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International audience; Aims: Sodium zirconium cyclosilicate (SZC, formerly ZS-9) is a selective K+ binder to treat adults with hyperkalaemia. HARMONIZE-Global examined the efficacy and safety of SZC among outpatients with hyperkalaemia from diverse geographic and ethnic origins.Methods and results: This phase 3, randomized, double-blind, placebo-controlled study recruited outpatients with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) at 45 sites in Japan, Russia, South Korea, and Taiwan. Following open-label treatment with thrice-daily SZC 10 g during a 48 h correction phase (CP), patients achieving normokalaemia (K+ 3.5-5.0 mmol/L) were randomized 2:2:1 to once-daily SZC 5 g, SZC 10 g, or placebo during a 28 day maintenance phase (MP). The primary endpoint was mean central-laboratory K+ level during days 8-29 of the MP. Of 267 patients in the CP, 248 (92.9%) entered the MP. During the CP, mean central-laboratory K+ was reduced by 1.28 mmol/L at 48 h vs. baseline (P < 0.001). During the MP (days 8-29), SZC 5 and 10 g once-daily significantly lowered mean central-laboratory K+ by 9.6% and 17.7%, respectively, vs. placebo (P < 0.001 for both). More patients had normokalaemia (central-laboratory K+ 3.5-5.0 mmol/L at day 29) with SZC 5 (58.6%) and 10 g (77.3%) vs. placebo (24.0%), with the greatest number of normokalaemic days in the 10-g group. The most common adverse events with SZC were mild or moderate constipation and oedema.Conclusions: Normokalaemia achieved during the CP was maintained over 28 days with SZC treatment among outpatients with hyperkalaemia.

BACKGROUND The rate of rebleeding from peptic ulcers could differ between Asian and Western populations. AIM To determine whether the observed twofold difference in rebleeding rates in two similarly designed clinical trials (one in Hong Kong [n=240], the other in a multinational Western population [n=764, http://ClinicalTrials.gov Identifier: NCT00251979]) can be explained by differences in baseline patient characteristics. METHODS Two-factor and multifactor analyses (adjusted by demographics, established risk factors for peptic ulcer and peptic ulcer bleeding, and disease severity variables) were performed using pooled data from the two studies. Cox regression analysis was used to predict the rebleeding risk at 3 days. RESULTS In the two-factor analysis (placebo vs esomeprazole/omeprazole and Western study vs Hong Kong study), data trended towards a reduced risk of rebleeding in the Western study (hazard ratio [HR]: 0.69; 95% confidence interval [CI] 0.44–1.07; p = 0.094). The risk of rebleedingwas similar in both studies after adjustment for multiple factors (HR: 1.10; 95% CI 0.60–1.99; p=0.767). The strongest predictor of rebleeding (apart from study drug) was a classification of American Society of Anesthesiologists (ASA) grade IV (HR: 4.15; 95% CI 1.49–11.56;p=0.006). When such patients were excluded, the difference in rebleeding rates between the studies reduced. CONCLUSIONS The difference in rebleeding rates between the two studies is explained by the factors in our analysis, most importantly a classification of ASA grade IV, suggesting that other differences, including ethnicity, did not influence the rebleeding rate. Copyright © 2017 John Wiley & Sons, Ltd.

SummaryBackground Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety. Aim To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies. Methods Safety data were collected from patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and changes in laboratory variables were analysed. Results Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12, folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the first year. Conclusion No major safety concerns arose during 5–12 years of continuous PPI therapy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn's disease (CD) in children.The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6-17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6 mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire.In the induction study (n = 108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean ± standard deviation, 9.1 ± 8.5 vs. 19.1 ± 10.1, p .001) with 58.1% of patients reaching remission (PCDAI10); HRQoL improved (p .001). In the maintenance study (n = 50), mean disease activity worsened (p = .047) with HRQoL unchanged (p = .33).Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946).

SummaryBackground Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). Aim To evaluate the process of ‘normalisation’ of the squamous epithelium morphology of the distal oesophagus on these therapies. Methods In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20–40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. Results A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. Conclusions Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are ‘normalised’ in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.

