Effect of Helicobacter pylori eradication on intestinal metaplasia and gastric epithelium proliferation

Gastric epithelial turnover increase in Helicobacter pylori infection has been demonstrated by interventional and non interventional methods for proliferating cell detection. We have observed a progressive hyperproliferation with the progression of Helicobacter pylori-induced mucosal lesions until the development of intestinal metaplasia. A similar result has been reported in other studies in the succession from normal mucosa to gastric carcinoma even if interventional techniques show less conspicuous differences in comparison to non interventional ones, which give an overestimated picture of proliferation. Later studies show that Helicobacter pylori-related hyperproliferation reverses after eradication. We have observed that this reversibility does not occur in areas of intestinal metaplasia, where the oncoprotein ras p21, involved in early gastric carcinogenesis, is expressed. This finding agrees with that demonstrating that hyperproliferation in intestinal metaplasia or gastric cancer is not affected by Helicobacter pylori. Other oncogenetic changes in intestinal metaplasia (i.e., p53 mutation) may further explain the persistently modified proliferative pattern of the epithelium. Recent studies suggest a lack of reversibility of intestinal metaplasia after Helicobacter pylori eradication, but this problem remains controversial. Our experience suggests that the persistence of the bacterium may increase the extent of this lesion. In conclusion the development of intestinal metaplasia is associated with an impaired regulation of gastric epithelial proliferation. Nevertheless, from the biological point of view, the progression towards carcinoma requires further DNA changes. Moreover, many questions need to be answered in order to establish clear guidelines for the clinical management.     

Circadian gastric acidity in Helicobacter pylori positive ulcer patients with and without gastric metaplasia in the duodenum

BACKGROUND: The presence of gastric metaplasia allows helicobacter pylori to colonise the duodenum and this condition is thought to be acquired as a response to acid hypersecretion. This functional disorder, however, is present only in a subgroup of duodenal ulcer patients and, in addition, surface gastric metaplasia has been frequently found in the proximal duodenum of normal subjects and patients with non-ulcer dyspepsia, who cannot be certainly considered as acid hypersecretors. AIMS: To clarify the role of acid in inducing gastric type epithelium in the duodenum. This study aimed at assessing whether the pattern of circadian gastric acidity differs between H pylori positive duodenal ulcer patients with and without duodenal gastric metaplasia. PATIENTS: Seventy one patients with duodenal ulcer confirmed by endoscopy and who were found to be positive for H pylori infection by histology on antrum biopsy specimens were enrolled into this study. METHODS: Gastric type epithelium in the duodenum was found in 49 of 71 ulcer patients (69%). Continuous 24 hour gastric pH metry was performed in 50 healthy subjects and in the two subgroups of duodenal ulcer patients with and without gastric metaplasia in the duodenum. Gastric acidity was calculated for 24 hours (1700-1659), night (2000-0759) and day-time (0800-1959). RESULTS: Ulcer patients without gastric metaplasia showed a significantly higher gastric acidity (p < 0.001) than controls for every time interval considered, while the ulcer subgroup with gastric metaplasia was more acid than healthy subjects (p < 0.001) during the whole 24 hour period and the daytime. There was no difference between the two subgroups of duodenal ulcer patients with and without gastric metaplasia during the various time segments analysed. CONCLUSION: The findings confirm that the circadian gastric acidity of duodenal ulcer patients is higher than that of controls. As there is no difference in gastric pH between duodenal ulcer patients with and without gastric metaplasia, gastric hyperacidity is not specific to patients with duodenal gastric metaplasia. It is probable that this histological change is a non-specific response to mucosal injury resulting from various factors and not exclusively to acid.     

