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

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

Computer-assisted propofol administration.

The use of propofol for sedation in endoscopy may allow for better quality of sedation, quicker recovery and facilitate greater throughput in endoscopy units. The cost-effectiveness and utility of propofol sedation for endoscopic procedures is contingent on the personnel and resources required to carry out the procedure. Computer-based platforms are based on the patients response to stimulation and physiologic parameters. They offer an appealing means of delivering safe and effective doses of propofol. One such means is the bispectral index where continuous EEG recordings are used to assess the degree of sedation. Another is the closed-loop target-controlled system where a set of physical parameters, such as muscle relaxation and auditory-evoked potential, determine a level of medication appropriate to achieve sedation. Patient-controlled platforms may also be used. These electronic adjuncts may help endoscopists who wish to adopt propofol sedation to change current practices with greater confidence.

Impact of Helicobacter pylori on the management of dyspepsia in primary care.

BACKGROUND: It is unclear what impact Helicobacter pylori infection has had on the management of dyspepsia in primary care and to what extent published guidelines on H. pylori are implemented in routine clinical practice. AIM: To assess the impact of H. pylori infection on the management of dyspepsia in primary care. METHODS: Patients referred by primary care doctors to an open-access 13-carbon urea breath test service over a 2-year period for their first urea breath test were included in the study. Individual breath results were linked with data on prescribing obtained from the General Medical Services prescription database. RESULTS: Of 805 patients, 374 (47%) had a positive urea breath test and 431 (54%) a negative urea breath test. Of positive urea breath test patients, only 245 (64%) were prescribed eradication therapy in the 3 months after the breath test and only 43% were referred back for re-testing. In the year after the urea breath test, there was a significant fall in prescribing of antisecretory therapy which was greatest in the patients who received H. pylori therapy (P < 0.001). CONCLUSIONS: There appears to be under and inappropriate treatment of H. pylori infection in primary care, and a low rate of re-testing after eradication, indicating that current guidelines are not well implemented in practice.

Helicobacter pylori serology in patients with angiographically documented coronary artery disease.

We studied the relation between angiographically defined coronary artery disease and serologic evidence of Helicobacter pylori infection in 488 patients undergo ing elective coronary angiography. There was no association between Helicobacter pylori infection and coronary artery disease (odds ratio 1.3, 95% confidence interval 0.83 to 2.16).

Nutritional therapy in Crohn's disease.

The value of nutritional support in the prevention and treatment of malnutrition in Crohn's disease is undisputed but its role in primary therapy continues to be debated. Controlled trials have demonstrated that enteral nutrition induces remission rates comparable to that of corticosteroid therapy in Crohn's disease and remains the treatment of choice for specific subgroups such as children with signs of growth impairment and patients with intolerable steroid-induced side effects. The mechanism by which an enteral diet induces remission in Crohn's disease is unclear. Bowel rest, reduced antigenic load, nutritional effects, the provision of trophic amino acids, modification of gut flora, intestinal permeability, or fecal pH have been proposed. Equally, the fat profile of the feed may reduce pro-inflammatory ecosanoid synthesis and thus modify disease activity. Maintaining long-term remission remains a challenge in the management of this disease. Cyclic administration of enteral diets, maintenance drug therapy, fat manipulated formulas, or fish oil therapy may be strategies to prolong diet-induced remission. In the future, nutrient derivatives that play a role in the protective processes of the intestinal mucosa may have application in nutritional therapy in Crohn's disease.

Review article: nutrition and adult inflammatory bowel disease.

