ABSTRACT
Background and Aims: A key unknown in eosinophilic esophagitis (EoE) is the long-term course of esophageal stenosis. Our aim was to evaluate the course of esophageal strictures using structured serial esophagrams and determine predictors of diameter improvement in patients with EoE. Methods: This was a retrospective study of 78 EoE patients who completed 2 structured esophagrams at an academic tertiary referral center between 2003 and 2021. Maximum and minimum esophageal diameters were measured during esophagram using a standardized protocol to reduce measurement errors. Results: The median age at first esophagram was 36.2 (12.9-64.3) years; 60.3% of patients were male; 41 patients had active EoE; and 9 were inactive. Of the patients, 39.7% had allergic rhinitis, asthma (32.1%), and atopic dermatitis (7.7%). Medical therapies at second esophagram and esophagogastroduodenoscopy included proton pump inhibitors (39.5%), swallowed topical steroids (31.6%), diet elimination (13.2%), biologic therapies (1.3%), and clinical trial medications (1.3%). Median maximum diameter significantly increased by 1.0 mm (Q1: -1.0 mm, Q3: 3.0 mm) (P = .034), independent of dilation (P = .744). Increase was most profound in patients starting in the lowest maximum diameter group (9-15 mm) with median increase of 3.0 mm. For patients in disease remission at the second esophagram, there was a significant increase in maximum diameter per year compared to active disease at 0.8 mm (Q1: 0.0 mm, Q3: 5.3 mm) and 0.0 mm (Q1: -0.4 mm, Q3: 0.6 mm) respectively (P = .019). Conclusion: Long-term improvement in esophageal strictures in patients with EoE may occur but is modest and likely occurs over years. Progression also appears to be minimal. Continuous medical treatment may reduce the rate of stricture recurrence and may improve stricture diameter over time.
ABSTRACT
BACKGROUND: Patients with benign esophageal strictures may not maintain a response to endoscopic dilation, stenting, incisional or injectional therapies. For patients with these refractory esophageal strictures, esophageal self-dilation therapy (ESDT), performed to maintain luminal patency, may provide persistent symptomatic benefit while reducing patients' reliance on healthcare services and the risk associated with repeated endoscopic procedures. AIMS: The aim of this study was to evaluate the efficacy and safety of EDST in a randomized controlled trial and prospective observational study. METHODS: Twenty-five patients with refractory benign esophageal strictures were recruited at two esophageal clinics between November 2018 and June 2021. Twelve patients participated in the randomized trial and 13 in the prospective observational study. The number of endoscopic dilations, impact of therapy on dysphagia, adverse events, and complications were recorded. RESULTS: In the randomized study, 50% of patients performing ESDT and 100% of controls required endoscopic dilation during follow-up (P = 0.02). In the observational study, the median (IQR) number of endoscopic dilations fell from 7 [7-10] in the 6 months prior to commencing ESDT to 1 [0-2] in the 6 months after (P < 0.0001). Most patients (22/25) were able to learn self-dilation. Few serious adverse events were noted. Dysphagia severity remained unchanged or improved. CONCLUSIONS: ESDT appears to be a safe effective therapy for benign esophageal strictures refractory to endoscopic treatment. CLINICAL TRIAL NUMBER: NCT03738566.
ABSTRACT
BACKGROUND AND AIMS: Upper GI bleeding (UGIB) is a common medical emergency associated with high resource utilization, morbidity, and mortality. Timely EGD can be challenging from personnel, resource, and access perspectives. PillSense (EnteraSense Ltd, Galway, Ireland) is a novel swallowed bleeding sensor for the detection of UGIB, anticipated to aid in patient triage and guide clinical decision-making for individuals with suspected UGIB. METHODS: This prospective, open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB was performed at a tertiary care center. The PillSense system consists of an optical sensor and an external receiver that processes and displays data from the capsule as "Blood Detected" or "No Blood Detected." Patients underwent EGD within 4 hours of capsule administration; participants were followed up for 21 days to confirm capsule passage. RESULTS: A total of 126 patients were accrued to the study (59.5% male; mean age, 62.4 ± 14.3 years). Sensitivity and specificity for detecting the presence of blood were 92.9% (P = .02) and 90.6% (P < .001), respectively. The capsule's positive and negative predictive values were 74.3% and 97.8%, and positive and negative likelihood ratios were 9.9 and .08. No adverse events or deaths occurred related to the PillSense system, and all capsules were excreted from patients on follow-up. CONCLUSIONS: The PillSense system is safe and effective for detecting the presence of blood in patients evaluated for UGIB before upper GI endoscopy. It is a rapidly deployed tool, with easy-to-interpret results that will affect the diagnosis and triage of patients with suspected UGIB. (Clinical trial registration number: NCT05385224.).
