title: 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.
  
  
  METHODS
  Prospective cross-sectional study.
  
  
  METHODS
  Referral center.
  
  
  METHODS
  A total of 32 patients undergoing ERCP for PSC and for CCA complicating PSC.
  
  
  METHODS
  ERCP, bile aspiration.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Sample size.
  
  
  CONCLUSIONS
  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. (
  
  
  BACKGROUND
  NCT01565460.).
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Udayakumar
authors.initials: U
authors.lastname: Navaneethan
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Mansour A
authors.initials: MA
authors.lastname: Parsi
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Vennisvasanth
authors.initials: V
authors.lastname: Lourdusamy
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Bhatt
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Norma G
authors.initials: NG
authors.lastname: Gutierrez
authors.affiliation: Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: David
authors.initials: D
authors.lastname: Grove
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Madhusudhan R
authors.initials: MR
authors.lastname: Sanaka
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Hammel
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Stevens
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Vargo
authors.affiliation: Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
mesh_terms: D000181:Acrylonitrile / Q000032:analysis; D019540:Area Under Curve; D001554:Benzene / Q000032:analysis; D001646:Bile / Q000737:chemistry*; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000378:metabolism*; D003430:Cross-Sectional Studies; D055088:Early Detection of Cancer; D005260:Female; D006586:Hexanes / Q000032:analysis; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010865:Pilot Projects; D011446:Prospective Studies; D012372:ROC Curve; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D006586:Hexanes; D055549:Volatile Organic Compounds; C000604282:3-methylhexane; D001554:Benzene; D000181:Acrylonitrile