Association of Helicobacter pylori infection with atrophic gastritis and intestinal metaplasia

AIMS: To evaluate the effect of Helicobacter pylori infection and aging on atrophy and intestinal metaplasia of the gastric mucosa. METHODS: One hundred and sixty-three patients were divided into three age groups and underwent an upper gastrointestinal endoscopy where no esophagitis, peptic ulcers, or malignancies were detected. Two biopsy specimens were obtained from the anterior and posterior walls of the antrum and of the fundus. These were used to evaluate the grade of gastritis, bacterial culture and histologic evidence of H. pylori infection. RESULTS: Helicobacter pylori infection was found to be directly associated with an increased risk of gastritis grade (odds ratio (OR) = 90 (95% CI; 30-270)). An age of 60 years and older along with H. pylori infection was also strongly associated with an increased risk of atrophy (OR = 6.6, (95% CI; 2.9-15.2)); OR = 9.8, (95% CI; 2.7-35.4)), as was intestinal metaplasia of the gastric mucosa (OR = 5.5, (95% CI; 1.7-17.6)); OR = 7.9, (95% CI; 2.8-46.1)). The prevalence of atrophic gastritis increased with advancing age in H. pylori-infected patients, but no such phenomenon was observed in H. pylori-uninfected patients. The prevalence of intestinal metaplasia significantly increased with advancing age, irrespective of the presence of H. pylori infection. In addition, H. pylori uninfected female patients had a decreased risk of intestinal metaplasia. CONCLUSIONS: These results suggest that atrophic gastritis is not a normal aging process, but instead is likely to be the result of H. pylori infection, while intestinal metaplasia is caused by both the aging process and H. pylori infection. A decreased risk of intestinal metaplasia found in uninfected female subjects may partly explain the lower prevalence of gastric cancer in females than in males.     

胃粘膜肠化中幽门螺杆菌感染与PCNA,c-erbB-2的表达

目的研究肠化胃粘膜幽门螺杆菌（Ｈｐ）阳性率与ＰＣＮＡ,ｃｅｒｂＢ２表达率之间关系,以探讨Ｈｐ感染在胃肠化发生、发展中作用．方法经病理检查证实的慢性胃炎伴肠化１１６例,对照组非溃疡性消化不良．应用改良ＷａｒｔｈｉｎＳｔａｒｙ法检测Ｈｐ,免疫酶组化ＳＰ法检测ＰＣＮＡ,ｃｅｒｂＢ２的表达,比较Ｈｐ阳性组和阴性组间ＰＣＮＡ,ｃｅｒｂＢ２的阳性表达率．结果胃粘膜肠化者Ｈｐ感染率增高（５８６％ｖｓ１８８％,χ２＝１０７９,Ｐ＜００１）,肠化胃上皮内少见Ｈｐ粘附,Ｈｐ阳性组ＰＣＮＡ,ｃｅｒｂＢ２表达高于阴性组（４８／６８ｖｓ１２／４８,χ２＝９０５,Ｐ＜００５;３６／７４ｖｓ２／４２,χ２＝１３２８,Ｐ＜００１）．结论Ｈｐ感染促进胃粘膜肠化,并使肠化胃粘膜细胞增殖迅速而启动恶性变,故Ｈｐ感染可能促进胃癌的形成．     

根除幽门螺杆菌对胃黏膜及肠化、不典型增生的影响

目的探讨根除幽门螺杆菌（Hp）后慢性胃炎的胃黏膜炎症及肠上皮化生、不典型增生的变化。方法选择172例伴有Hp感豢的慢性活动性胃炎病人分为两组：阴性组（68例）和阳性组（104例），观察阴性组治疗后的变化并与阳性组进行比较，并观察阴性组肠上皮化生和不典型增生在治疗前后的变化。结果阴性组的胃黏膜炎症有28例（41．2％）好转，2例（2．9％）治愈，明显高于阳性组（P〈0.01），其伴有的肠上皮化生有2例（25％）治愈，4例（50％）好转，不典型增生有7例（38．9％）好转，6例（33．3%）治愈。结论Hp感染阴转后慢性胃炎的治疗效果明显优于阳性者，其伴有的肠化和不典型增生亦能好转或治愈。因此，根除Hp是治疗Hp相关性胃炎和防止发生胃癌的重要措施。     

