Comparisons of Fluticasone to Budesonide in the Treatment of Eosinophilic Esophagitis.

BACKGROUND: Topical steroids are first-line treatment agents for eosinophilic esophagitis; however, some studies have demonstrated modest efficacy in inducing histologic remission. AIMS: The aim of this study was to determine response to two topical steroids (fluticasone and budesonide), compare their efficacy, and examine patient characteristics which could predict non-response to topical steroids. METHODS: We performed a retrospective review of an established EoE registry. Inclusion criteria were patients >1 year of age who were diagnosed with EoE as defined by the most recent consensus guidelines. All patients were treated with an 8-week course of either swallowed fluticasone or viscous budesonide. Responders were defined as achieving <15 eosinophils per high-power field (eos/hpf) in both proximal and distal esophageal biopsies. Demographic, clinical, endoscopic, and histologic features were examined. RESULTS: The study cohort included 75 EoE patients with a median age of 33 years (range 2-64 years), 71 % adults, 84 % male, and 76 % Caucasian. Overall histologic response rate to topical steroids was 51 %, while clinical response was 71 %. There was no significant differences in histologic response to treatment between children and adults (68 vs. 44 %, p = 0.111). There was no significant difference in response between males and females (47 vs. 73 %, p = 0.191) and between the two types of steroids (48 vs. 56 %, p = 0.632). Responders and non-responders were similar in clinical presentation and baseline endoscopic findings. Following treatment, responders had significantly less peak proximal (4.0 ± 4.4 vs. 46 ± 53, p < 0.001) and distal eosinophil counts (3.5 ± 3.8 vs. 60 ± 47, p < 0.001) compared to non-responders. There were no predictors of response to steroids identified. CONCLUSIONS: Histologic response to treatment was observed in approximately half the cohort, while more than two-thirds experienced clinical response to topical steroids. Response was similar between fluticasone and budesonide. Given the lack of differences in clinical presentation or endoscopic features, predictors of non-response were not seen.

Effects of Race and Sex on Features of Eosinophilic Esophagitis.

BACKGROUND & AIMS: Clinical and endoscopic features of eosinophilic esophagitis (EoE) differ between children and adults and among racial backgrounds. We investigated whether there were any associations between race or sex and clinical presentation, endoscopic features, and histologic findings from patients with EoE of various racial backgrounds. METHODS: We performed a retrospective, multicenter, cross-sectional analysis of 793 patients with EoE (476 adults and 317 children; mean age, 26 years; range, 0.1-84 years; 72% male) from clinical registries at 5 tertiary care centers in the United States. EoE was defined per consensus guidelines. Data with predetermined variables were extracted from clinical registries at each participating institution. RESULTS: Of the study cohort, 660 patients were white (83%), 77 were African American (10%), and 56 were of other races (7%). A significantly larger proportion of white persons than African Americans or other races had dysphagia (74%, 56%, and 53%, respectively; P < .001), food impaction (35%, 13%, and 13%, respectively; P < .001), and features of EoE that included rings (46%, 25%, and 18%, respectively; P < .001) or furrows (70%, 58%, and 55%, respectively; P = .012). Males and females had similar clinical presentations, histories of atopy, findings from endoscopy, and histologic characteristics. A higher proportion of males than females had strictures (17% vs 11%; P = .038). CONCLUSIONS: Race, and to a smaller degree sex, are associated with features of EoE. African Americans have different clinical symptoms and fewer endoscopic features of EoE than white persons. EoE should be considered in African Americans even without typical findings.

