Barrett's Esophagus Research Articles

Regulation of pro-apoptotic and anti-apoptotic factors in obesity-related esophageal adenocarcinoma

BackgroundObesity is a risk factor for esophageal adenocarcinoma (EAC). It was reported that obesity -associated inflammation correlates with insulin resistance and increased risk of EAC. The objective of the study is to investigate the role of obesity associated inflammatory mediators in the development of EAC.MethodsWe included 23 obese and nonobese patients with EAC or with or without Barrett’s esophagus (BE) after IRB approval. We collected 23 normal, 10 BE, and 19 EAC tissue samples from endoscopy or esophagectomy. The samples were analyzed for the expression levels of pro-apoptotic and anti-apoptotic factors, PKC-δ, cIAP2, FLIP, IGF-1, Akt, NF-kB and Ki67 by immunofluorescence and RT-PCR. We compared the expression levels between normal, BE, and EAC tissue using Students’ t-test between two groups.ResultsOur results showed decreased gene and protein expression of pro-apoptotic factors (bad, bak and bax) and increased expression of anti-apoptotic factors (bcl-2, Bcl-xL) in BE and EAC compared to normal tissues. There was increased gene and protein expression of PKC-δ, cIAP2, FLIP, NF-kB, IGF-1, Akt, and Ki67 in BE and EAC samples compared to normal esophagus. Further, an increased folds changes in mRNA expression of proapoptotic factors, antiapoptotic factors, PKC-δ, IGF-1, Akt, and Ki-67 was associated with obesity.ConclusionPatients with EAC had increased expression of cIAP2 and FLIP, and PKC-δ which is associated with inhibition of apoptosis and possible progression of esophageal adenocarcinoma.

Cost-effective identification of Barrett's esophagus in the community: A first step towards screening.

The first step towards developing a screening strategy for Barrett's esophagus (BE) is the identification of individuals in the community. Currently available tools include endoscopy, less-invasive non-endoscopic devices, and non-invasive risk stratification models. We evaluated the cost of potential strategies for identification of BE as a first step towards screening. Two hypothetical cohorts of the general population aged ≥50years with BE prevalence rates of 1.9% and 6.8% were modeled. Four potential screening tools were evaluated: (i) risk stratification based on non-weighted clinical factors according to US/European guidelines, (ii) weighted risk stratification using algorithmic models, (iii) less-invasive devices such as Cytosponge+trefoil factor 3 (TFF3), and (iv) endoscopy. Using a decision-analytic model, the cost per BE case identified and the cost-effectiveness were compared for six potential BE screening strategies based on combinations of the four screening tools; (i)+(iv), (ii)+(iv), (iii)+(iv), (i)+(iii)+(iv), (ii)+(iii)+(iv), and only (iv). The cost per BE case identified was lowest for the weighted risk stratification followed by Cytosponge-TFF3 then endoscopy strategy at both 1.9% and 6.8% BE prevalences (US$9282 and US$3406, respectively) although it was sensitive to the cost of less-invasive devices. This strategy was also most cost-effective for a BE prevalence of 1.9%. At BE prevalence of 6.8%, the Cytosponge-TFF3 followed by endoscopy strategy was most cost-effective. Incorporating weighted risk stratification and less-invasive devices such as Cytosponge-TFF3 into BE screening strategies has a potential to cost-effectively identify BE in the community although device cost and the community prevalence of BE will impact the optimal strategy.

P53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett’s oesophagus

BackgroundWhile p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear.ObjectiveThis study investigates the impact of p53 mutation...

Stratification of Barrett's esophagus surveillance based on p53 immunohistochemistry: a cost-effectiveness analysis by an international collaborative group.

