title: Comparative effectiveness of pyruvate kinase M2 in bile, serum carbohydrate antigen 19-9, and biliary brushings in diagnosing malignant biliary strictures.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section for Advanced Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Desk Q3, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH, 44195, USA, udhaykumar81@gmail.com.
authors.forename: Udayakumar
authors.initials: U
authors.lastname: Navaneethan
authors.forename: Vennisvasanth
authors.initials: V
authors.lastname: Lourdusamy
authors.forename: Earl
authors.initials: E
authors.lastname: Poptic
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Hammel
authors.forename: Madhusudhan R
authors.initials: MR
authors.lastname: Sanaka
authors.forename: Mansour A
authors.initials: MA
authors.lastname: Parsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000737:chemistry; D001652:Bile Ducts / Q000473:pathology; D001660:Biliary Tract Diseases / Q000097:blood / Q000175:diagnosis*; D018395:CA-19-9 Antigen / Q000097:blood*; D018281:Cholangiocarcinoma / Q000097:blood*; D002760:Cholangiopancreatography, Endoscopic Retrograde; D003251:Constriction, Pathologic / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood*; D011446:Prospective Studies; D011770:Pyruvate Kinase / Q000032:analysis*
chemical_list: D018395:CA-19-9 Antigen; D011770:Pyruvate Kinase