FISH in Diagnosis of Biliary Stricture

Not Applicable

• Conditions: Biliary Stricture
• Interventions: Procedure: ERCP with tissue sampling

• Registration Number: NCT04391153
• Lead Sponsor: University Hospital Olomouc

Brief Summary

The management of biliary strictures depends on their correct pre-operative evaluation which remains challenging. Despite the emerging multitudes of new diagnostic opportunities- modalities we have today, there is still a large number of biliary stenosis misdiagnosed with a profound negative impact on the patients´ outcome. The study aims to proove the feasibility and to evaluate the impact of Fluorescent In Situ Hybridization (FISH) on the tissue diagnostic of biliary strictures.

Detailed Description

The management of biliary strictures depends on their correct pre-operative evaluation which remains challenging. Biliary strictures have various etiologies (traumatic, inflammatory, tumoral, ischemic etc), which are necessarily needed to be known for the correct therapeutic approach. Despite the emerging multitudes of new diagnostic opportunities, there is still a large number of biliary stenosis misdiagnosed with a profound negative impact on the patients´ outcome. The dilemma that exists is how to balance the risk of missing the chance of curative surgery for some malignancy and preventing some patients from unnecessary surgery for benign etiologies and not to waste time. Different conventionnal sampling methods (as Brush-cytology, forceps biopsies during ERCP, endoscopic guided fine needle aspiration-EUS-FNA) have relatively low sensitivity. In such cases, the peroral cholangioscopy proves diagnostic accuracy of 90 %. This method remains expert dependent, costly and may be result in complications of cholangitis in 3-5 % of cases. Techniques or others methods less complicated and improving the preoperative diagnosis of biliary strictures are needed. Fluorescent in Situ Hybridization (FISH) was shown to improve the diagnostic yield of routine cytology.

This study will proove the feasebility and the clinical place of FISH in the diagnostic of biliary strictures and evaluate the impact of FISH on management of patients with biliary strictures.

FISH (Fluorecent In Situ Hybridization) is a molecular cytogenetic method, which enables the detection of fluorescently- labeled DNA/RNA or oligonucleotide probes hybridized to metaphase/ interphase. It uses probes to bind to specific DNA/RNA sequences. This enables the detection of aneuploidy for chromosomes 3, 7, 17 and loss of the 9p21 in patients with suspected malignant biliary strictures.

Different methods were used to take samples from the site of the stenosis. Brush-cytology and endocanal forceps biopsies during ERCP and FNA (fine needle aspiration) during EUS (endosonography). These sampling techniques have relatively low specificity and sensitivity. Reason why we will combine FISH with the sampling methods to maximize our chance to early determine the etiology of stenosis and avoid wasting time and unnecessary cholangioscopy. In this study, the positivity of FISH for Chromosomes 3,7,17 is defined by a presence of polysomy of these chromosomes and the positivity of FISH for Chromosomal region defined by a presence of heterozygous delection or homozygous delection for 9p21. Polysomy is defined by a gain of 2 or more chromosomes in 4 cells. For the chromosomal region, the delection or loss of 9p21 must be observed in 12 cells.

Methods:

* Tissue specimens obtained via either brush cytology, forceps biopsy or fine needle aspiration during ERCP or endosonography (EUS) were examined by routine cytology or histology (RC) methods.

* In addition, FISH using fluorescent-based polynucleotide probes targeting chromosomes 3, 7, 17 and locus 9p21 was performed (ZytoVysion®).

Success (positivity) is defined by the presence of polysomy for chromosomes 3, 7, 17 and/or the presence of delection or loss of the chromosomal region 9p21 in patients with suspected malignant biliary strictures.

Gold standard for final diagnosis should be the histology from surgery resection. In patients without surgery, a follow up of 12 months will be considered adequate to exclude or confirm malignant etiology of the stritures.

Study Timeline

• Status Verified: 2020-05
• Study Start: 2020-05-03
• Study First Submitted: 2020-05-10
• Study First Submitted QC: 2020-05-12
• Study First Posted: 2020-05-18
• Last Update Submitted: 2020-05-18
• Last Update Posted: 2020-05-20
• Primary Completion: 2020-12-31
• Study Completion: 2021-12-19

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

1. Suspected malignant biliary stricture
2. Localization: Extrahepatic biliary duct
3. Patient´s consent with a diagnostic procedure
4. Age : 18 years or more

Exclusion Criteria

1. Intrahepatic biliary strictures
2. Duodenal stenosis (endoscopically)
3. Age : < 18 years
4. Coagulopathy : (INR >1,5, Platelets < 100)
5. Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fluorescence in situ Hybridization (FISH)	ERCP with tissue sampling	Tissue specimens obtained via either of brush cytology, forceps biopsy or fine needle aspiration during ERCP or endosonography (EUS) were examined by routine cytology or histology methods. In addition, FISH inlcuding fluorescence-based polynucleotide probes targeting chromosomes 3, 7, 17 and locus 9p21 was performed. Gold standard for final diagnosis is the histology from surgical resection. In patients without surgery, a follow up of 12 months will be considered adequate to exclude or confirm malignant etiology.
conventional samplig	ERCP with tissue sampling	Patients with biliary strictures udergo ERCP or EUS. Tissue specimens obtained via either of brush cytology, forceps biopsy or fine needle aspiration during ERCP or endosonography (EUS) were examined by routine cytology or histology methods. Gold standard for final diagnosis is the histology from surgical resection. In patients without surgery, a follow up of 12 months will be considered adequate to exclude or confirm malignant etiology.

Primary Outcome Measures

Name	Time	Method
Proove the feasebility and the clinical place of FISH in the diagnostic of biliary strictures	1- 7 days	The the sensitivity (%) and specificity (%) of ERCP/ EUS with conventional tissue sampling - Brushing, forceps biopsy/EUS-FNA and ERCP/EUS with conventional tissue sampling completed with FISH in patients with suspected malignant stricture of the common bile duct are evaluated. Success (positivity) is defined by the presence of benign or malignant cells, adequate to make the final tissue diagnosis. Based on the previous studies and the experiences of our endoscopists and pathologist, we can expect the diagnostic yield with FISH will be increased of 20-30% in the study population (the samples size 96).

Secondary Outcome Measures

Name	Time	Method
evaluate the impact of FISH on management of patients with biliary stricture.	3-6 months	The proportion of patients (%) who will miss the chance of curative surgery for some malignancy and the proportion of patients (%) who will not have unnecessary surgery for benign etiologies are evaluated.

Trial Locations

Locations (1)

2nd Department of Internal Medicine, University Hospital and Palacký University,; 🇨🇿 Olomouc, Czechia