Major advances in the understanding of the aetio-pathogenesis and genetics of inflammatory bowel disease have been accompanied by an escalation in the sophistication of immunomodulatory inflammatory bowel disease therapeutics. However, the basic 'triple' therapy (5-aminosalicylates, corticosteroids, azathioprine) and nutrition have maintained their central role in the management of patients with inflammatory bowel disease over recent decades. This review provides an overview of the supportive and therapeutic perspectives of nutrition in adult inflammatory bowel disease. The objective of supportive nutrition is to correct malnutrition in terms of calorie intake or specific macro- or micronutrients. Of particular clinical relevance is deficiency in calcium, vitamin D, folate, vitamin B12 and zinc. There is justifiably a growing sense of unease amongst clinicians and patients with regard to the long-term use of corticosteroids in inflammatory bowel disease. This, rather than arguments about efficacy, should be the catalyst for revisiting the use of enteral nutrition as primary treatment in Crohn's disease. Treatment failure is usually related to a failure to comply with enteral nutrition. Potential factors that militate against successful completion of enteral nutrition are feed palatability, inability to stay on a solid-free diet for weeks, social inconvenience and transient feed-related adverse reactions. Actions that can be taken to improve treatment outcome include the provision of good support from dietitians and clinicians for the duration of treatment and the subsequent 'weaning' period. There is evidence to support a gradual return to a normal diet through exclusion-re-introduction or other dietary regimen following the completion of enteral nutrition to increase remission rates. We also review the evidence for emerging therapies, such as glutamine, growth factors and short-chain fatty acids. The future may see the evolution of enteral nutrition into an important therapeutic strategy, and the design of a 'Crohn's disease-specific formulation' that is individually tailored, acceptable to patients, cost-effective, free from adverse side-effects and combines enteral nutrition with novel pre- and pro-biotics and other factors.

Review article: treatment of Helicobacter pylori infection and factors influencing eradication.

Currently available Helicobacter pylori eradication therapies are considered very effective and safe. The most recent eradication guidelines proposed in the Maastricht 2-2000 Consensus Report recommend the use of proton pump inhibitors (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of amoxycillin and clarithromycin is preferred because it may favour best results with a second-line proton pump inhibitor quadruple therapy. The recommended second-line therapy includes a combination of a proton pump inhibitor (standard b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days. Extended proton pump inhibitor-based triple therapy can be used if bismuth is not available. Specialists should manage subsequent failures. Based on direct and indirect evidence from well-designed studies and clinical experience, eradication is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis, postgastric cancer resection, and in first-degree relatives of gastric cancer patients. The most common reason for treatment failure is poor compliance with eradication guidelines. Antibiotic resistance may be a significant factor in certain geographical areas. Proton pump inhibitors are an integral part of the eradication regimens as proved by meta-analyses of clinical trials. Novel agents used in secondary failure are few and depend on the use of new antibiotics. The role of H. pylori-specific antibiotics, probiotics, and vaccines is not established as yet. Widespread acceptance of the eradication guidelines should be regarded as the single most important factor in eradication success.

Review article: current therapeutic options for gastric antral vascular ectasia.

Gastric antral vascular ectasia, or 'watermelon stomach', is a rare but important cause of gastrointestinal blood loss and anaemia, which has characteristic endoscopic and histological features. The pathogenesis of this condition remains unclear; however, many associated disorders have been documented. Various medical, surgical and endoscopic therapeutic modalities have been attempted with variable success. Leading contenders for the therapeutic modality of choice include hormonal therapy, endoscopic Nd:YAG laser and argon plasma coagulation. Randomized controlled trials to identify the ideal treatment method are lacking at present.

Therapeutic potential of fish oil in the treatment of ulcerative colitis.

In a pilot study six patients with active ulcerative colitis and six healthy controls were given fish oil (MaxEPA) containing 3-4 g of eicosapentaenoic acid daily for a period of 12 weeks. There was a significant improvement in the patients' symptoms and histological appearance of the rectal mucosa by the end of the treatment period. There was significant fall in neutrophil chemiluminescence during treatment in patients, whereas no change was observed in the control group. Neutrophil leukotriene B4 levels fell significantly during treatment. Serum from patients receiving fish oil was significantly less chemotactic for neutrophils compared with control serum. Eicosapentaenoic acid inhibited neutrophil chemotaxis and chemiluminescence in vitro. The omega-3 fatty acids, which occur naturally in fish oils, may exert a beneficial effect by decreasing the production of inflammatory mediators.

