Digestive System Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Ear, Nose, and Throat Diseases

Gastroesophageal Reflux

Barrett Esophagus

Metaplasia

Esophageal Motility Disorders

Esophageal Spasm, Diffuse

Deglutition Disorders

Esophageal Diseases

Gastrointestinal Diseases

Precancerous Conditions

NBI-AFI imaging - Narrow Band Imaging- Patients will be evaluated with a standard magnification endoscope (Olympus GIF Q240Z, 115x or GIF-H180 or equivalent) using a NBI light source.

Autofluorescence Imaging (AFI)- Patients will be evaluated using a prototype autofluorescence endoscope (Olympus, Tokyo, Japan; excitation 395-475 nm, fluorescence detection 490-625 nm, red reflectance 600-620 nm and green reflectance 540-560 nm)

Standard Endoscopy- Patients will undergo EGD with biopsies using a standard diagnostic video endoscope (Olympus, GIF 140 or 160) using the Seattle protocol - 4 quadrant biopsies using standard biopsy forceps every 2 cms; stored in separate jars

Narrow Band Imaging- Patients will be evaluated with a standard magnification endoscope (Olympus GIF Q240Z, 115x or GIF-H180 or equivalent) using a NBI light source.Target biopsies with standard biopsy forceps will be obtained from the different visualized patterns in separate jars.

Autofluorescence Imaging- Patients will be evaluated using a prototype autofluorescence endoscope (Olympus, Tokyo, Japan; excitation 395-475 nm, fluorescence detection 490-625 nm, red reflectance 600-620 nm and green reflectance 540-560 nm).In this system, normal squamous and non-dysplastic BE appears green while the dysplastic areas appear magenta/purplish. Targeted biopsies will be obtained from the areas with abnormal fluorescence.

NBI-AFI imaging

Standard Endoscopy- Patients will undergo EGD with biopsies using a standard diagnostic video endoscope (Olympus, GIF 140 or 160) using the Seattle protocol - 4 quadrant biopsies using standard biopsy forceps every 2 cms; stored in separate jars.

Standard Endoscopy

Prateek Sharma, MD

Primary Aim: In patients with endoscopically suspected BE, compared to standard endoscopy, novel techniques (NBI and AFI) with target biopsies will

* Detect more patients with intestinal metaplasia
* Detect more areas of high grade dysplasia
* Require fewer biopsies and a shorter time for procedure completion

Secondary Aim:

* Compare the yield of high-grade dysplasia(HGD)using NBI/AFI versus standard endoscopy with biopsy.
* Compare the number of biopsies and procedure times for NBI/AFI versus standard endoscopy with biopsy.
* Compare the inter-observer variability in classifying different mucosal and vascular patterns observed by NBI/AFI using kappa statistics.

Barrett's esophagus (BE) is the pre-malignant lesion for adenocarcinoma of the esophagus and esophagogastric junction. It is a condition in which the squamous mucosa of the distal esophagus is replaced by columnar mucosa, specifically intestinal metaplasia. The incidence of esophageal adenocarcinoma has been rapidly rising and has increased 3-6 fold over the past two decades. This has driven efforts to identify patients with the pre-malignant lesion i.e. BE. Intestinal metaplasia within the columnar lined esophagus is the epithelial type that predisposes patients to the development of adenocarcinoma; the other two epithelial types being cardiac and fundic.

Since intestinal metaplasia is now included in the definition and is the epithelial type associated with cancer, obtaining biopsies from the columnar lined distal esophagus is mandatory. The sensitivity and the positive predictive value of standard EGD for diagnosing BE has been reported as 82% and 34% respectively. This is secondary to the patchy and mosaic presence of intestinal metaplasia in the columnar distal esophagus. Endoscopic screening is advocated in patients with chronic GERD symptoms for detection of BE with random biopsies being obtained if a columnar appearing distal esophagus is visualized. Once intestinal metaplasia is detected with these random biopsies and the diagnosis of BE is confirmed, patients are subsequently enrolled in a surveillance program. Similarly, the presence of dysplasia or early adenocarcinoma within a segment of BE is patchy and focal and standard endoscopy and random biopsies may fail to detect these lesions. New endoscopic imaging techniques to improve the accuracy of endoscopic diagnosis have recently been developed, and most are currently under evaluation.

METHODS Study Overview:Patient presenting to GI lab for BE screening and surveillance Informed consent signed and patient randomized, if endoscopic BE is suspected to NBI target biopsies or standard endoscopy with biopsies as the first procedure If randomized to NBI first: patterns noted, target biopsies obtained from specific patterns Same patient returns in 3-6 weeks for 2nd procedure Standard endoscopy: 4 quadrant every 2 cms. random biopsies (i.e. standard BE surveillance) Findings of NBI and random biopsies compared after all patients complete protocol and results analyzed A process similar to the one outlined above will be used in comparing autofluorescence imaging to conventional endoscopy in patients with Barrett's mucosa.

