Pre and post eradication gastric inflammation in Helicobacter pylori-associated duodenal ulcer.

BACKGROUND: Distribution and nature of gastritis are major determinants of clinical outcome of H. pylori infection. The gastric inflammatory changes associated with this infection in developing countries have not been systematically studied. AIMS: To evaluate the inflammatory changes in gastric antrum and corpus in patients with duodenal ulcer and H. pylori infection, before and after H. pylori eradication therapy. METHODS: Histology and H. pylori density were studied in gastric biopsies obtained from 53 consecutive patients with active duodenal ulcer and H. pylori infection. Biopsies were obtained before and 4 weeks after H. pylori eradication therapy, from the anterior and posterior walls of the antrum and corpus, and were evaluated according to the Sydney system. RESULTS: In the pre-H. py/ori eradication antral biopsies, chronic gastritis, active gastritis, atrophy, intestinal metaplasia (IM) and lymphoid follicles / aggregates were seen in 53 (100%), 49 (92%), 11 (21%), 7 (13%) and 28 (53%) patients, respectively. In the corresponding biopsies from gastric corpus, these changes were seen in 49 (92%), 23 (43%), 2 (4%), 2 (4%) and 8 (15%), respectively. All changes except IM were significantly more frequent and of higher grade in the antrum. The grade of chronic gastritis was significantly higher in antrum than corpus; the frequency of gastritis in the antrum and corpus was similar (100% vs. 92%). H. pylori density was also higher in the antrum and correlated well with the grades of chronic gastritis and activity at both sites. Eradication of H. pylori was achieved in 39 patients (74%), and led to significant decrease in gastritis; no change was seen in patients who did not eradicate the organism. CONCLUSIONS: Antral-predominant chronic gastritis and activity are present in more than 90% of patients with H. pylori infection associated with duodenal ulcer, and the grade of gastritis correlates with the density of the organism. Eradication therapy results in improvement of both chronic gastritis and activity.     

Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients

AIM: To compare Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients in different age groups and from different biopsy sites. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of gastric ulcer and chronic gastritis patients. Giemsa staining, improved Toluidine-blue staining and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of activity of H pylori infection, mucosal inflammation, glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: Total rate of H pylori infection, mucosal inflammation, activity of H pylori infection, glandular atrophy and intestinal metaplasia in 3 839 gastric ulcer patients (78.5%, 97.4%, 82.1%, 61.1% and 64.2%, respectively) were significantly higher than those in 4 102 chronic gastritis patients (55.0%, 90.3%, 56.2%, 36.8%, and 37.0%, respectively, P<0.05). The rate of H pylori colonization of chronic gastritis in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 33.3%, 41.7%, 53.6%, 57.3%, 50.7%, 43.5%, respectively; in corpus, it was 32.6%, 41.9%, 53.8%, 60.2%, 58.0%, 54.8%, respectively; in angulus, it was 32.4%, 42.1%, 51.6%, 54.5%, 49.7%, 43.5%, respectively. The rate of H pylori colonization of gastric ulcer in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 60.5%, 79.9%, 80.9%, 66.8%, 59.6%, 45.6%, respectively; in corpus, it was 59.7%, 79.6%, 83.6%, 80.1%, 70.6%, 59.1%, respectively; in angulus, it was 61.3%, 77.8%, 75.3%, 68.8%, 59.7%, 45.8%, respectively. The rate of H pylori colonization at antrum was similar to corpus and angulus in patients, below 50 years, with chronic gastritis and in patients, below 40 years, with gastric ulcer. In the other age- groups, the rate of H pylori colonization was highest in corpus, lower in antrum and lowest in angulus (all P<0.05). The rates of glandular atrophy and intestinal metaplasia were higher and earlier in H pylori-positive patients than those without H pylori infection (both P<0.01). In comparison of gastric ulcer patients with chronic gastritis patients, the rate of glandular atrophy and intestinal metaplasia was higher in H pylori-positive patients with gastric ulcer than in H pylori-positive patients with chronic gastritis (both P<0.01); the rate of glandular atrophy and intestinal metaplasia were also higher in H pylori-negative patients with gastric ulcer than in H pylori-negative patients with chronic gastritis (both P<0.01). Both glandular atrophy and intestinal metaplasia were much more commonly identified in the angulus than in the antrum, lowest in corpus (all P<0.01). CONCLUSION: Rate of H pylori infection, glandular atrophy and intestinal metaplasia in gastric ulcer were higher than in chronic gastritis in all-different age -groups. Distribution of H pylori colonization is pangastric in the younger patients. It is highest in corpus, lower in antrum and lowest in angulus in the older age groups. Progression of glandular atrophy and intestinal metaplasia seem to have a key role in the distribution of H pylori colonization. H pylori appears to be the most important risk factor for the development of glandular atrophy and intestinal metaplasia, but it is not the only risk.     