Comparative effect of lansoprazole/amoxicillin with omeprazole/amoxicillin for the eradication of Helicobacter pylori in patients with duodenal ulcer

Lansoprazole, a potent antisecretory drug, possesses on an equimolar basis a 4-fold higher in vitro anti-Helicobacter pylori activity than omeprazole. In a prospective randomized study we compared lansoprazole 30 mg b.i.d. and amoxicillin 1 g b.i.d. with omeprazole 40 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days followed by lansoprazole 30 mg q.d. or omeprazole 20 mg q.d. for 14 additional days in 50 H. pylori positive duodenal ulcer patients (14f, 36m, age 27-83 [mean 43] years). H. pylori infection was diagnosed by histology (3 antral biopsies and 2 from gastric body, H & E- and Giemsa stain), rapid urease test (CLO) and culture in 39 patients, or by histology and rapid urease test in 11 patients. Control endoscopy was performed 4-6 weeks after the end of treatment. For eradication, a negative result in all 3 diagnostic modalities was required. The eradication rate was 43% (9/21 patients) in both treatment groups. 8 patients were lost to follow-up. The ulcer healing rate was 100% in both groups. Nonsmokers had a significantly higher (p = 0.026) eradication rate than smokers. No relevant adverse effects of the therapy occurred. 24 patients with persistent H. pylori infection were subsequently treated with lansoprazole 60 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days. Eradication was achieved in 5/22 (23%) patients (3/14 smokers, 2/8 nonsmokers), while 2 patients were lost to follow-up. 17 patients with persistent H. pylori infection after the second treatment received quadruple therapy consisting of metronidazole 500 mg t.i.d., tetracycline 500 mg q.i.d. bismuth-subcitrate 120 mg q.i.d. and lansoprazole 30 mg for 10 days. H. pylori eradication was achieved in 12/15 patients (80%). In conclusion, lansoprazole plus amoxicillin was equal to omeprazole plus amoxicillin in the treatment of H. pylori infected duodenal ulcer patients. Patients with eradication failure after dual therapy were successfully treated by quadruple therapy. In contrast, high dose lansoprazole and amoxicillin therapy was effective in only 23% of patients with persistent infection after standard dual therapy.     

Is duodenal gastric metaplasia a consequence of Helicobacter pylori infection in children?

BACKGROUND: Duodenal gastric metaplasia (DGM) is commonly found in association with Helicobacter pylori (Hp)-associated gastritis in adults. DGM is also considered a risk factor for duodenal ulcer development. The prevalence of DGM in children and its association with gastritis, duodenitis, or the presence of Hp organisms is not clear. We investigated the prevalence of DGM in children and explore its association with several possible risk factors, including age, gender, gastritis, duodenitis, or Hp presence in the gastric antrum. METHODS: A retrospective analysis of 173 upper endoscopy procedures performed between 1993 and 1995 at Cabell Huntington Hospital, Huntington, WV, was done. Gastric and duodenal biopsies were stained with Giemsa for Hp detection, periodic acid-Schiff for DGM, and hematoxylin and eosin for histologic assessment. Gastric mucosal inflammation was graded according to Sydney criteria. RESULTS: Duodenal gastric metaplasia was identified in 23 of 173 (13%) patients. Duodenitis but not age, gender, gastritis, or the presence of Hp in the gastric antrum was associated with DGM development. In 4 of 23 DGM foci, Hp was identified. CONCLUSIONS: In children, DGM is not the consequence of Hp infection.     

Helicobacter pylori infection in patients with chronic pancreatitis and duodenal ulcer

BACKGROUND: The prevalence of duodenal ulcer is high in patients with chronic pancreatitis. Patients with simple duodenal ulcer without chronic pancreatitis are mostly Helicobacter pylori-infected, and the prevalence of IgG seropositivity is > 95%. The prevalence of H. pylori infection in patients with chronic pancreatitis is not known. METHODS: IgG antibodies against H. pylori were measured in a cross-sectional survey of consecutive patients who had their exocrine pancreas function examined with a Lundh meal test in the period 1988-95 and in a control group of patients with simple duodenal ulcer. RESULTS: Twenty-seven per cent of the patients with chronic pancreatitis had duodenal ulcer during the observation period. The prevalence of IgG antibodies against H. pylori was 22% in patients with chronic pancreatitis without duodenal ulcer as compared with 27% with non-organic abdominal pain. The prevalence of IgG antibodies against H. pylori was 60% in patients with chronic pancreatitis complicated by duodenal ulcer as compared with 86% in controls with simple duodenal ulcer. CONCLUSIONS: H. pylori infection contributes but may not be the only cause of duodenal ulcer in patients with chronic pancreatitis.     

