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The best approach forInternational multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empiricalManagement of

Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy.

This article summarizes the published literature concerning the epidemiology and public health implications of Helicobacter pylori infection published from April 2009 through March 2010. Prevalence of infection varied between 7 and 87% and was lower in European studies. All retrieved studies examining transmission of infection concluded that spread is from person-to-person. One study collecting stool and vomitus samples from patients with acute gastroenteritis detected H. pylori DNA in 88% of vomitus and 74% of stool samples. Proposed risk factors for infection included male gender, increasing age, shorter height, tobacco use, lower socioeconomic status, obesity, and lower educational status of the parents in studies conducted among children. Decision analysis models suggest preventing acquisition of H. pylori, via vaccination in childhood, could be cost-effective and may reduce incidence of gastric cancer by over 40%. As yet, no country has adopted public health measures to treat infected individuals or prevent infection in populations at risk.

Sonwalkar S A, Rotimi O, Scott N, Verghese E, Dixon M, Axon A T R A & Everett S M (2010) Histopathology 56, 900–907 A study of indefinite for dysplasia in Barrett’s oesophagus: reproducibility of diagnosis, clinical outcomes and predicting progression with AMACR (α-methylacyl-CoA-racemase) Aims: To assess interobserver variation in the diagnosis of dysplasia in Barrett’s oesophagus, especially indefinite dysplasia (IND) using the revised Vienna classification. A secondary aim was to study clinical outcome of IND cases and to evaluate expression of alpha-methyl-CoA racemase (AMACR) as a marker predictive of progression. Methods and results: Cases of Barrett’s oesophagus and dysplasia over a 20 year period were assessed. Three experienced histopathologists reviewed 101 cases on set criteria in a blinded fashion. Slides were immunostained for AMACR and evaluated for the presence, extent and location of AMACR expression. Clinical and progression data were collected. Overall agreement for the diagnosis of dysplasia was fair (k = 0.35) but that for IND was poor (k = 0.18). 6 IND cases progressed after a median follow-up of 31.4 months to a higher grade. The sensitivity of AMACR for the detection of abnormality was 22% for IND and specificity 100%. The positive predictive value of AMACR for progression was 0.44 and the negative predictive value was 0.92. Conclusion: Fair agreement was achieved for the diagnosis of dysplasia but poor agreement for IND. A proportion of IND cases progress. Re-diagnosis or consensus diagnosis did not predict progression. AMACR shows promise as a marker to indicate IND patients in need of more intensive surveillance.

Ethical and legal implications arise both when seeking a second medical opinion and when providing one. There has been debate as to whether a second opinion for a patient is a right or a concession and whilst today most would consider it to be a patient’s right, there are nevertheless some disadvantages associated with seeking a second opinion. This article addresses the reasons why patients seek second opinions, it considers when physicians themselves should refer patients and it covers the issues involved in providing a second opinion particularly in cases where there is the potential for an allegation of malpractice. Finally, the arguments for and against treating patients who are referred for a second opinion are addressed. This paper has been prepared following a round table discussion on this subject, which was addressed during a symposium on Ethics in Gastroenterology and Digestive Endoscopy held in Kos in 2006.

In spite of the recognition that Helicobacter pylori is responsible for most duodenal ulcer and peptic ulcer and that it is the underlying cause of most gastric cancer, little or no attention has been paid to its effect upon public health and in particular no measures have been put in place to address them. For over 20 years relatively inexpensive and noninvasive testing and treatment have been available, but no country has introduced a "screen-and-treat" policy, and relatively little research has been devoted to the identification of a vaccine for the disease. Health-care providers and doctors themselves are amenable to persuasion but in order to achieve appropriate investment in this area media pressure is required to publicize the arguments of health economics and equality of health that support the introduction of appropriate measures. There is a strong movement to eradicate inequalities of health. Population studies have shown that eradication of the infection can be provided at reasonable cost. Such a policy can easily be audited. Helicobacter pylori infection is the commonest environmental cause of cancer death after smoking, the diseases it causes represent a serious cost to health providers, and it affects the poorest members of our society. In the words of Kofi Annan, "Health should not be regarded as a blessing to be wished for, but a human right to be fought for."

Accepted 29 August 2007Background Infection with Helicobacter pylori (H. pylori) is acquired mainly in childhood,with studies demonstrating this is related to living conditions. Effects of siblingnumber and birth order on prevalence of infection have not been extensivelystudied.Methods The authors performed a cross-sectional survey of adults, aged between 50 and59 years, previously involved in a community-screening programme for H. pyloriin Leeds and Bradford, UK. Prevalence of H. pylori was assessed at baselinewith urea breath test. All individuals who were alive, and could be traced,were contacted by postal questionnaire in 2003 obtaining information onnumber of siblings and birth order. Data concerning childhood socioeconomicconditions were stored on file from the original study.Results 3928 (47%) of 8407 original participants provided data. Prevalence of infectionincreased according to sibling number (20% in those with none vs 63% witheight or more). Controlling for childhood socioeconomic conditions and birthorder using multivariate logistic regression, infection odds were substantiallyincreased with three siblings compared with none [odds ratio (OR) 1.51;95% confidence interval (CI) 1.06–2.15], and a gradient of effect continued up toeight or more siblings (OR 5.70; 95% CI 2.92–11.14). Odds of infection alsoincreased substantially with birth order, but the positive gradient disappearedon adjustment for sibling number and childhood socioeconomic conditions.Conclusions: In this cross section of UK adults, aged 50–59 years, sibling number in thehousehold, but not birth order, was independently associated with prevalenceof H. pylori infection.Keywords Birth order, Helicobacter pylori, prevalence, siblings

