Citations

Abstract Topic Esophageal Cancer: Barrett‘s Esophagus: High-Grade Dysplasia and Early Invasive Cancer Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying and are linked to increased gastroesophageal reflux, a recognized risk factor for Barrett’s esophagus (BE) progression to esophageal cancer (EC). Extended use of GLP-1 RAs facilitates weight loss, mitigating reflux, possibly offering a protective effect against EC. This large retrospective study aimed to assess the association between GLP-1 use with the development of dysplastic Barrett’s esophagus (BE) and EC in patients with non-dysplastic BE (NDBE). Methods We used ICD and CPT codes within the TriNetX (a large multicenter claims based) database to identify NDBE patients. The cohort was then categorized as GLP-1 users vs. non-users based on ATC code A10BJ. A 1:1 propensity matched analysis was performed with balancing of confounders (Table 1). Primary outcomes included incidence of dysplastic BE and EC. Time to event analyses were performed. Results A total of 4,534 patients were identified in the GLP-1 cohort and 55,621 in the non-GLP-1 cohort. After 1:1 matching, 4,530 patients were included in each cohort. Mean follow-up was 3.57 years in GLP-1 cohort and 3.30 years in non-GLP-1 cohort. Incidence of dysplastic BE/EC in the GLP 1 cohort was 1.24% (N=56) compared to 0.54% (N=24) in non-GLP 1 cohort. GLP-1 users demonstrated significantly higher risk of developing dysplastic BE/EC compared to non-users (RR: 2.30; 95% CI: 1.47–3.70, P = 0.0004. The cumulative incidence of dysplastic BE/EC was higher among GLP-1 cohort at 3 and 5 years—0.90 %, and 1.11%, respectively—compared to 0.47%, and 0.49 % in the non-GLP-1 group. Conclusion Our findings indicate that GLP-1 therapy was associated with an increased risk of progression to dysplastic BE/EC in patients with non-dysplastic BE. Further prospective studies are warranted to validate these results.

Abstract Topic Benign Disease: Other Background Lichen planus is a chronic immune-mediated skin disease that may involve the esophagus. Esophageal lichen planus (ELP) is considered rare, but likely underdiagnosed. Lack of published guidelines for ELP results in significant treatment variability. Given heterogeneous practice patterns and emerging treatments, further outcome data are needed. Methods A retrospective cohort of ELP patients was assembled from 3 academic centers. Patients ≥ 18 years old were identified by ICD10 code search (L43.8) in the electronic health record, from 2006 to 2025. Patients were included if they had initial endoscopy, histology, and follow-up endoscopy showing features of LP, and excluded if there was diagnostic uncertainty, unavailable procedural documentation, or other esophageal diseases. Endoscopic findings were assessed qualitatively by manual review of reports. Data abstracted included demographics, presenting symptoms, endoscopic/histologic findings, treatment, and clinical outcomes. Statistical analysis was performed in R. Results 193 patients met inclusion criteria. Mean age at index endoscopy was 65 years, 86% were female, 98% were non-Hispanic Caucasian, 39% were ever smokers, and mean BMI was 26. Dysphagia was the most common presenting symptom (90%). Strictures were common (73%), 58% underwent dilation during initial endoscopy. Endoscopic findings included presence of sloughing (20%), exudate (22%) and friability (23%). Histology showed lymphocytic infiltrate (47%), parakeratosis/dyskeratosis (42%) and Civatte bodies (17%). Topical steroids (71%) and PPIs (63%) were used most frequently for treatment. Immunosuppressives (tacrolimus, systemic steroids, mycophenolate, methotrexate, hydroxychloroquine, cyclosporine, azathioprine, JAK inhibitor) were used in 54% of patients. Endoscopic improvement was seen in 66%, with highest response rates in tacrolimus (100%), hydroxychloroquine (100%), and a JAK inhibitor (100%). Symptom improvement was seen in 63%, with the greatest benefit seen in patients treated with a JAK inhibitor (100%) and hydroxychloroquine (86%). Conclusion In this large, multisite cohort, ELP demonstrated significant morbidity, with high rates of dysphagia, strictures, and inflammatory changes. Dilation appeared to be safe, with only a single iatrogenic perforation identified. Esophageal squamous cell cancer risk was low but present, at 4%. Despite heterogeneous treatment practices, several therapies – tacrolimus, hydroxychloroquine, and JAK inhibitors – were associated with marked endoscopic and symptomatic improvement. Prospective studies are needed to clarify the optimal approach to pharmacological management of ELP.

