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

Navaneethan, Udayakumar MD1; Gutierrez, Norma G MD1; Venkatesh, Preethi GK MD1; Jegadeesan, Ramprasad MD1; Zhang, Renilang PhD2; Jang, Sunguk MD1; Sanaka, Madhusudhan R MD1; Vargo, John J MD, MPH1; Parsi, Mansour A MD, MPH1; Feldstein, Ariel E MD3; Stevens, Tyler MD, MS1

American Journal of Gastroenterology: June 2014 - Volume 109 - Issue 6 - p 895–902
doi: 10.1038/ajg.2014.60
Pancreas and Biliary Tract

OBJECTIVES: Ascertaining the benign or malignant nature of biliary strictures may be challenging. Oxidized phospholipids (oxPLs) play an important role in tumor apoptosis and may be elevated in malignant biliary strictures. The objective of the study was to investigate whether oxPLs are enriched in the bile of malignant biliary strictures.

METHODS: In this prospective single-blinded study, bile was obtained from 46 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and management of biliary strictures, including 17 with pancreatic cancer, 6 with primary sclerosing cholangitis (PSC), 8 with cholangiocarcinoma (CCA), and 15 with benign biliary conditions (sphincter of Oddi dysfunction (SOD) or choledocholithiasis or chronic pancreatitis). Bile samples were stored under conditions to minimize artificial oxidation. Levels of 10 different oxPLs were measured blindly by one investigator using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).

RESULTS: Of the 10 different phospholipids measured, the levels of two phosphatidylcholines (PCs; i.e., ON-PC and S-PC) were elevated in CCA as compared with other biliary strictures. Among these, ON-PC was most useful and a cutoff value of 6,020.1 nm distinguished CCA from other biliary strictures with a sensitivity and specificity of 85.7% and 80.3%, respectively (area under curve (AUC) 0.86). A combination of ON-PC and S-PC at a cutoff value of 6,032.2 nm distinguished CCA from other biliary strictures with a sensitivity and specificity of (100% and 83.3%, respectively (AUC 0.91).

CONCLUSIONS: The measurement of specific oxPL products may help to distinguish CCA from other biliary strictures. Measurement of these products in bile may enhance the endoscopic diagnosis of indeterminate biliary strictures.

1 Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA

2 Proteomics Core Laboratory, Lerners Research Institute, Cleveland Clinic, Cleveland, Ohio, USA

3 Division of Gastroenterology, Hepatology, and Nutrition, University of California, San Diego, San Diego, California, USA

Correspondence: Tyler Stevens MD, MS, Section for Advanced Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Desk Q3, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. E-mail:

Received 1 August 2013; accepted 18 February 2014

published online 8 April 2014

© The American College of Gastroenterology 2014. All Rights Reserved.
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