Barrett's Esophagus Research Articles

Outcomes of patients with Barrett's oesophagus with low-grade dysplasia undergoing endoscopic surveillance in a tertiary centre: a retrospective cohort study.

Barrett's oesophagus predisposes individuals to oesophageal adenocarcinoma (OAC), with the risk of progression to malignancy increasing with the degree of dysplasia, categorized as either low-grade dysplasia(LGD) or high-grade dysplasia (HGD). The reported incidence of progression to OAC in LGD ranges from 0.02% to 11.43% per annum. In patients with LGD, Australian guidelines recommend 6-monthly endoscopic surveillance. We aimed to describe the surveillance practices within a tertiary centre, and to determine the predictive value of surveillance as well as other risk factors for progression. Endoscopy and pathology databases were searched over a 10-year period to collate all cases of Barrett's oesophagus with LGD. Medical records were reviewed to document patient factors and endoscopic and histologic details. Because follow-up times varied greatly, survival analysis techniques were employed. Fifty-nine patients were found to have LGD. Thirteen patients (22.0%) progressed to either HGD or OAC (10 (16.9%) and three (5.1%) respectively); the annual incidence rates of progression to HGD/OAC and OAC were 5.5% and 1.1% respectively. All patients who developed OAC had non-guideline-adherent surveillance. A Cox model found only two predictors of progression: (i) guideline-adherent surveillance, performed in 16 (27.1%), detected progression to HGD/OAC four times earlier than non-guideline-adherent surveillance (95% confidence interval (CI) = 1.3-12.3; P = 0.016). (ii) The detection of visible lesions at exit endoscopy independently predicted progression (hazard ratio = 6.5; 95% CI = 1.9-22.8; P = 0.003). Barrett's oesophagus with LGD poses a significant risk of progression to HGD/OAC. Guideline-recommended surveillance is effective, but is difficult to adhere to. Clinical predictors for those who are more likely to progress are yet to be defined.

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.

769. CLINICAL EVALUATION OF CRYOBALLOON ABLATION FOR BARRETTS OESOPHAGUS: A UK FIRST MULTI-CENTRE EXPERIENCE

Abstract Introduction The Cryoballoon Focal Ablation System (CbFAS) (Pentax Medical Inc) is an innovative device designed for the endoscopic ablation of Barrett's-related neoplasia. This system has been shown to provide advantages such as reduced stricture rates and improved patient tolerance compared to the conventional standard of care, radiofrequency ablation (RFA). We report early outcomes from a prospective UK first multi-centre registry of consecutive patients who underwent Cryoablation for the endoscopic eradication (EET) of Barrett’s-related neoplasia. Methods Patients were prospectively enrolled from two tertiary referral centres for Barrett’s Oesophagus (BE). Inclusion criteria included patients with a BE segment no longer than 5cm with histologically-proven dysplasia on biopsy or endoscopic resection specimens suitable for EET of BE after MDT review. Cryoablation sessions were conducted at 3-month intervals until endoscopic eradication was complete. The standardised protocol involved administering 8 seconds per ablation for all enrolled patients with the CbFAS. Our primary outcome was complete eradication of BE. Secondary outcomes included the number of ablations performed, adverse events, device malfunction, stricture rate, patient tolerance, and endoscopist satisfaction which was evaluated using a 10-point Likert scale (1=poor, 10=excellent). Results Between January 2020 and December 2023, a total of 16 patients (35 treatment sessions) were treated. The median BE length was C0M2. Complete eradication of BE was achieved in 89% (8/9) of patients who had completed treatment. No instances of device malfunction or intraoperative adverse events were recorded. A stricture rate of 12.5% (2/16) was observed, both of which were successfully managed through endoscopic dilatation. All patients were recorded as tolerating the procedure well with sedation. The median endoscopist satisfaction score was 9 (+/- 2.4) with only one recorded instance of difficulty attributed to balloon positioning. Conclusions These preliminary results from the UK cryoablation registry suggest that cryoablation with the CbFAS is a safe and effective therapy for BE-related dysplasia. The stricture rate appears to be comparable to that observed with RFA and similar studies. With the planned enrolment of further centres and suitable patients, this registry will further enhance our understanding of the long-term efficacy and safety profile of cryoablation using the CbFAS.