Prevalence of Helicobacter pylori infection and gastric cancer precursor lesions in patients with dyspepsia

BACKGROUND: Helicobacter pylori infection has been considered to play significant role in gastric carcinogenesis, but only a minority of people who harbor this organism will develop gastric cancer. H. pylori infection first causes chronic non atrophic gastritis. Chronic non atrophic gastritis may evolve to atrophic gastritis and intestinal metaplasia and finally to dysplasia and adenocarcinoma. AIMS: To estimate the prevalence of H. pylori infection and the precancerous gastric lesions and their relationship, in patients with dyspeptic symptoms who underwent upper gastrointestinal endoscopy at a reference center in the central region of Rio Grande do Sul state, Brazil. METHODS: We analyzed gastric biopsies taken from corpus and antrum of patients who underwent upper gastrointestinal endoscopy for H. pylori detection, between 1994 and 2003. According to Sydney system, chronic non atrophic gastritis, atrophic gastritis and intestinal metaplasia were diagnosed by histological examination (H-E stain). The histological diagnoses were related to H. pylori infection status. RESULTS: Biopsies from 2,019 patients were included in the study. Patients mean age was 52 (+/-15) and 59% were female. Seventy six percent had H. pylori infection. Normal mucosa, chronic non atrophic gastritis, atrophic gastritis and intestinal metaplasia were diagnosed in 5%, 77%, 3% and 15%, respectively. The OR for any degree of gastric mucosa lesion in infected patients was 10 (CI95% 6.50 - 17%). The OR for infected patients had chronic non atrophic gastritis was 3 (CI95% 2,2 - 3,4). The OR for infected patients had atrophic gastritis or intestinal metaplasia was less than 1. CONCLUSIONS: The prevalence of H. pylori infection in this population was high (76%) and infected individuals had the probability 10 folds greater than non infected individuals to have any lesion of gastric mucosa. The prevalence of precancerous lesions was 77% for non atrophic chronic gastritis, 3% for atrophic gastritis and 15% for intestinal metaplasia. Infected patients had risk 3 folds greater than non-infected for the occurrence of non atrophic chronic gastritis. H. pylori infection did not show risk for occurrence of atrophic gastritis and intestinal metaplasia, suggesting that other risk factors should be involved in the carcinogenesis process.     

Comparison of He/icobacter py/ori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients

AIM: To compare Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients in different age groups and from different biopsy sites. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of gastric ulcer and chronic gastritis patients. Giemsa staining, improved Toluidine-blue staining and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylineosin staining was used for the histological diagnosis of activity of H pylori infection, mucosal inflammation, glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: Total rate of H pylori infection, mucosal inflammation, activity of H pylori infection, glandular atrophy and intestinal metaplasia in 3 839 gastric ulcer patients (78.5%, 97.4%, 82.1%, 61.1% and 64.2%, respectively) were significantly higher than those in 4 102 chronic gastritis patients (55.0%, 90.3%, 56.2%, 36.8%, and 37.0%, respectively, P<0.05). The rate of H pylori colonization of chronic gastritis in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 33.3%, 41.7%, 53.6%, 57.3%, 50.7%, 43.5%, respectively; in corpus, it was 32.6%, 41.9%, 53.8%, 60.2%, 58.0%, 54.8%, respectively; in angulus, it was 32.4%, 42.1%, 51.6%, 54.5%, 49.7%, 43.5%, respectively. The rate of H pylori colonization of gastric ulcer in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 60.5%, 79.9%, 80.9%, 66.8%, 59.6%, 45.6%, respectively; in corpus, it was 59.7%, 79.6%, 83.6%, 80.1%, 70.6%, 59.1%, respectively; in angulus, it was 61.3%, 77.8%, 75.3%, 68.8%, 59.7%, 45.8%, respectively. The rate of H pylori colonization at antrum was similar to corpus and angulus in patients, below 50 years, with chronic gastritis and in patients, below 40 years, with gastric ulcer. In the other age- groups, the rate of H pylori colonization was highest in corpus, lower in antrum and lowest in angulus (all P<0.05). The rates of glandular atrophy and intestinal metaplasia were higher and earlier in H pylori-positive patients than those without H pylori infection (both P<0.01). In comparison of gastric ulcer patients with chronic gastritis patients, the rate of glandular atrophy and intestinal metaplasia was higher in H pylori-positive patients with gastric ulcer than in H pylori-positive patients with chronic gastritis (both P<0.01); the rate of glandular atrophy and intestinal metaplasia were also higher in H pylori-negative patients with gastric ulcer than in H pylori-negative patients with chronic gastritis (both P<0.01). Both glandular atrophy and intestinal metaplasia were much more commonly identified in the angulus than in the antrum, lowest in corpus (all P<0.01). CONCLUSION: Rate of H pylori infection, glandular atrophy and intestinal metaplasia in gastric ulcer were higher than in chronic gastritis in all-different age -groups. Distribution of H pylori colonization is pangastric in the younger patients. It is highest in corpus, lower in antrum and lowest in angulus in the older age groups. Progression of glandular atrophy and intestinal metaplasia seem to have a key role in the distribution of H pylori colonization. H pylori appears to be the most important risk factor for the development of glandular atrophy and intestinal metaplasia, but it is not the only risk.     

