Indications for treatment of Helicobacter pylori infection: a systematic overview.

OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. DATA EXTRACTION: The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. DATA SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.     

Relationship of gastric metaplasia and age, sex, smoking and Helicobacter pylori infection in patients with duodenal ulcer and duodenitis

Gastric metaplasia is one of the factors in duodenal ulcer appearance. The aim of this study was to investigate the frequency of gastric metaplasia and its connection with age, sex, cigarette smoking and H. pylori infection. In the study 216 patients were included. There were 98 patients with duodenal ulcer, 60 with duodenitis, and 58 healthy control subjects. There was no statistically significant difference in gastric metaplasia frequency according to age and sex. Gastric metaplasia was statistically more significant in patients with duodenal ulcer (p < 0.01). In all the subjects cigarette smoking did not significantly influence gastric metaplasia. In smokers with duodenal ulcer, and those who besides duodenal ulcer and smoking had H. pylori infection gastric metaplasia was more frequent (p < 0.01). However, in patients with duodenal ulcer, there was no statistically significant difference of gastric metaplasia related to H. pylori presence. It may be suggested that H. pylori infection is not of indispensable significance for gastric metaplasia appearance.     

Helicobacter pylori associated gastric pathology.

Helicobacter pylori (HP), undoubtedly, the most common world-wide infection plays an important role in pathogenesis of peptic ulcer. Proof for a causal role for HP in peptic ulcer rests in two major points; 1) the majority of ulcer patients are HP infected and the prevalence of this infection for both gastric ulcer (GU) and duodenal ulcer (DU) is much higher than for gender- and age-adjusted controls and 2) the cure of HP infection dramatically reduces ulcer recurrence. Conclusions regarding the mechanisms by which HP induces peptic ulcer are restricted mainly to studies observing the consequences of its eradication by antibiotics combined with gastric inhibitors or bismuth agents. Several specific virulence factors such as cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) as well as other noxious substances including ammonia, lipopolysaccharide (endotoxin), platelet activating factor (PAF), nitric oxide (NO) and others have been implicated in gastritis and were found to be significantly more frequent in gastric cancer than in gender- and age-matched controls, especially in younger generation. Chronic inflammation, atrophic gastritis, intestinal metaplasia, impaired defense mechanisms combined with hypergastrinemia, deficiency of vitamin C in the stomach , excessive oxygen metabolites and epithelial cell proliferation have been associated with gastric cancer. This multi-step pathway originally proposed by Correa and his colleagues, long before the HP was discovered in the stomach, leads to cancer but may be reversed by eradication of HP. This is, however, a controversial issue because gastric atrophy and intestinal metaplasia may be also caused by other factors such as bile reflux, dietary irritants, and autoimmunity. The implication of HP in MALT-lymphoma is based on the observations that eradication of HP in early stage of low-grade of this tumor leads to complete remission. The significance of HP in non-ulcer dyspepsia remains questionable and requires further studies.     

Helicobacter pylori and Nonmalignant Diseases

The incidence of peptic ulcer disease has declined over the last few decades, particularly in Western populations, most likely as a result of the decrease in Helicobacter pylori infection and the widespread use of proton-pump inhibitors (PPI) in patients with dyspepsia. The hospital admission rate for uncomplicated duodenal and gastric ulcers has significantly decreased worldwide. In contrast, admissions for complicated ulcer disease, such as bleeding peptic ulcers and perforation, remained relatively stable. Prophylactic H.?pylori eradication was found to be associated with a reduced risk of both gastric and duodenal ulcers and their complications, including bleeding in chronic users of nonsteroidal anti-inflammatory drugs. The recent Helicobacter Eradication Relief of Dyspeptic Symptoms trial presented important data relating to symptoms and quality of life of H.?pylori-positive patients with functional dyspepsia (FD) and also demonstrated significant benefits from eradication compared with the control group. The new Asian consensus report on FD recommended that dyspepsia accompanied by H.?pylori infection should be considered a separate disease entity from FD and that H.?pylori infection should be eradicated before diagnosing FD. The association of H.?pylori with gastroesophageal reflux disease (GERD) is still controversial. Treatment for H.?pylori does not seem to increase GERD symptoms or reflux esophagitis. However, documented eradication of H.?pylori appears to significantly improve GERD symptoms. Additional long-term intervention studies are needed to provide more information on which to base clinical decisions.     