Surveillance of nondysplastic Barrett's esophagus (NDBE) is recommended to identify progression to dysplasia; however, the most cost-effective strategy remains unclear. Mutation of TP53 or aberrant expression of p53 have been associated with the development of dysplasia in BE. We sought to determine if surveillance intervals for BE could be stratified based on p53 expression. A Markov model was developed for NDBE. Patients with NDBE underwent p53 immunohistochemistry (IHC) and those with abnormal p53 expression underwent surveillance endoscopy at 1 year, while patients with normal p53 expression underwent surveillance in 3 years. Patients with dysplasia underwent endoscopic therapy and surveillance. On base-case analysis, the strategy of stratifying surveillance based on abnormal p53 IHC was cost-effective relative to conventional surveillance and a natural history model, with an incremental cost-effectiveness ratio (ICER) of $8258 for p53 IHC-based surveillance. Both the conventional and p53-stratified surveillance strategies dominated the natural history model. On probabilistic sensitivity analysis, the p53 IHC strategy ($28 652; 16.78 quality-adjusted life years [QALYs]) was more cost-effective than conventional surveillance ($25 679; 16.17 QALYs) with a net monetary benefit of $306 873 compared with conventional surveillance ($297 642), with an ICER <$50 000 in 96% of iterations. The p53-stratification strategy was associated with a 14% reduction in the overall endoscopy burden and a 59% increase in dysplasia detection. A surveillance strategy for BE based on abnormal p53 IHC is cost-effective relative to a conventional surveillance strategy and is likely to be associated with higher rates of dysplasia diagnosis.

S674 Efficacy and Safety of Radiofrequency Ablation in Management of Patients With Low-Grade Dysplasia in Barrett's Esophagus: A Systematic Review and Meta-Analysis

S674 Efficacy and Safety of Radiofrequency Ablation in Management of Patients With Low-Grade Dysplasia in Barrett's Esophagus: A Systematic Review and Meta-Analysis

S576 Radiofrequency Ablation and Cryoablation for Dysplastic Barrett's Esophagus: A Potential Cause of Esophageal Mucosal Eosinophilia

S576 Radiofrequency Ablation and Cryoablation for Dysplastic Barrett's Esophagus: A Potential Cause of Esophageal Mucosal Eosinophilia

Evaluation of super resolution technology for digestive endoscopic images

ObjectThis study aims to evaluate the value of super resolution (SR) technology in augmenting the quality of digestive endoscopic images. MethodsIn the retrospective study, we employed two advanced SR models, i.e., SwimIR and ESRGAN. Two discrete datasets were utilized, with training conducted using the dataset of the First Affiliated Hospital of Soochow University (12,212 high-resolution images) and evaluation conducted using the HyperKvasir dataset (2,566 low-resolution images). Furthermore, an assessment of the impact of enhanced low-resolution images was conducted using a 5-point Likert scale from the perspectives of endoscopists. Finally, two endoscopic image classification tasks were employed to evaluate the effect of SR technology on computer vision (CV). ResultsSwinIR demonstrated superior performance, which achieved a PSNR of 32.60, an SSIM of 0.90, and a VIF of 0.47 in test set. 90 % of endoscopists supported that SR preprocessing moderately ameliorated the readability of endoscopic images. For CV, enhanced images bolstered the performance of convolutional neural networks, whether in the classification task of Barrett's esophagus (improved F1-score: 0.04) or Mayo Endoscopy Score (improved F1-score: 0.04). ConclusionsSR technology demonstrates the capacity to produce high-resolution endoscopic images. The approach enhanced clinical readability and CV models’ performance of low-resolution endoscopic images.

Palmitoylethanolamide (PEA) for Prevention of Gastroesophageal Inflammation: Insights from In Vitro Models.