Expression of cell-cycle related proteins in Helicobacter pylori gastritis and association with gastric carcinoma

Helicobacter pylori (H. pylori) infection is associated with changes in epithelial turnover, through their significance of these in gastric carcinogenesis is still controversial. The purpose of this study was to determine the influence of H. pylori infection on cell proliferation and the relation with the cell-cycle regulators, and finally to provide insights into the mechanism by which H. pylori may lead to gastric carcinogenesis. We investigated Ki-67, p53, p21(Waf1/Cip1), cyclin D1 expression in 55 patients with H. pylori gastritis, and compared the results with patients those of non-H. pylori gastritis patients (n=21), gastric adenocarcinoma patients (n=8) and samples with normal gastric mucosa (n=12). Gastric biopsies were histologically evaluated for inflammatory reaction, intestinal metaplasia and atrophy according to the Sydney system. Overexpression of Ki-67, p53, p21(Waf1/Cip1) and cyclin D1 was found in H. pylori gastritis patients (32.7%, 10.9%, 20.0% and 7.3%, respectively), whereas only scattered expression in cells in the neck region of the crypts, but no overexpression was found in gastric antral epithelial cells in biopsy specimens from patients with non-H. pylori gastritis and noninflammed mucosa. A significant relationship was found between the grade of H. pylori colonization and Ki-67, p53, p21(Waf1/Cip1) and cyclin D1 expression. Expression was significantly higher in patients with intestinal metaplasia with atrophy, whereas no overexpression was found in patients without intestinal metaplasia with atrophy (p=0.05). H. pylori infection is associated with increased cell proliferation, increased epithelial DNA damage, and atrophy, which might contribute to the development of gastric cancer. Even if the exact mechanism has not been elucidated yet, our results suggest that H. pylori infection acts as a cofactor in gastric carcinogenesis.     

Grading of histology, expression of apoptosis and cell proliferation in gastric mucosa adjacent to gastric adenoma or adenocarcinoma]

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection can lead to gastric adenoma and carcinoma through atrophic gastritis and intestinal metaplasia. Imbalance between apoptosis and proliferation may play a role in gastric carcinogenesis. We tried to investigate H. pylori infection rate, grade of gastritis, environmental risk factors, expression rate of apoptosis and cell proliferation in mucosa adjacent to tumor, and we also tried to find significant factors associated with gastric carcinogenesis. METHODS: Endoscopically diagnosed twenty cases of intestinal type gastric carcinoma, 20 cases of gastric adenoma, and 40 cases of control (normal or gastritis) were enrolled. H. pylori infection rate, histologic grading, apoptosis and immunohistochemical stain (Ki-67 and p53) to check mucosal proliferation were done in endoscopically biopsied tissues at antrum and body at least 2 cm apart from adenoma or carcinoma. RESULTS: In three groups, H. pylori infection rates were not significantly different. In the multivariate analysis, only atrophy of gland was a significant risk factor for adenoma compared to control group (OR 3.7). Intestinal metaplasia in antrum and alcohol drinking were significant risk factors for carcinoma compared to control group (OR 4.4 and 4.9 respectively). Expressions of apoptosis, Ki-67 and p53 were not significantly different in three groups. CONCLUSIONS: Intestinal metaplasia in antrum and alcohol drinking are significant risk factors for gastric carcinoma. Degree of mucosal proliferation and apoptosis in gastric mucosa adjacent to tumor are not significantly different in three groups.     

