Comparative effectiveness of pyruvate kinase M2 in bile, serum carbohydrate antigen 19-9, and biliary brushings in diagnosing malignant biliary strictures.

Abstract

The role of M2-PK (pyruvate kinase) in bile has not been studied in comparison with brushings and carbohydrate antigen (CA) 19-9 in the diagnosis of malignant biliary strictures. To compare the diagnostic accuracy of biliary M2-PK with cytology and serum CA 19-9 METHODS: In this prospective cross-sectional study, bile was aspirated in 74 patients (discovery and validation cohort) undergoing endoscopic retrograde cholangiopancreatography. Levels of M2-PK were measured in bile and compared to brushings for cytology and CA 19-9. In the discovery cohort, the median bile M2-PK levels were significantly elevated in patients with malignant biliary strictures [187.9 U/l (interquartile range (IQR) 3.5, 3626.8)] compared to those with benign biliary conditions and primary sclerosing cholangitis [0 U/l (IQR 0, 15)] (P = 0.007). A M2-PK cutoff value of 109.1 U/l distinguished malignant from benign conditions with a sensitivity and specificity of 52.9 and 94.1 %, respectively, and area under curve (AUC) of 0.77. The sensitivity of CA 19-9 and brushings in diagnosing cancer was 52.9 % and 11.1 % and specificity 94.1 and 100 %, respectively. The presence of elevated M2-PK >109.1 U/l or CA 19-9 >33 U/ml or positive brushing was 88.2 % sensitive and 88.2 % specific, AUC of 0.89 in the diagnosis of malignancy. The diagnostic accuracy was confirmed in the validation cohort. As a stand-alone factor, none of the markers were able to distinguish benign from malignant biliary strictures with a high sensitivity. However, a combination was highly sensitive in diagnosing malignant biliary strictures.