Digestive System Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Ear, Nose, and Throat Diseases

Gastroesophageal Reflux

Barrett Esophagus

Metaplasia

Esophageal Motility Disorders

Esophageal Spasm, Diffuse

Deglutition Disorders

Esophageal Diseases

Gastrointestinal Diseases

Precancerous Conditions

Participants in this group are greater than or equal to 12 months status post radiofrequency ablation (RFA).

Participants in this group are part of a longitudinal portion of the study and are enrolled prior to their first radiofrequency ablation procedure and followed at 6 and 12 months after completion of RFA.

Participants in this group have been diagnosed with gastroesophageal reflux disease.

Participants in this group are asymptomatic controls and enrolled as part of the comparison group.

Nicholas Shaheen, MD, MPH

The investigators propose a study comparing the morphological and functional aspects of the neosquamous epithelium (NSE) after ablative therapy for dysplastic Barrett's esophagus (BE) to that of native squamous epithelium in normal controls as well as gastroesophageal reflux disease (GERD), non-Barrett's Esophagus (BE) subjects.

Purpose: We propose a study comparing the morphological and functional aspects of the neosquamous epithelium (NSE) after ablative therapy for dysplastic Barrett's esophagus (BE) to that of native squamous epithelium in normal controls as well as gastroesophageal reflux disease (GERD), non-BE subjects.

Participants: Eligible subjects will be women and men between the ages of 18-80, with one of the following:

1. Two or greater cm of dysplastic BE, who will undergo or have undergone radiofrequency ablation for BE at UNC, or
2. Diagnosed with GERD per a gastrointestinal (GI) physician undergoing upper endoscopy for other indications at UNC, or
3. Non-GERD controls per a GI physician with normal esophageal mucosa undergoing upper endoscopy for other indications at UNC.

Procedures (methods): Esophageal biopsies will be obtained specifically for research purposes before ablation therapy or, in subjects not receiving ablative therapy, after completion of the clinically indicated procedure and before withdrawal of the endoscope. Information from the medical record or from patient interview will be obtained regarding diagnosis (Barrett's esophagus, GERD, etc), and a questionnaire administered regarding the duration and frequency of reflux symptoms and complications of reflux disease. Subjects who are enrolled in the pre-ablation group will have additional biopsies and questionnaires administered during scheduled follow-up visits. On the last follow-up visit, this group will also undergo impedance-pH testing using standard methods, to assess for degree of control of esophageal acid exposure, and for number, duration and symptom correlation of non-acid reflux events.

Is the Neosquamous Epithelium "Normal" Following Endoscopic Ablation of Dysplastic Barrett's Esophagus?

To characterize reflux symptomatology before and after radiofrequency ablation in subjects with dysplastic BE. We will compare before and after gastroesophageal reflux disease (GERD) symptom assessment scale (GSAS) symptom scores using paired Student's t tests. As an exploratory analysis, we will further stratify the data by PPI use (once- vs. twice-daily.

To characterize the physiological and morphological properties of the NSE, compared to native esophageal squamous epithelium in healthy controls and subjects with non-Barrett's Esophagus (BE) gastroesophageal reflux disease (GERD). We will compare the physiologic measures of NSE (intercellular space, total electrical resistance (RT), and fluorescein flux) to positive and negative controls using χ2 and Student's t tests.

We will initially plot esophageal acid exposure (total time with esophageal pH\<4) against intercellular space, total electrical resistance (RT), fluorescein flux and gastroesophageal reflux disease (GERD) sysmptom assessment scale (GSAS) scores. R values will be generated. Regression models using each of the 3 physiologic measures (RT, fluorescein, and intercellular space) as the response variable, and acid exposure and number of non-acid reflux events as predictor variables will be generated to define the relationship between reflux type and findings.

American Society for Gastrointestinal Endoscopy

University of North Carolina, Chapel Hill

Professor of Medicine and Epidemiology Director, Center for Esophageal Diseases and Swallowing

Participants who self-identify as "not-Hispanic or Latino" and "White" and have been diagnosed by a physician with gastroesophageal reflux disease and do not have Barrett's esophagus.

Participants who self-identify as "not-Hispanic or Latino" and "African American" and have been diagnosed by a physician with gastroesophageal reflux disease and do no have Barrett's esophagus.

Participants who self-identify as "not-Hispanic or Latino" and "White" and have been diagnosed by a physician with Barrett's Esophagus.

Participants who self-identify as "not-Hispanic or Latino" and "African American" and have been diagnosed by a physician with Barrett's Esophagus.

Xiaoxin Chen, MD, PhD

The goal of the proposed research is to investigate the molecular mechanisms of racial disparity in Barrett's esophagus (BE), the premalignant lesion of esophageal adenocarcinoma. Specifically, the investigators hypothesize that environmental factors, genetic factors, and potentially gene environment interactions play crucial roles in the observed racial disparity in developing Barrett's esophagus.

Patients are recruited through UNC hospitals prior to scheduled esophagogastroduodenoscopy (EGD). Participants complete a questionnaire, have body measurements obtained, and have blood, biopsies, and gastric aspirate collected. Participants also complete a 24 hour pH impedance test.

The goal of the proposed research is to investigate the molecular mechanisms of racial disparity in Barrett's esophagus, the premalignant lesion of esophageal adenocarcinoma. Specifically, the investigators hypothesize that environmental factors, genetic factors, and potentially gene environment interactions play crucial roles in the observed racial disparity in developing Barrett's esophagus.