Gastroesophageal reflux disease (GERD) is a digestive disorder that can lead to chronic mucosal damage, causing esophagitis, Barrett's esophagus and esophageal cancer. GERD currently affects about 13% of the world's population and represent a major public health concern due to the increasing prevalence and incidence. The aim of this study was to explore complementary strategies for GERD management based the natural compound palmitoylethanolamide (PEA), alone or associated with plant extracts with demonstrated anti-GERD activity (Zingiber officinale, Musa × paradisiaca, Opuntia ficus-indica and Olea europaea). For this purpose, two in vitro models based on the esophageal mucosa CP-B cell line were chosen. The first one was based on the exposure of esophageal cells to HCl, while the second one was based on lipopolysaccharide (LPS) treatment to cause a strong inflammatory cell response. Inflammation induced was assessed using a Luminex® assay, measuring the secretion of IL-1β, IL-6, IL-10, IL-8 and TNF-α. Results obtained demonstrate that PEA strongly decreased the inflammatory response elicited by HCl exposure. Moreover, the effect of PEA was enhanced by the presence of natural extracts of Zingiber officinale, Musa × paradisiaca, Opuntia ficus-indica and Olea europaea. PEA should be considered as an anti-GERD natural compound of interest.

Exploring the incidence of dysplasia or adenocarcinoma in early onset Barrett's esophagus.

Currently data on the risk of progression to and lifetime risk of cancer are not available for patients with young onset Barrett's esophagus (BE). Our aim was to obtain epidemiologic data on the incidence of dysplasia or adenocarcinoma in young onset BE in the Netherlands by collecting data on all histologically confirmed cases over a prolonged period of 25 years between January 1, 1991 and December 31, 2015. Data were obtained from the Dutch National Pathology Registry. Patients were included if there was a suspicion of BE visualized in the esophagus during the endoscopic examination in combination with a concordant histologic diagnosis of intestinal metaplasia. 231 patients with early onset BE were identified (median age 26 years [range 0-29 years]), with 17 progressing to dysplasia (6 prevalent and 11 incident). For the patients with incident dysplasia, the median surveillance time between the diagnosis of early onset BE and diagnosis of dysplasia was 5 years (range 0-16 years). The incidence rate of dysplasia was 7.3 per 1000 person-years. There were three patients who developed adenocarcinoma (1 prevalent and 2 incident), who were diagnosed at ages 28, 35, and 36 years. The incidence rate of adenocarcinoma was 1.3 per 1000 person-years. In this 25-year period, 231 patients were diagnosed with early onset BE in the Netherlands, with 17 patients progressing to dysplasia and three developing adenocarcinoma. This corresponded to incidence rates of 7.3 per 1000 person-years for dysplasia and 1.3 per 1000 person-years for adenocarcinoma.

Lactate Suppresses Growth of Esophageal Adenocarcinoma Patient-Derived Organoids through Alterations in Tumor NADH/NAD+ Redox State.

Barrett's esophagus (BE) is a common precancerous lesion that can progress to esophageal adenocarcinoma (EAC). There are significant alterations in the esophageal microbiome in the progression from healthy esophagus to BE to EAC, including an increased abundance of a variety of lactate-producing bacteria and an increase of lactate in the tumor microenvironment, as predicted by metabolic modeling. The role of bacterial lactate in EAC is unknown. Here, we utilize patient-derived organoid (PDO) models of EAC and demonstrate that lactate inhibits the growth and proliferation of EAC PDOs through alterations in the tumor NADH/NAD+ redox state. Further RNA sequencing of EAC PDOs identifies ID1 and RSAD2 as potential regulatory molecules crucial in mediating lactate's ability to suppress glycolysis and proliferation. Gene ontology analysis also identifies the activation of inflammatory and immunological pathways in addition to alterations in the metabolic pathways in EAC PDOs exposed to lactate, suggesting a multi-faceted role for lactate in the pathogenesis of EAC.

Narrow band imaging: Important tool for early diagnosis, management, and improved outcomes in gastrointestinal lesions.

