Volatile Organic Compound Biomarker Signature in Bile to Distinguish Pancreatic Cancer From Chronic Pancreatitis: A Single Blinded Study: 2017 ACG Auxiliary Award (Member)

Abstract

Introduction: Early and accurate diagnosis of pancreatic cancer is important, particularly in at-risk populations with chronic pancreatitis. Volatile organic compounds (VOCs) are chemicals with high vapor pressures which allow them to easily diffuse and enter their gaseous forms.Our aim was to identify potential VOCs in the headspaces (gas above the sample) in bile that may help distinguish pancreatic cancer from chronic pancreatitis. Methods: In this prospective cross-sectional multi-center study, bile was obtained in 57 patients (47 pancreatic cancer; 11 chronic pancreatitis) undergoing ERCP for biliary obstruction. Selected ion flow tube mass spectrometry was used to analyze the concentration of 22 prevalent VOCs in bile samples. All the analysis was performed by one single investigator who was blinded to the final diagnosis. Logistic regression analysis was performed to build a predictive model for diagnosis of pancreatic cancer. In order to conduct internal model validation, we used bootstrap procedure for model discovery. Another independent cohort of bile samples (19 pancreatic cancer; 12 chronic pancreatitis) was employed as test set for validation of the biomarker signature. Results: A biomarker signature (three VOCs) was identified for the differential diagnosis between pancreatic cancer and chronic pancreatitis. The biomarker signature in the discovery set distinguished between pancreatic cancer and chronic pancreatitis with an area under the curve (AUC) of 0.98 (95% CI 0.95-1.00). The biliary model cut-off of 1.33 [0.158* age + 9.747* log (ammonia) - 3.994* log (acetonitrile) + 5.044* log (trimethyl amine)] had a sensitivity of 93.5%, specificity of 100% and a diagnostic accuracy of 96.5%. (Figure 1) Internal validation regarding model's calibration showed that the model correctly predicted pancreatic cancer and chronic pancreatitis rates at different risk levels (P=0.93) In the validation set, an AUC of 1.00 and, using the same cut-off, a sensitivity of 100% and a specificity of 100% were achieved, successfully validating the biomarker signature.Figure: ROC curves of the biomarker (biomarker signature) results on bile samples from all patients with pancreatic cancer versus patients with chronic pancreatitis.Conclusion: The measurement of VOCs in biliary fluid may be useful to diagnose pancreatic cancer in high risk chronic pancreatitis patients with high accuracy. A larger study with a longitudinal study design is required to confirm our observations to diagnose pancreatic cancer early in patients with chronic pancreatitis.