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.     

Quantitative assessment of histological changes in chronic gastritis after eradication of Helicobacter pylori.

AIMS: To evaluate the effect of 10 day triple treatment on H pylori eradication and associated gastritis. METHODS: Fifty patients with H pylori positive non-ulcer dyspepsia were treated for 10 days with amoxicillin, tinidazole, and bismuth salts. Histological examination of the antral mucosa was performed before (T0), six weeks (T1), and six months (T2) after treatment. The new Sydney classification of gastritis was used, using a score from 0 to 3 to grade degree of inflammation, atrophy, activity (intraepithelial or lamina propria damage) and H pylori. RESULTS: At T0 all patients had chronic active gastritis. Lymphoid follicules were present in 12 cases. At T1 33 patients were H pylori negative: the score showed a decrease of activity (from 2.5 to 0.54). The result was confirmed at T2 (mean score 0.22). Inflammation decreased from 1.8 to 1.4 at T2. Only one case of follicular gastritis was observed. In H pylori positive patients the scores did not show significant modifications. CONCLUSIONS: Ten day triple treatment is effective in eradicating H pylori in 69% of cases, causing a decrease of the total score for gastritis. Activity, defined by polymorph infiltration, was promptly reduced when H pylori was eradicated. There was a trend to a reduction in inflammation, but atrophy was irreversible.     

Sulphomucins favour adhesion of Helicobacter pylori to metaplastic gastric mucosa.

AIMS: To assess the influence of sulphomucin secretion on Helicobacter pylori colonisation and adhesion to metaplastic gastric cells. METHODS: Gastric biopsies from 230 H pylori positive patients with intestinal metaplasia were analysed. Sulphated mucins and H pylori were visualised using a new technique combining high iron diamine-alcian blue mucin stains with the Steiner silver stain for the bacteria. RESULTS: Sulphomucin secretion anywhere in the mucosa and a histological diagnosis of dysplasia increase the risk of H pylori adhesion to metaplastic cells (odds ratios 19.9 and 4.3, respectively). However, only 9.4% of cases showing sulphomucin secretion and 10.8% of cases with dysplasia had evidence of adhesion of H pylori bacteria to metaplastic cells. CONCLUSIONS: The findings suggest that H pylori may play a role in the advanced stages of carcinogenesis. It will be of interest to investigate if the relative small proportion of type III metaplasias that actually progress to carcinoma show persistence of H pylori.     

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.     

Effect of Helicobacter pylori eradication on gastric carcinogenesis

Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet the effects of bacterial eradication on carcinogenesis remain unclear. Animal models provide important insights into factors that are involved in gastric carcinogenesis, and we previously utilized such a model to demonstrate that an in vivo-adapted H. pylori strain, 7.13, rapidly and reproducibly induces inflammation-mediated gastric carcinoma. In the current study, we used this bacterial strain as a prototype to define the role of targeted antimicrobial therapy in gastric carcinogenesis. Mongolian gerbils were infected with H. pylori for 4 or 8 weeks, treated with antimicrobial agents or vehicle, and then euthanized at 8 weeks after the completion of therapy. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals receiving antimicrobial therapy. Gastric dysplasia or cancer developed in >60% of the gerbils that remained persistently colonized with H. pylori, but in none of the animals treated with antibiotics following 4 weeks of infection. Infection with H. pylori for 8 weeks prior to therapy resulted in an attenuation, but not complete prevention, of pre-malignant and malignant lesions. Similarly, antibiotic therapy initiated at 4, but not 8, weeks after H. pylori challenge significantly reduced expression of the Th1 pro-inflammatory cytokine interferon-gamma within colonized gastric mucosa. These results indicate that treatment of H. pylori in this model decreases the incidence and severity of lesions with carcinogenic potential. The effectiveness of eradication is dependent upon the timing of intervention, providing insights into mechanisms that may regulate the development of malignancies arising within the context of inflammatory states.     

Pathologic changes of gastric mucosa colonized by Helicobacter pylori.

