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Volatile Organic Compounds in Urine for Noninvasive Diagnosis of Malignant Biliary Strictures: A Pilot Study

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Abstract

Background

The use of volatile organic compounds (VOCs) in bile was recently studied and appeared promising for diagnosis of malignancy. Noninvasive diagnosis of malignant biliary strictures by using VOCs in urine has not been studied.

Aim

To identify potential VOCs in urine to diagnose malignant biliary strictures.

Methods

In this prospective cross-sectional study, urine was obtained immediately prior to ERCP from consecutive patients with biliary strictures. Selected-ion flow-tube mass spectrometry was used to analyze the concentration of VOCs in urine samples.

Results

Fifty-four patients with biliary strictures were enrolled. Fifteen patients had malignant stricture [six cholangiocarcinoma (CCA) and nine pancreatic cancer], and 39 patients had benign strictures [10 primary sclerosing cholangitis (PSC) and 29 with benign biliary conditions including chronic pancreatitis and papillary stenosis]. The concentration of several compounds (ethanol and 2-propanol) was significantly different in patients with malignant compared with benign biliary strictures (p < 0.05). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of malignant biliary strictures adjusted for age and gender based on VOC levels of 2-propranol, carbon disulfide, and trimethyl amine (TMA). The model [−2.4191 * log(2-propanol) + 1.1617 * log(TMA) − 1.2172 * log(carbon disulfide)] ≥ 7.73 identified the patients with malignant biliary stricture [area under the curve (AUC = 0.83)], with 93.3 % sensitivity and 61.5 % specificity (p = 0.009). Comparing patients with CCA and PSC, the model [38.864 * log(ethane) − 3.989 * log(1-octene)] ≤ 169.9 could identify CCA with 80 % sensitivity and 100 % specificity (AUC = 0.9).

Conclusions

Measurement of VOCs in urine may diagnose malignant biliary strictures noninvasively.

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Abbreviations

AUC:

Area under curve

CCA:

Cholangiocarcinoma

EUS:

Endoscopic ultrasound

ERCP:

Endoscopic retrograde cholangiopancreatography

FNA:

Fine-needle aspiration

FISH:

Fluorescence in situ hybridization

PSC:

Primary sclerosing cholangitis

TMA:

Trimethyl amine

VOCs:

Volatile organic compounds

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Acknowledgments

We also would like to thank the Clinical Research Unit members at the Cleveland Clinic who helped in processing the urine samples. The study was supported by a research grant from the American College of Gastroenterology (ACG) Grant (to U.N), BRCP 08-049 Tech 09-003 Third Frontier Program grant from the Ohio Department of Development (ODOD) [to R.D] and in part by the National Institutes of Health, National Center for Research Resources, CTSA, UL1TR 000439-06 Cleveland, Ohio. Dr Dweik was also supported by the following grants: HL107147, HL081064, HL103453, HL109250, and RR026231 from the National Institutes of Health (NIH).

Conflict of interest

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

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland, OH, USA

    Udayakumar Navaneethan, Mansour A. Parsi, Dennisdhilak Lourdusamy, Madhusudhan R. Sanaka, Jeffrey P. Hammel & John J. Vargo

  2. Department of Pathobiology, Lerners Research Institute, Cleveland Clinic, Cleveland, OH, USA

    David Grove & Raed A. Dweik

  3. Center for Interventional Endoscopy, Florida Hospital Institute for Minimally Invasive Surgery, 601 E Rollins Street, Orlando, FL, 32814, USA

    Udayakumar Navaneethan

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  1. Udayakumar Navaneethan
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  2. Mansour A. Parsi
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  4. David Grove
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Correspondence to Udayakumar Navaneethan.

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Navaneethan, U., Parsi, M.A., Lourdusamy, D. et al. Volatile Organic Compounds in Urine for Noninvasive Diagnosis of Malignant Biliary Strictures: A Pilot Study. Dig Dis Sci 60, 2150–2157 (2015). https://doi.org/10.1007/s10620-015-3596-x

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  • DOI: https://doi.org/10.1007/s10620-015-3596-x

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