Alexander, Jeffrey A.

ABSTRACTBackgroundAchalasia is associated with an increased risk of esophageal cancer; though reported incidence rates vary widely (0.4% to 9.2%) due to differences in demographics, follow‐up duration, and diagnostic methods. This study evaluates the risk of esophageal cancer and Barrett's esophagus (BE) in achalasia using a large national database and a propensity‐matched control cohort.MethodsAchalasia patients were identified utilizing the TriNetX database based on International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes for diagnostic procedures and lower esophageal sphincter (LES) directed therapies, including Heller myotomy, peroral endoscopic myotomy, and pneumatic dilation. A matched control group of celiac disease patients was used. A 1‐year lead time was applied to exclude secondary malignant achalasia. Outcomes included the incidence of esophageal cancer and BE, with subgroup analysis in patients following therapy.ResultsAmong 7863 achalasia patients (mean age 58.0, 51.9% female), the esophageal cancer risk was significantly higher than control (risk ratio 2.87, 95% CI: 1.56–5.27, p < 0.001). The absolute risk was low, with 40 cases (0.51%) over a mean follow‐up of 3.18 years. BE risk was also higher in achalasia (risk ratio 1.54, 95% CI: 1.24–1.90, p < 0.001), with 220 cases (2.80%). Subgroup analysis revealed no significant difference in BE risk between POEM and Heller myotomy (risk ratio 1.0, 95% CI: 0.42–2.40, p > 0.99).DiscussionThe elevated cancer risk in achalasia over a short follow‐up period warrants reconsideration of current endoscopic surveillance guidelines, despite the low absolute risk of esophageal cancer and BE.

Summary Introduction Peroral plication of the esophagus (POPE) can reduce sump size and improve symptoms in end-stage achalasia. However, its long-term efficacy and safety are unknown. Methods Patients with end-stage achalasia who underwent POPE at our institution (2016–2024) were identified. Data were abstracted for patient demographics, procedural details, and clinical and radiographic outcomes. Results Twelve patients underwent POPE. The technical success rate was 100%, with mean procedural time of 57 minutes and without adverse events. Symptomatic improvement occurred in 75% of patients (mean follow-up of 15 months), while 86% had radiographic improvement in sump size. Repeat POPE in 6 (50%) patients a mean of 2.6 years after index POPE and a third POPE in four (33%) patients a mean of 3.1 years later was performed, with similar technical success rates and outcomes to the index POPE. Conclusions POPE is a safe and repeatable long-term therapeutic option in end-stage achalasia.

SummaryBackgroundPredictive models for eosinophilic oesophagitis (EoE) may not fully rule in the diagnosis.AimTo develop a reverse model that predicts against EoE to eliminate the need for oesophageal biopsies.MethodsIn this two‐centre study, a predictive model was developed (Mayo Clinic) and validated (University of North Carolina [UNC]). Cross‐sectional data from consecutive adult patients without prior EoE who underwent upper enoscopy with oesophageal biopsies were used. EoE cases had ≥15 eosinophils/high‐power field while controls had no eosinophils. Data were collected on patient clinical and endoscopic features. Multiple variable logistic regression was used to identify predictors of non‐EoE status while maintaining specificity ≥95%. A secondary model was developed to predict against the need for endoscopy in patients suspected of having EoE without alarm symptoms.ResultsThe Mayo and UNC cohorts consisted of 345 (EoE = 94, non‐EoE = 251) and 297 patients (EoE = 84, non‐EoE = 213), respectively. A primary model based on clinical and endoscopic features predicted against EoE with c‐statistic 0.92 (95% CI: 0.88–0.96), specificity 95%, and sensitivity 65%. This model was validated (UNC) with c‐statistic 0.87 (95% CI: 0.82–0.92). A simplified scoring system was created and a threshold of ≥12 points excluded EoE with 95% specificity and 50% sensitivity. A secondary model based on clinical characteristics alone predicted against EoE with c‐statistic 0.86 (95% CI: 0.82–0.90), specificity 95% and sensitivity 39% and validated (UNC) with c‐statistic 0.78 (95% CI: 0.71–0.85).ConclusionA simplified scoring system accurately identified a group of patients with a low likelihood of EoE where unnecessary oesophageal biopsies can be avoided, potentially resulting in resource and cost savings.

