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The gram-negative bacterium Helicobacter pylori is known as a persistent colonizer of the human stomach, and probably less known is that it is also involved in extraintestinal diseases. Public awareness of its contribution in the development of gastric cancer is less than 15 years old. The efficacy of the current therapies based on antibiotics against H. pylori has been limited by difficulties such as antibiotic resistance and recurrence. As a consequence, the development of promising vaccines was prompted as the best preventive measure. Unfortunately, so far vaccines failed the transition from animal models to human trials. This keynote presentation is to provide a bird's eye view of H. pylori-related gastric diseases, including gastric cancer, with a synthesis of the molecular mechanisms involved, and an exhaustive presentation and discussion of the current therapeutic guidelines and future strategies for prevention or therapy.

Aim: To test the hypothesis that duodenal colonization represents the final crucial step in the development of Helicobacter pylori related duodenal ulcer., Methods: Patients with non-ulcer dyspepsia who had gastric colonization by H. pylori were included in the study. At baseline endoscopy, we evaluated the prevalence of duodenal colonization (culture, urease testing and histology), and cytotoxin-associated gene A status (polymerase chain reaction). No patients received eradication during 1 year follow-up. At this time, endoscopy was repeated and the incidence of duodenal ulcer was assessed., Results: Among 181 patients completing follow-up, 53 (29%) had duodenal colonization: 72% of them were cytotoxin-associated gene A positive, versus 37% patients without duodenal colonization (P < 0.001). Duodenal ulcer developed in 12 (22.6%) patients with duodenal colonization and in two (1.6%) without duodenal colonization (odds ratio for duodenal ulcer: 6.29, 95% confidence intervals 2.44-17.45). The incidence of duodenal ulcer was similar among cytotoxin-associated gene A positive and cytotoxin-associated gene A negative subjects with duodenal colonization: 21.05% versus 26.6%., Conclusions: The assessment of duodenal colonization by H. pylori in patients with non-ulcer dyspepsia is strongly predictive for the subsequent development of duodenal ulcer and may help to stratify patients at risk for this disease.

Background: Endoscopy represents the gold standard for the diagnosis of Helicobacter pylori infection. We evaluated three noninvasive tests in a group of children: the immunoassay for detection of H. pylori stool antigen, the polimerase chain reaction for identification of bacterial DNA on the oral cavity and the serum specific antibodies., Materials and Methods: One hundred and ninety children underwent endoscopy for various gastrointestinal symptoms. H. pylori stool antigen and anti-H. pylori antibodies were assayed by commercial kits. The bacterial DNA on saliva and oral plaque was detected by a seminested PCR., Results: Based on the positivity of culture or urease rapid test and histology, infection was detected in 47 patients. The statistical analysis showed that, for the detection of the infection, stool antigen assay is more effective in sensitivity and negative predictive value (91.5% and 96.5%), whereas specificity and positive predictive values appear slightly better in serology (89.6% and 76.0%). Correlations between serum IgG both with patients' age (r = 0.21, p < .05) and H. pylori stool antigen (r = 0.47, p < .01) were found. The search for bacterial DNA on oral samples proved to be very specific (99.1% on saliva and 98.2% on plaque), but insensitive (22.2% and 25.7%). CONCLUSIONS. In children H. pylori stool antigen represents a sensitive test, suitable for detecting H. pylori infection. Serum IgG proved to be more specific; the PCR on the oral cavity resulted as being a very specific, but insensitive test.

