Advanced endoscopic imaging in Barrett's esophagus
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Barrett's esophagus
Objective:To investigate the expression of BMP4 in Barrett’s esophagus and Esophageal adenocarcinoma.Methods: Immunohistochemistry was used to detect the expression of BMP4 in 20 cases of Barrett’s esophagus without dysplasia,20 cases of Barrett’s esophagus with low-grade dysplasia,20 cases of Barrett’s esophagus with high-grade dysplasia and 25 cases of Esophageal adenocarcinoma.Results:The positive rates of BMP4 expression in the four groups were 15 %,30%,75%,and 76%,respectively.The expression of BMP4 was slightly higher in Esophageal adenocarcinoma and Barrett’s esophagus with high-grade dysplasia than that in Barrett’s esophagus without dysplasia and Barrett’s esophagus with low-grade dysplasia(P0.05).Conclusion:BMP4 may play an im-portant role in the formation of Esophageal adenocarcinoma.
Barrett's esophagus
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Barrett's esophagus is the only known esophageal precursor for the development of esophageal adenocarcinoma. However, screening for Barrett's esophagus remains controversial. Although screening is advocated in selected populations, it is unclear how it should be implemented. In this review, the current definition of Barrett's esophagus will be discussed. There will be a review of the emerging evidence supporting the cost-effectiveness of screening and surveillance for Barrett's esophagus in preventing esophageal adenocarcinoma. The known risk factors for Barrett's esophagus and the development of esophageal adenocarcinoma, currently utilized to determine the appropriate populations to screen, will be reviewed. Finally we will review the standard techniques utilized to screen for Barrett's esophagus and examine new technologies that might improve the efficacy and availability of Barrett's esophagus screening.
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Confocal laser endomicroscopy (CLE) can provide real-time, microscopic visualization of the gastrointestinal mucosa, allowing an endoscopic approach to the histologic evaluation of Barrett's esophagus and Barrett's esophagus-associated neoplasia.Both endoscope-based (eCLE) and probe-based (pCLE) CLE systems have been used to evaluate Barrett's esophagus and Barrett's esophagus-associated neoplasia. Criteria for distinguishing Barrett's esophagus with neoplasia from nondysplastic Barrett's esophagus have been developed and validated for both eCLE and pCLE. Several studies have shown excellent detection of Barrett's esophagus neoplasia by CLE, and the technique may be used to guide endoscopic therapy. Advanced endomicroscopy systems and peptides and antibodies that target neoplasia are in development.CLE has provided a new way of evaluating Barrett's esophagus and Barrett's esophagus-associated neoplasia and is being used to improve detection and management of neoplasia in Barrett's esophagus.
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Barrett's esophagus can progress to dysplasia and adenocarcinoma. Although the incidence of adenocarcinoma of the gastroesophageal junction has increased suddenly in the United States and Europe, we do not know how much of this increase is related to Barrett's esophagus. Interest in mucosal cell abnormalities at the gastroesophageal junction has led researchers to re-examine short-segment Barrett's esophagus. In this recently described condition, specialized columnar epithelium is found in the distal 2 to 3 cm of the esophagus, yet it is not clear how it relates to conventional long-segment Barrett's esophagus, in which the metaplastic epithelium extends higher than 2 to 3 cm above the squamocolumnar junction. The reported prevalence of short-segment Barrett's esophagus found on diagnostic endoscopy varies from 8% to 32%. This wide variation would be lessened by standardized location of biopsy specimens and of endoscopic and histologic staining techniques. Based on the information available, it is apparent that the age range and sex ratios are similar. Although reflux symptoms may be more common in short-segment Barrett's esophagus, disturbances in esophageal motility are less severe and there is less reflux as measured by continuous pH monitoring. Furthermore, recognized complications of Barrett's esophagus, such as ulceration, stricture, high-grade dysplasia, and adenocarcinoma, appear to be uncommon in short-segment Barrett's esophagus.
Barrett's esophagus
Esophageal disease
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Barrett's esophagus
Esophageal disease
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Barrett's esophagus
Esophageal adenocarcinoma
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There is an unmet need for identifying novel biomarkers in Barrett's esophagus that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in Barrett's esophagus and Barrett's esophagus-related neoplasia, and assess their value as biomarkers for the diagnosis of Barrett's esophagus-related neoplasia and to predict neoplastic progression. Gene-expression analyses of ECM matrisome gene sets were performed using publicly available data on human Barrett's esophagus, Barrett's esophagus-related dysplasia, esophageal adenocarcinoma (ADCA) and normal esophagus. Immunohistochemical expression of basement membrane (BM) marker agrin (AGRN) and p53 was analyzed in biopsies of Barrett's esophagus-related neoplasia from 321 patients in three independent cohorts. Differential gene-expression analysis revealed significant enrichment of ECM matrisome gene sets in dysplastic Barrett's esophagus and ADCA compared with controls. Loss of BM AGRN expression was observed in both Barrett's esophagus-related dysplasia and ADCA. The mean AGRN loss in Barrett's esophagus glands was significantly higher in Barrett's esophagus-related dysplasia and ADCA compared with non-dysplastic Barrett's esophagus (NDBE; P < 0.001; specificity = 82.2% and sensitivity = 96.4%). Loss of AGRN was significantly higher in NDBE samples from progressors compared with non-progressors (P < 0.001) and identified patients who progressed to advanced neoplasia with a specificity of 80.2% and sensitivity of 54.8%. Moreover, the combination of AGRN loss and abnormal p53 staining identified progression to Barrett's esophagus-related advanced neoplasia with a specificity and sensitivity of 86.5% and 58.7%. We highlight ECM changes during Barrett's esophagus progression to neoplasia. BM AGRN loss is a novel diagnostic biomarker that can identify patients with NDBE at increased risk of developing advanced neoplasia.
