The Impact of Adjuvant Liquid Alginate on Endoscopic Ablation Therapy of Complicated Barrett's Esophagus

Barrett's esophagus (BE) is a pre-cancerous condition in the esophagus that results from
constant acid exposure and is a precursor to esophageal adenocarcinoma (EAC). Surprisingly,
EAC rates continue to rise despite efforts aimed at addressing BE. Patients with dysplastic
BE are at increased risk for developing EAC and in high grade dysplasia (HGD), this risk can
be as high as 6% per year. For these reasons, these patients are candidates for ablation
therapy, either with cryotherapy, endoscopic mucosal resection (EMR), and/or radiofrequency
ablation (RFA). In patients receiving ablative therapy, 3-5 treatments are typically required
before there is resolution of all Barrett's epithelium while patients remain on twice daily
proton pump therapy.

A recent case study by the current authors demonstrated initial failed response of BE with
HGD to RFA and subsequently cryotherapy. Only after initiation of a liquid alginate solution
(Gaviscon Advance - UK formulation) was there a subsequent rapid and complete response to
therapy. This case suggests that liquid alginate provided additional esophageal protection
allowing mucosal healing and an overall enhanced response to treatment. This finding is
mechanistically plausible given existing evidence demonstrating the carcinogenic properties
of bile acids and injurious activity of pepsin in non-acid refluxate, and liquid alginate's
unique ability to control these components and inhibit acid reflux. The investigators feel
further investigation is warranted in studying the role of adjunct liquid alginate solution
in patients undergoing treatment for BE.

The ingredient of interest in is alginic acid (alginate), a polysaccharide found in the cell
walls of brown algae. Alginates are unique in their ability to form a protective layer above
gastric contents upon exposure to gastric acid, thus limiting exposure of esophageal
epithelium to gastric acid, bile acid, pepsin, and other parts of the gastric contents.
Concurrently, the bicarbonate in alginate-based solutions forms carbon dioxide in the
presence of gastric acid, which converts the gel into foam which floats to the surface of the
gastric contents. Hence, alginate solutions form "rafts" which provide a physical barrier to
acid reflux, as well as a pH-neutral substitute which refluxes preferentially over gastric
acid.

Inclusion Criteria:

- (1) Age 18 (2) Biopsy-proven complicated BE (low/high grade grade dysplasia or IMC,
confirmed by our institution's GI pathologist) As part of standard of care, all
patients' biopsies will be confirmed with the institutions' GI pathologist and, either
with outside biopsies or from biopsies completed at the primary institution.

Exclusion Criteria:

- 1) Moderate to severe renal impairment, as defined by eGFR< 60 for 2 consecutive
readings (2) Lack of capacity for decision-making (3) Allergy to hydroxybenzoates (4)
Patients with uncontrolled hypertension or decompensated heart failure (5) Pregnancy-
patients of child-bearing potential will be tested. (6) Patients with elevated calcium
or potassium on screening laboratory testing (labs completed within the last month)