Falk, Gary W.

INTRODUCTION: Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations. METHODS: Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network. Endoscopic features were prospectively recorded using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS). Correlations were made between EG-REFS and clinical and histologic features. RESULTS: Of 98 patients with EG, 65 underwent assessments using EG-REFS. The most common findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings. A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001). The overall score and specific components of EG-REFS were more common in the antrum than in the fundus or body. EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field ( P = 0.0002). DISCUSSION: Prospective application of EG-REFS identified gastric features with a strong correlation with physician global assessment of endoscopic activity in EG. Endoscopic features demonstrated greater severity in patients with active histology and a predilection for the gastric antrum. Further development of EG-REFS should improve its utility in clinical studies.

Abstract Eosinophilic esophagitis (EoE), gastritis (EG), and/or duodenitis (EoD) are associated with accumulation and activation of eosinophils and mast cells in the esophagus, stomach, and/or duodenum, respectively. Lirentelimab (AK002), an antibody against siglec-8, depletes eosinophils and inhibits mast cells. We performed an open-label extension (OLE) study of subjects who completed ENIGMA (a randomized, double-blind, placebo-controlled phase 2 study of lirentelimab in adults with symptomatic, biopsy-confirmed EG and/or EoD, with or without EoE) to evaluate long-term responses. Methods Subjects who received 4 monthly infusions of lirentelimab or placebo during ENIGMA (n = 59) were eligible for the OLE; they received monthly, escalating doses of lirentelimab (0.3 or 1 mg/kg escalating to 3 mg/kg). Symptoms were assessed weekly using an electronic daily patient-reported outcome questionnaire and total symptom scores (TSS) were calculated. Patients underwent upper endoscopy with biopsy at screening and at the end of ENIGMA (day 99, week 16, blinded); in the OLE, endoscopies were performed on day 323 (30 weeks after the first dose in the OLE). Histopathology was assessed by a single pathologist. Results Fifty-eight subjects entered the OLE; 45 completed ≥52 weeks lirentelimab (including exposure during ENIGMA) and 29 completed 70 weeks. Mean TSS improved through week 70 (Figure 1). Subjects receiving 70 weeks lirentelimab (ENIGMA+OLE) had further improvements in TSS from baseline (mean reductions: 68% at weeks 29–30, 70% at weeks 51–52, 75% at weeks 69–70). Symptom scores (abdominal pain, nausea, vomiting, early satiety, appetite loss, abdominal cramping, bloating, diarrhea) decreased significantly from baseline. Treatment response was not associated with concomitant EoE. The most common adverse event was mild to moderate infusion-related reactions, usually with the first infusion. Conclusion In the OLE of the ENIGMA study, patients with EG and or EoD (with or without concomitant EoE) who received lirentelimab had sustained tissue eosinophil depletion and significant long-term symptom improvement. Symptoms continued to improve with duration of treatment. Lirentelimab appears to be a promising targeted treatment for EG and/or EoD.

AbstractBackgroundThe management of achalasia has improved due to diagnostic and therapeutic innovations. However, variability in care delivery remains and no established measures defining quality of care for this population exist. We aimed to use formal methodology to establish quality indicators for achalasia patients.MethodsQuality indicator concepts were identified from the literature, consensus guidelines and clinical experts. Using RAND/University of California, Los Angeles (UCLA) Appropriateness Method, experts in achalasia independently ranked proposed concepts in a two‐round modified Delphi process based on 1) importance, 2) scientific acceptability, 3) usability, and 4) feasibility. Highly valid measures required strict agreement (≧ 80% of panelists) in the range of 7–9 for across all four categories.Key ResultsThere were 17 experts who rated 26 proposed quality indicator topics. In round one, 2 (8%) quality measures were rated valid. In round two, 19 measures were modified based on panel suggestions, and experts rated 10 (53%) of these measures as valid, resulting in a total of 12 quality indicators. Two measures pertained to patient education and five to diagnosis, including discussing treatment options with risk and benefits and using the most recent version of the Chicago Classification to define achalasia phenotypes, respectively. Other indicators pertained to treatment options, such as the use of botulinum toxin for those not considered surgical candidates and management of reflux following achalasia treatment.Conclusions & InferencesUsing a robust methodology, achalasia quality indicators were identified, which can form the basis for establishing quality gaps and generating fully specified quality measures.

INTRODUCTION: Using the National Cancer Database, we assessed the relationship between facility overall esophageal adenocarcinoma (EAC) case volume and survival. METHODS: We categorized facilities into volume quintiles based on annual EAC patient volume and performed a multivariable Cox proportional hazards regression between facility patient volume and survival. RESULTS: In a cohort of 116,675 patients, facilities with higher vs lower (≥25 vs 1–4 cases) annual EAC patient volume demonstrated improved survival (adjusted hazard ratio: 0.80. 95% confidence interval: 0.70–0.91). DISCUSSION: This robust volume-outcome effect calls for centralization of care for EAC patients at high annual case volume facilities.