Impact of Helicobacter pylori eradication on morphological changes in gastric mucosa

The purpose of the study was to examine gastric mucosal morphological changes in patients with gastroduodenal pathology after eradication therapy for Helicobacter pylori (H. pylori). A hundred and thirty-eight patients (40 females and 98 males) were examined. Of them, there were 122 patients with duodenal peptic ulcer, 8 with gastric peptic ulcer, 5 with erosive gastritis, 2 with chronic atrophic antral gastritis, and 1 with non-atrophic gastritis. Two months and a year after therapy, manifestations of gastric mucosal atrophy, the degree of inflammation, and its activity significantly diminished in patients with complete H. pylori eradication. Positive changes were observed mainly in the antral portion of the stomach. In patients with partial eradication, chronic inflammation and its activity became less. Two months and a year following therapy, positive changes in the gastric mucosa were absent in patients without H. pylori eradication.     

根除儿童口腔幽门螺杆菌预防胃内幽门螺杆菌感染的多中心研究

目的:探讨根除儿童口腔幽门螺杆菌（Hp）预防胃内Hp感染的可能性。方法:采用多中心前瞻随机研究,选取口腔Hp阳性但胃内Hp阴性的幼儿园儿童共计427例,随机分为使用“无幽梅”牙膏组与普通牙膏组,分别接受“无幽梅”牙膏和普通牙膏。疗程结束后,再次检测口腔Hp,将口腔Hp阳性及阴性患者各分为一组,1年后行C13呼气试验检查,分析两组患者胃内Hp感染情况。口腔Hp检测方法采用特异度及敏感度双高的套式PCR方法。结果:随访1年,口腔Hp阴性组胃内Hp感染率为0.51%,口腔Hp阳性组胃内Hp感染率为6.51%,两组统计差异具有显著性（P<0.01）。结论:儿童根除口腔Hp可以降低胃内Hp感染的发生。     

Helicobacter pylori infection and gastric carcinogenesis in rodent models

Helicobacter pylori infection is an important factor for gastric carcinogenesis in human. In carcinogen-treated Mongolian gerbils, H. pylori infection enhances stomach carcinogenesis, while infection alone induced severe hyperplasia called heterotopic proliferative glands. A high-salt diet or early acquisition of the bacteria exacerbates inflammation and carcinogenesis. Oxygen radical scavengers or anti-inflammatory chemicals as well as eradication of H. pylori are effective to prevent carcinogenesis. H. pylori-associated inflammation induces intestinal metaplasia and intestinalization of stomach cancers independently. It is necessary to control cancer development not only in H. pylori-positive cases but also in H. pylori-negative metaplastic gastritis.     

Helicobacter pylori regulates TLR4 and TLR9 during gastric carcinogenesis

Objective: To investigated the influence of H. pylori on TLR4 and TLR9 in gastric mucosa during gastric carcinogenesis. Methods: Gastric biopsy specimens were taken from 148 patients and divided into five groups, including normal group (n = 10), chronic superficial gastritis group (n = 35), atrophy/intestinal metaplasia group (n = 35), dysplasia group (n = 34) and gastric carcinoma group (n = 34). Immunohistochemistry was used to detect the expression of TLR4 and TLR9. Geimsa staining and rapid urea test were used for determine H. pylori infection. Results: TLR4 was detected in gastric epithelium and monocytes/macrophages in superficial gastritis, atrophy/intestinal metaplasia, dysplasia or carcinoma. TLR9 was mainly accentuated in monocytes/macrophages. TLR4 positive cells in epithelium and in monocytes/macrophages with H. pylori infection were much more than those without H. pylori infection. Similar results were also found in TLR9. When gastric epithelium was accompanied with H. pylori infection, TLR4 was significant higher in superficial gastritis and atrophy/intestinal metaplasia groups compared with dysplasia and carcinoma groups. When gastric epithelium was infected by H. pylori, TLR9 was significant higher in carcinoma group compared with superficial gastritis, atrophy/intestinal metaplasia and dysplasia. TLR4 and TLR9 show significant correlation with the severity of inflammation. Conclusions: H. pylori infection was associated with increased expression of TLR4 and TLR9 in gastric mucosa. In superficial gastritis and atrophy/intestinal metaplasia the inflammation was predominately mediated by TLR4, while in gastric cancer the inflammation was mainly mediated by TLR9.     