Early Comparison of Inflammatory vs. Fibrostenotic Phenotype in Eosinophilic Esophagitis in a Multicenter Longitudinal Study.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that causes esophageal remodeling and stricture formation. We compared the clinical course of symptoms, endoscopic findings, histology, and changes in phenotype over time in EoE patients with inflammatory and fibrostenotic phenotypes. METHODS: Data were obtained from EoE patients from three medical centers and followed prospectively. Endoscopic features and histology from index and follow-up endoscopies were recorded. Behavior was classified as inflammatory if endoscopic findings demonstrated furrows or white plaques and as fibrostenotic if endoscopic findings included fixed rings or strictures. RESULTS: Two hundred and fifty-six EoE patients were included in the analysis. The mean age was 32±18 years, 25% of patients were <18 years, 89% of patients were Caucasians, and 74% of patients were male. The mean duration of symptoms before diagnosis was 6.8±7.2 years with a follow-up of 1.7±1.9 years (maximum follow-up of 12 years). Fifty-four percent of patients presented with fibrostenotic EoE, whereas 46% presented with inflammatory EoE. Patients with inflammatory disease were younger than those with fibrostenotic disease (24±19 vs. 39±15 years, P<0.001). Patients with fibrostenotic disease had a longer duration of symptoms than those with inflammatory disease (8.1±7.7 vs. 5.3±6.3 years, P=0.002). Over the study period, 47 (18%) had remission of inflammatory EoE, 68 (27%) continued to have inflammatory disease, 74 (29%) continued to have fibrostenotic disease, 65 (25%) fibrostenotic patients had regression of fibrosis, and 2 patients (1%) progressed from inflammatory disease to fibrostenotic disease. Patients who had regression from their fibrostenosis were more likely than patients who continued to demonstrate fibrostenosis to have a decrease in proximal (54% vs. 32%, P<0.001) and distal (70% vs. 38%, P<0.001) eosinophilia. CONCLUSIONS: Most EoE patients maintained their phenotype or had an improvement with <1% progressing from inflammatory to fibrostenosis. This suggests that early therapeutic strategies aimed at controlling inflammation may interrupt, decrease, or prevent the remodeling fibrosis in EoE.

Categorization of patients with reflux symptoms referred for pH and impedance testing while off therapy.

BACKGROUND & AIMS: Patients with suspected gastroesophageal reflux disease (GERD) often are treated empirically with proton pump inhibitors (PPIs). Patients whose symptoms are not reduced during the PPI trial are referred for further tests. We investigated whether patients referred for the evaluation of reflux symptoms had GERD. We also aimed to categorize patients with a poor response to PPIs into groups with hypersensitive esophagus or functional heartburn. METHODS: We performed a retrospective study, searching a clinical database of patients referred for GERD testing from 2006 through 2011. We collected data on all patients who underwent upper endoscopy, esophageal manometry, and 24-hour pH-impedance monitoring, and were off PPIs for at least 1 week. Evidence of GERD was determined by an abnormal upper endoscopy or 24-hour pH-impedance monitoring. Further categorization was determined by impedance results and the symptom association probability index. RESULTS: We identified 221 patients (mean age, 47.6 ± 13.3 y; 56% male; 61% Caucasians); 97% previously had been prescribed PPIs, before they were tested. The patients had erosive esophagitis (n = 21; 10%), nonerosive reflux disease with increased pH (n = 61; 27%), nonerosive reflux disease with abnormal impedance (n = 18; 8%), hypersensitive esophagus (n = 30; 14%), functional heartburn (n = 18; 8%), functional disorders other than heartburn (n = 30; 14%), and undetermined disorders (n = 43; 19%). CONCLUSIONS: In a retrospective analysis of 221 patients, roughly half of the patients referred for testing did not have evidence of GERD. Further categorization of patients can help guide diagnosis and management.

The dose of omeprazole required to achieve adequate intraesophageal acid suppression in patients with gastroesophageal junction specialized intestinal metaplasia and Barrett's esophagus.

