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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.).

SUBMITTER: Navaneethan U

PROVIDER: S-EPMC4375033 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Navaneethan Udayakumar U Parsi Mansour A MA Lourdusamy Vennisvasanth V Bhatt Amit A Gutierrez Norma G NG Grove David D Sanaka Madhusudhan R MR Hammel Jeffrey P JP Stevens Tyler T Vargo John J JJ Dweik Raed A RA

Gastrointestinal endoscopy 20141212 4

<h4>Background</h4>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.<h4>Objective</h4>Our aim was to identify potential VOCs in the headspaces (gas above the sample) in bile that may predict CCA in patients with PSC.<h4>Design</h4>Prospective cross-sectional study.<h4>Setting</h4>Referral center.<h4>Patients</h4>A total of ...[more]

PMID: 25500329

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Project description:Background & aimsPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. PSC is a complex disease of largely unknown aetiology that is strongly associated with inflammatory bowel disease (IBD). Diagnosis, especially at an early stage, is difficult and to date there is no diagnostic biomarker. The present study aimed to assess the diagnostic potential of volatile organic compounds (VOCs) in exhaled breath to detect (early) PSC in an IBD population.MethodsBreath samples were obtained from 16 patients with PSC alone, 47 with PSC and IBD, and 53 with IBD alone during outpatient clinic visits. Breath sampling was performed using the ReCIVA breath sampler and subsequently analysed by gas chromatography mass spectrometry. Random forest modelling was performed to find discriminatory VOCs and create a predictive model that was tested using an independent test set.ResultsThe final model to discriminate patients with PSC, with or without IBD, from patients with IBD alone included twenty VOCs and achieved a sensitivity, specificity, and area under the receiver-operating curve on the test set of 77%, 83%, and 0.84 respectively. Three VOCs (isoprene, 2-octanone and undecane) together correlated significantly with the Amsterdam-Oxford score for PSC disease prognosis. A sensitivity analysis showed stable results across early-stage PSC, including in those with normal alkaline phosphatase levels, as well as further progressed PSC.ConclusionThe present study demonstrates that exhaled breath can distinguish PSC cases from IBD and has potential as a non-invasive clinical breath test for (early) PSC.Impact and implicationsPrimary sclerosing cholangitis is a complex chronic liver disease, which ultimately results in cirrhosis, liver failure, and death. Detection, especially in early disease stages, can be challenging, and therefore therapy typically starts when there is already some irreversible damage. The current study shows that metabolites in exhaled breath, so called volatile organic compounds, hold promise to non-invasively detect primary sclerosing cholangitis, including at early disease stages.

Dataset Information

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

Publications

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

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