Progression Of Barrett's Esophagus Research Articles

GRAIL1 Stabilizes Misfolded Mutant p53 through a Ubiquitin Ligase-Independent, Chaperone Regulatory Function.

Frequent (>70%) TP53 mutations often promote its protein stabilization, driving esophageal adenocarcinoma (EAC) development linked to poor survival and therapy resistance. We previously reported that during Barrett's esophagus progression to EAC, an isoform switch occurs in the E3 ubiquitin ligase RNF128 (aka GRAIL-gene related to anergy in lymphocytes), enriching isoform 1 (hereby GRAIL1) and stabilizing the mutant p53 protein. Consequently, GRAIL1 knockdown degrades mutant p53. But, how GRAIL1 stabilizes the mutant p53 protein remains unclear. In search for a mechanism, here, we performed biochemical and cell biology studies to identify that GRAIL has a binding domain (315-PMCKCDILKA-325) for heat shock protein 40/DNAJ. This interaction can influence DNAJ chaperone activity to modulate misfolded mutant p53 stability. As predicted, either the overexpression of a GRAIL fragment (Frag-J) encompassing the DNAJ binding domain or a cell-permeable peptide (Pep-J) encoding the above 10 amino acids can bind and inhibit DNAJ-Hsp70 co-chaperone activity, thus degrading misfolded mutant p53. Consequently, either Frag-J or Pep-J can reduce the survival of mutant p53 containing dysplastic Barrett's esophagus and EAC cells and inhibit the growth of patient-derived organoids of dysplastic Barrett's esophagus in 3D cultures. The misfolded mutant p53 targeting and growth inhibitory effects of Pep-J are comparable with simvastatin, a cholesterol-lowering drug that can degrade misfolded mutant p53 also via inhibiting DNAJA1, although by a distinct mechanism. Implications: We identified a novel ubiquitin ligase-independent, chaperone-regulating domain in GRAIL and further synthesized a first-in-class novel misfolded mutant p53 degrading peptide having future translational potential.

Categorizing Risks within Barrett's Esophagus To Guide Surveillance and Interception; Suggesting a New Framework.

Barrett's esophagus is a precancerous condition that can progress in a stepwise manner to dysplasia and eventually esophageal adenocarcinoma (EAC). Once diagnosed, patients with Barrett's esophagus are kept on surveillance to detect progression so that timely intervention can occur with endoscopic therapy. Several demographic and clinical risk factors are known to increase progression toward EAC, such as longer Barrett's segments, and these patients are kept on tighter surveillance. While p53 IHC has been advocated as an adjunct to histopathologic diagnosis, use of this biomarker is variable, and no other molecular factors are currently applied. Given the new evidence available, it is time to consider whether other risk factors or tools could be applied in clinical practice to decide on closer or attenuated surveillance. In this commentary, we summarize the most relevant risk factors for Barrett's esophagus progression, highlight the most promising novel risk stratification tools-including nonendoscopic triage and commercial biomarker panels, and propose a new framework suggesting how to incorporate risk stratification into clinical practice.

Agrin Loss in Barrett's Esophagus-Related Neoplasia and Its Utility as a Diagnostic and Predictive Biomarker.

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.

A genomic instability-based model for Barrett's oesophagus progression.

A genomic instability-based model for Barrett's oesophagus progression.

Recommendations of the Russian Gastroenterological Association in Diagnosis and Treatment of Gastroesophageal Reflux Disease