ABSTRACT
Background: Patients with eosinophilic esophagitis (EoE) have a unique esophageal microbiome with increased presence of Haemophilus influenzae, but its role in the disease is unclear. Objective: Microbiome-derived bacterial LPS activation of Toll-like receptors (TLR) is a potential mechanism for inducing inflammation in other chronic inflammatory diseases, but it has not been studied in EoE. Our aim was therefore to study microbiome-derived bacterial LPS activation of TLRs in EoE. Methods: We studied 10 patients with active EoE, 9 patients with inactive EoE, and 10 control patients. Esophageal biopsy samples from the controls, patients with active EoE (>15 eosinophils/hpf), and patients with inactive EoE were immunostained for the presence of H influenzae LPS, presence of TLR4, and colocalization of LPS and TLR4. Staining intensity was measured by using confocal laser microscopy and scored on a scale from 0 to 3 as the average score assigned by 2 blinded observers. Results: H influenzae LPS was detected by positive staining in 20 of the 29 patients (69.0%), including 9 of the 10 patients with active EoE (90.0%), 8 of the 9 patients with inactive EoE (89.9%), and 3 of the 10 controls (30%); its level was greater in the patients with active EoE than in the controls (P = .063). TLR4 was detected by positive staining in 19 of the 29 patients (65.5%), including 9 of the 10 patients with active EoE (90.0%), 4 of the 9 patients with inactive EoE (44.4%), and 6 of the 10 controls (60.0%); its level was higher in the patients with active EoE than in those with inactive EoE (P = .096). The result of testing for colocalization of LPS and TLR4 was positive in 8 of 10 patients with active EoE (80.0%), 1 of 9 patients with inactive EoE (11.1%), and 1 of 10 control patients (10.0%), with greater colocalization of H influenzae LPS and TLR4 staining density in the samples from patients with active EoE than in the controls or the patients with inactive EoE (P = .009 and P = .018, respectively). Conclusion: Esophageal microbiome-rich H influenzae LPS colocalizes to TLR4 in active EoE. These data lend further support to a role for the esophageal microbiome in modulating the activity of EoE.
ABSTRACT
BACKGROUND: Predictive models for eosinophilic oesophagitis (EoE) may not fully rule in the diagnosis. AIM: To develop a reverse model that predicts against EoE to eliminate the need for oesophageal biopsies. METHODS: In 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. RESULTS: The 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). CONCLUSION: A 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.
Subject(s)
Eosinophilic Esophagitis , Adult , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/pathology , Cross-Sectional Studies , BiopsyABSTRACT
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.
Subject(s)
Eosinophilic Esophagitis , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Eosinophilic Esophagitis/pathology , Prospective Studies , Eosinophils/pathology , Inflammation/pathology , Endoscopy, GastrointestinalABSTRACT
OBJECTIVE: Flexible endoscopic Zenker's diverticulotomy (FEZD) is a procedure performed primarily by gastroenterologists for treatment of symptomatic Zenker's diverticulum (ZD). Given the lack of prior investigations with large sample sizes, we report on one of the largest series of patients who underwent FEZD. METHODS: A review of patients who underwent FEZD at our institution from 2006 to 2021 was performed. Data were abstracted for patient demographics, clinical features, procedural characteristics, adverse events, and outcomes. RESULTS: A total of 75 patients (37 women) with mean age of 77.9 (33-102) years and mean (range) follow-up of 1.1 (0-13.2) years were identified. 67.9 % of FEZD cases were performed under general anesthesia. The mean procedure time was 37.1 min. Same day discharge and resumption of oral intake was seen in 56.4 % and 57.1 % of cases, respectively. Adverse events included intraprocedural bleeding (15.7 %) controlled with endoscopic means, infection (4.8 %) exclusively managed with antibiotics in all but one case, subcutaneous emphysema (2.4 %), and perforation (10.7 %) conservatively managed in all but one case. 97.6 % of patients had sustained subjective improvement in symptoms following their procedure. Fifteen patients (20 %) experienced recurrence after undergoing initial FEZD-26.7 % percent of whom were sufficiently treated with repeat FEZDs. Younger age was associated with recurrence (p < 0.01). CONCLUSION: FEZD is an effective, safe procedure for the management of symptomatic ZD. It is a viable alternative for patients in whom otorhinolaryngological procedures via rigid endoscopy are not an option.
Subject(s)
Esophagoscopy , Zenker Diverticulum , Humans , Female , Aged , Esophagoscopy/methods , Retrospective Studies , Endoscopes , Zenker Diverticulum/surgery , Treatment OutcomeABSTRACT
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.
