Inclusion Criteria Aim1:
* Male and female ages 50-85
* Patients who have three or more risk factors for Barrett's Esophagus.
* Gastroesophageal reflux disease defined by:
* Diagnosis
* Use of one of the following drugs \>= 3 months over the last 5 years: omeprazole, esomeprazole, pantoprazole, rabeprazole, dexlansoprazole, lansoprazole, ranitidine, famotidine, cimetidine
* prior endoscopic diagnosis of erosive esophagitis
* Body mass index (BMI) \>= 30
Exclusion Criteria Aim1 and Aim 3:
* Previous history of:
* esophageal adenocarcinoma/cancer
* esophageal squamous carcinoma
* endoscopic ablation for Barrett's esophagus
* esophageal squamous dysplasia
* Current treatment with oral anticoagulation including Warfarin, Coumadin
* History of cirrhosis
* History of esophageal/gastric varices
* History of Barrett's esophagus
* Prior endoscopy in the last 5 years
Inclusion criteria Aim 2 and Aim 3:
* Subjects with known or suspected BE (cases).
* Patient between the ages 18 - 90.
* Patients with a BE segment ≥ 1cm in maximal extent endoscopically or suspected BE in medical record.
* Histology showing evidence of intestinal metaplasia with or without presence of dysplasia or suspected BE in medical record.
* Undergoing clinically indicated endoscopy.
* Subjects without known history of BE (controls).
* Undergoing clinically indicated diagnostic endoscopy.
Exclusion criteria Aim 2:
* Subjects with known BE.
* Patients with prior history of ablation (photodynamic therapy, radiofrequency ablation, cryotherapy, argon plasma coagulation). Patients with history of endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) alone will not be excluded.
* Patients with history of esophageal resection for esophageal carcinoma.
* For subjects with or without known evidence of BE (on history or review of medical records):
* Pregnant or lactating females.
* Patients who are unable to consent.
* Patients with current history of uninvestigated dysphagia (this does not apply to the brushings/biopsies only portion of the study).
* History of eosinophilic esophagitis, achalasia.
* Patients on oral anticoagulation including Coumadin, Warfarin (this does not apply to the brushings/biopsies only portion of the study).
* Patients on antiplatelet agents including Clopidogrel, unless discontinued for three to five days prior to the sponge procedure.
* Patients on oral thrombin inhibitors including Dabigatran and oral factor Xa inhibitors such as rivaroxaban, apixaban and edoxaban, unless discontinued for three to five days prior to the sponge procedure.
* Patients with history of known esophageal or gastric varices or cirrhosis.
* Patients with history of surgical esophageal resection for esophageal carcinoma.
* Patients with congenital or acquired bleeding diatheses.
* Patients with a history of esophageal squamous dysplasia.
* Patient has known carcinoma of the foregut (pancreatic, bile duct, ampullary, stomach, or duodenum) within 5 years prior to study enrollment.
* Patient has received chemotherapy class drugs or radiation to treat mediastinal or esophageal cancer.