Exploring vision transformers for classifying early Barrett's dysplasia in endoscopic images: A pilot study on white-light and narrow-band imaging.

Various deep learning models, based on convolutional neural network (CNN), have been shown to improve the detection of early esophageal neoplasia in Barrett's esophagus. Vision transformer (ViT), derived from natural language processing, has emerged as the new state-of-the-art for image recognition, outperforming predecessors such as CNN. This pilot study explores the use of ViT to classify the presence or absence of early esophageal neoplasia in endoscopic images of Barrett's esophagus. A BO dataset of 1918 images of Barrett's esophagus from 267 unique patients was used. The images were classified as dysplastic (D-BO) or non-dysplastic (ND-BO). A pretrained vision transformer model, ViTBase16, was used to develop our classifier models. Three ViT models were developed for comparison based on imaging modality: white-light imaging (WLI), narrow-band imaging (NBI), and combined modalities. Performance of each model was evaluated based on accuracy, sensitivity, specificity, confusion matrices, and receiver operating characteristic curves. The ViT models demonstrated the following performance: WLI-ViT (Accuracy: 92%, Sensitivity: 82%, Specificity: 95%), NBI-ViT (Accuracy: 99%, Sensitivity: 97%, Specificity: 99%), and combined modalities-ViT (Accuracy: 93%, Sensitivity: 87%, Specificity: 95%). Combined modalities-ViT showed greater accuracy (94% vs 90%) and sensitivity (80% vs 70%) compared with WLI-ViT when classifying WLI images on a subgroup testing set. ViT exhibited high accuracy in classifying the presence or absence of EON in endoscopic images of Barrett's esophagus. ViT has the potential to be widely applicable to other endoscopic diagnoses of gastrointestinal diseases.

361. PHOTODYNAMIC THERAPY IN THE TREATMENT OF ESOPHAGEAL MUCOSAL METAPLASIA IN CHILDREN

Abstract Background The urgency of the problem of gastroesophageal reflux disease (GERD) in pediatrics is due to the high prevalence of this pathology in children. The problem of GERD in childhood has become especially important, when a direct correlation between the duration of esophagitis and the development of Barrett's esophagus (BE) and, later, esophageal adenocarcinoma has been revealed. Photodynamic therapy (PDT) is used as one of the elements of complex treatment after antireflux surgeries for direct impact on metaplastic mucosa and restoration of normal esophageal lumen. Due to the increased detection of esophageal malignancies in adult patients, we aimed to investigate this method in the treatment of Barrett's esophagus in children. Methods There were 3 patients diagnosed with esophageal mucosal metaplasia in the thoracic surgery department. Intestinal esophageal metaplasia was detected and histologically confirmed in 1 patient, in 2 patients - gastric metaplasia of cardiac type. All patients were female. The average age of the patients was 15 years. Children underwent multiple sessions of balloon dilatation of esophageal stenosis with temporary positive effect. Taking into account persistent restenosis, presence of metaplasia areas we applied PDT. Intravenous injection of photosensitizer (PS) of chlorine series for 30 minutes was carried out 5 hours before the beginning of PDT. For PDT we used a laser unit with a wavelength of 662 nm, power of 1 W with exposure of 25-30 minutes (at the rate of 300 J/cm2), optical power meter, video gastroscope, spectroanalyzer. Results To achieve the result: complete destruction of metaplasia sites and recanalization of the esophageal lumen, 1 patient with intestinal metaplasia needed 3 sessions, 2 patients with gastric metaplasia of cardiac type - 4 sessions of PDT. In children with gastric metaplasia, an "initiation" method was developed and applied at first PDT session to induce inflammation in the esophageal mucosa. During PDT macroscopic changes of mucosa in the metaplasia area were registered: ischemia, edema and hyperemia, hemorrhagic manifestations, "parchment" mucosa. We were also focused on the amount of PS in tissues according to the graphic images of the spectroanalyzer. During control examinations we noted healing of the metaplasia zone with subsequent regeneration of the epithelium, which was confirmed histologically, and preservation of the normal esophageal lumen. Conclusion Thus, there is a possibility of effective use of photodynamic therapy for esophageal mucosal metaplasia in children and adolescents. Taking into account the minimally invasive technique, comparative cheapness of photosensitizers, equipment for generation of laser radiation, registration of photosensitizer concentration in tissues, it is possible to create the basis for conducting studies in the treatment of this pathology in children. The method of photodynamic therapy in Barrett's esophagus demonstrates high efficiency in its eradication. Increasing the number of observations will allow to make more meaningful conclusions in the future. Eradication of Barrett's esophagus in children meets the requirements of cancer vigilance.

