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Vascular Endothelial Growth Factor Levels in Bile Distinguishes Pancreatic Cancer from Other Etiologies of Biliary Stricture: A Pilot Study

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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.

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Abbreviations

AUC:

Area under curve

CCA:

Cholangiocarcinoma

ERCP:

Endoscopic retrograde cholangiopancreatography

PSC:

Primary sclerosing cholangitis

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We would like to thank Jeffrey Hammel for help with statistical analysis. The study is supported by a research grant from the Inflammatory Bowel Disease Working Group and American College of Gastroenterology grant (both to U.N) and in part by the National Institutes of Health, National Center for Research Resources, CTSA UL1TR 000439-06 Cleveland, Ohio.

Conflict of interest

The authors declared no financial conflict of interest pertaining to this paper. Dr. John Vargo is a consultant for Olympus America, Boston Scientific, Cook Medical, and Ethicon EndoSurgery.

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Authors and Affiliations

  1. 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

    Udayakumar Navaneethan, Norma G. Gutierrez, Ramprasad Jegadeesan, Preethi G. K. Venkatesh, Madhusudhan R. Sanaka, Sunguk Jang, John J. Vargo & Mansour A. Parsi

  2. Hybridoma Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Earl Poptic

  3. Department of Anatomic Pathology, Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA

    Xiuli Liu

Authors
  1. Udayakumar Navaneethan
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  2. Norma G. Gutierrez
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  3. Ramprasad Jegadeesan
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  4. Preethi G. K. Venkatesh
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  7. Madhusudhan R. Sanaka
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  8. Sunguk Jang
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  9. John J. Vargo
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  10. Mansour A. Parsi
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Correspondence to Udayakumar Navaneethan.

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Navaneethan, U., Gutierrez, N.G., Jegadeesan, R. et al. Vascular Endothelial Growth Factor Levels in Bile Distinguishes Pancreatic Cancer from Other Etiologies of Biliary Stricture: A Pilot Study. Dig Dis Sci 58, 2986–2992 (2013). https://doi.org/10.1007/s10620-013-2764-0

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  • DOI: https://doi.org/10.1007/s10620-013-2764-0

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