Extracellular vesicles in bile promising biomarker for malignant biliary stenoses

Last Updated: 2017-05-25

By Will Boggs MD

NEW YORK (Reuters Health) - The concentration of extracellular vesicles (EVs) in bile can be used as a biomarker to differentiate malignant from nonmalignant common bile duct stenoses, researchers report.

"Up to now, the diagnosis of malignant biliary stenoses is performed by collecting clinical data, imaging studies, and tissue samples, with low performance,�€ Dr. Annarita Farina and Dr. Jean-Louis Frossard from the University of Geneva, Switzerland, told Reuters Health in a joint email.

�€œMeasuring EVs in bile seems appealing and easy, provided the measurement method is standardized and implemented in daily routine,�€ they said. �€œWe were amazed by the huge difference between control and cancer cases; the results were crystal clear.�€

High concentrations of EVs have been found in the blood in the presence of various cancers, but temporary imbalances in EV concentration can arise due to other diseases as well.

Drs. Farina and Frossard and colleagues investigated whether concentrations of EVs in bile collected during endoscopic retrograde cholangiopancreatography (ERCP) could discriminate malignant from nonmalignant common bile duct stenosis in their study of 50 patients, including 20 with pancreatic cancer, five with cholangiocarcinoma, 15 with chronic pancreatitis and 10 with biliary stones (controls).

Median EV concentrations in bile were significantly higher in malignant versus nonmalignant samples in the discovery and verification cohorts, as were the median concentrations of EVs in malignant versus nonmalignant serum samples, they report in Gastroenterology, online May 4.

Bile EVs tended to be larger and to contain more proteins in malignant versus nonmalignant conditions, but these differences fell short of statistical significance.

The threshold values of the EV concentration that best differentiated malignant from nonmalignant controls were 9.46 x (10 to the 14th) nanoparticles/L in bile and 6.39 x (10 to the 13th) nanoparticles/L in serum.

Using the threshold for bile correctly classified all malignant and nonmalignant common bile duct stenoses (for a diagnostic accuracy of 100%), whereas the threshold for serum correctly classified seven of 15 malignant stenoses and 12 of 15 nonmalignant stenoses (for a diagnostic accuracy of 63.3%).

Among a variety of biochemical parameters, bile EV concentration was the only variable independently associated with the differential diagnosis of common bile duct stenosis.

�€œMeasuring EVs in fluid upstream a biliary stenosis in patients with jaundice takes only 3 minutes during endoscopy,�€ Drs. Farina and Frossard noted. �€œConsidering the fact that reaching a diagnosis in patients with presumed biliary or pancreatic cancer is difficult and time consuming (more than 1 endoscopy is needed in this setting), adding 3 minutes�€™ bile sampling during endoscopy seems very cost effective. However, larger cohorts of patients suffering from these specific clinical conditions should be studied before any generally implementation of this technique.�€

�€œMeasuring EVs in bile would be of interest in patients with primary sclerosing cholangitis, a hepatic condition that is complicated by cancer in 20-30% of the cases during the disease,�€ they added. �€œThe natural history of this disease is characterized by the development of cholestasis and progressive biliary stenosis the nature of which remains difficult to firmly assess using the current diagnostic tools (biopsy, brushing). We are now extending our approach to such patients, to verify the ability to discriminate between cancer and non-cancer conditions.�€

SOURCE: http://bit.ly/2qfAhcN

Gastroenterology 2017.