Neoplasms

All Conditions

Digestive System Diseases

Adenocarcinoma

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

Subjects will undergo standard of care (SOC) standard esophagogastroduodenoscopy (EGD) for the treatment of their condition (BE or IMC). Four (4) research biopsies will be taken from the midpoint of current disease. In cases where EMR (Endoscopic Mucosal Resection) is performed clinically, no research biopsies will be taken. Following CEIM, four (4) additional research biopsies will be collected, from the midpoint of previous BE site.

Laboratory Biomarker Analysis: Correlative studies

Esophagogastroduodenoscopy: Standard of care, research biopsies will be collected if clinical biopsies are taken

Four research biopsies collected at the midpoint of current BE or IMC at Baseline and after reaching CEIM. Biopsies will be used to calculate ML scores both pre and post EET.

Study Driven Procurement of Biopsies

Nicholas J Shaheen, MD

To evaluate association between mutational load (ML) from esophageal biopsy specimens in pre-endoscopic eradication therapy (EET) in Barrett's Esophagus (BE) or Intramucosal adenocarcinoma (IMC) patients and treatment resistance (treatment resistance will be defined as disease recurrence and/or need for additional intervention such as increased acid suppression, need for anti-reflux surgery, or use of alternate ablative modality).

Potential subjects will be identified via protocol and Institutional Review Board (IRB) methods prior to obtaining written informed consent. Once written informed consent is obtained, subjects will continue with planned routine care upper endoscopy. During the first study visit an upper endoscopy will be performed. At this visit, research specimens will be obtained for mutational load (ML) analysis and gastroenterologist (GI) pathologist diagnosis for the presence of adenocarcinoma or degrees of dysplasia. ML will be correlated to the pathology diagnosis on this research biopsy. Subjects will then undergo EET per routine standard of care at the treating institution until CEIM achieved. Subjects will be followed (data collection only) during treatment period until CEIM is achieved. After subjects reach CEIM, four additional research biopsies will be collected, from the midpoint of previous BE site.

Subjects will undergo a standard of care (SOC) esophagogastroduodenoscopy (EGD). At this visit, research biopsies will be obtained - 4 research biopsies at the midpoint of current Barrett's Esophagus (BE) OR slides will be cut from clinical Endoscopic Mucosal Resection (EMR). Slides will be analyzed for mutational load (ML) analysis and gastroenterologist (GI) pathologist diagnosis for the presence of adenocarcinoma or degrees of dysplasia. ML will be correlated to the pathology diagnosis on this research biopsy. Subjects will then undergo (Endoscopic Eradication Therapy) EET per routine standard of care at the treating institution until Complete Eradication of Intestinal Metaplasia (CEIM) is achieved. Subjects will be followed (data collection only) during treatment period until CEIM is achieved. After subjects reach CEIM, four additional research biopsies will be collected, from the midpoint of previous BE site.

Utility Of Mutational Load As A Predictor For Endoscopic Treatment Response In Barrett's Esophagus

Treatment resistance will be assessed as a dichotomous variable and defined as those with one or more of the following features: disease recurrence, need for increased acid suppression, need for anti-reflux surgery, or use of alternate ablative modality. The association between pre-EET ML and treatment resistance will be calculated using the difference between the two mean ML values.

The worst pathologic diagnosis at baseline will be recorded and ML between the three dysplasia groups (low grade dysplasia, high grade dysplasia, and esophageal adenocarcinoma) will be compared.

ML calculation will be compared to number of sessions required to achieve CEIM.

ML calculation will be compared to stricture rates.

Interpace Diagnostics Corporation

University of North Carolina, Chapel Hill

Symptoms and General Pathology

Metaplasia

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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.

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.

Nicholas Shaheen, MD, MPH

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.

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.

Prevalence of Dysplasia of the Gastric Cardia

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.

CSA Medical, Inc.

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Esophageal Cancer

Patients who have never received ablative therapy for Barrett's Esophagus and are receiving routine care surveillance upper endoscopy for their condition. Subjects will have esophageal biopsies, blood, and data collected for this study.

Patients who are receiving routine care upper endoscopy with ablative therapy for their Barrett's Esophagus for the first time. Subjects will have esophageal biopsies, blood, and data collected for this study.

Patients with a history of Barrett's Esophagus who are status post ablation and are receiving routine care follow-up EGD for their condition. Subjects will have esophageal biopsies, blood, and data collected for this study.

Patients with esophageal cancer who are receiving routine care upper endoscopy for their condition. Subjects will have esophageal biopsies, blood, and data collected for this study.

Patients with squamous cell cancer of the esophagus who are receiving routine care upper endoscopy for their condition. Subjects will have esophageal biopsies, blood, and data collected for this study.

* 1 10mL red tube and 1 8.5mL yellow tube for serum, plasma, and buffy collection
* Up to 10 research-specific biopsies obtained from the esophagus during the routine care EGD.
* Four biopsies will be taken from the midpoint of the current BE (or midpoint of previous BE if the patient has already received ablation for previous BE),
* Two biopsies from normal squamous epithelium, and
* One biopsy from each area of esophageal nodularity seen during the procedure
* Pathology slides from routine care biopsies taken during the enrollment procedure, as well as retrospective pathology slides from routine care biopsies taken prior to enrollment on the study.
* Up to 4 cytology brushes during the procedure.