One hundred eighty-nine consecutive gastric biopsies showing colonization by Helicobacter pylori (HP) were studied. Epigastric pain and bleeding were the clinical presentations in 167 cases (88.4%). Major endoscopic findings were gastritis (n = 72, 38.1%) and ulceration (n = 101, 53.4%). Duodenal ulcer was associated with 32 (44.4%) and 29 (28.7%) cases of gastritis and gastric ulcer, respectively. Histologically, the HP-colonized gastric epithelium showed characteristic degenerative changes that were topographically related to the bacteria but unrelated to the inflammatory infiltrate. Disintegration and loss of apical mucus with formation of epithelial pits was seen in nearly all cases. Other changes included microerosion, conventional erosion, and frank ulceration. Only the disintegration of apical mucus, epithelial pit, and microerosion were specific for HP colonization. These conditions were absent in areas not colonized by HP and in 79 consecutive HP-negative gastric biopsies seen during the same study period. The epithelial degenerative changes in HP-colonized gastric mucosa are easy to recognize in routine hematoxylin-eosin-stained sections and they could serve as histologic guides to the localization of the bacteria. It is proposed that HP-colonized gastric mucosa is a distinct pathologic entity with a pathologic spectrum ranging from active chronic gastritis to erosion and frank ulcer. Damage to the mucin-containing portion of the gastric epithelial cells appears to be the basic cytopathologic effect of HP on the gastric mucosa. As effective specific treatment for HP infection is available, identification of HP colonization in gastric biopsies should be attempted in all cases of gastritis and gastric ulcer.     

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。     

Infiltration of Helicobacter pylori in the gastric mucosa

It is our hypothesis that if Helicobacter pylori could be demonstrated conclusively to have transgressed the mucosal surface into the lamina propria, this would help explain how H pylori recruits inflammatory cells. We report our immunohistochemical and electron microscopic findings that demonstrate that H pylori can be detected in the lamina propria of the stomach, offering evidence of its invasive potential. We stained 67 endoscopic gastric biopsy specimens with Warthin-Starry silver and immunoperoxidase stains for H pylori. In addition, transmission electron microscopy was performed on 1 case. The presence of surface H pylori was associated significantly with active (P < .0001) and chronic (P < .0001) inflammation. H pylori could not be identified in the lamina propria using the Warthin-Starry silver stain alone. Immunoreactivity for H pylori in the lamina propria was detected in 20 (30%) of 67 gastric biopsy specimens. Transmission electron microscopy confirmed the immunohistochemical findings. H pylori can infiltrate the lamina propria of the gastric mucosa, thereby proving morphologic evidence of its invasive capability.     

Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes

Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.     

Improvement of gastric inflammation and resolution of epithelial damage one year after eradication of Helicobacter pylori.

AIMS--To investigate the effect of eradication of Helicobacter pylori infection on gastric epithelial damage and gastritis, scored according to the Sydney system. METHODS--Gastritis scores and epithelial damage were assessed in gastric biopsy specimens before, and five weeks and one year after anti-H pylori therapy in 66 patients with H pylori related gastritis. RESULTS--The mean initial levels of activity, inflammation, atrophy, intestinal metaplasia, and H pylori scores were higher in the antrum than in the corpus or fundus. Eradication of H pylori resulted in an improvement in the mean inflammatory score in antral biopsy specimens from 2.23 before treatment to 1.32 and 1.06, respectively, five weeks and one year after treatment. Corresponding values for fundic biopsy specimens were 1.30, 0.36 and 0.35. Activity scores improved from 1.41 before treatment to 0.13 and zero, respectively, five weeks and one year after treatment in antral biopsy specimens and from 0.60 before treatment to zero in fundic biopsy specimens. Before treatment, epithelial damage was present in 51% of biopsy specimens taken from the antrum and 23% of those from the corpus. Five weeks after eradication of H pylori none of the biopsy specimens revealed evidence of epithelial damage. CONCLUSION--Eradication of H pylori is followed by a rapid, significant improvement in the gastritis score and resolution of epithelial damage in antral and fundic mucosa.     

