Intestinal metaplasia in gallbladder correlates with high amylase levels in bile in patients with a morphologically normal pancreaticobiliary duct

We reported previously that intestinal metaplasia in the gallbladder is strongly associated with expression of caudal-related homeobox transcription factor Cdx2. It has been documented that occult pancreatobiliary reflux, even in the absence of pancreaticobiliary maljunction, is associated with elevated risk of biliary malignancy. We ascertained the correlation between intestinal metaplasia in the gallbladder and occult pancreatobiliary reflux. In 196 patients with a normal pancreaticobiliary ductal arrangement who had undergone laparoscopic cholecystectomy, we performed intraoperative cholangiography and measured amylase levels in bile sampled from the gallbladder. The cutoff value for high cystic amylase was defined as a biliary amylase level higher than the normal upper limit of serum amylase (215 IU/L). We also retrospectively reviewed the cholecystectomized tissue specimens to investigate the presence of intestinal metaplasia and expression of Cdx2. Then, we explored the relationship between intestinal metaplasia in the gallbladder and occult choledocho-pancreatic reflux. Intestinal metaplasia was found in 16.8% (33/196) of the gallbladders. The prevalence of choledocho-pancreatic reflux revealed by intraoperative cholangiography was not significantly different between cases with intestinal metaplasia (5/33, 15.2%) and those without (25/163, 15.3%; P = .81). However, in cases with intestinal metaplasia, the rate of high cystic amylase (13/33, 39.4%) was significantly higher compared with cases without intestinal metaplasia (26/163, 16.0%, P = .005). In conclusion, intestinal metaplasia in the gallbladder is significantly correlated with high amylase levels in bile in patients with a morphologically normal pancreaticobiliary ductal arrangement.