Confocal Endomicroscopy for Improved Diagnosis of Barrett's Esophagus and Early Esophageal Cancer(CEBE Study)

Study Overview
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Brief Summary
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Endomicroscopy (EM) can improve the diagnosis Barrett's esophagus (BE) and some early esophageal cancers (Intra Epithelial Neoplasia (IEN)). EM provides optical biopsies comparable to standard histology. Specifically, EM allows targeted biopsy rather than random mucosal biopsy during routine endoscopic surveillance of BE or evaluation EIN, which will improve the diagnostic yield of mucosal samples for BE IEN. Furthermore, when combined with high resolution endoscopy, EM may improve the overall in vivo detection of IEN in lesions as well as flat mucosa. EM will provide accurate place and size of IEN which will impact the physician's decision to biopsy or perform endoscopic mucosal resection (EMR). This could potentially minimize the number of unnecessary biopsies and as well as enable the physician to perform EMR at the time of the initial examination, rather than delaying endoscopic treatment after the pathology is available. This study is important because it will validate single center studies supporting the routine use of EM for screening and surveillance of BE.

Detailed Description
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The central hypothesis is that endomicroscopy (EM) can improve the efficiency of the endoscopic diagnosis of Barrett's esophagus (BE) and associated Intraepithelial neoplasia(IEN), providing in-vivo optical biopsies comparable to standard histology. Specifically, EM will enable targeted biopsy rather than random mucosal biopsy during routine endoscopic surveillance of BE or endoscopic evaluation of patients with suspected or proven unlocalized IEN, which will improve the diagnostic yield of mucosal samples for BE IEN. Furthermore, when combined with high resolution endoscopy, EM may improve the overall in vivo detection of IEN in lesions as well as flat mucosa. The investigators also hypothesize that EM will provide additional accurate information regarding the presence of IEN that will impact upon the physician's decision to obtain a mucosal biopsy or perform endoscopic mucosal resection (EMR). This could potentially minimize the number of unnecessary biopsies and as well as enable the physician to perform EMR at the time of the initial examination, rather than delaying endoscopic treatment to another procedure after the pathology from the mucosal biopsies are available. This study is important because it will validate single center studies supporting the routine use of EM for screening and surveillance of BE.

Official Title
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In Vivo Endomicroscopy (EM) for Improved Diagnosis of Barrett's Esophagus (BE) and Associated Neoplasia: A Multicenter Randomized Controlled Trial of Diagnostic Yield and Clinical Impact

Conditions
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Barrett's Esophagus, Esophageal Intraepithelial Neoplasia

Intervention / Treatment
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* Procedure: endomicroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Surveillance of Barrett's esophagus or suspected or known BE associated neoplasia Exclusion Criteria: Allergy or prior reaction to the fluorescent contrast agent fluorescein sodium Unable to give informed consent. Pregnant or breastfeeding women Known advanced adenocarcinoma in the esophagus Dysplastic or suspected malignant esophageal lesion 0 BE lesions 2 cm or more in size with Paris classification of 0-Ip (polypoid), 0-Is (protruding sessile), 0-IIa (flat elevated), or 0-IIb (flat) Lesions of any size with Paris 0-IIc (superficial shallow depressed) or 0-III (excavated) Acute gastrointestinal bleeding Coagulopathy defined by Partial Thromboplastin Time (PTT) > 50 sec, or International Normalized Ratio (INR) > 2.0, platelets < 40,000, or on chronic anticoagulation Inability to tolerate sedated upper endoscopy due to cardio-pulmonary instability or other contraindication to endoscopy. History of a severe allergic reaction (anaphylaxis) Known, untreated esophageal strictures, prior partial esophageal resection, or altered anatomy preventing passage of the endomicroscope

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: High Resolution endoscopy (HRE)<br>Standard of care, high resolution endoscopy surveillance/ evaluation of BE and or IEN | |
| Active Comparator: Endomicroscopy (EM)<br>Standard of care, high resolution endoscopy surveillance/ evaluation of BE and or IEN and endomicroscopy esophageal evaluation | Procedure: endomicroscopy<br>* endomicroscopy scope lens has capability to optically evaluate mucosa/submucosa as a microscope<br>* Other names: Confocal Laser Microscopy (CLE), EM, confocal microscopy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| compare diagnostic yield | Compare the diagnostic yield (defined as the proportion of mucosal biopsy samples with neoplasia) of HRE plus EM with directed biopsy (HRE-EM-DB) over HRE with directed biopsy of all mucosal lesions followed by random biopsy (HRE-DB-RB) to diagnose BE in flat mucosa and mucosal lesions The mean diagnostic yield for IEN will be calculated (number of mucosal biopsies and EMR specimens with High Grade Dysplasia (HGD) or Carcinoma (CA) divided by total number of mucosal biopsies obtained) by group and compared, using a chi square or Fisher's exact test for independent groups, depending on the distribution of the data. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assess clinical impact of EM | To prospectively assess the potential clinical impact of EM on the diagnosis and endoscopic surveillance of BE by determining if EM alters the decision to biopsy or EMR and change the total of biopsies per procedure. | 1 year | 
| compare the specificity and sensitivity of HRE with EM | To compare the performance (sensitivity and specificity) characteristics of HRE-EM-DB with HRE-RB for prediction of BE/IEN using the pathologic diagnosis of mucosal biopsies the as the reference standard. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Barrett's, BE, esophageal cancer, esophageal dysplasia