Background: It is uncertain whether Helicobacter pylori is associated with ischemic syndromes and whether this association is mediated by the induction of atherosclerosis. In this study, we tested the hypothesis that atherosclerotic stroke shows a selective association with virulent H pylori strains., Methods and Results: The seroprevalence of infection by H pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, was assessed by ELISA in 138 patients with large-vessel stroke (group A), in 61 patients with cardioembolic stroke (group B), and in 151 healthy control subjects. The 3 groups had a similar socioeconomic status. Serum levels of C-reactive protein were also measured by ELISA. The prevalence of infection was 71% in group A, 63.9% in group B, and 70.2% in the control group (P=NS), whereas the prevalence of CagA-positive strains was higher in group A than in group B (42.8% versus 19.7%, respectively; odds ratio 3.04, 95% CI 1.43 to 6.49; P<0.001) and higher in group A than in the control group (42.8% versus 17.9%, respectively; odds ratio 4.3, 95% CI 2.12 to 8.64; P<0.001), after adjusting for main cardiovascular risk factors and social class. A trend toward a difference in C-reactive protein was observed between CagA-positive (2.00+/-3.43 [mean+/-SD] mg/dL) and CagA-negative (1.31+/-1.72 [mean+/-SD] mg/dL) patients (P=0.072, Mann-Whitney U test)., Conclusions: The association between H pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H pylori strains in patients with atherosclerotic stroke.

Objective: The aim of this study was to evaluate whether different Helicobacter pylori genotypes are associated with different clinical stages of peptic ulcer disease (PUD)., Design: We assessed the virulence characteristics of H. pylori isolates from patients with active PUD (presence of an ulcer crater at endoscopy) and from those with PUD in remission (normal endoscopic findings or scar not induced by drugs in PUD patients)., Methods: H. pylori isolates from biopsies of the gastric antrum were examined for cagA and vacA genotypes by PCR amplification and Western blot analysis. Descriptive statistical techniques and multivariate polytomous logistic regression were used to estimate adjusted odds ratio (OR) for cagA and vacA genotypes in patients with active PUD or PUD in remission. Patients with non-ulcer dyspepsia (NUD) were used as negative controls., Results: The cagA genotype and phenotype were found to be differently associated with disease status. In fact, the multivariate regression model showed that gastric colonization by CagA+ H. pylori strains was associated with an increased risk of active PUD (OR 2.58), whereas the OR for patients with PUD in remission was 0.94., Conclusions: Our data indicate that the active ulcer status is more strongly associated with H. pylori strains carrying the pathogenicity island (PAI) than remission status. These results support the hypothesis that a dynamic equilibrium exists among bacterial populations with or without the PAI, and that the relapse of the peptic ulcer could be consequent to expansion of the H. pylori population carrying the PAI.

A positive association between Helicobacter pylori antibodies and food allergy presenting with gastrointestinal symptoms has recently been reported. A subset of a H. pylori strain possesses an antigen, CagA, as a virulence factor. Anti-H. pylori and anti-CagA IgG titre have been determined in children with atopic dermatitis (AD) as the sole clinical manifestation of food allergy. In this study, thirty patients with AD as the sole clinical manifestation of food allergy were examined (group A). For comparative purposes, 30 patients affected by food allergy with gastrointestinal symptoms (group B) and 30 affected by atopic asthma (group C) were studied. Anti-H. pylori and anti-CagA immunoglobulin G (IgG) were determined in all individuals by means of the enzyme-linked immunosorbent assay. The anti-H. pylori IgG titre was significantly higher in group A and group B vs. group C (p < 0.05); no significant difference was detected between group A and group B (p > 0.05). No significant difference in anti-CagA titre was found between the groups. These data demonstrate a positive association between H. pylori antibodies and AD as the sole manifestation of food allergy. Further investigations are needed to evaluate the cause-effect relationship between H. pylori seropositivity and AD.

Background: In children Helicobacter pylori has been involved as a pathogenetic factor in gastritis and duodenal ulcer and as a cofactor in protein-losing enteropathy, chronic diarrhoea, short stature, and gastritis lymphoproliferative disease. A subset of an H. pylori strain possesses an antigen, CagA, as a virulence factor. In the present study we determined anti-H. pylori IgG and anti-CagA IgG titres in children with food allergy., Methods: Ninety paediatric patients were studied: 30 with food allergy, 30 with atopic asthma, and 30 with inflammatory bowel disease. Anti-H. pylori IgG and anti-CagA IgG were determined in all children by means of a commercial enzyme immunoassay (ELISA)., Results: The anti-H. pylori IgG titre was significantly higher in allergic patients than in the other two groups. The anti-CagA IgG titre did not differ significantly between the patients., Conclusions: These findings show a positive association between H. pylori infection and food allergy in children. We hypothesize that virulence factors other than CagA may be involved in the pathogenesis of H. pylori infection in paediatric patients with food allergy.