Aim . Current recommendations of the Russian Gastroenterological Association are developed to acquaint medical practitioners with modern diagnostics, treatment and trends in rational drug therapy for gastroesophageal reflux disease (GERD). General provisions . Incidence rate of GERD in the Russian Federation varies from 11.3 to 23.6%. GERD is diagnosed with medical history and laboratory examination evidence. Esophagogastroduodenoscopy (EGDS) allows detection of reflux esophagitis of various severity and cylindrical epithelial metaplasia of esophagus. The refractory form of disease (lack of conclusive clinical and endoscopic remission during 4-8 weeks of standard-dose PPI therapy), presence of strictures and Barrett's esophagus require EGDS with esophageal biopsy and bioptic histological examination. Patients should be conclusively performed esophageal 24-hour pH-metry or pH-impedance monitoring, high-resolution manometry to thoroughly examine functionality of esophagus, esophagogastric junction and assess disease prognosis and therapy outcomes. Treatment of GERD should be personalised accounting for clinical manifestations and severity, as well as aimed at symptom improvement, lesion healing in erosive esophagitis, averting complications, Barrett's esophagus progression, dysplasia and esophageal adenocarcinoma. Proton pump inhibitors (PPIs) are most effective agents in primary (4-8 weeks) and maintenance anti-GERD therapy. Antacids are recommended in monotherapy for occasional nonerosive heartburn and complex anti-GERD settings for fast symptom improvement. Prokinetics can be used in combination with PPIs for their properties to recover normal functionality of esophagus through affecting pathogenetic mechanisms of GERD. Complicated patients (repeated bleedings, peptic esophageal strictures) are recommended anti-reflux surgery with prior examination of esophageal functionality using pH-impedance and high-resolution manometry. Conclusion . Current recommendations provide an up-to-date evidential medicial review of GERD and guidelines to advance special medical care and timely preventive measures.

Endoscopic Management of Barrett’s Esophagus and Early Esophageal Neoplasia

Gastroesophageal reflux disease is common in North America, affecting around 25% of the population. A small fraction of these patients develop Barrett esophagus and thus are at a risk of developing esophageal cancer. The progression of Barrett esophagus to esophageal cancer can be prevented with timely examinations and, when necessary, by performing treatments to eradicate it. This review describes the use of endoscopy techniques to diagnose and classify Barrett esophagus among high-risk patients and the use of ablative techniques in patients with dysplasia. The review also describes endoscopic resection techniques for early esophageal cancer, which can provide staging information as well as can be therapeutic in selected cases. This review contains 8 figures and 49 references. Key Words: acid reflux, Barrett esophagus, cryoablation, endoscopic mucosal resection, endoscopic submucosal dissection, esophageal cancer, esophagus ablation, GERD, radiofrequency ablation

Endoscopic Management of Barrett’s Esophagus and Early Esophageal Neoplasia

Gastroesophageal reflux disease is common in North America, affecting around 25% of the population. A small fraction of these patients develop Barrett esophagus and thus are at a risk of developing esophageal cancer. The progression of Barrett esophagus to esophageal cancer can be prevented with timely examinations and, when necessary, by performing treatments to eradicate it. This review describes the use of endoscopy techniques to diagnose and classify Barrett esophagus among high-risk patients and the use of ablative techniques in patients with dysplasia. The review also describes endoscopic resection techniques for early esophageal cancer, which can provide staging information as well as can be therapeutic in selected cases. This review contains 8 figures and 49 references. Key Words: acid reflux, Barrett esophagus, cryoablation, endoscopic mucosal resection, endoscopic submucosal dissection, esophageal cancer, esophagus ablation, GERD, radiofrequency ablation

Does anti-reflux surgery disrupt the pathway of Barrett's esophagus progression to cancer?

In patients with Barrett's esophagus (BE), anti-reflux surgery aims to sustainable control reflux symptoms and heal reflux induced esophageal mucosal inflammation and prevent progression of BE to adenocarcinoma. There is growing evidence that beside gastric acid, bile salts in refluxed duodenal juice are responsible for the development and progression of BE. However, the pathogenesis of BE progression and the metaplasia-dysplasia-carcinoma sequence of the adenocarcinoma of the esophagus (EAC) is multifactorial and occurs over long natural time course. After anti-reflux surgery significant levels of regression from metaplastic Barrett's to non-metaplastic epithelium as well as from dysplastic to non-dysplastic BE have been observed and a randomized trial showed that sufficient surgical reflux control reduces the risk of Barrett's progression significantly when compared to medical treatment. Thus, large cohort studies show significant reduced risk of EAC in patients suffering from gastroesophageal reflux disease (GERD) with and without BE after anti-reflux surgery. Even after anti-reflux surgery the risk for EAC remains elevated in patients with BE and the right moment of intercepting the progressive nature of GERD has to be discussed in future. The paper also addresses the impact of anti-reflux surgery, endoscopic ablation and life style therapies for the management of GERD, BE and cancer prevention.

