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Background & Aims: Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett''s esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. Methods: We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. Results: Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. Conclusions: We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies. [Copyright &y& Elsevier]

Background: Minimally invasive esophagectomy (MIE) has been performed using a variety of techniques evolving during the past decade. We present our initial experience and outcomes of patients undergoing transthoracic MIE using a circular end-to-side anastomosis created with the transorally directed EEA circular stapler OrVil (Covidien, New Haven, CT). Complications, including anastomotic leak and stricture occurrence, are reviewed. Methods: A retrospective review evaluated consecutive patients undergoing MIE for esophageal cancer or related disease with intrathoracic end-to-side anastomoses using the transorally directed EEA circular stapler from December 2007 to May 2010. Medical records were reviewed for demographics, staging, neoadjuvant chemoradiotherapy, comorbidities, adjuvant therapy, complications, and survival. Results: During this period, 51 consecutive patients (84% male; mean age, 65 years) underwent MIE. Neoadjuvant chemoradiotherapy was performed in 32 patients, and 4 had intraoperative radiotherapy. Mean operative time was 338 minutes (range, 211 to 565 minutes), including the 4 patients with intraoperative radiotherapy. Operative time improved with experience (excluding intraoperative radiotherapy) from a mean of 378 minutes (patients 1 to 14) to 300 minutes (patients 37 to 51). Median hospital stay was 11 days (range, 6 to 48 days). Anastomotic leaks occurred in 5 patients (9.8%). Postoperative deaths included 1 in-hospital (2.0%) and 2 (3.9%) after discharge. Stricture was diagnosed and treated in 7 patients (13.7%). Follow-up was a median of 12 months (range, 1 to 31 months). Conclusions: Transthoracic MIE using an end-to-side anastomosis with the transorally directed EEA circular stapler resulted in acceptable stricture and leak rates with good outcomes comparable to published outcomes for open surgical resections. [ABSTRACT FROM AUTHOR]

Background & Aims: Upper abdominal pain (UAP) in patients with gallstones is often treated by cholecystectomy but it frequently persists. We aimed to identify symptoms associated with relief. Methods: We followed 1008 patients who received cholecystectomy for gallstones and UAP at the Mayo Clinic (Rochester, Minnesota) or Kaiser Permanente (San Diego, California) for 12 months. A validated, self-completed biliary symptoms questionnaire identified features of UAP, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS); the questionnaire was given initially and 3 and 12 months after cholecystectomy, to identify features that predicted sustained relief of UAP. Results: Five hundred ninety-four patients (59%) reported relief from UAP. Factors associated univariately (P < .05) with relief included frequency of UAP ≤1 per month, onset ≤1 year preoperatively, usual duration (30 minutes to 24 hours, most often in the evening or night), and severity >5/10. Compared to no features, multiple predictive features of UAP (frequency, onset, duration, or timing) were associated with increasing odds ratios (95% confidence interval) for relief: 1, 2, or 3 features (4.2 [1.1–16]; P = .03) and 4 features (6.3 [1.6–25]; P = .008). Negative univariate associations included lower abdominal pain (LAP), usual bowel pattern, nausea ≥1 per week, often feeling bloated or burpy, GERD, and/or IBS. There was an inverse association between relief and somatization; relief was not associated with postprandial UAP. Multivariable logistic regression analysis revealed independent associations (P < .05) with UAP frequency, onset, and nocturnal awakening, but inverse associations with lower abdominal pain, abnormal bowel pattern, and frequent bloated or burpy feelings. Conclusions: UAP features and concomitant GERD, IBS, and somatization determine the odds for relief from UAP after cholecystectomy. [ABSTRACT FROM AUTHOR]

Background: Several small series have suggested an increased risk of complications associated with esophageal dilation in patients with eosinophilic esophagitis (EoE). Objective: To quantitate the risk and identify risk factors for esophageal complications in dilation in EoE patients. Design: Retrospective, uncontrolled, single-center study. Setting: Tertiary referral hospital. Patients: A total of 161 EoE patients (mean ± standard deviation age 44.3 ± 15.3 years, 112 men, 49 women, 150 white patients, 10 unknown, 1 Asian). Interventions: Through-the-scope balloon or Savary dilation of EoE. Main Outcome Measurements: The rate of complications defined as deep mucosal tear, major bleeding, or perforation, and determination of risk factors for complications. Results: A total of 293 dilations were performed in 161 patients. Complications reported were deep mucosal tear in 9.2% (n = 27), major bleeding in 0.3% (n = 1), and immediate perforation in 1.0% (n = 3). All patients with perforations were successfully treated medically without surgery (mean ± standard deviation hospital stay 5.3 ± 3.2 days). Factors associated with an increased risk of complications were luminal narrowing in the upper (odds ratio [OR], 5.62; 95% CI, 2.07-15.26; P < .001) and middle third of the esophagus (OR, 4.93; 95% CI, 1.64-14.83; P < .005) compared with lower third, luminal stricture unable to be traversed with a standard upper endoscope (OR, 2.48; 95% CI, 1.06-5.83; P = .037), and use of Savary dilator (OR, 2.63; 95% CI, 1.18-5.83; P = .018). Limitations: Retrospective design, uncontrolled study. Conclusions: Deep mucosal tears are common after dilation (9%), but the risk of immediate transluminal perforation with EoE is approximately 1%. The risk of severe complications is increased in patients with more proximal stricture and strictures that initially prevent endoscope passage. [Copyright &y& Elsevier]