Objective: It has been reported that pretreatment with omeprazole could decrease the efficacy of Helicobacter pylori eradication. Our aim was to compare the efficacy, safety, and tolerability of the eradicating regimen, omeprazole/amoxicillin/metronidazole. The two antibiotics were scheduled either during the first or during the last 2 wk of omeprazole administration., Methods: In this prospective controlled study conducted in a single center, 78 symptomatic peptic ulcer patients were treated for 4 wk with omeprazole 40 mg o.m.; the patients were randomly assigned to receive amoxicillin 1 g t.i.d. postprandially and metronidazole 250 mg t.i.d. postprandially, either during the first 2 wk (group A, n = 40) or the last 2 wk of therapy with omeprazole (group B, n = 38). H. pylori status was assessed by culture, histology, urease test, and IgG antibodies. Each patient's course was followed for 1 yr., Results: H. pylori infection was cured in 97.4% of group A (95% CI: 0.84-0.99) and in 89% of group B (95% CI: 0.73-0.96, p = 0.28). Healing was achieved in 80% of the patients in group A (95% CI: 0.63-0.90) and in 75.7% of patients in group B (95% CI: 0.60-0.90, p = 0.60) At 12-month follow-up, 72 patients were evaluated: 37/38 (97%) of patients in group A and 33/33 (100%) in group B were confirmed as cured of the infection (NS). Peptic ulcer healing rate reached 100% in the two groups. Furthermore, between the two groups, there were no significant differences in symptom relief or improvement. Both regimens were well tolerated, and no patient had to be withdrawn from therapy because of an adverse event. Minor side-effects appeared to be similar in the two groups (40% vs. 38%)., Conclusions: This randomized study clearly indicates that omeprazole pretreatment does not significantly reduce the efficacy of eradicating therapy for H. pylori in peptic ulcer patients.

To investigate the prevalence and the significance of Helicobacter pylori duodenal colonization, endoscopic duodenal biopsies were performed in 168 children with chronic abdominal pain, gastroesophageal reflux, gastrointestinal bleeding, and malabsorption syndrome. Helicobacter pylori infection was detected in 68 children (40.4%): in 31 of them H. pylori was present in the gastric antrum, and in 37 in the duodenum also. Duodenitis was observed in 25 children with duodenal H. pylori; gastric metaplasia in 3. Scanning electron microscopy revealed the presence of the micro-organism in 3/13 cases; the bacteria were located in the intercellular spaces and alterations of the epithelial surface were found. In conclusion, H. pylori gastritis in children is often associated with duodenal colonization which can cause duodenitis, and also without gastric metaplasia, which indicates a possible role of the micro-organism in the pathogenesis of the lesions.

Background: Although the OCN (omeprazole, clarithromycin and nitroimidazoles) short-term low-dose regimens are regarded as 'the standard' in the treatment of Helicobacter pylori infection, azithromycin is a new-generation, acid-stable macrolide which may prove particularly useful for a new short-term low-dose triple therapy regimen., Objective: To further improve OCN eradication treatments by reducing both the number of pills and the total cost., Methods: A new short-term low-dose triple therapy (LAM) using lansoprazole 30 mg once a day for 1 week, azithromycin 500 mg once a day for 3 days, and metronidazole 250 mg twice a day for the same 3 days, was administrated to 60 patients presenting with H. pylori-positive gastritis with or without peptic ulcer, and compared with the classic 'Bazzoli regimen' (OCT: omeprazole, clarithromycin, tinidazole) in 60 matched patients. H. pylori infection before and after therapy was evaluated by a rapid urease test, conventional histology and toluidine-stained semi-thin sections. Three biopsies from the corpus and three from the antrum were taken during endoscopical examination before and 7-8 weeks after discontinuation of the treatment. Patient compliance, drug tolerance and drug costs were also taken into consideration., Results: H. pylori infection was eradicated 7-8 weeks after treatment in 56 of the 60 patients in the LAM group (93.3%), and in 52 of the 57 patients in the OCT group who completed the treatment (91.2%), with no statistical difference. When gastric or duodenal ulceration was present, ulcer healing was observed in all cases., Conclusion: The new proposed short-term low-dose triple therapy (LAM) appears to be as effective as the OCT for the eradication of H. pylori infection. The new treatment, however, seems to have advantages in terms of drug tolerance, patient compliance and therapy cost.

