Prevalence of Dysplasia of the Gastric Cardia

• ClinicalTrials.gov Identifier: NCT01787864
• Recruitment Status: Completed
• First Posted: February 11, 2013
• Last Update Posted: May 16, 2017
• Sponsor: University of North Carolina, Chapel Hill
• Collaborator: CSA Medical, Inc.
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Study Description

Brief Summary:

We propose a tissue sample collection study for patients at UNC who have undergone or will undergo radiofrequency ablation therapy for Barrett's Esophagus (BE) or intramucosal adenocarcinoma as part of routine medical care.

Purpose:

To determine the prevalence of metaplasia and dysplasia in the gastric cardia before and after ablative therapy.

To determine the incidence of cardiac metaplasia and dysplasia as a function of ablative therapy.

To determine the correlation between dysplasia in the tubular esophagus, and dysplasia in the cardia.

To assess the ability of immunohistochemical (IHC) staining of cardia tissues to predict incident dysplasia in the cardia. Several well-characterized biomarkers, including p16, p53, Ki67, cyclin D1, and cyclin A, will be assessed.

Condition or disease
Barrett's Esophagus; Intestinal Metaplasia; Intramucosal Adenocarcinoma

Detailed Description:

This study will consist of a cross-sectional arm, as well as a prospective longitudinal arm, and will include patients who are undergoing ablative therapy at UNC. The cross-sectional arm will consist of patients who have undergone ablative therapy for Barrett's Esophagus (BE) and have had at least one clear pathology report with no evidence of Barrett's Esophagus (BE) since their first ablation. Concurrently enrolled will be a prospective longitudinal arm which will consist of patients prior to their first ablation procedure. The prospective cohort will be followed for 12 months or longer if Barrett's Esophagus (BE) is not yet clear 6 months after the initial treatment.

Sampling of the gastric cardia for clinical pathology has become common in patients who are receiving or have received ablation therapy based on evidence from previous research suggesting concern for dysplasia in the gastric cardia. In each group, research biopsies will be taken at the top of the gastric folds (TGF) as well as the gastric cardia (TGF+1cm) and distal esophagus (TGF-1).

Clinical biopsies will consist of standard esophageal biopsies from the distal esophagus as well as biopsies from TGF, TGF+1cm and TGF+2 cm. Clinical biopsy specimens will be fixed and reviewed by a pathologist to determine the presence of any metaplastic, dysplastic, or neoplastic changes, as per our usual clinical practice. Research specimens will undergo immunohistochemical (IHC) staining for a number of biomarkers that have been found to be positive in patients with dysplastic BE (p16, p53, Ki67, cyclin D1, and cyclin A). 1-4 Cross-sectional participants will receive one-time study biopsies. Prospective longitudinal participants will receive biopsies prior to ablation therapy and 6 and 12 months after the initial treatment. If Barrett's Esophagus (BE) is not yet clear at 6 months, biopsies will be taken at the first endoscopy after Barrett's Esophagus (BE) clearance and again at the next clinically scheduled follow-up visit.

Study Design

• Study Type: Observational
• Actual Enrollment: 170 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: Prevalence of Dysplasia of the Gastric Cardia
• Study Start Date: February 2013
• Actual Primary Completion Date: May 2017
• Actual Study Completion Date: May 2017

Groups and Cohorts

Group/Cohort
Cross-Sectional Post-Ablation; The cross-sectional arm will consist of patients who have undergone ablative therapy for Barrett's Esophagus (BE) and have had at least one clear pathology report with no evidence of Barrett's Esophagus (BE) since their first ablation. Cross-sectional participants will receive one-time study biopsies during a routine care follow-up endoscopy.
Prospective Longitudinal Pre-Ablation; Concurrently enrolled will be a prospective longitudinal arm which will consist of patients prior to their first ablation procedure. The prospective cohort will be followed for 12 months or longer if Barrett's Esophagus (BE) is not yet clear 6 months after the initial treatment. Prospective longitudinal participants will receive biopsies prior to ablation therapy and 6 and 12 months after the initial treatment. If Barrett's Esophagus (BE) is not yet clear at 6 months, biopsies will be taken at the first endoscopy after Barrett's Esophagus (BE) clearance and again at the next clinically scheduled follow-up visit.