Background: Numerous studies examining the prevalence and natural history of dyspepsia in the general population have been conducted. However, few have reported the effect of quality of life on the development of dyspepsia. A 10-year longitudinal follow-up study examining the effect of quality of life on subsequent dyspepsia was performed. Methods: Individuals originally enrolled in a population-screening programme for Helicobacter pylori were contacted through a validated postal dyspepsia questionnaire. Baseline demographic data, quality of life at original study entry, and dyspepsia and irritable bowel syndrome (IBS) symptom data were already on file. Consent to examine primary-care records was sought, and data regarding non-steroidal anti-inflammatory drugs (NSAID) and aspirin use were obtained from these. Results: Of 8407 individuals originally involved, 3912 (46.5%) provided symptom data at baseline and 10-year follow-up. Of 2550 (65%) individuals asymptomatic at study entry, 717 (28%) developed new-onset dyspepsia at 10 years, an incidence of 2.8% per year. After multivariate logistic regression, lower quality of life at study entry (OR 2.63; 99% CI 1.86 to 3.71), higher body mass index (OR per unit 1.05; 99% CI 1.02 to 1.08), presence of IBS at study entry (OR 3.1; 99% CI 1.51 to 6.37) and use of NSAIDs and/or aspirin (OR 1.32; 99% CI 0.99 to 1.75) were significant risk factors for new-onset dyspepsia. Conclusions: The incidence of new-onset dyspepsia was almost 3% per year. Low quality of life at baseline exerted a strong effect on the likelihood of developing dyspepsia at 10 years.

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.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.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, p0.001) and chronic inflammation and polymorph activity were also greater, especially in the corpus (Mann-Whitney U test, p0.001). 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.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.

Background & Aims: Population screening and treatment of Helicobacter pylori has been advocated as a means of reducing mortality from gastric cancer, as well as dyspepsia and dyspepsia-related resource use. Previous programs have failed to demonstrate a significant effect on mortality or resource use, but follow-up was only for 1 or 2 years. We aimed to determine the effect of screening for H pylori on dyspepsia and dyspepsia-related resource use over 10 years. Methods: H pylori –positive individuals, aged 40–49 years, enrolled in a community screening program, randomized to eradication therapy or placebo in 1994, were sent a validated dyspepsia questionnaire by mail 10 years later, and primary care records were reexamined. Consultation, referral, prescribing, and investigation data related to dyspepsia were extracted. United Kingdom costs were applied to derive total cost per person (£1 = $1.8). Results: Of 2324 original participants, 1864 (80%) were traced and contacted. Of these, 1086 (47%) responded, and 919 (40%) agreed to a review of their primary care records. There was a 10-year mean saving in total dyspepsia-related costs of $117 per person (95% confidence interval [CI] = $11–$220, P = .03) with eradication therapy. Those symptomatic at baseline showed a nonsignificant trend toward resolution of symptoms at 10 years with eradication therapy (relative risk of remaining symptomatic, 0.89; 95% CI: 0.77–1.03). Conclusions: There were significant reductions in total dyspepsia-related health care costs. The savings made were greater than the initial cost of H pylori screening and treatment.

Previously doctors decided what was right or wrong in medicine, today our individual freedom is more limited. External influences including the human rights act, government initiatives, management protocols, professional guidelines, multi-disciplinary decision-making and financial restrictions intervene between the doctor and the patient. Furthermore the move away from paternalism in the doctor–patient relationship to patient empowerment (informed consent) has put patients in charge of their medical destiny. Increased public expectations leading to health screening, genetic profiling and treatment of unwanted physiological changes mean that doctors now manage healthy patients for ‘potential’ or ‘virtual’ disease. This implies a greater ethical burden than treatment of the sick. Finally, death is no longer regarded by many as a physiological process, but a consequence of disease. The investigation and management of patients with incurable conditions can lead to difficult ethical dilemmas. Gastroenterology and endoscopy generate specific ethical problems which among others include training in endoscopy, percutaneous endoscopic gastrostomy placement, informed consent and live endoscopy demonstrations. This article addresses some of these issues in order to draw attention to potential difficulties in modern ethical practice. It should be read in conjunction with the other publications stemming from the 1st Symposium on Ethics in Gastroenterology and Endoscopy, Kos, June 2002.

Reactive oxygen species have been implicated inHelicobacter pylori-mediated gastric carcinogenesis, whereas diets high in antioxidant vitamins C and E are protective. We have examined the effect of vitamin C and E supplements in combination withH. pylorieradication on reactive oxygen species activity inH. pylorigastritis.H. pylori-positive patients were randomized into four groups: triple therapy alone (Bismuth chelate, tetracycline, and metronidazole for 2 weeks), vitamins alone (200 mg vitamin C and 50 mg vitamin E, both twice per day for 4 weeks), both treatments or neither. Plasma and mucosal ascorbic acid, malondialdehyde and reactive oxygen species were determined before and after treatment. Compared with normal controls (n61),H. pylori-positive patients (n117) had higher mucosal reactive oxygen species and malondialdehyde levels and lower plasma ascorbic acid. Plasma ascorbic acid doubled in both groups of patients receiving vitamins and mucosal levels also increased. Malondialdehyde and reactive oxygen species fell in patients in whomH. pyloriwas eradicated but vitamin supplements were not effective either alone or in combination withH. pylorieradication. Supplements of vitamins C and E do not significantly reduce mucosal reactive oxygen species damage inH. pylorigastritis.

