High bile titer and high bile to serum ratio of CYFRA 21-1 reliably discriminate malignant biliary obstruction caused by cholangiocarcinoma

Abstract Introduction Previously we demonstrated that elevated serum CYFRA 21 − 1 is a reliable diagnostic and prognostic biomarker for biliary tract cancers. This study aims to explore the diagnostic performance of bile CYFRA 21 − 1 (bCYFRA 21 − 1) in discriminating malignant biliary obstruction (MBO) caused by cholangiocarcinoma (CCA). Methods 77 CCA patients ((17 intrahepatic CCA (iCCA), 49 perihilar CCA (pCCA) and 11 distal CCA (dCCA)) and 43 benign patients with MBO were enrolled. Serum and bile levels of CYFRA 21 − 1, carcinoembryonic antigen (CEA) and carbohydrate antigen 19 − 9 (CA19-9) were quantified. Diagnostic performances of these biomarkers were estimated by receiver operator characteristic curves. Subgroups analysis of these tumor markers among CCA subtypes was performed. Results High bCYFRA 21 − 1 (cut-off value of 59.25 ng/mL with sensitivity of 0.889 and specificity of 0.750) and high bile to serum ratio of CYFRA 21 − 1 (b/sCYFRA 21 − 1, cut-off value of 31.55 with sensitivity of 0.741 and specificity of 0.778) achieved better diagnostic performance than any other biomarker in discriminating MBO. Subgroup analysis revealed that bCYFRA 21 − 1 was significantly elevated in all CCA subtypes; moreover b/sCYFRA 21 − 1 was upregulated in pCCA and dCCA (the mean b/sCYFRA 21 − 1 of pCCA was highest among CCA subtypes: 57.90, IQR 29.82-112.27). Conclusions Both high bCYFRA 21 − 1 and high b/sCYFRA 21 − 1 were reliable diagnostic biomarkers for MBO caused by CCA.