Study Design:This study is part of a multicenter randomized controlled trial being conducted at two sites, the other one being Medical University of South Carolina. Patients will be randomized (opaque sealed envelopes generated by statistician) to undergo NBI/AFI or standard endoscopy with biopsies on day 1. The same patient will return for the alternative procedure with biopsies within 3-6 weeks of the 1st procedure and will be maintained on acid suppressive therapy during this time interval. Each patient will thus act as his/her own control. At the time of performing the 2nd procedure (either NBI/AFI target biopsies or standard endoscopy), the endoscopist will be blinded and will not be aware of the biopsy results from the 1st procedure. Every attempt will also be made to keep the endoscopists blinded to the past history of the patient i.e. non dysplastic BE, LGD, HGD etc.

Risk and benefit to the study participant:Data on newer imaging method like NBI and AFI are mostly in the form of case series. This has not led to a change in the standard of care. The early data is very encouraging but not conclusive due to lack of randomized, controlled trials. Hence, we chose a study design of randomized controlled trial of the newer modalities versus the existing conventional endoscopy. This design necessitates the performance of a repeat endoscopy. Upper endoscopy is very safe, routinely done procedure with a low risk of complications. A repeat procedure may, indeed, increase the potential for risks associated with the procedure but the magnitude is small. The added advantage of second endoscopy would be increased detection of dysplasia and adenocarcinoma resulting in potential benefit to the patients. The main reason for the performance of the current study is the limitation of conventional endoscopy with the implication that dysplasia and adenocarcinoma will be missed on the initial endoscopy. In clinical practice, this usually warrants a follow up endoscopy that is performed at 1-3 yr intervals due to time and cost constraints. For the study population of this trial, the second endoscopy has the potential for increased detection of dysplasia/early adenocarcinoma in the Barrett's segment that could lead to initiation of curative therapy.

Study Population:Patients undergoing BE screening and surveillance will be enrolled after written, informed consent. BE definition- columnar mucosa in the distal esophagus of any length with intestinal metaplasia on biopsy. The BE length will be measured from the gastroesophageal junction to the proximally displaced squamo-columnar junction. The patient demographics (age, gender and ethnicity) and the BE length will be recorded. Total time required for each procedure will be recorded - from endoscope insertion to removal.

Narrow Band Imaging: Patients will be evaluated with a standard magnification endoscope (Olympus GIF Q240Z, 115x or GIF-H180 or equivalent) using a NBI light source (already available at both centers). The outer diameter of the endoscope is 10.8 mm similar to standard diagnostic endoscopes. No special processing or cleaning of the endoscope is required - similar to the standard Olympus GIF-100. A cap may or may not be fitted on the distal tip of the endoscope allowing the mucosa in contact with the cap to be magnified without the motility of the esophagus affecting visualization. The different patterns will be grouped into ridge/villous, circular and irregular/distorted. Target biopsies with standard biopsy forceps will be obtained from the different visualized patterns in separate jars.

Autofluorescence Imaging: Patients will be evaluated using a prototype autofluorescence endoscope (Olympus, Tokyo, Japan; excitation 395-475 nm, fluorescence detection 490-625 nm, red reflectance 600-620 nm and green reflectance 540-560 nm). The AFI scope has two different CCD (charge coupled device to detect the light waves emitted/reflected from the biological tissue - similar to the chip used in a digital camera), one for conventional and another for AFI endoscopy. There is also a rotary filter that allows blue, red or green light to be generated selectively. The video processor constructs video images (AFI images or normal optical images) based on the signals provided by CCD at the distal end of the endoscope. In this system, normal squamous and non-dysplastic BE appears green while the dysplastic areas appear magenta/purplish. Targeted biopsies will be obtained from the areas with abnormal fluorescence. Both the NBI and AFI equipment will be supplied by Olympus America Inc.

Standard Endoscopy: Patients will undergo EGD with biopsies using a standard diagnostic video endoscope (Olympus, GIF 140 or 160) using the Seattle protocol - 4 quadrant biopsies using standard biopsy forceps every 2 cms; stored in separate jars.

Histology: All biopsy specimens will be stained with H\&E and alcian blue at pH 2.5 \& will then be reviewed by two pathologists (SM) and (DL), one at each site, who will be blinded to the NBI/AF results and patterns. Any disagreement in the histological diagnosis will be resolved by a consensus diagnosis. Dysplasia will be classified as no dysplasia, LGD, HGD and adenocarcinoma.