Effects of Helicobacter pylori infection on mucin expression in gastric carcinoma and pericancerous tissues

BACKGROUND: Helicobacter pylori infection is one of the major causes of human gastric carcinoma and can disturb the gastric mucosa barrier. Mucins have not only lubricating and protecting functions, but are also related to signal transduction, turnover of gastric epithelium and carcinogenesis of gastric mucosa. The aim of this study was to investigate the relationship between H. pylori infection and aberrant mucin expression in patients with gastric carcinoma. METHODS: H. pylori infection was diagnosed by the Warthin-Starry staining method. Different kinds of mucins were detected using an immunohistochemical method. RESULTS: Of 46 patients with gastric carcinoma, there were 26 patients who had H. pylori infection (56.5%). Of 21 pericancerous mucosas from the H. pylori-positive patients, 14 had MUC2 expression (66.7%), seven had strong MUC1 expression (+ + +) (33.7%), seven had strong MUC6 expression (+ + +) (33.3%), and five had strong MUC5AC expression (+ + +) (23.8%). In contrast, only six of 18 H. pylori-negative pericancerous mucosas had MUC2 expression (33.3%) (P < 0.05 compared with H. pylori-positive pericancerous mucosas), 12 had strong MUC1 expression (+ + +) in 16 H. pylori-negative pericancerous mucosas (75%) (P < 0.05), 11 had strong MUC6 expression (+ + +) in 16 H. pylori-negative pericancerous mucosas (68.8%) (P < 0.05), and 10 had strong MUC5AC expression (+ + +) in 14 H. pylori-negative pericancerous mucosas (71.4%) (P < 0.01). Of the H. pylori-positive cancerous tissues, 50% (13/26) had MUC1 expression and 38.5% (10/26) had MUC6 expression. In comparison, of the H. pylori-negative cancerous tissues, 80% (16/20) had MUC1 expression (P < 0.05) and 80% (16/20) had MUC6 expression (P < 0.01). CONCLUSIONS: The results indicate that H. pylori infection can alter the expression of some mucin genes in pericancerous mucosa and cancerous tissues of gastric carcinoma, then destroy the gastric mucosa barrier.     

根除幽门螺杆菌对胃黏膜肠化的影响

目的　幽门螺杆菌 (Hp)感染可导致慢性活动性胃炎进一步发展为慢性萎缩性胃炎、胃黏膜肠化、最终发展成肠型胃癌。通过 5年随访 ,探讨根除Hp是否对胃黏膜肠化逆转、发生及发展有影响。方法　将 1996年快速尿素酶试验及组织学方法检测Hp均为阳性的 398例病人随机分为治疗组和对照组。治疗组 2 0 1例 ,进行根除Hp治疗 ;对照组 197例 ,给予安慰剂 ;服药前及 5年后分别从胃窦部及胃体部取材检测胃炎、胃炎活动性及肠化。结果　 5年后治疗组中 15 1/2 0 1例Hp为阴性 ,对照组中 16 1/197例Hp为阳性 ;治疗组中Hp被根除的病人胃炎活动性的检出率明显减少 ,与对照组持续Hp感染者比较 ,差异有显著性 (P <0 .0 0 0 1) ;对照组中持续Hp感染者 5年后肠化检出率与自身 5年前、治疗组成功根除Hp者 5年前和 5年后比较均增高 ,差异有显著性 (P均 <0 .0 0 1) ,治疗组根除Hp的病人 5年前后比较差异无显著性 ;对照组中持续Hp感染者胃窦部 5年后肠化检出率与自身 5年前、治疗组根除Hp者 5年前和 5年后比较均增高 ,差异有显著性 (分别为P <0 .0 0 1,P <0 .0 0 1和P<0 .0 1) ,治疗组根除Hp感染的病人 5年前后比较差异无显著性 ;对照组持续Hp感染的病人与治疗组根除Hp感染的病人胃窦部肠化新增及新减情况比较无差异。 结论　 5年     

Histological characteristics of gastric mucosa prior to Helicobacter pylori eradication may predict gastric cancer

