Enhanced detection of cholangiocarcinoma with serum trypsinogen-2 in patients with severe bile duct strictures.
OBJECTIVE
Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma. Our aim was to evaluate the diagnostic value of trypsinogen-1, trypsinogen-2, tumour-associated trypsin inhibitor, human chorionic gonadotropin beta and trypsin-2-alpha(1)-antitrypsin for cholangiocarcinoma and to compare them with CA19-9 and CEA.


METHODS
The study consisted of 84 patients with either PSC or cholangiocarcinoma or both referred for liver transplantation or other liver surgery. The serum concentrations were determined by time-resolved immunofluorometric assays.


RESULTS
Forty-six patients were transplanted due to PSC; in 3 of the explanted livers cholangiocarcinoma was found incidentally. All transplanted patients had severe biliary strictures together with cirrhosis or pre-cirrhosis. Twenty-nine of 38 patients with cholangiocarcinoma were candidates for intervention. In all, 8 patients had both PSC and cholangiocarcinoma. Receiver-operating characteristics curve analysis showed that serum trypsinogen-2 had the highest accuracy in differentiating between cholangiocarcinoma and PSC. The area under the curve (AUC) value was 0.804 for trypsinogen-2 and 0.613 for CA19-9. Serum trypsinogen-2 also showed the highest accuracy for differentiation between PSC and PSC with simultaneous cholangiocarcinoma with an AUC value of 0.759.


CONCLUSIONS
Our results suggest that serum trypsinogen-2 is a most useful marker for diagnosing patients with cholangiocarcinoma, and it is superior to serum CA19-9 and CEA.
Lempinen
Marko
M
Clinic of Surgery, Department of Transplantation and Liver Surgery, Helsinki University Hospital, P.O. Box 263, FIN 00029, Helsinki, Finland. marko.lempinen@hus.fi
Isoniemi
Helena
H
Mäkisalo
Heikki
H
Nordin
Arno
A
Halme
Leena
L
Arola
Johanna
J
Höckerstedt
Krister
K
Stenman
Ulf-Håkan
UH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology* / Q000503:physiopathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D018395:CA-19-9 Antigen / Q000032:analysis / Q000097:blood; D018281:Cholangiocarcinoma / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D003251:Constriction, Pathologic / Q000209:etiology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000032:analysis / Q000097:blood; D012680:Sensitivity and Specificity; D014357:Trypsin / Q000032:analysis / Q000097:blood*; D014362:Trypsinogen / Q000032:analysis / Q000097:blood*
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D011956:Receptors, Cell Surface; C065686:carcinoembryonic antigen binding protein, human; C064831:PRSS2 protein, human; D014362:Trypsinogen; D014357:Trypsin