Epidemiology and role of Helicobacter pylori virulence factors in gastric cancer carcinogenesis

Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.     

Two- to four-year histological follow-up of gastric mucosa after Helicobacter pylori eradication.

In a 2- to 4-year prospective study, the reversibility of gastritis after Helicobacter pylori eradication was analysed. Sixty-three H. pylori-positive, chronic duodenal ulcer patients were studied after the successful eradication of bacteria in the period from 1990 to 1993. H. pylori eradication was obtained by triple antimicrobial regimens (colloidal bismuth subcitrate, amoxycillin, and metronidazole) applied for at least 14 days. The criteria for eradication were the absence of bacteria from two antral and two body of stomach biopsies stained with haematoxylin, eosin, and Warthin Starry, and a negative antral biopsy culture. The same diagnostic procedures were repeated, at regular follow-up endoscopies, each year for up to 4 years. Neutrophil-granulocyte infiltration of gastric mucosa disappeared in 2 months after bacterial eradication. Mononuclear cellular infiltration was disappearing with statistical significance up to the second year and normal mucosa was observed in the majority of patients in the fourth year of follow-up. Degeneratively changed lymphoid aggregates were also present in the fourth year in the antrum (12.5 per cent of patients) and in the body of stomach (14 per cent of patients). There was no significant change in antral intestinal metaplasia during the 4 years of follow-up. Antral atrophy declined significantly in the period from 1 to 3 years of follow-up. In conclusion, 3-4 years are needed for gastric mucosa to become normal after H. pylori eradication, although some residual lymphoid aggregates persist even after that period.     

Decreased gastric proliferation of foveolar epithelial cells after the eradication of Helicobacter pylori.

Increased epithelial cell proliferation is associated with an increased risk of gastric carcinoma. Helicobacter pylori infection is an established risk factor for gastric cancer and the organism has recently been classified as a group I carcinogen by an IARC working group. In this study, we describe differences in gastric epithelial cell proliferation between a H. pylori eradicated group (n = 21) and a not eradicated group (n = 8) after anti-H. pylori eradication therapy to show that increased cell proliferation is associated with H. pylori infection. H. pylori infection was determined by rapid urease test and immunohistochemical method with anti-H. pylori polyclonal antibody. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Ki-67 positive cells in H. pylori associated chronic active gastritis were observed in the glandular neck and the upper portion of foveolar epithelium. Patients who cleared their H. pylori infections showed a significant decrease of Ki-67 labeling index after therapy (0.73 +/- 0.10 vs. 0.48 +/- 0.08, p < 0.01). By contrast, Ki-67 labeling index before and after treatment in patients who remained positive for H. pylori showed no significant difference (0.78 +/- 0.08 vs 0.74 +/- 0.10, p > 0.05). These results indicate that H. pylori infection increases the proliferation of gastric foveolar epithelium, which is reduced by the eradication therapy. We suggest that anti-H. pylori eradication therapy can prevent mucosal cell proliferation to be closely associated with gastric carcinogenesis.     

The EPIYA-ABCC motif of Helicobacter pylori cagA gene and gastric carcinogenesis in Casablanca population

