Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

The natural history of gastro-oesophageal reflux symptoms in the community and its effects on survival: a longitudinal 10-year follow-up study.

BACKGROUND: Gastro-oesophageal reflux symptoms (GERS) are common in the community. However, few studies have examined their long-term natural history, or impact on survival. AIM: To examine these issues in individuals recruited into a community-based screening programme for Helicobacter pylori in 1994. METHODS: Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, gastrointestinal symptoms and quality of life were recorded at study entry. The effect of all these factors on persistent and new-onset GERS, and 10-year mortality, were examined using univariate and multivariate analysis, with results expressed as odds ratios (ORs) or hazard ratios (HR) with 99% confidence intervals (CI). RESULTS: Of 3967 individuals providing complete GERS data at baseline and 10 years, 549 (13.8%) had GERS at baseline. Of these, 183 (33.3%) had persistent symptoms. Among 3418 individuals asymptomatic at baseline, approximately 0.8% per year developed new-onset GERS. No predictors of persistent GERS were identified. New-onset symptoms were associated with lower quality of life or presence of irritable bowel syndrome (IBS) at baseline, and higher body mass index (BMI) at 10 years. There were 8331 (99.1%) of 8407 subjects providing complete GERS data at baseline, 1289 (15.5%) of whom were symptomatic. Presence of GERS at baseline did not affect survival (HR: 0.84; 99% CI: 0.44-1.59). CONCLUSIONS: Gastro-oesophageal reflux symptoms persisted in one-third of individuals, whilst new-onset gastro-oesophageal reflux symptoms were associated with poor quality of life, irritable bowel syndrome and higher body mass index. Gastro-oesophageal reflux symptoms did not impact adversely on survival.

Review article: methods of measuring gastric acid secretion.

BACKGROUND: Gastric acid has an important pathophysiological role in human beings. Numerous methods have been evaluated over the years in an attempt to measure gastric acid and stomach acidity, to study the role of gastric acid in gastrointestinal diseases in humans and to evaluate the effects of acid suppressing drugs. AIM: To review methods that have been used to measure gastric acid and gastric acidity. METHODS: Searches of the electronic databases PUBMED, MEDLINE and EMBASE, were performed with articles restricted to English language and human subjects. References were also identified from the bibliographies of selected articles. RESULTS: Methods for measuring gastric acid include both invasive and non-invasive techniques. Invasive tests include the conventional gastric acid aspiration tests, gastric pH measurement techniques and endoscopic methods. Non-invasive methods use urinary analysis, breath analysis, serum pepsinogens assay, scintigraphic techniques, impedence tomography and alkaline tide for measurement of gastric acid. CONCLUSIONS: Several methods of measuring gastric acid exist. Invasive tube tests are uncomfortable and time consuming, whereas most of the non-invasive methods are at best semiquantitative and useful in detecting low or absent acid secretion. Further attempts to explore new methods for measuring gastric acid are therefore warranted.

Sedation in digestive endoscopy: the Athens international position statements.

BACKGROUND: Guidelines and practice standards for sedation in endoscopy have been developed by various national professional societies. No attempt has been made to assess consensus among internationally recognized experts in this field. AIM: To identify areas of consensus and dissent among international experts on a broad range of issues pertaining to the practice of sedation in digestive endoscopy. METHODS: Thirty-two position statements were reviewed during a 1 (1/2)-day meeting. Thirty-two individuals from 12 countries and four continents, representing the fields of gastroenterology, anaesthesiology and medical jurisprudence heard evidence-based presentations on each statement. Level of agreement among the experts for each statement was determined by an open poll. RESULTS: The principle recommendations included the following: (i) sedation improves patient tolerance and compliance for endoscopy, (ii) whenever possible, patients undergoing endoscopy should be offered the option of having the procedure either with or without sedation, (iii) monitoring of vital signs as well as the levels of consciousness and pain/discomfort should be performed routinely during endoscopy, and (iv) endoscopists and nurses with appropriate training can safely and effectively administer propofol to low-risk patients undergoing endoscopic procedures. CONCLUSIONS: While the standards of practice vary from country to country, there was broad agreement among participants regarding most issues pertaining to sedation during endoscopy.

Fluctuation of gastrointestinal symptoms in the community: a 10-year longitudinal follow-up study.