Background & Aims: Lichen planus is a relatively uncommon, presumed autoimmune disease that affects middle-aged patients and is manifested in the skin, nails, and mucous membranes. Reports of esophageal involvement have been rare, despite the classification of the esophagus as a mucous membrane. Methods: Assuming esophageal involvement might not be as rare as expected, we reviewed the Mayo Clinic Pathology Database for all cases from 2000 to the present. Results: Twenty-seven cases were identified, with a mean age of 64 years; 25 were women. Patients presenting with esophageal lichen planus as the initial manifestation and those with a diagnosis of lichen planus involving other sites were equal in number. Many patients had received multiple dilations and reflux treatments before diagnosis. All patients presented with dysphagia. Endoscopy and radiology studies demonstrated a wide range of abnormalities, including strictures of varying length and location, small-caliber esophagus, and a mucosal appearance of sloughing, white discoloration, erythema, thickening, and superficial ulceration. Treatment regimens varied markedly, with some patients responding to topical or systemic corticosteroids. Conclusions: Esophageal lichen planus is rare but probably more common than previously suspected. It presents with a wide range of endoscopic signs and is commonly the presenting sign of lichen planus. In evaluating middle-aged patients with strictures, particularly proximal esophageal strictures in women, physicians should consider a diagnosis of lichen planus even in the absence of extraesophageal manifestations. [Copyright &y& Elsevier]

Abstract: Background: To assess the effect of Roux-en-Y gastric bypass (RYGB) at a tertiary referral Center of Excellence for bariatric surgery on the length and presence of dysplasia in morbidly obese patients with Barrett’s esophagus (BE). Esophageal reflux of gastroduodenal contents (acid, bile) contributes to the development of BE and progression in the dysplasia-carcinoma sequence. Obese patients have a high prevalence of gastroesophageal reflux and might be at an increased risk of developing BE and esophageal adenocarcinoma. The effect of eliminating duodenogastroesophageal reflux on BE is not known. Methods: We performed a retrospective review of all patients with pre-existing, biopsy-proven, long-segment (>3 cm) BE undergoing RYGB at our institution. Only patients with >1 year of endoscopic, biopsy-controlled follow-up (mean 34 mo) were included. Results: Five patients (3 men and 2 women) were identified. The mean ± standard error of the mean preoperative length of BE was 6 ± 2 cm; 2 patients had low-grade dysplasia and 1 indeterminate dysplasia. At the postoperative follow-up (>1 yr) examinations, the length of BE had decreased in 4 patients; the overall length was 2 ± 1 cm; and only 1 patient had dysplasia. All patients experienced a decrease in the length of BE (n = 4), complete disappearance of BE (n = 2), or improvement in the degree of dysplasia (n = 3). The body mass index had decreased from 43 ± 4 kg/m2 to 33 ± 3 kg/m2, and all experienced subjective improvement in reflux symptoms postoperatively. RYGB resulted in complete or partial regression of BE in 4 of 5 patients and improvement in reflux symptoms in all. Conclusion: Our results suggest that RYGB might be the procedure of choice in morbidly obese patients with BE requiring surgical treatment for gastroesophageal reflux disease. [Copyright &y& Elsevier]