Specimen Collection

Aim 1: To develop a prospective tissue and blood biorepository from patients with a history of Barrett's Esophagus (BE) or esophageal cancer (ECA) presenting to UNC hospitals for routine care upper endoscopy for their condition.

Aim 2: To collect clinical data from patients with a history of Barrett's Esophagus (BE) or esophageal cancer (ECA) that includes demographic data, endoscopic procedure data, and pathology data.

Aim 3: To integrate Aim 1 and 2 in a manner that will provide an efficient bi-directional flow of clinical information and specimens between laboratory and clinical scientists in order to foster innovative translational research.

Aim 4: To create a biorepository for future Institutional Review Board (IRB) approved studies that have tissue and/or blood specimen component.

Patients will be identified during GI clinic visits or procedure visits with Dr. Nicholas Shaheen or his colleagues at UNC. Patients may also be identified by research personnel during review of the endoscopy schedule and medical records. If eligible, interested participants will be provided with a consent form during their clinic or procedure visit. Enrolled subjects will be assigned a unique identification (ID) number for data collection.

Patients will be recruited by Dr. Nicholas Shaheen and his colleagues or by other study personnel prior to their routine care endoscopy at UNC. An investigator, study coordinator, or other personnel trained in the protocol and referenced in the IRB application will obtain consent during the patient's visit in the GI clinic or prior to an upper endoscopy. Potential subjects will have an opportunity to carefully review the consent form, the details of the study will be reviewed verbally, and all questions will be answered to the satisfaction of the patient. Only English-speaking adults with the ability to consent will be eligible for enrollment in this study. After the subject signs the consent, a copy of the signed consent will be provided to the subject and the coordinator will collect demographic and historical information from the patient pertaining to illnesses, medication and other relevant information. The consent process will be documented in the subject's research file.

After obtaining informed consent, blood will be obtained and subjects will proceed with their routine care upper endoscopy. The endoscopist, as per routine practice, will note findings in the procedure report and photograph or record video to confirm and document key findings, as well as take biopsies as indicated for routine care. During the procedure up to 10 research biopsies will be collected as part of this study. Research biopsies will be collected in addition to routine care biopsies and will be obtained with a standardized biopsy protocol (below). The total number of research biopsies may vary based on presence/absence of nodularity but will not exceed 10 research-specific biopsies. This number of esophageal biopsies is within the standard of care for biopsying the esophagus.

Biopsies for clinical care are taken prior to any consideration of research biopsies. Research biopsies are taken only if the additional biopsies do not significantly increase the patient's risk or interfere with routine care procedures. The research biopsy protocol may be modified by the physician performing the procedure if necessary.

In addition to research blood and biopsies, up to 4 cytology brushings for research purposes may also be obtained during the procedure.

Specimens collected for this research study will include:

* 1 10mL red tube and 1 8.5mL yellow tube for serum, plasma, and buffy collection
* Up to 10 research-specific biopsies obtained from the esophagus during the routine care esophagogastroduodenoscopy (EGD).

  * Four biopsies will be taken from the midpoint of the current Barrett's Esophagus (BE) (or midpoint of previous Barrett's Esophagus (BE) if the patient has already received ablation for previous Barrett's Esophagus (BE)),
  * Two biopsies from normal squamous epithelium, and
  * One biopsy from each area of esophageal nodularity seen during the procedure
* Pathology slides from routine care biopsies taken during the procedure as well as retrospective pathology slides from routine care biopsies taken prior to enrollment on the study.
* Up to 4 cytology brushes during the procedure

Biopsies will be immediately frozen on liquid nitrogen then transferred to the -80 biorepository freezer for long term storage. Blood will be immediately processed and transferred to the -80 biorepository freezer for long-term storage.

The translational pathology lab (TPL) maintains formalin fixed paraffin embedded (FFPE) blocks from biopsies taken for routine care. Slides will be cut from these blocks for this study. Slide requests for this research study will not exhaust the archived tissue and will leave a substantial amount of the formalin fixed paraffin embedded (FFPE) block for potential future clinical use.

If subjects return for additional esophagogastroduodenoscopies (EGDs) as part of routine care, then all study procedures will be repeated as part of this registry as detailed below.

For subjects receiving routine care surveillance esophagogastroduodenoscopy (EGD) for current or previous Barrett's Esophagus (BE) or current or previous esophageal cancer (ECA): Specimens and data will be collected at each routine care surveillance EGD as part of this study.

For subjects receiving routine care treatment EGD for current BE/ECA: Specimens and data will be collected at the initial treatment EGD, but not during subsequent treatment EGDs. Once treatment is complete and BE or ECA is clear, this group will begin surveillance EGDs as part of routine care for their condition. Specimens and data will be collected during subsequent follow-up surveillance EGDs after treatment is complete.

