Narrow Band Imaging for Gastric Neoplasia
Narrow Band Imaging for Gastric Neoplasia
It is thought that the development of cancer of the stomach follows a series of stages in
 which the lining becomes increasingly abnormal. Early detection of precursors of gastric
 cancer likely enable less invasive treatment.

 The assessment of gastric mucosa using the endoscope is used to detect cancers and these
 precursor lesions. Narrow band imaging uses filtered light already built into modern
 endoscopoes to identify the early changes in the gastric lining.

 The investigators' hypothesis is that narrow band imaging improves detection of precursor
 lesions and is a method amenable to international standardization.

 The investigators will conduct a prospective trial in which standard random biopsy, white
 light guided biopsy, and narrow band imaging guided biopsy will be performed for each
 patient. The yield of the different methods for gastric cancer precursors will thus be
 compared.
1 BACKGROUND

 Precursor Lesions

 Gastric cancer is the fourth most common cancer and second leading cause of malignant death
 in the world. It often presents only with vague symptoms of dyspepsia and consequently is
 frequently diagnosed at advanced stages.

 Gastric cancer develop in a series of steps beginning with H. pylori infection. 2-4 It
 induces an inflammatory reaction with the surrounding gut epithelium which is theorized to
 drive a subsequent progression in some patients to mucosal atrophy, intestinal metaplasia,
 dysplasia, and finally gastric adenonocarcinoma.

 Systematic biopsy protocols

 In the evaluation for precancerous gastric lesions and Helicobacter pylori, experts recommend
 that biopsies be obtained from the antrum (3cm from pylorus), body (8cm from the pylorus),
 and insisura/angle. Both the greater and lesser curvature should be sampled. Additionally,
 recently developed staging systems including OLGIM (operative clinic on intestinal
 metaplasia) scores require histologic assessment (via the updated Sydney score) from two
 sites (antrum and corpus).

 Narrow Band Imaging in endoscopy

 Patients with H. pylori gastritis, gastric atrophy, intestinal metaplasia most commonly have
 no visible lesions on white-light endoscopy, although endoscopic findings may include antral
 nodularity, absent rugae, prominent gastric vessels white mucosal deposits. However, the
 sensitivity and specificity of these gross findings for underlying histological findings is
 poor. Therefore a number of image-enhancement techniques including chromoendoscopy using
 mucosal dyes or endoscopy-based virtual chromo-endoscopy (e.g., narrow band imaging) have
 been proposed. Narrow band imaging is the most widely investigated.

 Narrow band imaging is an electronic, noninvasive technique in which the illuminating light
 from the endoscope is filtered to enable passage primarily of two narrow bands of light,
 415nm and 540nm. These wavelengths correspond to the hemoglobin absorption wavelength in the
 capillaries and submucosal vessels respectively. This enhances evaluation of the mucosal
 surface patterns and vascular irregularities. NBI has been shown to be useful in the
 detection of dysplasia in Barrett's esophagus and characterization of small colonic adenomas.

 Recently, a simple NBI classification using high-definition white light endoscopy was
 proposed for gastric mucosal examination.18 The NBI interpretation using this classification
 was compared with histological examination of mucosal biopsies, with both NBI and histology
 determined in blinded fashion. This classification which defines the mucosal pattern of the
 stomach had an accuracy exceeding 80% and excellent interobserver agreement (kappa=0.75) for
 normal mucosa, intestinal metaplasia, and dysplasia. However, the study was done at a
 referral center where 34% of patients had dysplasia and NBI was not compared with a white
 light assessment or standardized gastric biopsy protocol. Additionally, the results were not
 provided on a per patient basis, which is the most relevant endpoint in clinical practice.

 2.0 OBJECTIVES AND PURPOSE Prompt detection of gastric cancer precursors enables early
 detection and less invasive treatment options such as endoscopic resection. Narrow band
 imaging is a completely noninvasive technique which uses filtered light to enhance assessment
 of mucosa. Our aim is to gauge whether biopsies targeted by narrow band imaging improves the
 detection of gastric intestinal metaplasia and gastric dysplasia relative to standard white
 light techniques on a per patient basis. A secondary aim will be to assess whether the
 technique is amenable to standardization so that it might be used more broadly to identify
 patients with early gastric neoplasia. While NBI is built into the vast majority of
 endoscopes in use few physicians are aware of its potential use.