Helicobacter pylori gastritis of the gastric cancer phenotype in relatives of gastric carcinoma patients.

OBJECTIVE: Infection with Helicobacter pylori is associated with gastric cancer. However, a hereditary risk of gastric cancer has also been reported. Hence, we decided to evaluate H. pylori gastritis in relatives of gastric cancer patients in comparison with matched controls. DESIGN: Case-controlled study. METHODS: A total of 237 patients with merely H. pylori gastritis (i.e. not associated with either peptic ulcer or gastric malignancy), and either first-degree (93.7%) or second-degree (6.3%) relatives with gastric cancer, were age- and sex-matched with 237 patients with H. pylori gastritis unassociated with a family history of gastric cancer. From each patient, antral and corpus biopsy specimens were obtained and investigated for degree (lymphocyte/plasma cell infiltration) and activity (polymorph infiltration) of gastritis (score: 0-4). Intestinal metaplasia was recorded as present or absent. RESULTS: The results show that relatives of gastric cancer patients have a significantly greater expression of gastritis due to a higher grade of gastritis in the antrum and corpus (P < 0.0001) and a greater activity of gastritis in the corpus (P < 0.0001). Intestinal metaplasia occurs more often in relatives of gastric cancer patients (antrum: P < 0.0001; corpus: P = 0.0237). CONCLUSION: Since the grade of H. pylori gastritis in relatives of gastric cancer patients is significantly higher than in controls, there appears to be a genetic susceptibility influencing the expression of H. pylori gastritis.     

Histological patterns of gastritis in H. pylori-infected individuals with a family history of gastric cancer

OBJECTIVE: Different types of chronic gastritis, including antral predominant, corpus predominant, and multifocal pangastritis, are associated with Helicobacter pylori infection. Specific patterns of H. pylori gastritis that might characterize individuals with family histories of noncardia gastric cancer (GC) were investigated. METHODS: Histopathological changes associated with H. pylori gastritis were assessed in 111 individuals with family histories of GC and in 77 without from a region with high prevalence of H. pylori infection and GC. Gastric biopsies were taken from 12 sites (antrum, five; corpus, six; and cardia, one). RESULTS: Individuals (age < 36 yr) with family histories of GC developed pangastritis and had higher H. pylori bacterial scores (p < 0.05) in the gastric corpus, whereas those without family histories of GC typically had antral predominant gastritis. The correlation between density of polymorphonuclear leukocytes and density of H. pylori at each biopsy site was statistically significant (p < 0.01). Pangastritis was associated with a higher density of lymphoid aggregates and follicles (p < 0.05) in the corpus of younger individuals (age < 36) and in the antrum of older individuals (age > or = 48) with positive family histories of GC. CONCLUSIONS: Pangastritis and high lymphoid follicle density associated with H. pylori infection were found in patients with family histories of GC. Because a family history of gastric carcinoma is associated with increased risk of gastric cancer development, characterization of histological patterns of gastritis may be applicable to gastric cancer screening and surveillance, especially in relatively young at-risk populations.     

Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study

BACKGROUND AND AIMS: Infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. However, most patients with H. pylori infection will not develop gastric cancer. The aims of the present study were to examine which histological features, including H. pylori infection, would increase the risk of gastric cancer using a case-control study. METHODS: Three gastric biopsy specimens were taken from 72 patients with early gastric cancer and 72 age- and sex-matched control subjects. The grade of gastritis was examined according to the updated Sydney System. The presence of H. pylori infection was determined by serology and histology. Odds ratio (OR) of developing gastric cancer was calculated for H. pylori positivity and histological features using conditional logistic regression. For patients with H. pylori infection, histological features in cancer patients and control subjects were compared. RESULTS: The OR of the presence of mononuclear cell infiltration in the corpus and intestinal metaplasia in the angulus were significantly elevated. The grade of mononuclear cell infiltration in the corpus and antrum was significantly higher in both types of cancer patients than controls. Glandular atrophy and intestinal metaplasia were increased in patients with intestinal-type cancer in the angulus and antrum. Bacterial density in the corpus and polymorphonuclear cell infiltration in the antrum were increased in patients with diffuse-type cancer. CONCLUSIONS: Severe chronic gastritis induced by H. pylori infection seems to be associated with diffuse-type gastric cancer. Glandular atrophy and intestinal metaplasia, which occur in gastric mucosa with chronic inflammation, are significantly associated with intestinal-type cancer.     