SummaryBackgroundThe Th2 allergic pathway in eosinophilic oesophagitis (EoE) responds to food antigen exposure.AimTo compare the presence and temporal pattern of food antigen penetration in oesophageal mucosa in active and inactive EoE and controlsMethodsThirty‐two patients with EoE (20 active) and 10 controls were asked to eliminate all wheat and/or dairy 12, 24, 48, 72 or 96 hours before endoscopy. Immunostaining on endoscopic biopsies was performed for gliadin, casein and whey.ResultsGluten, casein and whey were detected by positive staining in 17/32 (53.1%), 21/32 (65.6%), and 30/32 (92.0%) of patients, respectively. In active vs inactive EoE, 70.0% vs 25.0% (P < 0.05), 80.0% vs 41.5%, and 90.0% vs 90.9% patients had detectable gliadin, casein and whey, respectively. Casein and whey (20.0% and 100%, respectively) but not gliadin, were present in controls. The gliadin staining density was greater in active compared to inactive disease at ≤ 24 vs >24 hours after exposure (P = 0.05) but no differences were detected when comparing active and inactive patients for casein and whey. There was greater staining density for whey than casein for all patients at ≤24 hours (mean 2.14 ± 0.91 and 1.07 ± 1.33, P = 0.02). In active EoE, IgG4 was present in 14/20 compared to one inactive patient.ConclusionThe oesophageal epithelium is selectively permeable and has relatively long dwell times for food antigens known to trigger EoE. The precise mechanism of antigen‐specific mucosal entry and the factors that determine the induction or effector trigger of the Th2 pathway activation merit further study.

LINKED CONTENTThis article is linked to Wang et al papers. To view these articles, visit https://doi.org/10.1111/apt.17221 and https://doi.org/10.1111/apt.17312

SummaryBackgroundDietary therapy successfully treats eosinophilic oesophagitis (EoE), but limited data exist on predictors of patient response.AimsTo determine response rates and to identify predictors of histologic response to elimination diets in adults with EoEMethodsThis was a retrospective, single‐centre study of adults with PPI‐refractory EoE undergoing dietary therapy with six food elimination diet (SFED) or extended six food elimination diet (ExSFED) in an outpatient setting from January 2012 to January 2019. Patient demographics, radiologic and endoscopic findings, endoscopic reference (EREF) scores, histology and symptoms were evaluated before and after food elimination. Histologic response was assessed via tissue obtained from endoscopically‐guided biopsy or Cytosponge. Dietary therapy adherence was assessed via structured phone interview. Multivariable logistic regression analysis was performed to identify predictors of dietary response.ResultsWe included 68 patients, of whom 62% had a histologic response to dietary therapy (81% to SFED, 19% to ExSFED). Median duration of follow‐up was 45 months (IQR, 34–53 months). On multivariable analysis, higher pre‐SFED EREF score was the only variable associated with dietary non‐response (OR 0.07, 95% CI 0.49, 0.98; p = 0.04).ConclusionsIn adults with EoE, histologic dietary non‐response to SFED was associated with a higher pre‐SFED EREF score, suggesting that fixed structural disease may predict dietary non‐response. Our additional observations of poor correlation between symptomatic and histologic flares, and identification of ExSFED responders, suggest that histologic confirmation should be sought before committing patients to lifelong dietary changes. We also recommend the consideration of restricting legumes and corn in SFED non‐responders as ExSFED detected additional dietary responders.

INTRODUCTION: We aimed to assess the diagnostic utility of eosinophil peroxidase (EPX) staining on Cytosponge (CS) samples in eosinophilic esophagitis (EoE). METHODS: Esophageal biopsy (BX) samples from adult subjects with EoE were assessed using peak eosinophils per high-power field (eos/hpf), EPX, and the EoE histologic scoring system. EPX staining and eos/hpf were compared (BX vs CS). RESULTS: CS EPX positivity correlated with eos/hpf (CS [ r = 0.82, P < 0.0001]; BX [ r = 0.65, P < 0.0001]) and EoE histologic scoring system (grade [ r = 0.62, P < 0.00001]; stage [ r = 0.61, P < 0.0001]). CS EPX identified subjects with active EoE (area under the curve = 0.86, P < 0.0001). DISCUSSION: The correlation of CS EPX with eosinophilic inflammation and histologic disease severity supports its diagnostic utility in EoE.