• Aim 1 - Screening Population [ Time Frame: 5 years ]
  To measure the positive and negative predictive value of the sponge capsule Barrett's esophagus test in a screening population.
• Aim 2 - Case/Control Population BE Detection [ Time Frame: 5 years ]
  Compare the sensitivity and specificity of a predetermined BE prediction algorithm for those with and without GERD and assess the influence of other covariates (age, sex, ever smoking, ethnicity and BMI) on this algorithm.
• Aim 3 - Dysplasia Detection Sensitivity and Specificity [ Time Frame: 5 years ]
  Measure the sensitivity and specificity of a predetermined MDM panel assayed on SOS specimens from BE patients identified in Aims 1 and 2, for the detection of HGD /EAC, using surveillance histology as the criterion standard.

• Aim 1 - Screening Population Predictive Value [ Time Frame: 5 years ]
  Compare positive predictive value and negative predictive value of the sponge capsule Barrett's Esophagus test between those with and without chronic GERD.
• Aim 1 - Screening Population Safety and Tolerability of sponge capsule procedure [ Time Frame: 5 years ]
  Safety and tolerability of the sponge capsule device in a screening population as measured by a Tolerability Questionnaire with sponge capsule procedure. Participants will rate their tolerability by rating questions using a scale of 0-10 (1 is none and 10 is severe or 0 is good and 10 is not good).
• Aim 2 - Case/Control Population Sensitivity and Specificity [ Time Frame: 5 years ]
  Validate specificity and sensitivity cut offs of a BE prediction algorithm in an independent patient cohort
• Aim 3 - Dysplasia Detection Rate of Missed Dysplasia [ Time Frame: 5 years ]
  Measure diagnostic uncertainty bias in the criterion standard, specifically, the rate of dysplasia missed by surveillance histology

• Barrett Esophagus
• Esophageal Adenocarcinoma

• Screening Population
  Those that have gastroesophageal reflux or other risk factors for Barrett's Esophagus will be contacted and if agreeable undergo sponge capsule procedure and fill out questionnaires.
  Intervention: Device: Sponge Capsule
• Upper endoscopy - Barrett's Esophagus
  Those that have a diagnosis of Barrett's Esophagus and are scheduled for an upper endoscopy will be approached and if agreeable undergo sponge capsule procedure as well as endoscopic biopsies and brushings of the esophagus.
  Intervention: Device: Sponge Capsule
• Upper endoscopy - No Barrett's Esophagus
  Those that have no known Barrett's Esophagus and are scheduled for an upper endoscopy will be approached and if agreeable undergo sponge capsule procedure as well as endoscopic biopsies and brushings of the esophagus.
  Intervention: Device: Sponge Capsule

Inclusion Criteria arm 1:

1. Male and female ages 50-85
2. Primary Care patients from Mayo Clinic Rochester or Mayo Clinic Health Systems.
3. Patients who have three or more risk factors for Barrett's Esophagus.

Exclusion Criteria arm 1:

1. History of Barrett's esophagus or esophageal adenocarcinoma. 2. Prior endoscopy in the last 10 years. 3. Pregnant or lactating females. 4. Patients who are unable to consent. 5. Patients with current history of uninvestigated dysphagia 6. History of eosinophilic esophagitis, achalasia. 7. Patients on oral anticoagulation including Coumadin, Warfarin.

1. Patients on antiplatelet agents including Clopidogrel (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).

8. Patients on oral thrombin inhibitors including Dabigatran and oral factor X a inhibitors such as rivaroxaban, apixaban and edoxaban (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).

9. Patients with history of known varices or cirrhosis. 10. Patients with history of esophageal or gastric resection. 11. Patients with congenital or acquired bleeding diatheses. 12. Patients with a history of esophageal squamous dysplasia or esophageal squamous carcinoma.

Inclusion criteria arm 2:

1. Subjects with known BE (cases).

   1. Patient between the ages 18 - 90. 2. Patients with a BE segment ≥ 1cm in maximal extent endoscopically. 3. Histology showing evidence of intestinal metaplasia with or without presence of dysplasia.

   4. Undergoing clinically indicated endoscopy.

2. Subjects without known history of BE (controls). 1. Undergoing clinically indicated diagnostic endoscopy.

Exclusion criteria arm 2:

1. Subjects with known BE.

   1. Patients with prior history of ablation (photodynamic therapy, radiofrequency ablation, cryotherapy, argon plasma coagulation). Patients with history of endoscopic mucosal resection alone will not be excluded.
   2. Patients with history of esophageal or gastric resection.

2. Subjects with or without known evidence of BE (on history or review of medical records).

   2. Pregnant or lactating females. 3. Patients who are unable to consent. 4. Patients with current history of uninvestigated dysphagia (this does not apply to the brushings only portion of the study).

   5. History of eosinophilic esophagitis, achalasia. 6. Patients on oral anticoagulation including Coumadin, Warfarin. 7. Patients on antiplatelet agents including Clopidogrel, unless discontinued for three to five days prior to the sponge procedure.

   8. Patients on oral thrombin inhibitors including Dabigatran and oral factor X a inhibitors such as rivaroxaban, apixaban and edoxaban, unless discontinued for three to five days prior to the sponge procedure.

   9. Patients with history of known varices or cirrhosis. 10. Patients with history of esophageal or gastric resection. 11. Patients with congenital or acquired bleeding diatheses. 12. Patients with a history of esophageal squamous dysplasia.