FISH in Diagnosis of Biliary Stricture

NCT ID: NCT04391153

Last Updated: 2020-05-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-03
• Study Completion Date: 2021-12-19

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.

Conditions

Biliary Stricture

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

ERCP with tissue sampling

Intervention Type: PROCEDURE

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.

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.

Group Type: ACTIVE_COMPARATOR

ERCP with tissue sampling

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Olomouc

OTHER

Sponsor Role: lead

Responsible Party

Vincent Zoundjiekpon

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vincent Zoundjiekpon, MD

Role: PRINCIPAL_INVESTIGATOR

2nd Department of Internal Medicine, University Hospital Olomouc, Czech Republic

Locations

2nd Department of Internal Medicine, University Hospital and Palacký University,

Olomouc, , Czechia

Site Status: RECRUITING

Countries

Czechia

Central Contacts

Vincent Zoundjiekpon, MD

Role: CONTACT

vincent04@post.cz

00420608080209 ext. 001

Ondrej Urban, MD, PhD

Role: CONTACT

Facility Contacts

MD

Role: primary

vincent04@post.cz

00420608080209

Ondrej Urban, MD, PhD

Role: backup

ondrej.urban@fnol.cz

00420588443255

Other Identifiers

UHO003

Identifier Type: -

Identifier Source: org_study_id