BACKGROUND: The mainstay of medical therapy for Barrett's esophagus is normalization of esophageal acid exposure with proton pump inhibitors (PPIs). However, the optimal dose and whether once daily or twice daily is required for acid suppression is unknown. AIM: The purpose of this study was to assess whether adequate intra-esophageal acid suppression could be achieved with once daily versus twice daily omeprazole in patients with gastroesophageal specialized intestinal metaplasia (GEJSIM), short-segment (SSBE) and long-segment Barrett's esophagus (LSBE). METHODS: Patients with GEJSIM and Barrett's esophagus underwent upper endoscopy with 48-h wireless pH capsule while on once daily 20 mg omeprazole for at least 1 week. If intra-esophageal acid was not adequately controlled, defined as pH value <4 for greater than 4.2 % of the time during the second 24-h period, omeprazole was increased to twice daily for 1 week and upper endoscopy with wireless pH capsule was repeated. RESULTS: A total of 36 patients completed the study (10 patients had GEJSIM, 16 patients had SSBE, and 10 patients had LSBE). Normalization of intraesophageal pH was achieved in 28 patients (78 %) with once daily PPI and eight patients required twice daily PPI. There was no significant difference between the three groups in the proportion of patients requiring high dose PPI (GEJSIM 10 %, SSBE 25 %, LSBE 30 %, p = 0.526). CONCLUSIONS: The majority of patients with Barrett's esophagus were controlled with once daily low dose PPI and only a minority required twice daily dosing, regardless of the length of Barrett's mucosa.

Efficacy of cryospray ablation for the treatment of chronic radiation proctitis in a pilot study.

AIM: Radiation proctitis, a common condition associated with radiotherapy for the treatment of pelvic cancers, is characterized by difficult to manage rectal pain and bleeding. Cryotherapy is a novel technique, previously used in the treatment of vascular ectasias in the upper gastrointestinal tract. The aim of the present study was to determine the efficacy of cryospray application in the treatment of radiation proctitis. METHODS: This is a prospective case-series pilot study. Ten patients with symptomatic chronic radiation proctitis were consecutively enrolled over a 2-year period. Baseline clinical data were collected and an endoscopic score was calculated based on the density of ectasias and circumferential involvement. Subjects underwent up to four cryospray ablation treatment sessions at approximately 4-week intervals or until resolution of the proctitis. The endpoints of the study were endoscopic and clinical improvement in radiation proctitis. RESULTS: Ten patients (nine males and one female) with a mean age of 74 ± 7 years underwent cryospray treatment; sessions ranged from one to four (six patients had one session, three patients had two sessions, and one patient underwent four sessions). Endoscopic score significantly decreased from a mean of 10.2 ± 3.0 to 4.0 ± 2.8 (P = 0.016). Rectal pain significantly decreased from a mean of 3.1 ± 3.0 to 1.2 ± 1.7 (P = 0.042) and rectal bleeding improved in 86% (six out of seven) of patients. Nine patients reported improvement in overall well-being. No major complications were encountered. CONCLUSIONS: Cryotherapy is an effective method in the management of chronic radiation proctitis with minimal complications.

Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia.

OBJECTIVES: Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole. METHODS: This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15 eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gastroesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440 mcg twice daily or esomeprazole 40 mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, defined as <7 eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validated Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment. RESULTS: Forty-two patients (90% male, 81% white, mean age 38 ± 10 years) were randomized into fluticasone (n = 21) and esomeprazole (n = 21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm (n = 4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P = 0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group (P = 0.029). In GERD-negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P = 1.00). The MDQ score significantly decreased after treatment with esomeprazole (19 ± 21 vs. 1.4 ± 4.5, P<0.001), but not with fluticasone (17 ± 18 vs. 12 ± 16, P = 0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups. CONCLUSIONS: Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

Esophageal motor disorders in adults with eosinophilic esophagitis.