Eradication of Helicobacter pylori infection in the management of patients with dyspepsia and non-ulcer dyspepsia.

Although H. pylori infection has been recognized as a major etiological agent for the development of chronic active gastritis, duodenal ulcer and benign non-NSAID related gastric ulcer, its role in the development of symptoms in patients with dyspepsia remains uncertain. Results from population-based epidemiological studies have been conflicting regarding a causal link between H. pylori infection and dyspepsia. Abnormalities in gastric acid secretion may exist in some dyspeptic patients. Whether disordered gastric motility seen in dyspeptic patients is related to the infection is not clear based on the results in the literature. Numerous clinical trials have been undertaken to eradicate H. pylori infection and improve the symptoms in dyspeptic patients; however, the results have been discrepant between studies. Many published studies suffer from methodological problems that have made interpretation difficult. Large, well-conducted, randomized, placebo-controlled, clinical trials with long-term follow-up are needed to justify the beneficial effect of H. pylori eradication treatment in dyspeptic patients seen in some small studies. H. pylori eradication therapy is cost-effective in H. pylori-infected dyspeptic patients although this benefit may take a long time to accrue, especially in younger patients.     

The influence of cholecystokinin on gastric myoelectrical activity in duodenal ulcer following Helicobacter pylori eradication--an electrogastrographic study.

Cholecystokinin (CCK) plays an important role in the regulation of postprandial gastric motor activity which was found to be abnormal in duodenal ulcer patients. This study was designed to compare the influence of CCK on gastric myoelectrical function in duodenal ulcer patients and healthy controls. Fifteen patients with active duodenal ulcer and Helicobacterpylori (H. pylori) infection and 15 healthy controls were included into this study. Electrogastrography (EGG) was performed before and 4 weeks after the eradication of H. pylori in ulcer patients and in healthy controls. We compared EGG parameters in the fasting and postprandial period and during intravenous infusion of caerulein, an analog of CCK with or without addition of loxiglumide, a specific CCK-1 receptor antagonist. The amplitude of fasting EGG in duodenal ulcer patients was similar to that in control subjects and was not affected by H. pylori eradication. In contrast, the amplitude of postprandial EGG was markedly increased in duodenal ulcer patients when compared to that in healthy controls and it was significantly reduced following the eradication of H. pylori. The blockade of CCK-1 receptors with loxiglumide in healthy controls or H. pylori eradicated ulcer patients significantly enhanced postprandial EGG amplitude almost to the level observed in the infected duodenal ulcer patients, but failed to affect this amplitude in ulcer patients. Exogenous caerulein, an analog of CCK, failed to affect EGG amplitude in duodenal ulcer patients with H. pylori infection, but it reduced significantly EGG amplitude in these patients after H. pylori eradication and in control subjects. This inhibitory effect of caerulein in H. pylori negative ulcer patients and healthy controls was abolished by the addition of loxiglumide. Ulcer patients showed significant dysrhythmia with tachygastria up to 20% of the recording time both under basal conditions and postprandially and H. pylori eradication was followed by a significant decrease in tachygastria to about 5%, the value being similar to that in healthy controls. We conclude that the amplitude and frequency of gastric myoelectrical activity are enhanced in duodenal ulcer patients and impaired in response to CCK but these changes can be normalized by successful H. pylori eradication.     