Abstract

Objective. Although Helicobacter pylori (H. pylori) eradication has been shown to inhibit gastric cancer, it does not completely suppress it. Therefore, risk factors of gastric cancer development following H. pylori eradication were examined. Material and methods. A total of 2355 patients (1501 males and 824 females) underwent successful eradication of H. pylori. Endoscopic atrophy, histological gastritis, atrophy, intestinal metaplasia (IM), and operative link for gastritis assessment (OLGA) staging were subsequently evaluated. Results. Following eradication, 33/2355 patients (25 males and 8 females) developed gastric cancer. Compared to a nongastric cancer group that was matched according to gender and age, the incidence of endoscopic atrophy (3.52 ± 1.45 vs. 4.85 ± 1.18, p < 0.001), histological atrophy at the greater curvature of the antrum (1.42 ± 0.80 vs. 1.95 ± 0.86, p = 0.0059), inflammation (2.05 ± 0.59 vs. 2.33 ± 0.66, p = 0.031), IM at the greater curvature of the corpus (0.06 ± 0.30 vs. 0.24 ± 0.54, p = 0.029), the ratio of OLGA-stage 0–II/III, IV (13/8 vs. 55/11, p = 0.038) were significantly higher for the gastric cancer group. Multivariate analysis also showed the highest odds ratio (6.26, 95% confidence interval or CI, 1.28–30.60, p = 0.023) for IM at the greater curvature of the corpus. Conclusions. Severe endoscopical atrophy, OLGA staging, histological atrophy at the antrum, inflammation, and particularly IM at the corpus, were identified as risk factors for gastric cancer development following H. pylori eradication. Therefore, eradication should be performed before these predictors develop.     

Helicobacter pylori infection induces a reversible expression of the CDX2 transcription factor protein in human gastric epithelium

Objective. The homeobox gene CDX2 is implicated in the appearance of intestinal metaplasia in Helicobacter pylori gastritis. The aim of this study was to investigate whether CDX2 expression in gastric mucosa occurs before the appearance of overt intestinal metaplasia in H. pylori gastritis, and whether or not this expression is reversible. Material and methods. CDX2 was studied by immunohistochemistry in a cohort of 38 patients with H. pylori gastritis before and after eradication (mean follow-up 6.3 years) of H. pylori. A cohort of 49 individuals with healthy stomachs was analysed as a control. Results. In the control group no immunostaining of CDX2 in the epithelial cells of the gastric body was found, while in 57% of the cases a mild, aberrant nuclear immunostaining of CDX2 in the non-metaplastic epithelial cells in antrum, designated as “positive staining of single cells” (PSSC), was found. In H. pylori gastritis, the PSSC was seen in antrum and corpus in 100% and 26% of the cases, respectively. The prevalence of antral PSSC was significantly increased (on average by 4-fold) in H. pylori gastritis as compared with controls. After eradication of H. pylori, the prevalence of PSSC decreased significantly in antrum but not in corpus. Conclusions. Expression of CDX2 at low intensity is common in the epithelium of normal antrum, and this expression is enhanced in H. pylori gastritis. Expression of CDX2 is reversible at least in antrum after eradication of H. pylori infection.     

Effects of Helicobacterpylori eradication on atrophic gastritis and intestinal metaplasia： A 3-year follow-up study

AIM: To investigate the effect of H pylori eradication on atrophic gastritis and intestinal metaplasia (IM). METHODS: Two hundred and fifty-nine patients with atrophic gastritis in the antrum were included in the study, 154 patients were selected for H pylori eradication therapy and the remaining 105 patients served as untreated group. Gastroscopy and biopsies were performed both at the beginning and at the end of a 3-year follow-up study. Gastritis was graded according to the updated Sydney system. RESULTS: One hundred and seventy-nine patients completed the follow-up, 92 of them received H pylori eradication therapy and the remaining 87 H pylori-infected patients were in the untreated group. Chronic gastritis, active gastritis and the grade of atrophy significantly decreased in H pylori eradication group (P<0.01). However, the grade of IM increased in H pylori -infected group (P<0.05). CONCLUSION: H pylori eradication may improve gastric mucosal inflammation, atrophy and prevent the progression of IM.     