Cost-effectiveness analysis of the eradication of Helicobacter pylori as treatment for duodenal ulcer

OBJECTIVE: To assess the cost-effectiveness of H. pylori eradication in patients with duodenal ulcer in Spain. METHODS: A decision model was used to compare the cost per cured patient and the cost per patient without recurrence in one year for four treatment strategies: 1) intermittent antisecretory therapy, 2) initial antisecretory therapy and H. pylori eradication if ulcer recurrence, 3) initial H. pylori eradication with antibiotics and antisecretory drugs, 4) antisecretory therapy followed by continuous maintenance therapy with ranitidine. Clinical variables were obtained from published studies made in Spain. RESULTS: Initial H. pylori eradication is the cheapest strategy (74,702-82,028 ptas per cured patient) and the most effective (83.3-85.2% patients without recurrence in one year). Intermittent antisecretory therapy is one of the most expensive (94,891-105,324 ptas per cured patient) and the less effective (12% patients without recurrence in one year). CONCLUSION: Initial eradication of H. pylori is the treatment of choice in patients with duodenal ulcer.     

Sch?nlein-Henoch purpura in association with duodenal ulcer and gastric Helicobacter pylori infection

Associations between specific foot-care behaviors and foot lesions in patients with non-insulin-dependent diabetes mellitus were prospectively investigated. Data from a randomized controlled trial for preventing diabetic foot lesions were analyzed as a prospective cohort using logistic regression. Independent variables included foot-care behaviors, patient self-foot examination, going barefoot, availability of foot-care assistance, and visits to health-care providers. The dependent variable was a foot wound on each foot at follow-up. In the final multivariate model, patients who rarely lubricated their feet had an increased risk of foot lesions. Increasing patient use of emollients may be key to preventing foot lesions.     

Helicobacter pylori eradication as a surrogate marker for the reduction of duodenal ulcer recurrence

OBJECTIVES: An abundance of data exists documenting the association of H. pylori eradication with the reduction in duodenal ulcer recurrence. AIM: To evaluate the validity of using H. pylori eradication as a surrogate marker for the reduction in duodenal ulcer recurrence using rigorously controlled studies. METHODS: Three controlled clinical trials were conducted in patients with uncomplicated, active duodenal ulcers. Patients were treated with various combinations of omeprazole and amoxycillin. Ulcer healing and H. pylori eradication were assessed. For patients whose duodenal ulcer healed, duodenal ulcer recurrence was determined over a 6-month period in patients with H. pylori eradication and those remaining positive for H. pylori at least 4 weeks after treatment. To support the data obtained from these clinical trials, a search of the medical literature was conducted to identify additional human clinical trials in which duodenal ulcer recurrence rates were measured and categorized by H. pylori status at least 1 month post-treatment. RESULTS: In 11 controlled trials, the overall 6-18-month duodenal ulcer recurrence rate was 54% among patients remaining positive for H. pylori at least 4 weeks after treatment compared to 6% among patients with H. pylori eradication following treatment. This finding was corroborated by the uncontrolled trials, in which the duodenal ulcer recurrence rate was 64% among patients found to be H. pylori-positive and 6% for patients found to be H. pylori-negative at least 4 weeks after treatment. A time course of duodenal ulcer recurrence rates using pooled data from both controlled and uncontrolled studies demonstrated that duodenal ulcer recurrence rates for H. pylori-negative patients persisted for up to 4 years following treatment. Duodenal ulcer recurrence rates for H. pylori-positive patients increased for the first year, then levelled off. A comparison of the duodenal ulcer recurrence rates for different treatment regimens revealed that eradication regimens based on omeprazole plus antibiotics and bismuth plus antibiotics exhibited similar duodenal ulcer recurrence rates for H. pylori-positive and -negative patients. CONCLUSION: Regardless of treatment regimens, H. pylori eradication produced a consistent and significant reduction in duodenal ulcer recurrence. Therefore H. pylori eradication, 4 weeks post-therapy, can be used as a surrogate marker for reduced duodenal ulcer recurrence in investigational clinical trials.     