BACKGROUND: There are few studies examining the stability of gastrointestinal symptoms during prolonged periods of follow-up. AIM: To examine this issue in individuals previously recruited into a community screening programme for Helicobacter pylori providing symptom data at study entry. METHODS: All traceable participants were sent dyspepsia and IBS questionnaires by post at 10 years. Symptom subgroups were assigned at baseline and 10-year follow-up. Individuals symptomatic at both time points who changed subgroup were compared with those symptomatic and remaining in the same subgroup. RESULTS: Three-thousand eight hundred and nineteen individuals provided data. At baseline, 2417 (63%) were asymptomatic or did not meet diagnostic criteria for a subgroup. Of these, 1648 (68%) remained asymptomatic at 10 years, whilst 769 (32%) reported symptoms. Of the 1402 individuals symptomatic at baseline, 404 (29%) remained in the same subgroup at 10 years, 603 (43%) changed subgroup and symptoms resolved or did not meet criteria for a subgroup in 395 (28%). Symptom stability was more likely in males [odds ratio (OR): 1.50; 99% confidence interval (CI): 0.97-2.31] and older subjects (OR per year: 1.09; 99% CI: 1.01-1.17). CONCLUSION: Of those subjects symptomatic at baseline, almost three-quarters remained symptomatic at 10 years, but over 40% changed symptom subgroup.

A mechanism for the anti-fibrogenic effects of the pregnane X receptor (PXR) in the liver: inhibition of NF-kappaB?

The liver is susceptible to chronic damage through exposure to a variety of toxins (e.g. alcohol) and viruses (e.g. hepatitis C). Obesity, autoimmune diseases (e.g. autoimmune hepatitis) and a variety of genetic diseases (e.g. Wilson's disease) also lead to chronic liver damage. This damage results in scarring fibrogenesis, structural disruption and functional impairment of the organ. Recent work suggests that there is cross-talk between the PXR and NF-kappaB pathways. This cross-talk may explain the observation that PXR activators inhibit liver fibrosis in in vitro and in vivo animal models of the disease. This reveiw will focus on the two transcription factors and their potential interaction.

Mycophenolate mofetil therapy for refractory inflammatory bowel disease.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunomodulatory drug, and its use in inflammatory bowel disease has previously been reported. The aim of this study was to review the Leeds Colitis Clinic experience of the safety and efficacy of MMF in treating patients with refractory Crohn's disease (CD) and ulcerative colitis (UC). This is an extension of a previously published study from our center with a longer follow-up period and approximately twice the number of patients. METHODS: A retrospective analysis was performed of the records of all patients treated with MMF for inflammatory bowel disease over a 5-year period. RESULTS: Of 70 patients identified, 67 had previously been treated with azathioprine unsuccessfully. Seventeen of the 70 patients had been successfully maintained in remission with MMF for an average duration of 33 months. Treatment with MMF was discontinued for 53 patients, 17 because of side effects and 36 because they had not responded to the treatment. CONCLUSIONS: In our series, 17 patients (24.3%) had a sustained steroid-free remission with MMF therapy. Nineteen patients (27%) experienced side effects, of which 17 (24.3% of the total group) had to discontinue therapy. An additional 36 (51.4%) required an escalation in medical therapy or surgery because of failure of the MMF therapy. MMF may have a role in the treatment of refractory inflammatory bowel disease, especially in patients who have previously failed standard therapies such as azathioprine.

Clinical trial: knowledge of negative Helicobacter pylori status reduces subsequent dyspepsia-related resource use.

BACKGROUND: Screening for Helicobacter pylori reduces dyspepsia and dyspepsia-related costs in positive individuals. AIMS: To assess effect of knowledge of H. pylori status on healthcare-seeking in negative individuals. METHODS: H. pylori-negative subjects in a community screening programme were randomized to placebo triple therapy or informed of their negative H. pylori status. Dyspepsia-related resource data were extracted from primary care records at 2 years, and National Health Service reference costs were applied to calculate the total cost per subject. Proportions of individuals incurring any cost were compared using a relative risk (RR) and 95% confidence interval (CI). Differences in costs were compared using an independent sample t-test. RESULTS: A total of 1353 H. pylori-negative individuals were randomized to placebo whilst 1355 were informed of their infection status. In the placebo arm, 212 (16%) subsequently incurred any dyspepsia-related cost compared to 172 (13%) informed of their infection status (RR of incurring cost = 0.81; 95% CI: 0.67-0.97). Those informed of their infection status incurred lower costs (mean saving per individual = pound 11.02; 95% CI: - pound 3.52 to 25.56). CONCLUSIONS: H. pylori-negative individuals informed of infection status sought health care for dyspepsia less often than those who were unaware. Population screening may reduce dyspepsia-related costs in uninfected, as well as infected individuals.

