Background-Endoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of disease chronicity. However, there is a serious lack of agreement about how to describe and classify the appearance of reflux oesophagitis Aims-To examine the reliability of criteria that describe the circumferential extent of mucosal breaks and to evaluate the functional and clinical correlates of patients with reflux disease whose oesophagitis was graded according to the Los Angeles system. Methods-Forty six endoscopists from diVerent countries used a detailed worksheet to evaluate endoscopic video recordings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clinical trials of omeprazole treatment (277 patients). Results-Evaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended between the tops of mucosal folds, gave acceptable agreement (mean value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0-25%, 26-50%, 51-75%, 76-99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean values 0-0.15) for all but the lowest category of extent (mean value 0.4). Severity of oesophageal acid exposure was significantly (p<0.001) related to the severity grade of oesophagitis. Preteatment oesophagitis grades A-C were related to heartburn severity (p<0.01), outcomes of omeprazole (10 mg daily) treatment (p<0.01), and the risk for symptom relapse oV therapy over six months (p<0.05). Conclusions-Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis. (Gut 1999;45:172-180)

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.

As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedancepH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

Esophageal adenocarcinoma (EAC) has been rapidly increasing in Western countries during the past half century, especially in white men. Esophageal squamous cell carcinoma (ESCC) used to be the dominant type of esophageal malignancy both in Western and Asian countries. The rapid increase of EAC in Western countries has occurred in parallel with an increased prevalence of gastroesophageal reflux disease (GERD) and its major determinant, obesity. Such an increase in EAC has not yet been observed in Asia, despite a recent increase in prevalence of GERD. In this mini-review, we analyze possible factors influencing such east-west ('Orient to Occident') differences, particularly possible roles of ethnicity and environmental factors, such as Helicobacter pylori infection and nutritional factors, and how these might interact with socioeconomic differences. Development of Barrett's esophagus and esophageal adenocarcinoma appears to be strongly affected by ethnic factors, with populations resident at the west end of the Eurasian continent, such as Anglo-Celtics, being more prone to both conditions. On the other hand, ethnic groups from the eastern and southern ends of Eurasia, such as Chinese, Koreans and Japanese, and Africans might be more prone to developing esophageal squamous cell carcinoma. Future trends will also be discussed.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Background-Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals. Aims-To evaluate the eVect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH. Subjects-Ten IBS patients diagnosed by Rome criteria and 10 healthy controls. Methods-CRH (2 µg/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. Results-CRH induced motility of the descending colon in both groups (p<0.001) and induced greater motility indexes in IBS patients than in controls (p<0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p<0.05). CRH induced significant increases in plasma ACTH levels in both groups (p<0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p<0.001). Conclusion-Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH. (Gut 1998;42:845-849) Keywords: irritable bowel syndrome; corticotropin releasing factor; adrenocorticotropic hormone; colonic motility; duodenal motility Stress can alter gastrointestinal function but the mechamism of the stress induced intestinal response is still obscure.1 The detail of the brain-gut interaction is one of the most important factors of stress induced intestinal response and irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link. 2 We have reported that psychological stress induces colonic segmental contractions and irregular contractile activity (phase II) of the duodenal migrating motor complex (MMC) in humans and that these responses are exaggerated in IBS patients. Wrap restraint stress in rats is also reported to facilitate colonic motility and to inhibit small intestinal motility.5 6 These phenomena in rats are mimicked by intracerebroventricular [6][7][8][9] or intravenous 9 administration of corticotropin releasing hormone (CRH) and are blocked by the CRH antagonist, helical CRH 9-41 . 6-9Stress induces anxiogenic behaviour in rats and intracerebroventricular administration of CRH mimics the behavioural changes under stress. 10Furthermore, intravenous administration of CRH decreases slow wave sleep in humans. 11These findings led us to hypothesise that CRH plays a major role in the stress response of humans, both normal subjects and IBS patients. The purpose of this study was to determine whether intravenous administration of CRH aVects human gastrointestinal motility and whether CRH discriminates physiological responses in normal control subjects from those in IBS patients. Methods SUBJECTSTen normal healthy volunteers and 10 IBS patients were studied. Both groups consisted of five men and five women. Ages (controls...

ObjectiveTo determine the efficacy of acotiamide, an acetylcholinesterase inhibitor, in patients with functional dyspepsia (FD) in a 4-week trialMethodsA multicentre, randomised, placebo-controlled, parallel-group, phase III trial was carried out, in which patients with FD received 100 mg of acotiamide or placebo three times a day for 4 weeks, with 4 weeks post-treatment follow-up. The primary efficacy end points were global assessment of overall treatment efficacy (OTE) and elimination rate of all three meal-related symptoms (postprandial fullness, upper abdominal bloating and early satiation), as derived from daily diaries. Secondary efficacy end points were individual symptom scores and quality of life. Adverse events were monitored.Results52.2% of those receiving acotiamide and 34.8% in the placebo group (p<0.001) were classified as responders according to a global assessment of OTE. Over 4 weeks, the elimination rate for all three meal-related symptoms was 15.3% among patients receiving acotiamide compared with 9.0% in the placebo group (p=0.004). The significant benefit of acotiamide over placebo in OTE and elimination rate was maintained during the 4 week post-treatment follow-up. All other secondary efficacy end points, including quality of life, were significantly improved with 100 mg of acotiamide as compared with placebo. The number needed to treat was 6 for OTE and 16 for symptom elimination rate. The incidence of adverse events was similar between the acotiamide group and placebo group and no significant cardiovascular effects due to treatment were seen.ConclusionsOver 4 weeks, acotiamide significantly improved symptom severity and eliminated meal-related symptoms in patients with FD.Trial registration numberhttp://ClinicalTrials.gov number, NCT00761358.

No abstract