography and/or MRI).
CA 19-9 was useful in different studies (4;9;13). In a case control study, a level > 100 U/ml had 75 % sensitivity and 80 % specificity (4). In a large study on 333 patients, sensitivity and specificity were 68 and 81 % for CEA and 67 and 98 % for CA 19-9, respectively (13). However, elevated levels are also found in patients not carrying cholangiocarcinoma (5). In contrast, Ramage et al. found a combined accuracy of CA 19-9 and CEA of 86 % with no false positives (10). Recently, K-ras mutations in bile where found to predict but not diagnose cholangiocarcinoma (11).

Suggested screening:

• Ultrasonography and determination of CEA, and CA 19-9 every six months.
• ERC and brush cytology if there is stenosis.
• Evaluate for OLT when Mayo risk score > 4.

Reference List

1.  Bergquist A, Glaumann H, Persson B, Broomé U. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: A case-control study. Hepatology 1998; 27(2):311-316.
2. Broomé U, Löfberg R, Veress B, Eriksson LS. Primary sclerosing cholangitis and ulcerative colitis: Evidence for increased neoplastic potential. Hepatology 1995; 22:1404-1408.
3. Broomé U, Olsson R, Lööf L, Bodemar G, Hultcrantz R, Danielsson Å et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996; 38:610-615.
4. Chalasani N, Baluyut A, Ismail A, Zaman A, Sood G, Ghalib R et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: A multicenter case-control study. Hepatology 2000; 31(1):7-11.
5. Hultcrantz R, Olsson R, Danielsson B, Järnerot C, Lööf L, Ryden BO et al. A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. J Hepatol 1999; 30(4):669-673.
6. Kornfeld D, Ekbom A, Ihre T. Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis - A population-based study. Scand J Gastroenterol 1997; 32(10):1042-1045.
7. Miros M, Kerlin P, Walker N, Harper J, Lynch S, Strong R. Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before transplantation. Gut 1991; 32:1369-1373.
8. Nashan B, Schlitt HJ, Tusch G, Oldhafer KJ, Ringe B, Wagner S et al. Biliary malignancies in primary sclerosing cholangitis: Timing for liver transplantation. Hepatology 1996; 23:1105-1111.
9. Nichols J, Gores GJ, LaRusso NF, Wiesner RH, Nagorney DM, Ritts RE. Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis. Mayo Clin Proc 1993; 68:874-879.
10. Ramage JK, Donaghy A, Farrant JM, Iorns R, Williams R. Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. GE 1995; 108:865-869.
11. S Kubicka, F Kühnel, P Flemming, B Hain, N Kezmic, K L Rudolph, M Manns, P N Meier. K-ras mutations in the bile of patients with primary sclerosing cholangitis. Gut 2001; 48:403-408.
12. Fleming KA, Boberg KM, Glaumann H et al. Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing cholangitis. J. Hepatol. 2001, 34: 360-365.
13. Siquera E, Schoen RE, Silverman W et al. Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. Gastrointest.Endosc. 2002, 56:40-47.