Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

BACKGROUND: The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. AIMS: (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). METHODS: Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. RESULTS: EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. CONCLUSION: The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

Use of the Esophageal Sponge in Directing Food Reintroduction in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS: In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS: The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS: In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS: gov, Number NCT02599558.

Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound.

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

Magnet-assist endoscopic augmentation of the lower esophageal sphincter for treatment of gastroesophageal reflux disease: cadaveric and survival studies in a porcine model (with video).

BACKGROUND: Augmentation of the lower esophageal sphincter (LES) is the primary goal of both surgical and endoscopic therapies for gastroesophageal reflux disease (GERD). The feasibility, efficacy, safety, and reversibility of a newly developed endotherapy for GERD using intraluminal magnets referred to as a magnet closure device (MCD) were evaluated. METHODS: This study involved nine cadaveric and six survival pigs. The MCD consisted of a ring neodymium magnet attached to a 2-0 polypropylene suture and suture anchor. The MCD was deployed onto the esophageal wall at the region of the LES using an endoscopic suturing device. Two to three MCDs were placed on opposing walls to induce closure of the esophageal lumen. LES pressures were measured using high-resolution manometry at the index procedure (baseline and immediately post-MCD placement) and at survival endoscopy. Endoscopic removal of the devices was performed followed by necropsy at week 2. RESULTS: MCDs were successfully deployed in all cadaveric (n = 22) and survival animals (n = 12). In cadavers, 20/22 (91%) sutures were full-thickness with no adjacent organ injury. In survival animals, mean LES pressure increased from 8.4 mmHg (baseline) to 32.4 mmHg immediately post-procedure (p < 0.01). No clinically significant adverse events occurred. Repeat endoscopy at two weeks showed intact MCDs in 4/6 (67%) animals with significant increase in median LES pressure (n = 4, 24.0 mmHg versus 7.4 mmHg [baseline], p < 0.05). Endoscopic removal of MCDs was successfully achieved. CONCLUSIONS: Endoscopic augmentation of the LES using a new MCD was feasible, safe and reversible with significantly increased LES pressures recorded. Future studies are needed to enhance durability. These preliminary results on a reversible technique are promising and may represent an attractive alternative to endoluminal GERD therapy.

Mucosal penetration and clearance of gluten and milk antigens in eosinophilic oesophagitis.

BACKGROUND: The Th2 allergic pathway in eosinophilic oesophagitis (EoE) responds to food antigen exposure. AIM: To compare the presence and temporal pattern of food antigen penetration in oesophageal mucosa in active and inactive EoE and controls METHODS: Thirty-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. RESULTS: Gluten, 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. CONCLUSION: The 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.

Postobesity Surgery Esophageal Dysfunction: A Combined Cross-Sectional Prevalence Study and Retrospective Analysis.

INTRODUCTION: Esophageal dysmotility including features of achalasia may develop because of bariatric surgery. However, the prevalence of these complications is unknown. We sought to define the prevalence of dysphagia and major esophageal motility disorders including achalasia after bariatric surgery through a large retrospective database review. METHODS: Patients with a history of laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass who underwent a diagnostic high-resolution impedance manometry (HRIM) either before or after bariatric surgery across 3 large tertiary referral sites from June 2012 through February 2019 were identified from a procedural database. HRIM studies were interpreted per the Chicago classification v3.0 by a blinded investigator (K.R.). Demographic/clinical features were collected. In addition, patients who underwent bariatric surgery from January 2014 to April 2015 were contacted and administered a validated symptom assessment survey to gauge the overall prevalence of dysphagia in a postbariatric population. RESULTS: A total of 137 patients were identified, including 97 who underwent HRIM after bariatric surgery (laparoscopic sleeve gastrectomy [n = 39, 40.1%]; Roux-en-Y gastric bypass [n = 58, 59.8%]) at a median of 5.84 years (interquartile range 2.1-12.5) postoperatively and 40 preoperative bariatric surgery candidates with medically complicated obesity. A manometric pattern consistent with achalasia was identified in 7 (7.2%) postsurgical patients compared with none in the preoperative group (P = 0.08). We further identified a separate achalasia-like pattern defined by aperistalsis and increased intragastric pressure (postobesity surgery esophageal dysfunction [POSED]) in 5 (5.2%) postsurgical patients vs none found preoperatively (P = 0.14). Achalasia or POSED was associated with postbariatric surgery (12.4% vs 0%, P = 0.02). Increasing time since surgery was independently associated with the development of achalasia (median 12.5 vs 5.8 years, P = 0.02), POSED (median 15.0 vs 5.8 years, P = 0.02) and major motility disorders (6.6 vs 4.9 years, P = 0.01). Furthermore, among 271 postbariatric surgery patients contacted for symptom assessment via survey, the prevalence of dysphagia was 13.7% at a mean 3.9 years after surgery. DISCUSSION: Postoperative dysphagia is a common long-term complication of bariatric surgery. This is potentially the consequence of a time-dependent association with the development of postoperative esophageal dysmotility, particularly achalasia and POSED. Consequently, esophageal dysmotility may be an important under-recognized complication of bariatric surgery.