The rate of rebleeding from peptic ulcers could differ between Asian and Western populations. This study aimed to determine whether the observed twofold difference in rebleeding rates in two similarly designed clinical trials (one in Hong Kong [n = 240], the other in a predominantly Western population [n = 764, ClinicalTrials.gov identifier: NCT00251979]) can be explained by differences in baseline patient characteristics.Two-factor and multifactor analyses (adjusted by demographics, established risk factors for peptic ulcer and peptic ulcer bleeding, and disease severity variables) were performed using pooled data from the two studies. Cox regression analysis was used to predict the rebleeding risk at 3 days.In the two-factor analysis (placebo vs esomeprazole/omeprazole and Western study vs Hong Kong study), data trended towards a reduced risk of rebleeding in the Western study (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.44-1.07, P = 0.094). The risk of rebleeding was similar in both studies after adjusted for multiple factors (HR 1.10, 95% CI 0.60-1.99, P = 0.767). The strongest predictor of rebleeding (apart from study drug) was a classification of American Society of Anesthesiologists (ASA) grade IV (HR 4.15, 95% CI 1.49-11.56, P = 0.006). When such patients were excluded, the difference in rebleeding rates between the studies reduced.The difference in rebleeding rates between the two studies is explained by the factors in our analysis, most importantly a classification of ASA grade IV, suggesting that other differences, including ethnicity, did not influence the rebleeding rate.

Most patients with gastroesophageal reflux disease experience symptomatic relapse after stopping acid-suppressive medication. The aim of this study was to compare willingness to continue treatment with esomeprazole on-demand versus continuous maintenance therapy for symptom control in patients with non-erosive reflux disease (NERD) after 6 months. This multicenter, open-label, randomized, parallel-group study enrolled adults with NERD who were heartburn-free after 4 weeks’ treatment with esomeprazole 20 mg daily. Patients received esomeprazole 20 mg daily continuously or on-demand for 6 months. The primary variable was discontinuation due to unsatisfactory treatment. On-demand treatment was considered non-inferior if the upper limit of the one-sided 95 % confidence interval (CI) for the difference between treatments was

SUMMARY Background Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients. Aim To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis. Methods This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse. Results Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P < 0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration £5 years. Conclusions Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.

Summary Background The ability to predict symptom response to reflux oesophagitis-healing therapy may optimize treatment decisions. Aim To identify factors associated with heartburn resolution in patients receiving acid-suppressive therapy for reflux oesophagitis. Methods In this multicentre, randomized, double-blind trial (EXPO; AstraZeneca study code: SH-NEG-0008), patients with endoscopically confirmed reflux oesophagitis and reflux symptoms received once-daily proton pump inhibitor therapy [esomeprazole 40 mg (n = 1562) or pantoprazole 40 mg (n = 1589)] for ≥4 weeks. Factors associated with heartburn resolution after 4 weeks were identified by multiple logistic regression analysis. Results Esomeprazole therapy, positive Helicobacter pylori status and greater age were associated with an increased likelihood of heartburn resolution [odds ratio (95% confidence interval): 1.31 (1.12, 1.54), 1.44 (1.19, 1.74) and 1.013 (1.007, 1.019) per year, respectively; all P

To compare esomeprazole-based triple therapy with esomeprazole alone for the eradication of Helicobacter pylori (H. pylori), healing of ulcer and prevention of relapse in H. pylori-related gastric ulcer (GU) diseases.In this double-blind study, 401 H. pylori-positive patients with more than or equal to two GUs were randomized to: esomeprazole (20 mg) twice daily (bid) and amoxicillin (1000 mg) bid and clarithromycin (500 mg) bid (EAC) for 1 week, followed by placebo for 3 weeks (EAC and placebo); EAC for 1 week, followed by esomeprazole (20 mg) once daily (E20) for 3 weeks (EAC and E20); or esomeprazole (20 mg) bid and placebo antimicrobials for 1 week, followed by E20 for 3 weeks (E20 bid and E20). Patients with unhealed GUs at 4 weeks received E20 for an additional 4 weeks. Healed patients were followed up for 12 months.Eradication rates at 4 weeks or 8 weeks were 82% for EAC and E20, 77% for EAC and placebo and 9.5% for E20 bid and E20 (intention-to-treat analysis). Significantly more patients receiving EAC than those receiving esomeprazole alone remained free of GUs during follow-up [EAC and E20, 90%; EAC and placebo, 87%; P=0.0005 for combined group vs. esomeprazole alone [E20 bid and E20 (74%)]. All treatments were well tolerated.Esomeprazole-based triple therapy is effective for the eradication of H. pylori, healing of GU and prevention of relapse. Esomeprazole monotherapy for 3 weeks after triple therapy may be beneficial in terms of healing.