Pathology, Chemoprevention, and Preclinical Models for Target Validation in Barrett Esophagus.

Despite esophageal adenocarcinoma (EAC) being the most widespread among gastrointestinal cancers, with an 11-fold increase in the risk of cancer for patients with Barrett esophagus (BE), its prognosis is still poor. There is a critical need to better perceive the biology of cancer progression and identification of specific targets that are the hallmark of BE's progression. This review explores the established animal models of BE, including genetic, surgical and nonsurgical approaches, potential chemoprevention targets, and the reasoning behind their applications to prevent Barrett-related EAC. The key methodological features in the design feasibility of relevant studies are also discussed. Cancer Res; 78(14); 3747-54. ©2018 AACR.

Abstract 5410: An miRNA signature selects patients at risk for Barrett's Esophagus progression to dysplasia and cancer

Abstract Background: Esophageal adenocarcinoma (EAC) is an aggressive malignancy with an increasing incidence in the US. Progression of Barrett's Esophagus (BE) to EAC occurs via a stepwise process, and consequently periodic esophageal biopsies are utilized in order to monitor patients with BE. While a small percent of BE patients will progress to dysplasia and cancer, the majority of them will continue to have long-standing BE without progression. In the absence of dysplasia, the behavior of BE cannot be predicted based on evaluation of histologic features alone. Studies have demonstrated the utility of microRNAs in differentiating between the specific evolutionary events in the progression of BE to dysplasia and cancer. To date, there has yet to be a comparison between cases of BE that have not progressed to dysplasia or carcinoma, or cases of BE-Non-progression (BEN), and cases of BE that have progressed to dysplasia and/or carcinoma, or cases of BE- Progression (BEP). Through miRNA profiling, we have determined an assay of candidate miRNAs that reliably differentiate cases of BEN from BEP. Methods: Fifty cases of BE were profiled with two different miRNA profiling techniques: the HTG EdgeSeq miRNA WT Assay and the nanoString Assay. There were 15 cases of BEN (follow up &amp;gt;7 years) as well as of 11 cases of BEP (progression to dysplasia and/or EAC within 3 years). These cases were used for miRNA discovery and miRNA prediction model training. Another independent patient data set of 24 BE cases (13 cases of BEN and 11 cases of BEP; namely Normalized Nano), was profiled with nanoString miRNA Assay. This set was used as an independent validating cohort. Results: Six significant miRNAs were identified and confirmed using two different statistical methods (Limma test and Wilcoxen rank sum test). Family-wise error rate for type I error (FWER) was set to less than 0.05 in order to minimize the probability of discovering false positives. The final miRNA model demonstrated a high prediction performance at the optimal cutoff with a specificity of 80% and 50%; as well as sensitivity 100% and 75% for the two sets in order to capture a high proportion of the BEPs. We then independently validated this miRNA signature with the Normalized Nano set, which demonstrated a sensitivity of 70% and a specificity of 67.5% in this independent validation. While the prediction performance was weaker, we consistently validated its prediction power and clinical utility on an independent patient cohort with a completely different miRNA profiling technique. Conclusion: The reliability of these candidate miRNAs support further investigation in a larger population of patients, and may have potentially prognostic utility in the evaluation of BE patients with the goal of early detection of BE progression. Citation Format: James Saller, Kun Jiang, Kevin Neill, Zachary Mayer, Jae Lee, Luis Pena, F. Scott Corbett, Jose Pimiento, Mokenge Malafa, Anthony Magliocco, Domenico Coppola. An miRNA signature selects patients at risk for Barrett's Esophagus progression to dysplasia and cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5410.