Mutant p53 expression and apoptotic activity of Helicobacter pylori positive and negative gastritis in correlation with the presence of intestinal metaplasia

BACKGROUND: Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. METHODS: Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. RESULTS: In the absence of intestinal metaplasia, both the apoptotic index (0.0272 +/- 0.011 vs 0.0128 +/- 0.006) and expresssion of p53 (35.55 +/- 31.16 vs 18.33 +/- 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P < 0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 +/- 0.004 vs 0.011 +/- 0.004), or p53 ratio (70.16 +/- 22.54 vs 68.50 +/- 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P < 0.05). CONCLUSION: In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.     

胃黏膜癌前病变中p53、p21^ras蛋白表达与幽门螺杆菌感染的关系

目的观察幽门螺杆菌(Helicobacterpylori)感染及根除H.pylori二年后p53、p21ras在二组胃黏膜上皮细胞的表达,探讨H.pylori在胃癌发生、发展中的作用.方法应用免疫组织化学染色、尿素酶快速试验(RUT)、组织学Warthin-Starry染色.198例H.pylori感染患者,慢性胃炎86例,慢性胃炎伴肠化生67例,慢性胃炎伴异型增生45例;对照组为根除H.pylori 2年后共86例,其中慢性胃炎54例,慢性胃炎伴肠化生32例,慢性胃炎伴异型增生10例.全部病例做p53、p21ras免疫组织化学染色.结果 H.pylori感染组p53、p21 ras 阳性表达率15.7%、18.7%,明显高于H.pylori根除组2.3%、7%,差异显著(P＜0.05);慢性胃炎伴肠化病变中,p53、p21ras在H.pylori感染组阳性表达率17.9%、18.4%均高于H.pylori根除组0%、9.4%,差异显著(P＜0.05)慢性胃炎伴异型增生病变中,p53、p21 ras在H.pylori感染组阳性表达率31.1%、40%均高于H.pylori根除组20%、30.4%,差异显著(P＜0.05);H.pylori 感染组p53、p21ras在慢性胃炎,肠化生,异型增生表达水平依次增高p53、p21ras共同表达阳性37例.结论在胃黏膜癌前病变中p53、p21ras 在H.pylori感染组阳性表达率高于H.pylori根除组,差异显著(P＜0.05);在慢性胃炎,肠化生,异型增生p53、p21ras表达水平在增高;p53、p21 ras表达呈正相关;H.pylori感染在胃癌发生、发展过程中起一定作用,p53、p21ras表达可能是H.pylori致癌的作用机理之一.     

Helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer

AIM: To evaluate the histological features of gastric mucosa, including Helicobacter pylori infection in patients with early gastric cancer and endoscopically found superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of all the patients. Giemsa staining, improved toluidine-blue staining, and Hpylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of gastric mucosa inflammation, gastric glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: The overall prevalence of H pylori infection in superficial gastritis was 28.7%, in erosive gastritis 57.7%, in gastric erosion 63.3%, in gastric ulcer 80.8%, in early gastric cancer 52.4%. There was significant difference (P<0.05), except for the difference between early gastric cancer and erosive gastritis. H pylori infection rate in antrum, corpus, angulus of patients with superficial gastritis was 25.9%, 26.2%, 25.2%, respectively; in patients with erosive gastritis 46.9%, 53.5%, 49.0%, respectively; in patients with gastric erosion 52.4%, 61.5%, 52.4%, respectively; in patients with gastric ulcer 52.4%, 61.5%, 52.4%, respectively; in patients with early gastric cancer 35.0%, 50.7%, 34.6%, respectively. No significant difference was found among the different site biopsies in superficial gastritis, but in the other diseases the detected rates were higher in corpus biopsy (P<0.05). The grades of mononuclear cell infiltration and polymorphonuclear cell infiltration, in early gastric cancer patients, were significantly higher than that in superficial gastritis patients, lower than that in gastric erosion and gastric ulcer patients (P<0.01); however, there was no significant difference compared with erosive gastritis. The grades of mucosa glandular atrophy and intestinal metaplasia were significantly highest in early gastric cancer, lower in gastric ulcer, the next were erosive gastritis, gastric erosion, the lowest in superficial gastritis (P<0.01). Furthermore, 53.3% and 51.4% showed glandular atrophy and intestinal metaplasia in angular biopsy specimens, respectively; but only 40.3% and 39.9% were identified in antral biopsy, and 14.1% and 13.6% in corpus biopsy; therefore, the angulus was more reliable for the diagnosis of glandular atrophy and intestinal metaplasia compared with antrum and corpus (P<0.01). The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pyloripositivity was 50.7%, 34.1%; of erosive gastritis 76.1%, 63.0%; of gastric erosion 84.8%, 87.8%; of gastric ulcer 80.6%, 90.9%; and of early gastric cancer 85.5%, 85.3%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pylorinegativity was 9.9%, 6.9%; of erosive gastritis 42.5%, 42.1%; of gastric erosion 51.1%, 61.9%; of gastric ulcer 29.8%, 25.5%; and of early gastric cancer 84.0%, 86.0%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis, erosive gastritis, gastric erosion, and gastric ulcer patients with H pylon positivity was significantly higher than those with H pylori negativity (P<0.01); however, there was no significant difference in patients with early gastric cancer with or without H pylori infection. CONCLUSION: The progression of the gastric pre-cancerous lesions, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis and gastric ulcer was strongly related to H pylori infection. In depth studies are needed to evaluate whether eradication of H pylori infection will really diminish the risk of gastric cancer.     