Relatives of Helicobacter pylori positive patients show a higher incidence of Helicobacter pylori infection than the general population, probably due to relapses and/or reinfections between members of the family. Aim of this study was to evaluate the prevalence of the infection in 121 relatives of 41 children with Helicobacter pylori positive gastritis. Specific IgG antibodies (ELISA) were evaluated, and bacteria on gastric biopsy specimens were investigated by urease-rapid test, culture test and GIEMSA or acridine orange staining. Of the eighty-two relatives, 68% were antibody positive. Thirty-five agreed to undergo endoscopy. With the exception of one brother, all subjects (97%) were found to be infected by Helicobacter pylori. Two symptomatic relatives, with normal antibody titres, were submitted to endoscopy and found to be colonized by Helicobacter pylori. The present data confirm the high prevalence of infection within families and appear to demonstrate the usefulness of endoscopy for all subjects showing positive antibody titres as well as for symptomatic relatives, even if serologically negative, to confirm the presence of any pathological conditions and reduce the risk of relapses within families.

A 17-year-old boy who developed a symptomatic duodenal ulcer at 10 years of age with melena, and was then treated continuously for 6 years with ranitidine therapy that only partially controlled symptoms and peptic lesions, came to us with vomiting due to duodenal bulb stenosis and active ulcer. Four months of omeprazole (40 mg/die o.m.) did not modify the endoscopic picture. The diagnosis of H. pylori infection and its treatment with triple therapy led to the cure of both duodenal ulcer and bulbar stenosis. Afterwards he remained asymptomatic without any lesions or complications for 18 months. This case illustrates that H. pylori eradication: a) is able to cure refractory duodenal ulcer; b) resolves severe complications such as duodenal stenosis.

We evaluated in children with abdominal complaints the prevalence of Helicobacter pylori gastric and duodenal colonization and the histological features of gastric and duodenal mucosae. Fifty patients, aged 1-17 years, underwent upper endoscopy for recurrent abdominal pain, vomiting and/or gastrointestinal bleeding. With serological, bacteriological and/or histological methods twenty-eight children were demonstrated to be Helicobacter pylori-positive. No statistically significant differences were observed with regard to age, sex and indication to perform endoscopy. Eighty-two percent of Helicobacter pylori-positive patients had gastritis and/or duodenitis. The Helicobacter pylori-positive children had higher Helicobacter pylori specific IgG levels than the Helicobacter pylori-negative ones (p < 0.001). No statistically significant differences were found between Helicobacter pylori-positive and Helicobacter pylori-negative subjects, for gastrin and pepsinogen I. Since the frequency of Helicobacter pylori infection in children with gastrointestinal complaints is high, in patients undergoing upper endoscopy, the sistematical examination of bioptic samples for bacteriological and histologic procedures is of great importance.