Background & Aims: We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes. Methods: We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole. Results: In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China. AstraZeneca. ClinicalTrials.gov identifier, NCT01757275.

Summary Background : Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. Aim : To compare endoscopic and symptomatic remission rates over 6 months’ maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. Methods : Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. Results : A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P

Summary Aim: To assess the efficacy of the 8-week therapy with esomeprazole 40 mg vs. pantoprazole 40 mg for healing erosive oesophagitis (EE) as part of a management study. Methods: Patients had a history of gastro-oesophageal reflux disease symptoms (≥6 months) and had suffered heartburn on at least 4 of the 7 days preceding enrolment. Endoscopies were performed to grade EE severity using the Los Angeles (LA) classification system at baseline, 4 and 8 weeks (if unhealed at 4 weeks). Heartburn severity was recorded by patients on diary cards. The primary end point was healing of EE by week 8 of treatment. Results: Of 3170 patients randomized, the intent-to-treat population consisted of 3151 patients (63% male, mean age: 50.6 years, 27%Helicobacter pylori-positive). Esomeprazole 40 mg healed a significantly greater proportion of EE patients than pantoprazole 40 mg at both 4 weeks (life table estimates: esomeprazole 81%, pantoprazole 75%, P

Introduction : Esomeprazole, the first proton pump inhibitor to be developed as an optical isomer, has demonstrated more effective healing vs. omeprazole and lansoprazole in patients with reflux oesophagitis (RO). However, RO recurs in a high proportion (∼80%) of these patients within 12 months of initial therapy, highlighting the importance of maintenance treatment. Previous studies have shown esomeprazole to be effective as maintenance therapy in healed RO patients. Aim: This study was conducted to compare esomeprazole 20 mg once daily (o.d.) with lansoprazole 15 mg o.d. for the prevention of recurrence of RO. Methods: 1391 patients with endoscopically verified RO (LA classification) were enrolled in this randomized, double-blind, parallel-group, multicentre trial. During the initial healing phase of the study, all patients received 4–8 weeks' open treatment with esomeprazole 40 mg: 1236 healed (identified by endoscopy at 4 and 8 weeks) and symptom-free (i.e. no heartburn or acid regurgitation) patients were randomized to 6 months' maintenance treatment with esomeprazole 20 mg o.d. or lansoprazole 15 mg o.d.. Time to relapse (relapse of RO and/or discontinuation due to symptom recurrence) was analysed using a log-rank test. Results: Esomeprazole maintained a significantly higher proportion of patients in remission than lansoprazole over the 6-month course of treatment (P

To assess the long-term effect on symptoms and quality of life of esomeprazole 20 mg once daily, a recommended dose for maintenance therapy of gastroesophageal reflux disease (GERD).This is a post hoc analysis of 5 year data from patients in the LOTUS trial (ClinicalTrials.gov identifier: NCT00251927) who were randomized to esomeprazole 20 mg once daily. All participants had chronic, symptomatic GERD responsive to treatment. Gastrointestinal symptoms were assessed by physicians and by using patient-reported outcome instruments. Investigations included gastrointestinal endoscopy (with biopsy sampling), 24 hour esophageal pH monitoring and laboratory measurements.In total, 157 of 256 patients randomized to esomeprazole 20 mg once daily remained on this dose until the end of follow-up or study discontinuation, whereas 99 patients had their dose increased because of inadequate symptom control (of these, 29 subsequently returned to the allocated dose). On logistic regression, a long objectively defined GERD history, smoking, female sex, absence of Helicobacter pylori infection and high supine baseline acid reflux into the esophagus were associated with an increased likelihood of requiring dose escalation to esomeprazole 40 mg daily (all p 0.05). Symptoms were fairly stable and quality of life was normal throughout follow-up in patients remaining on esomeprazole 20 mg once daily, with no more than mild symptom severity, and mean (standard deviation) percentage time with intraesophageal pH4 was reduced from 10.7 (10.7) pre-randomization to 6.3 (10.2) at 6 months and 4.9 (7.3) at 5 years. The number of serious adverse events was low (0.079 per patient per year).Post hoc analysis with no control group.Esomeprazole at a maintenance dose of 20 mg once daily offers effective long-term treatment for chronic GERD in patients initially responsive to the medication, with durable symptom control and sustained reductions in intraesophageal acid exposure.