Purpose of review A substantial proportion of esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD) cases in Barrett's esophagus (BE) are diagnosed after a dysplasia-negative endoscopy before the next recommended surveillance interval. These are classified as postendoscopy esophageal carcinoma (PEEC) or postendoscopy esophageal neoplasia (PEEN) and represent critical failures of BE surveillance. This review summarizes current definitions, epidemiology, potential etiologies, and evolving strategies to reduce PEEC/PEEN and improve the quality of BE surveillance. Recent findings High-quality endoscopic examination using high-definition white-light endoscopy (HD-WLE) and virtual chromoendoscopy (CE), adherence to the Seattle biopsy protocol, adequate inspection time, and training in the recognition of visible lesions harboring prevalent dysplasia/EAC, are critical in reducing PEEC/PEEN. Initial data on the use of adjunctive tools (wide-area transepithelial sampling) and molecular biomarkers (p53, DNA methylation panels, and Tissue Systems Pathology tests) demonstrate promising results for detecting prevalent dysplasia and for reducing PEEC and PEEN. BE surveillance quality metrics, such as cancer and neoplasia detection rates, have been shown to be inversely associated with PEEN. Summary PEEC and PEEN reflect critical gaps in the effectiveness of BE surveillance. Improving the quality of endoscopic surveillance is essential, including meticulous mucosal inspection, appropriate use of advanced imaging techniques, and adherence to systematic biopsy protocols, to minimize missed neoplasia.

Abstract The proliferation of advanced endoscopic resection techniques has provided a minimally invasive alternative to esophagectomy and revolutionized outcomes for patients with early-stage esophageal adenocarcinoma (EAC). This paradigm shift and the resulting research data on clinical and histologic determinants of treatment outcome have highlighted the heterogeneity of outcomes within EAC staged as T1 by invasion depth. Multidisciplinary cancer care teams are now routinely facing difficult decisions regarding the management of high-risk T1 EAC to balance the risk of long-term lymph node (LNM) or distant metastasis against the risks of surgical resection. In this review, we summarize the current state of knowledge regarding the staging and risk stratification of T1 EAC, with particular attention to features that contribute to a higher risk of LNM and cancer mortality. We review recent clinical trial data on positioning the use of endoscopic resection (cap-assisted or submucosal dissection) versus surgical resection in high-risk T1 EAC patients and describe adjunctive techniques to further improve risk stratification and treatment. Finally, we explore emerging and future directions, such as artificial intelligence and advanced biomarker analysis to further aid decision-making and enhance patient outcomes.

Introduction: Young-onset esophageal adenocarcinoma (EAC) often presents at advanced stages and is associated with poor outcomes. We aimed to examine the epidemiology of young-onset Barrett’s esophagus (BE) using the TriNetX database. Methods: Young-onset BE patients (age 18 to younger than 50 y) with esophagogastroduodenoscopy (EGD) within 1 year before index BE diagnosis between 2014 and 2023 were included. Negative binomial regression was used to evaluate incident-time trends, and logistic regression to assess for independent predictors of young-onset BE. Results: BE diagnosis was present in 76,691 (3.3%) of 2,337,786 patients that underwent EGD, of which 14,120 (18%) had prevalent young-onset BE. BE dysplasia/EAC was present in 6% of young-onset patients at initial diagnosis. Conventional BE risk factors also predicted young-onset BE: GERD (OR=2.4), White race (OR=2.4), male sex (OR=2.2), smoking (OR=1.2), and obesity (OR=1.1). Each additional risk factor increased the probability of BE prevalence by 74% in young patients versus 54% in older patients. The prevalence of young-onset BE was 4.5% with GERD and ≥3 additional risk factors, and 2.3% when ≥3 risk factors were present. Discussion: Young-onset BE accounts for 18% of all BE cases, demonstrates a striking 6% rate of dysplasia/neoplasia at initial diagnosis, and has a prevalence of 4.5% in those with GERD and ≥3 risk factors. These findings suggest that young-onset BE is an important patient population that merits further study. Additional studies are necessary to study the cost-effectiveness of BE screening in younger patients with multiple risk factors.

INTRODUCTION: Ongoing surveillance after successful endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is essential to detect and manage recurrence. Despite established surveillance interval recommendations after complete eradication of intestinal metaplasia (CE-IM), patient compliance with repeat endoscopy is frequently suboptimal. Understanding patient drivers to adherence is essential to inform interventions that address the high rates of overdue surveillance and loss to follow-up. METHODS: Patients with BE-related neoplasia who achieved CE-IM were eligible for inclusion and classified as delayed or on-time for endoscopic surveillance. Patients were prospectively enrolled and participated in structured virtual interviews designed to explore barriers and facilitators to on-time care. A rapid qualitative analysis approach was applied, continuing until thematic saturation was reached. RESULTS: Thirty-nine patients were interviewed: 22 (56.4%) were delayed, and 17 (43.6%) were on-time for surveillance. Patients in the delayed group had longer mean BE segment lengths and a higher prevalence of tobacco use. Geographic distance from the treatment center was the most frequently cited barrier to follow-up (n = 17; 43.5%). Other common barriers were access limitations, financial concerns, misunderstanding of disease course, and test-related anxiety. DISCUSSION: Patient-related drivers of delay in postendoscopic eradication therapy surveillance are largely logistical, socioeconomical, and psychological in nature. Solutions to reduce the significant burden on the patient and achieve timely surveillance may include transitioning patients back to their local endoscopists after CE-IM or incorporating nonendoscopic surveillance methods through patient centered approaches.

