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Introduction: Management of Helicobacter pylori infection (H. pylori) re-quires co- treatment with proton pump inhibitors (PPIs) and the use of an- tibiotics to achieve successful eradicationAims & Methods: To evaluate the role of PPIs in the eradication of H. py-lori, based on the “European Registry onHelicobacter pylori Management” (Hp- EuReg).The Hp-EuReg is a multicentre, prospective, non-interventional, registry assessing decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. Countries recruiting more than 1, 000 patients were included. Effectiveness was assessed by modi- fied intention-to-treat (mITT). Data were quality reviewed.Results: Overall, 22, 078 patients from 5 countries were analysed. Optimal (»90%) first-line mITT effectiveness was achieved with the following treatments: 14-day clarithromycin- amoxicillin- bismuth quadruple therapy, and 14- day metronidazole-tetracycline-bismuth quadruple therapy, both inde-pendently of the PPI dose prescribed ; in all 10- or 14-day therapies with high-dose PPIs (except with standard 10-day triple therapy) ; in 10-day se-quential and 10- day quadruple clarithromycin-amoxicillin- bismuth, and 10-day quadruple metronidazole- tetracycline- bismuth with standard-dose PPIs. None of the 7-day therapies achieved optimal cure rates re-gardless of the PPI dose used. The PPI dose was significantly associated with the effectiveness of: 10- or 14- day standard triple and quadruple con-comitant therapies, and 10-day quadruple sequential and metronidazole-tetracycline-bismuth therapies. Table 1 details the mITT effectiveness by duration and PPI dose used.Conclusion: In first-lineH. pylori treatment, ≥90% effectiveness is obtained with standard-dose PPIs in 10-day sequential and 10- or 14-day bismuth quadruple therapies and with high-dose PPIs in all 10- or 14-day therapies except with standard 10-day triple therapy.

BACKGROUND: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. METHODS: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. RESULTS: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:9 issue:3 pages:287-306 ispartof: location:England status: published

European Registry on the management of Helicobacter pylori infection («Hp-EuReg») - a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group, conducted in 27 European countries in order to evaluate the real clinical practice of diagnosis and treatment of H. pylori and its comparison with international recommendations.The analysis of 2360 patients entered in the register by the Russian centres of «Hp-EuReg» in 2013-2017, who were underwent 1st line eradication therapy.The most common methods of primary diagnosis of H. pylori are histological (37.7%), rapid urease test (29.2%) and serology (29.7%). The duration of eradication therapy in 9.4% of cases was 7 days, in 65.3% - 10 days, and in 25.3% - 14 days. To control the effec- tiveness of treatment, H. pylori antigen in feces (31.3%), urea breath test (23.4%) and histological method (23.3%) were used. In 3.6% cases was used serology by mistake. In 17.3% of patients control was not carried out. The effectiveness of triple therapy with a PPI, amoxicillin, clar- ithromycin (per protocol) was 67.6%, with 7-day course, 81.1% at 10-day and 86.7% at 14-day course. Eradication rate of triple therapy with addition of bismuth (per protocol) reached 90,6% in the group receiving 10-day scheme and 93.6% in the group receiving the 14-day treatment.Significant deviations of clinical practice from expert recommendations, most pronounced at the stage of monitoring the effectiveness of therapy, were noted. The suboptimal efficacy of triple therapy is shown.

SummaryBackground Empiric triple therapy for Helicobacter pylori should be abandoned when clarithromycin resistance rate is >15–20%. Optimisation of triple therapy (high-dose acid suppression and 14-day duration) can increase eradication rates by 10%. Aim To compare the efficacy and safety of optimised triple (OPT-TRI) and nonbismuth quadruple concomitant (OPT-CON) therapies. Methods Prospective multicentre study in 16 Spanish centres using triple therapy in clinical practice. In a 3-month two-phase fashion, the first 402 patients received an OPT-TRI therapy [esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin (500 mg b.d) for 14 days] and the last 375 patients an OPT-CON treatment [OPT-TRI therapy plus metronidazole (500 mg b.d)]. Results Seven-hundred seventy-seven consecutive patients were included (402 OPT-TRI, 375 OPT-CON). The OPT-CON therapy achieved significantly higher eradication rates in the per-protocol [82.3% (95% CI = 78–86%) vs. 93.8% (91–96%), P 90%) compared to OPT-TRI therapy. Addition of metronidazole to OPT-TRI therapy increased eradication rates by 10%, resulting in more mild adverse effects, but without impairing compliance with therapy.

