Citations

Summary Barrett’s esophagus (BE) is the only recognized precursor to esophageal adenocarcinoma, but progression risk is highly heterogeneous. While most patients with nondysplastic BE have an annual cancer risk less than 0.5%, a subset with dysplasia or adverse molecular profiles carries markedly higher risk. This variability necessitates precision risk stratification to optimize surveillance and intervention. We review the evolution of BE risk stratification from historical consensus frameworks to contemporary clinical, histologic, and molecular models. Key clinical predictors, validated scoring systems, and recent advances in biomarker-based and imaging-driven surveillance are summarized, with emphasis on their validation and clinical applicability. Established clinical risk factors—age, male sex, smoking, segment length, and dysplasia—remain central to risk prediction. Biomarker assays, including p53 immunohistochemistry, tissue systems pathology and methylation-based assays may provide risk stratification beyond histology. Advances in endoscopic imaging, wide-area transepithelial sampling, and non-endoscopic capsule-based collection platforms could transform surveillance into a risk-adapted paradigm. The management of BE is shifting from a one-size-fits-all surveillance model toward personalized, biomarker-guided care. Integration of clinical, histologic, and molecular data—underpinned by artificial intelligence and real-world validation—promises to refine surveillance, reduce overtreatment, and improve early cancer detection in Barrett’s esophagus.

Goals: This study aimed to assess perspectives and practices among expert gastroenterologists regarding the screening, diagnosis, and management of BE. Background: Significant variability in the management of Barrett’s esophagus (BE) persists among physicians despite the development and dissemination of several clinical practice guidelines. Study: An online survey was conducted with 38 expert gastroenterologists specializing in BE management. The 38-question survey evaluated demographics, medical management, and attitudes toward endoscopic treatment, with responses analyzed for trends and variations. Results: Of the 38 experts, 34 (89%) responded. Respondents were primarily male (85%), with 82% affiliated with academic hospitals and 53% clinically focused on BE. Half discussed BE risks during initial consultations for gastroesophageal reflux disease (GERD). Most (61.8%) agreed BE should be considered in women with chronic GERD, and 88.2% regularly used narrow-band imaging (NBI). However, 44% were neutral or disagreed with diagnosing BE based solely on community gastroenterologist biopsies, and acceptance of Wide-Area Transepithelial Sampling with 3D Analysis (WATS-3D) for Barrett’s esophagus diagnosis and surveillance was limited. Fifty-three percent recommended ablation for nondysplastic BE. Fifty-two percent recommended indefinite daily PPI therapy after complete eradication of intestinal metaplasia (CEIM), regardless of symptoms. When encountering cardia intestinal metaplasia after endoscopic eradication, 38% recommended ablation, while 47% continued surveillance. Conclusion: This study highlights substantial variations in the management of BE among expert gastroenterologists, despite the existence of updated guidelines. Identifying these discrepancies is crucial for optimizing care. Further efforts are needed to standardize practices and enhance the implementation of evidence-based guidelines in clinical settings.

Abstract Aberrant DNA methylation and copy-number alterations (CNA) drive Barrett’s esophagus progression to esophageal adenocarcinoma; however, their combined utility for early detection is unclear. We aimed to identify and validate methylated DNA markers (MDM) and CNAs to distinguish esophageal adenocarcinoma/high-grade dysplasia (HGD) from nondysplastic Barrett’s esophagus (NDBE). In this multiphase, multicenter study, we discovered and validated MDMs and quantified CNAs utilizing whole-genome methylation sequencing of esophageal brushings. DNA biomarkers identified from discovery were further validated in independent patients with paired esophageal brushing and swallowed capsule sponge samples. MDMs were filtered against a reduced representation bisulfite sequencing dataset obtained from independent tissue samples to advance only concordant candidates. CNA burden was quantified using ichorCNA-derived aneuploidy scores (AS). Two hundred MDMs discovered in HGD (N = 18) and esophageal adenocarcinoma (N = 18) versus NDBE brushing samples (N = 18) were tested in independent samples (N = 146). A 52-MDM panel achieved a cross-validated AUC of 0.88 [95% confidence interval (CI), 0.82–0.95]; the addition of AS improved discrimination of HGD/esophageal adenocarcinoma from NDBE to 0.91 (95% CI, 0.86–0.97) AUC. At 80% specificity, the combined model detected 93% of esophageal adenocarcinoma and 88% of HGD cases. In paired capsule sponge samples, a 58-MDM panel achieved a cross-validated AUC of 0.77 (95% CI, 0.66–0.88); a combined 58-MDM and AS model achieved AUC 0.80 (95% CI, 0.7–0.9). MDMs and AS discerned HGD/esophageal adenocarcinoma from normal esophagus/NDBE in endoscopic brushing and capsule sponge samples. This approach may improve Barrett’s esophagus surveillance. Prevention Relevance: This study demonstrates that combining epigenetic and genomic biomarkers across minimally invasive sampling methods can accurately distinguish HGD/esophageal adenocarcinoma from nondysplastic Barrett’s esophagus, offering promising, less invasive strategies to improve BE surveillance and enable endoscopic therapy for esophageal adenocarcinoma prevention and treatment.