Gastric cancer and peptic ulcer between them cause the death of over a million people each year. A number of articles this year have studied changes in the prevalence of the infection in a variety of countries and ethnic groups. They confirm the known risk factors for infection, principally a low standard of living, poor education, and reduced life span. The prevalence of infection in developed countries is falling, but more slowly now than was the case before, meaning that a substantial number of the population will remain infected in the years to come. Reinfection is more common in less developed countries. The incidence of gastric cancer is highest in populations with a high prevalence of infection. Population test and treat is a cost-effective means of preventing gastric cancer. Peptic ulcer is the commonest cause of death in patients undergoing emergency surgery. The alleged risk that treatment may cause some to develop reflux esophagitis remains controversial.

Background & Aims: Observational studies have suggested that Helicobacter pylori may protect against gastrointestinal reflux disease (GERD), but these results could be due to bias or confounding factors. We addressed this in a prospective, double blind, randomized, controlled trial. Methods: H. pylori –positive patients with at least a 1-year history of heartburn with a normal endoscopy or grade A esophagitis were recruited. Patients were randomized to 20 mg omeprazole, 250 mg clarithromycin, and 500 mg tinidazole twice a day for 1 week or 20 mg omeprazole twice a day and identical placebos. A second concurrently recruited control group of H. pylori –negative patients were given open label 20 mg omeprazole twice a day for 1 week. All patients received 20 mg omeprazole twice a day for the following 3 weeks and 20 mg omeprazole once daily for a further 4 weeks. Omeprazole was discontinued at 8 weeks and patients were followed up for a further 10 months. A relapse was defined as moderate or severe reflux symptoms. H. pylori eradication was determined by 13 C-urea breath test. Results: The H. pylori –positive cases were randomized to antibiotics (n = 93) or placebo (n = 97). Relapse of GERD occurred in 83% of each of the antibiotic, placebo, and H. pylori –negative groups during the 12-month study period. Life tables revealed no statistical difference between the 2 H. pylori –positive groups (log rank test, P = 0.84) or between the 3 groups (log rank test, P = 0.94) in the time to first relapse. Two patients in each group developed grade B esophagitis at 12 months. Conclusions: H. pylori eradication therapy does not seem to influence relapse rates in GERD patients. GASTROENTEROLOGY 2001;121:1120-1126

Background.Helicobacter pylori colonization and associated inflammation are influenced by local acid output. Infected subjects with acid-related diseases, such as gastroesophageal reflux disease (GERD) are likely to have an antral-predominant gastritis. We hypothesized that long-term acid suppression would result in relatively greater bacterial colonization in the corpus leading to diffuse or corpus-predominant gastritis and that this would be prevented by prior H. pylori eradication. Materials and Methods. To investigate this, we conducted a prospective, double-blind trial of the effect on gastric histology of 12-month maintenance treatment with omeprazole in H. pylori–positive GERD patients randomly assigned to either an eradication or omeprazole-alone regime. A control group of 20 H. pylori–negative GERD patients also received omeprazole throughout the study period. Biopsies taken at baseline and at 12 months were graded “blind” by a single observer according to the updated Sydney System. The 41 H. pylori-positive subjects with grade B or C esophagitis were randomly assigned (20 to omeprazole alone, 21 to eradication) and 33 subjects completed the 12-month study. Results. There was a significant decline in antral chronic inflammation in initially positive patients between baseline and end in both the eradication group (p = .035) and the omeprazole-alone group (p = .008). However, corpus chronic inflammation increased in the omeprazole-alone group (p = .0156) but decreased in the eradication group. The change toward corpus predominance between baseline and end for the omeprazole-alone group is highly significant (p = .0078). Furthermore, 5 of 11 in the omeprazole-alone group developed mild corpus atrophy, compared to 0 of 8 who had undergone H. pylori eradication. The change in frequency of corpus atrophy between the two groups is significant (p = .02). Conclusion. In H. pylori–positive subjects with GERD, long-term acid suppression leads to a shift from antral- to corpus-predominant gastritis that can be prevented by prior eradication. The shift is accompanied by an increase in corpus atrophy. H. pylori infection should be eradicated prior to long-term acid suppression with proton pump inhibitors.

OBJECTIVES To review the results of a 13-year surveillance programme of patients with Barrett's oesophagus to determine the incidence of adenocarcinoma. Although the risk of cancer in Barrett's oesophagus is well established, the magnitude of this risk is still controversial. DESIGN Records of all patients with histologically confirmed Barrett's oesophagus in our 13-year surveillance programme were examined retrospectively. SETTING Integrated gastroenterology and gastrointestinal surgical service in a large teaching hospital. PARTICIPANTS During the study period, 597 patients had a diagnosis of Barrett's oesophagus; of these, 357 entered a yearly endoscopy and biopsy surveillance programme. MAIN OUTCOME MEASURES The development of oesophageal adenocarcinoma. RESULTS After a mean follow-up of 43 months, 12 patients, all with specialized epithelium, developed adenocarcinoma (11 men), an incidence for men of one cancer per 69 patient-years; and for women, one cancer per 537 patient-years follow-up (P < 0.01). If only patients with specialized mucosa were included the incidence of cancer was one per 95 patient-years of follow-up (men, one per 61 patient-years; women, one per 468 patient-years). CONCLUSIONS Whilst the role of screening patients with Barrett's oesophagus remains controversial, this study supports the routine surveillance of male patients with specialized epithelium.

