Asymmetrical elevation of esophagogastric junction pressure suggests hiatal repair contributes to antireflux surgery dysphagia.

The radial distribution of esophago-gastric junction (EGJ) pressures with regard to troublesome dysphagia (TDysph) after antireflux surgery is poorly understood. Before and after antireflux surgery, end-expiratory and peak-inspiratory EGJ pressures were measured at eight angles of 45° radial separation in patients with reflux disease. All 34 patients underwent posterior crural repair, then either 90° anterior (N = 13) or 360° fundoplication (N = 21). Dysphagia was assessed prospectively using a validated questionnaire (score range 0-45) and TDysph defined as a dysphagia score that was ≥5 above pre-op baseline. Compared with before surgery, for 90° fundoplication, end-expiratory EGJ pressures were highest in the left-anterolateral sectors, the position of the partial fundoplication. In other sectors, pressures were uniformly elevated. Compared with 90° fundoplication, radial pressures after 360° fundoplication were higher circumferentially (P = 0.004), with a posterior peak. Nine patients developed TDysph after surgery with a greater increase in end-expiratory and peak-inspiratory EGJ pressures (P = 0.03 and 0.03, respectively) and significantly higher inspiratory pressure at the point of maximal radial pressure asymmetry (P = 0.048), compared with 25 patients without TDysph. Circumferential elevation of end-expiratory EGJ pressure after 90° and 360° fundoplication suggests hiatal repair elevates EGJ pressure by extrinsic compression. The highly localized focal point of elevated EGJ pressure upon inspiration in patients with TDysph after surgery is indicative of a restrictive diaphragmatic hiatus in the presence of a fundoplication.

An Interactive Web-Based Educational Tool Improves Detection and Delineation of Barrett's Esophagus-Related Neoplasia.

BACKGROUND & AIMS: Endoscopic detection of early Barrett's esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. METHODS: We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett's esophagus. Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase one, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared the assessors' interpretations with those from experts. These data informed the selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. RESULTS: A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P < .001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all, P < .001). Scores improved independent of assessors' country of origin or level of endoscopic experience. CONCLUSIONS: We developed a web-based teaching tool for endoscopic recognition of BORN that is easily accessible, efficient, and increases detection and delineation of neoplastic lesions. Widespread use of this tool might improve management of Barrett's esophagus by general endoscopists.

Diagnosis of gastro-oesophageal reflux disease is enhanced by adding oesophageal histology and excluding epigastric pain.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) in clinical practice is limited by the sensitivity and specificity of symptoms and diagnostic testing. AIM: To determine if adding histology as a criterion and excluding patients with epigastric pain enhances the diagnosis for GERD. METHODS: Patients with frequent upper gastrointestinal symptoms who had not taken a proton pump inhibitor in the previous 2 months and who had evaluable distal oesophageal biopsies were included (Diamond study: NCT00291746). Epithelial hyperplasia was identified when total epithelial thickness was at least 430 µm. Investigation-based GERD criteria were: presence of erosive oesophagitis, pathological oesophageal acid exposure and/or positive symptom-acid association probability. Symptoms were assessed using the Reflux Disease Questionnaire and a pre-specified checklist. RESULTS: Overall, 127 (55%) of the 231 included patients met investigation-based GERD criteria and 195 (84%) met symptom-based criteria. Epithelial hyperplasia was present in 89 individuals, of whom 61 (69%) met investigation-based criteria and 83 (93%) met symptom-based criteria. Adding epithelial hyperplasia as a criterion increased the number of patients diagnosed with GERD on investigation by 28 [12%; number needed to diagnose (NND): 8], to 155 (67%). The proportion of patients with a symptom-based GERD diagnosis who met investigation-based criteria including epithelial hyperplasia was significantly greater when concomitant epigastric pain was absent than when it was present (P < 0.05; NND: 8). CONCLUSIONS: Histology increases diagnosis of GERD and should be performed when clinical suspicion is high and endoscopy is negative. Excluding patients with epigastric pain enhances sensitivity for the diagnosis of GERD.

A randomised phase II trial and feasibility study of palliative chemotherapy in frail or elderly patients with advanced gastroesophageal cancer (321GO).

