Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy

Esophageal Adenocarcinoma is a Lethal Cancer with a Rapidly Increasing Incidence. Barrett's
Esophagus (BE) is the Strongest Risk Factor for Esophageal Adenocarcinoma. Endoscopic
Ablation Induces Reversion of Barrett's Esophagus, and Decreases Progression of Disease.
Unfortunately, data demonstrate a risk of recurrence of BE following successful eradication.
Recent data published by the candidate and colleagues from the Ablation of Intestinal
Metaplasia Containing Dysplasia (AIM Dysplasia) study demonstrate that approximately 25% of
subjects who experience successful eradication of dysplastic BE will develop recurrent BE.

Therefore, following successful endoscopic ablation, patients receive ongoing endoscopic
surveillance. More recently, a simple, non-endoscopic device, termed the Cytosponge, has been
developed for endoscopic screening of subjects at risk for BE. Cytosponge demonstrated a
sensitivity of 90% and a specificity of 94% for the detection of BE.

We expect these investigations to lead to a less costly, highly accurate, less invasive and
more preferred screening paradigm for the large number of subjects who have undergone
endoscopic ablative therapy.

The Cytosponge is a simple, non-endoscopic device developed for endoscopic screening of
subjects at risk for Barrett's esophagus (BE) by investigators at the University of Cambridge
in the U.K. The Cytosponge is an ingestible capsule enclosing a compressed spherical mesh
sponge of 3 cm diameter, the center of which is attached to a string. The capsule and string
are swallowed with water. The string is held at the mouth without tension by means of a
cardboard tab attached to the string, and esophageal peristalsis and gravity move the capsule
into the stomach. After 5 minutes (during which the capsule dissolves and the sponge is
liberated), the sponge is withdrawn by gentle traction on the string and as it does so,
collects cells from the lining of the esophagus. The sponge is placed in fixative, then the
cells are pelleted, and processed into paraffin blocks. The pellets are immunostained with
trefoil factor 3, which is interpreted simply as either positive or negative by the presence
of any staining.

Inclusion Criteria:

1. Male or female subjects, age 18-80 years,

2. Meets the following:

2.1. Previous diagnosis of Barrett's Esophagus (BE) with dysplastic low grade
dysplasia (LGD) or high grade dysplasia (HGD), as evidenced by both classical
endoscopic appearance of salmon-colored mucosa in the tubular esophagus, as well as
endoscopic biopsies from the involved areas demonstrating columnar metaplasia with
goblet cells. The diagnosis of dysplasia must have been confirmed by a second expert
pathologist. Previous endoscopic mucosal resection (EMR) of focal nodular high grade
dysplasia (HGD) or superficial intramucosal cancer (IMC) is allowable, as long as the
EMR specimen shows complete resection of any IMC with clear margins, and biopsies
following ablation confirm excision of the lesion, AND 2.1.1. A history of complete
eradication of both dysplasia and intestinal metaplasia by radiofrequency ablation.
Complete eradication is defined as a normal endoscopic appearance of the tubular
esophagus, and histologic confirmation by biopsies in 4 quadrants every cm from
throughout the length of the previous BE (post-RFA cohort).OR 2.2. Current diagnosis
of BE, presenting for routine care endoscopy (BE cohort).

3. Good general health, with no severely debilitating diseases, active malignancy, or
condition that would interfere with study participation.

Exclusion Criteria:

1. Current use of blood thinners such as coumadin, warfarin, clopidogrel, heparin and/or
low molecular weight heparin (requires discontinuation of medication 5 days prior to
and 7 days after esophagogastroduodenoscopy [EGD] and Cytosponge administration,
aspirin use is OK).

2. Known bleeding disorder

3. For the post-RFA cohort, prior ablative therapy of the esophagus other than
radiofrequency ablation (RFA), including photodynamic therapy (PDT), more than one
session of spray cryotherapy, and any other ablation therapies is exclusionary.
However, prior endoscopic mucosal resection (EMR) is acceptable and up to two prior
treatments of thermal/coagulation therapy (other than RFA) for focal residual disease
following otherwise successful RFA therapy is acceptable.

4. History of esophageal stricture precluding passage of the endoscope or sponge,

5. Pregnancy, or planned pregnancy during the course of the study,

6. Any history of esophageal varices, liver impairment of moderate or worse severity
(Child's- Pugh class B & C) or evidence of varices noted on any past endoscopy,

7. Any history of esophageal surgery, except for uncomplicated fundoplication, and,

8. History of coagulopathy, with INR>1.3 and/or platelet count of <75,000.