Data Collection:Patient demographics, order of randomization, endoscopy findings (BE length, NBI patterns, AFI patterns), procedure time, number of biopsies and histology reports will be collected and recorded by the study coordinator. All this information will be transferred into an ACCESS database

Statistical Power \& Data Analysis:For the primary outcome, to determine if NBI/AFI target biopsies can diagnose BE (intestinal metaplasia) in 90% of the patients assuming that standard endoscopy with biopsy can diagnose Barrett's in 70%, we would need 122 patients in order to detect a significant difference between the two with 80% power and a type I error rate of 5% using McNemar's test for paired dichotomous responses.

For the secondary outcome of detection of HGD will be based on number of biopsies harboring HGD. If we assume that NBI/AFI can detect areas of HGD (within the BE segment) in 90% of the biopsies from irregular/distorted patterns compared to 60% by standard endoscopy, we would need to study 59 areas/biopsies of HGD in order to detect a significant difference between the two with 80% power and a type 1 error rate of 5% using McNemar's test for paired dichotomous responses. If we enroll at least 10-12 patients with HGD with an average BE length of 5 cms, we will be able to evaluate \> 60 areas of HGD with each procedure. Each site will have to enroll approximately 30-35 BE patients (including 5-6 with HGD) each year.

McNemar's test will be used to compare paired categorical data while continuous paired data will be compared using non-parametric methods such as the Wilcoxon Sign Rank Test. A p value of \<0.05 will be considered significant.

For the initial 30 consecutive patients enrolled in the study, inter-observer variability will be studied on the mucosal and vascular patterns and autofluorescence patterns.

Novel Imaging Techniques in Barrett's Esophagus

Detection Of Intestinal Metaplasia And High Grade Dysplasia In Barrett's Esophagus Using Novel Imaging Techniques - A Randomized Controlled Trial.

Kansas City Veteran Affairs Medical Center

Medical University of South Carolina

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Midwest Biomedical Research Foundation

Professor of Medicine

Rare Diseases

Esophageal Neoplasms

Esophageal Cancer

* IV-administration of EMI-137: all patients will receive 0.13 mg/kg of the fluorescent tracer EMI-137 intravenously.
* Molecular Fluorescence Endoscopy: approximately 2,5 hours after tracer administration, Molecular Fluorescence Endoscopy will be performed with additional measurements of fluorescence signals.

Intravenous administration of 0.13 mg/kg of the fluorescent tracer EMI-137 approximately 2.5 hours prior to the endoscopy procedure.

IV-administation of EMI-137

A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working-channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the endoscopic resection, during the same endoscopy procedure.

Molecular Fluorescence Endoscopy platform

W.B. Nagengast, MD, PhD, PharmD

G.M. van Dam, MD, PhD

To improve detection of esophageal (pre)malignant lesions during surveillance endoscopy of patients at risk of developing malignancies, for example in Barrett's Esophagus (BE), there is a need for better endoscopic visualization and the ability for targeted biopsies. Optical molecular imaging of neoplasia associated biomarkers could form a promising technique to accommodate this need. It is known that the biomarker c-Met is overexpressed in dysplastic and neoplastic areas in BE segments versus normal tissue and has proven to be a valid target for molecular imaging.

Edinburgh Molecular Imaging Ltd (EMI) has developed a fluorescent tracer specifically targeting c-Met by labeling a small peptide to a fluorescent fluorophore: 'EMI-137'. The investigators hypothesize that when EMI-137 is administered intravenously, it accumulates in c-Met expressing high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC), enabling (early) cancer visualization using a newly developed fluorescent fiber-bundle. This hypothesis will be tested in the current pilot intervention study.

Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions

Molecular Fluorescence Endoscopy for the Detection of (Pre)Malignant Lesions in Barrett's Esophagus Using a Fluorescent Tracer 'EMI-137' Targeting c-Met: a Single-center Feasibility and Safety Study

Calculation of the in vivo tumor-to-background ratio (\> 1.5) based on fluorescence intensities in (pre)malignant lesions compared to surrounding healthy esophageal tissue.

University Medical Center Groningen

Adenocarcinoma

Esophagitis

Gastroenteritis

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Vitamins

Acetic Acid

Retinol acetate

Vitamin A

Retinol palmitate

Anti-Bacterial Agents

Adjuvants, Immunologic

Immunologic Factors

Protective Agents

Retinol

* Patients with known Barrett's metaplasia under surveillance
* Patients with Barrett's metaplasia who had undergone endoscopic treatment for neoplasia previously and were under surveillance for metachronous neoplasia
* Patients suspected of neoplasia referred for endoscopic mucosal resection or other targeted endoscopic treatment of the lesion

Prospective observational pilot study.

We would examine patients with Barrett's epithelium that is either healthy or has suspected areas of neoplasia. We will apply acetic acid spray to areas of healthy Barrett's metaplasia and time how long it takes for the aceto whitening to disappear. We will repeat this in cases referred with SM invasive cancer, intramucosal cancer, suspected high grade dysplasia and possible low grade dysplasia. We will record how long it takes for the acetowhitening to disappear. We will biopsy these areas to confirm the diagnosis.