Participants: Patients aged 18-80 presenting at the Gastrointestinal (Gl) Endoscopy Clinic at UNC-Chapel Hill for elective upper endoscopy with a primary or secondary indication of reflux symptoms.

Procedures (methods): Endoscopic biopsy, pH impedance and sampling of gastric secretions will be performed according to our standard protocol. A series of questionnaires assessing demographics, environmental exposure (e.g., smoking, drinking), markers of socioeconomic status (SES), body measurement, previous health history, and gastroesophageal reflux disease (GERD) symptomatology will be administered to our subjects.

serum, plasma, buffy, esophageal biopsies

Racial Disparity in Barrett's Esophagus

Odds ratios (ORs) and 95% confidence intervals (CI) will be used to estimate the association between gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) among Caucasian Americans and African Americans, separately, in relation to patterns of the exposures of interest (tobacco use, alcohol consumption, fruit and vegetable intake and other dietary measures, no NSAID use, and various measures of SES), with adjustments made for the frequency matching factors, age at reference (date of diagnosis for cases and date of identification for controls) and sex.

The promoter regions of Cdxl and Cdx2 genes will be examined for single nucleotide polymorphisms (SNPs). Pyrosequencing will be used to quantitatively determine the methylation status of Cdxl and Cdx2 promoters in esophageal biopsy tissues. For the single functional genotype analyses, conventional unconditional logistic regression will be used and ORs will be estimated for "at-risk" homozygotes and heterozygotes relative to "wild-type" homozygotes by creating indicator variables for each genotype.

National Cancer Institute (NCI)

Rare Diseases

Esophageal Neoplasms

Disease Progression

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Esophageal Cancer

Marcia Canto, M.D.

The purpose of this study is to determine if there are any early changes in DNA markers of blood and esophageal tissue in people with gastric reflux, Barrett's esophagus or esophageal cancer that can warn of a progression to esophageal cancer.

Patients with Barrett's esophagus (BE) have an increased risk of esophageal adenocarcinoma which is 40-125 fold higher than in the general population. However, the current techniques of detecting dysplasia and observing abnormal p53 immunohistochemical staining are not accurate or reliable methods for determining which BE patients will progress to cancer. DNA hypermethylation is an epigenetic process that occurs in the promoter region of certain genes, resulting in suppression of gene expression. Inactivation of specific genes via hypermethylation has been highly associated with cancer.

The primary objective of this research is to determine whether DNA hypermethylation is a biomarker that will predict which patients with BE are likely to progress to adenocarcinoma. Patients with BE and/or esophageal adenocarcinoma who undergo endoscopy at the Johns Hopkins Hospital will comprise the cohort of subjects. Gene hypermethylation will be assessed by performing methylation-specific Polymerase Chain Reaction (PCR) on a panel of 8 cancer-related genes.

Specific Aim 1: To compare the prevalence of gene hypermethylation in BE patients with different grades of dysplasia and/or adenocarcinoma, using archived specimens.

Specific Aim 2: To determine whether the presence of gene hypermethylation in initial biopsies of BE patients is associated with progression to adenocarcinoma, using archived specimens. To compare gene hypermethylation with currently available markers for neoplastic progression.

Specific Aim 3: To determine whether methylated DNA from BE and/or adenocarcinoma can be detected in the peripheral blood of patients, by comparing methylation profiles of esophageal biopsy specimens with peripheral blood samples taken at the same time in prospectively enrolled patients.

If hypermethylation of one or more genes is detected at an early stage in BE patients who later progress to adenocarcinoma, hypermethylation could be used as an early predictor for adenocarcinoma even before pathologic changes are evident. Furthermore, this research will help determine the specific genetic events that occur in the neoplastic transformation from BE to adenocarcinoma.

The long-term goal of this project is to determine whether hypermethylation can identify BE patients who are at high risk for neoplastic progression, thus allowing for early intervention in the form of more frequent endoscopic surveillance, chemoprevention, ablative therapy, or surgery.

approx. 24 ml blood, 1-8 esophageal mucosal pinch specimens and or esophageal brushings

Novel Biomarkers in the Neoplastic Progression of Barrett's Esophagus

Novel Biomarkers in the Neoplastic Progression of Barrett's Esophagus (Previously: Methylation in Cancer Progression of Barrett's Esophagus

To see if changes in certain areas of DNA can predict risk for esophageal cancer

Study title	NCT ID	Conditions	Eligibility	Organization
Is the Neosquamous Epithelium "Normal" Following Endoscopic Ablation of Dysplastic Barrett's Esophagus?	NCT01373125	Barrett's Esoph... Intestinal Meta... Gastroesophagea...	18 Years - 80 Years	University of North Carolina, Chapel Hill
Racial Disparity in Barrett's Esophagus	NCT01374074	Barrett's Esoph... Gastroesophagea... Intestinal Meta...	18 Years - 80 Years	University of North Carolina, Chapel Hill
Is the Neosquamous Epithelium "Normal" Following Endoscopic Ablation of Dysplastic Barrett's Esophagus?	NCT01373125	Barrett's Esoph... Intestinal Meta... Gastroesophagea...	18 Years - 80 Years	University of North Carolina, Chapel Hill
Novel Biomarkers in the Neoplastic Progression of Barrett's Esophagus	NCT00431756	Barrett Esophag... Esophageal Neop... Gastroesophagea...	18 Years - 95 Years	Johns Hopkins University

Spots Global Cancer Trial Database for gastroesophageal reflux disease (gerd)