Bile-volatile organic compounds in the diagnostics of pancreatic cancer and biliary obstruction: A prospective proof-of-concept study

Abstract

Objectives: Detection of volatile organic compounds (VOCs) from bodily fluids with field asymmetric waveform ion mobility spectrometry (FAIMS) and related methods has been studied in various settings. Preliminary results suggest that it is possible to detect prostate, colorectal, ovarian and pancreatic cancer from urine samples. In this study, our primary aim was to differentiate pancreatic cancer from pancreatitis and benign tumours of the pancreas by using bile samples obtained during endoscopic retrograde cholangiopancreatography (ERCP). Secondarily, we aimed to differentiate all pancreatic region malignancies from all other kinds of benign causes of biliary obstruction.

Methods: A bile sample was successfully aspirated from 94 patients during ERCP in Tampere University Hospital. Hospital and patient records were prospectively followed up for at least two years after ERCP. Bile samples were analysed using a Lonestar chemical analyser (Owlstone, UK) using an ATLAS sampling system and a split-flow box. Diagnoses and corresponding data from the analyses were matched and divided into two subcategories for comparison. Statistical analysis was performed using linear discriminant analysis, support vector machines, and 5-fold cross-validation.

Results: Pancreatic cancers (n=8) were differentiated from benign pancreatic lesions (n=9) with a sensitivity of 100%, specificity of 77.8%, and correct rate of 88%. All pancreatic region cancers (n=19) were differentiated from all other kinds of benign causes of biliary obstruction (n=75) with corresponding values of 21.1%, 94.7%, and 80.7%. The sample size was too small to try to differentiate pancreatic cancers from adjacent cancers.

Conclusion: Analysing bile VOCs using FAIMS shows promising capability in detecting pancreatic cancer and other cancers in the pancreatic area.

Keywords: ERCP; FAIMS; VOC; bile; biliary obstruction; cholangiocarcinoma; pancreatic cancer; pancreatitis.

Figure 1

FAIMS spectra of bile in pancreatic cancer and benign pancreatic lesion groups and their differences. In the first row, water molecules bend far left in the electric field, while indistinguishable molecules composing the background spike bend to the far right. Discriminative molecules are found between these two. In the second row, the differences are accentuated by calculating third roots.