BACKGROUND: Elderly patients are commonly under-represented in cancer clinical trials. The 321GO was undertaken in preparation for a definitive phase three trial assessing different chemotherapy regimens in a frail and/or elderly population with advanced gastroesophageal (GO) cancer. METHODS: Patients with advanced GO cancer considered unfit for conventional dose chemotherapy were randomly assigned in a 1 : 1 : 1 ratio to: epirubicin, oxaliplatin and capecitabine (EOX); oxaliplatin and capecitabine (OX); and capecitabine alone (X) (all 80% of full dose and unblinded). The primary end point was patient recruitment over an 18-month period. A registration study recorded treatment choice for all patients with advanced GO cancer at trial centres. RESULTS: A total of 313 patients were considered for palliative chemotherapy for GO cancer over the 18-month period: 115 received full dose treatment, 89 less than standard treatment or entered 321GO and 111 no treatment. Within 321GO, 55 patients were randomly assigned (19 to OX and X; 17 to EOX). Progression-free survival (PFS) for all patients was 4.4 months and by arm 5.4, 5.6 and 3.0 months for EOX, OX and X, respectively. The number of patients with a good overall treatment utility (OTU), a novel patient-centred endpoint, at 12 weeks was 3 (18%), 6 (32%) and 1 (6%) for EOX, OX and X, respectively. At 6 weeks, 22 patients (41%) had experienced a non-haematologic toxicity ⩾grade 3, most commonly lethargy or diarrhoea. The OTU was prognostic for overall survival in patients alive at week 12 (logrank test P=0.0001). CONCLUSIONS: It is feasible to recruit elderly and/or frail patients with advanced GO cancer to a randomised clinical trial. The OX is the preferred regimen for further study. Overall treatment utility shows promise as a comparator between treatment regimens for feasibility and randomised trials in the elderly and/or frail GO cancer population.

Open access follow-up care for early breast cancer: a randomised controlled quality of life analysis.

This study evaluated the acceptability of a supportive model of follow-up. One hundred and twelve women recovering from breast cancer were randomised to receive standard breast clinic aftercare (Control n = 56) or on demand by open access aftercare by breast care nurses (Intervention n = 56). Participants attended a support-based psycho-educational programme delivered in four half-day group sessions. Three quality of life questionnaires (EORTC QLQ-C30, QLQ-BR23, HADS) were administered at baseline and 6-monthly intervals for 2 years. Multilevel linear regression modelling methods were used for evaluation. Age was found to be a statistically significant predictor of quality of life in several sub-scales. Increasing age was negatively associated with sexual functioning, systematic therapy side effects and physical functioning, and positively associated with future perspective. Aftercare assignment was not found to be a statistically significant predictor. Women treated for early breast cancer were not disadvantaged by allocation to the open access supportive care model in terms of quality of life experienced. The model for follow-up was demonstrated to be a feasible alternative to routinised hospital-based follow-up and adds to the evidence for stratified follow-up for low-risk cancer patients, incorporating self-management education. Stratified follow-up pathways are viewed as a preferable approach.

Sleep disturbance due to heartburn and regurgitation is common in patients with functional dyspepsia.

BACKGROUND: Reflux symptoms (heartburn and regurgitation) are common in patients with functional dyspepsia who do not have gastroesophageal reflux disease (GERD). OBJECTIVE: The purpose of this study was to assess the relationship of reflux symptoms with sleep disturbances in patients with functional dyspepsia without GERD and in those with GERD. METHODS: This post-hoc analysis of data from the Diamond study (NCT00291746) included patients with frequent upper gastrointestinal symptoms, of whom 137 had functional dyspepsia and 193 had GERD (diagnosed by endoscopy and pH monitoring). Patients completed symptom questionnaires and were interviewed by physicians. RESULTS: During the seven nights before study entry, 46.0% of patients with functional dyspepsia and 64.8% of those with GERD reported sleep disturbances (any frequency) related to reflux symptoms. Frequent (often/every night) sleep disturbances were experienced by 12.4% of patients with functional dyspepsia and 24.9% of those with GERD (p = 0.005). Among patients with functional dyspepsia, the prevalence of sleep disturbances was highest in those whose heartburn and/or regurgitation were moderate to severe (vs mild/very mild) and frequent (4-7 vs 1-3 days/week). CONCLUSIONS: Sleep disturbances due to reflux symptoms are common in patients with functional dyspepsia who do not have GERD, and become more frequent with increasing reflux symptom severity and frequency.