Narrow band imaging-magnifying endoscopy (NBI-ME) is used to identify changes in mucosal or vascular pattern observed on GI endoscopy in real time on the basis of optical image enhancement.It has a significant role in early detection of dysplasia, premalignant, and Malignant lesions along with its depth of invasion. Upper and lower GI endoscopy performed in 1742 patients who presented with gastrointestinal symptoms at this tertiary center over 5years out of which 1623 were evaluated with both NBI-ME and histopathology. Real time endoscopic assessment was performed. Targeted biopsies were taken for comparative analysis. Of the 1742 patients, 119 were excluded from the study. 807 underwent upper GI endoscopy and 816 underwent lower GI endoscopy. Mean age of presentation was 38 +/- 2.7years. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of NBI-ME for neoplastic esophageal lesions were 96.3%, 90.6%, 91.1%, 96.03%, respectively. For Barrett's esophagus it was 95.4%, 90.7%, 86.1%, and 90.7%; For gastric neoplastic lesions the values were 96.1%, 91.04%, 83.8%, and 97.9%. For colorectal it was 96.7%, 91.3%, 88.0%, and 97.7%. Overall sensitivity, specificity, PPV, andNPVof NBI-ME for neoplastic lesions (both upper and lower GI) were 96.2%, 91.0%, 96.2%, and 97.2%. Of the 1623 patients, 951 received medical management with regular surveillance and 672 patients with high-grade dysplasia, premalignant, and malignant conditions underwent interventions in form of either endoscopy or surgery. NBI-ME has a greater role and can be considered as an effective tool in making early diagnosis and guiding optimum treatment.

Causal effects of genetically determined metabolites and metabolite ratios on esophageal diseases: a two-sample Mendelian randomization study

BackgroundEsophageal diseases (ED) are a kind of common diseases of upper digestive tract. Previous studies have proved that metabolic disorders are closely related to the occurrence and development of ED. However, there is a lack of evidence for causal relationships between metabolites and ED, as well as between metabolite ratios representing enzyme activities and ED. Herein, we explored the causality of genetically determined metabolites (GDMs) on ED through Mendelian Randomization (MR) study.MethodsTwo-sample Mendelian randomization analysis was used to assess the causal effects of genetically determined metabolites and metabolite ratios on ED. A genome-wide association analysis (GWAS) encompassing 850 individual metabolites along with 309 metabolite ratios served as the exposures. Meanwhile, the outcomes were defined by 10 types of ED phenotypes, including Congenital Malformations of Esophagus (CME), Esophageal Varices (EV), Esophageal Obstructions (EO), Esophageal Ulcers (EU), Esophageal Perforations (EP), Gastroesophageal Reflux Disease (GERD), Esophagitis, Barrett's Esophagus (BE), Benign Esophageal Tumors (BETs), and Malignant Esophageal Neoplasms (MENs). The standard inverse variance weighted (IVW) method was applied to estimate the causal relationship between exposure and outcome. Sensitivity analyses were carried out using multiple methods, including MR-Egger, Weighted Median, MR-PRESSO, Cochran's Q test, and leave-one-out analysis. P < 0.05 was conventionally considered statistically significant. After applying the Bonferroni correction for multiple testing, a threshold of P < 4.3E-05 (0.05/1159) was regarded as indicative of a statistically significant causal relationship. Furthermore, metabolic pathway analysis was performed using the web-based MetaboAnalyst 6.0 software.ResultsThe findings revealed that initially, a total of 869 candidate causal association pairs (Pivw\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${P}_{ivw}$$\\end{document} < 0.05) were identified, involving 442 metabolites, 145 metabolite ratios and 10 types of ED. However, upon applying the Bonferroni correction for multiple testing, only 36 pairs remained significant, involving 28 metabolites (predominantly lipids and amino acids), 5 metabolite ratios and 6 types of ED. Sensitivity analyses and reverse MR were performed for these 36 causal association pairs, where the results showed that the pair of EV and 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE (p-16:0/18:2) did not withstand the sensitivity tests, and Hexadecenedioate (C16:1-DC) was found to have a reverse causality with GERD. The final 34 robust causal pairs included 26 metabolites, 5 metabolite ratios and 5 types of ED. The involved 26 metabolites predominantly consisted of methylated nucleotides, glycine derivatives, sex hormones, phospholipids, bile acids, fatty acid dicarboxylic acid derivatives, and N-acetylated amino acids. Furthermore, through metabolic pathway analysis, we uncovered 8 significant pathways that played pivotal roles in five types of ED conditions.ConclusionsThis study integrated genomics with metabolomics to assess causal relationships between ED and both metabolites and metabolite ratios, uncovering several key metabolic features in ED pathogenesis. These findings have potential as novel biomarkers for ED and provide insights into the disease's etiology and progression. However, further clinical and experimental validations are necessary

