Potential Biomarkers in Bile Provide Accurate, Cost Effective Diagnosis in Pancreatic Cancer

Determining benign from malignant biliary strictures can be challenging with current methods, but several Cleveland Clinic studies are shedding light on potential biomarkers and imaging techniques that are faster, more accurate and cost effective.

Mansour A. Parsi, MD, MPH, head of the Center for Endoscopy and Pancreatobiliary Disorders in Cleveland Clinic’s Digestive Disease Institute, says current endoscopic retrograde brush cytology methods used to look at biliary strictures provide good specificity, but sensitivity is low, leading to false negative results.

“When I get a negative result, I really don’t know if it is truly negative or false negative,” he explains. “That’s a problem. For that reason, we need better bio markers or imaging techniques to find out who has malignant disease and who does not.”

Dr. Parsi led several parallel pilot studies looking at a variety of markers in differentiating malignant and benign biliary strictures:

• LC-MS/MS study – Presented at the 2014 American College of Gastroenterology meeting, this study looked at various proteins in bile. Using liquid chromatograph mass spectrometer (LC-MS/MS) to detect biomarkers in bile was shown to be promising in differentiating malignant from benign biliary strictures at an earlier stage, improving prognosis. Dr. Parsi says lipidomic and proteomic techniques are in the preliminary stages of being translated into clinical practice.
• VEGF study – One study, published in the journal Digestive Diseases and Sciences in 2013, looked at vascular endothelial growth factor (VEGF) levels in bile aspirated during endoscopic retrograde cholangiography (ERCP). The study, which won the Governor’s Award for Excellence in Clinical Research at the 2013 American College of Gastroenterology meeting , found biliary VEGF levels were significantly higher in patients with pancreatic cancer. VEGF is known to be important in recruiting blood vessels to feed cancer cells. The study results suggest measuring VEGF levels can distinguish patients with pancreatic cancer from other etiologies of biliary strictures.
• VOC study – A third study, published in the journal Gastrointestinal Endoscopy in 2014, identified potential volatile organic compounds (VOCs) in bile that can be detected in the headspace (the gas space above a bile sample) leading to the ability to differentiate patients with pancreatic cancer from those with benign biliary conditions. Patients with pancreatic cancer may have a unique profile of VOCs. Detecting VOCs in the headspace can mean faster and more accurate diagnosis. The preliminary results validate the concept of breath testing — a noninvasive, simple, inexpensive test — for cancer diagnosis. Breath testing was recently studied in patients with various liver diseases, and VOCs were identified in the breath of patients with colorectal cancer at 75 percent accuracy. Dr. Parsi says his team intends to recruit more patients to confirm its observations of VOCs in the bile and breath of patients.

In addition to the biomarker studies, Dr. Parsi and his team are investigating various imaging techniques, including cholangioscopy with narrow-band imaging (NBI), to improve detection of malignant biliary diseases. These techniques are expected to enhance visualization of the bile ducts, improving diagnosis of patients with indeterminate biliary strictures

Dr. Parsi’s team evaluated high-definition cholangioscopy with NBI using prototype digital cholangioscopes as an adjunct to ERCP. The technique, an improvement on the currently available cholangioscopy systems, proved helpful in evaluating various biliary disorders. The results of these studies were published in the journals Gastroenterology, Clinical Gastroenterology and Hepatology,and Gastrointestinal Endoscopy.

For more information, contact Dr. Parsi at 216.445.4880 or parsim@ccf.org.