Lipidomic Profiling of Bile in Distinguishing Benign From Malignant Biliary Strictures: A Pilot Study

Abstract

Purpose: Ascertaining the benign or malignant nature of biliary strictures may be challenging. Oxidized phospholipids play an important role in tumor apoptosis and may be elevated in malignant biliary strictures. Our aim was to investigate whether oxidized phospholipids are enriched in the bile of malignant biliary strictures. Methods: Bile was obtained in 28 patients undergoing ERCP for the diagnosis and management of biliary strictures, including 10 with pancreatic cancer, five with primary sclerosing cholangitis (PSC), four with cholangiocarcinoma (CCA), and 9 with benign biliary conditions (sphincter of Oddi dysfunction or choledocholithiasis). Bile samples were stored under conditions to minimize artificial oxidation. Levels of 10 different oxidized phospholipids were measured using liquid chromatography electrospray ionization tandem mass spectrometry. Results: 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphatidylcholine (ON-PC) and levels of 1-palmitoyl-2-azelaoyl-sn-glycero-3-pghosphocholine (A-PC) were both useful in discriminating CCA from other etiologies of biliary stricture. (Table) 1-palmitoyl-2-(4-oxobutyryl)-sn-glycero-3-phosphatidylcholine (OB-PC) was most useful for distinguishing pancreatic cancer from benign biliary conditions. A cut-off value of 20.5 nM distinguished pancreatic cancer from benign biliary conditions with a sensitivity and specificity of 77.8% and 77.8%, respectively. There was no significant difference in the median age at diagnosis of strictures in patients with pancreatic cancer, CCA, PSC or benign etiologies.TableConclusion: The measurement of specific oxidized phospholipid products helps to distinguish malignant from benign biliary strictures. Measurement of these products in bile may enhance the endoscopic diagnosis of indeterminate biliary strictures.