Background: Guidelines on the management of Helicobacter pylori , which cover indications for management and treatment strategies, were produced in 2000. Aims: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer. Results: Eradication of H pylori infection is recommended in ( a ) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; ( b ) patients with atrophic gastritis; ( c ) first degree relatives of patients with gastric cancer; ( d ) patients with unexplained iron deficiency anaemia; and ( e ) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a “test and treat” strategy if other causes are excluded. Eradication of H pylori infection ( a ) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and ( b ) may prevent peptic ulcer in patients who are naive users of non-steroidal anti-inflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility. Conclusion: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development.

Ulcerative Colitis (UC) is a chronic inflammatory condition that frequently affects men and women of childbearing age. Concerns are often raised by both patients and clinicians regarding the effects of the disease and its treatments on reproduction and lactation. Many studies have examined fertility in UC patients in comparison with the general population. Most of these have not demonstrated a significant difference between the two groups. The observed decrease in fertility in some reports was largely attributable to patient choice, and the use of certain drugs such as sulfasalazine in men. Decreased fertility was also reported in women who have undergone surgery for their disease. Pregnancy is considered high risk in patients with UC. Numerous studies have described the obstetric and neonatal outcomes of these patients, and reported similar pregnancy outcomes in comparison to the general population. However some population-based studies have found an increased incidence of low birth weight and preterm delivery in UC patients. This observed difference seems to be mainly related to disease activity and severity during pregnancy and the appropriate treatment required. On the other hand pregnancy does not appear to increase the risk of disease relapse or severity. The course of UC during pregnancy is partly determined by its activity at conception. Therefore UC patients should be advised to attempt to conceive during periods of disease remission. Patients are often concerned about the safety of UC pharmacotherapy during pregnancy and lactation. Some patients choose to discontinue their maintenance therapy at least until the birth of their baby while others rely on their treating clinician to make the appropriate and safe decision regarding their treatment. Two issues have to be considered in this setting; first is the relative safety of the drug and secondly the benefit risk ratio of its use in pregnancy and lactation. A large amount of safety data is available on drugs that have been in use for decades, however modern medicine has witnessed the introduction of new therapeutic agents that have revolutionized the treatment of inflammatory diseases but there is limited data available regarding their safety during pregnancy and breast feeding. The topic of UC and pregnancy is quite complex involving a range of issues including the effects of both the disease and its treatment options on fertility, pregnancy and lactation, in addition to the effects of pregnancy and lactation on the course of the disease. The aim of this chapter is to review the available data and discuss this topic in more detail.

There is no international agreement on scoring systems used to measure disease activity in ulcerative colitis, nor is there a validated definition for disease remission.To review the principles and components for defining remission in ulcerative colitis and propose a definition that will help improve patient outcomes.A review of current standards of remission from the perspective of clinical trials, guidelines, clinical practice and patients was conducted by the authors. Selected literature focused on the components of a definition of remission, the utility of a definition and treatment strategies, based on current definitions.Different definitions of remission affect the assessment of outcome and make it difficult to compare trials. In the clinic, endoscopy is rarely used to confirm remission, because mucosal healing has only recently begun to be related to the duration of subsequent remission in a way that will affect clinical practice. Histopathology may be the ultimate arbiter of mucosal healing. There is no agreement on the definition of remission in current guidelines. Patient-defined remission may predict endoscopic remission, but has yet to be shown to predict duration of remission.A standard based on clinical symptoms and endoscopy is proposed. Histopathology is a third dimension of remission that may have prognostic value. The definition of remission should help predict long-term outcome. The expectations of patients and their physicians need to be raised, as the goal of treatment of active ulcerative colitis should be to induce remission.

Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary.To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes.Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis.Over 10 years, 630 UC and 318 CD patients had 22,823 and 11,871 cycles. The most frequent clinical outcomes were medical/surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases engendered high costs in the cohort.Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses.