Immunoblotting for the serodiagnosis of Helicobacter pylori infection in Brazilian patients with and without gastric carcinoma

We evaluated the performance of a commercial immunoblotting in the serodiagnosis of Helicobacter pylori infection in Brazilian patients. The presence of anti-H. pylori antibodies was also investigated in a group of 20 duodenal ulcer patients after successful treatment. One hundred and ninety one patients were studied. Among the 164 infected patients, 46 had gastric carcinoma. The duodenal ulcer patients were treated with antimicrobial drugs and the eradication of the microorganism was confirmed in all of them one month after the end of the treatment by the 13C-urea breath test. Sera were assayed for H. pylori antibodies using the Helicoblot 2.0 (Genelabs Diagnostics, Singapore). The sensitivity, specificity, positive, and negative predictive values of the test were 93.9%, 92.6%, 98.7%, and 71.4%, respectively. The sensitivity of the test was similar in patients with (93.5%) and without (95.7%) gastric carcinoma. Twenty-four months after the end of the treatment, the band of 116 kDa was still detected in one of the patients. In conclusion, the Helicoblot 2.0 is an accurate test to diagnose H. pylori infection and although it can not be employed to monitor the bacterium eradication, it may be useful for diagnosing past infection, especially in gastric carcinoma patients.     

Acid, helicobacter and immunity: a new paradigm for oesophagogastric cancer.

Epidemiological evidence has clearly shown a highly significant relationship between Helicobacter pylori infection and the development of duodenal ulcer and distal gastric adenocarcinoma. Despite H. pylori being a common aetiological factor for both disorders, the two disease phenotypes are virtually mutually exclusive. This indicates that the host response to infection has a pivotal role in determining outcome; these disease phenotypes relate to the effect of infection on gastric acid secretion, duodenal ulcer being closely related to sustained acid secretion whereas gastric cancer follows gastric atrophy and impaired gastric acid secretion. Cancer at the oesophageal junction and that associated with Barrett's oesophagus is now the most rapidly increasing tumour in the gastrointestinal tract. The challenge for the next millennium, therefore, is to try and develop methods for identifying patients at risk of developing oesophagogastric cancer. A common feature in the pathogenesis of both gastric and oesophageal adenocarcinoma is inflammation presenting clinically as gastritis and oesophagitis. The pathway from gastritis to gastric atrophy, dysplasia and carcinoma is thought to be a multi-step process, probably triggered by free radicals within the gastric epithelium and increased exposure to luminal carcinogens. However, it has been unclear as to which aspect of the host response determines whether an individual will move along the neoplasia pathway. Recent work has shown that qualitative aspects of the immune environment in the stomach may account for a substantial part of the phenotypic divergence following H. pylori infection. Interleukin-1 beta polymorphisms relate closely to the propensity for an individual to develop distal gastric cancer and maybe useful for predicting risk in family members. In Barrett's oesophagus, we have recently shown that the immune environment may also be important in determining whether an individual will develop cancer. Although we did not find that Barrett's oesophagus was a profoundly inflammatory condition (unlike esophagitis in the squamous epithelium), where there was evidence of inflammation it was qualitatively different from that of oesophagitis in that a Th-2 response with increased expression of IL-4 predominated in Barrett's, whereas a Th-1 proinflammatory response characterised oesophagitis in squamous epithelium. It seems likely that the specific immune environment within Barrett's metaplasia may be an important driver towards dysplasia and carcinoma. Thus, the immune environment in the stomach and esophagus may be critical in determining whether an individual is at risk of developing neoplastic complications of H. pylori infection and gastroesophageal reflux. Identification of the genetic factors which underpin these responses may ultimately result in development of methods to identify individuals at high risk.     

Helicobacter pylori infection as a cause of gastritis,duodenal ulcer,gastric cancer and nonulcer dyspepsia: a systematic overview.

OBJECTIVE: To evaluate current evidence for a causal relation between Helicobacter pylori infection and gastritis, duodenal ulcer, gastric cancer and nonulcer dyspepsia. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori, gastritis, duodenal ulcer, gastric cancer, dyspepsia and clinical trial; abstracts were excluded. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: Original studies with at least 25 patients, case reports and reviews that examined the relation between H. pylori and the four gastrointestinal disorders; 350 articles were on gastritis, 122 on duodenal ulcer, 44 on gastric cancer and 96 on nonulcer dyspepsia. DATA EXTRACTION: The quality of the studies was rated independently on a four-point scale. The strength of the evidence was assessed using a six-point scale for each of the eight established guidelines for determining a causal relation. DATA SYNTHESIS: There was conclusive evidence of a causal relation between H. pylori infection and histologic gastritis. Koch''s postulates for the identification of a microorganism as the causative agent of a disease were fulfilled for H. pylori as a causative agent of gastritis. There was strong evidence that H. pylori is the main cause of duodenal ulcers not induced by nonsteroidal anti-inflammatory drugs, but all of Koch''s postulates were not fulfilled. There was moderate epidemiologic evidence of an association between chronic H. pylori infection and gastric cancer. There was a lack of convincing evidence of a causal association between H. pylori and nonulcer dyspepsia. CONCLUSIONS: The evidence supports a strong causal relation between H. pylori infection and gastritis and duodenal ulcer and a moderate relation between such infection and gastric cancer. Further studies are needed to clarify the role of H. pylori in these disorders. Thus far, there is no evidence of a causal relation between H. pylori and nonulcer dyspepsia.     

Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview.

Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.     

Effect of Helicobacter pylori eradication on extent of duodenal gastric metaplasia and grade of gastritis

The extent of the regression of duodenal gastric metaplasia (DGM) after the eradication of Helicobacter pylori infection is controversial. Therefore, we decided to assess the degree of DGM before, sex weeks and one year after H. pylori eradication. 105 consecutive Helicobacter pylori positive patients with endoscopically proven duodenal ulcer, with DGM and Helicobacter pylori infection were recruited for this study. The diagnosis of Helicobacter pylori infection was based on CLO-test and histology, and DGM was assessed on four bulb biopsies taken before, sex weeks and one year after Helicobacter pylori eradication. Histological assessment of Helicobacter pylori associated gastritis was performed according to the Sydney classification. Follow up study on 98 patients before, six weeks and one year after the eradication of Helicobacter pylori showed that the mean extent of DGM did not change significantly after eradication and did not differ when compared with 14 patients with persisting infection. Our results show that the inflammatory process related to Helicobacter pylori does not play the main role in the development of DGM.     

Helicobacter pylori and Non-malignant Diseases

It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.     

Eradication of Helicobacter pylori does not reduce the incidence of gastroduodenal ulcers in patients on long-term NSAID treatment: double-blind, randomized, placebo-controlled trial

BACKGROUND: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results. OBJECTIVE: To investigate whether H. pylori eradication in patients on long-term NSAIDs reduces the incidence of gastroduodenal ulcers. METHODS: Patients on long-term NSAID treatment and who are H. pylori positive on serologic testing, were randomly assigned to either H. pylori eradication (omeprazole, amoxicillin, and clarithromycin) or placebo. Primary endpoint was the presence of endoscopic gastric or duodenal ulcers 3 months after randomization. RESULTS: One hundred sixty-five (48%) of a total of 347 patients were on gastroprotective medication. At endoscopy, gastroduodenal ulcers were diagnosed in 6 (4%) and 8 (5%) patients in the eradication and placebo group, respectively (p = .65). During follow-up of 12 months, no symptomatic ulcers or ulcer complications developed. No significant differences were found in the development of gastroduodenal erosions, dyspepsia, or in quality of life. CONCLUSION: H. pylori eradication therapy in patients on long-term NSAID treatment had no beneficial effect on the occurrence of ulcers, erosions, or dyspepsia. Ulcer rates in both study arms are remarkably low, in both patients with and without gastroprotective therapy.     

Effect of Helicobacter pylori eradication on peptic ulcer disease complicated with outlet obstruction

Background. At present, the prevalence of Helicobacter pylori ( H. pylori ) in complicated peptic ulcer and the effect of H. pylori eradication on complicated peptic ulcer have not been fully established. In this study, we report the prevalence of H. pylori in peptic ulcer patients complicated with gastric outlet obstruction, effectiveness of oral eradication therapy on these patients, and their long-term follow up.
Patients and Methods. Ten consecutive patients presenting with clinically and endoscopically significant obstructed peptic ulcers were included in this study. During each endoscopy, seven gastric biopsy specimens were obtained and analyzed for H. pylori colonization.
Results. The antral mucosal biopsy specimens were positive for H. pylori in nine patients. H. pylori infection was eradicated and complete ulcer healing was observed in all patients. The mean follow-up period was 14 (7–24) months. One patient had duodenal perforation and underwent surgical intervention following medical treatment, despite the eradication of H. pylori. Ulcer recurrence was noted in two (22.2%) of nine patients, and in one of them the recurrent ulcer was complicated with obstruction (11.1%). The mean time to ulcer recurrence was 17 months (range, 10–24 months). The biopsies and CLOtests were H. pylori negative at the time of ulcer or erosion recurrence in two patients.
Conclusion. We suggest that H. pylori eradication may improve the resolution in obstructive ulcer cases with colonization.     