Fruit, vegetable and vitamin C intakes and plasma vitamin C: cross-sectional associations with insulin resistance and glycaemia in 9-10 year-old children.

AIM: To examine whether low circulating vitamin C concentrations and low fruit and vegetable intakes were associated with insulin resistance and other Type 2 diabetes risk markers in childhood. METHODS: We conducted a cross-sectional, school-based study in 2025 UK children aged 9-10 years, predominantly of white European, South-Asian and black African origin. A 24-h dietary recall was used to assess fruit, vegetable and vitamin C intakes. Height, weight and fat mass were measured and a fasting blood sample collected to measure plasma vitamin C concentrations and Type 2 diabetes risk markers. RESULTS: In analyses adjusting for confounding variables (including socio-economic status), a one interquartile range higher plasma vitamin C concentration (30.9 µmol/l) was associated with a 9.6% (95% CI 6.5, 12.6%) lower homeostatic model assessment of insulin resistance value, 0.8% (95% CI 0.4, 1.2%) lower fasting glucose, 4.5% (95% CI 3.2, 5.9%) lower urate and 2.2% (95% CI 0.9, 3.4%) higher HDL cholesterol. HbA1c concentration was 0.6% (95% CI 0.2, 1.0%) higher. Dietary fruit, vegetable and total vitamin C intakes were not associated with any Type 2 diabetes risk markers. Lower plasma vitamin C concentrations in South-Asian and black African-Caribbean children could partly explain their higher insulin resistance. CONCLUSIONS: Lower plasma vitamin C concentrations are associated with insulin resistance and could partly explain ethnic differences in insulin resistance. Experimental studies are needed to establish whether increasing plasma vitamin C can help prevent Type 2 diabetes at an early stage.

Effects of aromatase inhibitors and body mass index on steroid hormone levels in women with early and advanced breast cancer.

BACKGROUND: Aromatase inhibitors (AIs) are central to the management of oestrogen receptor-positive breast cancer in the adjuvant and metastatic setting. Levels of circulating steroid hormones (SHs) were measured in patients established on AIs to investigate: the influence of body mass index (BMI) in both the adjuvant and metastatic setting; the class of AI utilized in the adjuvant setting (steroidal versus non-steroidal); and differences in SH levels between women treated adjuvantly and those receiving a second-line AI for locally advanced/metastatic disease. METHODS: Plasma levels of androstenedione, 5-androstene-3ß,17ß-diol, dehydroepiandrosterone, oestradiol and testosterone were measured by radioimmunoassay in women with breast cancer who were receiving AIs in either an adjuvant or a metastatic setting. Differences between mean SH levels by class of AI, BMI, and second-line versus adjuvant therapy were assessed. RESULTS: Sixty-four women were receiving AI therapy, 45 (70 per cent) in an adjuvant setting and 19 (30 per cent) were taking a second-line AI. There was no significant correlation between BMI and SH levels. However, BMI was significantly higher in the second-line AI cohort compared with the adjuvant cohort (29.8 versus 26.2 kg/m2 respectively; P = 0.026). In the adjuvant setting, patients receiving a steroidal AI had significantly higher levels of all five hormones (P < 0.050). In the second-line AI cohort, oestradiol levels were significantly higher than in the adjuvant cohort (4.5 versus 3.3 pg/ml respectively; P = 0.022). Multivariable analysis adjusted for BMI confirmed the higher residual oestradiol level in the second-line AI group (P = 0.063) and a significantly higher androstenedione level (P = 0.022). CONCLUSION: Residual levels of SH were not significantly influenced by BMI. However, the significant differences in residual SH levels between the second-line and adjuvant AI cohort is of relevance in the context of resistance to AI therapy, and warrants further investigation.

