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

• Published in: Gastrointestinal endoscopy 2015-04, Vol.81 (4), p.943-949.e1
• Main Authors: Navaneethan, Udayakumar, MD, Parsi, Mansour A., MD, MPH, Lourdusamy, Vennisvasanth, MD, Bhatt, Amit, MD, Gutierrez, Norma G., MD, Grove, David, PhD, Sanaka, Madhusudhan R., MD, Hammel, Jeffrey P., MS, Stevens, Tyler, MD, MS, Vargo, John J., MD, MPH, Dweik, Raed A., MD
• Format: Article
• Language: English
• Subjects: Acrylonitrile - analysis; Area Under Curve; Benzene - analysis; Bile - chemistry; Bile Duct Neoplasms - diagnosis; Bile Duct Neoplasms - metabolism; Biomarkers, Tumor - analysis; Cholangiocarcinoma - diagnosis; Cholangiocarcinoma - metabolism; Cholangitis, Sclerosing - complications; Cholangitis, Sclerosing - metabolism; Cross-Sectional Studies; Early Detection of Cancer; Female; Gastroenterology and Hepatology; Hexanes - analysis; Humans; Male; Mass Spectrometry; Pilot Projects; Prospective Studies; ROC Curve; Volatile Organic Compounds - analysis
• ISSN: 0016-5107; 1097-6779
• DOI: 10.1016/j.gie.2014.09.041

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 .)