BackgroundH. pylori infection induce atrophic gastritis (AG) and intestinal metaplasia (IM) that can lead to gastric cancer (GC). The severity of gastric lesions is related to H. pylori genetic diversity. The oncogenic potential of H. pylori cagA virulence factor is linked to its high polymorphic EPIYA motifs.ObjectivesOur aim was to evaluate the association of EPIYA motifs with the risk of AG and IM in Casablanca population.MethodsA total of 210 patients suffering from gastric lesions (chronic gastritis, AG, and IM) was enrolled. H. pylori infection and the type of lesions were diagnosed by ureC PCR and histological examination, respectively. Detection of the cagA gene, and the type of EPIYA motifs, were carried out by PCRResultsThe prevalence of H. pylori and cagA gene was 95% and 37%, respectively. CagA-positive strains were associated with the risk of IM. The EPIYA motifs detected were: EPIYA-ABC (58%), EPIYA-ABCC (22%), and EPIYA-AB (20%). The EPIYA-ABCC motif was associated with the risk of IM (p-value = 0.007), compared to AG (p-value = 0.28).ConclusionThe EPIYA-ABCC motif might be a useful marker for the identification of patients at high risk of developing IM that can lead to GC.     

Helicobacter pylori and gastric carcinoma

A retrospective study was performed on gastric carcinomas to establish the prevalence of Helicobacter pylori infection in gastric epithelium adjacent to the tumour. A total of 105 carcinomas were studied. The overall prevalence of Helicobacter pylori infection was 59%. The prevalence in different age cohorts from patients with gastric carcinoma was compared with that in patients suffering from non-ulcer dyspepsia and, based on serological testing, with that in healthy blood donors. The presence of Helicobacter pylori in cancer patients aged 41-50 and 51-60 was significantly higher than in blood donors. No difference was seen in comparison with non-ulcer dyspepsia patients. The presence of Helicobacter pylori showed an inverse correlation with the extent of intestinal metaplasia. The intestinal type of carcinoma was associated with a higher bacterial load than the diffuse type. These data suggest that the presence of Helicobacter pylori in gastric mucosa could play a role in the pathogenesis of gastric carcinoma, especially in the young age group.     

Helicobacter pylori & gastric disease

Since the discovery of Helicobacter pylori(H. pylori), causal linkage between H. pylori infection and some of gastric disease has been generally accepted from the results of many studies. Indeed the usefulness of H. pylori eradication therapy for acute gastritis, peptic ulcer, gastric polyp and MALT lymphoma etc. has been reported. In the low grade MALT lymphoma, the regression rate by this therapy is about 70%. On the other hand, we should pay the caution to several adverse effects, such as drug resistance and GERD, of H. pylori eradication therapy. However, based on the several results of comparative studies between antibiotic therapy and the other one, the antibiotic therapy for peptic ulcer is only covered by national health insurance at present. The reversibility of gastric precancerous conditions such as mucosal atrophy, intestinal metaplasia and dysplasia by antibiotic therapy has been studied, but its significance is not clear yet. In animal experiment, H. pylori infection induced gastric adenocarcinoma in Mongolian Gerbils. However, this phenomenon is limited to this kind of animal only. To proof the causal link between H. pylori infection and genesis of gastric cancer in human being, clinical intervention trials are ongoing in the world. If these trials can clarify it, the H. pylori eradication therapy will be established as preventive measure for gastric carcinogenesis.     

Helicobacter pylori and gastric adenocarcinoma

Gastric cancer is the second most common cause of cancer death worldwide. A large body of evidence supports a causal role of Helicobacter pylori in the majority of gastric malignancies. Great strides have been made in understanding the pathogenesis of this relationship, but much remains to be learned. Moreover, because of the high prevalence of infection, the lack of definitive trials, and the challenges of H. pylori treatment, there remains no consensus on the role of routine screening and treatment of this infection to prevent cancer. This article reviews the current knowledge on H. pylori and gastric cancer and presents some of the clinical and public health challenges associated with this pathogen.     

Time course of gastric mucosal changes in the assessment of long-term results of Helicobacter pylori eradication

The impact of Helicobacter pylori (H. pylori) eradication on the gastric mucosa (GM) was studied in patients with gastroduodenal ulcers. Clinical and morphological changes in the GM were assessed in 122 patients 3-7 years (mean 4.4 +/- 1.3 years) after eradication therapy and in 12 patients who had undergone H. pylori eradication. Successful H. pylori eradication in the gastric antral and body mucosa reduced inflammation, the degree of chronic inflammation, the number of lymphoid follicles, and the magnitude of gland atrophy. There were no statistically significant changes in intestinal metaplasia. The patients who had not received eradication therapy showed no significant GM changes as compared to the baseline values. In the unsuccessful eradication group, inflammation statistically significantly diminished in the gastric antrum and body with a reduction in the density of H. pylori contamination.     

