350 Head-Space Analysis of Bile for Early Diagnosis of Cholangiocarcinoma in Primary Sclerosing Cholangitis-a Single Blinded Pilot Study

Abstract

350 Head-Space Analysis of Bile for Early Diagnosis of Cholangiocarcinoma in Primary Sclerosing Cholangitis-a Single Blinded Pilot Study Udayakumar Navaneethan*, Amit Bhatt, Mansour a. Parsi, Norma G. Gutierrez, Madhusudhan R. Sanaka, Sunguk Jang, Jeffrey Hammel, David Grove, Frank Cikach, Raed a. Dweik Gastroenterology, The Cleveland Clinic, Cleveland, OH; Pathobiology, The Cleveland Clinic, Cleveland, OH Background: Differentiating benign and malignant strictures in primary sclerosing cholangitis (PSC) may be challenging. Breath testing is an ideal non-invasive test that detects volatile organic compounds (VOCs) which diffuse from the body into the lungs. Our aim was to identify potential VOCs in the headspaces (gas above the sample) of bile from patients with cholangiocarcinoma (CCA) and PSC. Methods: In this prospective single-blinded study, bile was obtained in 20 patients (12 with PSC and 8 with CCA) undergoing ERCP for the diagnosis and management of biliary strictures. Bile samples were frozen (70 C) within 30 minutes of collection until time of analysis. The samples were heated to 40 C to allow the VOCs in the headspace to come into equilibrium with the sample. 20 milliliters of headspace was removed from the samples and analyzed with a selected ion flow tube mass spectrometry (VOICE200R SIFT-MS instrument, (Syft Technologies Ltd, Christchurch, New Zealand). Our selected ion monitoring (SIM) analysis focused on 22 preselected compounds that are most commonly found in breath. Logistic regression analysis was performed to build a predictive model for CCA. Results: The headspaces from 20 bile samples were analyzed. We identified 7 compounds (acetonitrile, acetaldehyde, benzene, carbon disulfide, dimethyl sulfide, pentane and 3-methylhexane) whose levels were significantly different in patients with CCA compared with PSC. (P!.05) [Table 1] Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of CCA based on VOC levels of acetaldehyde, acetonitrile and carbon disulfide. The model [0.4154 * log (acetaldehyde) + 0.4150 * log (acetonitrile) + 0.7963 * log (carbon disulfide)] identified the patients with CCA (AUCZ0.83), with 100% sensitivity and 62.5% specificity. [Figure 1] There was no significant difference in the median age at diagnosis of strictures in patients with CCA, or PSC. Conclusions: The measurement of VOCs in biliary fluid helps to distinguish CCA from PSC. Measurement of these products in bile may enhance the endoscopic diagnosis of indeterminate biliary strictures in PSC patients. Comparison of Volatile Organic Compunds in Patients with Primary Sclerosing Cholangitis and Cholangiocarcinoma