Clinical features of gastroesophageal reflux disease and erosive esophagitis: Insights from patients undergoing esophagogastroduodenoscopy in resource-limited Ethiopia.

Gastroesophageal reflux disease (GERD) is a common disease worldwide with varying clinical presentations and risk factors. Prevalence data for Africa is lacking, but an increasing trend is expected due to demographic and epidemiological transitions. Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis (EE), no studies in Ethiopia have investigated the clinical characteristics, risk factors, and severity of GERD using esophagogastroduodenoscopy (EGD). To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE. We conducted a multicenter, retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022. Data were collected from electronic medical records and phone call interviews. We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value < 0.05. The mean ± SD age of the patients was 44.8 (± 15.9) years, with a male-to-female ratio of 1.6:1. The most commonly reported symptom was epigastric pain (80.5%), followed by heartburn (43%). Los Angeles (LA)-A EE was diagnosed in 71.1% of patients, followed by LA-B (14.9%), LA-C (7.7%), and LA-D (5.9%). Multivariate analysis showed that age 50 or above, presence of bleeding, and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE (P < 0.05). Stricture and Barrett's esophagus were observed in 4.5% and 1.36% of patients with EE, respectively. Most of the patients had milder EE with fewer complications. However, severe EE was more prevalent in older patients and those with duodenitis/duodenopathy.

Analytical Validation of Esopredict, an Epigenetic Prognostic Assay for Patients with Barrett's Esophagus.

EsopredictTM is a prognostic assay that risk-stratifies Barrett's esophagus patients to predict future progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Established based on foundational studies at Johns Hopkins University, a risk algorithm was developed and clinically validated in two independent studies (n = 320). EsopredictTM is currently offered as a clinical test under the Clinical Laboratory Improvement Amendments (CLIA) guidelines. Here we present the analytical validation by repeated testing of FFPE tissues (n = 26 patients), cell lines, and contrived DNA controls to determine assay performance regarding analytical sensitivity (as defined by the limit of detection (LOD)), analytical specificity (as defined by the limit of blank (LOB)), accuracy as determined from the average positive and negative agreement, repeatability, and reproducibility. The LOD for the assay at 1.5% DNA methylation was significantly higher than the LOB, as determined by an unmethylated DNA control (0% methylated DNA). Inter- and intra-assay average positive agreement (APA) were 88% and 94%, respectively, while average negative agreement (ANA) values were 90% and 94%, respectively. Average inter- and intra-assay precision were <9% and <5% coefficient of variation (CV), respectively. These results confirm that EsopredictTM is a highly reproducible, sensitive, and specific risk categorization assay for the prediction of progression to HGD or EAC within 5 years.

Optimization of saliva sampling methods for analysis of bile acids by UHPLC-MS

This study investigated methods for sampling bile acids in saliva, a potential non-invasive diagnostic biofluid. Bile acids have been implicated in causing damage and permanent changes to the esophageal mucosa and increasing the risk of developing Barrett's esophagus, a condition that can potentially progress to esophageal cancer. Three saliva collection methods were compared: spitting, Salivette® swabs, and Salivette Cortisol® swabs. Spitting emerged as the superior method with the highest recoveries and the least interference, likely due to Salivette swabs retaining bile acids or introducing unknown interferences. All saliva samples were analyzed by UHPLC-MS/MS using the Zorbax RRHD Eclipse Plus C18 column (3 × 50 mm, 1.8 µm) in gradient elution of 0.1 % formic acid in water and methanol. Saliva sample stability was assessed over 14 days, reflecting typical storage times. The levels of detected bile acids were stable for the measured period (RSD ≤ 22 %) and no degradation was observed. Bile acid levels in saliva fluctuated throughout the day, with the greatest changes observed for glycine-conjugated bile acids after meals. To minimize sampling variability, saliva collection by spitting after overnight fasting is recommended for future studies. Our findings are applicable for standardized bile acid sampling and are currently applied in a large clinical study evaluating bile acids as potential susceptibility markers for Barrett's esophagus diagnostics.