To evaluate endoscopic and histological findings after Helicobacter pylori eradication therapy in gastric ulcer (GU) patients after 12 months' follow-up.A total of 401 GU patients were randomized to receive either twice-daily (b.i.d.) esomeprazole 20 mg+amoxicillin 1000 mg+clarithromycin 500 mg (EAC) for 1 week followed by placebo for 3 weeks, EAC followed by once-daily (o.d.) esomeprazole 20 mg for 3 weeks or esomeprazole 20 mg b.i.d. plus placebo antibiotics for 1 week followed by esomeprazole 20 mg o.d. for 3 weeks. Endoscopy with biopsy was performed at baseline, after treatment and at 6 and 12 months' follow-up (healed patients).Endoscopic abnormalities, particularly in the stomach, were common at baseline and remained similar during follow-up, regardless of ulcer status and treatment. Helicobacter gastritis was present (antrum or corpus) in approximately 20% of patients following eradication therapy (versus approximately 80% with esomeprazole alone); these effects were sustained during follow-up. Similar trends were observed for other histological variables (granulocyte and lymphoplasmocytic cell infiltration, replacement of gastric surface cells by regenerative epithelium, and mucous depletion). No changes in atrophy or intestinal metaplasia were observed. Eighteen gastric cancer cases were detected: 11 at baseline endoscopy, and seven during treatment and follow-up.Endoscopic abnormalities are common in GU patients and persist after proton-pump inhibitor-based triple therapy for H. pylori eradication, which is associated with large, sustained improvements in histological variables. Follow-up endoscopy and histology may be necessary, even in patients with apparently non-malignant GU, to improve the detection rate of gastric malignancy in populations with a high prevalence of gastric cancer.

The long-term management of gastroesophageal reflux in patients with Barrett’s esophagus (BE) is not well supported by an evidence-based consensus. We compare treatment outcome in patients with and without BE submitted to standardized laparoscopic antireflux surgery (LARS) or esomeprazole treatment. In the Long-Term Usage of Acid Suppression Versus Antireflux Surgery trial (a European multicenter randomized study), LARS was compared with dose-adjusted esomeprazole (20–40 mg daily). Operative difficulty, complications, symptom outcomes [Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD)], and treatment failure at 3 years and pH testing (after 6 months) are reported. Of 554 patients with gastroesophageal reflux disease, 60 had BE—28 randomized to esomeprazole and 32 to LARS. Very few BE patients on either treatment strategy (four of 60) experienced treatment failure during the 3-year follow-up. Esophageal pH in BE patients was significantly better controlled after surgical treatment than after esomeprazole (p = 0.002), although mean GSRS and QOLRAD scores were similar for the two therapies at baseline and at 3 years. Although operative difficulty was slightly greater in patients with BE than those without, there was no difference in postoperative complications or level of symptomatic reflux control. In a well-controlled surgical environment, the success of LARS is similar in patients with or without BE and matches optimized medical therapy.

OBJECTIVES: We aimed to determine the incidence, natural history, and recurrence rate of esophageal stricture diagnosed in primary care. METHODS: From the U.K. General Practice Research Database, we identified patients with a stricture diagnosis recorded between 1994 and 2000. Diagnoses were confirmed by general practitioner-completed questionnaires. Patients with stricture were compared to an age- and sex-matched sample of controls from the original source population. We estimated the incidence of stricture, potential risk factors, and comorbidities, and relative risk (RR) for subsequent stricture recurrence and mortality. RESULTS: The incidence of esophageal stricture was 1.1 per 10,000 person-years and increased markedly with age. Incidence of stricture decreased from 1994 to 2000, concomitant with a substantial increase in proton pump inhibitor (PPI) use. The majority of stricture cases (68%) were peptic. Prior dysphagia, gastroesophageal reflux disease (GERD), hiatus hernia, peptic ulcer disease, and heavy alcohol use were associated with an increased risk of stricture. The rate of stricture recurrence was 11.1 per 100 person-years. Risk of recurrence associated with long-term PPI use adjusting for other factors was 0.6 (95% CI 0.3-1.1). Mortality in patients with peptic stricture was similar to that in the control population. CONCLUSIONS: Esophageal stricture is a rare event, and most cases in primary care are peptic strictures. Prior GERD, hiatus hernia, and peptic ulcer are associated with an increased risk of peptic stricture. Incidence of stricture decreased from 1994 to 2000.