Does smoking influence the eradication of Helicobacter pylori and duodenal ulcer healing with different regimens?

To determine the effect of smoking on Helicobacter pylori eradication and ulcer healing, we investigated 232 patients with H. pylori-positive duodenal ulcer. Patients were given one of seven different treatment protocols and divided into three groups according to smoking habits. Group 1 (n = 128) consisted of non-smokers, group 2 (n = 65) of mild smokers (5-20 cigarettes/day) and group 3 (n = 39) of heavy smokers (> 20/day). The eradication of H. pylori and ulcer healing rate was controlled eight weeks later after ceasing the therapy. The overall eradication rate was 66% in all patients and 68%, 66%, 59% in each group, respectively. The eradication rates showed no statistical difference between groups. Complete ulcer healing was achieved in 84% of all patients and ulcer healing rate between groups did not show any significance (85%, 83% and 82% respectively). These results suggest that smoking status does not influence the eradication of H. pylori and duodenal ulcer healing rates at eight weeks in patients on different treatment schedules.     

Helicobacter pylori infection after gastrectomy and vagotomy in duodenal ulcer patients

The eradication of Helicobacter pylori (Hp) is known to reduce the recurrence rate of duodenal ulcer (DU) to similar extent as gastrectomy but it is not clear what is the prevalence of Hp in DU patients after surgical interventions such as gastrectomy or vagotomy. The purpose of this study was to evaluate the influence of gastrectomy or truncal vagotomy with pyloroplasty on the prevalence of Hp in 51 DU patients just before and 6-8 months after these procedures. Using C14-urea breath test (UTB), rapid CLO-test and histology of the biopsy samples of gastric mucosa obtained during gastroscopy, the Hp was detected in all DU subjects submitted to operation. Following distal gastric resection (antrectomy) with Billroth II anastomosis (N = 32) due to an ulcer resistance to conservative therapy, peptic ulceration was not observed during 6-8 months in any of the examined subjects and the Hp was only rarely observed (only in 3 out of 32 operated patients). Histologically, in antral biopsies taken prior to surgery, all DU patients presented chronic active gastritis. After the surgery, the absence of Hp was confirmed also by histology. Histological evaluation of gastrectomy stump biopsies revealed typical chronic gastritis with concomitant foveolar hyperplasia and focal gland dilation. Following selective vagotomy and pyloroplasty (N = 19), the scarring of duodenal bulb (without active ulcer) was seen in 4 out of 19 operated patients but the Hp was detected in all (100%) cases. Gastric biopsies prior and after vagotomy revealed chronic active gastritis associated with Hp infection. Basal plasma gastrin was reduced after gastrectomy by about 30% and basal and maximal pentagastrin-induced acid secretion was decreased by about 60% and 70%, respectively. Vagotomy did not reduce activity of the mucosal inflammation and the incidence of Hp. Basal plasma gastrin level was increased by about 60%, while basal and pentagastrin induced acid secretion was decreased by 25% and 40%, respectively. Because of the high ulcer recurrence rate after vagotomy as opposed to low recurrence after gastrectomy, it is reasonable to conclude that (1) the disappearance of Hp and reduction in plasma gastrin and gastric acid secretion were probably the major factors responsible for the high efficacy of gastrectomy in prevention of ulcer recurrence, (2) in non-complicated DU, gastric surgery should be avoided and replaced by conservative anti-Hp therapy involving both antisecretory or bismuth agents and antimicrobial drugs which should provide similar therapeutic effects as surgery and (3) vagotomy should be eliminated as the method of treatment of DU because of the high recurrence of peptic ulceration and the failure of this procedure to affect the Hp status.     