Recurrence following successful eradication of neoplasia with endoscopic mucosal resection compared with endoscopic submucosal dissection in Barrett's esophagus: a retrospective comparison.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are effective treatments for Barrett's neoplasia. However, little is known about recurrence rates following these techniques. We compared long-term neoplasia recurrence rates following EMR and ESD. This study included patients with Barrett's neoplasia (high grade dysplasia/adenocarcinoma) treated between July 2019 and December 2023 at a tertiary referral center in Canada. Outcomes were residual neoplasia at first follow-up, complete remission of neoplasia (CRN), and neoplasia recurrence following CRN. 157 patients were included (87 EMR, 70 ESD). Compared with EMR, the ESD group had larger lesions (median 2 vs. 3 cm, P<0.05), more adenocarcinoma (85.1% vs. 94.3%, P = 0.07), and deeper submucosal invasion (T1a: 71.6% vs. 75.8%; T1b-SM1: 25.7% vs. 6.1%; T1b≥SM2: 2.7% vs. 18.2%; P<0.05). Among 124 patients with follow-up (71 EMR, 53 ESD), 84.9% of ESD-treated patients had curative resections (i.e. R0 resection with low risk for lymph node metastasis), whereas 94.4% of EMR-treated patients had deep margin R0 resection of low risk lesions. At first follow-up, residual neoplasia (14.1% vs. 11.3%) and CRN (97.2% vs. 100%) were similar in the EMR and ESD groups, but neoplasia recurrence following CRN was significantly higher with EMR (13% vs. 1.9%, P<0.05), with cumulative probability of recurrence at 3 years of 18.3% vs. 4.2%, respectively. Neoplasia recurrence following CRN was significantly higher following EMR compared with ESD, suggesting that ESD may be superior to EMR in preventing neoplasia recurrence in Barrett's esophagus.

789. EFFICACY AND SAFETY OF CRYOBALLOON-180 ABLATION FOR THE TREATMENT OF DYSPLASTIC BARRETT ESOPHAGUS: PRELIMINARY RESULTS FROM A PROSPECTIVE MULTICENTER STUDY