In this brief review we discuss the potential reasons underlying and follow up of patients who have a positive non-endoscopic swallowable cell collection device+biomarker (such as TFF3) test but no evidence of Barrett’s esophagus on endoscopy. We discuss the potential role of careful examination of the gastroesophageal junction and targeted biopsies of any visible lesions, as well endoscopic follow up in 3-5 years in the absence of any alarm symptoms. Considerations of the use of new technologies such as wide area transepithelial sampling in this situation are also discussed.

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: The risk of progression to esophageal adenocarcinoma in Barrett's esophagus (BE) increases with advancing degrees of dysplasia. There is a critical need to improve the diagnosis of BE dysplasia, given substantial interobserver variability and overcalls of dysplasia during manual community pathologist reads. We aimed to externally validate a previously cross-validated BE dysplasia diagnosis deep learning model (BEDDLM) that predicts dysplasia grade on whole slide images (WSIs). METHODS: We digitized nondysplastic BE (NDBE), low-grade (LGD), and high-grade dysplasia (HGD) histology slides from 3 external academic centers. A consensus read by 2 expert study pathologists was used as the criterion standard. Slide stain characteristics were normalized using cycle-generative adversarial networks. WSIs were assessed by BEDDLM using an ensemble approach, combining a “You Only Look Once” model followed by a ResNet101 classifier model. RESULTS: We included 489 WSIs. Consensus histopathology revealed 232 NDBE, 117 LGD, and 140 HGD WSIs. The mean age (SD) was 66.9 (11.4) years; 413 (84.7%) were men. Using the BEDDLM ensemble model, sensitivity and specificity for NDBE were 73.3% (95% confidence interval [CI]: 67.09%–78.85%) and 93.4% (95% CI: 89.62%–96.10%); for LGD, 84.6% (95% CI: 76.78%–90.62%) and 80.6% (95% CI: 76.26%–84.54%); and for HGD, 80.7% (95% CI: 73.19%–86.89%) and 94.8% (95% CI: 91.97%–96.91%), respectively. The F1 score was 0.81, 0 0.69, and 0.83 for NDBE, LGD, and HGD, respectively. DISCUSSION: Our externally validated deep learning model demonstrates substantial accuracy for the diagnosis of BE dysplasia grade on WSIs.

AbstractAlthough endoscopic submucosal dissection (ESD) is associated with higher en-bloc and R0 resection rates than cap-assisted endoscopic mucosal resection (cEMR), its comparative impact on achieving complete remission of dysplasia (CRD) and intestinal metaplasia (CRIM) in BE endoscopic eradication therapy (EET) is not well defined. We aimed to compare the journey of patients from initial endoscopic resection (ER) with ESD and cEMR to achieving CRD and CRIM.Patients undergoing ESD or cEMR followed by ablation for BE neoplasia at two academic institutions in the United States were included. Primary outcomes included CRD and CRIM rates following ER in the two groups. Secondary outcomes included the number of resection/ablative procedures from initial ER to achieving CRD and CRIM. Inverse probability treatment weighting (IPTW) was used to balance confounding variables between groups.A total of 801 patients (606 cEMR, 195 ESD) were included. ESD group patients had higher en-bloc resection rates (ESD 94.4%, cEMR 44.7%). Higher rates of CRD were observed in patients undergoing initial ESD (HR 1.53, P < 0.01). With time-to-event and IPTW analyses, rates of achieving CRD and CRIM were comparable between the groups. There were no significant differences in mean number of endoscopic resection or ablative procedures among patients undergoing initial cEMR resection compared with those treated with initial ESD.Despite larger lesion sizes and more cancers in patients undergoing ESD, the EET journey to achieving CRD and CRIM was comparable to that in patients receiving cEMR. Prospective studies are required to further study differences between these two treatment approaches.