Systematic review with network meta-analysis: comparative effectiveness of topical steroids vs. PPIs for the treatment of the spectrum of eosinophilic oesophagitis.

BACKGROUND: Controversy surrounds the clinical and histological response to topical steroids in patients with eosinophilic oesophagitis (EoE). AIM: To perform a systematic review and network meta-analysis of randomised controlled trials to assess the efficacy of topical steroids compared with placebo or proton pump inhibitor (PPIs) for the management of eosinophilic oesophagitis. METHODS: Cochrane Central Register of Controlled Trials and MEDLINE from inception to 1 July 2015 was searched. Data were extracted independently by two authors. Methodological quality was assessed using the Cochrane risk of bias tool. A network meta-analysis was performed using the Bayesian methods under random-effects multiple treatment comparisons. Results were summarised as odds ratio along with credibility intervals. We also calculated the ranking probability for each treatment based on surface under the cumulative ranking curve (SUCRA). RESULTS: The overall methodological quality of included studies was low. SUCRA ranking probability indicated that PPI had the highest probability of being the best treatment for achieving histological remission and mean change in eosinophils (0.81 and 0.85, respectively), followed by budesonide (0.74 and 0.63, respectively) and fluticasone (0.5 and 0.5, respectively). None of the comparisons indicated a statistically signicant difference. CONCLUSIONS: The results from network meta-analysis show that there is no statistically significant difference between PPI, budesonide and fluticasone for the treatment of EoE as assessed by the histological and clinical response. The evidence is limited by serious risk of bias and imprecision, which emphasises the urgent need for large RCTs with adequate sample size and methodological rigour to provide conclusive evidence.

Case report of proton pump inhibitor responsive esophageal eosinophilia: why 2 months of proton pump inhibitors is required.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease defined by the 2nd EoE consensus panel as: 'symptoms related to esophageal dysfunction, ≥15 eosinophils per high-power field, eosinophilia that persists after a trial of proton pump inhibitor (PPI) therapy, and exclusion of other secondary causes of esophageal eosinophilia'. After Ngo et al. first reported a case series of 3 patients initially diagnosed with eosinophilic esophagitis responding endoscopically and histologically to PPI therapy, the term PPI-responsive esophageal eosinophilia has evolved. Several studies have since confirmed the existence of this entity. Although recent ACG guidelines call for a 2-month course of PPI followed by endoscopy biopsies this recommendation is classified as a strong recommendation with 'low evidence', and has not been proven in the literature. We present a case of PPI-REE treated with rabeprazole 20 mg BID for 2 months, and describe simultaneous symptom resolution with histological and endoscopic remission of disease. This unique case with serial endoscopy and histology at baseline and monthly suggests the current recommendation of at least two months therapy with PPIs dosed twice daily is appropriate. Future studies will need to address duration of high dose therapy, whether patients can be stepped down to once a day PPI, and therapeutic strategy for transient responders.

Multinucleated histiocytes in esophageal squamous mucosa secondary to gastroesophageal reflux disease in a patient with esophageal stricture.

We present a novel finding of multinucleated histiocytes associated with acute and chronic inflammation secondary to gastroesophageal reflux in a patient with a history of esophageal stricture, representing the first documented case after a review of the literature. Multinucleated squamous cells, while rare, are a more common finding in association with reactive and inflammatory conditions and have been reported in other areas of the body, such as the vulva, skin, and colon. Esophageal involvement with multinucleated epithelial giant cells appears to be a much less frequently encountered occurrence with only one previous report in the literature. We add to this series an interesting case of esophageal multinucleated giant cells that are histiocytes rather than epithelial cells, supported with positive CD68 immunohistochemical staining. Our patient had severe esophageal dysphagia with stricture with history of food impaction, requiring several dilation sessions to achieve an esophageal luminal diameter of 17 mm. There was marked clinical and endoscopic improvement with proton pump inhibitor and endoscopic therapy. The multinucleated mucosal histiocytes at the time of biopsy were likely due to reactive changes from chronic injury due to food stasis and reflux.

Intrabolus pressure on high-resolution manometry distinguishes fibrostenotic and inflammatory phenotypes of eosinophilic esophagitis.