738. WHICH PATIENTS WITH BARRETT'S ESOPHAGUS ARE MOST LIKELY FOR MALIGNIZATION? UNI AND MULTIVARIANT STUDY. RISK GROUPS

Abstract Background Barrett's esophagus (BE) is a premalignant pathology that can sometimes progress to adenocarcinoma (ADC) of the esophagus. Although the percentage of malignancy is low, one in every 200 patients/year, in the world literature there is great variability (0,1-1 % patients/year). This important discrepancy arises because we know that not all patients with BE have the same risk of malignancy. The objective of this work is allowing us to stratify patients according to their risk of malignancy. Methods We have 147 patients with a mean (range) follow-up is 13.3 years (2-33). During this period, 16 patients progressed to early esophageal ADC (10.8%), malignancy rate of 0.8 patients/year. Two study groups were obtained: 1. Patients with non-malignant BE: 131 (median age 43 years (10-79). 96 men (73%). 2. Patients with malignant BE: 16 (median age 51 years (21-74). 15 men (94%). Statistical method A univariate and multivariate statistical study was carried out to detect which factors have a greater risk of malignancy. We analyzed epidemiological, clinical, endoscopic, histological, functional factors (motility and pH) and therapeutic. RESULTS Age: 22 patients over 65 years, 22.7% of malignancy, and only 8.8% patients under 65 (p=0.05, OR=3.048). Sex 13.5 % men progressed and only 2.8 % women (p=0.045). Familial Barrett's esophagus was positive in 6 patients, 66.6% malignant, while only 8.5% without familial BE progressed (p=0.0001). EB length: patients with metaplastic segments greater than 4 cm have a 12 times greater risk of malignancy. Low grade dysplasia: 39 % patients had a diagnosis of LGD became malignant, and only 7 % patients with not LGD (p&amp;lt;0.0001, OR 8.49). Proliferation Ki67 and p53 high expression patients were malignant in 69.2% and 91.7 % (p&amp;lt;0.0001, OR 29.25 and 242.00). Esophageal functional studies 22.6% patients with esophageal body hypomotility became malignant and only 3.2 % with preserved esophageal body motility (p=0.001, OR 8.75). Neither the mean LES pressure nor the percentage of patients with hypotensive LES were statistically significant. 20.4% patients with severe acid reflux (pH &amp;lt;4 greater than 24%) became malignant versus 6.1 % patients suffered from less reflux (p=0.009, OR 3.93). Type and effectiveness of treatment Malignancy according to treatment, no differences are observed (10 % and 11.6 % en medical and surgical groups). Only 3.9 % patients with effective treatment became malignant, while in 48.1% who failed treatment (p=0.0001, OR 22.9). Multivariate analysis Only LGD reached statistical significance (p=0.007) with an OR 7.18, and the high expression of p53 (p&amp;lt;0.0001) with an OR 89.14. Risk groups Based on statistical analysis, we have established three risk groups (figure 1). We included 5 patients with High Risk (3.5%, F-U 8.6 years), all malignant (100%, 11.6% patients/year). Intermediate Risk 33 patients (22.5%, F-U 11.97 years, with progression in 11 patients (33.3%, 2.7% patients/year). Low Risk to 109 patients (74%), none became malignant. (p&amp;lt;0.0001, OR: 1.78). Conclusion In patients with high and intermediate risk, therapeutic options and endoscopic follow-up should be different than in patients with the absence of these disease characteristics, classified as low risk.