BACKGROUND: An association between eosinophilic esophagitis (EoE) and esophageal motility disorders has been described in small studies. AIMS: The aim of this study was to describe the prevalence of esophageal motor disorders in a large cohort of adults with EoE and examine whether an association exists between esophageal dysmotility and dysphagia. METHODS: A retrospective review of esophageal manometry studies in adult EoE patients was performed. Tracings were reviewed for abnormalities including nutcracker esophagus and ineffective swallows, defined as low amplitude peristalsis (<30 mmHg) or non-propagating contractions. Ineffective esophageal motility (IEM) was categorized as mild (30-40% ineffective swallows), moderate (50-60% ineffective swallows), and severe (≥70% ineffective swallows). Dysphagia was graded on a 0-3 scale for frequency and severity. RESULTS: Seventy-five tracings from EoE patients were reviewed (85% male, mean age 41 ± 12 years). IEM was identified in 25 patients and categorized as mild (n = 13), moderate (n = 6), and severe (n = 6). Nutcracker esophagus was found in three patients. There was no significant difference in eosinophil count among the motility groups: normal 46.5 ± 3.1, mild IEM 56.9 ± 36.9, moderate IEM 45.5 ± 23.7, severe IEM 34.3 ± 12.6 (P = 0.157). CONCLUSIONS: In this cohort of EoE patients, the majority had normal esophageal motility studies, although a subset of these patients had some esophageal dysmotility. It is unlikely that esophageal dysmotility is a major contributing factor to dysphagia, although it is reasonable to consider esophageal manometry testing in EoE patients to identify potential abnormalities of the smooth muscle esophagus.

CT colonography may improve colorectal cancer screening compliance.

OBJECTIVE: While colonoscopy is currently the preferred test for colorectal cancer (CRC) screening, the invasive and time-consuming characteristics of the test are often cited as reasons for noncompliance with screening. CT colonography (CTC) is a less invasive screening method that is comparable to colonoscopy for the detection of advanced neoplasia. The aim of this project was to assess patient preferences between colonoscopy and CTC in an open access system. MATERIALS AND METHODS: Two hundred fifty consecutive average-risk patients undergoing CRC screening completed a survey that assessed reasons for choosing CTC in lieu of colonoscopy, compliance with CRC screening if CTC was not offered, and which of the two tests they preferred. RESULTS: The most common reasons for undergoing CTC included convenience (33.6%), recommendation by referring provider (13.2%), and perceived safety (10.8%). Had CTC not been an available option, 91 of the 250 patients (36%) would have foregone CRC screening. Among the 57 patients who had experienced both procedures, 95% (n = 54) preferred CTC. CONCLUSION: These findings show the importance of providing CTC as an alternative screening option for CRC at our institution, which may increase CRC adherence screening rates.

Chronic proton pump inhibitor therapy associated with increased development of fundic gland polyps.

BACKGROUND: Fundic gland polyps (FGP) have been implicated with long-term proton pump inhibitor (PPI) use. AIMS: We attempted to investigate the impact of length and dosage of PPI therapy on the development of FGP. METHODS: A retrospective cohort study of all patients who had gastric polyps removed during elective upper endoscopy between March and September 2007 as part of a prior prospective study protocol was carried out. FGP were determined histologically. Prior to endoscopy, all patients completed a questionnaire regarding PPI use and length of therapy (no PPI use, 1-48 months, >48 months). The dosage of PPI was obtained via a thorough chart review of electronic medical records. RESULTS: Three hundred and eighty-five patients completed upper endoscopy and a questionnaire reporting PPI use (252 [65.4%] patients on PPI). On endoscopy, 55 patients had polyps, with the majority (43/55, 78%) being FGP, resulting in an overall prevalence of 11.1% (43/385). On univariate analysis, FGP were associated with Caucasian race (15 vs. 6%; P=0.009) and chronic PPI therapy (>48 months) (31.9 vs. 7.5%, P<0.001). There was a significant linear-by-linear association between PPI dosage and FGP prevalence (no PPI use, 7.5%; once daily, 10.8%; twice daily 17.4%, P=0.026). On logistic regression, the only independent predictor of FGP was duration of PPI use >48 months (P=0.001, odds ratio [OR] 4.7 [2.0-12.9]). CONCLUSIONS: The only independent predictor of FGP development in our study was duration of PPI therapy greater than 48 months. Increased dosage of therapy did not significantly impact the development of FGP.