Effect of gastric environment on Helicobacter pylori adhesion to a mucoadhesive polymer

Helicobacter pylori infection has been associated with several gastric diseases. This bacterium colonizes the gastric mucosa of half of the world’s population, and available treatments are unsuccessful in practically one in every five patients. Mucoadhesive polymers, such as chitosan, are being investigated as gastric drug delivery systems. However, since chitosan is also known for its antimicrobial properties, this work aims to evaluate H. pylori interactions with chitosan under simulated gastric environments, namely using various pHs (2.6, 4 and 6), pepsin and urea. To enable the visualization of adherent bacteria, ultrathin chitosan films were produced by spin-coating on gold/glass surfaces, cross-linked with genipin and characterized by Fourier transform infrared reflection absorption spectroscopy, ellipsometry and electrokinetic analysis. Films with homogeneous thickness of 11.7 ± 0.6 nm were produced, and were stable and protonated at all the pHs used. Furthermore, they adsorbed pepsin in all these pHs, in contrast to urea, of which a small adsorption was only observed at pH 6. H. pylori binding to chitosan was higher at pH 2.6 although most of adherent bacteria were dead. The presence of pepsin decreased bacterial adhesion, but increased its viability while in a more stressed morphology (coccoid form). The presence of urea did not affect the amount, morphology or viability of chitosan-adherent bacteria. In suspension, the decrease in pH changed H. pylori zeta potential from negative to positive. Moreover, bacteria were only culturable when incubated in pH 6 with and without urea (without pepsin). This work demonstrates that chitosan has the capacity to bind and kill H. pylori in a range of pHs independently of urea. This opens new perspectives for the application of chitosan-based materials to the elimination of H. pylori gastric colonization, though pepsin might appear to be an obstacle.     

Helicobacter pylori in duodenal ulcer disease and its eradication

Antral biopsy specimens were processed for Helicobacter pylori by Gram staining, rapid urease test (RUT) and culture from 25 patients with symptoms of duodenal ulcer, amongst whom the positivity rate was 84%. Follow up of 16 patients after appropriate therapy showed complete regression of the disease in 87.5% of cases whereas in 12.5% of cases a decrease in the extent of duodenal ulceration was noted.     

Personalized treatment in the eradication therapy for Helicobacter pylori

Helicobacter pylori (HP) is known to be a causative bacterium of gastritis and peptic ulcers. The combination treatment consisting of a proton pump inhibitor (PPI), amoxicillin and clarithromycin (CAM) is widely used in eradication therapy, but the eradication fails in some patients. The main causes are CAM resistance of HP and individual variability in PPI metabolism related to the activity of the cytochrome P450 2C19 (CYP2C19) enzyme. In this study, we examined the usefulness of the prediction of the pharmacotherapeutic efficacy using a newly developed analysis system for HP CAM resistance and CYP2C19 genotypes. After obtaining the informed consent from 45 subjects with HP-positive peptic ulcers, biopsy specimens of the gastric mucosa were obtained by endoscopy. HP DNA extracted from the gastric mucosa was examined by the SELMAP-PCR method, the direct sequencing method or the single-nucleotide primer extension (SNuPE) method. HP detection rates by culture and the SELMAP-PCR method were 71% and 100%, respectively. Among 32 cultured HP, CAM resistance was confirmed in 6 samples by the in vitro drug susceptibility test. CAM-resistant gene mutations were also examined by the SELMAP-PCR method using 32 DNAs from cultured HP and the results were consistent with the drug susceptibility test. Among 22 patients, the eradication rate was 77%. Among 4 patients with CAM resistance determined by both the in vitro drug susceptibility test and the SNuPE method, eradication was successful in one intermediate metabolizer (IM), but not in three extensive metabolizers (EMs). Patients were divided into three groups according to their CYP2C19 phenotype: EMs, IMs and poor metabolizers (PMs). The eradication rates for 6 EMs, 12 IMs and 4 PMs were 33.3%, 91.7% and 100%, respectively. Based on these results, the information on CAM resistance in HP and CYP2C19 phenotypes in carriers could predict the pharmacotherapeutic efficacy and probability of eradication. It can then be possible to vary the dosing or to select another drug by the prediction of the pharmacotherapeutic efficacy.     

