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

Inclusion 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.

Exclusion Criteria:

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.