Abstract Background Integrating advanced artificial intelligence (AI) into clinical decision-support often requires the sharing of sensitive patient data with external services, raising privacy concerns. Homomorphic encryption (HE) allows computing directly on encrypted data, without revealing the underlying patient information. Objectives To develop a large language model (LLM)-assisted diagnosis framework while preserving patient privacy in the clinical text analysis, by leveraging HE and using rare disease (RD) diagnosis as a representative application. To demonstrate HE does not hinder the system performance. Materials and Methods Texts from patient histories and a RD knowledge base were embedded by LLMs into vectors, then encrypted using HE to obscure private information while retaining the semantic nuances. Diagnostic recommendations were generated by computing and ranking the similarities between the patient history and RD vectors in the encrypted space. The system was evaluated using 50 synthetic case reports (5 RDs, each with 10 reports). Results Applying HE did protect private information from reverse-embedding attacks. HE imposed little disruption to the diagnostic accuracy, with normalized discounted cumulative gains (nDCG) of 0.6108 ± 0.3412 (encrypted) versus 0.6083 ± 0.3415 (unencrypted). The accuracy and computational performance were tunable and consistent, as demonstrated across five different LLMs. Discussion Our privacy-preserving framework opens tremendous opportunities toward hosting and serving powerful AI solutions across institution boundaries, which would remove the need for local deidentification and incentivize users to access secure external decision-support services. Conclusions Integrating HE with LLM retrieval can promote the dissemination of nonredundant, high-capacity AI services by preserving both privacy and accuracy.

Abstract Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related mortality worldwide, and there are limited molecular screening options. Following a prior discovery and validation studies in subjects from the United States, China, and Iran, we aimed to validate methylated DNA markers (MDM) for ESCC detection in Malawi, a country with one of the highest ESCC incidence. Fourteen MDMs were tested on 177 tissue samples. Ten MDMs showed excellent performance (AUCs ≥ 0.85); a random forest model achieved an AUC of 0.97. The consistent cross-population performance suggests potential for universal application of these MDMs and further justifies exploring nonendoscopic sampling methods, such as swallowed cell collection devices in combination with MDMs, for efficient and cost-effective screening in high-incidence populations. Prevention Relevance: This study validates MDMs for early detection of ESCC in Malawi, supporting their potential role in noninvasive, population-based screening strategies in Africa to enable early detection and timely intervention for cancer interception, potentially reducing cancer burden in high-incidence, resource-limited regions.

Summary Central obesity is a risk factor for esophageal adenocarcinoma (EAC) independent of acid reflux. However, about a quarter of patients with Barrett’s esophagus (BE) and EAC have a normal body mass index (BMI). One hypothesis is that chronic systemic inflammation is as critical to the cancer pathway than the BMI alone. Therefore, we hypothesized that lean patients with BE/EAC would have a high prevalence of metabolic diseases. We aimed to compare metabolic diseases among lean patients with BE/EAC and overweight/obese BE/EAC and lean control without BE/EAC. We performed a propensity score–matched case–control study including patients with BE/EAC and a control group without BE/EAC from the Rochester Epidemiology Project (REP). The groups were compared using chi-square χ 2 and Student t-test as appropriate. Adjusted logistic regression models were used to compare the association with metabolic diseases. We included a total of 2504 patients (631 EAC, 621 BE, and 1252 controls). A quarter of patients (24.6%) with BE/EAC were lean. When compared to controls without BE/EAC, lean patients with BE were more likely to have diabetes (32.2% vs. 11.2%, P < 0.001) and hyperlipidemia (76.2% vs. 53%, P < 0.001). When comparing lean EAC patients to controls without BE/EAC, lean patients had a higher association with smoking (73.3% vs. 58.6%, P: 0.002) and diabetes (18.7% vs. 11.2%, P: 0.03). When compared to overweight/obese BE patients, lean BE were less likely to have NASH (7.7% vs. 20.3%, P: 0.001), diabetes (32.3% vs. 42.1%, P: 0.03), hyperlipidemia (77.2% vs. 87%, P: 0.003), and metabolic syndrome (24% vs. 54%, P < 0.001). Similarly, when compared to overweight/obese patients with EAC, lean EAC patients were less likely to have NASH (0% vs. 15.5%, P < 0.001), diabetes (18.7% vs. 34.1%, P < 0.001), hyperlipidemia (37.3% vs. 51.8%, P: 0.002), hypertension (37.3% vs. 55.3%, P < 0.001), and metabolic syndrome (8% vs. 37.6%, P < 0.001). A quarter of patients with BE/EAC are lean. Although lean BE/EAC patients have a more favorable metabolic profile compared to overweight/obese BE/EAC patients, diabetes and smoking are more common among lean patients with EAC compared to lean controls. The higher association with smoking and diabetes among lean EAC challenges traditional risk factor paradigms, suggesting a significant role for insulin resistance and chronic inflammation in EAC pathogenesis, especially in patients without typical risk factors. BMI-determined obesity may need to be supplemented with inflammatory metabolic diseases to improve assessment of BE/EAC risk in lean patients.