Sachdeva, Karan

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.

AbstractEndoscopic eradication therapy (EET) is recommended for the management of dysplastic Barrett’s esophagus (BE) and intramucosal adenocarcinoma. Both radiofrequency (RFA) and cryoballoon ablation (CBA) can induce complete remission of intestinal metaplasia (CRIM). We aimed to compare long-term durability following CRIM in patients treated with RFA vs. CBA.We conducted a retrospective cohort study to analyze patient outcomes following EET with RFA or CBA at two referral centers. We measured and compared the recurrence rate of BE, with or without dysplasia, after CRIM, using Cox proportional hazard models and propensity score-matched analyses. Our secondary aim was to identify predictors of recurrence.681 patients who achieved CRIM were included (RFA 610; CBA 71), with median follow-up of 4.1 years and 4.4 years following RFA and CBA, respectively. A multivariable model revealed a higher risk of any recurrence with RFA (hazard ratio [HR] 2.19, 95%CI 1.18–4.06; P = 0.01), but not dysplastic recurrence (HR 0.88, 95%CI 0.39–1.97; P = 0.75). However, a comparable risk of “any recurrence” was observed after excluding intestinal metaplasia of the gastroesophageal junction (HR 1.18, 95%CI 0.61–2.30; P = 0.62). Propensity score-matched analysis (54 cases in each group) showed that the two groups had comparable recurrence risk. Baseline maximum BE length was associated with a higher risk of any recurrence (HR 1.07; P<0.001) and dysplastic recurrence (HR 1.11; P = 0.001).The rates of any BE recurrence and dysplastic recurrence were comparable with the two modalities in this nonrandomized study.

INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51–1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56–1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.

INTRODUCTION: Screening for Barrett's esophagus (BE) is suggested in those with risk factors, but remains underutilized. BE/esophageal adenocarcinoma (EAC) risk prediction tools integrating multiple risk factors have been described. However, accuracy remains modest (area under the receiver-operating curve [AUROC] ≤0.7), and clinical implementation has been challenging. We aimed to develop machine learning (ML) BE/EAC risk prediction models from an electronic health record (EHR) database. METHODS: The Clinical Data Analytics Platform, a deidentified EHR database of 6 million Mayo Clinic patients, was used to predict BE and EAC risk. BE and EAC cases and controls were identified using International Classification of Diseases codes and augmented curation (natural language processing) techniques applied to clinical, endoscopy, laboratory, and pathology notes. Cases were propensity score matched to 5 independent randomly selected control groups. An ensemble transformer-based ML model architecture was used to develop predictive models. RESULTS: We identified 8,476 BE cases, 1,539 EAC cases, and 252,276 controls. The BE ML transformer model had an overall sensitivity, specificity, and AUROC of 76%, 76%, and 0.84, respectively. The EAC ML transformer model had an overall sensitivity, specificity, and AUROC of 84%, 70%, and 0.84, respectively. Predictors of BE and EAC included conventional risk factors and additional novel factors, such as coronary artery disease, serum triglycerides, and electrolytes. DISCUSSION: ML models developed on an EHR database can predict incident BE and EAC risk with improved accuracy compared with conventional risk factor-based risk scores. Such a model may enable effective implementation of a minimally invasive screening technology.