Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori

Background and Aims: The results of a randomized controlled study and meta‐analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers. Methods: The subjects were 18 early‐stage gastric cancer specimens resected from 17 patients who had received successful eradication of H. pylori from February 1995 to March 2009. The control group consisted of 36 specimens from noneradicated patients with persistent H. pylori infection who were matched with the subjects in age, sex, and depth of invasion. Clinicopathological features and mucin phenotypes of gastric cancer were clinically and immunohistologically evaluated. Results: The average diameter of gastric cancer was smaller and Ki‐67 index was lower in the eradication group. The morphological distribution of depression types was significantly lower in the control group. Immunohistochemical phenotyping revealed that 72.2% of the lesions in the eradicated group were complete gastric type or gastric predominant mixed type, whereas the percentages of gastric type and intestinal type in the control group were similar. Conclusion: Our findings indicate that the clinicopathological characteristics of gastric cancers detected after H. pylori eradication are different from those of gastric cancers in patients with persistent H. pylori infection. H. pylori eradication may suppress intestinalization during the development of gastric cancer.     

Efficacy and safety of faropenem in eradication therapy of Helicobacter pylori

Aims: While triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is the standard therapy for Helicobacter pylori eradication, it is ineffective against clarithromycin‐resistant strains. To seek a better regimen for eradication therapy, we assessed the sensitivity of clinical strains seen in Japan to faropenem and then evaluated the efficacy and safety of eradication therapy containing this antibiotic. Methods: Minimum inhibitory concentrations (MICs) of faropenem were determined in 78 Japanese clinical H. pylori isolates using the agar dilution method. H. pylori‐positive patients were consecutively assigned to a 7‐day eradication therapy protocol with LAF (lansoprazole 60 mg/day, amoxicillin 2000 mg/day, and faropenem 600 mg/day), and then to a 14‐day protocol. The outcomes of the therapies were assessed by ¹³C‐urea breath tests. Results: All 78 strains showed MICs of faropenem that were equal to or less than 0.2 µg/mL. The eradication rates according to intention‐to‐treat analyses were 46.5% with the 7‐day therapy (n = 43) and 62.5% with the 14‐day therapy (n = 32). No special measures were required to treat the adverse events observed in approximately one‐third of the patients. Conclusions: Faropenem was found to have good antimicrobial action against H. pylori in vitro. The 14‐day LAF therapy successfully eradicated H. pylori in about two‐thirds of the patients although the incidence of adverse events was high.     

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis

Background

The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions.

Materials and Methods

PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses.

Results

Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81–0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17–1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69–0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30–2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15–1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37–2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47–1.70), Hp eradication had no advantage compared to placebo or no treatment.

Conclusions

Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.     

Impact of furazolidone-based quadruple therapy for eradication of Helicobacter pylori after previous treatment failures

Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third‐line (salvage) therapy. Methods. All patients with previous H. pylori treatment failure after a clarithromycin‐metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI‐B‐T‐M) three times a day (tid) for 1 week. In the case of treatment failure with this second‐line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI‐B‐T‐F) instead of metronidazole (sequential study design). Results. Eighteen consecutive patients were treated with PPI‐B‐T‐M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI‐B‐T‐F. Final cure of H. pylori with PPI‐B‐T‐F was achieved in 9/10 patients (90%) nonresponsive to PPI‐B‐T‐M. Conclusions. In the presence of metronidazole resistance, PPI‐B‐T‐M as a recommended second‐line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second‐line quadruple therapy may be best suited in case of a metronidazole‐free first line‐regimen (e.g. PPI‐clarithromycin‐amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI‐B‐T‐F combination does not have a cross‐resistance potential to metronidazole and is a promising salvage option after a failed PPI‐B‐T‐M regimen.     

Does Helicobacter pylori eradication affect symptoms in nonulcer dyspepsia: a 5-year follow-up study

The role of Helicobacter pylori infection in nonulcer dyspepsia remains controversial. To date studies exploring the effect of H. pylori eradication on symptoms have reported conflicting results. Randomised control trials employing validated outcome measures have also been difficult to interpret because of several important issues such as the large placebo response seen in patients with nonulcer dyspepsia and both the natural variability in symptoms and symptom severity with time. The association of symptom improvement with resolution of gastritis has meant that the length of follow up employed in most studies has been insufficient. We report the findings of a randomised placebo controlled trial (n = 100), using a validated symptom questionnaire and 5 year follow up to determine the effect of H. pylori eradication on symptoms in nonulcer dyspepsia. In all 64 that were reviewed at 5 years there was a significant difference between patients who were H. pylori negative and those who remained positive with regard to complete symptom resolution, consumption of relevant medications and peptic ulcer disease development, in favour of active treatment. There was a trend for gradual symptom improvement over time irrespective of H. pylori status, which may reflect the natural history of this condition. For those who remained symptomatic at 5 years, there was no difference in symptom severity based on H. pylori status. The findings of this study support the use of H. pylori eradication in symptomatic patients with nonulcer dyspepsia both to induce symptom resolution and to prevent disease progression.     

