Nitrous Oxide For Endoscopic Ablation of Refractory Barrett's Esophagus (NO FEAR-BE)

Eligibility Criteria

• 1. History of BE with LGD or HGD confirmed with biopsy, or resected intramucosal cancer (IMC) with low risk of recurrence defined as EMR/ESD pathology results negative for: positive margin, \>T1a stage, poorly differentiated carcinoma, and lymphovascular invasion.
• 2. Prior treatment with RFA who meet either of the following criteria at the enrolling EGD:
• 2.1. History of at least 3 RFA treatments, with one or more of the following:
• * 2.1.1. Residual BE Prague \>=C1
• * 2.1.2. Residual BE \>=M1
• * 2.1.3. One or more islands of residual BE \>=1 cm in diameter
• * 2.1.4. Any residual dysplasia in tubular esophagus 2.2. History of at least 2 RFA treatments and \< 50% eradication of BE, as judged by estimation of the treating physician.
• 3. 18 or older years of age at time of consent.
• 4. Provides written informed consent.
• 5. Willing to undergo an alternative approved standard of care treatment for their condition.
• 6. Willing and able to comply with study requirements for follow-up.
• 7. No prior history of balloon or spray cryotherapy esophageal treatment. Prior APC is allowable.
• 1. Residual BE Prague length measuring \>C3 or \>M8 after RFA treatment.
• 2. Dysplasia or IM confined only to the gastric cardia.
• 3. Pre-existing esophageal stenosis/stricture preventing advancement of a therapeutic endoscope during screening/baseline EGD. Subjects are eligible if the stenosis/stricture is dilated to at least 15mm, but baseline treatment may need to be delayed per protocol.
• 4. Symptomatic, untreated esophageal strictures.
• 5. 5. Any endoscopically visualized abnormalities such as ulcers, masses, or nodules found in the BE during screening/baseline EGD. Subjects with nodular dysplasia or IMC identified during screening/baseline EGD may be treated with EMR or ESD and return for baseline treatment in this study at least 6 weeks later given that: 5.1. Follow-up endoscopy must be negative for nodular dysplasia (visually clear of nodular dysplasia).
• 5.2. Patients with IMC must be at low risk for recurrence, confirmed by EMR/ESD pathology results negative for: positive margin, \>T1a stage, poorly differentiated carcinoma, and lymphovascular invasion.
• 6. EMR or ESD \< 6 weeks prior to baseline treatment.
• 7. Untreated invasive esophageal malignancy, including margin-positive EMR/ESD.
• 8. Active reflux esophagitis grade B or higher in the BE assessed during screening/baseline EGD.
• 9. Severe medical comorbidities precluding endoscopy or limiting life expectancy to less than 2 years in the judgment of the endoscopist.
• 10. Uncontrolled coagulopathy.
• 11. Inability to hold use of anti-coagulation medications or non-aspirin anti-platelet agents (APAs) for the duration recommended per ASGE guidelines for a high-risk endoscopy procedure.
• 12. Active fungal esophagitis.
• 13. Known portal hypertension, visible esophageal varices, or history of esophageal varices.
• 14. General poor health, multiple co-morbidities placing the patient at risk, or otherwise unsuitable for trial participation.
• 15. Pregnant or planning to become pregnant during period of study participation.
• 16. Patient refuses or is unable to provide written informed consent.
• 17. Prior esophageal surgery with the exception of uncomplicated nissen fundoplication.