Systematic review: relationships between sleep and gastro-oesophageal reflux.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep, but the mechanism remains unclear. AIM: To review the literature concerning gastro-oesophageal reflux during the sleep period, with particular reference to the sleep/awake state at reflux onset. METHODS: Studies identified by systematic literature searches were assessed. RESULTS: Overall patterns of reflux during the sleep period show consistently that oesophageal acid clearance is slower, and reflux frequency and oesophageal acid exposure are higher in patients with GERD than in healthy individuals. Of the 17 mechanistic studies identified by the searches, 15 reported that a minority of reflux episodes occurred during stable sleep, but the prevailing sleep state at the onset of reflux in these studies remains unclear owing to insufficient temporal resolution of recording or analysis methods. Two studies, in healthy individuals and patients with GERD, analysed sleep and pH with adequate resolution for temporal alignment of sleep state and the onset of reflux: all 232 sleep period reflux episodes evaluated occurred during arousals from sleep lasting less than 15 s or during longer duration awakenings. Six mechanistic studies found that transient lower oesophageal sphincter relaxations were the most common mechanism of sleep period reflux. CONCLUSIONS: Contrary to the prevailing view, subjective impairment of sleep in GERD is unlikely to be due to the occurrence of reflux during stable sleep, but could result from slow clearance of acid reflux that occurs during arousals or awakenings from sleep. Definitive studies are needed on the sleep/awake state at reflux onset across the full GERD spectrum.

Enhancing clinical skill development through an Ambulatory Medicine Teaching Programme: an evaluation study.

BACKGROUND: Teaching of clinical skills traditionally takes place in hospital wards and outpatient settings. However high acuity and short hospital stays means there are fewer suitable inpatients available for teaching; and time pressures limit students' involvement in other settings. The Ambulatory Medicine Programme was established to develop undergraduate medical students' clinical skills by providing increased exposure to patients with a wide range of chronic medical conditions, in a dedicated learning environment. METHOD: A mixed qualitative/quantitative approach was used to evaluate the Programme. This research focuses on staff and student perspectives of teaching and learning in Ambulatory Medicine compared with inpatient and outpatient settings; identifies which teaching methods are considered most effective; and determines the transferability of learning. Patients' perspectives of being involved in student teaching are also reported. RESULTS: Results show that the programme has made a positive impact on students' development of clinical skills, which are transferable to the clinical setting. Patients enjoy being involved and find it personally satisfying. CONCLUSIONS: The Ambulatory Medicine Programme is an effective way of developing medical students' clinical skills by providing focussed teaching with real patients in a dedicated learning environment.

Susceptibility to dysphagia after fundoplication revealed by novel automated impedance manometry analysis.

BACKGROUND: Conventional measures of esophageal pressures or bolus transport fail to identify patients at risk of dysphagia after laparoscopic fundoplication. METHODS: Liquid and viscous swallows were evaluated with impedance/manometry in 19 patients with reflux disease before and after surgery. A new method of automated impedance manometry (AIM) analysis correlated esophageal pressure with impedance data and automatically calculated a range of pressure and bolus movement variables. An iterative analysis determined whether any variables were altered in relation to dysphagia. Standard measures of esophago-gastric junction pressure, bolus presence time, and total bolus transit time were also evaluated. KEY RESULTS: At 5 months postop, 15 patients reported some dysphagia, including 7 with new-onset dysphagia. For viscous boluses, three AIM-derived pressure-flow variables recorded preoperatively varied significantly in relation to postoperative dysphagia. These were: time from nadir esophageal impedance to peak esophageal pressure (TNadImp-PeakP), median intra-bolus pressure (IBP, mmHg), and the rate of bolus pressure rise (IBP slope, mmHgs(-1) ). These variables were combined to form a dysphagia risk index (DRI=IBP×IBP_slope/TNadImp-PeakP). DRI values derived from preoperative measurements were significantly elevated in those with postoperative dysphagia (DRI=58, IQR=21-408 vs no dysphagia DRI=9, IQR=2-19, P<0.02). A DRI >14 was optimally predictive of dysphagia (sensitivity 75% and specificity 93%). CONCLUSIONS & INFERENCES: Before surgery, a greater and faster compression of a swallowed viscous bolus with less bolus flow time relates to postoperative dysphagia. Thus, susceptibility to postfundoplication dysphagia is related to a pre-existing sub-clinical variation of esophageal function.