A randomized comparison of methylene blue-directed biopsy versus conventional four-quadrant biopsy for the detection of intestinal metaplasia and dysplasia in patients with long-segment Barrett's esophagus.

OBJECTIVES: Methylene blue (MB) selectively stains specialized intestinal metaplasia (SIM) and may assist in surveying a columnar-lined esophagus for Barrett's esophagus associated dysplasia. METHODS: This is a prospective, randomized crossover study comparing 4-quadrant random biopsies (4QB) versus MB-directed biopsies for the detection of SIM and dysplasia in 48 patients with long segment Barrett's esophagus (LSBE). Patients randomly underwent two endoscopies over a 4-wk time period with either 4QB or MB-directed biopsies as their first or second exam. Our aim was to correlate stain intensity with histology. RESULTS: The sensitivity of MB for SIM and dysplasia was 75.2% and 83.1%, respectively. The yield of 4QB for identifying nondysplasia SIM was 57.6% (523/917) and for dysplasia was 12% (111/917). Dark staining was significantly associated with histologic grade (P < 0.007). The final diagnosis was correct in 43 (90%) patients using MB and in 45 (94%) using 4QB. The 4QB technique missed dysplasia in 3 of 21 patients while MB biopsies missed dysplasia in 5 of 21 patients. The discordance between the two techniques was not significant (P= 0.727, McNemar's test). The mean number of biopsies taken during 4QB was 18.92 +/- 6.36 and with MB was 9.23 +/- 2.89 (P < 0.001). CONCLUSION: MB requires significantly fewer biopsies than 4QB to evaluate for SIM and dysplasia. Dark staining correlates more with HGD than LGD in our experience. While MB is not more accurate than 4QB, MB may help to define areas to target for biopsy during surveillance endoscopy in patients with LSBE.

Wireless capsule endoscopy in a community gastroenterology practice.

GOALS: This study was performed to evaluate the use of wireless capsule endoscopy in a community gastroenterology practice. BACKGROUND: Experience with wireless capsule endoscopy at referral centers has been reported, but little has been reported about community gastroenterologists' experience. STUDY: A retrospective review of charts and wireless capsule endoscopies performed at a community hospital was performed. RESULTS: A total of 99 wireless capsule endoscopies were reviewed and complete data were available in 72 cases. Indications included suspected obscure GI bleeding in 97% of cases; 55% of patients were taking anti-platelet or anti-coagulant medications; 71% of examinations were complete. Pathologic findings included angioectasias (36%), gastritis/erosions (21%), bleeding (18%), small bowel ulcers (16%), duodenitis (7%), and small bowel erosions (6%). Strictures, Crohn's disease, and tumors were each seen in 3%. There were no abnormal findings in 37%. One complication, nonnatural excretion of the capsule, caused a transient bowel obstruction but passed without endoscopic intervention or surgery. CONCLUSIONS: In a community-based gastroenterology setting, wireless capsule endoscopy is a safe tool that shows abnormalities in a significant proportion of exams.

Schatzki's rings do not protect against acid reflux and may decrease esophageal acid clearance.

Schatzki's rings (SR) are a common cause of intermittent solid food dysphagia, but their etiology is unclear. Many believe they are related to acid reflux, hypothesizing that the rings act as a protective barrier against further reflux. The purpose of this study was to determine whether dilation of SR affected the degree of acid reflux. Twenty patients participated in the study. All patients underwent esophageal manometry and 24-hr pH monitoring off all acid inhibitory medications before and two weeks after esophageal dilation. No significant differences were noted in any of the reflux parameters measured before and after dilation. However, there was a trend toward reduction in symptom score in all patients, a decrease in Johnson-DeMeester score, and a decrease in supine reflux time in patients with thick SR after dilation. There was no correlation between ring diameter and the presence or absence of reflux. In conclusion, Schatzki's rings do not prevent esophageal reflux, and they may act to decrease esophageal acid clearance, especially in the supine position, thereby increasing esophageal acid exposure.