563. CURRENT AND PROPOSED TREATMENT STRATEGIES FOR LOCALLY ADVANCED ESOPHAGEAL ADENOCARCINOMA OF THE ESOPHAGOGASTRIC JUNCTION

Abstract Background The optimal treatment strategy for locally advanced esophageal adenocarcinoma of the esophagogastric junction (AEG) is still unclear, and no consensus exists whether to treat it as an esophageal cancer or as a gastric cancer, which would include adjuvant therapy. The purpose of this study was to determine the optimal lymph node dissection, considering lymph node metastases and to develop a strategy for treatment that includes adjuvant therapy to improve the survival rate. Methods The patients were selected from a retrospective study by the Department of Surgery, Institute of Gastroenterological Surgery, Tokyo Women’s Medical University, that was conducted from 1990 to 2019. We studied 88 cases of advanced AEG in patients who underwent surgery with lymph node dissection. We retrospectively investigated the patient characteristics, pathological findings, surgical procedures, optimum extent of lymph node dissection, location of metastatic lymph nodes, recurrence pattern, and survival curves. Results Positivity for H. pylori was 29.8%. Barrett esophagus was found in 33%. Barrett esophagus was low. The calculated index for each nodal station was in stations 1, 2, 3, 7, 11 and 110 for 3-year survival and in stations 1, 2, 3 and 7 for 5-year survival. The proportion with undifferentiated histological type was high. The surgical approach underwent lower esophagectomy + proximal gastrectomy. Double-tract reconstruction was performed in 45%. Adjuvant (postoperative) chemotherapy was given to 51% patients. Preoperative (neoadjuvant) chemoradiotherapy was 17%. The 5-year overall survival rates were 24%. Conclusion We found that the optimal lymph node resection consists of the inferior mediastinum (No. 110), the lesser curvature (Nos. 1, 3, 7), No. 2, and No 11. When esophageal involvement was &amp;gt; 40 mm, we performed esophagectomy including upper thoracic lymph nodes. We were not satisfied with the result of surgical treatment including lymph node dissection alone in advanced AEG. We will recommend nab-paclitaxel combined with radiotherapy for advanced AEG to improve the survival rate.

435. PREVALENCE OF OESOPHAGEAL PREMALIGNANT LESIONS AMONG PATIENTS REFERRED FOR GASTRO-OESOPHAGEAL-DUODENOSCOPY AT A TERTIARY CARE HOSPITAL IN NORTHERN, SRI LANKA

Abstract Background Oesophageal cancer is the second leading cause of cancer-related mortality in Sri Lanka, where a higher prevalence is found among Tamil-speaking Sri Lankans. Endoscopic screening with Lugol’s chromo endoscopy in high-incidence populations reduces mortality from oesophageal cancer. The objective of this study is to determine the prevalence of premalignant oesophageal lesions - squamous dysplasia and Barrett’s oesophagus and the associated risk factors among Tamil patients undergoing oesophageal-gastro-duodenoscopy (OGD). Methods Consecutive patients undergoing OGD for dyspeptic and gastric acid reflux symptoms were recruited. An interviewer-administered questionnaire was used for data collection. During OGD, the oesophagus was examined under white light imaging, narrow band imaging (NBI), and Lugol’s iodine chromo endoscopy. Biopsies were taken from abnormal mucosa and sent for pathological diagnosis. Statistical software SPSS (V25) was used to analyse the data. Results The study incorporates 410 participants. The majority (61.7%) were females and the median age was 57 (Interquartile range 21) years. On Endoscopy under white light and NBI 11.0%(n=45) had squamous neoplasia. Of them, 16.0% had Low grade dysplasia (LGD), 2.0% had invasive carcinoma and the remaining 82.0% had inflammatory or reactive changes. Endoscopic Barrett’s oesophagus (BO) was found in 17.0% (n=69) and 5.0% (n=19) had both endoscopic and histological confirmation of BO. Of them, 21.0% had LGD. In regression analysis, male gender was at higher risk for BO (OR- 1.251, 95%CI 0.420 – 3.730). Overall, 3.0% of the participants had premalignant lesions. Conclusions The prevalence of premalignant lesions in a symptomatic population was only 3.0%. Further studies with a larger number of targeted population is needed to assess the exact prevalence.