The impact of Helicobacter pylori eradication on peptic ulcer healing

OBJECTIVE: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status. METHODS: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients. RESULTS: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7, p < 0.01), duodenal ulcer 95% vs 76% (OR 5.6, p < 0.0001), and peptic ulcer 95% vs 76% (OR 6.6, p < 0.0001), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (< or = 6, 7-8, and 10-12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all p < 0.0001, Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94-96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7-20% improved healing rates, whereas patients becoming HP-negative did not profit. CONCLUSION: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.     

The role of Helicobacter pylori in the pathophysiology of duodenal ulcer disease and gastric cancer

Helicobacter pylori infection is now recognized to be an important acquired factor in the pathogenesis of duodenal ulcer disease. There is also an association between H pylori and the subsequent development of gastric cancer. The mechanism of the association between the infection and those disorders is incompletely understood but there is increasing evidence that H pylori-induced disturbances of gastric function play a pivotal role. In this article we review the role of H pylori infection in the pathophysiology of these important upper gastrointestinal diseases.     

Treatment of primary low-grade gastric lymphomas with eradication of Helicobacter pylori

There is evidence associating Helicobacter pylori (HP) with both mulosa-associated lymphoid tissue (MALT) and MALT-lymphoma. Recently, three studies including 65 patients have shown that the eradication of HP can lead to regression in about 60-70% of primary low-grade gastric B-cell MALT-lymphomas. Prolonged follow-up will be necessary to see whether these remissions are lasting, and whether eradication of HP in combination with conventional therapy is more effective than either of these treatments alone. Until then we recommend that HP is eradicated in these lymphomas before referral to standard treatment with chemotherapy and/or radiotherapy.     

Helicobacter pylori: 6-day triple therapy in duodenal ulcer

OBJECTIVES: To investigate the risk of lymphatic and haematopoietic malignancies in deck crew on tankers exposed to cargo vapours. METHODS: The study design was as a nested case-referent study in two cohorts of male Swedish seamen 20-64 years of age at the national census 1960 (n 13,449) and 1970 (n 11,290), respectively. Cases were detected by record linkage with the Swedish Cancer Register 1961-79 and 1971-87, respectively. For each case, three to five age matched referents from the population were selected. Exposure was assessed from data in the Swedish Registry of Seamen and from a register of Swedish ships. RESULTS: Seamen in the 1970 cohort, who had been exposed to cargo vapours for at least one month on chemical or product tankers, had an increased risk of lymphatic and haematopoietic malignancies (Mantel-Haenszel odds ratio (OR) 2.6, 95% confidence interval (95% CI) 1.1 to 5.9)) with a significant exposure-response relation (conditional logistic regression analysis, p = 0.04). The ORs were increased for both lymphoma (3.2), multiple myeloma (4.0), and leukaemia (1.6), but the increase was only significant for non-Hodgkin's lymphoma (OR 3.3, 95% CI 1.1 to 10.6). There were no significantly increased risks for the 1960 cohort or for seamen exposed only on crude oil tankers, but these groups had few exposed cases and low cumulative exposure to benzene and other light petroleum products. CONCLUSIONS: Seamen exposed to cargo vapours from gasoline and other light petroleum products on chemical or product tankers had an increased incidence of lymphatic and haematopoietic malignancies. One possible cause is exposure to benzene during loading, unloading, and tank cleaning operations.