Low-grade dysplasia in Barrett's esophagus has a high risk of progression.

BACKGROUND AND STUDY AIMS: Surveillance in Barrett's esophagus relies on the detection of dysplasia by histopathology. However, the natural history of this condition, particularly that of low-grade dysplasia (LGD) is poorly understood. This paper describes our experience of LGD over a period of 21 years. PATIENTS AND METHODS: Between 1984 and January 1995, 357 patients with Barrett's esophagus without dysplasia were recruited for annual surveillance: 34 of these patients developed LGD during this period. This was a retrospective cohort study of this group in terms of survival and cancer outcomes >/= 8 years after the original diagnosis of LGD, comparing them with the patients who did not develop LGD over the same period, with a histopathological review of the original diagnoses of LGD. The outcomes of 356/357 (99.7 %) of the patients were established in December 2004. RESULTS: After 8 years, high-grade dysplasia (HGD) or cancer had developed in 9/34 patients with LGD (27 %) and in 16/322 controls (5 %). Cox's proportional hazards model revealed that the time from the first diagnosis of Barrett's esophagus to the first "event" of either HGD, esophageal cancer, or death did not show a statistically significant difference between the two groups. A further analysis treating death as "loss to follow-up" showed a significantly increased risk for the LGD group to progress to HGD or cancer (hazard ratio 5.9 [95 % confidence interval 2.6 - 13.4], P< 0.001). The histopathology review demonstrated a fair level of agreement between pathologists, with a kappa value of 0.48. CONCLUSIONS: Patients diagnosed with LGD during surveillance of Barrett's esophagus are at a considerably increased risk of progressing to develop esophageal cancer over an 8-year period but most deaths are not cancer-related.

Relationship between Helicobacter pylori gastritis, gastric cancer and gastric acid secretion.

Epidemiological evidence strongly indicates that Helicobacter pylori infection is an essential factor for the development of most non-cardia gastric cancer. Furthermore, the identification of an effective animal model and a plausible biological hypothesis provide further compelling evidence for its pathogenic role. Nevertheless, it will be some years before prospective studies in humans are able to confirm cause and effect beyond any doubt. In the meantime sceptics point out that the prevalence of Helicobacter pylori in different countries do not always correlate with the incidence of gastric cancer. It is unclear why patients with duodenal ulcer (who are almost invariably infected) are protected from the disease. Cancer often develops in patients from whom Helicobacter disappeared from the stomach years previously. This paper discusses the relationship between Helicobacter pylori infection, the development of gastritis and its evolution to non-cardia gastric cancer. It also addresses possible reasons why the incidence of gastric cancer does not always mirror the prevalence of Helicobacter infection throughout the world and why patients with duodenal ulcer may be protected from developing gastric cancer.

Why does Japan have a high incidence of gastric cancer? Comparison of gastritis between UK and Japanese patients.

BACKGROUND AND AIMS: The incidence of gastric cancer in Japan is four times higher than in the UK. It usually arises in a stomach with corpus predominant or pangastritis that has undergone extensive atrophy and intestinal metaplasia. We hypothesised that a Japanese population would have a more severe gastritis with a corpus predominant or pangastritis pattern and a greater degree of atrophy and intestinal metaplasia than that found in the UK. To test this we designed a comparative trial. METHODS: A total of 252 age matched consecutive patients were recruited from the endoscopy services in Leeds and Tokyo. In each centre, 21 patients were prospectively selected from each decennial, between the ages of 20-80 years. All had epigastric discomfort as their predominant symptom. Patients with peptic ulcer, cancer, and oesophagitis were excluded. Five gastric biopsies were examined by two histopathologists using the updated Sydney system. Helicobacter pylori infection was assessed by histology and culture of biopsies and enzyme linked immunosorbent assay and immunoblot of plasma. RESULTS: Gastritis was found by both pathologists in 59 (47%) UK and 76 (60%) Japanese patients (chi(2) test, p = 0.04). In those patients with gastritis, corpus predominant or pangastritis was commoner in the Japanese (63% Japan v 36% in the UK (chi(2) test, p = 0.003) Atrophy and intestinal metaplasia were more extensive and severe (Mann-Whitney U test, p<0.001) and chronic inflammation and polymorph activity were also greater, especially in the corpus (Mann-Whitney U test, p<0.001). Fifty three of 59 UK gastritis patients (90%) and 67/76 (88%) (chi(2) test, p = 1) Japanese gastritis patients were positive for H pylori. Using a previously described "gastric cancer risk index" among H pylori positive patients, there were significantly more Japanese than UK subjects with a "high risk" score. CONCLUSION: In Japanese as opposed to English patients, gastritis is more prevalent and severe with more corpus predominant atrophy and intestinal metaplasia. These differences may partially explain the higher incidence of gastric cancer in Japan.