547. DISEASE SPECIFIC MORTALITY OF EARLY-STAGE ESOPHAGEAL NEOPLASIA IN BARRETT’S ESOPHAGUS TREATED WITH ENDOSCOPIC THERAPY

Abstract Background High-grade dysplasia (HGD) and intramucosal (T1a) esophageal adenocarcinoma (EAC) are indication for endoscopic eradication therapy (EET) with endoscopic resection (ER) and/or radiofrequency ablation (RFA). The goal of the endoscopic therapy is to prevent progression to advanced EAC and cure the underlying Barrett’s esophagus (BE) when present. Previous studies have showed high rate of success of EET in short term, however little is known about long term results of EET. We aimed to evaluate long-term outcome of EET with particular reference to disease specific mortality and progression to major surgery. Methods We conducted a single center retrospective study including patients who underwent EET for HGD and T1a EAC January 2005-December 2022. We excluded patients with gastric disease and evidence of T1b EAC at baseline ER. Primary outcomes assessed disease specific mortality (DSM) of esophageal cancer in this longitudinal cohort, which is defined as death within 12 months of progression to advanced cancer. Secondary outcomes evaluate endoscopic recurrence, progression to esophagectomy, post-procedure complications and 5-year overall survival. Results 299 patients were included in this study. 252 were treated with a combination of ER and RFA, whereas 47 only received primary RFA. Median number of EET sessions in both patient groups is 4(p=0.48). Patients with HGD were more likely to be detected on surveillance compared to those with T1a EAC (p=0.004). We demonstrate a DSM rate of 2.7%(n=8), with a 5-year overall survival of 74.6%(n=223). 5.7%(n=17) of patients sustained severe post-procedure complications (Clavien-Dindo&amp;gt;3). Endoscopic recurrence occurred in 18.7%(n=56) and 6.7%(n=20) developed disease progression that required surgical intervention. Baseline T1a was associated with higher rates of esophagectomy compared to HGD (p=0.0135). Conclusion EET is a safe and effective treatment for patients with early-stage esophageal neoplasia. In comparison to esophago-gastric surgery, EET offers excellent results with a significantly lower morbidity and mortality risk. However, it is resource intensive as patients often require multiple treatments with long-term, routine surveillance. Patients also require strict compliance to maximize therapeutic outcomes and prevent recurrence or progression. Further studies are required to improve risk-stratification in this cohort and determine the optimal surveillance strategy post EET.

787. THE CHALLENGE OF GASTRO-ESOPHAGEAL ONCOLOGICAL SURGERY AFTER BARIATRIC PROCEDURES: EXPERIENCE OF A REFERRAL HIGH-VOLUME UPPER GI SURGICAL CENTER