Shallow Whole Genome Sequencing can Detect Copy Number Changes in FFPE Material in the Progression of Barrett's Esophagus

Shallow Whole Genome Sequencing can Detect Copy Number Changes in FFPE Material in the Progression of Barrett's Esophagus

A non-endoscopic device to sample the oesophageal microbiota: a case-control study

SummaryBackgroundThe strongest risk factor for oesophageal adenocarcinoma is reflux disease, and the rising incidence of this coincides with the eradication of Helicobacter pylori, both of which might alter the oesophageal microbiota. We aimed to profile the microbiota at different stages of Barrett's carcinogenesis and investigate the Cytosponge as a minimally invasive tool for sampling the oesophageal microbiota.MethodsIn this case-control study, 16S rRNA gene amplicon sequencing was done on 210 oesophageal samples from 86 patients representing the Barrett's oesophagus progression sequence (normal squamous controls [n=20], non-dysplastic [n=24] and dysplastic Barrett's oesophagus [n=23], and oesophageal adenocarcinoma [n=19]), relevant negative controls, and replicates on the Illumina MiSeq platform. Samples were taken from patients enrolled in the BEST2 study at five UK hospitals and the OCCAMS study at six UK hospitals. We compared fresh frozen tissue, fresh frozen endoscopic brushings, and the Cytosponge device for microbial DNA yield (qPCR), diversity, and community composition.FindingsThere was decreased microbial diversity in oesophageal adenocarcinoma tissue compared with tissue from healthy control patients as measured by the observed operational taxonomic unit (OTU) richness (p=0·0012), Chao estimated total richness (p=0·0004), and Shannon diversity index (p=0·0075). Lactobacillus fermentum was enriched in oesophageal adenocarcinoma (p=0·028), and lactic acid bacteria dominated the microenvironment in seven (47%) of 15 cases of oesophageal adenocarcinoma. Comparison of oesophageal sampling methods showed that the Cytosponge yielded more than ten-times higher quantities of microbial DNA than did endoscopic brushes or biopsies using quantitative PCR (p<0·0001). The Cytosponge samples contained the majority of taxa detected in biopsy and brush samples, but were enriched for genera from the oral cavity and stomach, including Fusobacterium, Megasphaera, Campylobacter, Capnocytophaga, and Dialister. The Cytosponge detected decreased microbial diversity in patients with high-grade dysplasia in comparison to control patients, as measured by the observed OTU richness (p=0·0147), Chao estimated total richness (p=0·023), and Shannon diversity index (p=0·0085).InterpretationAlterations in microbial communities occur in the lower oesophagus in Barrett's carcinogenesis, which can be detected at the pre-invasive stage of high-grade dysplasia with the novel Cytosponge device. Our findings are potentially applicable to early disease detection, and future test development should focus on longitudinal sampling of the microbiota to monitor for changes in microbial diversity in a larger cohort of patients.FundingCancer Research UK, National Institute for Health Research, Medical Research Council, Wellcome Trust, The Scottish Government (RESAS).

1328P - Immunohistochemical biomarkers for risk stratification of neoplastic progression in Barrett esophagus

1328P - Immunohistochemical biomarkers for risk stratification of neoplastic progression in Barrett esophagus

Sa1255 Low Risk of Neoplastic Progression of Barrett's Esophagus in Women: Results From a Large Multi-Center Consortium

Sa1255 Low Risk of Neoplastic Progression of Barrett's Esophagus in Women: Results From a Large Multi-Center Consortium

Paired exome analysis of Barrett's esophagus and adenocarcinoma.