Erosive Esophagitis Portends a Benign Clinical Course in the Majority of Patients.

INTRODUCTION: Indefinite proton pump inhibitor (PPI) therapy and endoscopic evaluation for Barrett's esophagus is recommended for erosive esophagitis (EE). However, the clinical course of EE remains undefined. METHODS: Adults with EE on esophagogastroduodenoscopy (EGD) were identified at Mayo Clinic Rochester between January 2003 and September 2005. Patients with repeat EGD performed after index endoscopy were included. Patients with a history of upper gastrointestinal surgery, esophageal cancer, achalasia, or Barrett's on initial EGD were excluded. RESULTS: Of 219 patients identified, 98 had LA grade A, 72 LA grade B, and 49 LA grade C esophagitis. Persistent EE was found in 27% on repeat endoscopy. No patients progressed to more severe grades of esophagitis. While discontinuation of PPI was associated with persistent esophagitis, long-term healing of esophagitis occurred in the majority of patients despite discontinuation of PPI. Grade A or B esophagitis and the absence of hiatal hernia were also independent predictors of esophagitis healing on multivariate analysis. The rate of Barrett's esophagus was similar among patients with LA grade A/B and C esophagitis on initial EGD (5% vs. 14%, p = 0.6). CONCLUSION: The majority of patients with EE demonstrated healing at follow-up endoscopy regardless of continued PPI use. A small proportion developed Barrett's esophagus, including those with LA grade A and B esophagitis, highlighting a potential role for repeat endoscopy in all grades of EE. A more conservative long-term PPI strategy may be reasonable in patients with LA grade A or B esophagitis in the absence of hiatal hernia.

Prospective multicenter study to evaluate capsule endoscopy competency using a validated assessment tool.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is an established, noninvasive modality for examining the small bowel. Minimum training requirements are based primarily on guidelines and expert opinion. A validated tool to assess the competence of CE is lacking. In this prospective, multicenter study, we determined the minimum number of CE procedures required to achieve competence during gastroenterology fellowship; validated a capsule competency test (CapCT); and evaluated any correlation between CE competence and endoscopy experience. METHODS: We included second- and third-year gastroenterology fellows from 3 institutions between 2013 and 2018 in a structured CE training program with supervised CE interpretation. Fellows completed the CapCT with a maximal score of 100. For comparison, expert faculty completed the same CapCT. Trainee competence was defined as a score ≥90% compared with the mean expert score. Fellows were tested after 15, 25, and 35 supervised CE interpretations. CapCT was validated using expert consensus and item analysis. Data were collected on the number of previous endoscopies. RESULTS: A total of 68 trainees completed 102 CapCTs. Fourteen CE experts completed the CapCT with a mean score of 94. Mean scores for fellows after 15, 25, and 35 cases were 83, 86, and 87, respectively. Fellows with at least 25 interpretations achieved a mean score ≥84 in all 3 institutions. CapCT item analysis showed high interobserver agreement among expert faculty (k = 0.85). There was no correlation between the scores and the number of endoscopies performed. CONCLUSION: After a structured CE training program, gastroenterology fellows should complete a minimum of 25 supervised CE interpretations before assessing competence using the validated CapCT, regardless of endoscopy experience.

A decreased abundance of clostridia characterizes the gut microbiota in eosinophilic esophagitis.

Abnormalities in the gut microbiome are associated with suppressed Th2 response (Belizario et al., 2018 Mediators Inflamm. 2018:2037838) and predisposition to atopic disease such as asthma and eczema. We investigated if this applies to eosinophilic esophagitis (EoE). Stool bacterial DNA was extracted and followed by 16S rRNA amplification from 12 patients with eosinophilic esophagitis and 12 controls. Alpha- and beta-diversity were analyzed. Only two patients had asthma or atopy and one patient was on budesonide. No patients were on PPIs. Patients with EoE had lower gut microbiota alpha diversity (species richness, P = 0.09; Shannon index, P = 0.01). The microbial composition was distinct as evidenced by significantly different beta diversity (P = 0.03) when compared to healthy controls. There were also significant differences in relative abundance at multiple taxonomic levels when comparing the two communities; at the phylum level, we observed a marked decrease in Firmicutes and increase in Bacteroidetes and at the order and family level there were significant decreases in Clostridia and Clostridiales in patients with EoE (q ≤ 0.1). We conclude that there are significant differences in microbial community structure, microbial richness, and evenness and a significant decrease in taxa within the Clostridia in patients with EoE. Our data suggest that Clostridia based interventions could be tested as adjuncts to current therapeutic strategies in EoE.