The aim of this investigation was to determine the motility patterns of inflammatory and fibrostenotic phenotypes of eosinophilic esophagitis (EoE) utilizing high-resolution manometry (HRM). Twenty-nine patients with a confirmed diagnosis of EoE according to clinicopathological criteria currently being managed at the Joy McCann Culverhouse Swallowing Center at the University of South Florida were included in the retrospective analysis. Only patients who completed HRM studies were included in the analysis. Patients were classified into inflammatory or fibrostenotic subtypes based on baseline endoscopic evidence. Their baseline HRM studies prior to therapy were analyzed. Manometric data including distal contractile integral, integrated relaxation pressure, and intrabolus pressure (IBP) values were recorded. HRM results were interpreted according to the Chicago Classification system. Statistical analysis was performed with SPSS software (Version 22, IBM Co., Armonk, NY, USA). Data were compared utilizing Student's t-test, χ(2) test, Pearson correlation, and Spearman correlation tests. Statistical significance was set at P < 0.05. A total of 29 patients with EoE were included into the retrospective analysis. The overall average age among patients was 40 years. Male patients comprised 62% of the overall population. Both groups were similar in age, gender, and overall clinical presentation. Seventeen patients (58%) had fibrostenotic disease, and 12 (42%) displayed inflammatory disease. The average IBP for the fibrostenotic and inflammatory groups were 18.6 ± 6.0 mmHg and 12.6 ± 3.5 mmHg, respectively (P < 0.05). Strictures were only seen in the fibrostenotic group. Of the fibrostenotic group, 6 (35%) demonstrated proximal esophageal strictures, 7 (41%) had distal strictures, 3 (18%) had mid-esophageal strictures, and 1 (6%) patient had pan-esophageal strictures. There was no statistically significant correlation between the level of esophageal stricture and degree of IBP. Integrated relaxation pressure, distal contractile integral, and other HRM metrics did not demonstrate statistical significance between the two subtypes. There also appeared no statistically significant correlation between patient demographics and esophageal metrics. Patients with the fibrostenotic phenotype of EoE demonstrated an IBP that was significantly higher than that of the inflammatory group.

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the esophageal diagnostic working group.

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms.

Population-based assessment of heartburn in urban Black Americans.

Prevalence data for heartburn in the urban Black American community is lacking. In order to estimate prevalence for this community, we analyzed data from an ongoing cohort study in progress at our hospital. Comprehensive interviews allowed for exploration of factors associated with heartburn. Complex, stratified sampling design was the method used. Survey invitations are hand-delivered to random blocks in a single zip code tabulation area. One member per eligible household is invited to complete a computer-based survey. Heartburn was defined as ≥ 3 days/week of symptoms as defined by the Montreal Definition and Classification of gastroesophageal reflux disease. Scaling and weighting factors were utilized to estimate population level prevalence. Multivariate logistic regression was used to identify independent predictor variables for heartburn. Enrolled 379 participants corresponding to a weighted sample size of 22,409 (20,888-23,930) citizens. Demographic characteristics of the sample closely matched those of the entire targeted population. Overall, the weighted prevalence of heartburn ≥ 3 times per week was 17.6% (16.4-18.8%). Variables independently associated with heartburn were body mass index, daily caloric and fat intake, diabetes mellitus (odds ratio = 2.95; 2.59-3.36), cigarette smoking, and alcohol consumption (odds ratio = 2.55; 2.25-2.89). Factors inversely associated included illicit drug use and increased physical activity. Waist : hip ratio showed no relationship. The prevalence of heartburn ≥ 3 times per week is high in the Black American community. Adverse lifestyle behaviors showed particularly important associations. Our study needs to be replicated in other communities with similar demographics.

Review article: oesophageal dilation in adults with eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis is a chronic inflammatory disorder of the oesophagus, characterised by the proton pump inhibitor-refractory accumulation of eosinophils in the oesophageal epithelium (>15 intraepithelial eosinophils/high powered field). Adults present with solid food dysphagia and recurrent food impactions. Oesophageal remodelling produces the characteristic endoscopic feature of adult eosinophilic oesophagitis including strictures, rings and a narrow calibre oesophagus. AIM: To evaluate the safety and efficacy of oesophageal dilation as the initial therapy for adults with eosinophilic oesophagitis. METHODS: Medline search from 1975 to November 2010 for all reports of the treatment of patients with eosinophilic oesophagitis using search words: eosinophilic oesophagitis treatment, dilation and eosinophilic oesophagitis, steroids and eosinophilic oesophagitis. RESULTS: Our systematic review found that 92% of patients treated with oesophageal dilation had improvement in their dysphagia symptoms for up to 1-2 years. Three case series clearly showed clinical resolution of dysphagia symptoms, independent of the degree of eosinophil infiltration, which was unchanged after dilation. Postprocedure pain for several days is common, due to some degree of mucosal tear, but true perforation very rare (<0.1%). CONCLUSIONS: Oesophageal dilation is an acceptable option for healthy adult eosinophilic oesophagitis patients with anatomic narrowing, possibly followed by a course of topical steroids to reduce inflammation and retard remodelling. Future studies should include a head-to-head comparison of topical steroids and oesophageal dilation, bougie vs through-the-scope balloon dilation and maintenance topical steroids compared with on-demand treatment.