One of the most frequently asked questions during consultation with those affected by inflammatory bowel disease is what are its effects on pregnancy, and how the treatment will impact on conception and pregnancy outcomes.To review available data regarding the safety of biological therapies during pregnancy, primarily in woman with inflammatory bowel disease.A Medline search was performed and available original research and review articles relating to the use of biological (antitumour necrosis factor-alpha) therapies in inflammatory bowel disease were reviewed. Where information regarding the use of a drug in inflammatory bowel disease during pregnancy was limited, articles referring to its use for other indications, such as rheumatoid arthritis, were reviewed.Based on available data, biological therapies appear to be safe in pregnancy. Most studies looking at the effects of any one medication on pregnancy in inflammatory bowel disease are confounded by the fact that most patients are on multiple medications and have varying levels of disease activity. Stopping therapy in the third trimester should be considered. Large registries with longer follow-up periods will be necessary before firm conclusions about the safety of antitumour necrosis factor-alpha therapies during conception and pregnancy can be drawn.

Inflammatory bowel disease (IBD) affects mainly the young population. The effect of IBD and its treatment on fertility and pregnancy is therefore an important clinical consideration.To review the best management of IBD in the reproductive and pregnant population.A MEDLINE and an EMBASE search were performed using mainly the search phrases 'pregnancy AND IBD,''sulphasalazine AND male fertility,''abdominal surgery AND female fertility,''AZA AND placenta' and 'infliximab AND pregnancy.' No language or date restrictions were placed. References of review articles were examined.Overall male and female fertility are not affected by IBD. Sulphasalzine reduces male fertility. No other drugs used in IBD affect significantly fertility in humans. The risk of pregnancy-related complications and the disease behaviour during pregnancy depends mainly on disease activity at time of conception. Proactive treatment for maintenance of disease remission during gestation is recommended. Except for methotrexate, drugs used in IBD appear safe in pregnancy. Breast feeding should be encouraged.The management of IBD in the young and pregnant population remains controversial because the literature comes mostly from retrospective studies. Further studies particularly large prospective trials are needed to guide clinicians in decision making.

Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis.To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis.A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment.One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo.This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.

The high prevalence of Helicobacter pylori resistance to metronidazole demands treatments more effective than standard bismuth-based triple therapy against these strains.To evaluate the H. pylori eradication rate in both metronidazole-sensitive and -resistant strains following quadruple therapy using single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole.One hundred and seventy valid patients with duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were treated in eight centres located in five countries. H. pylori was confirmed at baseline using 13C-urea breath test, histology and/or culture. Patients received three single-triple capsules q.i.d. and omeprazole, 20 mg b.d., for 10 days. Each capsule contained bismuth biskalcitrate, 140 mg (as 40 mg Bi2O3 equivalent), metronidazole, 125 mg, and tetracycline, 125 mg. 13C-Urea breath test was repeated at least 4 and 8 weeks post-treatment.Overall eradication rates were 93% (158/170) by modified intention-to-treat analysis and 97% (142/146) by per protocol analysis. Eradication rates were 93% (40/43) and 95% (38/40) for strains resistant to metronidazole and 95% (82/86) and 99% (75/76) for strains sensitive to metronidazole by modified intention-to-treat and per protocol analysis, respectively.This omeprazole-bismuth biskalcitrate-metronidazole-tetracycline 10-day regimen is a very effective and well-tolerated treatment, which overcomes metronidazole resistance.

Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21-22 September 2000. A "test and treat" approach is recommended in adult patients under the age of 45 years (the age cut-off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro-oesophageal reflux disease symptoms, non-steroidal anti-inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test. As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low-grade gastric mucosa-associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first-degree relatives of gastric cancer patients and according to patients' wishes after full consultation. It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long-term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro-oesophageal reflux disease in most cases, and does not exacerbate existing gastro-oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non-steroidal anti-inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non-steroidal anti-inflammatory drugs. Treatment should be thought of as a package which considers first- and second-line eradication therapies together. First-line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second-line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second-line therapy should be with proton pump inhibitor-based triple therapy. If second-line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case-by-case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradication should always be confirmed by urea breath test or an endoscopy-based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are well-recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prosta- glandin metabolism. Clinical trials on the interrelation- ship between H. pylori, NSAIDs and gastroduodenal mucosal injury have yielded conflicting results. No consensus has been reached on what recommenda- tions should be implemented with regard to H. pylori eradication in patients on long-term NSAID therapy. At present, the presence of H. pylori is identified at endoscopy and eradication is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients at risk of gastrointestinal haemorrhage, and on NSAID therapy, acid suppression therapy should be prescribed.