Endoscopic duodenitis, gastric metaplasia and Helicobacter pylori

BACKGROUND AND AIMS: The purpose of this study was to investigate the relationship between gastric metaplasia and Helicobacter pylori in patients with endoscopic duodenitis. METHODS: The subjects were 57 patients with endoscopic duodentitis with or without H. pylori-associated gastritis. Biopsy specimens were obtained from the stomach and duodenal bulb to assess the histological findings and H. pylori infection. Gastric metaplasia was divided into three types: complete, intermediate and incomplete, according to the amount of mucus in the metaplastic cells. In 10 H. pylori-positive patients, endoscopic and histological findings of duodenitis were compared before and after eradication of the bacteria. RESULTS: There was no significant difference in the extent of gastric metaplasia or the appearance and severity of endoscopic duodenitis between H. pylori-positive and -negative groups. The complete type of gastric metaplasia was frequently detected in the H. pylori-negative group, whereas the incomplete type was frequently observed in the H. pylori-positive group. After eradication of H. pylori, the incomplete type changed to the complete type with a decrease of histological inflammation. CONCLUSIONS: The complete type of gastric metaplasia occurred frequently without H. pylori infection, whereas the incomplete type was frequently associated with H. pylori infection.     

胃黏膜炎症和肠上皮化生与幽门螺杆菌关系的远期观察

[目的]远期追踪幽门螺杆菌(Hp)相关胃炎及Hp阴性的胃炎胃黏膜炎症和肠上皮化生(IM)在病程演变中的关系.[方法]经胃镜检查确诊的Hp阳性胃炎86例(A组),Hp阴性的胃炎92例(B组),对照观察两组5年前后的逆转变化,胃黏膜炎症和IM的程度积分.[结果]5年后A组86例中Hp阳性者61例(70.9%)、转阴者25例(29.1%);5年后两组Hp阳性者、5年前后的炎症程度积分差异无统计学意义;B组Hp阴性者、A组Hp阳性者5年前后比较差异无统计学意义;5年后B组中Hp仍阴性者与A组Hp仍阳性者,其胃黏膜炎症和IM积分比较差异有统计学意义(P＜0.01).[结论]Hp在胃黏膜内存在的时间越长,其炎症和IM的程度越重,发生率也增加,而Hp阴性的胃炎和Hp阳性胃炎转阴后其炎症和IM的程度及发生率均有下降.     

Correlations among Helicobacter pylori infection and the expression of cyclooxygenase‐2 and vascular endothelial growth factor in gastric mucosa with intestinal metaplasia or dysplasia

Background and Aims: To examine the rate of Helicobacter pylori infection and the expression of cyclooxygenase‐2 (COX‐2) and vascular endothelial growth factor (VEGF) in gastric mucosa with intestinal metaplasia or dysplasia, and explore their correlations in precancerous gastric lesions. Methods: A total of 172 patients were included in the study. H. pylori infection was evaluated by hematoxylin–eosin and modified Giemsa staining. The expression of COX‐2 and VEGF proteins was detected by immunohistochemistry. Results: The rates of H. pylori infection in gastric mucosal dysplasia (DYS), intestinal metaplasia in gastric mucosa (IM), chronic atrophic gastritis (CAG) and chronic superficial gastritis (CSG) patients were significant differences (P = 0.001). The average optical density (AOD) values of COX‐2 staining in CSG, CAG, IM and DYS patients were 13.81 ± 5.53, 45.28 ± 21.44, 73.67 ± 26.02 and 91.23 ± 45.11, respectively, with significant differences among CSG, CAG and IM patients (P = 0.037, 0.001 and 0.047 for CSG vs CAG, CSG vs IM and CAG vs IM, respectively). The expression level of VEGF in DYS patients was significantly higher than those in other patients (P = 0.001, 0.001 and 0.001 for DYS vs CSG, DYS vs CAG and DYS vs IM, respectively). The expression levels of COX‐2 in H. pylori‐positive IM, CAG and DYS patients were significantly higher than those in H. pylori‐negative counterparts (P = 0.043, 0.009, 0.001, respectively). Additionally, the expression level of COX‐2 was positively correlated with that of VEGF with the aggravation of gastric mucosal lesions (r = 0.640, P = 0.006). Conclusion: H. pylori infection might be able to induce the expression of COX‐2 in precancerous gastric lesions, which in turn upregulates the expression of VEGF.     