Effect of Helicobacter pylori infection on p53 expression of gastric mucosa and adenocarcinoma with microsatellite instability

AIM: To investigate the relationship between Helicobacter pylori (H pylori) infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elucidate the mechanism of gastric carcinogenesis relating to H pylori infection. METHODS: One hundred and eight endoscopic biopsies and gastric adenocarcinoma were available for the study including 33 cases of normal, 45 cases of gastritis, 30 cases of intestinal metaplasia, and 46 cases of gastric adenocarcinoma. Peripheral blood samples of these patients were also collected. H pylori infection and p53 expressions were detected by means of streptavidin-peroxidase (SP) immunohistochemical method. Microsatellite loci were studied by PCR-SSCP-CE using the markers BAT-26, D17S261, D3S1283, D2S123, and D3S1611. MSI was defined as the peak shift in the DNA of the gastric tissue compared with that of the peripheral blood samples. Based on the number of mutated MSI markers, specimens were charac-terized as high MSI (MSI-H) if they manifested instability at two or more markers, low MSI (MSI-L) if unstable at only one marker, and microsatellite stable (MSS) if they showed no instability at any marker. RESULTS: H pylori infection was detected in the samples of gastritis, intestinal metaplasia, and gastric adenocarcinoma and the infection frequencies were 84.4%, 76.7%, and 65.2%, respectively, whereas no H pylori infection was detected in the samples of normal control. There was a significant difference in the infection rates between gastritis and carcinoma samples (P= 0.035). No MSI was detected in gastritis samples, one MSI-H and two MSI-L were detected among the 30 intestinal metaplasia samples, and 12 MSI-H and 3 MSI-L were detected in the 46 gastric carcinomas. In those gastric carcinomas, the MSI-H frequency in H pylori-positive group was significantly higher than that in H pylori- negative group. No p53 expression was detected in the normal and gastritis samples from dyspeptic patients. P53-positive immunohistochemical staining was detected in 13.3% of intestinal metaplasia samples and in 43.5% of gastric carcinoma samples. The levels of p53 in H pylori-positive samples were higher than those in the negative group when the carcinoma samples were subdivided into H py/ori-positive and -negative groups (P=0.013). Eight samples were detected with positive p53 expression out of the 11 MSI-H carcinomas with H pylori infection and no p53 expression could be seen in the H pylori-negative samples. CONCLUSION: H pylori affect the p53 pattern in gastric mucosa when MMR system fails to work. Mutations of the p53 gene seem to be an early event in gastric carcinogenesis.     

幽门螺杆菌及胃粘膜肠上皮化生与CD_(44)V_6表达的关系

目的　探讨幽门螺杆菌 (Hp)感染及慢性萎缩性胃窦炎伴肠上皮化生与CD4 4V6表达程度之间的关系。方法　以单克隆抗体及免疫组化技术等方法对Hp阴性单纯慢性胃炎、Hp阴性萎缩性胃炎伴肠上皮化生、Hp阳性萎缩性胃窦炎伴肠上皮化生、胃窦腺癌的胃镜下活检组织标本进行测定分析。结果　在Hp阴性单纯性胃炎组粘膜上皮未见CD4 4V6表达 ,Hp阴性萎缩性胃窦炎伴肠上皮化生、Hp阳性萎缩性胃窦炎伴肠上皮化生、胃窦腺癌各组CD4 4V6表达程度依次逐渐升高 ,各组之间比较差异有显著性 (P <0 .0 5 )。结论　CD4 4V6的表达可能是上皮细胞癌前病变出现的早期生物学信号 ,肠上皮化生细胞可能诱导CD4 4V6的表达 ,而Hp感染则有促进这种诱导表达的作用。     