To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer.A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology.Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively.The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer.This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months.The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P0.001). Treatment was well tolerated and compliance was high.The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.

A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens.To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease.Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a 13C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment.Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n = 262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P = 0.85, chi-squared test) with regard to the healing of duodenal ulcer disease.The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

Studies in young dyspeptic patients have suggested that screening strategies based on non-invasive H. pylori testing can reduce endoscopy workload by 25-40%. Such strategies usually propose that only H. pylori-positive individuals should undergo endoscopy. This approach may fail to diagnose idiopathic ulcers, ulcers in patients whose screening test is falsely negative and reflux disease.To investigate a hypothetical screening strategy in which endoscopy is initially performed only in H. pylori-negative dyspeptics.Seventy-two consecutive patients under 45 years of age undergoing investigation for 'ulcer-like' dyspepsia had invasive and non-invasive determination of H. pylori status. Individuals found to be H. pylori-positive at endoscopy received 1 week of proton pump inhibitor-based triple therapy. H. pylori-negative individuals received therapy tailored to their diagnosis. Endoscopy was repeated in the positive group to confirm successful eradication. Results were analysed according to our strategy, i.e. serologically-positive patients would have received eradication therapy without endoscopy, but patients found to be negative would have been referred for endoscopy.According to the serology test there were 39 positive and 33 negative results. Symptoms failed to resolve during follow-up in nine of the serological positives despite successful eradication. There were also five false positives who were deemed likely treatment failures. Thus according to our strategy, these 14 serologically-positive patients would ultimately have required an endoscopy and the other 25 serologically-positive patients would have avoided an endoscopy, resulting in a 35% reduction in endoscopy usage in this population. In the serologically-negative group there were three cases of peptic ulcer disease where the test was falsely negative, but they were detected by the strategy. No cases of gastric malignancy were detected at endoscopy. Thus our strategy would have reduced initial endoscopy referrals by 35% in this selected population.A strategy of empirical H. pylori eradication therapy can safely reduce the requirement for endoscopy in young dyspeptic patients without sinister symptoms.

Eradication of Helicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis.To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori.Men or women with H pylori positive duodenal ulceration or gastritis, or both.A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pylori status. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment.H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported.All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.

cohort showed substantially more ileocolonic (71%) and upper GI (28%) involvement. Immunomodulator use was higher: 57% in CD and 40% of UC paediatric patients; 20% from the latter required a colectomy. Conclusions: The preliminary results from this first Australian population natural history study show high rates of inflammatory disease and immunosuppression suggesting earlier diagnosis and aggressive treatment. Future data will identify prognostic factors of severe disease, as well as health care costs.