Palliative excisional surgery for primary colorectal cancer in patients with incurable metastatic disease. Is there a survival benefit? A systematic review.

AIM: Patients with stage IV colorectal cancer with unresectable metastases can either receive chemotherapy or palliative resection of the primary lesion. In the absence of any randomized data the choice of initial treatment in stage IV colorectal cancer is not based on firm evidence. METHOD: A search of MEDLINE, Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010 for studies comparing palliative resection in stage IV colorectal cancer with other treatment modalities. Audits and observational studies were excluded. Median survival was the primary outcome measure. The morbidity and mortality of surgical and nonsurgical treatments were compared. RESULTS: Twenty-one studies (no randomized controlled trials) were identified. Most demonstrated a survival benefit for patients who underwent palliative resection. Multivariate analysis indicates that tumour burden and performance status are both major independent prognostic variables. Selection bias, incomplete follow up and nonstandardized reporting of complications make the data difficult to interpret. CONCLUSION: The studies indicate that there may be a survival benefit for primary resection of colorectal cancer in stage IV disease. The findings suggest that resection of the primary tumour should be based on tumour burden and performance status rather than on the presence or absence of symptoms alone.

Systematic review: ageing and gastro-oesophageal reflux disease symptoms, oesophageal function and reflux oesophagitis.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is thought to become more prevalent with age. AIM: To assess systematically how age affects the prevalence of GERD and its oesophageal complications. METHODS: Systematic PubMed searches were used to identify population-based studies on the age-related prevalence and incidence of GERD, and clinical studies on age-related changes in oesophageal complications in GERD. RESULTS: Nine population-based studies and seven clinical studies met the inclusion criteria. Four of seven prevalence studies observed no significant effect of age on GERD symptom prevalence, two did not report on statistical significance and one observed a significant age-related increase in symptom prevalence. The two population-based endoscopic surveys showed no significant effect of age on reflux oesophagitis prevalence. Clinical studies in patients with GERD showed an increase in reflux oesophagitis severity and a decrease in heartburn severity with age, and age-related increases in oesophageal acid exposure and anatomical disruption of the gastro-oesophageal junction. CONCLUSIONS: Epidemiological studies do not show an increase in GERD symptom prevalence with age. However, in individuals with GERD, ageing is associated with more severe patterns of acid reflux and reflux oesophagitis; despite this, symptoms associated with GERD become less severe and more nonspecific with ageing. Thus, the real prevalence of GERD may well increase with age.

The effects of high-dose esomeprazole on gastric and oesophageal acid exposure and molecular markers in Barrett's oesophagus.

BACKGROUND: Acid reflux is often difficult to control medically. AIM: To assess the effect of 40 mg twice daily esomeprazole (high-dose) on gastric and oesophageal pH and symptoms, and biomarkers relevant to adenocarcinoma, in patients with Barrett's oesophagus (BO). METHODS: Eighteen patients, treated with proton pump inhibitors as prescribed by their treating doctor, had their therapy increased to high-dose esomeprazole for 6 months. RESULTS: At entry into the study, 9/18 patients had excessive 24-h oesophageal acid exposure, and gastric pH remained <4 for >16 h in 8/18. With high-dose esomeprazole, excessive acid exposure occurred in 2/18 patients, and gastric pH <4 was decreased from 38% of overall recording time and 53% of the nocturnal period to 15% and 17%, respectively (P < 0.001). There was a reduction in self-assessed symptoms of heartburn (P = 0.0005) and regurgitation (P < 0.0001), and inflammation and proliferation in the Barrett's mucosa. There was no significant change in p53, MGMT or COX-2 expression, or in aberrant DNA methylation. CONCLUSIONS: High-dose esomeprazole achieved higher levels of gastric acid suppression and control of oesophageal acid reflux and symptoms, with significant decreases in inflammation and epithelial proliferation. There was no reversal of aberrant DNA methylation.

Dyspepsia and irritable bowel syndrome in China: a population-based endoscopy study of prevalence and impact.