Gastric epithelial cell proliferation and cagA status in Helicobacter pylori gastritis at different gastric sites

OBJECTIVE: Helicobacter pylori infection causes hyperproliferation which is believed to predispose to the development of gastric carcinoma. The aim of this study was to analyze epithelial cell proliferation topographically in H. pylori gastritis in relationship to cagA status. MATERIAL AND METHODS: The proliferative index (PI: Ki-67-labeled nuclei/total number of foveolar nuclei) was determined in gastric mucosa biopsies taken at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 78 patients with H. pylori gastritis and 20 H. pylori-negative patients. H. pylori and cagA status were determined by polymerase chain reaction (PCR) and serology. RESULTS: PIs were significantly higher in H. pylori- and cagA-positive patients, in comparison with H. pylori- and cagA-negative patients, at all sites (p相似文献   

原位杂交方法检测胃癌及其癌前病变中抑癌基因p53的表达

目的用原位杂交方法检测胃粘膜癌前病变及胃癌组织中ｐ５３ｍＲＮＡ的表达,并观察感染Ｈｐ对其表达的影响．方法病理证实为慢性胃炎６６例和胃癌１６例,用地高辛标记的ｃＤＮＡ为探针进行原位杂交实验,检测其胃粘膜组织中ｐ５３ｍＲＮＡ表达,用单克隆抗体ＤＯ０１进行免疫组化检测Ｐ５３蛋白的表达．结果在慢性萎缩性胃炎、肠化生、异型增生及胃癌中,原位杂交方法检测ｐ５３ｍＲＮＡ表达率分别为５３９％,５２３％,４２８％和２５％,免疫组化方法检测Ｐ５３蛋白的表达率分别为００％,５３％,１５４％和２５％．ｐ５３ｍＲＮＡ的表达与蛋白的表达无明显的一致性,ｐ５３ｍＲＮＡ的表达可以在Ｐ５３蛋白阴性及阳性的细胞中．在２６例萎缩性胃炎中,１４例检测到ｐ５３ｍＲＮＡ的表达,而其中１６例（包括１４例阳性病例）无一例检测到Ｐ５３蛋白的表达．在肠化生、异型增生及胃癌组织中也发现有类似的情况．Ｈｐ感染组与未感染组,ｐ５３ｍＲＮＡ表达率之间统计学检验Ｐ＜００５．结论在胃癌及其癌前病变中,随着病变的发展,ｐ５３ｍＲＮＡ的表达率随之下降,Ｈｐ对其表达有明显的影响     

Comparative classification and grading of Helicobacter pylori gastritis in patients with gastric cancer and patients with functional dyspepsia

BACKGROUND: It has previously been shown that corpus-dominant grade and activity of Helicobacter pylori gastritis in combination with intestinal metaplasia in the antrum or corpus are risk markers for the development of stomach cancer. If one point is scored for each of these three parameters, a gastric cancer risk index is obtained that permits prediction of the risk of gastric cancer developing on the soil of H. pylori gastritis. The aim of the present study was to evaluate the accuracy of the gastric cancer risk index based on a large number of patients compared with dyspeptic controls. METHODS: In 415 biopsied patients with gastric carcinoma, biopsy specimens taken from the antrum and corpus were investigated retrospectively. From this group of patients, 244 patients positive for H. pylori were compared with 244 sex- and age-matched H. pylori-infected patients with functional dyspepsia. RESULTS: H. pylori gastritis was detected in 395 carcinoma patients (95.2%). The 244 sex- and age-matched patients significantly more frequently had corpus-dominant H. pylori gastritis (compared with NUD controls). The incidence of intestinal metaplasia was also significantly increased. For a gastric cancer risk index score of 3 points (i.e. corpus pronounced grade and activity of gastritis, and intestinal metaplasia in antrum or corpus), a sensitivity of 93% and a specificity of 85% for the presence of gastric carcinoma can be calculated. CONCLUSION: Using the proposed risk index, the topographic grading of H. pylori gastritis in the antrum and corpus enables the diagnosis of a 'risk gastritis' to be made.     

Helicobacter pylori infection affects the expression of PCNA, p53, c-erbB-2 and Bcl-2 in the human gastric mucosa.