Barrett’s esophagus, is thought to progress to esophageal adenocarcinoma (EAC) through a step-wise progression with loss of CDKN2A followed by p53 inactivation and aneuploidy. Here, we present whole exome sequencing from 25 pairs of EAC and Barrett’s and five patients whose Barrett’s and tumor were extensively sampled. Our analysis revealed that oncogene amplification typically occurred as a late event and that TP53 mutations often occur early in Barrett’s progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data revealed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations with more frequent oncogenic amplifications and less frequent inactivation of tumor suppressors, including CDKN2A. These data suggest that many EACs emerge not through gradual accumulation of tumor suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by acquisition of oncogenic amplifications.

Reflux control is important in the management of Barrett’s Esophagus: results from a retrospective 1,830 patient cohort

It is unknown whether acid/reflux control prevents progression in Barrett's esophagus. In this study, we investigate whether medical or surgical control of reflux is associated with a decreased risk of progression to dysplasia/esophageal adenocarcinoma. We retrospectively collected and analyzed data from a cohort of Barrett's esophagus patients participating in this single-center study comprised of all patients diagnosed with Barrett's esophagus at NorthShore University Health System hospitals and clinics over a 10-year period. Patients were followed in order to identify those progressing from Barrett's esophagus to low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. We collected information from the patient's electronic medical records regarding demographic, endoscopic findings, histological findings, smoking/alcohol history, medication use including proton-pump inhibitors, and history of bariatric and antireflux surgery. Risk-adjusted modeling was performed using multivariable logistic regression. This study included 1,830 total Barrett's esophagus patients, 102 of which had their Barrett's esophagus progress to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma (confirmed by biopsy) with an annual incidence rate of 1.1%. Mean follow-up period was 5.51 years (10,083 patient-years). Compared to the group that did not progress, the group that progressed was older (69.3 ± 13.7 vs. 63.9 ± 13.4 years. p < 0.001) and likely to be male (75 vs. 61%, p < 0.01). In the multivariable analysis, patients who had a history of antireflux surgery (n = 44) or proton-pump inhibitor use without surgery (n = 1,641) were found to progress at significantly lower rates than patients who did not have antireflux surgery or were not taking PPI's (OR 0.18, 95% CI 0.09-0.36). Reflux control was associated with decreased risk of progression to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma. These results support the use of reflux control strategies such as proton-pump inhibitor therapy or surgery in patients with non-dysplastic Barrett's esophagus for the prevention of progression to dysplasia/adenocarcinoma.

Molecular Occurrences in the Neoplastic Progression of Barrett Esophagus

AbstractBarrett esophagus is the known precursor lesion of esophageal adenocarcinoma; however, the natural history of Barrett esophagus and its associated dysplasia is a matter of considerable debate and difficult to establish on a patient-by-patient basis. Clinical management and surveillance are c

MicroRNA Expression Signatures during Malignant Progression from Barrett's Esophagus to Esophageal Adenocarcinoma

Barrett's esophagus is the precursor lesion of esophageal adenocarcinoma, whose progression follows sequential stages. However, the low progression rate and the inadequacy and subjective interpretation of histologic grading in predicting Barrett's esophagus progression call for more objective biomarkers that can improve risk prediction. We conducted a genome-wide profiling of 754 human microRNAs (miRNA) in 35 normal epithelium, 34 Barrett's esophagus, and 36 esophageal adenocarcinoma tissues using TaqMan real-time PCR-based profiling. Unsupervised hierarchical clustering using 294 modestly to highly expressed miRNAs showed clear clustering of two groups: normal epithelium versus Barrett's esophagus/esophageal adenocarcinoma tissues. Moreover, there was an excellent clustering of Barrett's metaplasia (without dysplasia) tissues from normal epithelium tissues. However, Barrett's esophagus tissues of different stages and esophageal adenocarcinoma tissues were interspersed. There were differentially expressed miRNAs at different stages. The majority of miRNA aberrations involved upregulation of expression in Barrett's esophagus and esophageal adenocarcinoma tissues, with the most dramatic alterations occurring at the Barrett's metaplasia stage. Known oncomiRs, such as miR-21, miR-25, and miR-223, and tumor suppressor miRNAs, including miR-205, miR-203, let-7c, and miR-133a, showed progressively altered expression from Barrett's esophagus to esophageal adenocarcinoma. We also identified a number of novel miRNAs that showed progressively altered expression, including miR-301b, miR-618, and miR-23b. The significant miRNA alterations that were exclusive to esophageal adenocarcinoma but not Barrett's esophagus included miR-375 downregulation and upregulation of five members of the miR-17-92 and its homologue clusters, which may become promising biomarkers for esophageal adenocarcinoma development.

