Volatile organic compounds in bile for early diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis: a pilot study

Abstract

Background: The diagnosis of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) is particularly difficult. The role of volatile organic compounds (VOCs) for diagnosis of CCA in patients with PSC is not known.

Objective: Our aim was to identify potential VOCs in the headspaces (gas above the sample) in bile that may predict CCA in patients with PSC.

Design: Prospective cross-sectional study.

Setting: Referral center.

Patients: A total of 32 patients undergoing ERCP for PSC and for CCA complicating PSC.

Interventions: ERCP, bile aspiration.

Main outcome measurements: Selected ion flow tube mass spectrometry was used to analyze the concentration of 22 prevalent VOCs in bile samples. Logistic regression analysis was performed to build a predictive model for diagnosis of CCA.

Results: Levels of several compounds (ethanol, acrylonitrile, acetonitrile, acetaldehyde, benzene, carbon disulfide, dimethyl sulfide, 2-propranolol) were significantly different in patients with CCA complicating PSC compared with those having PSC (P < .05). By using receiver operating characteristic curve analysis, we developed a model for the diagnosis of CCA adjusted for age and sex based on VOC levels of acrylonitrile, 3-methyl hexane, and benzene. The model (2.3239*log [acrylonitrile] + 0.9871*log [3-methyl hexane] + 0.8448*log [benzene]) < -0.12 identified the patients with CCA (area under the curve [AUC] = 0.89), with 90.5% sensitivity and 72.7% specificity (P = .02).

Limitations: Sample size.

Conclusion: The measurement of VOCs in biliary fluid may be useful to diagnose CCA in patients with PSC. A larger study with a longitudinal study design is required to confirm our pilot observations to diagnose CCA early in patients with PSC. (

Clinical trial registration number: NCT01565460.).

Conflict of interest statement

Conflict of Interest

The authors declared no financial conflict of interest pertaining to this paper.

Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Demonstrates the spectrum of compounds which are seen in bile. The various colors demonstrate the varying compounds.

Figure 2

Figure demonstrates the box-plot of the various volatile organic compounds (panels A–D) in patients with cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC)

Figure 3

Figure demonstrates the box-plot of the various volatile organic compounds (panels A–D) in patients with cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC)

Figure 4

Receiver operating characteristics (ROC) curve and ROC characteristics as defined by area under the curve (AUC) for volatile organic compounds and the logistic regression model for differentiation of cholangiocarcinoma from primary sclerosing cholangitis. A value