FISH in Diagnosis of Biliary Stricture

Fluorescent in Situ Hybridization in Diagnosis of Biliary Stricture: A Feasibility Study

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.

Study Overview

• Status: Unknown
• Conditions: Biliary Stricture
• Intervention / Treatment: Procedure: ERCP with tissue sampling

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 Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vincent Zoundjiekpon, MD; Phone Number: 001 00420608080209; Email: vincent04@post.cz
• Study Contact Backup: Name: Ondrej Urban, MD, PhD

Study Locations

• Czechia
  • Olomouc, Czechia, 771 00
    • Recruiting
    • 2nd Department of Internal Medicine, University Hospital and Palacký University,
    • Contact: MD; Phone Number: 00420608080209; Email: vincent04@post.cz
    • Contact: Ondrej Urban, MD, PhD; Phone Number: 00420588443255; Email: ondrej.urban@fnol.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: conventional samplig; 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.	Procedure: ERCP with tissue sampling; Patients with biliary strictures undergo ERCP o 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. 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.
Active Comparator: Fluorescence in situ Hybridization (FISH); 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.	Procedure: ERCP with tissue sampling; Patients with biliary strictures undergo ERCP o 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. 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proove the feasebility and the clinical place of FISH in the diagnostic of biliary strictures	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).	1- 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluate the impact of FISH on management of patients with biliary stricture.	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.	3-6 months

Collaborators and Investigators

• Sponsor: University Hospital Olomouc
• Investigators: Principal Investigator: Vincent Zoundjiekpon, MD, 2nd Department of Internal Medicine, University Hospital Olomouc, Czech Republic

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2020
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 19, 2021

Study Registration Dates

• First Submitted: May 10, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: endoscopic retrograde cholangiopancreatography; suspected malignant biliary stricture; fluorescence in situ hybridization; brushing; forceps biopsy; endosonography/ EUS-FNA
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Biliary Tract Diseases; Bile Duct Diseases; Constriction, Pathologic; Cholestasis
• Other Study ID Numbers: UHO003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No