Prevalence:
10 - 20 % (1). In the large Swedish study encompassing
305 patients 8 % developped cholangiocarcinoma during a median follow-up
of 63 months (3). In another Scandinavian study, the cumulative incidence
was 10 % over 10 years (6). There is a marked increase in risk of malignancy
when the Mayo risk score exceeds 4.4; the risk in the Mayo clinic series
was 14.3 and 33.3 % in the low and moderate risk groups, respectively (8).
Therefore, these authors recommend transplantation when the risk score
is > 4.
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
-
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.
-
Broomé U, Löfberg R, Veress B, Eriksson LS. Primary
sclerosing cholangitis and ulcerative colitis: Evidence for increased neoplastic
potential. Hepatology 1995; 22:1404-1408.
-
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.
-
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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
-
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.
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Siquera E, Schoen RE, Silverman W et al. Detecting cholangiocarcinoma
in patients with primary sclerosing cholangitis. Gastrointest.Endosc. 2002,
56:40-47.