Do non-steroidal anti-inflammatory drugs have an effect on gastric cell turnover?

AIM: To study the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on gastric cell turnover using an in vitro immunohistochemical method of bromodeoxyuridine (BrDU) uptake. METHODS: Thirty patients undergoing routine upper gastrointestinal endoscopy were studied. Sixteen had taken NSAIDs daily for more than 3 months and there were 14 age-matched controls. Endoscopic gastric antral biopsies were obtained and stained immediately using the BrDU technique. Cell proliferation was expressed as a labelling index percentage (LI%) defined as the number of BrDU-labelled nuclei in 10 gastric glands, expressed as a percentage of the total cells in the gastric gland. RESULTS: Gastric infection with Helicobacter pylori was excluded in all patients. Of the 16 patients on NSAIDs, four had gastritis, four had erosions or ulceration and eight had a normal examination. Endoscopy was normal in all patients in the control group. The LI% (mean +/- S.E.M.) in the entire NSAID group was 4.09 +/- 0.29 and in the control group 3.57 +/- 0.29. No significant difference was observed. In the NSAID patients with gastritis and erosions or ulceration, the LI% was 4.99 +/- 0.61 and 3.07 +/- 0.32, respectively. There was no significant difference in LI% between the endoscopic subgroups of patients on NSAIDs or between patients on NSAIDs who had normal endoscopy and the control patients. CONCLUSION: These results provide evidence that refutes the hypothesis that the prevalence of NSAID gastropathy is due to an effect on gastric cell turnover.

Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice.

BACKGROUND: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined. AIMS: To evaluate proton pump inhibitor-based triple therapies as first-line eradication regimens in clinical practice, and to establish the efficacy of second-line regimens in the context of an initial failed eradication attempt. METHODS: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first-line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2-week proton pump inhibitor-based triple therapy regimen as described, and 12 patients received a further 1-week proton pump inhibitor-based triple therapy regimen. RESULTS: Including 308 patients, the intention-to-treat (ITT) eradication rates for OAC and OMC as first-line regimens were 72% (95% CI: 63-80%) and 73% (95% CI: 67-79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow-up gives an initial eradication rate of 78% (95% CI: 69-86%) for OAC and 79% (95% CI: 73-85%) for OMC. There were 60 patients (21%; 95% CI: 17-26%) in whom the initial eradication attempt was unsuccessful. With second-line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58-73%) patients. The eradication rates with the quadruple regimen and 2-week triple therapy regimens were 75% (95% CI: 56-94%) and 80% (95% CI: 63-98%) respectively (P = 0. 71). The eradication rate with a repeat 1-week regimen was 33% (95% CI: 7-60%). CONCLUSIONS: The eradication rates achieved in this 'in practice' study with recommended first-line 1-week proton pump inhibitor-based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1-week proton pump inhibitor-based triple therapy regimen was not successful as a salvage therapy. Both the 2-week proton pump inhibitor-based triple therapy regimen and the 1-week quadruple therapy regimen were successful second-line treatments in >/=75% of patients.

A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?

BACKGROUND: Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non-ulcer dyspepsia is made. The pathophysiology of non-ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity. AIM: To determine the sensitivity of serotonin receptors in non-ulcer dyspepsia. METHODS: Using a randomized, double-blind, placebo-controlled design, we compared buspirone (a serotonin type 1a partial agonist)-stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was administered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart. RESULTS: Overall, patients with non-ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most significant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female subjects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females. CONCLUSIONS: Patients with non-ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Blockade of such receptors might be an appropriate therapeutic strategy.

Review article: test and treat or test and scope for Helicobacter pylori infection. Any change in gastric cancer prevention?

A 'test and treat' strategy is advocated for patients with dyspepsia under the age of 45 years, with endoscopy reserved for those with alarm symptoms or aged over 45 years. One of the consequences of this strategy will be a reduction in population infection rates of Helicobacter pylori. It is now clear that H. pylori is one of the prime initiators of gastric cancer with up to 70% of gastric cancers attributable to H. pylori. What remains unclear is if H. pylori reduction will lead to a reduction in gastric cancer.