Occurrence of Campylobacter pylori in gastric mucosa and selected parameters of cell-mediated immunity in patients with duodenal ulcer and individuals with non-ulcerative dyspepsia]

The study was aimed at investigating a relationship between Campylobacter pylori infection in the gastric mucosa and selected parameters of cell-mediated immunity in patients with duodenal ulcer and the individuals with non-ulcerative dyspepsia. A relationship between Campylobacter pylori and gastritis has also been studied. Endoscopic and immunological tests were carried out in the group of 45 patients, including 14 patients with duodenal ulcer and 29 with non-ulcerative dyspepsia. Specimens of gastric mucosa were collected endoscopically for histological and bacteriological examinations. Immunological tests included an assessment of the number of lymphocytes T (and their subpopulations) forming active rosettes (ARFC); total - (TRFC) and theophylline-resistant in active rosettes fraction (ARFC-TR); total (TRFC-TR) and theophylline-sensitive lymphocytes in both fractions (ARFC-TS and TRFC-TS) in 1 mm3 of the peripheral blood. Results suggest, that there is correlation between an infection of the gastric mucosa by Campylobacter pylori and duodenal ulcer and gastritis. No correlation between the infection by Campylobacter pylori and examined parameters of immunity in both patients with duodenal ulcer and non-ulcerative dyspepsia was found.     

Genetic factors in the development of gastric precancerous lesions--a role of Helicobacter pylori ?

Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric precancerous alterations. There is a well known predisposition to gastric cancer and the risk of developing it is greater in relatives of patients with familial cases of this malignancy. The aim of this study was to determine the prevalence of gastric precancerous lesions (atrophy and intestinal metaplasia) and their association with Hp infection in first-degree relatives in patients with noncardia gastric cancer. METHODS: Hp status and gastric histology assessed by upper gastrointestinal endoscopy, biopsies from the antral and body region, the rapid urease test and staining for Hp, inflammation, activity, atrophy and intestinal metaplasia (prevalence and grading) were studied in 108 first-degree relatives of patients with noncardia gastric cancer and compared with 73 controls with mild non-ulcer dyspepsia who had no cancer relatives and were examined in the same way. RESULTS: subjects with and without cancer relatives had a similar prevalence of Hp infection (49 vs. 47%). Endoscopy revealed a few asymptomatic duodenal ulcers and small hiatus hernias in Hp positive subjects of both groups. Hp positive relatives of gastric cancer had a markedly higher prevalence of atrophy than those with Hp negativity without cancer relatives (29 vs. 9%) and those with Hp negativity and cancer relatives (29 vs. 3%. Prevalence of intestinal metaplasia was also higher in those with Hp positivity and cancer relatives than in those without cancer relatives (15 vs. 5% and was not present in Hp negative subjects with cancer relatives. Inflammation and activity showed similar scores in subjects with and without cancer relatives with higher scores in both Hp positive groups. The prevalence of precancerous lesions in the relatives of gastric cancer was nearly always confined to those with Hp positivity. One year after eradication the prevalence of atrophy in cancer relatives decreased from 29 to 14%; prevalence of intestinal metaplasia remained without substantial changes. Scores for inflammation and activity were also lower after eradication. CONCLUSIONS: First-degree relatives of patients with gastric cancer have an increased prevalence of gastric precancerous abnormalities which are strongly confined to those with Hp infection. Eradication of Hp in these subjects with cancer relatives reduces the prevalence of precancerous lesions (atrophy) and grades of inflammation and activity. In view of these results, eradication of Hp should be offered to such subjects.     