Introduction A once-only flexible sigmoidoscopy (FS) screening at age around 60 has been proposed as a cost-effective and acceptable method of reducing colorectal cancer (CRC) incidence and mortality. We undertook a large randomised controlled trial in a general population sample to compare CRC incidence and mortality rates following a single FS screen. Methods and baseline results Between 1994 and 1999, we sent a questionnaire to 375 744 men and women, aged 55 to 64 years, in 14 UK centres, asking whether they would have the FS screening if invited. Those who responded ‘yes definitely' or ‘yes probably' and were found to be eligible (n = 170 432) were randomised to the control or intervention arms of the trial in a 2:1 ratio. Of 57 254 people invited, 40 674 (71%) were screened. Following screening, 38 525 (95%) had either no pathology or only low-risk adenomas and were discharged and 2051 had high risk adenomas detected and underwent colonoscopy. Biannual updates on status (emigration, cancer diagnoses or deaths) were obtained by matching with the National Health Service Central Register, Office of National Statistics, UK cancer registries, and Hospitals Episodes Statistics records. Results of follow-up The median follow-up time to death, emigration or 31st December 2008 is currently 11 years. A total of 2491 participants developed CRC during 1.85 million person years of follow-up: 1523 developed a distal cancer (rectum or sigmoid colon), 894 developed cancer in the proximal colon, 34 developed cancer in both sites, and in 40 cases the site was not known. On an intent-to-treat analysis, a significant reduction in incidence of total and distal CRC was observed among those invited for screening. A greater reduction was seen among those who attended for screening. Colorectal cancer mortality rates were also reduced significantly. Adjustment for self-selection bias in attenders using Cuzick et al's method (Stat Med 1997;16:1017-29) made little difference to the rate ratios or significance. Conclusion By 11 years, total and distal colorectal cancer incidence rates were reduced significantly among people offered a single flexible sigmoidoscopy screen between ages 55 and 64 years, and so far no attenuation of effect has been observed. Detailed results will be presented.

1David Geffen School of Medicine at UCLA and CURE Digestive Diseases Research Center, Los Angeles, CA, USA; 2Glasgow Royal Infirmary, Glasgow, UK; 3AstraZeneca RD 4Division of Gastroenterology, McGill University Health Center, Montreal, Canada; 5Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; 6Medizinische Klinik und Poliklinik II, University of Leipzig, Leipzig, Germany; 7Institute of Digestive Diseases, Chinese University of Hong Kong, Shatin, Hong Kong, China

the adequacy of current screening interval. Methods: Three hundreds one medical records from the patients who underwent surgical treatment for primary GC at Korea University Ansan Hospital from January 2002 through December 2006 were reviewed retrospectively. After patients were divided into three groups according to the previous history of gastric endoscopy and the motivation for endoscopic examination based on the presence or absence of symptoms: the group I, patients with repeated endoscopy within the last 2 years (before the detection of GC) regardless of symptom (nZ12), the group II, asymptomatic patients without endoscopic screening within the last 2 years (nZ37), and the group III, symptomatic patiens without endoscopy (nZ252), the clinicopathologic characteristics of three groups were compared. Results: The proportion of early gastric cancer and the tumor size among the 3 groups were 75% vs. 68% vs. 41% (pZ0.001) and 2.7 ! 3.6 cm vs. 4.1 ! 2.5 cm vs. 5.2 ! 3.3 cm (p Z 0.012), respectively. GC in the group I and II was characterized by smaller cancer in an earlier stage. However, notable differences among the 3 gropus were not found in age, sex, tumor location and histology. Conclusion: Endoscopic screening for asymptomatic patients is useful for detecting GC at the early stage. Probably, periodic(2 years interval) endoscopy enables early detection of GC at a smaller size regardless of symptom.