Endoscopic Evaluation of Premalignant Lesions in the Biliary Tract and Pancreatic Ducts

Study Overview
=================
Brief Summary
-----------------
Single operater pancreatico-cholangioscopy is performed through the working channel of conventional duodenoscopes. A visual evaluation of the biliary and pancreatic ductal systems is completed and obvious or suspicious macroscopic lesions are targeted by biopsy forceps. Evaluation of the usefulness of probe based confocal laser endomicroscopy in the evaluation of suspected premalignant lesions in the biliary duct and in the pancreas.

Detailed Description
-----------------
Diagnosis of early preneoplastic lesions is always a problem, but especially when it comes to hidden organs such as the bile ducts and the pancreas. The recent developments in endoscopy encompass mini endoscopes (mother-baby; Spyglas®), which allow visualization of the bile ducts and the pancreas and the possibility to take biopsies under direct vision. An even newer technique is an adaptation of the existing confocal laser scanning microscopy (CLSM) to a small probe, which fits into the 1 mm working channel of the Spyglas. This application of CLSM was coined probe-based confocal laser endomicroscopy (pCLE). It is the aim of this project to systematically and prospectively evaluate the usefulness of pCLE in two distinct patient groups: patients with PSC prone to develop a bile duct cancer (CCC) and patients with chronic pancreatitis/family history of pancreatic cancer prone to develop pancreatic cancer or have suspected IPMN. Patients&Methods Patients with suspected diagnosis of PSC who have to undergo ERCP for diagnosis or therapy or suspected CCC will receive Spyglass investigations under a current clinical protocol. The investigators will add pCLE to these patients. Patients with chronic (hereditary) pancreatitis and suspected malignancy, patients with suspected premalignant lesions (e.g. IPMN), and individuals at risk from familiar pancreatic cancer syndromes who under the surveillance (MRCP with secretin) demonstrate a pancreatic pathology will undergo ERCP with Spyglass as a diagnostic procedure. In these patients, the investigators will add pCLE. Spyglass will be introduced during ERCP and the ducts will be visually inspected. In areas of stenosis and/or suspected pathology, pCLE will be executed. Finally, these areas will be biopsied, if possible. Bile and pancreatic juice will be taken for cytology and molecular analysis. Diagnostic yield and accuracy will be determined of ERCP (x-ray), Spyglas, CLSM, and histology (PAD). This will be firstly an explorative study because the diagnostic criteria for assessing malignancy with CLSM are under development and the investigators group as one of the few doing Spyglas routinely will contribute to establishing such criteria. For statistical calculations, a total of 100 patients will be necessary. It is their plans to do this prospectively together with several centers once the diagnostic criteria are set in order to fulfill the statistical needed numbers. Significance An early diagnosis of both CCC developing in PSC patients and PDAC developing in CP, IPMN patients or individuals with familiar history of PDAC would allow us to treat these patients in good time with surgery or transplantation (LTX). This, in turn, is the only way to improve the diagnosis of these tumors as the have amongst the worst prognosis of all solid tumors in man.

Official Title
-----------------
Endoscopic Evaluation of Premalignant Lesions in the Biliary Tract and Pancreatic Ducts

Conditions
-----------------
Benign Neoplasm of Liver and/or Biliary Ducts, Neoplasm of Uncertain Behavior of Biliary System, Benign Neoplasms of the Pancreas, Neoplasms of the Pancreas

Intervention / Treatment
-----------------
* Procedure: Duodenoscopy, pancreatoscopy, cholangioscopy, confocal microscopy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Suspicious lesions of the hepatobiliary pancreatic duct systems. Exclusion Criteria: Unwillingness to participate Unfit for the investigation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mother-baby endoscopy<br>Spyglass mother-baby endoscopy in conjunction with ERCP | Procedure: Duodenoscopy, pancreatoscopy, cholangioscopy, confocal microscopy<br>* The intervention consists of mother-baby endoscopy of the bile and/or pancreatic duct with visual inspection, confocal laser microscopy, collection of fluid for cytology, and eventually biopsy.<br>* Other names: pCLE;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of single operator endoscopy plus pCLE in the biliary and pancreatic ductal system diagnosing premalignant and malignant lesions. | Beside the safety, technical feasibility and efficacy, we will record and calculate the diagnostic accuray by comparing the outcome of Spyglass/pCLE (endoscopic judgement) with histology (biopsy) and eventual surgical pathology. Outcome measures will be 1) diagnosis of malignant/suspicious lesion by Spyglass and/or pCLE versus final diagnosis with biopsy (Spyglass, other) and/or surgical pathology (resection). | Two years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PSC, mother-baby endoscopy, ERCP, IPMN