Helicobacter pylori and hormones.

Helicobacter pylori affects gastric acid secretion via several mechanisms. One of these is by changing gastric regulatory physiology. The infection elevates plasma gastrin levels and decreases gastric mucosal expression of the inhibitory peptide somatostatin. These changes may be due to products of H. pylori itself or inflammatory cytokines released in H. pylori infection: acid secretion is inhibited less by a low intra-gastric pH, infusions of cholecystokinin and gastric distention in infected persons. Eradication of H. pylori rapidly decreases basal acid secretion and gastrin-releasing, peptide-stimulated acid secretion. There are now reports that maximally-stimulated acid secretion, a measure of the parietal cell mass, falls significantly six and 12 months after eradication of H. pylori from duodenal ulcer patients. This might be due to withdrawal of the trophic effect of gastrin. However H. pylori can also decrease gastric acid secretion, both through the mechanisms described in Dr. Cave''s paper and by causing gastric mucosal atrophy with loss of parietal cells. The net effect on acid presumably depends on which mechanism predominates. The processes involved may be crucial determinants of clinical outcome. For example, infection with little atrophy and high acid secretion is associated with duodenal ulcers, while infection with atrophy and low acid secretion increases the risk of gastric cancer of the intestinal-type.     

Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein

BACKGROUND: Helicobacer pylori infection is a major gastric cancer risk factor. Deficient DNA mismatch repair (MMR) caused by H. pylori may underlie microsatellite instability (MSI) in the gastric epithelium and may represent a major mechanism of mutation accumulation in the gastric mucosa during the early stages of H. pylori-associated gastric carcinogenesis. In this study, we examined the expression of DNA MMR protein (hMLH1 and hMSH2) in patients with chronic H. pylori infection before and after eradication of the infection. MATERIALS AND METHODS: Gastric tissue samples were collected from 60 patients with H. pylori gastritis and peptic ulcer disease before and after eradication of the infection. The DNA MMR protein expression (hMLH1 and hMSH2) was determined by immunohistochemical staining in 60 patients before and after H. pylori eradication. The percentage of epithelial cell nuclei and intensity of staining were then compared in gastric biopsies before and after eradication. RESULTS: The percentage of hMLH1 (76.60 +/- 20.27, 84.82 +/- 12.73, p=.01) and hMSH2 (82.36 +/- 12.86, 88.11 +/- 9.27, p<.05) positive epithelial cells significantly increased in 53 patients who became H. pylori-negative after eradication therapy. However, the intensity of hMLH1 and hMSH2 staining was not significantly different. In those 7 patients, who did not respond to the eradication therapy and were still H. pylori-positive, the percent positivity and intensity of hMLH1 and hMSH2 staining did not change. CONCLUSIONS: The expression of DNA MMR proteins increased in the gastric mucosa after H. pylori eradication, indicating that H. pylori gastritis may be associated with a reduced DNA MMR system during infection. The effect of H. pylori infection on MMR protein expression appears to be at least partially reversible after H. pylori eradication. These data suggest that H. pylori gastritis might lead to a deficiency of DNA MMR in gastric epithelium that may increase the risk of mutation accumulation in the gastric mucosa cells during chronic H. pylori infection.     

Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding

AIM: To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long-term study including more than 400 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. H. pylori infection was confirmed by rapid urease test, histology or (13)C-urea breath test. Several eradication regimens were used. Ranitidine 150 mg was administered daily until eradication was confirmed by breath test 8 weeks after completing eradication therapy. Patients with therapy failure received a second or third course of therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy, and were controlled yearly with a repeated breath test. RESULTS: Four hundred and twenty-two patients were followed up for at least 12 months, with a total of 906 patient-years of follow up. Mean age was 59 years, and 35% were previous nonsteroidal anti-inflammatory drug (NSAID) users. Sixty-nine percent had duodenal, 24% gastric, and 7% pyloric ulcer. Recurrence of bleeding was demonstrated in two patients at 1 year (incidence: 0.22% per patient-year of follow up), which occurred after NSAID use in both cases. CONCLUSION: Peptic ulcer rebleeding does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved.