Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT00590239 |
| Other study ID # |
PS0044 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 15, 2007 |
| Est. completion date |
December 30, 2026 |
Study information
| Verified date |
March 2023 |
| Source |
Midwest Veterans' Biomedical Research Foundation |
| Contact |
April Higbee, BN |
| Phone |
8168614700 |
| Email |
April.Higbee[@]va.gov |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
- The use of high resolution endoscopy (HRE), narrow band imaging (NBI) and
chromoendoscopy increases the detection rates of Barrett's esophagus (BE) and early
neoplasia.
- Endoscopic mucosal resection (EMR) will improve the accuracy for detection of
dysplasia/early neoplasia.
Specific Aim 1 - To create a video-atlas of non-dysplastic and dysplastic/early neoplastic
lesions in patients with BE. This will be used for training purposes and to assess learning
curve associated with these new technologies.
Specific Aim 2 - To create a standardized classification system for the mucosal and vascular
patterns observed in patients with BE.
Specific Aim 3 - To determine the interobserver agreement using the video-atlas for the
mucosal and vascular patterns classification agreed upon.
Specific Aim 4 - To determine the endoscopic detection rate of esophageal cancer or
precancerous lesions removed during endoscopy.
Specific Aim 5 - To determine the pathologic and clinical outcomes of patients undergoing
EMR/ablation; including morbidity, mortality and complications of the procedure.
Results to date (June 2008) : this study is active and open to enrollment. Currently 26
patients have enrolled in this study at the Kansas City VA medical center. In order to
participate, patients must be eligible for care at the KCVA hospital.
Description:
B. BACKGROUND AND SIGNIFICANCE Burden of disease Barrett's esophagus (BE) is an acquired
condition resulting from chronic gastroesophageal reflux disease and is a well recognized
pre-malignant condition for the development of esophageal adenocarcinoma (EAC) (1, 2). BE is
defined as the displacement of the squamocolumnar junction proximal to the gastroesophageal
junction with the presence of intestinal metaplasia (15). This condition entails a 30 to 50
fold greater risk for the development of EAC and has an incidence of development of EAC that
approaches 0.5% annually (3, 4). EAC is a highly lethal cancer and is the most rapidly
increasing cancer in the United States and Western Europe with an incremental increase of
4-10% per year. Although survival rates have improved during the recent years in some
countries, the overall 5-year survival rate is still a dismal 10% in most Western populations
(5-7). Clinical strategies for preventing deaths from this cancer focus on techniques for
identification of esophageal neoplasms in an asymptomatic, early, and curable stage.
Therefore, endoscopic screening of subjects with chronic reflux symptoms has been recommended
as a method of detecting BE and early cancer (8). Patients with BE are then routinely
enrolled in surveillance programs in an attempt to identify those who might benefit from
treatment at a pre-invasive stage of EAC with an ultimate aim of reducing cancer related
deaths (8).
Limitations of current Barrett's surveillance protocol Current guidelines for surveillance
include taking biopsy specimens from endoscopically visible mucosal abnormality followed by
random 4-quadrant biopsies every 2 cm throughout the entire length of BE (15). Unfortunately,
the effectiveness of this strategy is hampered by numerous factors. Apart from being labor
intensive and time consuming for the patient; the accuracy of this protocol is limited by
sampling errors. Biopsy specimens from short segments or tongues of columnar mucosa generally
reveal intestinal metaplasia in only 40-60% of patients (16). In a study of 570 patients
undergoing upper endoscopy, BE was suspected in 146 patients; however, only 60 patients had
diagnosis confirmed by biopsy. Short segment BE (SSBE) was more frequently suspected than
long segment BE (LSBE) but was correctly diagnosed only 25% of the time compared with 55% for
LSBE (17). Similar to the distribution of the metaplastic tissue, the presence of dysplasia
or early adenocarcinoma within a Barrett's segment is patchy and focal. Standard endoscopy
and random biopsies might fail to detect these lesions. Early neoplastic lesions are not
visible to the eye of the endoscopist at standard endoscopy and random biopsies sample only a
small proportion of the epithelium at risk. Also, this "hit and miss" nature of biopsy
increases the cost of the procedure and limits the reliability of histologic interpretation
of dysplasia. The increasing use of endoscopy has led to more and more patients being
diagnosed with BE and offered surveillance. Also, the number of patients being followed up,
and to whom potentially curative therapy can be offered, have increased. The advent of newer
methods of endoscopic treatment of high-grade dysplasia (HGD) and early EAC in the form of
ablative therapy and EMR makes it highly desirable to diagnose dysplasia and EAC early in the
disease process. This may help in alleviating the morbidity and mortality associated with
esophagectomy for EAC. These compelling reasons coupled with the limitations of current
surveillance protocols make the development of new approaches aimed at improving efficacy of
Barrett's surveillance mandatory.