Trends and perioperative outcomes of inpatient antireflux surgery in the United States, 1993-2006.

Antireflux surgery is an effective treatment for gastroesophageal reflux disease, but postoperation complications and durability may be problematic. The objective of the study was to determine whether inpatient antireflux surgery continued to decline in the United States due to concerns about its long-term effectiveness and the popularity of gastric bypass surgery and to assess recent changes in its perioperative outcomes. Using the Nationwide Inpatient Sample, we identified adult patients undergoing inpatient antireflux surgery during 1993-2006 and compared the trends of inpatient antireflux surgery with inpatient gastric bypass surgery. Perioperative complications included laceration, splenectomy, transfusion, esophageal dilation, total parenteral nutrition, and infection. Inpatient antireflux surgery increased from 9173 in 1993 to 32 980 in 2000 (+260%) but then decreased to 19 668 in 2006 (-40%). Compared with 2000, patients undergoing inpatient antireflux surgery in 2006 were older (49.9 ± 32.4 vs. 54.6 ± 33.6 years) and had a longer length of stay (3.1 ± 10.0 vs. 3.7 ± 13.4 days), more complications (4.7% vs. 6.1%), and higher mortality (0.26% vs. 0.54%) (all P < 0.05). Compared with inpatient gastric bypass surgery, length of stay was longer and mortality was higher for inpatient antireflux surgery in 2006, but neither was significant controlling for age. In 2006, perioperative outcomes of inpatient antireflux surgery were better in high-volume hospitals (all P < 0.01). Inpatient antireflux surgery continued to decline in the United States from 2000 to 2006, concomitant with a dramatic increase in inpatient gastric bypass surgery. Older patient age and worsening perioperative outcomes for inpatient antireflux surgery suggest increased medical complexity and possibly a larger share of reoperations over time. Designating centers of excellence for antireflux surgery based on local expertise may improve outcomes.

Esophageal dilation: simple and effective treatment for adults with eosinophilic esophagitis and esophageal rings and narrowing.

The goal of this article is to present the results of the long-term treatment with esophageal dilation of a consecutive series of adults with eosinophilic esophagitis (EoE). EoE in adults is a disease of middle aged white males, with recurrent food impactions and dysphagia. The exact treatment of EoE is unknown due to the uncertainty of the pathogenesis. Currently, the long-term follow-up of adult EoE patients is limited. Sixteen consecutive adult patients (12 males/4 females between ages 27 and 58 years) with EoE underwent a detailed history and baseline upper gastrointestinal endoscopy (EGD) with multiple esophageal biopsies. Thirteen had esophageal dilation. Fifteen were on proton pump inhibitor (PPI) therapy. After dilation, one patient was treated with a restrictive diet. One patient took prn fluticasone. Most of the patients had allergy testing for food and aeroallergens. Follow-up evaluation with similar testing was on average 22 months (range: 12-40 months). Six patients were not available for follow-up. None of the remaining 10 patients had a food impaction; one required further esophageal dilation. Only two patients had intermittent dysphagia. The average dysphagia score decreased from 2.1 to 0.3 (P < 0.002). The average number of eosinophils at follow-up was not significantly different from baseline (120 eosinophils/HPF proximally and 165 eosinophils/HPF distally (P= 0.75). The gross endoscopy findings were unchanged in all patients except one who normalized. A total of 62% and 75% of patients had positive tests for aeroallergens and food allergens, respectively. Over an average of two years, esophageal dilation provided excellent symptomatic relief among 10 adult EoE patients despite no improvement in the mucosal eosinophilia or gross endoscopic appearance.

Dysphagia lusoria: a comprehensive review.