* 1 10mL red tube and 1 8.5mL yellow tube for serum, plasma, and buffy collection
* Up to 10 research-specific biopsies (tissue samples) obtained from the esophagus during the routine care EGD.
* Pathology slides from routine care biopsies taken during the procedure as well as retrospective pathology slides from routine care biopsies taken prior to enrollment on the study.
* Up to 4 cytology brushes during the procedure

University of North Carolina (UNC) Barrett's Esophagus and Esophageal Cancer Biorepository

UNC Barrett's Esophagus and Esophageal Cancer Biorepository

To develop a prospective tissue and blood biorepository from patients with a history of Barrett's Esophagus (BE) or esophageal cancer (ECA) presenting to UNC hospitals for routine care upper endoscopy for their condition.

To create a biorepository for future IRB approved studies that have a tissue and/or blood specimen component.

To collect clinical data from patients with a history of Barrett's Esophagus (BE) or esophageal cancer (ECA) that includes demographic data, endoscopic procedure data, and pathology data.

integrate Aim 1 and 2 in a manner that will provide an efficient bi-directional flow of clinical information and specimens between laboratory and clinical scientists in order to foster innovative translational research.

Jacques Bergman, MD

Barrett's esophagus (BE) is a pre-neoplastic condition formed by the metaplasia of the normal squamous mucosa of the distal esophagus into a specialized intestinal mucosa. Its development is mostly associated with chronic injury from gastroesophageal reflux. BE is widely considered the leading risk factor for the development of esophageal adenocarcinoma (EAC).

Volumetric laser endomicroscopy (VLE) can be thought of as an analogous technique to ultrasound, however, instead of producing an image from the scattering of sound waves, it utilizes optical scattering based on differences in tissue composition to form a two-dimensional image. The benefit of VLE over ultrasound is that it is capable of generating cross-sectional images of tissues with an axial-resolution of up to 10 micrometers, which is comparable to low-power microscopy.

The proposed trial will evaluate the ability of physicians to use VLE to visualize high grade intraepithelial neoplasia (HGIN) or intramucosal adenocarcinoma (IMC) in both the ex-vivo and in-vivo setting and correlate those images to standard histology of endoscopic mucosal resection specimens as the gold standard.

The diagnosis of dysplasia and early adenocarcinoma in BE remains challenging. At present, endoscopy with biopsy of suspected BE lesions is the only available method. However, the endoscopic recognition of early dysplasia in BE relies on the subjective visual recognition by an endoscopist. The subtle mucosal variations and early dysplastic changes in the esophagus may easily be missed. The development of a wide-field, high resolution endoscopic microscopy could enhance the early detection and treatment of dysplasia in BE.

Endoscopic Mucosal Resection (EMR). With this technique, the mucosa is resected by injecting a liquid in the submucosal space, after which the thus created pseudopolyp can be resected using a snare and electrocoagulation. The histological processing of the ex-vivo EMR specimen will be carried out according to hospital standards

A Comparison of Volumetric Laser Endomicroscopy (VLE) and Endoscopic Mucosal Resection (EMR) in Patients With Barrett's Dysplasia or Intramucosal Adenocarcinoma

All VLE images will be evaluated by two independent reviewers (not the trial endoscopist performing the scan), who are blinded to the histological finding of the corresponding EMR specimen. A predefined classification scheme will be used for VLE assessment.

All VLE images will be evaluated by two independent reviewers (not the trial endoscopist performing the scan), who are blinded to the histological finding of the corresponding EMR specimen.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Utility Of Mutational Load As A Predictor For Endoscopic Treatment Response In Barrett's Esophagus	NCT04316975	Barretts Esopha... Intramucosal Ad...	Study Driven Pr...	18 Years -	University of North Carolina, Chapel Hill
Utility Of Mutational Load As A Predictor For Endoscopic Treatment Response In Barrett's Esophagus	NCT04316975	Barretts Esopha... Intramucosal Ad...	Study Driven Pr...	18 Years -	University of North Carolina, Chapel Hill
Prevalence of Dysplasia of the Gastric Cardia	NCT01787864	Barrett's Esoph... Intestinal Meta... Intramucosal Ad...		18 Years - 80 Years	University of North Carolina, Chapel Hill
Utility Of Mutational Load As A Predictor For Endoscopic Treatment Response In Barrett's Esophagus	NCT04316975	Barretts Esopha... Intramucosal Ad...	Study Driven Pr...	18 Years -	University of North Carolina, Chapel Hill
University of North Carolina (UNC) Barrett's Esophagus and Esophageal Cancer Biorepository	NCT02427269	Barrett's Esoph... Esophageal Canc... Intramucosal Ad...	Specimen Collec...	18 Years -	University of North Carolina, Chapel Hill
University of North Carolina (UNC) Barrett's Esophagus and Esophageal Cancer Biorepository	NCT02427269	Barrett's Esoph... Esophageal Canc... Intramucosal Ad...	Specimen Collec...	18 Years -	University of North Carolina, Chapel Hill
A Comparison of Volumetric Laser Endomicroscopy (VLE) and Endoscopic Mucosal Resection (EMR) in Patients With Barrett's Dysplasia or Intramucosal Adenocarcinoma	NCT01862666	Barrett'S-assoc... Intramucosal Ad...		18 Years -	NinePoint Medical

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