W. Asher Wolf

Dietary Elimination Therapy Is an Effective Option for Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is an immune-mediated disorder. Food elimination is an established treatment for children, but data in adults are limited. We aimed to determine the response of adults with EoE to dietary therapy. METHODS This was a retrospective cohort study using the University of North Carolina EoE database from 2006 to 2012. Subjects were age 18 and older, had EoE by consensus guidelines, and had undergone dietary therapy either with a targeted elimination diet or a 6-food elimination diet (SFED). Outcomes were symptomatic, endoscopic, and histologic improvement. Demographic, endoscopic, symptomatic, and laboratory predictors of response to dietary therapy were assessed. RESULTS Of 31 adults who underwent dietary therapy (mean age, 36 y; 48% male; 90% white; mean baseline eosinophil count, 78 eos/hpf), 22 had a targeted elimination diet and 9 had SFED. Symptoms improved in 71% (68% in targeted, 78% in SFED), and endoscopic appearance improved in 54% (53% in targeted, 56% in SFED). After dietary therapy, the mean eosinophil count decreased to 43 eos/hpf (P = .009). Eleven subjects (39%) responded with fewer than 15 eos/hpf (32% in targeted and 56% in SFED; P = .41). No clinical, endoscopic, or histologic factors predicted response to dietary therapy. Of the 11 responders, 9 underwent food re-introduction to identify trigger(s), and 4 (44%) reacted to dairy, 4 (44%) reacted to eggs, 2 (22%) reacted to wheat, 1 (11%) reacted to shellfish, 1 (11%) reacted to legumes, and 1 (11%) reacted to nuts. CONCLUSIONS Dietary elimination is a successful treatment modality for adults with EoE. Further research should emphasize which factors can predict effective dietary therapy.

Incidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett’s Esophagus

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barretts esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

Original ResearchFull Report: Clinical—Alimentary TractIncidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett’s Esophagus

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barretts esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

Effects of the Learning Curve on Efficacy of Radiofrequency Ablation for Barrett’s Esophagus

BACKGROUND & AIMS Complete eradication of Barretts esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.

Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression

BackgroundTopical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE).AimsWe aimed to summarize published manuscripts that report outcomes of these therapies for EoE.MethodsWe performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis.ResultsSystematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2–96.0%] for fluticasone, 76.8% (95% PL 36.1–95.1%) for budesonide, and 69.0% (95% PL 31.9–91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0–56.7), 62.5 (95% PL 125.6 to −0.67, and 44.6 (95% PL 26.5–62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1–91.1%), 87.9% (95% PL 42.7–98.6%), and 87.3% (95% PL 64.5–96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations’ baseline eosinophil count and age.ConclusionsThe literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis

Background & Aims Topical corticosteroids or dietary elimination are recommended as first‐line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6‐food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. Methods We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort‐member level. Simulation parameters were defined by systematic review and meta‐analysis to determine the base‐case estimates and bounds of uncertainty for sensitivity analysis. Meta‐regression models included adjustment for differences in study and cohort characteristics. Results In the base‐case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5‐year time horizon (

Spatial predisposition of dysplasia in Barrett's esophagus segments: a pooled analysis of the SURF and AIM dysplasia trials.

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Optimal Histologic Cutpoints for Treatment Response in Patients With Eosinophilic Esophagitis: Analysis of Data From a Prospective Cohort Study

5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base‐case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive. Conclusions In a cost utility analysis comparing topical corticosteroids and SFED for first‐line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient‐level costs or quality of life.

Radiofrequency Ablation of Barrett's Esophagus Reduces Esophageal Adenocarcinoma Incidence and Mortality in a Comparative Modeling Analysis

Objectives:Surveillance endoscopy detects dysplasia within Barrett’s esophagus (BE) and dictates treatment. Current biopsy regimens recommend uniformly spaced random biopsies. We assessed the distribution of dysplasia in BE to develop evidence-based biopsy regimens.Methods:We performed analysis of the distribution of dysplasia within BE using pretreatment biopsy data from two randomized controlled trials (RCTs) of radiofrequency ablation for dysplastic BE: the SURF (Surveillance vs. Radiofrequency Ablation) trial and the AIM Dysplasia (Ablation of Intestinal Metaplasia (AIM) Containing Dysplasia) trial. We used generalized linear models with generalized estimating equations (GEE) to estimate prevalence differences for dysplasia depending on the standardized location of biopsies. We performed Monte Carlo simulation of biopsy regimens to estimate their yield for any dysplasia within segments.Results:Dysplasia preferentially resides in the proximal-most half of the BE segment that is almost twice as likely to demonstrate dysplasia as the distal-most quartile. In pooled analysis, compared with the distal-most quarter, the prevalence difference in the proximal-most quarter was 22.6%, in the second proximal-most quarter 23.1%, and in the second distal-most quarter 15.3%. The best performing biopsy regimen in simulation studies acquired 8 biopsies in the most proximal cm of BE, 8 biopsies in the second cm, and 2 biopsies in each cm thereafter (q1cm: 8, 8, 2, 2…). A slightly simpler q2cm (every 2 cm) regimen (q2cm: 12, 12, 4…) was nearly as effective.Conclusions:The post hoc analysis of two RCTs reveals a substantially increased prevalence of dysplasia proximally in BE segments. Our simulations suggest an altered biopsy regimen could increase sensitivity of biopsies in short-segment BE by >30%.

778 Durability of Radiofrequency Ablation (RFA) in Barrett's Esophagus With Dysplasia: the AIM Dysplasia Trial At Five Years

BACKGROUND AND AIMS: No prospective studies substantiate 15 eos/hpf as an appropriate endpoint for treatment of eosinophilic esophagitis (EoE). We aimed to determine a histologic cutpoint that identifies successful treatment of EoE by assessing symptomatic and endoscopic improvement. METHODS: We performed a prospective cohort study of 62 consecutive adult patients undergoing outpatient esophagogastroduodenoscopy at the University of North Carolina from 2009 through 2014. At diagnosis of EoE and after 8 weeks of standard treatment, symptom and endoscopic responses were measured using a visual analogue scale and an endoscopic severity score (ESS), and eosinophil counts were assessed. Receiver operator curves and logistic regression models evaluated the histologic threshold that best predicted symptomatic and endoscopic response. For symptoms, analysis was limited to patients without baseline esophageal dilation. RESULTS: The mean eosinophil count at diagnosis was 124 eos/hpf, falling to 35 eos/hpf after treatment. The mean visual analogue scale decreased from 3.4 at baseline to 1.7 after treatment, and the mean ESS decreased from 3 to 1.6. Twenty‐nine patients had symptom responses (47%) and 34 had endoscopic responses (55%). Post‐treatment eosinophil count thresholds of 8, 15, and 5 eos/hpf best predicted symptom, endoscopic and combined responses, respectively. On logistic regression, decreasing eosinophil count was significantly associated with the probability of symptomatic (P = .01) and endoscopic response (P < .001). CONCLUSIONS: In a prospective study of patients with EoE, we found that a cutpoint of <15 eos/hpf identifies most patients with symptom and endoscopic improvements, providing support for the current diagnostic threshold. A lower threshold (<5 eos/hpf) identifies most patients with a combination of symptom and endoscopic responses; this cutpoint might be used in situations that require a stringent histologic threshold.