OBJECTIVES: Host genetic factors, including the IL1 gene cluster, play a key role in determining the long-term outcome of Helicobacter pylori infection. The aim of the study was to investigate the relationship between selected IL1 loci polymorphisms and gastric cancer risk in an Italian population. METHODS: In a case-control study we compared the IL1B−31 and IL1B+3954 biallelic and IL1RN pentaallelic variable number of tandem repeats (VNTR) polymorphisms in 185 gastric cancer patients and 546 controls randomly sampled from the general population of an area at high gastric cancer risk (Tuscany, Central Italy). RESULTS: Genotype frequencies of the IL1B−31 T/C, IL1B+3954 C/T, and IL1RN polymorphisms among our population controls were in Hardy-Weinberg equilibrium. In multivariate analyses, no increase in gastric cancer risk was observed for the IL1B−31* C− and IL1B+3954* T− carriers; a significant 50% increase emerged for IL1RN*2 allele carriers (OR = 1.49; 95% CI: 1.01–2.21). Analyses based on combined genotypes showed also that the association with IL1RN*2 allele was limited to two-variant allele carriers who were also homozygous for the IL1B−31* T allele (OR = 2.23; 95% CI: 1.18–4.23) with a statistically significant interaction between these two genotypes ( p= 0.043). Haplotype analysis showed an increased risk for the haplotype IL1RN*2/ IL1B−31* T. CONCLUSIONS: Our results suggest that host genetic factors (such as the IL1RN and the IL1B−31 polymorphisms) interact in the complex process of gastric carcinogenesis in this high-risk Italian population. Overall, this effect appears more modest than previously reported in other populations, supporting the hypothesis that other still-to-be-defined factors are important in gastric carcinogenesis. These findings might be due to a haplotype effect. (Am J Gastroenterol 2005;100:1–8) [ABSTRACT FROM AUTHOR]

: To test the hypothesis that duodenal colonization represents the final crucial step in the development ofHelicobacter pylorirelated duodenal ulcer.: Patients with non-ulcer dyspepsia who had gastric colonization byH. pyloriwere included in the study. At baseline endoscopy, we evaluated the prevalence of duodenal colonization (culture, urease testing and histology), and cytotoxin-associated gene A status (polymerase chain reaction). No patients received eradication during 1 year follow-up. At this time, endoscopy was repeated and the incidence of duodenal ulcer was assessed.: Among 181 patients completing follow-up, 53 (29%) had duodenal colonization: 72% of them were cytotoxin-associated gene A positive, versus 37% patients without duodenal colonization (P < 0.001). Duodenal ulcer developed in 12 (22.6%) patients with duodenal colonization and in two (1.6%) without duodenal colonization (odds ratio for duodenal ulcer: 6.29, 95% confidence intervals 2.44–17.45). The incidence of duodenal ulcer was similar among cytotoxin-associated gene A positive and cytotoxin-associated gene A negative subjects with duodenal colonization: 21.05% versus 26.6%.: The assessment of duodenal colonization byH. pyloriin patients with non-ulcer dyspepsia is strongly predictive for the subsequent development of duodenal ulcer and may help to stratify patients at risk for this disease. [ABSTRACT FROM AUTHOR]

Presents a study which measured Helicobacter pylori antibodies in the serum of pediatric patients with food allergy, atopic disease and inflammatory bowel disease. Method; Results; Conclusion.

Background. It is uncertain whether Helicobacter pylori (H. pylori) is associated with ischemic syndromes and whether this association is mediated by the induction of atherosclerosis. In this study, we tested the hypothesis that atherosclerotic stroke shows a selective association with virulent H. pylori strains. Methods and Results. The seroprevalence of infection by H. pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, was assessed by enzyme-linked immunoadsorbent assay in 138 patients with large vessel stroke (group A), 61 with cardioembolic stroke (group B), and in 151 healthy controls. The three groups had a similar socioeconomic status. Serum levels of C-reactive protein (CRP) were also measured by enzyme immunoassay. The prevalence of infection was 71% in group A, 63.9% in group B, and 70.2% in controls (P = NS), whereas the prevalence of Cag-A positive strains was higher in group A than in group B patients (42.8% vs 19.7%; odds ratio [OR]: 3.04, 95% confidence intervals [CI6.49; P < 0.001) and controls (42.8% vs 17.9%; OR: 4.3, 95% CI, 2.12 to 8.64; P < 0.001), after adjusting for main cardiovascular risk factors and social class. A trend toward a difference in CRP (mg/dl, mean ± SD) was observed among patients with stroke, between CagA positive (2.00 ± 3.43) and CagA negative ones (1.31±1.72), (P = 0.072, Mann-Whitney U test). Conclusions. The association between H. pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H. pylori strains in patients with atherosclerotic stroke. [ABSTRACT FROM AUTHOR]