Smoking found to increase the rate of progression of Barrett esophagus to adenocarcinoma

Smoking found to increase the rate of progression of Barrett esophagus to adenocarcinoma

Su1911 Increasing Clonal Diversity Predicts Progression in Barrett Esophagus Patients, Results From a Phase IV 5 Year Prospective Follow up Study

BACKGROUND: Progression in Barrett esophagus is typically illustrated as a sequential selection of increasingly more fit or dominant genetic clones. It was demonstrated that a high level of genetic diversity, as determined by the Shannon Diversity index (SDI), is associated with an increased risk for progression of Barrett esophagus (BE). AIM: By using our two marker sets, to evaluate the prognostic value of the Shannon diversity index (SDI) in a 5 year prospective follow study of a BE surveillance cohort. METHODS: Between the period of 2002 until 2008, all BE patient with no dysplasia/indefinite for dysplasia (ND/ IND) were included from seven different hospitals. All patients with LGD, HGD or EAC at the index endoscopy or histological progression within 6 months and/or previous treatment for BE were excluded. At the index endoscopy (t=0) biopsies following ACG guidelines, and brush cytology specimens were taken. All patients underwent prospective surveillance. We evaluated seven DNA FISH markers on the BE brush cytology specimens, which included the marker set 1: p16, p53 and aneusomy for 17 &7, and the marker set 2: Her-2, 20q and C-Myc. DNA FISH for these seven different markers was performed on brushes obtained at t=0 and after an average of 5 years of follow up (t=1). Per brush sample 100 nuclei were scored for each probe. The SDI was calculated using the following formula SDI =-pi ln(pi), which takes into account the sum and frequency of the different clones. The endpoints were histological progression of ND/IND into LGD/HGD/EAC, or a FU of 60 months. RESULTS: A total of 296 ND BE patients were evaluated using the DNA FISH assay and reached an average follow up of 50 months. Of these 296 patients, 27 progressed: 23 progressed to LGD and 4 to HGD/EAC. At t=0 the median SDI for the non progressors (n=269) for set 1 was 0.39 (SD±0.20) and for set 2 0.38 (SD ± 0.21). For the progressors, the median SDI for set 1 was 0,43 (SD±0.22) and for set 2 0.52 (SD ± 0.17). At t=0, for both sets the SDI's were higher in the progressors (t-test; p=0.01). After 5 years, the SDI's for both sets decreased to 0.15 (SD ±0.16 ) and 0.1 (SD± 0.17) in the non progressors. The progressors, however, showed significantly increased SDI's of 0.68 (SD±0.2) and 0.75 (SD±0.18) for set 1 and 2 respectively (t-test; p-value 0.01)( figure 1). CONCLUSIONS: Using two marker sets on brush cytology specimens of BE, SDI's proved to be significantly lower in BE patients who did not progress compared to those who progressed during prospective follow up. We conclude that an increasing SDI measured at different time points during surveillance is associated with an increased risk for progression of BE. BE patients who do not progress show lower SDI's, which remain stable or decrease during follow up. Determining SDI's in BE patients is a useful tool to identify BE patients at risk.