Introduction Faecal immunochemical tests (FIT) are acceptable to a large part of the general population but used alone are poor at detecting adenomas. An ELISA which measures faecal M2-pyruvate kinase (M2-PK) has been shown to be useful for detecting colonic pathology. Aims To prospectively compare M2-PK and FIT in screening for colonic polyps and cancer in the second round of our pilot FIT-based Colorectal cancer screening programme. Methods The second round of our FIT pilot programme was conducted over a two year period. Patients were sent invites by post to return a FIT sample from each of two days. All participants were aged 50 – 74 and living locally to our hospital. As part of this round, over a six month period all invitations additionally included containers to collect a single M2-PK stool sample. All FIT’s returned on time were measured locally. All M2-PK samples received within 48 hours of passing stool were frozen and analysed centrally by ScheBo Biotech AG (Germany). All FIT positive (>100 ngHb/ml) or M2-PK positive (>4 U/ml) patients were contacted and assessed for colonoscopy. All colonoscopies were conducted in the same way between both groups. Results Over the six month period 1,800 combined M2-PK and FIT invites have been sent. 879 samples were returned and analysed for faecal M2-PK and FIT; of these 245 were positive for either one or both of these markers. After being contacted 34 (13%) of this group were excluded as they had a colonoscopy within 3 years and were all in polyp surveillance programmes. Of the remaining patients: 30 (3.4% of 879) were FIT positive M2-PK negative; 160 (18.2%) were positive for M2-PK ( > 4U/ml) negative for FIT and 21 (2.3%) were positive for both markers. In the FIT positive M2-PK negative group there were 10 patients with adenomas (adenoma detection rate 33%). In those who were M2-PK positive but FIT negative there were 34 people with adenomas (ADR 23%). Therefore these adenomas would not have been detected by relying on FIT alone. Of the remaining 21 positive for both, 6 (29%) had adenomas and another 4 (19%) had colitis/proctitis. There have not been any cancers in this group to date. Interestingly sessile serrated adenomas were detected in 5 (4.4%) of people M2-PK positive but only two (less than 1%) in our entire FIT positive group. Conclusion Studies have shown FIT has relatively low sensitivity for adenomas. The addition of another stool marker such as faecal M2-PK increases the detection of polyps in a screening population. A single M2-PK sample detects more adenomas than two day FIT alone. Also M2-PK appears to be more sensitive for serrated adenomas than FIT but further studies are needed to confirm this. Disclosure of Interest None Declared

Dyspepsia is a poorly understood term that is used to describe symptoms that originate in the upper gastrointestinal tract. There is increasing evidence that Helicobacter pylori infection plays an aetiological role in some forms of dyspepsia. H. pylori infection is more common in dyspeptic patients than asymptomatic controls. Clinical trials of the benefit of H. pylori eradication therapy in non-ulcer dyspepsia have given conflicting results. This may be due to methodological flaws in the studies to date. Trials in non-ulcer dyspepsia may have several end-points. Future studies should be long-term, placebo-controlled, double-blind, and use a validated symptom questionnaire. Acid secretion studies demonstrate acid hypersecretion in non-ulcer dyspepsia that is intermediate between that seen in duodenal ulcers and asymptomatic carriers. This suggests that H. pylori gastritis represents a spectrum of disease that includes duodenal ulceration, whose natural history is one of relapses and remissions, and non-ulcer dyspepsia.

In 1893 the Italian pathologist G. Bizzozzero first described the presence of “curved bacilli” in the stomach of dogs [1]. During the following years other authors reported the detection of curved bacilli in the stomach of mammals such as rats and cats [2], in the stomach of patients with ulcerated neoplasms [3] and in the stomach of subjects with gastroduodenal peptic ulcers [4]. These findings were confirmed by later studies [5, 6]. However, none of these curved bacilli was ever isolated, and the theory of their role in human diseases progressively declined. However, in 1983 Warren and Marshall [7] succeeded in isolating spiraliform bacteria from human stomachs. These were first called Campylobacter pyloridis, then Campylobacter pylori and, eventually, Helicobacter pylori (HP). These two Australian researchers also suspected that antral gastritis and duodenal ulcers were of infectious origin and have to their credit the definition of the culture conditions necessary for the growth of this microorganism, so that it has been thereafter possible to perform several clinical studies on HP. Thus, we currently know that some 70%–92% of people with chronic gastritis are carriers of HP, and that it is found in about 86% and in 65% of subjects with duodenal and gastric ulcer [8], respectively.

The ability of nine blood containing media to support the growth of H. pylori was compared. Eighteen strains of H. pylori isolated from antral biopsies were cultivated in two dilutions, for colony counts on the media to be tested. Columbia base chocolate agar without additives was found to be the best medium for growth of H. pylori. However, all other fresh blood containing media also supported the growth of this organism satisfactorily.

Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms.

Seventy-one patients whose duodenal ulcers had healed after a 4-week treatment period with tripotassium dicitrato bismuthate (TDB) were randomly allocated to receive maintenance treatment with either one TDB swallow tablet nocte (equivalent to 120 mg Bi2O3) or an identical placebo. During 12 months of follow-up, no side-effects were reported by TDB-treated patients, blood bismuth levels did not rise above discontinuation threshold concentrations (greater than 50 micrograms/L in the first 6 months, or greater than 100 micrograms/L in the second 6 months), and there were no adverse effects on haematological or biochemical indices. Ulcer relapse was significantly less in TDB-treated patients (P less than 0.025). Cumulative relapse rates at 6 and 12 months were 51% and 66%, respectively, for placebo-treated patients and 26% and 31%, respectively, for those who received TDB. It is likely that TDB is a safe and effective maintenance treatment for patients with duodenal ulcer disease.