Clinical and pathological implications of IgG antibody responses to Helicobacter pylori and its virulence factors in non-ulcer dyspepsia.

AIM: To determine whether pre-treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non-ulcer dyspepsia. METHODS: H. pylori-positive patients with non-ulcer dyspepsia received 1-week omeprazole-based triple therapy, or omeprazole plus placebos. Symptoms were assessed using a validated Likert scale. Gastric biopsies taken before and 12 months after treatment were used for histological examination. Pre-treatment blood samples were used for the detection of anti-H. pylori immunoglobulin G (IgG) antibodies, and specific IgG antibodies to 19.5-, 26.5-, 30-, 35-, 89- (VacA) and 116-kDa (CagA) antigens of H. pylori. RESULTS: IgG antibodies to the six antigens were detected in 62%, 96%, 88%, 47%, 54% and 78% of patients, respectively. The presence of antibody to 19.5-, 26.5- or 30-kDa antigen was associated with an increased anti-H. pylori IgG absorbance index. IgG absorbance indices were greater in those with H. pylori eradication (vs. persistent infection). The prevalence of antibodies to the six antigens was not significantly different between those with symptom relief vs. those without. The 19.5-kDa antigen (P = 0.018) and VacA (P = 0.001) were independent risk factors for body gastritis. CONCLUSIONS: An increased pre-treatment anti-H. pylori IgG absorbance index may be a useful predictor of the success of eradication therapy. Although the 19.5-kDa antigen and VacA were associated with body gastritis, none of the six antigens tested predicted symptom relief after triple therapy.

The safety and efficacy of ranitidine bismuth citrate in combination with antibiotics for the eradication of Helicobacter pylori.

BACKGROUND: Ranitidine bismuth citrate is a novel salt of ranitidine and a bismuth citrate complex. It has intrinsic antisecretory and anti-Helicobacter pylori activity, but monotherapy rarely eradicates H. pylori infection in man. AIM: A pilot study to investigate rates of H. pylori eradication achieved by co-prescription of ranitidine bismuth citrate with antibiotics, and to identify several regimens which would merit further investigation. METHOD: One hundred dyspeptic patients infected with H. pylori were randomly allocated to treatment with ranitidine bismuth citrate 800 mg b.d. plus either amoxycillin, metronidazole, clarithromycin, cefuroxime axetil, tetracycline, tetracycline plus metronidazole or clarithromycin plus tetracycline for 14 days. Eradication of infection was assessed using the 13C-urea breath test 4 weeks after the end of treatment. RESULTS: In a per protocol analysis eradication of H. pylori ranged between 22 and 100%; the intention-to-treat eradication rates ranged between 15 and 92%. No adverse events were specifically attributed to ranitidine bismuth citrate. CONCLUSION: Co-prescription therapy, using ranitidine bismuth citrate and one or more antibiotics, is suitable for further investigation in large-scale clinical trials in patients infected with H. pylori.

Enhanced cultivation of Helicobacter pylori in liquid media.