BACKGROUND: Dyspepsia and irritable bowel syndrome (IBS) are common in Western populations. AIM: To determine the epidemiology of dyspepsia and IBS in China. METHODS: A representative sample of 18 000 adults from five regions of China were asked to complete the modified Rome II questionnaire; 20% were asked to complete the 36-item Short Form Health Survey (SF-36). Participants from Shanghai were invited to provide blood samples and undergo oesophago-gastroduodenoscopy. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using a multivariate logistic regression model. RESULTS: The survey was completed by 16 091 individuals (response rate: 89.4%). Overall, 387 participants (2.4%) had dyspepsia and 735 (4.6%) had IBS. All SF-36 dimension scores were at least five points lower in individuals with than without dyspepsia or IBS (P < or = 0.001). In Shanghai, 1030 (32.7%) of the 3153 respondents agreed to endoscopy; neither dyspepsia nor IBS was found to be associated with reflux oesophagitis, peptic ulcer disease or Helicobacter pylori infection. CONCLUSIONS: Prevalence estimates for dyspepsia and IBS in China are lower than in Western populations. In China, dyspepsia or IBS symptoms are generally not associated with underlying organic disease.

Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care.

BACKGROUND: Accurate diagnosis and effective management of gastro-oesophageal reflux disease (GERD) can be challenging for clinicians and other health care professionals. AIM: To develop a patient-centred, self-assessment questionnaire to assist health care professionals in the diagnosis and effective management of patients with GERD. METHODS: Questions from patient-reported GERD instruments, previously documented in terms of content validity and psychometric properties (RDQ, GSRS and GIS) and data on the diagnosis of GERD in primary and secondary care were used in the formal development of a diagnostic and management tool, the GerdQ, involving psychometric validation and piloting in patient focus groups. RESULTS: Analyses of data from over 300 primary care patients, moderated by patient input from qualitative interviews, were used to select specific items from the existing instruments to create a new six-item diagnostic and management tool (GerdQ). ROC analysis indicated a sensitivity for GerdQ of 65% and a specificity of 71% for the diagnosis of GERD, similar to that achieved by gastroenterologists. CONCLUSION: The GerdQ is a potentially useful tool for family practitioners and other health care professionals in diagnosing and managing GERD without initial specialist referral or endoscopy.

Clinical trial design in adult reflux disease: a methodological workshop.

BACKGROUND: The development of well-tolerated acid suppressant drugs has stimulated substantial growth in the number of trials assessing therapy options for gastro-oesophageal reflux disease (GERD). AIM: To develop consensus statements to inform clinical trial design in adult patients with GERD. METHODS: Draft statements were developed employing a systematic literature review. A modified Delphi process including three rounds of voting was used to reach consensus. Between voting, statements were revised based on feedback from the Working Group and additional literature reviews. The final vote was at a face-to-face meeting that included discussion time. Voting was conducted using a six-point scale. RESULTS: At the last vote, 93% of the final 102 statements achieved consensus (defined a priori as being supported by >or=75% of the votes). The Working Group strongly supported the development of validated patient-reported outcome instruments. Symptom assessments carried out by the investigator were considered unacceptable. There was agreement that exclusion from clinical trials should be minimized to improve generalizability, that prospective evaluation ideally requires electronic timed/dated methods and that endoscopists should be blinded to patient symptom status. CONCLUSIONS: Implementation of the consensus statements will improve the quality and comparability of trials, and make them compatible with regulatory requirements.

Pathogenesis of gastro-oesophageal reflux disease and novel options for its therapy.

Better understanding of the mechanisms that lead to reflux disease is an important area for future research, given the very high prevalence of this problem. During the lifetime of this journal, much has been learnt about the pathophysiology of reflux disease. Abnormally, frequent acid reflux plays a key role in pathogenesis: this reflux occurs predominantly during transient lower oesophageal sphincter relaxations. Analysis of the literature suggests that the importance of transient relaxations as the major permissive event for occurrence of acid reflux is currently substantially underestimated. 'Transient relaxation' is an inexact descriptor, as this motor programme includes inhibition of the diaphragmatic hiatus and distal oesophageal body circular muscle and contraction of the oesophageal longitudinal muscle. Laxity of the diaphragmatic hiatus and hiatus hernia are probably important factors that increase the probability for acid reflux to occur during transient relaxations and in allowing strain-induced reflux episodes. The importance of straining and low basal tone of the lower oesophageal sphincter in causing abnormal reflux has probably been overestimated, but these need more investigation. High resolution manometry is the key method for acquisition of important new insights into the normal and disordered mechanics of the antireflux function of the gastro-oesophageal junction, but as yet, the potential of this technique has been tapped relatively little. In the future, improved understanding of the mechanics of the gastro-oesophageal junction should lead to improved physical antireflux procedures. Much progress has been made in defining the control of transient relaxations and this has been translated into several promising options for a new class of drug that treats reflux disease by inhibition of transient relaxations. Clinical trials on these agents appear imminent.