OBJECTIVE: Helicobacter pylori infection has been related to gastric carcinogenesis. This association is based on epidemiological data, pathological changes observed in the gastric mucosa, and chemical products from bacteria that may induce damage of DNA. In the present study we examined gastric endoscopic biopsies from patients with chronic gastritis, with and without H. pylori infection, and surgical biopsies from gastric cancer patients to evaluate whether this bacteria may induce changes in the expression of molecular markers associated with carcinogenesis. PATIENTS AND METHODS: the study involved 57 biopsies from the antral region of the stomach of patients with chronic gastritis and gastric cancer that were analyzed by immunohistochemistry. Molecular markers examined were: PCNA (Proliferating Cell Nuclear Antigen), p53, c-erbB-2, Bcl-2, and p21 H-ras. RESULTS: PCNA content of epithelial cells was significantly higher in H. pylori infected biopsies. Treatment aimed to eradicate H. pylori decreased the level of PCNA-positive cells in the group of patients that became H. pylori-negative as well as in H. pylori-positive patients. Nuclear p53 expression (used here as a surrogate marker for p53 mutation/inactivation) and c-erbB-2 expression were observed only in the group of patients that remained with the bacteria after treatment. A higher bcl-2 expression in lymphoid cells was observed in H. pylori-positive biopsies, and treatment did not change the expression of this protein. No significant expression of p21 H-ras was observed in the studied biopsies. CONCLUSION: this study suggests that H. pylori is involved in the induction of molecular changes that might predispose human gastric mucosa cells to pre-neoplastic and neoplastic events.     

Histopathological profile of gastritis in adult patients seen at a referral hospital in Kenya

AIM： To conduct a detailed histological study of gastritis in adult patients attending an endoscopy clinic at a Kenyan teaching and referral hospital.
METHODS： Biopsy specimens from consecutive patients were examined and graded according to the Updated Sydney System for H pylori infection, chronic inflammation, neutrophil activity, glandular atrophy and intestinal metaplasia. Also documented were gastric tissue eosinophil counts and presence of lymphoid follicles.
RESULTS： The rate of the graded variables, in the antrum and corpus respectively, were as follows： H pylori infection （91%, 86%）, chronic inflammation （98%, 93%）, neutrophil activity （91%, 86%）, glandular atrophy （57%, 15%） and intestinal metaplasia （11%, 2%）. Lymphoid follicles were noted in 11% of cases. Duodenal and gastric ulcers were documented in 32% and 2% respectively. The mean eosinophil count was 5.9 ±0.74 eosinophils/ HPF and 9.58 ± 0.93 eosinophils/HPF in the corpus and antrum respectively. Significant association was found between the degree of H pylori colonisation with chronic inflammation, neutrophil activity and antral glandular atrophy. Biopsies from the antrum and corpus showed significant histopathological discordance for all the graded variables. H pylori negative cases were associated with recent antibiotic use.
CONCLUSION： The study the chief cause of gastritis reaffirms that H pylori is in this environment. The majority of patients show a moderate to high degree of inflammation but a low degree of glandular atrophy and intestinal metaplasia. The study shows that interrelationships between the histological variables in this African population are similar to those found in other populations worldwide including non-African populations.     

Ornithine decarboxylase activity is a marker of premalignancy in longstanding Helicobacter pylori infection.

BACKGROUND: Longstanding Helicobacter pylori infection may increase the risk of developing gastric adenocarcinoma. The sequence of chronic active gastritis leading to gastritis with atrophy and subsequent intestinal metaplasia is thought to be a key step in gastric carcinogenesis. Ornithine decarboxylase (ODC) activity is increased in some pre-malignant gastrointestinal conditions and is essential for malignant transformation in vitro. AIMS: To measure ODC activity in the antrum of H pylori infected and non-infected subjects and to relate this to histological abnormalities associated with recent and longstanding H pylori infection. METHODS: Six antral mucosal biopsy specimens were obtained from 75 patients for detailed histological assessment and measurement of ODC activity. Samples were measured in duplicate and results expressed as median, interquartile range in pmol/mg protein/h. RESULTS: ODC activity was significantly higher in H pylori positive (164, 88-259 pmol/mg/h) than H pylori negative subjects (99.8, 55-158 pmol/mg/h, p = 0.003). However the presence of gastritis, irrespective of the severity of inflammation or activity had no influence on ODC activity. Gastritis with atrophy was associated with increased ODC activity, which was closely related to the severity of the atrophy (p = 0.01). Similarly, ODC activity was significantly increased in subjects with intestinal metaplasia (196, 83-25) compared with those without intestinal metaplasia (111.7, 65-175, p < 0.04). CONCLUSIONS: These results indicate that the histological changes associated with longstanding H pylori infection rather than inflammation alone are associated with increased polyamine biosynthetic activity. This may be relevant to H pylori associated gastric carcinogenesis.