Effect of Helicobacter pylori infection on cyclooxygenase‐2 expression in gastric antral mucosa

OBJECTIVE: Helicobacter pylori infection is a major etiological cause of chronic gastritis. Inducible cyclooxygenase (COX‐2) is an important regulator of mucosal inflammation. Recent studies indicate that expression of COX‐2 may contribute to gastro­intestinal carcinogenesis. The aim of this study was to investigate the effects of H. pylori infection and eradication therapy on COX‐2 expression in gastric antral mucosa. METHODS: Antral biopsies were taken from 46 H. pylori‐infected patients, who also had chronic gastritis, both before and after anti‐H. pylori treatment. The COX‐2 protein was stained by using immunohistochemical methods and COX‐2 expression was quantified as the percentage of epithelial cells expressing COX‐2. Gastritis and H. pylori infection status were graded according to the Sydney system. RESULTS: Cyclooxygenase‐2 expression was detected in the cytoplasm of gastric antral epithelial cells both before and after the eradication of H. pylori. Cyclooxygenase‐2 expression in mucosa with H. pylori infection was compared with the corresponding mucosa after successful H. pylori eradication (20.1 ± 13.1%vs 13.8 ± 5.9%; P < 0.05). At the same time, COX‐2 expression in H. pylori‐infected mucosa was com­pared with the normal controls (18.0 ± 14.1%vs 12.3 ± 4.6%, P < 0.05). Expression of COX‐2 was correlated with the degree of chronic inflammation (r= 0.78, P < 0.05). CONCLUSIONS: Our results showed that H. pylori infection leads to gastric mucosal overexpression of COX‐2 protein, suggesting that the enzyme is involved in H. pylori‐related gastric pathology in humans.     

Long-term effects of Helicobacter pylori eradication in Mongolian gerbils

Background: In this study, to clarify whether Helicobacter pylori eradication alters the course of the development of gastric mucosal changes in the stomach, we examined the long-term effects of H. pylori eradication on H. pylori-inoculated gerbils. Methods: A total of 40 H. pylori-inoculated gerbils were randomized and subjected, at 22 months after inoculation, to eradication treatment with dual therapy of omeprazole plus clarithromycin, or with therapy with a novel quinolone compound, Y-34867, alone. The animals were killed at the start of administration (control group) or at 8 months after the completion of therapy (vehicle or eradication-treatment groups). Results: Severe histopathological changes in the gastric mucosa were observed in all H. pylori-inoculated gerbils at the start of administration. At 8 months after completion of therapy, the frequency of gastritis, erosion, intestinal metaplasia, and gastric carcinoid in the eradication therapy groups was markedly reduced compared with that in the control and vehicle groups. Values for anti-H. pylori IgG titer, bacterial counts, and gastrin also decreased significantly. Conclusions: These results suggest that H. pylori eradication may have had a therapeutic effect not only on gastritis, erosion, and gastric ulcer but also on glandular atrophy, intestinal metaplasia, and gastric carcinoid. Received: November 8, 2001 / Accepted: May 31, 2002 Reprint requests to: F. Hirayama     

Short-term celecoxib to regress long-term persistent gastric intestinal metaplasia after Helicobacter pylori eradication

Background and Aim:  The intestinal metaplasia (IM) has overexpressions of cyclooxygenase-2 (COX-2) and β-catenin. This pilot study assessed whether celecoxib, a selective COX-2 inhibitor, could regress IM that persisted long term after Helicobacter pylori eradication.
Methods:  Thirty-three patients with H. pylori eradication were enrolled in the present study due to the persistence of IM after a 3-year follow up. These patients received celecoxib 200 mg/day for 8 weeks, and were serially checked for levels of blood urea nitrogen and creatinine once per 2 weeks. After 8-week celecoxib treatment, IM regression was assessed by panendoscopy. The gastric specimens, taken before and after celecoxib, were immunochemically stained for COX-2 and β-catenin.
Results:  The intention-to-treat and per-protocol analyses to the rates of IM regression by 8-week celecoxib treatment were 24.2% (8/33) and 28.6% (8/28), respectively. All enrolled patients had no renal impairment. Even in the patients without total IM regression, mean IM scores in the antrum decreased after 8-week celecoxib treatment ( P  = 0.007). The patients with complete regression of IM after 8-week celecoxib treatment had a significantly lower COX-2 expression, but not β-catenin expression, at enrollment than those patients without IM regression ( P  = 0.031).
Conclusion:  Short-term celecoxib treatment can be safe and promising to regress long-term persistent IM after H. pylori eradication.     

