Lipidomic profiling of bile in distinguishing benign from malignant biliary strictures: a single-blinded pilot study.
OBJECTIVE
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.
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Udayakumar
U
Navaneethan
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Norma G
NG
Gutierrez
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Preethi Gk
PG
Venkatesh
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Ramprasad
R
Jegadeesan
Proteomics Core Laboratory, Lerners Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Renilang
R
Zhang
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Sunguk
S
Jang
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Madhusudhan R
MR
Sanaka
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
John J
JJ
Vargo
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Mansour A
MA
Parsi
Division of Gastroenterology, Hepatology, and Nutrition, University of California, San Diego, San Diego, California, USA.
Ariel E
AE
Feldstein
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Tyler
T
Stevens
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000378:metabolism*; D001660:Biliary Tract Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D002760:Cholangiopancreatography, Endoscopic Retrograde; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism*; D010865:Pilot Projects; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D053719:Tandem Mass Spectrometry
D010743:Phospholipids