Effect of Helicobacter pylori Eradication on Incidence of Gastric Cancer in Human and Animal Models: Underlying Biochemical and Molecular Events

Background:  Gastric cancer remains one of the most common cancers worldwide. A strong association exists between Helicobacter pylori infection and the risk of developing noncardia gastric cancer. H. pylori eradication by antibiotic treatment is regarded as a primary chemoprevention strategy to reduce gastric cancer incidence.
Aim:  To analyze the efficacy of H. pylori eradication in preventing gastric cancer in human and animal models, and to discuss whether biochemical, genetic, and epigenetic changes associated with H. pylori infection are reversible after curing the infection.
Results:  Several intervention trials have indicated that in some patients, H. pylori eradication leads to regression and prevents the progression of precancerous lesions. The eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. A few recent intervention studies in Japan have demonstrated significant prophylactic effects of eradication therapy on the development of gastric cancer, suggesting the use of eradication therapy in high-risk populations as a gastric cancer reduction strategy. However, gastric cancer may still develop despite successful eradication therapy. Studies in animal models have confirmed the use of eradication therapy at an early point of infection to prevent gastric cancer development.
Conclusion:  H. pylori eradication may not completely abolish the risk of gastric cancer. However, eradication therapy may be used in high-risk populations to reduce gastric cancer incidence. It can reverse many biochemical, genetic, and epigenetic changes that H. pylori infection induces in the stomach.     

The effects of probiotics on PPI-triple therapy for Helicobacter pylori eradication

Background: This study was performed to evaluate whether the addition of probiotics to proton pump inhibitor (PPI)‐based triple therapy increases the likelihood of successful Helicobacter pylori eradication. Materials and Methods: Three hundred and forty‐seven H. pylori‐infected patients were randomized into a triple‐plus‐yogurt group (yogurt group, n = 168) or a triple‐only group (control group, n = 179). Triple therapy consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d. for 7 days. Yogurt group received triple therapy for 1 week and one bottle of Will yogurt per day for at 3 weeks, starting on the first day of triple therapy. Will yogurt (a Korean brand) contains Lactobacillus acidophilus HY2177, Lactobacillus casei HY2743, Bifidobacterium longum HY8001, and Streptococcus thermophilus B‐1. ¹³C‐urea breath test was performed at least 4 weeks after completion of triple therapy. Eradication rates, compliances, and adverse events were compared. Results: By intention‐to treat analysis the H. pylori eradication rates in the yogurt group 79.2% (133 of 168) was similar to that in the control group 72.1% (129 of 179) (p = .124). However, by per‐protocol (PP) analysis, the eradication rate in the yogurt group, 87.5% (133 of 152) was higher than that in the control group, 78.7% (129 of 164) (p = .037). Common adverse events were metallic taste (11.8%) and diarrhea (8.6%). The frequency of adverse effects in the yogurt group 41.1% (69/168) were higher than in the control group, 26.3% (47 of 179) (p = .003). However, most adverse events were mild to moderate in intensity, and the severities of adverse effects were similar in both groups (p = .401). Conclusions: The addition of Will yogurt to triple therapy did not reduce the side‐effects of triple therapy. But it increased the H. pylori eradication rate by PP analysis, encouraging more research in this field.     

Helicobacter pylori public health implications

Population Helicobacter pylori screening and treatment has the potential to dramatically reduce global gastric cancer mortality. There is overwhelming evidence that the infection is a major cause of distal gastric adenocarcinoma. There is also randomized controlled trial evidence that H. pylori eradication reverses or ameliorates histological changes in the gastric mucosa that are important in carcinogenesis. Preliminary randomized controlled trial data suggest that screening and treatment may reduce the risk of gastric cancer although the number of cancer cases was small. Population H. pylori screening and treatment will also reduce mortality from peptic ulcer complications and reduce the burden of dyspepsia in the community. The reduction in health service dyspepsia costs means that this could be the first programme to pay for itself. From a scientific perspective, we still have insufficient evidence to conclude the benefits of population H. pylori screening are greater than the possible harms and we need more randomized controlled trial data. From a public health perspective however, sometimes screening programmes are developed with imperfect information. The medical community should be consistent and if we are instituting other population screening programmes without randomized controlled trial evidence then H. pylori testing and treatment should also be considered.     