Abstract Background The effectiveness of bariatric surgery for weight loss in morbidly obese patients has been well established and it's becoming more common as many surgeons are trained to perform them safely, even in older patients. Obesity is associated with reflux and hormonal imbalances that increase the risk of Barrett's esophagus, esophageal adenocarcinoma and gastric cancer. Bariatric procedures alter gastric anatomy, vascularization and lymphatic drainage and render subsequent upper gastrointestinal surgery for malignancies a technical challenge, that will present more and more in the future. We present laparoscopic sleeve gastrectomy, gastric bypass and gastric banding conversion to oncological respective surgeries. Methods We retrospectively reviewed the medical records of our referral high-volume center for upper gastrointestinal surgery and identified patients who underwent upper gastrointestinal oncologic surgery from January 1998 to May 2024. We selected all patients who had previously undergone bariatric surgery (laparoscopic sleeve gastrectomy, laparoscopic gastric bypass, gastric banding, or other less common procedures). Three patients met our criteria, and we recorded: demographic characteristics, surgical technique, oncologic surgical outcome, postoperative complications, long-term complications, and oncologic follow-up. Results A hybrid IvorLewis esophagectomy was performed years after a sleeve gastrectomy for distal esophageal adenocarcinoma. The sleeve was used for gastric pull-up, adequately vascularized by the right gastroepiploic artery as demonstrated by intraoperative indocyanine green. A patient developed adenocarcinoma of the cardia after Roux-en-Y gastric bypass, infiltrating the gastric pouch, the gastric remnant and liver S2. After neoadjuvant chemotherapy, an open Ivor-Lewis esophagectomy was performed using the gastric remnant for a pull-up. In a third patient, a locally advanced adenocarcinoma of the stomach developed after gastric banding. After neoadjuvant chemotherapy, an open total gastrectomy with Roux-en-Y esophagojejunostomy was performed. Conclusion We report three cases of successful esophago-gastric oncological surgery in patients with altered anatomy and vascularization due to previous bariatric surgery, without major postoperative complications or mortality. Oncologic benchmarks for both esophageal and gastric surgery were met as a high lymph node yield and oncologic margins were maintained. Our heterogeneous series suggests that sleeve gastrectomy, gastric bypass, and gastric banding surgery can be successfully converted to resective surgeries after a metachronous neoplasia diagnosis in high-volume upper gastrointestinal centers. These and similar modified reconstructive techniques are likely to be used in the future as metabolic surgery and esophago-gastric cancer are increasing.

Laparoscopic revisional antireflux and hiatal hernia surgery results in a higher rate of complications and severity at 90 days than primary surgery

ObjectiveData on graded complications and their frequency after laparoscopic revisional antireflux and hiatal hernia surgery compared with primary surgery are lacking. We describe 30- and 90-day morbidity using the Clavien-Dindo classification. MethodsA total of 298 patients underwent revision surgery between 2003 and 2020 and were propensity matched to primary surgeries (1:2 ratio) based on age, sex, body mass index, American Society of Anesthesiology classification, Los Angeles grade esophagitis, presence of Barrett's, and indication for surgery. Complications were graded using the Clavien-Dindo classification, with the highest grade of complication reported per patient. ResultsAfter matching, both groups had a majority of female patients, with a median age of 60 years and a median body mass index of 29.5 kg/m2. Most were healthy, with nonerosive esophagitis and modest levels of Barrett's esophagus. A laparoscopic Nissen fundoplication was most common; however, a partial fundoplication was more common in revisions. Mesh, relaxing incisions, and Collis were more common in revisional surgery. At 30 days, total complications were similar (23.5% [70/298] vs 20.6% [123/596], P = .373) with 1 death in each group. Minor complications (less than Clavien-Dindo 3A) were comparable. Patients undergoing revisional surgery experienced Clavien-Dindo 3B complications (4.7% [14] vs 0.8% [5], P > .001) more frequently, with esophageal obstruction requiring revision and esophageal/gastric leak being most common. Grade Clavien-Dindo 4 A/B complications were comparable in both groups. At 90 days, patients undergoing revisional surgery experienced overall complications (7.1% [21] vs 2.0% [12], P = .003), and Clavien-Dindo 3B complications (1.0% [3] vs 0, P = .037) more frequently, with intra-abdominal abscess washout being the most common Clavien-Dindo 3B complication. ConclusionsRevisional surgery results in similar total complications at 30 days, but additional complications can occur out to 90 days.