幽门螺杆菌长期感染与胃黏膜炎症和肠上皮化生的关系

目的探讨幽门螺杆菌(Hp)长期感染及根除与胃黏膜炎症和肠上皮化生(IM)的关系。方法随访71例5年前和78例10年前Hp感染者,分析对比其前后Hp感染情况、胃黏膜炎症和IM的变化。结果5年前Hp阳性71例中,现在52例(73.2％)Hp仍呈阳性,19例(26.8％)转阴;10年前Hp阳性的78例中,现在59例(75.6％)Hp仍呈阳性,19例(24.4％)转阴。Hp长期阳性者5年前和现在及10年前和现在慢性炎症严重程度积分分别为1.635±0.376与1.808±0.301(P>0.05)和1.661±0.398与2.232±0.335(P<0.01);IM的发生率分别为17.3％(9/52)与26.9％(14/52)(P>0.05)和11.9％(7/59)与39.0％(23/59)(P<0.01);IM严重程度积分分别为1.444±0.527与1.667±0.442(P>0.05)和1.571±0.534与2.286±0.488(P<0.05)。Hp转阴者5年前和现在及10年前和现在慢性炎症严重程度积分分别为1.684±0.369与1.369±0.426(P<0.05)和1.647±0.389与1.182±0.396(P<0.01);IM的发生率为31.6％(6/19)和52.6％(10/19);IN严重程度积分分别为1.333±0.516与1.167±0.775(P>0.05)和1.600±0.516与1.100±0.316(P<0.05)。结论Hp感染持续时间越长,胃黏膜炎症越严重,IM程度亦越严重且发生率高;根除Hp不仅能减轻胃黏膜的炎症程度和IM程度,而且能防止IM的发生。     

CDX2 MUC2在胃黏膜肠上皮化生组织中的表达情况及其临床意义研究

目的 探讨尾型同源盒转录因子2(CDX2)、黏蛋白2(MUC2)在胃黏膜肠上皮化生组织中的表达情况及其临床意义.方法 选择2011年1月至2014年5月于宁夏医科大学总医院消化内科就诊并行内镜活检的152例患者,根据病理检查结果将其分为非萎缩性胃炎组(32例)、萎缩性胃炎组(31例)、低级别上皮内瘤变组(24例)、高级...     

Duodenal gastric metaplasia and Helicobacter pylori infection in high and low duodenal ulcer-prevalent areas in India

Background: Previous reports, based on surgery, showed duodenal ulcer (DU) to be more common in the rice‐eating areas of southern India than in the northern wheat‐eating areas. Aims: Does this difference persist? Can it be explained by risk factors other than diet? Methods: A total of 20 053 records from patients undergoing endoscopy for dyspepsia, and 590 endoscopy patients from two northern and two southern centers in India were studied prospectively. Records were scrutinized to determine the relative incidence of DU and non‐ulcer dyspepsia in wheat‐ and rice‐eating areas. Age, sex, length of history, smoking and medication were recorded. Three antral biopsies and one from each duodenal quadrant were taken. A rapid urease test was carried out on one of the antral biopsies; the others were examined for Helicobacter pylori, gastritis, duodenitis and duodenal gastric metaplasia. Results: The difference in diet‐associated prevalence persisted. No differences in smoking, Helicobacter pylori infection or duodenal gastric metaplasia were found between the two regions, but all three were more common in DU than in non‐ulcer dyspeptic patients from both dietary areas. Conclusions: The dietary differences between the regions remain the only factor to account for the differences in DU prevalence. A strong interrelationship between duodenal gastric metaplasia and cigarette smoking is demonstrated.