Eluri, Swathi

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.

INTRODUCTION: The adjunctive use of p53 immunohistochemistry has been proposed as a potential tool to improve risk stratification in Barrett's esophagus (BE) with conflicting results. We performed a systematic review and meta-analysis to evaluate the performance of p53 in predicting progression to advanced neoplasia (high-grade dysplasia [HGD] and esophageal adenocarcinoma [EAC]) among patients with BE. METHODS: We searched multiple databases for studies that evaluated the use of aberrant p53 in esophageal biopsies among patients with BE and reported progression rates to HGD/EAC. The outcomes were p53 test characteristics and incidence and risk ratio (RR) for progression to HGD/EAC in patients with and without aberrant p53 using random effects models. RESULTS: Among the 27 included studies, the proportion of patients with aberrant p53 expression at baseline was 20% (95% CI: 14%, 27%). The rate of progression with and without aberrant p53 was 8 per 100 person-years (95% CI: 6, 11) and 0.3 per 100 person-years (95% CI: 0.1, 0.6), respectively. Compared with patients without aberrant p53 expression, those with aberrant p53 had a higher risk for progression to HGD/EAC in cohort studies (RR = 10.2 [95% CI: 6.9, 15.0]) and case control studies (RR = 3.3 [95% CI: 2.5, 4.4]). The sensitivity for progression for non-dysplastic Barrett's esophagus and low-grade dysplasia/indefinite for dysplasia was 42% and 77% and specificity was 96% and 76%, respectively. DISCUSSION: While aberrant p53 expression has been associated with an increased risk of progression to advanced neoplasia in patients with BE undergoing surveillance, the diagnostic characteristics are suboptimal precluding uniform clinical adoption. Prospective studies with standardized grading protocols are needed to determine whether p53-guided surveillance strategies can meaningfully improve patient outcomes.

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 Accurate identification of dysplasia in Barrett's esophagus (BE) remains a challenge. Advanced optical imaging techniques may allow for better localization of dysplasia in BE. Here, we have assessed the potential clinical utility of a previously described multimodal imaging probe combining optical coherence tomography (OCT) with angle‐resolved low coherence interferometry (a/LCI) to prospectively identify dysplasia in BE. Imaging was conducted on 37 patients undergoing endoscopic surveillance of BE, yielding co‐registered biopsies of 50 esophageal sites. The a/LCI nuclear morphology data were compared to a previous decision line to prospectively predict dysplasia, demonstrating 100% sensitivity, 93% specificity, and 94% overall accuracy. The NPV was 100%, comparable to previous a/LCI studies. The addition of OCT imaging markedly improved PPV and specificity, compared to previous studies with a/LCI alone, illustrating the clinical utility of the combined platform. These findings suggest that combining OCT and a/LCI enables better detection of dysplasia by providing better guidance.

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.

Summary The eosinophilic esophagitis (EoE) Endoscopic Reference Score (EREFS) measures endoscopic severity. While a score of ≤2 has been proposed for endoscopic response, it is unknown whether achieving this threshold results in clinically important outcomes. We aimed to determine whether an EREFS response to topical steroids (tCS) is associated with a decreased need for future esophageal dilation. In this retrospective cohort study, we included patients with a new diagnosis of EoE who underwent esophageal dilation, were then treated with tCS, and had at least two follow-up endoscopies. Endoscopic response was defined as EREFS ≤2. Histological and global symptom responses were recorded. We compared patients with and without endoscopic response and calculated the number of subsequent dilations in each group. Of 113 EoE patients, 55 (49%) had endoscopic response post-tCS. Compared to endoscopic non-responders, responders were older (43.4 vs 34.4 years; p = 0.001) and had lower EREFS (4.4 ± 1.6 vs. 6.3 ± 1.5; p < 0.001) at baseline. EREFS responders required fewer dilations on their initial post-treatment endoscopy (65% vs 90%; p = 0.002) and had greater symptom (92% vs 64%; p = 0.005) and histologic responses (82% vs 24% <15 eos/hpf; p < 0.001). Over the median follow-up time of 1106 days, EREFS responders required fewer dilations than non-responders (4.5 ± 2.9 vs 6.2 ± 4.5; p = 0.03). Endoscopic responders to tCS required fewer esophageal dilations compared to non-responders. Responders also had better symptom and histologic responses. These results provide evidence that endoscopic response is associated with important clinical outcomes including a reduction in future esophageal dilations.

Summary While it is commonly known that patients with rheumatologic diseases can have esophageal dysfunction, this association is insufficiently understood. The aim is to determine the prevalence and characteristics of esophageal motility disorders in patients with rheumatic diseases. This is a single-center retrospective study of adults with rheumatologic disease who underwent high-resolution esophageal manometry (HREM). Those with and without a motility disorder (defined per Chicago classification CCv3.0 criteria, given the timing of the prior studies) were compared and multivariable logistic regression was used to determine odds of motility disorder by rheumatic disease. Of 289 patients, the mean age was 60.5 ± 13.8 years. Rheumatic diseases included Raynaud’s (42%), rheumatoid arthritis (RA) (39%), Sjogren’s (21%), systemic lupus erythematous (19%), systemic sclerosis (17%), and mixed connective tissue disease (13%). On HREM, 58% had an esophageal motility disorder: achalasia (5%), EGJ outflow obstruction (20%), jackhammer (8%), diffuse esophageal spasm (1%), ineffective esophageal motility (28%), and fragmented peristalsis (2%). Of note, 50% of the sample with a normal barium swallow had an esophageal dysmotility disorder on HREM. Those with psoriatic arthritis were less likely to have esophageal dysmotility (73% vs. 27%; P = 0.04). There was decreased odds of esophageal hypocontractility in those with RA (OR [95%CI]: 0.27 [0.12–0.58]) and increased odds (OR [95%CI]: 3.13 [1.16–8.41]) of esophageal hypocontractility among those with scleroderma. Esophageal motor disorders were found in more than half of patients with rheumatologic diseases who underwent HREM. HREM should be considered in patients with rheumatic conditions presenting with esophageal symptoms.