Outcome Measures

Primary Outcome Measures :

1. Presence of dysplasia before and after ablation [ Time Frame: Enrollment and 6 and 12 months post treatment ]
   Simple proportions will be generated to describe the prevalence of cardiac dysplasia prior to endoscopic ablation. To compare the proportion of subjects demonstrating cardiac dysplasia who have had complete eradication of Barrett's Esophagus (BE) to the proportion of subjects demonstrating cardiac dysplasia who have not had complete eradication of Barrett's Esophagus (BE), due to the dichotomous nature of the variable, we will initially create 2x2 contingency tables and perform bivariate analysis using χ2, which will serve as our primary statistical analysis. Effects will be summarized as risk ratios. To analyze the operating characteristics of various biomarkers to predict cardiac dysplasia, sensitivity, specificity, positive predictive value and negative predictive value of each biomarker to predict the presence of dysplasia at 6 and 12 months will be calculated.

Biospecimen Retention:   Samples With DNA

Esophageal and gastric cardia biospies

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

This study will consist of a cross-sectional arm, as well as a prospective longitudinal arm, and will include patients who are undergoing ablative therapy at UNC. The cross-sectional arm will consist of patients who have undergone ablative therapy for Barrett's Esophagus (BE) and have had at least one clear pathology report with no evidence of BE since their first ablation. Concurrently enrolled will be a prospective longitudinal arm which will consist of patients prior to their first ablation procedure. The prospective cohort will be followed for 12 months after initial treatment or longer if BE is not yet clear 6 months after the initial treatment.

Criteria

Inclusion Criteria:

• English speaking males or females aged 18 to 80.

• Meet one of the following:

  1. Individuals who have undergone ablation therapy for dysplastic Barrett's Esophagus (BE) or intramucosal adenocarcinoma and have had at least one clear pathology report with no BE since their first ablation (cross-sectional) OR
  2. Individuals with dysplastic Barrett's Esophagus (BE) or intramucosal adenocarcinoma who will undergo ablation therapy at UNC for the first time (prospective longitudinal)
• Able to read, comprehend, and complete the informed consent form.

Exclusion Criteria:

• Bleeding disorder or other contraindication of endoscopic biopsy.
• Current use of blood thinners such as coumadin, warfarin, heparin and/or low molecular weight heparin (requires discontinuation of medication 5 days prior to and 6 days after Esophagogastroduodenoscopy (EGD)).
• History of partial or complete esophagectomy.
• Current diagnosis of invasive esophageal cancer.
• Prior ablation of the cardia.
• Patients who have received or will receive endoscopic mucosal resection (EMR) on the day of enrollment of the gastric cardia or distal esophagus, defined as the top of the gastric folds (TGF) +2 centimeters through the top of the gastric folds -1 centimeter (TGF+2 through TGF-1). Prior EMR and/or EMR on the day of enrollment of areas other than TGF+2 through TGF-1 are OK.
• Pregnant women.

Contacts and Locations

Locations

United States, North Carolina

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

University of North Carolina, Chapel Hill

CSA Medical, Inc.

Investigators

• Principal Investigator: Nicholas Shaheen, MD, MPH; UNC Chapel Hill

More Information

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT01787864
• Other Study ID Numbers: 12-0336
• First Posted: February 11, 2013
• Last Update Posted: May 16, 2017
• Last Verified: May 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No plans to share data

Keywords provided by University of North Carolina, Chapel Hill:

Barrett's Esophagus; Intestinal metaplasia; Intramucosal Adenocarcinoma; Gastric Cardia; High Cardia Dysplasia; Radiofrequency ablation (RFA)

Additional relevant MeSH terms:

Adenocarcinoma; Barrett Esophagus; Metaplasia; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Precancerous Conditions; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pathologic Processes