Cell damage and proliferation in human gastric mucosa infected by Helicobacter pylori--a comparison before and after H pylori eradication in non-atrophic gastritis

Helicobacter pylori (HP) is believed to be involved in the transition from normal gastric mucosa to atrophic gastritis and intestinal metaplasia. Infection with the organism is one of the risk factors for development of intestinal-type gastric adenocarcinoma, possibly through altered cell turnover. Medical eradication of HP is widely performed for the treatment of peptic ulcers and other upper gastrointestinal disorders. Eradication of HP may affect altered cell turnover of the gastric mucosa caused by the infection, but there are few reports comparing sterilized mucosa with HP-infected and non-infected mucosa. In this study, we examined cell damage using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), in situ nick translation (ISNT), and cell proliferation by Ki 67 immunohistochemistry staining in gastric mucosa before and after HP eradication and in non-infected gastric mucosa. We then compared these findings using endoscopic gastric biopsy specimens. Labeling indices of TUNEL (2.46 +/- 1.22), ISNT (1.13 +/- 0.42), and Ki67 (21.8 +/- 6.14) in tissue from which HP had been eradicated were significantly lower than those of HP-infected mucosa (6.36 +/- 2.26, 4.00 +/- 1.62, 45.8 +/- 5.35, for TUNEL, ISNT, and Ki67, respectively). There were no significant differences between formerly infected and non-infected mucosa (TUNEL: 2.26 +/- 0.69, ISNT: 1.29 +/- 0.63, Ki67: 23.5 +/- 8.20). These results indicate that medical HP eradication results in decreased cell proliferation and damage, restoring the condition seen in non-infected mucosa. Thus, HP eradication may be effective, not only in the treatment of gastric ulcers or gastric symptoms, but also in the prevention of gastric carcinoma.     

抗幽门螺杆菌血清IgE和胃粘膜肥大细胞在Hp致病中的作用

目的探讨机体免疫反应在幽门螺杆菌（Ｈｐ）致病中的作用。方法采用间接ＥＬＩＳＡ法检测了１４９例患者血清中抗ＨｐＩｇＥ,并用改良甲苯胺蓝染色法检测其胃粘膜中肥大细胞（ＭＣ）。结果①Ｈｐ阳性者血清抗ＨｐＩｇＥ含量、阳性率和胃粘膜中ＭＣ总数及脱颗粒比均显著高于Ｈｐ阴性者（Ｐ＜０．０１）;②不同胃部疾病之间血清抗ＨｐＩｇＥ含量、阳性率和胃粘膜中ＭＣ总数及脱颗粒比有显著差异,活动性胃炎显著高于非活动性胃炎和消化性溃疡（Ｐ＜０．０１）,中重度胃炎显著高于轻度胃炎（Ｐ＜０．００１）;③血清抗ＨｐＩｇＥ阳性者胃粘膜内ＭＣ总数及脱颗粒比均显著高于抗ＨｐＩｇＥ阴性者（Ｐ＜０．０１）,且血清抗ＨｐＩｇＥ含量与胃粘膜内ＭＣ脱颗粒比呈正相关（ｒ＝０．６０,Ｐ＜０．００１）。结论血清抗ＨｐＩｇＥ参与了Ｈｐ的致病过程,其机制可能为刺激ＭＣ脱颗粒,而致胃粘膜损伤。     

Adherence of Helicobacter pylori to areas of type II intestinal metaplasia in Korean gastric mucosa.

The aim of this study was to examine whether Helicobacter pylori (H. pylori) attaches to areas of intestinal metaplasia in Korean patients. Gastric biopsy specimens with intestinal metaplasia from 8 gastric cancers, 24 gastric ulcers, 11 duodenal ulcers, and 57 chronic gastritis were examined. The specimens were stained with periodic acid-Schiff/alcian blue pH 2.5 and high-iron diamine/alcian blue pH 2.5 to identify the subtype of intestinal metaplasia, and then immunohistochemical stain was done with rabbit anti-H. pylori polyclonal antibody. In 17 patients, H. pylori attached to areas of type II intestinal metaplasia. All areas of intestinal metaplasia showing adherence contained sialomucin, and H. pylori was not detected in the areas of intestinal absorptive cells and sulfomucin-containing metaplastic cells.     

