High Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia

Study Overview
=================
Brief Summary
-----------------
The overall objective of this multicenter trial is to determine whether the use of a low-cost, high-resolution microendoscope during diagnostic upper endoscopy can improve the efficiency and accuracy of endoscopic screening for esophageal squamous cell neoplasia. This is a multicenter clinical trial of a novel technology, a miniaturized, lower cost (< $3, 500) microscope device which can be used during upper endoscopy to image the gastrointestinal epithelium. This high-resolution microendoscope (HRME) was developed by our collaborators at RICE University and provides >1000X magnified images of the esophageal mucosa.

Detailed Description
-----------------
Our central hypothesis is that HRME can improve the efficiency and clinical impact of endoscopic screening and surveillance of esophageal squamous cell neoplasia by providing in-vivo optical biopsies comparable to standard histology. Specifically, HRME will allow more detailed evaluation of Lugol's abnormal areas, allowing selective biopsy or removal of neoplastic mucosa. We hypothesize that this will improve the accuracy and diagnostic yield of mucosal sampling. We also hypothesize the HRME will provide additional, more accurate information regarding the presence of neoplasia that will impact upon the physician's decision to obtain a mucosal biopsy or perform endoscopic therapy (endoscopic mucosal resection or ablation). This could potentially minimize the number of unnecessary biopsies and enable the physician to perform endoscopic therapy at the time of the initial examination, rather than delaying endoscopic treatment to another procedure following pathologic confirmation of the initial biopsies. Primary Aims: To compare the efficiency of HRME + Lugol's chromoendoscopy (HRME + LC) to that of Lugol's chromoendoscopy alone (LC) for the diagnosis of esophageal squamous cell neoplasia. Efficiency will be defined as: Diagnostic Yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who receive biopsies. 'Patients saved': # patients who receive no biopsies Procedure time: Total procedure time in the HRME-LC arm compared to the LC arm. To prospectively determine the potential clinical impact of HRME + Lugol's chromoendoscopy (HRME-LC) to Lugol's Chromoendoscopy (LC) by determining if HRME changes the decision to perform endoscopic therapy (endoscopic mucosal resection or ablation) or perform a mucosal biopsy. To prospectively compare the performance characteristics of HRME-LC to LC for the prediction of squamous esophageal neoplasia in flat mucosa and mucosal lesions using histopathology as the gold standard: (a) To determine the sensitivity, specificity, positive and negative predictive value for the identification of neoplasia on a per biopsy and per patient analysis To determine the cost-effectiveness of HRME-LC to LC alone for the endoscopic screening and surveillance of esophageal squamous neoplasia in the US and China.

Official Title
-----------------
High Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: A Randomized, Multicenter Trial of Accuracy, Yield, and Clinical Impact

Conditions
-----------------
Suspected or Known Squamous Cell Neoplasia, Prior History of Squamous Cell Dysplasia and /or Neoplasia

Intervention / Treatment
-----------------
* Drug: Proflavine, high resolution imaging


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All inclusive outpatients undergoing routine (standard of care) Lugol's chromoendoscopic evaluation for suspected or known squamous cell neoplasia will be enrolled as well as any outgoing patients referred to the clinic with any prior history of squamous cell dysplasia and/or neoplasia will also be considered eligible as they will serve as study population for the surveillance group. Exclusion Criteria: Allergy or prior reaction to the fluorescent contrast agent proflavine Patients who are unable to give informed consent Known advanced squamous cell carcinoma of the distal esophagus, or dyplastic/suspected malignant esophageal lesion greater than or equal to 2cm in size not amenable to endoscopic therapy Patient unable to undergo routine endoscopy with biopsy: women who are pregnant or breastfeeding prothrombin time greater than 50% of control; PTT greater than 50 sec, or INR greater than 2.0 inability to tolerate sedated upper endoscopy due to cardio-pulmonary instability or other significant medical issues

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

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proflavine, high resolution imaging<br>5-10 ml of proflavine hemisulfate (0.01%) will be sprayed on the esophageal mucosa. The HRME will then be inserted through the endoscope and gently placed against the mucosa. Imaging of abnormal tissues will be performed. | Drug: Proflavine, high resolution imaging<br>* 5-10 ml of proflavine hemisulfate (0.01%) will be sprayed on the esophageal mucosa. The HRME will then be inserted through the endoscope and gently placed against the mucosa. Imaging of abnormal tissues will be performed.<br>* Other names: Proflavine hemisulfate;|
| No Intervention: Standard of care<br>No invention | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the efficiency of HRME+Lugol's chromoendoscopy (HRME+LC) to that of Lugol's chromoendoscopy alone (LC) for the diagnosis of esophageal squamous cell neoplasia. | Efficiency Diagnostic yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who received biopsies. 'Patient saved': # of patients who received no biopsies Procedure time: Total procedure time in the HRME-LC arm compared to the LC arm. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination whether HRME changes the decision to perform endoscopic therapy or perform a mucosal biopsy | Clinical Impact | 1 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Squamous cell neoplasia, Proflavine, Lugol's chromoendoscopy