Cytological Evaluation of Biliary Epithelium After Endoscopic Sphincterotomy

November 15, 2010 updated by: University of Athens

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Informed consent will be obtained from all patients. ERCP will be conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio General Hospital, Athens, Greece. Pethidine, midazolam or propofol will be used for patient sedation. ERCP will be conducted with the use of a side viewing endoscope. After catheterization of the common bile duct through the previous sphincterotomy, cellular material will be obtained with the use of an endoscopic brush from the bile ducts. With the same way, brush cytology will be performed in the control group after performing ES.

Material obtained from each patient will be smeared on five glass slides. Four slides will be fixed with ethanol solution 95% and the fifth will be air dried. The brush will be fixed in suitable liquid for performing liquid phase cytology. Immunocytology with immunofluorescence p-53 antibody will be performed in samples with hyperplasia, dysplasia or atypia. The cytology department of Tzaneio Hospital will conduct examination and evaluation of all samples.

Samples based on their morphological characteristics will be classified in five categories: a. inadequate sample (very small cell number, presence of blood, inadequate fixation) b. negative for malignancy (adequate cell number with benign morphologic characteristics) c. reactive with or without atypia (cells with reactive/proliferative or inflammatory characteristics. Malignancy is rare but cannot be excluded) d. suspicious for malignancy e. positive for malignancy [21,22].

Examination and evaluation of the specimens will be done by two specialized cytologists, separately, in order to achieve more objective results.

Study Type

Observational

Enrollment (Anticipated)

56

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Athens, Greece
        • University of Athens Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

patients undergoing ERCP and ES for benign disease

Description

inclusion criteria

  • age >18
  • perform endoscopic sphincterotomy
  • benign disease
  • cholelithiasis
  • biliary colic
  • choledocholithiasis
  • cholangitis
  • biliary pancreatitis

exclusion criteria

  • biliary stricture
  • malignancy any kind

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
study group-previous sphincterotomy
Procedure: brush cytology
brush cytology during ERCP
control group-not previous sphincterotomy
Procedure: brush cytology
brush cytology during ERCP

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Athens

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

June 1, 2010

First Submitted That Met QC Criteria

June 2, 2010

First Posted (Estimate)

June 3, 2010

Study Record Updates

Last Update Posted (Estimate)

November 16, 2010

Last Update Submitted That Met QC Criteria

November 15, 2010

Last Verified

October 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10438 (Other Identifier: TUSDM IRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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