The proportion of upper gastrointestinal symptoms in the community associated with helicobacter pylori , lifestyle factors, and nonsteroidal anti-inflammatory drugs

Summary Background Infection with Helicobacter pylori is the main cause of peptic-ulcer disease. Treatment of this infection might lower the prevalence of dyspepsia in the community and improve quality of life. We investigated this possibility in a double-blind randomised controlled trial. Methods Individuals aged 40–49 years were randomly selected from the lists of 36 primary-care centres. A researcher interviewed participants with a validated dyspepsia questionnaire and the psychological general wellbeing index (PGWB). H pylori status was assessed by the carbon-13-labelled urea breath test. Infected participants were randomly assigned active treatment (omeprazole 20 mg, clarithromycin 250 mg, and tinidazole 500 mg, each twice daily for 7 days) or identical placebo. Participants were followed up at 6 months and 2 years. Findings Of 32 929 individuals invited, 8455 attended and were eligible; 2324 were positive for H pylori and were assigned active treatment (1161) or placebo (1163). 1773 (76%) returned at 2 years. Dyspepsia or symptoms of gastro-oesophageal reflux were reported in 247 (28%) of 880 in the treatment group and 291 (33%) of 871 in the placebo group (absolute-risk reduction 5% [95% CI 1–10]). H pylori treatment had no significant effect on quality of life (mean difference in PGWB score between groups 0·86 [−0·33 to 2·05]). Interpretation Community screening and treatment for H pylori produced only a 5% reduction in dyspepsia. This small benefit had no impact on quality of life.

Background : The management of dyspepsia is controversial. Methods : An international Working Party was convened in 1998 to review management strategies for dyspepsia and functional dyspepsia, based on a review of the literature and best clinical practice. Results : Dyspepsia, defined as pain or discomfort centred in the upper abdomen, can be managed with reassurance and over-the-counter therapy if its duration is less than 4 weeks on initial presentation. For patients with chronic symptoms, clinical evaluation depends on alarm features including patient age. The age cut off selected should depend on the age specific incidence when gastric cancer begins to increase, but in Western nations 50 years is generally an acceptable age threshold. In younger patients without alarm features, Helicobacter pylori test and treatment is the approach recommended because of its value in eliminating the peptic ulcer disease diathesis. If, after eradication of H. pylori, symptoms either are not relieved or rapidly recur, then an empirical trial of therapy is recommended. Similarly, in H. pylori-negative patients without alarm features, an empirical trial (with antisecretory or prokinetic therapy depending on the predominant symptom) for up to 8 weeks is recommended. If drugs fail, endoscopy should be considered because of its reassurance value although the yield will be low. In older patients or those with alarm features, prompt endoscopy is recommended. If endoscopy is non-diagnostic, gastric biopsies are recommended to document H. pylori status unless already known. While treatment of H. pylori is unlikely to relieve the symptoms of functional dyspepsia, the long-term benefits probably outweigh the risks and treatment can be considered on a case-by-case basis. In H. pylori-negative patients with documented functional dyspepsia, antisecretory or prokinetic therapy, depending on the predominant symptom, is reasonable, assuming reassurance and explanation are insufficient, unless patients have already failed this approach. Other treatment options include antidepressants, antispasmodics, visceral analgesics such as serotonin type 3 receptor antagonists, and behavioural or psychotherapy although these are all of uncertain efficacy. Long-term drug treatment in functional dyspepsia should be avoided; intermittent short courses of treatment as needed is preferred. Conclusion : The management of dyspepsia recommended is based on current best evidence but must be tailored to local factors such as practice setting, the background prevalence of H. pylori and structural disease, and costs.

Summary Background Helicobacter pylori is a common human pathogen implicated in certain gastrointestinal diseases. In the search for new non-invasive techniques to diagnose H pylori infection, we evaluated an EIA for H pylori antigen in stool (HpSA). Methods In a prospective multicentre study, stool specimens from 501 patients (276 men, 225 women; age range 17–88 years, mean 52) undergoing gastroscopy in 11 centres throughout Europe were tested with HpSA and the carbon-13-urea breath test. At endoscopy, four biopsy samples were taken for histology (haematoxylin and eosin) and H pylori detection (giemsa in both antrum and corpus, culture and rapid urease test). Patients were defined as positive for H pylori if histology (antrum, corpus, or both) and urease test were positive, or if culture was positive. Patients classified as having H pylori infection received an eradication regimen; 107 were reassessed 4 weeks after therapy. Findings Of 272 patients with H pylori infection by the predefined criteria, 256 were positive by HpSA (sensitivity 94·1% [95% CI 90·6–96·6]). Of 219 patients without infection, 201 were negative by HpSA (specificity 91·8% [87·3–95·1]). Interpretation The stool assay was a reliable and easy-to-use tool for diagnosis of H pylori infection. The test was accurate even shortly after treatment.

