Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis

Abstract

There is limited information on test performance for detecting cholangiocarcinoma in primary sclerosing cholangitis (PSC), particularly when used sequentially. This study aimed to characterize diagnostic performance of serum carbohydrate antigen 19-9 (CA 19-9), ultrasonography, computed tomography, magnetic resonance imaging, cholangiography, and biliary cytologic techniques for detecting cholangiocarcinoma in PSC. All consecutive patients with PSC were screened and followed for development of cholangiocarcinoma from 2000 through 2006. Of 230 patients, 23 developed cytopathologically confirmed cholangiocarcinoma with an annual incidence of 1.2%. The optimal cutoff value for serum CA 19-9 was 20 U/mL, which yielded a sensitivity of 78%, specificity of 67%, positive predictive value (PPV) of 23%, and negative predictive value (NPV) of 96%. Serum CA 19-9 combined with either ultrasonography, computed tomography, or magnetic resonance imaging provided a sensitivity of 91%, 100%, and 96%, specificity of 62%, 38%, and 37%, PPV of 23%, 22%, and 24%, and NPV of 98%, 100%, and 98%, respectively, if at least one method was positive. Subsequent cholangiographic examinations in these patients increased specificity to 69% and PPV to 42% while maintaining sensitivity of 91% and NPV of 96%. Following this group, conventional cytology, aneuploidy detection by digital imaging analysis, and aneusomy detection by fluorescence in situ hybridization in brushing samples of biliary strictures had a sensitivity of 50%, 57%, and 86%, specificity of 97%, 94%, and 83%, PPV of 86%, 89%, and 80%, and NPV of 83%, 74%, and 88%, respectively, for detecting cholangiocarcinoma.

Conclusion: Tumor serology combined with cross-sectional liver imaging may be useful as a screening strategy and cholangiography with cytologic examination is helpful for the diagnosis of cholangiocarcinoma in patients with PSC.