A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis.
OBJECTIVE
Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing cholangiocarcinoma (CC), which is notoriously difficult to diagnose since these patients may have increased levels of bilirubin due to benign strictures. To evaluate the validity of different tumor markers as an aid to diagnosing CC, we have carried out serial serum tumor marker analyses in patients with PSC who have been followed for several years.


METHODS
Seventy-five patients with PSC, without any clinical signs of CC were included in the study. They were investigated every 6th months for 3 years, with extensive liver function tests and four tumor serum markers CEA, CA 19-9, CA 50 and CA 242. The patients were then followed for 5 years to exclude the possibility that CC remained unrecognized.


RESULTS
Of the 75 patients, two (3%) developed CC during the 3-year period. One of these had normal levels, and one had significantly increased levels of the tumor markers. In the follow-up part of the study two further patients died from CC and one from hepatocellular carcinoma, 3 and 4 years after the 3-year study, respectively. Twenty-one patients had an increase of one of the markers on at least one occasion. Five patients had a transient increase of more than double the upper normal limit of the tumor markers on more than one occasion. There was a good correlation between CA 19-9, CA 50 and CA 242, but not with CEA. Fourteen of the 75 patients had periods of increased bilirubin levels, but none of these showed increased tumor markers.


CONCLUSIONS
The serum tumor markers CEA, CA 19-9, CA 50 and CA 242 are of limited value for the detection of CC in patients with PSC because of low specificity. However, we found no falsely increased values in patients with hyperbilirubinemia.
Hultcrantz
R
R
Department of Gastroenterology and Hepatology, Karolinska Hospital, Stockholm, Sweden.
Olsson
R
R
Danielsson
A
A
Järnerot
G
G
Lööf
L
L
Ryden
B O
BO
Wahren
B
B
Broomé
U
U
D000328:Adult; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D001650:Bile Duct Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D018281:Cholangiocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D015209:Cholangitis, Sclerosing / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D003078:Colchicine / Q000627:therapeutic use; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D013997:Time Factors
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; C074601:CA 242 antigen; D018395:CA-19-9 Antigen; C082699:CA-50 antigen; D002272:Carcinoembryonic Antigen; D003078:Colchicine