Objectives: To examine whether screening and eradication of Helicobacter pylori by population-based invitation or opportunistic screening by general practitioners reduces costs to the National Health Service (NHS) of treating dyspepsia.Methods: A limited dependent, variable, two-step regression analysis was used to explore the baseline annual health care costs of dyspepsia for men and women aged 40–49 enrolled in the Leeds H. pylori screening and eradication trial.Results: Epidemiological and clinical questionnaires, general practitioner notes, and 13C urea breath test results were available for 4,754 individuals. After adjusting for covariates, H. pylori was associated with a 6.7% increased probability of incurring gastrointestinal-related NHS costs (p < .0001) in the population aged 40-49. Additionally, H pylori increased average costs in those who seek medical care (p = .001). In consequence, H. pylori is associated with an average increased cost to the NHS of £0.30 per year (95% CI: £0.17 to £0.45) per adult aged 40–49. In those consulting for dyspepsia, the increased cost to the NHS was £1.04 per year (95% CI: £0.42 to £1.75) per patient. The cost of population screening and treatment would not be recovered in reduced dyspepsia costs in the lifetime of those screened. Assuming laboratory-based serology screening is used opportunistically in patients presenting with dyspepsia, it is estimated that costs would be recouped in 18 years.Conclusions: This observational data set suggests that the costs of screening and treatment in all individuals aged 40–49 or in those presenting in primary care with dyspeptic symptoms are unlikely to be attractive on the basis of cost savings alone.

There is an increased risk of colorectal cancer in patients who have had an attack of chronic ulcerative colitis, and there is evidence to suggest that patients with Crohn's disease are also at risk. It is difficult to give a precise estimate of the increased danger that patients with inflammatory bowel disease have over the normal population because published results are inconsistent. Twenty years ago patients with long-standing extensive ulcerative colitis were often advised to undergo proctocolectomy to protect against the development of cancer, but since then most physicians have adopted a policy of regular colonoscopic surveillance in an attempt to detect early cancer or pre-cancer. When published studies of surveillance results are critically analyzed, it appears that relatively little benefit accrues from this approach. Better methods of surveillance are needed to determine which individuals with chronic ulcerative colitis are most likely to develop cancer.

BackgroundHelicobacter pylori is the cause of chronic (type B) gastritis, duodenal ulceration (DU), and gastric ulceration (GU). Smoking is associated with delayed ulcer healing. Epidermal growth factor (EGF) is produced in the salivary and Brunner's glands of the upper gastrointestinal tract, inhibits gastri acid secretion, and is a powerful mitogen. Materials and Methods.We sought to determine gastric luminal EGF (GL-EGF) in smokers and patients with Hp-associated DU and the effect of Hp eradication. Our aim was to determine GL-EGF in patients with GU and the effect of ulcer healing and to measure serum EGF in patients with Hp gastritis with or without DU disease. Results.GL-EGF was reduced in smokers compared to control (p= .008). Subjects with HP gastritis had reduced GL-EGF compared to controls (p= .0002). There was no difference in GL-EGF between Hp-positive subjects who had DU and those with chronic gastritis alone. Eradication of Hp from those patients with DU had no effect on the low levels of GL-EGF. There was no difference between GL-EGF in Hp gastritis alone and in Hp-associated active GU. GL-EGF fell after ulcer healing (p= .04), a difference confirmed by analysis of paired samples from patients before and after ulcer healing (p= .03). There was no difference in serum EGF between controls and subjects with Hp infection. There was no difference in serum EGF in subjects with DU-associated and non-ulcer-associated gastritis. Conclusions.Subjects with Hp gastritis, or those who smoke, had low concentrations of GL-EGF regardless of whether DU was present. Eradication of Hp did not return the concentrations of GL-EGF to normal in DU subjects. Individuals with Hp gastritis and inactive GU had low levels of GL-EGF compared to non-ulcer Hp infection. The relative increase in GL-EGF that occurred with ulceration of the gastric mucosa may have resulted from the development of an ulcer-associated cell lineage. Serum EGF did not play a role in the pathogenesis of Hp gastritis or of associated DU ulcer disease.

The aim of this study was to determine what factors are important for the achievement of perfect anal continence after restorative proctocolectomy. One hundred patients underwent paired studies of anorectal physiology before and one year after restorative proctocolectomy with pelvic ileal reservoir (11 S, 25 J, 64 W) with stapled ileoanal anastomosis, without mucosectomy. Fifty seven patients attained perfect anal continence and were able to discriminate flatus from faeces with such confidence that they were able to release flatus safely without fear of faecal soiling. The remaining 43 patients experienced minor problems in this regard. Four factors were found to correlate significantly with a perfect functional result (median, perfect v imperfect): maximum resting anal pressure (72 v 57 cm H2O, p < 0.02), the sensory threshold in the upper and mid-anal canal (7.3 v 8.6 and 5.3 v 7.0 mA, p < 0.05 and p < 0.02), compliance of the ileal reservoir (12.4 v 7.6 ml/cm H2O, p < 0.01), and the presence of a pouch-anal inhibitory reflex (56 of 57 patients v 29 of 43 patients, p < 0.01). The quality of anal continence depends on several factors: a complaint ileal reservoir, a strong sensitive anal sphincter, and normal reflex coordination of the activities of the reservoir and the sphincter. Excellent pouch-anal coordination is obtainable irrespective of the design of the reservoir, provided that these criteria are satisfied.

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for radiological visualization of the common bile duct. In addition to its diagnostic applications, ERCP, along with sphincterotomy, is a standard therapy for bile duct calculi. The advent of laparoscopic cholecystectomy (LC) has focused much attention on the role of ERCP in the management of bile duct calculi. The use of ERCP before LC should be selective, with ERCP restricted to patients with a high risk of bile duct calculi. ERCP should be performed after LC in patients with continuing symptoms suggestive of bile duct calculi or when operative cholangiography has demonstrated calculi. Intravenous cholangiography (IVC) has no role as a screening test for bile duct calculi, and percutaneous transhepatic cholangiography (PTC) should be restricted to those patients in whom bile duct calculi is highly suspected and in whom ERCP has failed. Elderly and frail patients with bile duct calculi may be satisfactorily managed by ERCP alone. Although a "minimally invasive" procedure, ERCP is not without risks. Local practice will depend to a great extent on the availability of ERCP expertise.