 3.0 STUDY DESIGN

 The study will be a prospective tandem endoscopy trial. All EGDs will have already been
 planned as part of standard clinical care.

 High definition white light endoscopy will initially be performed. The specific location of
 all mucosal findings in the stomach such as ulceration or nodularity which require biopsy
 will be noted by the endoscopist and research coordinator but will not be biopsied until
 after NBI. This is done so that blood will not distort or bias NBI assessment. Any abnormal
 findings in other parts of the GI tract examined using the scope (esophagus and duodenum)
 will be noted and biopsied.

 At the completion of the white light exam, while the scope is in the stomach, the white light
 endoscopist will press a button on the scope which changes the view to the narrow band
 imaging.

 At this point the NBI endoscopist who is initially blinded to the white light findings will
 enter the procedure room and examine the stomach using NBI. The type and location of NBI
 abnormalities will be noted and biopsies obtained.

 At the end of the NBI exam the NBI endoscopist will switch the scope view back to white light
 mode. The white light endoscopist will return to the room and biopsy any sites identified and
 recorded during the initial white-light endoscopy. A research coordinator present for the
 entire procedure will verify and record that all sites identified during the initial white
 light exam are biopsied.

 Subsequently, random biopsies will be performed by taking 2 biopsies from the lesser
 curvature (body and antrum), 2 biopsies from the greater curvature (body and antrum), and one
 from the angle.

 The biopsies obtained by white light exam, narrow band imaging exam, and random sampling will
 be separately coded and submitted to pathology. Histologic analysis will be performed by
 expert GI pathologists blinded to the acquisition approach.

 Short 10 second video clips of each site targeted for biopsy by white light narrow band
 imaging will be recorded. They will be matched with the final biopsy results and stored
 WITHOUT personal health identifiers. These short videos may be used for training and shared
 with collaborators to assess inter-observer variability and standardize the interpretation of
 NBI of the stomach.

 The primary outcome measure will be yield of NBI, high definition white light endoscopy, and
 random biopsy for the detection of atrophic gastritis, IM and dysplasia on a per patient
 basis. A secondary endpoint will be the number of regions found by each method to exhibit
 atrophic gastritis, IM, and dysplasia (per lesion (region) yield). The yields of H. Pylori by
 method and the total number of biopsies guided per method will be additional outcomes.

 Patients will be enrolled at the Los Angeles County Hospital of the University of Southern
 California as well as the Gastroenterology Unit at the University of Porto in Porto Portugal.
 The protocol originates from and statistical analysis will be done at the University of
 Southern California. No personal health identifiers will be exchanged at any point between
 the two institutions.

 Prior to the formal initiation of the study there will be a lead in period of 10-20 patients
 with gastric symptoms. The initial patients will be examined using the white light, NBI, and
 gastric biopsy protocol. After this the images will be discussed by the investigators at the
 two centers to make certain that NBI interpretation of gastric premalignant changes is
 standardized. The LAC+USC investigators will also review the Portugese video training library
 on gastric NBI. Any changes in performance of the lead in versus the study will be noted to
 address the secondary aim of developing a standardized approach to NBI which may help this
 technique be used widely to identify patients with early gastric neoplasia.

 4 STATISTICAL CONSIDERATIONS

 The Fisher's exact chi squared test will be used for dichotomous outcomes such as the
 accurate detection of the highest level histology and number of biopsies. Adverse reactions
 will be reported in a descriptive manner.

 Based on previous research which showed 74% correction detection of gastric cancer precursors
 with white light endoscopy versus 89% with NBI and given our anticipated gastric cancer
 prevalence of 20% we performed preliminary sample size estimates for a range of OR using
 G*Power (alpha=0.05, beta =0.20). We anticipate an N of 200 will be sufficient to show a
 significant difference between methods.
Inclusion Criteria:

 -  presenting for upper endoscopy for gastric indications

 -  gastric indications include upper abdominal pain dyspepsia abnormal gastric imaging
 iron deficiency anemia gastric ulcer management of GI blood loss without active
 bleeding reflux weight loss.

 Exclusion Criteria:

 -  Subjects who are incarcerated, younger than 18, or unable to give informed consent
 will be excluded.

 -  Patients who have evidence of active gastrointestinal bleeding will be excluded

 -  Patients taking anti-thrombotic agents including clopidogrel, ticlopidine, coumadin,
 heparin, enoxaparin, and direct II or Xa inhibitors

 -  Patients with INR >1.5, platelet count <75,000