Novel imaging techniques and endoscopic therapies Significant effort has been expended on
development of new GI techniques in order to provide a precise and even a "real time"
endoscopic diagnosis. Chromoendoscopy is a technique that involves the application of agents
to improve characterization of the mucosa resulting in selective uptake or enhancement of
mucosal surface pattern (11). HRE units are equipped with charge-coupled devices with up to a
million pixels that allow clear visualization of fine mucosal details which may facilitate
the detection of early neoplastic lesions (9). NBI is a novel endoscopic technique that is
based on the optical phenomenon that the depth of light penetration into tissues is dependent
on the wavelength; the shorter the wavelength, the more superficial the penetration. Use of
blue light with narrow band filters enables detailed imaging of the mucosal and vascular
surface patterns within the BE segment with a high level of resolution and contrast without
the need for chromoendoscopy. The main chromophore in esophageal tissues in the visible
wavelength is hemoglobin, which has a maximum absorptive wavelength near 415 nm. This is
within the wavelength for NBI and responsible for revealing the superficial vasculature (10).
Esophagectomy was considered as the criterion standard for treatment of patients with early
EAC. However, it is associated with significant morbidity and mortality, even in experienced
surgical hands and high-volume surgical centers. EMR has been used increasingly to replace
surgery as a curative treatment modality for early EAC in patients with BE (12, 13). It
allows effective local treatment of early cancer, histological analysis of all resected
specimens and thus confirmation of diagnosis and complete resection of the lesion. Ablative
therapies in BE patients have provided promising results as well (18, 19).
C. PRELIMINARY DATA Our group recently assessed the potential of NBI for the prediction of
histology during screening and surveillance endoscopy in BE patients (10). Images obtained by
this system were classified according to the mucosal (ridge/villous, circular,
irregular/distorted) and vascular (normal, abnormal) patterns and correlated with histology
in a prospective and blinded fashion. The sensitivity, specificity, and positive predictive
value of the ridge/villous pattern for the diagnosis of intestinal metaplasia without
high-grade dysplasia (HGD) were 93.5%, 87%, and 95% respectively. The sensitivity,
specificity, and positive predictive value of the irregular/distorted patterns for HGD were
100%, 99%, and 95% respectively. These promising results have been validated by other
investigators. Similarly, Dr. Sharma has published several studies involving the use of
chromoendoscopy in patients with BE. In a study of 80 patients with columnar lined esophagus
using indigo carmine dye and 115x magnification endoscopy, three mucosal patterns as stated
above were identified. The presence of ridge/villous pattern for detecting intestinal
metaplasia had high sensitivity, specificity, and positive predictive value (97%, 76%, and
92% respectively). Six patients had an irregular/distorted pattern and biopsies revealed HGD
in all these patients (11). Our group has been active in evaluating the role of ablative
therapies in patients with BE.
We recently assessed the long-term efficacy of achieving complete reversal (endoscopic and
histologic) between multipolar electrocoagulation and argon plasma coagulation in patients
with BE and assessed factors influencing successful ablation. A total of 35 BE patients were
followed for at least 2 years following ablative therapy and complete reversal of BE was
achieved in 70% of the patients, regardless of the ablative technique (19). The International
Working Group on the Classification of Oesophagitis has been at the forefront for the
classification and grading of acid-peptic related esophageal diseases such as erosive
esophagitis and BE. Sharma et al developed and validated an endoscopic grading system for BE
(Prague C & M criteria). The criteria includes assessment of the circumferential (C) and
maximal (M) extent of the endoscopically visualized BE segment along with endoscopic
landmarks. This grading system demonstrated a high validity for the endoscopic assessment of
visualized BE lengths (20).
D. RESEARCH DESIGN AND METHODS Overview Patients with known / suspected BE Pre-registration,
informed consent
Standard endoscopy followed by HRE, NBI and chromoendoscopy
Digital video-recording of endoscopy findings (Subsequent de-identification of all patient
information)
Target biopsies of suspected lesions
Removal of abnormal lesions with EMR / mucosal ablation
Pathologist for histologic interpretation
This is a part of a multicenter study initiated at Kansas City. Patients will be recruited
from Amsterdam, Mainz, Wiesbaden and Kansas City.
Methods Physical examination and questionnaire All patients will complete a validated GERD
questionnaire (GERQ) (21) that records duration, severity, and frequency of heartburn and
regurgitation with supplemental information on medications such as acid suppressive therapy,
aspirin, NSAIDs, etc. Demographic information and clinical findings such as height, weight
and waist circumference will be recorded .
Endoscopic procedure The endoscopic procedures will be performed with a high-resolution
endoscope (Olympus GIF-Q240Z, GIF-Q160Z, or more recent versions) that has the capability of
performing NBI with the push of a switch. Standard methods of conscious sedation and
cardiopulmonary monitoring will be used during each procedure. The distal esophagus will be
carefully inspected for the presence of erosions, nodules and plaques. The presence and size
of hiatal hernia will be recorded. A plastic disposable distal attachment cap (e.g. Olympus
D-201-11802) with a free distal distance of 2-3 mm will be attached to the endoscope in order
to fix mucosal areas of interest until images and biopsies have been taken. The endoscopist
will be blinded to the previous BE histology of the patient. The classification of mucosal
and vascular patterns will be performed in a standardized manner into groups as described
above. Details of endoscopy findings and digital video recordings will be entered into an
endoscopy form .