Editor,—The Maastricht Consensus Report ( Gut 1997; 41 :8–13) is a welcome benchmark summarising current opinion and scientific evidence regarding the role of Helicobacter pylori in gastroduodenal disorders. Whereas the management of peptic ulcer disease is no longer controversial and is very evidence-based the same is not yet true for the syndrome of non-ulcer dyspepsia and the management of the uninvestigated dyspeptic patient. The recommendation of the Maastricht Report reflects this uncertainty. They recommend that at the specialist level, eradication therapy for H pylori infected non-ulcer dyspepsia is “advisable”, based on supportive scientific evidence, but only after “full investigation” including endoscopy, ultrasound and other tests. However, in the management algorithm for the uninvestigated dyspeptic in primary care, non-invasive testing (with a breath test) and treatment is recommended for patients who are at a low risk of gastric carcinoma. Why such a difference? If it is recommended that a breath test is investigation enough of dyspepsia in primary care then an endoscopy and biopsy should be adequate in specialist practice if there are no other clinical indicators of another diagnosis (such as biliary colic) and the patient is at low risk of malignancy. The difficulty is that non-ulcer dyspepsia will remain a hard target and even several studies of symptom response after eradication therapy due to be reported shortly will not resolve the issues as there will be perennial debate about inclusion and exclusion criteria in such trials and these will have a great bearing on outcomes. Moreover, the ability to quantitate the lifetime risk reduction of peptic ulcer disease and perhaps even gastric carcinoma in patients who have eradication therapy will remain contentious. Medico-legal issues and patient preferences will also continue to be important factors influencing the decision to investigate and treat. At present the suggested test and treat …

Crohn’s disease is an inflammatory bowel disease the aetiology of which is unknown. It was first described 47 years ago (Crohn et af. 1932). There appears to be a real increase in its incidence in the last 20 years. A working definition of Crohn’s disease is ‘a condition in which there is a chronic enteritis usually characterized by areas of intestinal stenosis, and pathologically by non-caseating granulomata in the bowel wall’ (Weterman et al. 1975). As the definition implies the diagnosis is made on clinical, radiological and histological grounds. The clinical picture of patients with Crohn’s disease is that of weight loss, abdominal pain, diarrhoea and stunted growth in children. They may have extra-intestinal manifestations such as pyrexia, uveitis and arthritis. Treatment The treatment of Crohn’s disease can be divided into five main categories: surgery, general symptomatic and supportive treatment, antimicrobial treatment, anti-inflammatory treatment and nutritional treatment. Resection of the affected bowel was once thought to be the definitive treatment but recurrence of the disease is common and now surgery is reserved for the complications of Crohn’s disease unresponsive to medical therapy such as obstruction, unremitting inflammation and haemorrhage, toxic megacolon, free perforation and fistula formation. The aim of medical treatment is to induce a remission. No treatment has been shown to produce a permanent cure for Crohn’s disease. As the disease course is characterized by its chronicity and morbidity a lot of emphasis is placed on symptomatic and supportive treatment. This would include anxiolytic, analgesic and anti-diarrhoeal agents. Broad spectra antibiotics are used for the complications of Crohn’s disease such as abscess formation or perforation. There have been reports that Metronidazole (Ursing & Kamme, 1975) and broad spectra antibiotics (Moss et al. 1978) are effective treatment in acute Crohn’s disease. There are three types of drugs in the anti-inflammatory group: corticosteroids, azothiaprine and salazopyrine. Corticosteroids have been shown to be more effective than azothiaprine or salazopyrine (Singleton, I 976). Nutritional therapy is a new concept introduced in the treatment of Crohn’s disease when it was found that patients were in negative nitrogen balance. There are two methods of putting patients into positive N balance, either by parenteral nutrition or the use of an elemental diet.