HSC Section 6 Nov2016 Green Book

white plaques, mucosal tearing/friability, strictures, Schatzki rings, and erosive esophagitis. The MDQ was completed by all patients at the end of the study. Histopathology All biopsy samples were embedded in formalin and stained with hematoxylin and eosin. Samples to include slides from index endoscopy and following treatment were reviewed and read by a single-blinded expert gastrointestinal pathologist. Each slide had three separate sections and all were reviewed. Eosinophils were counted in all available fields limited by the size of the biopsy specimens. A high-powered field was considered ×40 magnifica- tion on our microscopes, which measured 0.19mm 2 . The total number of eosinophils in all fields was counted and the peak eosinophil count per hpf was reported. Findings of eosinophilic microabscesses, intercellular edema, evidence of eosinophilic degranulation, epithelial basilar hyperplasia, and whether eosi- nophils were confined to the epithelial basal layer or extended to the epithelial surface (full thickness involvement) were also noted. End points The primary end point measuredwas histological response defined as achieving <7 eos/hpf in both proximal and distal esophageal biopsies following 8 weeks of treatment. Secondary outcomes measured included symptomatic change in dysphagia on the basis of the score from the MDQ and interval change in endoscopic and other histological findings. Statistical analysis Sample size estimation was based on the following assumptions: 10% of patients will be GERD positive and respond to PPIs compared with 55% of the patients treated with topical steroids. Controlling the probability of a Type I error at α = 0.05, a sample of 38 patients in the treatment groups (19 in each arm) will have 80% power to detect a difference in treatment response of 45%. Data were collated and analyzed with SPSS 15.0 statistical analysis package (SPSS Inc, Chicago, IL). Categorical data are expressed as frequency and percentage, and continuous data as means and stand- ard deviation (s.d.). Histological response, comparison of histologi- cal markers, and endoscopic features between the two treatment groupswere analyzedusing Fisher’s exact test.Within each treatment arm, the change in MDQ score after treatment was compared with Wilcoxon signed rank test. Adherence to treatment was compared using Mann–Whitney U test. Spearman rank correlation coefficient ( r s ) was used to assess the relationship between reflux impedance episodes in the proximal and distal esophagus to eosinophil counts, as well as the relationship of change in MDQ and eosinophils count post treatment. A P value of <0.05 was considered statistically significant. Analysis was performed as intention to treat. RESULTS Forty-two patients with esophageal eosinophilia were enrolled into the study. The mean age ± s.d. was 38 years old ±10, 81% were Caucasian, 10% Hispanic, 7% African American, and 1%

other. Sixty-two percent of patients had a history of coexisting atopic diathesis (33% seasonal allergies, 29% food allergies, 10% asthma, and 5% eczema). The primary indication for endoscopy was dysphagia (69%), followed by food impaction (19%), heart- burn (12%), and other (2%). Nineteen percent (8/42) had GERD by Johnson-DeMeester score and were equally stratified into each treatment arm. Endoscopy revealed Los Angeles Grade A erosive esophagitis in seven patients, all of whom had GERD by John- son-DeMeester score. There were significantly more acid reflux episodes on 24-h pH monitor in the FP arm compared with the ESO arm (45.8±40.6 vs. 25.5±19.3, P =0.045), as well as imped- ance reflux episodes (63.6±23.1, 44.8±21.4, P =0.012) ( Table 1 ). There was no significant change in mean eosinophil counts before and after treatment in either arm (FP: 55.9±25 vs. 39.2±29.4, P =0.102; ESO: 42.9±18.9 vs. 30.5±33.7, P =0.174) ( Figure 1 ). His- tological response was achieved in 33% (7/21) of ESO patients vs. 19% (4/21) of FP patients, P =0.484. Among the eight patients with GERD, all four patients randomized to ESO achieved histo- logical response, whereas none of the four patients randomized to FP achieved a histological response, P =0.029. In the 34 GERD- negative patients, response was achieved in 18% (3/17) of ESO patients vs. 24% (4/17) of FP patients, P =1.000. Among patients with coexisting allergies, response was similar between the two treatment groups, FP: 27% (3/11) vs. ESO: 33% (5/15), P =1.000. The histological response for FP vs. ESOwas similar in the proxi- mal esophagus (29 vs. 55%, P =0.118) and in the distal esopha- gus (19 vs. 40%, P =0.181). In two patients of the FP arm and four patients of the ESO arm, histological response was achieved in the proximal but not distal esophagus. Improvement in other histo- logical markers of EoE following treatment (basal cell hyperpla- sia, intercellular edema, eosinophilic microabscess, eosinophilic degranulation, and eosinophilic distribution within the epithe- lium) was similar between the two treatment arms ( Table 2 ). Frequency and severity of dysphagia were similar at baseline between the two treatment arms. The majority of patients reported moderate to severe dysphagia on question no. 3 of the MDQ with no significant difference between the two groups, (FP 77% vs. ESO 83%, P =0.512). In terms of frequency of dysphagia (question no. 4), the majority of patients reported symptoms from less than once per week to several times per week with no difference between the two treatment arms (FP 89% vs. ESO 83%, P =0.646). Only three patients indicated symptoms with every meal. On baseline questionnaire, 30% of patients randomized to FP avoided fibrous foods (meat, chicken, bread, celery, salad) compared with 42% of patients randomized to ESO, P =0.381. The MDQ score before and after therapy significantly improved in the ESO group (19±21 vs. 1.4±4.5 P =0.001), but not in the FP group (17±18 vs. 12±16, P =0.162) ( Figure 2 ). A similar finding was noted among GERD-negative patients: there was a significant difference in MDQ score before and after treatment with ESO (16±14 to 1.7±5.0, P =0.001) but not with FP (18±19 to 10±16, P =0.086). Overall, there was no significant correlation between the change in symptoms by MDQ and the change in eosinophil count in the proximal ( r s =0.001, P =0.996) and distal ( r s =0.101, P =0.558) esophagus.

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