Vascular endothelial growth factor levels in bile distinguishes pancreatic cancer from other etiologies of biliary stricture: a pilot study

Dig Dis Sci. 2013 Oct;58(10):2986-92. doi: 10.1007/s10620-013-2764-0. Epub 2013 Jul 5.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile / metabolism*
  • Bile Duct Neoplasms / diagnosis
  • Bile Duct Neoplasms / metabolism
  • Bile Ducts, Intrahepatic
  • Biliary Tract / metabolism*
  • Biliary Tract / physiopathology*
  • Biomarkers / metabolism
  • Cholangiocarcinoma / diagnosis
  • Cholangiocarcinoma / metabolism
  • Cholangitis, Sclerosing / diagnosis
  • Cholangitis, Sclerosing / metabolism
  • Choledocholithiasis / diagnosis
  • Choledocholithiasis / metabolism
  • Constriction, Pathologic / diagnosis
  • Constriction, Pathologic / metabolism
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism*
  • Pilot Projects
  • Sphincter of Oddi Dysfunction / diagnosis
  • Sphincter of Oddi Dysfunction / metabolism
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Biomarkers
  • Vascular Endothelial Growth Factor A