Subject(s)
Eosinophilic Esophagitis , Humans , Biopsy , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Eosinophilic Esophagitis/pathology , Eosinophils/pathology , Prospective StudiesABSTRACT
BACKGROUND: Dietary therapy successfully treats eosinophilic oesophagitis (EoE), but limited data exist on predictors of patient response. AIMS: To determine response rates and to identify predictors of histologic response to elimination diets in adults with EoE METHODS: This 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. RESULTS: We 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). CONCLUSIONS: In 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.
Subject(s)
Eosinophilic Esophagitis , Adult , Humans , Eosinophilic Esophagitis/diagnosis , Retrospective Studies , Diet , Food , BiopsyABSTRACT
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.
Subject(s)
Eosinophilic Esophagitis , Adult , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/pathology , Eosinophil Peroxidase , Eosinophils/pathology , Staining and LabelingABSTRACT
Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard. Therapeutic endoscopy in patients with adverse events of EoE may also be required. In particular, dilation may be essential to treat and attenuate progression of the disease in select patients to minimize further fibrosis and stricture formation. Using a modified Delphi consensus process, a group of 20 expert clinicians and investigators in EoE were assembled to provide guidance for the use of endoscopy in EoE. Through an iterative process, the group achieved consensus on 20 statements yielding comprehensive advice on tissue-sampling standards, gross assessment of disease activity, use and performance of endoscopic dilation, and monitoring of disease, despite an absence of high-quality evidence. Key areas of controversy were identified when discussions yielded an inability to reach agreement on the merit of a statement. We expect that with ongoing research, higher-quality evidence will be obtained to enable creation of a guideline for these issues. We further anticipate that forthcoming expert-generated and agreed-on statements will provide valuable practice advice on the role and use of endoscopy in patients with EoE.
Subject(s)
Eosinophilic Esophagitis , Esophageal Stenosis , Dilatation , Endoscopy, Gastrointestinal , Eosinophilic Esophagitis/complications , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/pathology , Esophageal Stenosis/therapy , HumansABSTRACT
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.
Subject(s)
Eosinophilic Esophagitis , Humans , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/pathology , Anti-Inflammatory Agents/therapeutic use , Retrospective Studies , Prospective Studies , Budesonide/therapeutic use , Treatment Outcome , Steroids/therapeutic useABSTRACT
BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.
Subject(s)
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Consensus , Enteritis/diagnosis , Enteritis/complications , Gastritis/diagnosis , Gastritis/complications , Eosinophilia/diagnosis , Eosinophilia/complications , Eosinophilic Esophagitis/complicationsABSTRACT
BACKGROUND AND AIMS: Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. METHODS: Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). RESULTS: The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of .472-.736 and .469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of .580-.828 and .581-.828, respectively). Strictures were least reliably assessed (ICC, .072-.385). The original EREFS was highly responsive (SES, 1.126 [95% confidence interval {CI}, .757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI, .858-1.643]; all items expanded: SES, 1.252 [95% CI, .880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. CONCLUSIONS: EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.
Subject(s)
Eosinophilic Esophagitis , Eosinophilic Esophagitis/diagnosis , Esophagoscopy/methods , Humans , Proton Pump Inhibitors , Reproducibility of Results , Severity of Illness IndexABSTRACT
BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
Subject(s)
Eosinophilic Esophagitis/therapy , Patient Reported Outcome Measures , Adult , Aged , Child , Eosinophilic Esophagitis/pathology , Eosinophilic Esophagitis/psychology , Female , Humans , International Cooperation , Male , Middle Aged , Quality of LifeABSTRACT
BACKGROUND: Eosinophilic esophagitis is an inflammatory condition in which eosinophil infiltration leads to esophageal remodeling and stricturing, with dilation therapy often needed. Achieving histologic remission reduces the need for repeat dilation, although little is known about the effects of long-term maintenance therapy. AIMS: To further assess the relationship between short-term histologic remission and maintenance therapy on need for repeat dilation in eosinophilic esophagitis. METHODS: A total of 77 patients with eosinophilic esophagitis (59.7% male; mean age 41.6 years) seen at a single medical center from June 2000 to August 2017 were included. Information on history of dilation and therapy [proton pump inhibitors (PPIs), steroids, elimination diet] was collected. Mean follow-up was 164 weeks. Fifty-one patients achieved histologic remission and 42 of these remained on maintenance therapy (23 PPIs, 14 topical steroids, and 5 dietary therapy). Standard phone interview was completed in cases with lack of follow-up. Only patients who underwent esophageal dilation to ≥ 17 mm were included. RESULTS: A significantly lower proportion of patients on maintenance therapy required repeat dilation (12/42) compared with patients not on maintenance therapy (8/9) (hazard ratio 0.12; p < 0.001). Of patients who received maintenance therapy, 9.1% required re-dilation. The difference in need for repeat dilation in patients who achieved histologic remission on therapy (14/26) versus those who did not (20/51) was not significant (hazard ratio 1.34; p = 0.45). CONCLUSION: In a retrospective analysis of patients with eosinophilic esophagitis, we found that a significantly lower proportion who received maintenance therapy (PPIs, steroids, or dietary exclusions) required repeat dilation.
