Cytological Evaluation of Biliary Epithelium After Previous Endoscopic Sphincterotomy for Benign Disease

PROTOCOL

Introduction: The introduction of endoscopic retrograde cholangio-pancreatography (ERCP) and endoscopic sphincterotomy (ES) in 1974 has dramatically changed the treatment of biliary and pancreatic diseases. ES permits transection of Oddi's sphincter, allowing the endoscopist to remove stones and place stents.

The main indications for ERCP are: 1. Removal of common bile duct stones 2. Dilation of benign biliary ducts strictures 3. Stent placement in patients with malignancy 4. Acute biliary pancreatitis 5. Removal of stones and dilation of strictures of the main pancreatic duct in patients with chronic pancreatitis and 6. Treatment of biliary fistulae after surgical operations .

Complications of ES can be described as early (within one month after ES) and late. Early complications have approximately a 10% incidence and include: 1.acute pancreatitis (5,4%) 2.bleeding (2%) 3.acute cholangitis (1%) 4.acute cholecystitis (0,5%) 5. Perforation and others (1,1%). Late complications are mainly the recurrence of choledocholithiasis (2,5%), narrowing of the previous ES and recurrent acute cholangitis. Furthermore, there is a debate in the literature about late development of cholangiocarcinoma.

Carcinogenesis after surgical sphincteroplasty and biliary-enteric anastomosis has been described. Previous studies have shown late development of cholangiocarcinoma after transduodenal sphincteroplasty and biliary-enteric anastomosis for benign disease. The incidence is up to 7% in a twenty-year follow up, while in the general population is approximately 1/ 100.000 . In addition, Tocchi et al showed that the rate of cholangiocarcinoma after transduodenal sphincteroplasty and choledochoduodenal anastomosis is up to 5-7% and after other choledochi-enteric anastomoses approximately 1,9%. It seems that the ablation of sphincter function causes prolonged pancreatobiliary and duodenobiliary reflux. Proteolytic pancreatic enzymes are activated and bacterial intestinal flora colonizes the biliary epithelium, causing recurrent inflammation. Chronic inflammatory irritation may lead to hyperplasia, dysplasia and atypia of epithelium, ultimately inducing carcinogenesis.

Eleftheriadis et al, studied changes of the biliary epithelium in patients who underwent choledochi-duodenal anastomosis for benign disease, and hyperplasia of the biliary epithelium was demonstrated. The same results and atypia of biliary epithelium were reported by Kurumado et al, in mice models with choledochi-duodenal anastomosis. Anomalous pancreatobiliary junction and choledochal cysts produce the same histologic alterations of the biliary epithelium.

These facts raise a great amount of concern about late development of cancer after ES. Bergman et al in a small trial argues that after ES, the function of the biliary sphincter is permanently lost. On the other hand, Sugiyama et al demonstrated the reduction of pancreatobiliary reflux 1 year after ES. In addition, large population-based studies have shown no causal association between ES and cholangiocarcinoma, but with enough limitations in study design. In conclusion, the long term cytologic changes of the biliary epithelium after ES for benign disease are not well known.

During ERCP, brush cytology can be performed to evaluate bile duct strictures. The use of endoscopic brushing after ES has no reported complications .

Objective: To evaluate cytologic alterations of the biliary epithelium after previous endoscopic sphincterotomy for benign disease.