Most anti-Helicobacter pylori (Hp) regimens available have drawbacks. Standard triple therapy using bismuth, metronidazole, and tetracycline gives good eradication rates but at the expense of a long, complicated regimen associated with significant side effects, and results are not as good in areas where there is a high resistance to nitroimidazoles. The introduction of eradication regimens based on acid suppression in combination with antibiotics has yielded promising results. Dual therapy using a proton pump inhibitor (PPI) with either amoxicillin or clarithromycin has yielded eradication rates above 80% with relatively few side effects, but results have been somewhat inconsistent from center to center. The combination of acid suppression with two antibiotics has provided better results, with centers achieving eradication rates of over 90%. The new PPI lansoprazole possesses some theoretical advantages as an acid-suppressing drug, and its preliminary use in a number of studies suggests that it may have an important role to play in Hp eradication regimens. Considerably more work, however, is required to identify the ideal dosage and combination that will give the best eradication rates with the simplest regimen and fewest side effects.

OBJECTIVES Most chronic and recurrent gastrointestinal (GI) symptoms in the community are caused by functional GI disorders, such as functional dyspepsia and irritable bowel syndrome (IBS). It is not known, however, whether these conditions affect mortality. We present the results of a large community-based prospective study that examines this issue. METHODS This was a 10-year follow-up, conducted in 2004, of individuals recruited into a community-based screening program for Helicobacter pylori. Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, GI symptoms, and quality of life were recorded at study entry. The effect of all these factors on 10-year mortality was examined using univariate analysis and multivariate Cox regression analysis. All results were expressed as hazard ratios (HRs) with 99% confidence intervals (CIs). RESULTS Symptom data were available for 8,323 (99.0%) of 8,407 individuals originally enrolled, comprising over 84,000 years of follow-up: 3,169 (38.1%) subjects had dyspepsia, and 264 (3.2%) IBS. There were 137 (1.65%) individuals who had died at 10 years. After multivariate analysis, there was no significant difference in likelihood of death at 10 years in those with dyspepsia (HR: 0.94; 99% CI: 0.58-1.54) or IBS (HR: 1.35; 99% CI: 0.36-5.10), compared with those not meeting the criteria for either condition. CONCLUSIONS Dyspepsia was not associated with an increased mortality in the community. Data for any effect of IBS on survival were less clear. Further studies are required to assess the impact of functional GI disorders on life expectancy.

Objective: To describe a patient with coeliac disease complicated by small bowel bacterial overgrowth and acute fatty liver. Design: A single patient case report. Patient: A 63-year-old female patient with a brief history of steatorrhoea presented with subtotal villous atrophy on a jejunal biopsy, and small intestinal bacterial overgrowth. Results: On examination, the patient's liver biochemistry was found to be abnormal. Despite treatment with a gluten-free diet and oral tetracycline, she continued to deteriorate and became increasingly jaundiced. A liver biopsy demonstrated severe large and small droplet fatty change. There was no evidence of lymphoma on computed tomography of the abdomen. Following adherence to a gluten-free diet, her jaundice was resolved

Helicobacter pylori is closely associated with a wide spectrum of gastroduodenal disease. This worhshop report reviews the increasing understanding of the pathogenesis, the problems and progress associated with eradication treatment. The scope and direction of future research focuses on clarifying the role of H. pylori as a cause of inflammation and the long-term consequences of chronic gastritis, i.e. its progression to carcinogenesis.

Objective: To investigate mucosal secretion of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in inflammatory bowel disease patients and controls. Design: Prospective study of patients recruited from the colonoscopy lists and the colitis clinic of a teaching hospital gastroenterology unit. Methods: Mucosal biopsies from patients with inflammatory bowel disease and controls were cultured for 24h and secretion of IL-6 and TNF-α was determined by enzyme-linked immunosorbent assay. Results: Interleukin-6 and TNF-α production in vitro from patients with active ulcerative colitis was significantly greater than from patients with inactive ulcerative colitis (P < 0.005), inflamed mucosa in patients with Crohn's disease (P < 0.05) and controls (P < 0.005)

AIMS--To determine the prevalence of Helicobacter pylori colonisation in the mouths of patients with H pylori gastritis. METHODS--A nested polymerase chain reaction test for the 16S ribosomal RNA gene of H pylori was used on saliva, dental plaque, gastric juice and gastric biopsy specimens from patients attending a dyspepsia clinic. RESULTS--Thirteen patients had histologically confirmed Helicobacter associated gastritis. Twelve of these had positive gastric aspirates by PCR. Five had at least one positive oral specimen. Eight patients with normal gastric biopsy specimens had no PCR positive oral specimens or gastric aspirates. All, however, had PCR positive gastric biopsy specimens. In an attempt to determine the origin of these positive results in normal patients, it was shown that biopsy forceps could contaminate specimens with DNA from previous patients. CONCLUSION--The demonstration of the organism in the mouths of a substantial proportion of dyspeptic patients has major implications for the spread of H pylori and identifies a potential source for reinfection following eradication of the organism from the stomach.