Dysphagia lusoria is a rare vascular anomaly identified in a small number of patients being evaluated for dysphagia. The purpose of this paper is to present an illustrative case and provide a comprehensive review of the underlying anatomy, diagnosis, and management of dysphagia lusoria based on a review of the medical and surgical literature over the past 20 years.

High-resolution solid-state manometry of the antropyloroduodenal region.

Manometric recording from the pyloric channel is challenging and is usually performed with a sleeve device. Recently, a solid-state manometry system was developed, which incorporates 36 circumferential pressure sensors spaced at 1-cm intervals. Our aim was to use this system to determine whether it provided useful manometric measurements of the pyloric region. We recruited 10 healthy subjects (7 males:3 females). The catheter (ManoScan(360)) was introduced transnasally and, in the final position, 15-20 sensors were in the stomach and the remainder distributed across the pylorus and duodenum. Patients were recorded fasting and then given a meal and recorded postprandially. Using pressure data and isocontour plots, the pylorus was identified in all subjects. Mean pyloric width was 2.1 +/- 0.1 cm (95% CI: 1.40-2.40). Basal pyloric pressure during phase I was 9.4 +/- 1.1 mmHg, while basal antral pressure was significantly lower (P = 0.003; 95% CI: 2.4-8.4). Pyloric pressure was always elevated relative to antral pressure in phase I. For phases II and III, pyloric pressure was 7.7 +/- 2.3 mmHg and 9.4 +/- 1.1 mmHg, respectively. Pyloric pressure increased similarly after both the liquid and solid meal. In addition, isolated pressure events and waves, which involve the pylorus, were readily identified.

Review article: the management of heartburn in pregnancy.

Heartburn is a normal consequence of pregnancy. The predominant aetiology is a decrease in lower oesophageal sphincter pressure caused by female sex hormones, especially progesterone. Serious reflux complications during pregnancy are rare; hence upper endoscopy and other diagnostic tests are infrequently needed. Gastro-oesophageal reflux disease during pregnancy should be managed with a step-up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first-line drug therapy. If symptoms persist, any of the histamine2-receptor antagonists can be used. Proton pump inhibitors are reserved for women with intractable symptoms or complicated reflux disease. All but omeprazole are FDA category B drugs during pregnancy. Most drugs are excreted in breast milk. Of systemic agents, only the histamine2-receptor antagonists, with the exception of nizatidine, are safe to use during lactation.

Review article: extraoesophageal manifestations of gastro-oesophageal reflux disease.

Although recent studies suggest that gastro-oesophageal reflux disease may frequently contribute to ear, nose and throat and respiratory diseases, the cause-and-effect relationship is far from proven. The review will address this controversial topic emphasizing recent literature raising concerns about the credibility of this association and our tests to make this diagnosis. The author believes these extraoesophageal symptoms suspected to be secondary to gastro-oesophageal reflux disease are an unresolved issue, but selective use of aggressive proton-pump inhibitor therapeutic trials may help to resolve this problem in our individual patients.

Prevention of erosive oesophagitis relapse with pantoprazole.

AIM: To compare the safety and efficacy of pantoprazole and ranitidine in maintaining erosive oesophagitis healing. METHODS: Gastro-oesophageal reflux disease patients (349) with endoscopically documented healed erosive oesophagitis (grade 0 or 1) were randomly assigned to receive pantoprazole (10, 20 or 40 mg/q.d.s.) or ranitidine (150 mg/b.d.). Erosive oesophagitis status was assessed endoscopically at months 1, 3, 6 and 12 or when relapse symptoms appeared (relapse = reappearance of erosive oesophagitis grade 2 within 12 months). Symptom-free days were also assessed. RESULTS: Pantoprazole 20- and 40-mg were significantly more effective than ranitidine in maintaining healing regardless of initial erosive oesophagitis grade. Response was dose-related. After 12 months 78, 55, 46 and 21% of patients remained healed (40-, 20-, 10-mg pantoprazole and ranitidine). Pantoprazole 40-mg produced significantly more symptom-free days (83%) than ranitidine (58%). Heartburn-free days/nights were significantly higher with pantoprazole 40-mg (92 and 93%) than ranitidine (73 and 77%). The most frequent reason for discontinuation, unsatisfactory efficacy, occurred most often with ranitidine (P < 0.001). CONCLUSION: Once-daily pantoprazole therapy prevented relapse of healed erosive oesophagitis more effectively than ranitidine and with fewer heartburn days. Response to pantoprazole was dose-related. Pantoprazole 40-mg was the most effective regimen and consistent in maintaining erosive oesophagitis healing with a good safety and tolerability profile.