Helicobacter pylori eradication has no effect on metabolic and inflammatory parameters

BACKGROUND: An increased risk in coronary heart disease associated with Helicobacter pylori (H. pylon) appears to be partially mediated by modifications of the atherogenic lipoprotein and inflammatory parameters. We conducted a controlled trial aimed at evaluating the changes of metabolic and inflammatory parameters after H. pylon eradication. METHODS: We included in the study 169 patients with H. pylori infection and conducted a retrospective longitudinal survey of 87 subjects (76 men, 11 women) who received treatment for H. pylon eradication and 82 control subjects (63 men, 19 women) who did not receive treatment. We compared pre- and posteradication (one year after) the metabolic and inflammatory parameters, such as blood sugar, lipid profiles, insulin resistance, white blood cell count and C-reactive protein. RESULTS: No significant changes from the baseline in metabolic and inflammatory parameters within each group were observed. Changes in the serum levels of metabolic and inflammatory parameters were similar between the two groups. CONCLUSIONS: Metabolic and inflammatory parameters, including blood sugar, lipid profiles, insulin resistance, white blood cell count and C-reactive protein, were not changed after H. pylori eradication treatment. H. pylori eradication has no effect on metabolic and inflammatory parameters.     

Expression of Lewis antigens and their precursors in gastric mucosa: relationship with Helicobacter pylori infection and gastric carcinogenesis

Lewis (Le)-associated antigens are carbohydrates that are related biochemically to the ABO blood groups, and may have a role in Helicobacter pylori adherence. To evaluate their relationship to clinicopathological outcomes, gastric Le expression, including type 1 precursor, type 1 H, Le(a), Le(b), Le(x), Le(y) and sialylated Le(a) (CA19-9), was evaluated immunohistochemically in 233 gastric biopsy specimens obtained at routine gastroscopy. Expression was also investigated in gastric tissues showing chronic gastritis, intestinal metaplasia, and carcinoma from 42 patients with gastric cancer. A polymerase chain reaction was performed for H. pylori and the bacterial babA2 gene. We identified type 1 precursor expression in 34.3%, type 1 H in 55.8%, Le(a) in 44.2%, Le(b) in 82.0%, Le(x) in 44.2%, Le(y) 56.7%, and CA19-9 in 16.3% of the 233 gastric biopsy specimens. Expression of type 1 H, Le(b), and CA19-9 was significantly associated with H. pylori infection and histological features (p < 0.05), and expression of type 1 H was an independent predictive factor for H. pylori infection by multivariate logistic regression (p = 0.020). Positivity for the babA2 genotype correlated significantly with H. pylori infection and type 1 H expression in gastric biopsy specimens (p < 0.05). The babA2 genotype was more frequent in gastric mucosa from the gastric cancer patients than in gastric biopsy specimens from routine gastroscopy (p = 0.009). In the 42 gastric cancer patients, the frequency of type 1 precursor, Le(a), and Le(x) expression was significantly higher in intestinal metaplasia and carcinoma than in chronic gastritis (p < 0.05), but the frequency of type 1 H and Le(b) expression was significantly lower in intestinal metaplasia and carcinoma (p < 0.05). In conclusion, Le expression, especially that of type 1 H, was significantly associated with clinicopathological features. In gastric cancer patients, Le expression was altered in intestinal metaplasia and carcinoma in comparison with chronic gastritis.