Comparative Effectiveness of Pyruvate Kinase M2 in Bile, Serum Carbohydrate Antigen 19-9, and Biliary Brushings in Diagnosing Malignant Biliary Strictures

Abstract

Introduction: The role of M2-PK (pyruvate kinase) in bile has not been studied in comparison to brushings and carbohydrate antigen (CA) 19-9 in the diagnosis of malignant biliary strictures. Our aim was 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 84 patients undergoing ERCP. Among the 84 patients, 34 patients were included in the discovery cohort and 40 patients were included in the validation cohort. Levels of M2-PK were measured in bile and compared to brushings and CA 19-9 in the serum. Results: In the discovery cohort, the median bile M2-PK levels were significantly elevated in patients with malignant biliary strictures (187.9 U/mL; interquartile range [IQR] 3.5, 3626.8) compared to those with benign biliary conditions and primary sclerosing cholangitis (PSC; 0 U/mL; IQR 0, 15; p=0.007). A M2-PK cut-off value of 109.1 U/mL 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 of 94.1% and 100%, respectively. Presence of elevated M2-PK >109.1 U/mL or CA 19-9 >33 U/mL or positive brushing was 88.2% sensitive and 88.2% specific, AUC of 0.89 in diagnosis of malignancy. The positive predictive value (PPV), negative predictive value (NPV) and the diagnostic accuracy were 88.2%. The diagnostic accuracy was also confirmed in the validation cohort. Conclusion: 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 of these was highly sensitive in distinguishing benign from malignant biliary strictures.Table 1: Logistic Regression Analysis for the Presence of Malignant Stricture