Diagnosis of Acid Reflux Disease Using Novel Imaging: A Prospective Study

Gastroesophageal reflux disease (GERD), a common chronic disorder in the veteran population,
is associated with drug costs exceeding $ 10 billion/year. Only 30-40% of patients with
reflux symptoms have erosive esophagitis. The vast majority suffers from NERD; a condition in
which standard endoscopy fails to identify any mucosal breaks and is unable to confirm the
diagnosis. Unfortunately, a gold standard for the diagnosis of NERD does not exist. 24-hour
esophageal pH monitoring and histologic esophageal mucosal changes in NERD patients have
limited accuracy to be routinely used in clinical practice.

Narrow band imaging (NBI) utilizes spectral narrow band filters (incorporated into standard
endoscopes) and enables imaging of features such as intrapapillary capillary loops (IPCLs);
features not identified during standard endoscopy. Preliminary results have shown that NBI
endoscopy may represent a significant improvement over standard endoscopy for the diagnosis
of NERD. Our hypothesis is that NBI identifies changes in the distal esophagus that are
specific for diagnosing patients with NERD. Specific Aim #1: To compare NBI features in the
distal esophagus in patients with NERD (cases) and controls. Specific Aim #2: To determine
whether the NBI features in NERD patients resolve after PPI therapy. Specific Aim #3: To
correlate NBI findings with esophageal histology. Specific Aim #4: To assess the intra- and
interobserver agreement for recognition of the proposed criteria for diagnosing NERD. Cases
will be defined as patients with reflux symptoms (assessed by two validated questionnaires)
with absent macroscopic erosions and abnormal esophageal pH results (NERD group). Control
subjects will include patients with no reflux symptoms, absent macroscopic erosions and a
normal esophageal pH result. To identify NBI findings as predictors of response, response to
therapy in cases randomized to the PPI arm will be assessed using a validated GERD
questionnaire and correlated with IPCL number and presence of microerosion. In addition, NBI
findings in patients with reflux symptoms, no macroscopic erosions and normal esophageal pH
result will also be compared with controls. Two biopsies will be obtained from the distal
esophagus along with digital images and videorecordings.

Statistical analysis will be done as follows: Aim 1 - chi-square and t-test; with logistic
regression and calculation of odds ratios, Aim 2- McNemar's test and kappa statistic, Aim 3-
Spearman's correlation coefficient and Aim 4- intraclass correlation coefficient. Potential
impact on Health Care: GERD is common among patients and by obviating the need for additional
investigations and reducing unnecessary drug costs, NBI endoscopy could have a considerable
positive impact on patients with NERD.

VA Project

Inclusion Criteria:

- 18 years of age

- Capable of giving informed consents.

- Cases of NERD will be recruited on the basis of presence of heartburn and/or
regurgitation using two validated GERD questionnaires in conjunction with an abnormal
esophageal pH result and absence of erosions at standard endoscopy.

- Control subjects will include patients referred for an upper endoscopy for evaluation
of non-reflux symptoms such as iron deficiency anemia, heme positive stools, screening
of esophageal varices amongst others. A negative esophageal pH result and absence of
erosions will be inclusion criteria for these patients.

Exclusion Criteria:

- Presence of macroscopic erosive esophagitis

- Pregnancy/lactation

- Chronic anticoagulation

- Patients with significant medical comorbidities (oxygen dependent chronic obstructive
pulmonary disease, NYHA class III or IV congestive heart failure, recent diagnosis of
cancer with a life-expectancy < 5 years)

- History of Barrett's esophagus

- Presence of columnar lined distal esophagus on endoscopy with intestinal metaplasia

- Presence of cancer or mass lesion in the esophagus or stomach

- Esophageal strictures

- Peptic ulcer disease and Helicobacter pylori infection

- Prior history of esophageal surgery

- Allergic to PPIs

- Patients on drugs known to cause pill-related esophagitis (e.g. potassium supplements)

- Patients with HIV or other immunocompromised conditions who may have infectious
esophagitis

- Eosinophilic esophagitis