Helicobacter pylori associated gastric diseases and lymphoid tissue hyperplasia in gastric antral mucosa

AIM: To investigate the relation between Helicobacter pylori associated gastroduodenal diseases and lymphoid tissue hyperplasia in the antral mucosa and to pursue its evolution after eradication of H pylori. METHODS: Gastric antral biopsy specimens were obtained from 438 patients with H pylori positive gastroduodenal diseases (185 chronic gastritis, 69 gastric ulcer, and 184 duodenal ulcer) and 50 H pylori negative healthy controls. Lymphoid follicles and aggregates were counted and other pathological features were scored according to the updated Sydney system for classification of chronic gastritis. After a course of anti-H pylori treatment, biopsy specimens were obtained at four to six weeks, 12 months, and 24 months in the chronic gastritis patient group. RESULTS: The total prevalence of lymphoid follicles and aggregates in the biopsies was 79.9% (350 of 438; 95% confidence intervals (CI), 0.76 to 0.84). The prevalence and density of lymphoid follicles and aggregates were significantly different in the various gastroduodenal diseases. The highest prevalence (89.9%; 95% CI, 0.83 to 0.97) and density (0.82) of lymphoid follicles and aggregates occurred in patients with gastric ulcers. The lowest prevalence of lymphoid follicles and aggregates was found in patients with chronic gastritis (74.6%; 95% CI, 0.68 to 0.81), and the lowest density of lymphoid follicles and aggregates (0.56) was seen in patients with duodenal ulcers. The prevalence and density of lymphoid follicles and aggregates correlated strongly with the activity and severity of gastric antral mucosal inflammation. The eradication of H pylori resulted in a decrease in the prevalence and density of lymphoid follicles and aggregates. CONCLUSION: The prevalence and density of lymphoid follicles and aggregates in gastric antral mucosal biopsies correlated closely with H pylori infection.     

Acute inflammation of the proliferative zone of gastric mucosa in Helicobacter pylori gastritis.

The neutrophilic infiltration has been regarded to represent the activity of Helicobacter pylori gastritis. It may involve the epithelium and/or lamina propria. The incidence and degree of the two types of infiltration do not correlate with each other frequently. We correlated the two types of neutrophilic infiltration with H. pylori infection and other pathologic parameters respectively in 300 randomly selected gastric biopsies as well as serial biopsies from a separate group of 95 patients who were treated for H. pylori infection. The "random biopsies" had chronic gastritis of various degrees, and the organisms were identified in 239 cases (79.7%); in the "treated group," the organisms disappeared completely in 62 cases (65.3%). Characteristically, the intraepithelial neutrophilic infiltration was predominantly localized to the proliferative zone of the gastric mucosa (zone 2) where the density of H. pylori was considerably lower than the surface epithelium. In the "random biopsies," both acute epithelial and interstitial neutrophilic infiltration correlated significantly (p < 0.01) with the H. pylori infection. In the "treated group," however, only acute epithelial inflammation correlated significantly (p < 0.01) with the eradication of infection while acute interstitial inflammation did not. Acute epithelial inflammation was no less frequently present in advanced chronic gastritis than in early chronic gastritis. Acute epithelial inflammation of the proliferative zone is a characteristic pathologic finding of H. pylori gastritis, and appears to be directly associated with the pathogenesis of H. pylori gastritis and its progression.     

Electron microscopic study of association between Helicobacter pylori and gastric and duodenal mucosa.

AIM--To study the ultrastructural appearances of Helicobacter pylori in antral and duodenal biopsy specimens and its relation with the epithelial cells. METHODS--Endoscopically obtained antral and duodenal biopsy specimens were examined using transmission electron microscopy and freeze fracture analysis. RESULTS--Most bacteria looked curved, but in the duodenal bulb coccoid bacteria were relatively common. Bacteria were often found around intercellular junctions. freeze fracture examination indicated abnormalities of the tight junction complexes in patients with H pylori infection. In many biopsy specimens bacteria were seen closely attached to the epithelial cell membrane by different forms of adhesion. In addition to what looked like intracytoplasmic penetration by bacteria, several examples of genuine penetration were observed. CONCLUSION--H pylori is commonly found adhering to epithelial cells. Occasionally, H pylori may also penetrate cells. These features may contribute to the pathogenic action of the organism.