This article summarizes the published literature concerning the epidemiology and public health implications of Helicobacter pylori infection published from April 2009 through March 2010. Prevalence of infection varied between 7 and 87% and was lower in European studies. All retrieved studies examining transmission of infection concluded that spread is from person-to-person. One study collecting stool and vomitus samples from patients with acute gastroenteritis detected H. pylori DNA in 88% of vomitus and 74% of stool samples. Proposed risk factors for infection included male gender, increasing age, shorter height, tobacco use, lower socioeconomic status, obesity, and lower educational status of the parents in studies conducted among children. Decision analysis models suggest preventing acquisition of H. pylori, via vaccination in childhood, could be cost-effective and may reduce incidence of gastric cancer by over 40%. As yet, no country has adopted public health measures to treat infected individuals or prevent infection in populations at risk.

Digestive endoscopy covers a wide variety of procedures; the need for sedation is governed by the invasiveness and length of the procedure, the wishes of the patient, the desire of the operator for a compliant patient, and safety. Many patients are prepared to undergo upper digestive endoscopy using throat spray without sedation, while fewer accept unsedated colonoscopy. There are clinical advantages as well as disadvantages in employing sedation and sometimes general anaesthesia is the preferred option. This paper provides an introduction to the choices available and the approaches that are employed in endoscopic sedation practice.

Forty six consecutive patients with early gastric cancer were treated between 1970 and 1990. The proportion of cases of early gastric cancer increased significantly (p < 0.01) from 1% of all cases in the first five year period to 15% in the last five year period, because of greater awareness of the condition and more widespread use of endoscopy. There were 33 men and 13 women, of median age 69 years (range 38-86). Most patients (91%) presented with symptoms indistinguishable from those of peptic ulceration. The median duration of symptoms was four months (range 0.1-36 months). All 46 patients were treated surgically. Three patients (6.5%) died after operation and a further 10 (22%) suffered postoperative complications. None of the surviving patients has been lost to follow up and 25 have been followed up for a minimum period of five years. Five year survival by life table analysis was 98%. These findings suggest that in Britain in the 1990s, as in Japan, it may be possible to diagnose an increasing proportion of patients with gastric cancer at a relatively early pathological stage, when most patients can be cured by radical surgical resection with lymphadenectomy.

Background Gastric acid secretion is subject to complex control mechanisms, and varies widely between individuals and populations. Its measurement has previously required intubation of the stomach with ingestion of a test meal or injection of a secretion stimulant Aim We describe a novel method of measuring gastric acid secretion noninvasively - the Calcium Carbonate Breath Test Methods 13 C-labelled calcium carbonate is ingested by a fasting participant. The carbonate neutralizes gastric acid to produce 13 CO 2 , which is expired in the breath. Measurement of the excess 13 CO 2 in the breath allows back-calculation of the amount of gastric acid secreted during the test, provided that other variables affecting CO 2 production and excretion are minimized or controlled for. Results Studies on a single healthy individual have shown reproducible estimations of acid secretion and over 80% suppression of acid secretion after the proton pump inhibitor treatment. Conclusion The method seems to be promising, but further studies on other individuals need to be carried out. The Calcium Carbonate Breath Test may have wide applications in epidemiological studies, clinical management of acid-related diseases, screening for hypochlorhydria and development of new acid-suppressing treatments.

The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in gastric mucosal histology, local and systemic humoral immune response, and gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epigastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in gastric juice ascorbic acid concentration.

To determine the relevance of gastric juice factors to gastric carcinogenesis, 56 patients with unoperated stomachs undergoing endoscopy for dyspepsia had gastric juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite, nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C estimation. Antral and body biopsies were assessed for gastritis, Helicobacter pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic gastritis (n = 17) had lower gastric juice ascorbic acid concentrations (P less than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with chronic gastritis and IM (n = 11) had higher gastric juice pH (P less than 0.01) and total bile acid concentrations (P less than 0.05), and lower gastric ascorbic acid concentrations (P less than 0.01) than those with chronic gastritis and no IM (n = 24). In chronic gastritis, high nitrite concentrations were associated with high pH (P less than 0.01). However, there were no significant differences in plasma vitamin C or gastric nitrite, nitrate or total NOC concentrations in relation to gastric histology. We conclude that the premalignant condition IM is associated with H. pylori infection, low gastric ascorbic acid levels and elevated total bile acids, but not to elevation in nitrite or total NOCs in fasting gastric juice.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. The natural history of the condition has been studied extensively, but few studies have examined factors that predict its new onset or health care-seeking behavior.Individuals, now aged 50-59 yr, originally enrolled in a population-screening program for Helicobacter pylori (H. pylori) were contacted via postal questionnaire, utilizing the Manning criteria for IBS diagnosis. Baseline demographic data, quality of life, and IBS and dyspepsia symptom data were already on file. Consent to examine primary care records was sought, and data regarding IBS- and dyspepsia-related consultations were extracted.Of 8,407 individuals originally involved, 3,873 (46%) provided symptom data at baseline and 10-yr follow-up. Of 3,659 individuals without IBS at baseline, 542 (15%) developed new-onset IBS at 10-yr follow-up. After multivariate logistic regression, lower quality of life at baseline (odds ratio [OR] 4.41, 99% confidence interval [CI] 2.92-6.65), dyspepsia at baseline (OR 1.77, 99% CI 1.28-2.46), and female gender (OR 2.14, 99% CI 1.56-2.94) were significant risk factors for new-onset IBS. Of 651 individuals with IBS at either baseline or 10-yr follow-up, 113 (17%) consulted a primary care physician with symptoms. H. pylori infection (OR 1.93, 99% CI 1.03-3.62) and any dyspepsia-related consultation (OR 2.14, 99% CI 1.15-4.00) significantly increased the likelihood of consultation.Poor quality of life at baseline was a strong predictor of new-onset IBS, but not of IBS-related consultation behavior, which was associated with consultation for dyspepsia during the study period.