AIMS: To evaluate a technique for culture of Helicobacter pylori in large quantities of liquid media and to determine the factors that could influence the results. METHODS: Fifteen clinical isolates of H pylori and a reference strain of H pylori NCTC11637 were used to evaluate a method to cultivate the organism in 100 ml liquid medium comprising brain heart infusion broth with 5% horse serum and 0.25% yeast extract. Tissue culture flasks containing the inoculated liquid medium were placed in a CO2 incubator with 5% CO2 for 2 hours and then incubated in a shaking incubator at 120 rpm. RESULTS: All the clinical isolates and the reference strain grew in the broth, although only a moderate growth of the reference strain occurred. Inoculum size significantly influenced the kinetics of growth of H pylori in the liquid medium. Vancomycin, nalidixic acid, and amphotericin B, used to suppress contamination, did not affect growth of H pylori in the medium. CO2 was essential for H pylori to grow or survive in the liquid medium. Incubation with CO2 in a CO2 incubator for 30 minutes or 2 hours did not affect the results. CONCLUSIONS: H pylori can be cultivated in large quantities of brain heart infusion broth with 5% horse serum and 0.25% yeast extract. Initial inoculum concentrations influence the kinetics of H pylori growth in the liquid medium. Vancomycin, nalidixic acid, and amphotericin B can be used as selective antimicrobial agents. CO2 is essential for initial growth of H pylori in liquid media. The findings in this study may provide a useful, reproducible, and simple method for biochemical, molecular, and physiological studies of H pylori, when those require large quantities of the organism.

Identification of genes regulated by prolonged acid exposure in Helicobacter pylori.

To investigate the influence of prolonged acid exposure on the gene expression, transcripts of Helicobacter pylori, grown under pH 5.5 and pH 7.4 for five successive passages, were analysed by differential display PCR. Eight genes were regulated by prolonged acid exposure. These genes included topA, tufB, ureB, flaA, atoE in the H. pylori genome and a cDNA fragment with 54% identity of the predicted amino acid sequence to a Bacillus cereus YkoW protein. The remaining two cDNA fragments had no significant homology to known sequences. Our data suggest that most of these genes might be required for the resistance of H. pylori to prolonged acid exposure.

Determination of the optimal transport system for Helicobacter pylori cultures.

A range of solid and liquid media was evaluated for the ability to maintain survival of Helicobacter pylori strains under different conditions. Chocolate agar slopes maintained survival of most strains for longer than 3 days, some strains surviving for up to 9 days, despite a decreased number of viable cells. Temperature and atmosphere did not significantly influence the performance of these slopes. The BBL Campy Pouch system also achieved a considerable recovery rate of H. pylori after storage for 3 days at the same range of temperatures. Brain-heart infusion broth with horse serum was superior among the liquid media tested, maintaining the viability of H. pylori for c. 3 days at temperatures ranging from -4 degrees C to 21 degrees C. Chocolate agar slopes are recommended as suitable for transport of H. pylori strains.

Pre-formed urease activity of Helicobacter pylori as determined by a viable cell count technique--clinical implications.

The pre-formed urease activity of three NCTC reference strains and five clinical isolates of Helicobacter pylori was determined at room temperature (21 degrees C) and 37 degrees C by a viable cell count technique with a conventional urea slope test (Christensen's agar) as well as the commercial CLO-test. The urease activity of two gastroduodenal commensals, Proteus mirabilis and Klebsiella pneumoniae, was also tested. H. pylori strains produced positive reactions with viable cell counts of 10(6)-10(8) cfu within 30 min and with counts of 10(3)-10(6) cfu within 2 h. For some strains, smaller numbers of organisms were needed with the CLO-test than with the conventional test, and incubation of the CLO-test strips at 37 degrees C slightly decreased the number of organisms required for positive results. P. mirabilis produced a positive result on urea slopes with an initial inoculum of 10(7)-10(8) cfu at 2 h, but no positive reaction occurred for K. pneumoniae at 12 h, even with an initial inoculum of 10(11) cfu. However, both P. mirabilis and K. pneumoniae gave a positive result after incubation for 24 h with initial inocula of < 10(1) cfu and 10(3)-10(4) cfu respectively. Incubation at 37 degrees C significantly reduced the inoculum size of these organisms required for a positive result after incubation for 4 h when tested with the slopes, but not with the CLO-test. These findings indicate that H. pylori possesses much greater pre-formed urease activity than P. mirabilis and K. pneumoniae. False negative results for clinical detection of H. pylori in gastroduodenal biopsies may be due to small numbers of organisms, especially after treatment with antimicrobial agents, and false positive results may arise from gastroduodenal commensals or contaminants.

Increased mast cells in the irritable bowel syndrome.

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.