Review article: gastro-oesophageal reflux disease--the extent of the problem.

There have been little review data on the period prevalence of heartburn symptoms in the community. We analysed reflux symptom data from a test-and-treat trial that evaluated community Helicobacter pylori levels and added these to data identified from a literature search. We found 31 papers reporting on 77,671 subjects who provided information on the frequency of heartburn symptoms in the community. Pooled data from these papers suggested that, in Western populations, 25% had symptoms at least once per month, 12% had symptoms at least weekly and 5% had heartburn daily. Reflux symptoms were less common in East Asian populations with only 7% having heartburn at least once per month. Heartburn is a significant problem in Western societies.

Gastro-oesophageal reflux is more prevalent in Western dyspeptics: a prospective comparison of British and South-East Asian patients with dyspepsia.

BACKGROUND: There is a paucity of data directly comparing dyspepsia in Western and Eastern populations. AIM: To compare clinical symptoms, epidemiological factors and endoscopic diagnoses in two sample populations with dyspepsia from the United Kingdom and South-East Asia in a cross-sectional study. METHODS: Patients with uncomplicated dyspepsia attending endoscopy units in Leeds, UK, and Kuala Lumpur, Malaysia, were prospectively interviewed and underwent subsequent endoscopy. RESULTS: A total of 1003 Malaysian patients (January 2002 to August 2003) and 597 Caucasian British patients (January 2000 to October 2002) were studied. The mean age was 48.7 +/- 15.8 and 47.5 +/- 13.8 years for the Malaysian and British patients respectively (P = NS). There was a higher proportion of cigarette smoking (35.7% vs. 12.4%, P < 0.0001) and alcohol consumption (34.4% vs. 2.0%, P < 0.0001) amongst British patients, but no difference in non-steroidal anti-inflammatory drug use nor having Helicobacter pylori infection. Gastro-oesophageal reflux disease (GERD) symptoms were more common in British compared with South-East Asian patients [heartburn (72% vs. 41%), regurgitation (66% vs. 29.8%) and dysphagia (21.1% vs. 7.3%), P < 0.0001]. This correlated with an increased endoscopic finding of oesophagitis (26.8% vs. 5.8%) and columnar-lined oesophagus (4.4% vs. 0.9%) amongst British patients (P < 0.001). A logistic regression model revealed that British Caucasian race (OR 9.7; 95% CI = 5.0-18.8), male gender (OR 2.0; 95% CI = 1.4-2.9) and not having H. pylori infection (OR 0.5; 95% CI = 0.3-0.7) were independent predictors for oesophagitis. CONCLUSION: GERD is more common in British compared with South-East Asian dyspeptic patients suggesting that race and/or western lifestyle are important risk factors.

Personal view: to treat or not to treat? Helicobacter pylori and gastro-oesophageal reflux disease - an alternative hypothesis.

Helicobacter pylori causes acute on chronic gastritis and is responsible for most peptic ulcers and gastric cancer. However, recent papers have suggested that it may protect against gastro-oesophageal reflux, Barrett's oesophagus and oesophageal cancer. Furthermore, the rapid increase in gastro-oesophageal reflux disease, Barrett's oesophagus and adenocarcinoma of the oesophagus in the developed world has been attributed by some to the falling prevalence of H. pylori. These considerations have led to the suggestion that H. pylori infection should not necessarily be treated, especially in patients with gastro-oesophageal reflux disease. Conversely, data from prospective randomized studies have shown that H. pylori eradication does not cause gastro-oesophageal reflux disease in patients with duodenal ulcer or in the normal population, nor does it worsen the outcome of pre-existing gastro-oesophageal reflux disease. Therefore, although H. pylori is negatively associated with gastro-oesophageal reflux disease, its eradication does not induce the disease. A hypothesis is presented suggesting that the increased prevalence of gastro-oesophageal reflux disease is a result of rising acid secretion in the general population, which, in turn, is a consequence of the increased linear height (a predictor of acid secretion). The greater acid secretion could also explain the decline in the prevalence of H. pylori and perhaps account for the inverse relationship between H. pylori and gastro-oesophageal reflux disease. These considerations are explored in discussing whether H. pylori infection should be treated in infected patients presenting with gastro-oesophageal reflux disease.