Subject(s)
Dilatation/methods , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Adult , Cohort Studies , Diet Therapy/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Proton Pump Inhibitors/therapeutic use , Retrospective Studies , Steroids/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Identification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management. STUDY DESIGN: A retrospective analysis of patients diagnosed with EoE from 2011 to 2018 was conducted. Clinical and diagnostic variables including demographics, endoscopic, and esophagram findings were compared between PPI responders and PPI nonresponders. All patients underwent a standard 8-week twice-daily PPI trial, with PPI responsiveness defined as < 15 eos/hpf on repeat EGD. Univariate and multivariable analyses were conducted to identify risk factors for nonresponse, and ROC curves were created to identify cutoff values. RESULTS: A total of 223 EoE patients (135 male, median age 39 (29-51)) were identified, with PPI nonresponse (PPI-NR) in 71% of patients. PPI-NR was seen in all 10 patients with failure of scope passage, with an OR of 9.06 by univariate analysis (P = 0.1485). In a multivariable model, age per 10 years (OR 0.71; P = 0.007), BMI per 1 kg/m2 (OR 0.94; P = 0.03), and peripheral eosinophil count per 100 per mm3 (OR 1.37; P = 0.003) were independent risk factors. Dichotomization to maximize sensitivity and specificity identified age ≤ 36 years old, BMI ≤ 25.2 kg/m2, and peripheral eos > 460 per mm3 as predictive thresholds for PPI-NR. The probability of PPI-NR was 72.4-84.5% with 1 risk factor, 87.9-93.8% with 2 risk factors, and 97.2% with all 3 risk factors. CONCLUSIONS: Young age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.
Subject(s)
Drug Resistance , Endoscopy/methods , Eosinophilic Esophagitis , Eosinophils , Esophagus , Proton Pump Inhibitors , Adult , Biopsy/methods , Body Mass Index , Drug Monitoring/methods , Eosinophilic Esophagitis/blood , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/epidemiology , Esophagus/diagnostic imaging , Esophagus/pathology , Female , Humans , Leukocyte Count/methods , Male , Predictive Value of Tests , Prognosis , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Retrospective Studies , Sensitivity and Specificity , United States/epidemiologyABSTRACT
BACKGROUND: Opioid-induced esophageal dysfunction (OIED) is a recognized complication of chronic opioid use. However, the impact of acute opioid administration on esophageal motility remains unclear. METHODS: Opioid naïve patients with high-resolution manometry (HRM) <480 min following esophagogastroduodenoscopy (EGD) (opioid-HRM) and a control group with HRM <36 h prior to EGD between January 1, 2016, and November 10, 2018, from a single institution were identified. EGDs were performed exclusively with versed and fentanyl. KEY RESULTS: One hundred and seventy-four patients were identified, with 83 (47.7%) opioid-HRM and 91 (52.3%) controls. Mean time from EGD to HRM was 229 (78-435) min. Baseline clinical features and HRM indications were similar between opioid-HRM and controls. Chicago classification v3.0 defined HRM findings were similar between groups. Major motility disorders as defined by the Chicago classification v3.0 occurred at a similar frequency among opioid-HRM and controls (27.7% vs. 36.3%, p = 0.23). Mean distal contractile integrity (DCI) was higher in opioid-HRM (1939.3 ± 1318.9 vs. 1792.2 ± 2062.3 mmHgâcmâs, p = 0.043), but maximum DCI, distal latency, and integrated relaxation pressure did not differ between groups. Subgroup analysis assessing time and dose dependency did not identify differences in individual manometric parameters and Chicago classification v3.0 diagnosis between patients with HRM <240 min after EGD, >240 min after EGD, ≥125 mcg of IV fentanyl, <125 mcg IV fentanyl and controls. CONCLUSIONS AND INFERENCES: Same-day acute opioid administration did not affect HRM findings in opioid naïve patients. Studies assessing the pathophysiology of and duration-dependent relationship with opioids in OIED are needed.
Subject(s)
Analgesics, Opioid/pharmacology , Endoscopy, Digestive System/methods , Esophageal Motility Disorders/diagnosis , Esophagus/drug effects , Fentanyl/pharmacology , Manometry/methods , Adult , Aged , Anesthetics, Intravenous/pharmacology , Chest Pain , Conscious Sedation , Deglutition Disorders , Dyspepsia , Esophagus/physiology , Esophagus/physiopathology , Female , Gastroesophageal Reflux , Humans , Male , Midazolam/pharmacology , Middle AgedABSTRACT
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.