Endoscopic findings in a cohort of newly diagnosed gastroesophageal reflux disease patients registered in a UK primary care database.

Gastroesophageal reflux disease (GERD) may be accompanied by erosive complications that are diagnosed by endoscopy. This study aimed to describe the characteristics of patients newly diagnosed with GERD who are referred for endoscopy, and the factors associated with esophageal endoscopic findings. This study included patients aged 2-79 years with a first recorded diagnosis of GERD in 1996, as identified in a previous cohort study in the UK General Practice Research Database. The rate and results of endoscopy were recorded. Unconditional logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals for the relationship between a range of factors and endoscopy and its findings. Of the 7159 patients with a new GERD diagnosis, 805 (11%) underwent endoscopy close to the time of first consultation for GERD. Endoscopic findings indicative of esophageal damage were recorded in 73% of these patients. Esophageal endoscopic findings were significantly more likely in males, older patients, and individuals with a history of peptic ulcer disease or gastrointestinal bleeding. Use of acid-suppressive drugs, particularly proton pump inhibitors, was inversely associated with erosive endoscopic findings. Patients with erosive endoscopic findings were more likely to start a new course of treatment with a proton pump inhibitor. In conclusion, relatively few patients are referred for endoscopy close to the first consultation for GERD, and the majority of these individuals have esophageal findings. Male gender, increasing age and a history of bleeding were risk factors for esophageal complications.

[The Montreal definition and classification of gastroesophageal reflux disease: a global, evidence-based consensus paper]. / Die Montreal-Definition und -Klassifikation der gastroösophagealen Refluxkrankheit: Ein globales evidenzbasiertes Konsensus-Papier.

AIM: A world-wide recognised and accepted definition and classification of gastroesophageal reflux disease (GERD) would be highly desirable for research and clinical practice. The purpose of this project was to develop such a generally accepted definition and classification that could be used equally by patients, physicians, and supervisory bodies. METHODS: In order to ensure a consensus among the participating experts a modified delphi process with a step-wise selection modality was employed. For this the working group of five persons formulated a series of statements on the basis of a systematic search of the literature using three databases (Embase, Cochrane-Study register, Medline). Then these statements were developed further for two years, revised and finally passed as consensus. The consensus group consisted of 44 experts from 18 countries. Each key vote was held on the basis of a six-point scale. A "consensus" was considered to have been reached when two-thirds of the participants voted in favour of the respective statement. RESULTS: The level of agreement between the experts increased in the course of the multistep decision process, in the individual voting steps requiring at least two-thirds of the participants, the results were at first 86%, then 88% through to 94% and finally 100% in favour of the chosen statement. In the final voting, 94% of the final 51 statements were accepted by 90% of the consensus group. 90% of all statements were accepted unanimously or with only minor reservations. GERD was defined as a disease that is associated with troublesome symptoms and/or complications on account of reflux of stomach contents into the esophagus. The complaints are divided into esophageal and extra-esophageal syndromes. Among the novel aspects of this definition are the patient-orientated approach that is independent of endoscopic findings, the classification of the ailment into independent syndromes as well as the consideration of laryngitis, cough, asthma and dental problems as possible GERD syndromes. Furthermore, a new definition of suspected or demonstrated Barrett's esophagus is proposed. CONCLUSION: Irrespective of country-specific differences in terminology, language, prevalence and manifestations of this disease, evidence-based, world-wide valid consensus definitions are possible. A global consensus definition of GERD will simplify disease management, make mutual research possible and help in the design of generally valid studies. This will not only help the patient but also the physician and supervisory bodies.