title: Vascular endothelial growth factor levels in bile distinguishes pancreatic cancer from other etiologies of biliary stricture: a pilot study.
abstract: BACKGROUND
  Determining the benign or malignant nature of biliary strictures can be challenging. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether VEGF levels in bile aspirated during endoscopic retrograde cholangiography (ERCP) can distinguish pancreatic cancer from other causes of biliary stricture.
  
  
  METHODS
  Bile was directly aspirated in 53 consecutive patients from March 2012 to October 2012 during ERCP from the common bile duct including 15 with pancreatic cancer, 18 with primary sclerosing cholangitis (PSC), nine with cholangiocarcinoma (CCA), and 11 with benign biliary conditions (sphincter of Oddi and choledocholihiasis). Levels of VEGF in bile were measured. The diagnostic performance was then validated in a second, independent validation cohort of 18 patients (pancreatic cancer n = 10, benign n = 8).
  
  
  RESULTS
  A total of 53 consecutive patients were recruited. The median bile VEGF levels were significantly elevated in patients with pancreatic cancer (1.9 ng/ml (interquartile range [IQR] 0.7, 2.2) compared to those with benign biliary conditions (0.3 ng/ml [IQR 0.2, 0.6]; p < 0.001), PSC (0.7 ng/ml [IQR 0.5, 0.9]; p = 0.02) or CCA (0.4 ng/ml [IQR 0.1, 0.5]; p < 0.001). A VEGF cut-off value of 0.5 ng/ml distinguished pancreatic cancer from CCA with a sensitivity and specificity of 93.3 and 88.9 %, respectively, and area under curve (AUC) of 0.93, and from benign conditions with a sensitivity and specificity of 93.3 and 72.7 %, respectively, with AUC of 0.89. The diagnostic accuracy of biliary VEGF was confirmed in the second independent validation cohort.
  
  
  CONCLUSIONS
  This study suggests that measurement of biliary VEGF-1 levels distinguishes patients with pancreatic cancer from other etiologies of biliary stricture. This may be particularly relevant in approaching patients with indeterminate biliary stricture.
authors.affiliation: Section for Advanced Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Desk A30, The Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH, 44195, USA, udhaykumar81@gmail.com.
authors.forename: Udayakumar
authors.initials: U
authors.lastname: Navaneethan
authors.forename: Norma G
authors.initials: NG
authors.lastname: Gutierrez
authors.forename: Ramprasad
authors.initials: R
authors.lastname: Jegadeesan
authors.forename: Preethi G K
authors.initials: PG
authors.lastname: Venkatesh
authors.forename: Earl
authors.initials: E
authors.lastname: Poptic
authors.forename: Xiuli
authors.initials: X
authors.lastname: Liu
authors.forename: Madhusudhan R
authors.initials: MR
authors.lastname: Sanaka
authors.forename: Sunguk
authors.initials: S
authors.lastname: Jang
authors.forename: John J
authors.initials: JJ
authors.lastname: Vargo
authors.forename: Mansour A
authors.initials: MA
authors.lastname: Parsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic; D001659:Biliary Tract / Q000378:metabolism* / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000378:metabolism; D042883:Choledocholithiasis / Q000175:diagnosis / Q000378:metabolism; D003251:Constriction, Pathologic / Q000175:diagnosis / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D010865:Pilot Projects; D046628:Sphincter of Oddi Dysfunction / Q000175:diagnosis / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A