Effect of Helicobacter pylori eradication on the treatment of gastro-oesophageal reflux disease.

The important issue of whether Heliobacter pylori eradication leads to increased reflux has been the subject of many apparently contradictory publications, but when we asked two leading authorities to give us their views, there turned out to be considerable consensus, as you can read below.

Observer variation in the diagnosis of superficial oesophageal adenocarcinoma.

BACKGROUND AND AIMS: When to perform oesophagectomy for neoplastic progression in Barrett's oesophagus is controversial. Some resect for high grade dysplasia whereas others defer treatment until intramucosal adenocarcinoma is diagnosed. Interobserver agreement for a diagnosis of high grade dysplasia or intramucosal adenocarcinoma remains unknown and may have therapeutic implications. METHODS: Histological slides from 75 oesophagectomy specimens with high grade dysplasia or T(1) adenocarcinoma were blindly reviewed by two gastrointestinal pathologists and one general surgical pathologist, and classified as high grade dysplasia, intramucosal adenocarcinoma, or submucosal adenocarcinoma. A subsequent re-review of all 75 cases by the same observers following establishment of uniform histological criteria was undertaken. Interobserver agreement was determined by kappa statistics. Coefficients <0.21, 0.21-0.40, 0.41-0.60, 0.61-0.80, and >0.80 were considered poor, fair, moderate, good, and very good agreement, respectively. RESULTS: Interobserver agreement among all pathologists and between gastrointestinal pathologists when comparing high grade dysplasia with intramucosal adenocarcinoma was only fair (k=0.42; 0.56, respectively) and did not substantially improve on subsequent re-evaluation following establishment of uniform histological criteria (K=0.50; 0.61, respectively). CONCLUSIONS: When evaluating resection specimens and after implementation of uniform histological criteria, even experienced gastrointestinal pathologists frequently disagree on a diagnosis of high grade dysplasia versus intramucosal adenocarcinoma. Treatment strategies based on the histological distinction of high grade dysplasia from intramucosal adenocarcinoma using limited biopsy specimens should be re-evaluated.

Timed barium oesophagram: better predictor of long term success after pneumatic dilation in achalasia than symptom assessment.

BACKGROUND: Symptom relief post pneumatic dilation is traditionally used to assess treatment success in achalasia patients. Recently, we showed that symptom relief and objective oesophageal emptying are concordant in about 70% of patients, while up to 30% of achalasia patients report near complete symptom relief despite poor oesophageal emptying of barium. AIMS: We now report the results of long term clinical follow up in these two groups of achalasia patients, assessing differences in symptomatic remission rates. METHODS: Achalasia patients undergoing pneumatic dilation since 1995 were evaluated both symptomatically and objectively at regular intervals. Pre and post dilation symptoms were recorded. Barium column height was measured five minutes after ingesting a fixed volume of barium per patient to assess oesophageal emptying. Patients who initially reported near complete symptom relief were divided into two groups based on objective findings on barium study: (1) complete oesophageal emptying (concordant group), and (2) poor oesophageal emptying (discordant group). Patients were followed prospectively for symptom recurrence. RESULTS: Thirty four patients with complete symptom relief post pneumatic dilation were identified. In 22/34 (65%) patients, the degree of symptom and barium height improvements was similar (concordant group). In 10/34 (30%) patients, there was < 50% improvement in barium height (discordant group). Significantly (p<0.001) more discordant (9/10; 90%) than concordant (2/22; 9%) patients failed therapy at the one year follow up. Seventeen of 22 (77%) concordant patients were still in remission while all discordant patients had failed therapy by six years of follow up. Length of time in symptom remission (mean (SEM)) post pneumatic dilation was significantly (p=0.001) less for the discordant group (18.0 (3.6) months) compared with the concordant group (59.0 (4.8) months). CONCLUSIONS: (1) Poor oesophageal emptying is present in nearly 30% of achalasia patients reporting complete symptom relief post pneumatic dilation. (2) The majority (90%) of these patients will fail within one year of treatment. (3) Timed barium oesophagram is an important tool in the objective evaluation of achalasia patients post pneumatic dilation.