A man, aged 73 years, complaining of anorexia, cough, and rhinorrhea for a week, underwent a barium meal examination, which was followed up by an upper gastrointestinal (GI) endoscopic examination to rule out abnormalities. A lesion of about 5 mm in diameter was found in the corpus and was biopsied.Two months later he underwent endoscopic ultrasonographic examination and shortly thereafter endoscopic resection was performed. The resection margins were free of tumor. On follow-up endoscopic examinations, no local recurrence was found.

The natural history of gastric epithelial dysplasia and its relation to gastric cancer are ill defined. A consecutive series of 40 patients with an initial diagnosis of gastric epithelial dysplasia based on examination of endoscopic biopsies has been reviewed to determine the clinical outcome and to evaluate a two tier histological grading system as a predictor of the risk of cancer. On review, only 20 of the 40 patients were considered to have true dysplasia: seven patients had low grade dysplasia and 13 had high grade dysplasia. Of the 13 patients with high grade dysplasia, 11 (85%) were found to have gastric cancer within 15 months. Of the 10 patients with high grade dysplasia who underwent gastrectomy, six were found to have early gastric cancer, three had cancer invading into the muscularis propria, and none had lymph node metastases. High grade dysplasia is thus a marker of gastric cancer. Moreover, the cancers associated with high grade dysplasia are usually pathologically favourable and curable. The finding, by an experienced pathologist, of high grade dysplasia in two separate sets of endoscopic biopsies is therefore an indication for radical surgical treatment, provided that the patient's age and general condition permit such an approach.

OBJECTIVE: Dyspepsia is common, and the condition is often chronic, with a relapsing and remitting nature. Factors influencing the decision to consult a physician with symptoms remain unclear. METHODS: The authors conducted a 10-yr follow-up longitudinal survey of individuals originally involved in a community-screening program for Helicobacter pylori (H. pylori). All surviving, traceable participants were contacted by validated postal dyspepsia questionnaire. Baseline demographic data, dyspepsia and irritable bowel syndrome (IBS) symptom data, and quality of life at study entry were already on file. Consent to examine primary care records was requested, and data regarding nonsteroidal anti-inflammatory drug and aspirin use, and dyspepsia and IBS-related consultations over the 10-yr study period were extracted from these. RESULTS: Of 8,407 individuals originally involved, 3,266 (39%) gave consent to examination of primary care records. The mean age of included individuals was 55 yr, and 1,467 (45%) were male. 1,738 (53%) had dyspepsia, and 729 (42%) of these consulted a primary care physician as a result. Following multivariate logistic regression, H. pylori infection (odds ratio [OR] 1.76, 99% confidence interval [CI] 1.30‐2.39), lower socioeconomic status (OR 1.68, 99% CI 1.02‐2.76), frequent (OR 2.61, 99% CI 1.69‐4.01) or severe (OR 1.87, 99% CI 0.99‐3.52) symptoms, and increasing age (OR per year 1.06, 99% CI 1.0‐1.11) were independent risk factors for consultation. CONCLUSIONS: Reasons for consulting a physician with dyspepsia are multifactorial, but H. pylori infection, lower socioeconomic status, frequent or severe symptoms, and increasing age are independent predictors of consultation. (Am J Gastroenterol 2007;102:957‐965)

Pan-European Registry on H. pylori Management (HP-EuReg): Bacterial Resistance Adrian G. McNicholl, Antonio Gasbarrini, Bojan Tepes, Dmitry S. Bordin, Frode Lerang, Marcis Leja, Theodore Rokkas, Dino Vaira, Oleg Shvets, Limas Kupcinskas, Angeles Perez Aisa, Anthony T. Axon, Gyorgy M. Buzas, Ilkay Simsek, Miroslava Katicic, Jose C. Machado, Vincent Lamy, Krzysztof Przytulski, Lyudmila Boyanova, Peter Bytzer, Christoph Beglinger, Lisette Capelle, Adrian Goldis, Lea Veijola, Miroslav Vujasinovic, Alain Huerta, Jorge Perez-Lasala, Maria Caldas, Mercedes Ramas, Francis Megraud, Colm A. O'Morain, Javier P. Gisbert

Pan-European Registry on H. pylori Management (HP-EuReg): Bacterial Resistance Adrian G. McNicholl, Antonio Gasbarrini, Bojan Tepes, Dmitry S. Bordin, Frode Lerang, Marcis Leja, Theodore Rokkas, Dino Vaira, Oleg Shvets, Limas Kupcinskas, Angeles Perez Aisa, Anthony T. Axon, Gyorgy M. Buzas, Ilkay Simsek, Miroslava Katicic, Jose C. Machado, Vincent Lamy, Krzysztof Przytulski, Lyudmila Boyanova, Peter Bytzer, Christoph Beglinger, Lisette Capelle, Adrian Goldis, Lea Veijola, Miroslav Vujasinovic, Alain Huerta, Jorge Perez-Lasala, Maria Caldas, Mercedes Ramas, Francis Megraud, Colm A. O'Morain, Javier P. Gisbert