Background & Aims: Guidelines for reporting Barrett’s esophagus and hiatal hernia measurements and reflux esophagitis grades have been developed to improve consistency, communication, and, ultimately, patient care. Our aims were to assess the percentage of cases in which findings were reported in accordance with guidelines and to assess the impact of education and feedback on reporting behavior. Methods: Prospective cross-sectional study design was used. Chart reviews were performed for all adult patients who underwent esophagogastroduodenoscopy at a tertiary care center during three 2-month time periods during a 12-month interval: Time 1 (March 1, 2004–April 30, 2004), Time 2 (July 1, 2004–August 31, 2004), and Time 3 (March 1, 2005–April 30, 2005). Standardized educational sessions began 2 years before Time 1. No intervention took place between Time 1 and Time 2; data were collected to examine secular change. Between Time 2 and Time 3, individual and group feedback and refresher sessions were given. Results: Five thousand six hundred nine eligible esophagogastroduodenoscopies were performed, of which 2675 demonstrated Barrett’s esophagus, hiatal hernia, and/or reflux esophagitis. At baseline, Barrett’s esophagus and hiatal hernia measurements were dictated correctly in a median of 67% and 86% of cases, respectively, improving to 100% (P < .05) and 98% (P < .01) of cases, respectively. The Los Angeles Classification system was used in a median of 100% of cases at baseline and at follow-up. Conclusions: Anonymous individual and group feedback, in combination with brief, structured didactic educational sessions, significantly improves compliance with established guidelines for the reporting of Barrett’s esophagus and hiatal hernia. Once successfully incorporated into clinical practice, adherence to the esophagitis Los Angeles Classification System is easy to maintain. [Copyright &y& Elsevier]

Eosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE. For the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0–100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8). The distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0–6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from –4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P =.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P =.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P =.11). Assessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT 01386112 [ABSTRACT FROM AUTHOR]

Background & Aims Risks for some cancers increase with height. We investigated the relationship between height and risk of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). Methods We analyzed epidemiologic and genome-wide genomic data from individuals of European ancestry in the Barrett's and Esophageal Adenocarcinoma Consortium, from 999 cases of EAC, 2061 cases of BE, and 2168 population controls. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height and risks of EAC and BE. We performed a Mendelian randomization analysis to estimate an unconfounded effect of height on EAC and BE using a genetic risk score derived from 243 genetic variants associated with height as an instrumental variable. Results Height was associated inversely with EAC (per 10-cm increase in height: OR, 0.70; 95% CI, 0.62–0.79 for men and OR, 0.57; 95% CI 0.40–0.80 for women) and BE (per 10-cm increase in height: OR, 0.69; 95% CI, 0.62–0.77 for men and OR, 0.61; 95% CI, 0.48–0.77 for women). The risk estimates were consistent across strata of age, education level, smoking, gastroesophageal reflux symptoms, body mass index, and weight. Mendelian randomization analysis yielded results quantitatively similar to those from the conventional epidemiologic analysis. Conclusions Height is associated inversely with risks of EAC and BE. Results from the Mendelian randomization study showed that the inverse association observed did not result from confounding factors. Mechanistic studies of the effect of height on EAC and BE are warranted; height could have utility in clinical risk stratification. [ABSTRACT FROM AUTHOR]

Background& Aims: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett''s esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E2 in patients with BE with no dysplasia or low-grade dysplasia. Methods: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE2 (the primary end point). Results: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE2 was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P = .02 vs arm A). Conclusions: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903. [Copyright &y& Elsevier]

Background & Aims: We evaluated the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic esophagitis (EoE). Methods: We performed a double-blind, randomized, placebo-controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that swallowed 880 μg of aerosolized fluticasone twice daily (n = 21), or took a placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were symptomatic and histologic response. Results: A complete histologic response (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who received placebo (P < .001), based on intention-to-treat analysis; histologic responses were observed in 68% of subjects who received fluticasone (13 of 19) compared with none of those who received placebo (0 of 15) by per-protocol analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8% who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of subjects who received fluticasone (12 of 21) compared with 33% who received placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced in 63% of patients who received fluticasone (12 of 19) and 47% of those who received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but in none of the subjects in the placebo group (P = .05). Conclusions: Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To use a population-based approach to describe survival trends in patients diagnosed as having gastric or esophageal adenocarcinoma. PATIENTS AND METHODS: A population-based complete chart re- view of all inpatient and outpatient records, using the resources of the Rochester Epidemiology Project, was conducted in Olmsted County, Minnesota (population 124,277), a primarily rural county with one large urban area. All residents of Olmsted County who were diagnosed as having gastric or esophageal adenocarcinoma from January 1, 1971, through December 31, 2000, were included in the study. The main outcomes were median survival and 2-year and 5-year survival rates, by decade of diagnosis. RESULTS: From 1971 through 2000, medIan survival for patients with gastric adenocarcinoma (n=121) decreased from 5.5 months to 3.2 months, whereas median survival for patients with esophageal adenocarcinoma (n=65) increased from 8.5 months to 11.7 months. Decade of diagnosis was not significantly associated with patient survival for either gastric or esophageal adenocarcinoma (P~'.05). There was no significant shift In stage of disease at diagnosis during the 30-year period for either gastric or esophageal adenocarcinoma (P>05). CONCLUSION: No significant change has occurred in the survival rates of this patient population with gastric or esophageal adenocarcinoma, which is representative of the US white population. [ABSTRACT FROM AUTHOR]