We will correlate the histology to the aceto-whitening time to see if there is a correlation between the degree of neoplasia and the aceto-whitening time after acetic acid dye spray.

Acetic acid chromoendoscopy

Gaius Longcroft-Wheaton, MD, MRCP

Pradeep Bhandari, MD, FRCP

Acetic acid chromoendoscopy is an established standard technique used to detect dysplasia within the gastrointestinal tract. Acetic acid spray helps to identify neoplasia by highlighting the surface pattern, highlighting the vascular pattern and by a process known as the aceto-whitening reaction, where tissues take acetic acid and turn white for a brief period and then slowly revert back to a normal colour. The neoplastic surface and vascular pattern are all very well described, and have played a big role in the recognition of early cancer. The aceto-whitening reaction is well described but the differential in timing between neoplastic and non-neoplastic areas is not well understood.

The investigators aim to establish the differential in the timing of the disappearance of the aceto-whitening reaction between healthy tissue, dysplastic tissue, intramucosal cancer and invasive cancer after acetic acid dye spray in the oesophagus and colon. By understanding this better, the investigators may be able to predict with greater accuracy whether a highlighted abnormal area is cancer or high grade dysplasia, or whether it is low grade dysplasia or inflammation, which has significant prognostic implications for the patient.

The investigators hypothesize that the differential in the timing of the disappearance of the aceto-whitening reaction between normal and abnormal tissue could help in the detection of gastrointestinal neoplasia.

This is a prospective pilot study. It is standard practice within our unit to use acetic acid for the detection of neoplasia. No patient would receive any additional intervention that would not normally be performed.

We will record the surface and vascular patterns before and after acetic acid spray. As usual we will then apply acetic acid spray to the Barrett's epithelium and time how long it takes for the aceto whitening to disappear. It is the timing of the disappearance that is the key study intervention. We will biopsy these areas to confirm the diagnosis. Again this is standard practice and no patient will be denied an intervention that is normally performed, and no extra interventions will be performed over and above the standard clinical practice.

We will correlate the histology to the aceto-whitening disappearance time to identify a threshold time which can serve as a cut off between neoplastic and non-neoplastic tissue.

We hypothesise that the aceto-whitening reaction lasts much longer in the normal epithelium of Barrett's oesophagus and colon. This reaction will be much shorter in areas with abnormal pathology like dysplasia or cancer.

Only pathology retained is for NHS purposes only. No separate tissue retained for the study

Aceto-whitening in the Assessment of Gastrointestinal Neoplasia

Acetowhitening Time as a Novel Objective Tool for the Diagnosis of High Risk Neoplasia in Barrett's Oesophagus

To quantify the differential in the timing of the disappearance of the aceto-whitening reaction between metaplastic tissue, dysplastic tissue and invasive cancer after acetic acid dye spray in the oesophagus and colon.

To differentiate high grade displasia and intramucosal cancer from invasive cancer using the aceto-whitening timing

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Novel Imaging Techniques in Barrett's Esophagus	NCT00576498	Barrett Esophag... Gastroesophagea...	NBI-AFI imaging Standard Endosc...	18 Years -	Midwest Veterans' Biomedical Research Foundation
Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions	NCT03205501	Barrett Esophag... Esophageal Canc... Dysplasia in Ba...	IV-administatio... Molecular Fluor...	18 Years -	University Medical Center Groningen
Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions	NCT03205501	Barrett Esophag... Esophageal Canc... Dysplasia in Ba...	IV-administatio... Molecular Fluor...	18 Years -	University Medical Center Groningen
Aceto-whitening in the Assessment of Gastrointestinal Neoplasia	NCT01618643	Barrett Esophag... Barrett Metapla... Barrett Oesopha... Barrett Adenoca...	Acetic acid chr...	18 Years -	Portsmouth Hospitals NHS Trust
Novel Imaging Techniques in Barrett's Esophagus	NCT00576498	Barrett Esophag... Gastroesophagea...	NBI-AFI imaging Standard Endosc...	18 Years -	Midwest Veterans' Biomedical Research Foundation
Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions	NCT03205501	Barrett Esophag... Esophageal Canc... Dysplasia in Ba...	IV-administatio... Molecular Fluor...	18 Years -	University Medical Center Groningen
Aceto-whitening in the Assessment of Gastrointestinal Neoplasia	NCT01618643	Barrett Esophag... Barrett Metapla... Barrett Oesopha... Barrett Adenoca...	Acetic acid chr...	18 Years -	Portsmouth Hospitals NHS Trust

Spots Global Cancer Trial Database for hgd

Every month we try and update this database with for hgd cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hgd

Every month we try and update this database with for hgd cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hgd cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.