Low efficacy rate of moxifloxacin-containing Helicobacter pylori eradication treatment: in an observational study in a Turkish population

BACKGROUND: Standard triple therapy for Helicobacter pylori has an eradication rate of about 50% in Turkey. It may be due to an increased resistance of H. pylori to antibiotics. Therefore, we aimed to investigate the effectiveness of a new second-generation fluoroquinolone, moxifloxacin-containing triple therapy in H. pylori eradication. MATERIAL AND METHODS: This is an open-label, prospective, single-center, pilot study. We studied 71 dyspeptic patients infected with H. pylori diagnosed by both histology and rapid urease test. Out of 71 dyspeptic patients, 64 had non-ulcer dyspepsia and seven had peptic ulcer. Patients received pantoprazole (40 mg b.i.d.) plus moxifloxacin (400 mg/day) and amoxicillin (1000 mg b.i.d.) for 14 days. Eradication was assessed 4 weeks after completing the therapy by histology and rapid urease test. Per-protocol and intention-to-treat eradication rates were determined. RESULTS: The eradication rate was 42.2% for the intention-to-treat analysis and 47.6% for the per-protocol analysis. Of all patients included in the study, 29.5% had side-effects and only 2.8% of the patients discontinued the treatment because of side-effects. Most of the complications were mild and self-limiting. CONCLUSION: Triple therapy with pantoprazole, moxifloxacin, and amoxicillin for 14 days yielded unacceptably low eradication rates. However, using tests of susceptibility to antibiotics, further studies with larger sample sizes are needed to judge these eradication rates of moxifloxacin containing eradication treatment.     

Helicobacter pylori eradication therapy on histologic change in the distal esophagus

BACKGROUND: Although cases of reflux esophagitis (RE) developing after treatment to eradicate Helicobacter pylori have been discussed in some detail, no reports are available concerning the histologic examination of RE both before and after eradication therapy. MATERIALS AND METHODS: Sixty-one patients and 111 specimens were investigated using endoscopic and histologic techniques. The histologic findings including basal zone height, papillar height, Ki-67 labeling index, and COX-2 expression before and after treatment for H. pylori infection were compared with those in normal controls and patients with endoscopic RE. RESULTS: Twelve months after eradication therapy, the incidence of newly developed endoscopic RE was 20% (5/25). Basal zone height and papillar height had increased at 1 month, but had returned to pretreatment levels after 12 months of eradication therapy. The Ki-67 labeling index was significantly increased 1 and 12 months after eradication therapy compared to values before treatment. COX-2 expression gradually increased after the treatment. The phenomena linked to esophagitis appeared after eradication therapy. However, the severity and extent of these signs were not so high after the treatment of H. pylori than those in patients with overt reflux esophagitis. Focusing on the patients with hiatal hernia, papillar height and Ki-67 labeling index increased significantly after eradication therapy, values being almost the same as those in the patients with endoscopic RE. CONCLUSIONS: Hiatal hernia plays an important role in the possible occurrence of hidden RE after treatment for a H. pylori infection.     

Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate

Background: In the eradication of H. pylori infection, even today, the main international guidelines recommend the triple therapy as first‐line regimen, although its effectiveness is clearly decreasing. As second‐line treatment, the bismuth‐containing quadruple therapy is the most used regimen, although several other therapies are studied. The Italian guidelines recommend, alternatively, sequential therapy or triple therapy as first‐line treatment and levofloxacin‐containing triple therapy as second‐line regimen. We wanted to assess the overall eradication rate of Helicobacter pylori infection in two therapeutic rounds following the Italian guidelines in clinical practice. Materials and Methods: We treated 231 consecutive Helicobacter pylori‐positive patients by sequential therapy and we verified the eradication 8–10 weeks after treatment by stool antigen test. Patients positive for stool antigen test received levofloxacin‐containing triple therapy, as second‐line therapy, according to Italian Guidelines and they were again submitted to the fecal test 8–10 weeks after the end of treatment. Results: In the first‐line regimen, we obtained an eradication rate of 92.6%, in the second‐line of 75.0% and as cumulative result we achieved a 97.8% of eradication, in per‐protocol analysis. Conclusions: Sequential therapy as first‐line and levofloxacin‐containing triple therapy as second‐line represent a good combination to eradicate Helicobacter pylori infection in only two rounds.