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Esophageal disease
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The microbiome has been increasingly associated with different disease processes, but its role in esophagus is largely unknown. Our goal was to determine the associations of the esophageal microbiota with Barrett's esophagus.A total of 74 patients were included in this prospective study, including 34 patients with Barrett's esophagus and 40 patients without Barrett's esophagus. Esophageal swabs were obtained from the uvula, and mucosal biopsies were obtained from the proximal esophagus and distal esophagus in each patient. The microbiome of each sample was assessed using a customized Esophageal Microbiome qPCR array (EMB). For each clinical sample, we completed a detection/non-detection analysis for each organism in the EMB. The limit of detection (LOD) for each target was established by analysis of plasmid dilutions.Average age was 60.2 years. There were significantly different microbial detection patterns in patients with Barrett's esophagus compared to the control population. There were a greater number of organisms which had different likelihoods of detection in the distal esophagus, compared to the proximal esophagus or uvula. In addition, as the length of the Barrett's column increased, multiple organisms were less likely to be detected. This decreased likelihood occurred only in the distal esophagus. Beside Barrett's esophagus, no other demographic factors were associated with differences in detection patterns.Microbial community structures differ between patients with and without Barrett's esophagus. Certain organisms are less likely to be detected as the severity of Barrett's esophagus worsens. These results suggest that particular organisms may have a protective effect against the development of Barrett's esophagus.
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<div>AbstractPurpose:<p>There is an unmet need for identifying novel biomarkers in Barrett's esophagus that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in Barrett's esophagus and Barrett's esophagus–related neoplasia, and assess their value as biomarkers for the diagnosis of Barrett's esophagus–related neoplasia and to predict neoplastic progression.</p>Experimental Design:<p>Gene-expression analyses of ECM matrisome gene sets were performed using publicly available data on human Barrett's esophagus, Barrett's esophagus–related dysplasia, esophageal adenocarcinoma (ADCA) and normal esophagus. Immunohistochemical expression of basement membrane (BM) marker agrin (AGRN) and p53 was analyzed in biopsies of Barrett's esophagus–related neoplasia from 321 patients in three independent cohorts.</p>Results:<p>Differential gene-expression analysis revealed significant enrichment of ECM matrisome gene sets in dysplastic Barrett's esophagus and ADCA compared with controls. Loss of BM AGRN expression was observed in both Barrett's esophagus–related dysplasia and ADCA. The mean AGRN loss in Barrett's esophagus glands was significantly higher in Barrett's esophagus–related dysplasia and ADCA compared with non-dysplastic Barrett's esophagus (NDBE; <i>P</i> < 0.001; specificity = 82.2% and sensitivity = 96.4%). Loss of AGRN was significantly higher in NDBE samples from progressors compared with non-progressors (<i>P</i> < 0.001) and identified patients who progressed to advanced neoplasia with a specificity of 80.2% and sensitivity of 54.8%. Moreover, the combination of AGRN loss and abnormal p53 staining identified progression to Barrett's esophagus–related advanced neoplasia with a specificity and sensitivity of 86.5% and 58.7%.</p>Conclusions:<p>We highlight ECM changes during Barrett's esophagus progression to neoplasia. BM AGRN loss is a novel diagnostic biomarker that can identify patients with NDBE at increased risk of developing advanced neoplasia.</p></div>
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<div>AbstractPurpose:<p>There is an unmet need for identifying novel biomarkers in Barrett's esophagus that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in Barrett's esophagus and Barrett's esophagus–related neoplasia, and assess their value as biomarkers for the diagnosis of Barrett's esophagus–related neoplasia and to predict neoplastic progression.</p>Experimental Design:<p>Gene-expression analyses of ECM matrisome gene sets were performed using publicly available data on human Barrett's esophagus, Barrett's esophagus–related dysplasia, esophageal adenocarcinoma (ADCA) and normal esophagus. Immunohistochemical expression of basement membrane (BM) marker agrin (AGRN) and p53 was analyzed in biopsies of Barrett's esophagus–related neoplasia from 321 patients in three independent cohorts.</p>Results:<p>Differential gene-expression analysis revealed significant enrichment of ECM matrisome gene sets in dysplastic Barrett's esophagus and ADCA compared with controls. Loss of BM AGRN expression was observed in both Barrett's esophagus–related dysplasia and ADCA. The mean AGRN loss in Barrett's esophagus glands was significantly higher in Barrett's esophagus–related dysplasia and ADCA compared with non-dysplastic Barrett's esophagus (NDBE; <i>P</i> < 0.001; specificity = 82.2% and sensitivity = 96.4%). Loss of AGRN was significantly higher in NDBE samples from progressors compared with non-progressors (<i>P</i> < 0.001) and identified patients who progressed to advanced neoplasia with a specificity of 80.2% and sensitivity of 54.8%. Moreover, the combination of AGRN loss and abnormal p53 staining identified progression to Barrett's esophagus–related advanced neoplasia with a specificity and sensitivity of 86.5% and 58.7%.</p>Conclusions:<p>We highlight ECM changes during Barrett's esophagus progression to neoplasia. BM AGRN loss is a novel diagnostic biomarker that can identify patients with NDBE at increased risk of developing advanced neoplasia.</p></div>
Barrett's esophagus
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