Abstract Background Cryoballoon-ablation is a relatively novel method for the eradication of dysplastic Barrett esophagus (BE). While the focal cryoballoon-ablation system has shown to be efficacious for BE of limited extent, the cryoballoon180-ablation system (CBAS180) is developed to treat longer BE segments by semi-circumferential ablation over 3cm, in a single step. A first-in-human study demonstrated the feasibility of CBAS180 treatment, yet the optimal dose needs to be determined. The current prospective, multicenter study, investigates CBAS180 at lower dosages for patients with dysplastic BE. Methods A total of 62 patients with ablation naïve BE (C≤3 and M≥1) will be enrolled in six Dutch Barrett expert centers. Treatment consists of a full circumferential ablation over 3 cm of length, using two semi-circumferential ablations at a dose of 1.2 mm/sec. Follow-up consisted of phone calls at days 1, 7 and 30, a symptom diary during 14 days, and an endoscopy after 3 months. Outcomes included (1) technical success rate; (2) BE regression percentage at follow-up scored by an independent adjudication committee; (3) incidence of adverse events; (4) post-procedural pain (scored on a scale of 0-10); and (5) post-procedural dysphagia (scored on a validated scale of 0-4). Follow-up treatment consisted of focal cryoballoon-ablation until complete eradication of visible BE was achieved, confirmed by biopsies from the neo-Z-line. Results So far, 25 patients (80% male; mean age 67) with a median BE length of C0M2 (p25-p75 C0-1M2-4) were included. Technical success rate was 92% (23/25; 95% CI 74-99%). In two patients, treatment was technically unsuccessful due to unstable positioning of the balloon (n=1) or a device malfunction (n=1). Median procedure time was 14 (p25-p75 11-16) 4) minutes and median ablation time was 5 (p25-p75 3-5) minutes. All 23 successfully treated patients completed follow-up endoscopy at 3 months. Median BE regression was 90% (p25-p75 75%-100%) evaluated by the independent adjudication committee. Overall, CBAS180 adverse event rate was 8% (2/23); one patient developed esophageal stricture (1/23; 4% [95% CI 1-16%]) resolved after a single endoscopic dilation. Another patient (1/23; 4% [95% CI 1-16%]) experienced post-procedural bleeding, with re-endoscopy without intervention. The CBAS180 procedure was well tolerated with low post-procedural pain (median 2 [p25-p75 1-4] at day 1 and 0 [p25-p75 0-1] at day 7) and dysphagia (56% and 70% of patients with score 0 at days 1 and 7, respectively) scores. So far, 22/23 (95%) patients were additionally treated with focal cryoballoon-ablation and 18/22 (82%) achieved a complete endoscopis and histologic eradication of BE after median 1 (p25-p75 1-3) treatment, the other 4 are still under treatment. After focal cryoballoon-ablation, 2/22 patients developed strictures, resolved after 1 and 2 endoscopic dilatations. Conclusion Based on these preliminary results, circumferential ablation with CBAS180 at 1.2 mm/sec, followed by focal cryoballoon-ablation, emerges as an effective and safe procedure for dysplastic BE eradication in the hands of expert endoscopists. Further avenues for exploration should encompass the assessment of multiple CBAS180 ablations stacked on top of each other in larger segments and the validation of outcomes in a larger patient cohort.

365. METHYLATION BIOMARKERS TO STRATIFY BARRETT’S ESOPHAGUS PATIENTS PROGRESSING AND NON-PROGRESSING TO ESOPHAGEAL ADENOCARCINOMA

Abstract Background Over the last forty years, North America and Europe have witnessed a notable surge in cases of esophageal adenocarcinoma (EAC). This malignancy typically arises from Barrett esophagus (BE), a condition characterized by the replacement of normal squamous epithelium with specialized metaplastic cells. Our study aims to identify specific methylation markers capable of distinguishing between BE patients that will and will not progress to EAC. Methods We conducted differential expression analysis on RNASeq public dataset GSE210647 to distinguish BE progressors from non-progressors. Reads were aligned to hg38 genome using STAR aligner, normalized and analyzed with DESeq2. Significant genes were selected by |log2 fold change| ≥ 0.2 and padj &amp;lt; 0.01. GO, pathway enrichment, and transcription factor (TF) network analyses were performed to uncover biological disparities. Integration with previous methylation data (N.R. Dehkordi et al., 292. Specific methylation markers associated with changes in gene expression distinguish EAC and sub-types of BE patients, ISDE 2023) allowed the identification of overlapping biomarkers, aiding in better discrimination between the two groups. Results Differential expression analysis of GSE210647 identified 2261 significative DEGs between BE progressors and non-progressors. Pathway enrichment analysis in BE progressors revealed significant associations with cellular morphogenesis and reprogramming, alongside the induction of the bile acid pathway, known for its implications in invasiveness and cancer stem cell expansion. TF network analysis identified key regulators such as TBX20, FOXS1, and ZNF454, shedding light on their roles in esophageal carcinogenesis. Among the 505 CpG markers acquired in prior analyses, 127 genomic regions were linked with overexpressed genes either in progressors or in non-progressors BE patients. Leveraging this marker panel, BE samples were stratified into discrete subtypes, aligning either with normal esophageal tissue or EAC, and suggesting a potential stratification by disease progression. Conclusions The integration of expression and methylation analyses allows the identification of key genomic and epigenomic loci able to distinguish BE patients progressing or not-progressing towards EAC. The identified biomarkers are pivotal for personalized risk assessment and for the design of targeted interventions, holding promises for enhanced surveillance protocols, refined early EAC detection approaches, and improved therapeutic strategies aimed at mitigating the risk of EAC development in BE population.

507. LONG BARRETT´S ESOPHAGUS IN MONOZYGOTIC TWINS WITH ADENOCARCINOMA DEVELOPMENT

Abstract Background Familial aggregation of Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) suggests a genetic pattern in fewer than 10% of patients with the former diseases. In 1983, BE was described in identical twins, underlining the hereditary influence on the development of mucosal dysplasia in some patients with this epithelial alteration. At present, some studies have attempted to identify chromosomal alterations among patients with familial aggregation of BE or EA, but there is not a clear pattern. Methods Description of the case report of a male patient who underwent esophagectomy due to EA on a long BE, who had a monozygotic twin without gastroesophageal reflux symptoms and no upper GI endoscopies before. Results A 53-year-old man was diagnosed with EA and a long BE (8 cm length) in 2017. He underwent CROSS neoadjuvant treatment and minimally invasive Ivor-Lewis esophagectomy. The pathological report indicated a GI T3N1M0 adenocarcinoma. Unfortunately, the patient developed lung metastases and passed away in 2019. Before that, the patient recalled that he had an identical twin brother with no gastroesophageal reflux symptoms, but we decided to scope him in 2017. The gastroscopy report revealed a 2 cm hiatal hernia with a long BE (C4M6 Prague Classification) but with no dysplasia. Nowadays, the twin patient is under close follow-up with proton pump inhibitors (PPI) and has not developed dysplasia. Conclusion Monozygotic twins provide a perfect model to study the possible influence of genetic predisposition to develop BE and EA. The development of EA in a patient guided us to diagnose and treat a long BE in his asymptomatic identical twin. More studies should be done to find the possible genetic alterations linked to familial aggregation of BE and EA.

429. BARRETT'S ESOPHAGUS IN CHILDREN

Abstract Background In children, Barrett's esophagus (BE) is much less common than in adults and has its own characteristics. If in adult practice the treatment tactics are quite restrained, then in childhood they are, on the contrary, as radical as possible. Barrett's esophagus is a consequence of pathological gastroesophageal reflux disease, which is considered an obligate precancerous disease, which determines the relevance of research in this direction. Material and research methods 345 children with GERD were examined over 10 years. BE was detected in 52 children, which accounted for 14% of cases. Of these, 20 children had peptic stricture of the esophagus. They were included in the 2nd group of the study. The first group - 32 children without peptic stenosis of the esophagus. The treatment tactics for patients in the first group are fundoplication, after 3 months eradication of BE (electrodestruction or cryodestruction). In the second group - a course of bougienage, fundoplication, with destruction BE, or extirpation of the esophagus for extended peptic strictures of the esophagus. Results Of the 52 children, boys predominated (71%). The average age was 10.2 years In all cases in the first group, antireflux surgery produced a positive result, although it did not affect the regression of metaplasia in the category of patients with an endoscopically negative form. In all patients of the second group, a positive result was obtained, GER was stopped, stenosis and metaplasia of the esophagus were eliminated. Eradication of metaplasia in 45% (9 children) of cases was achieved by extirpation of the esophagus due to extensive peptic stenosis (4-6 cm), and in 55% (11 children) - postoperative endoscopic destruction BE. Conclusions BE detected in childhood is subject to eradication upon its detection, regardless of the absence of signs of high-grade dysplasia, which is more likely to occur in adulthood. Patients with an endoscopically negative form of BE require clinical observation with morphological control once a year. Extirpation of the esophagus with simultaneous coloesophagoplasty is indicated in children with peptic strictures (4-6 cm) that are not amenable to balloon dilatation against the background of fundoplication for 6 months or more.