Prevalence of H pylori associated ‘high risk gastritis＇ for development of gastric cancer in patients with normal endoscopic findings

AIM: To investigate the prevalence of H pylori associated corpus-predominant gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM) in patients without any significant abnormal findings during upper-GI endoscopy. METHODS: Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System. Eight hundred and forty-five patients (mean age 54.8 +/- 2.8 years) with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scoring systems. RESULTS: The prevalence of severe H pylori associated changes like pangastritis, CPG, IM, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years. CONCLUSION: The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk for gastric cancer development--only a proper follow-up can provide this information.     

胃幽门螺杆菌感染与胃癌：胃癌低发和高发区胃镜调查对照

我们在胃癌低发区和广州和高发区兰州市各选一间医院，对同月接受胃镜检查的全部病人进行活检组织学，幽门螺杆菌尿素酶法检测。结果显示兰州市胃癌和胃溃疡检出率高，该地区慢性胃炎病人ＨＰ感染病高，感染年龄提前，胃炎的组织学模式也有特点，即胃炎多犯及全胃，胃粘膜萎缩发生率高。     

Effects of the myeloperoxidase 463 gene polymorphisms on development of atrophy in H pylori infected or noninfected gastroduodenal disease

AIM: To investigate the relationship between myelo- peroxidase polymorphisms as a host-related factor and atrophy caused by H pylori. METHODS: Our study enrolled 77 patients. Biopsy materials obtained during gastrointestinal endoscopies were evaluated for the presence of H pylori. Polymerase chain reaction-restriction fragment length polymorphism assay was used to characterize myeloperoxidase genotypes. RESULTS: Forty four patients (57.1%) were Hp (+) and 33 (42.9%) were Hp (-). Sixty six (85.7%) had GG genotype, 10 (12.9%) had GA genotype and 1 (1.29%) had AA genotype. The change in atrophy in relation to neutrophil infiltration was significant in Hp (+) patients (P = 0.0001). The change in atrophy in relation to neutrophil infiltration in patients with GG genotype was significant (P = 0.002). However, the change in atrophy in relation to neutrophil infiltration was not significiant in patients with Hp (+) GG genotype (r = 0.066, P = 0.63). CONCLUSION: Myeloperoxidase genotype is critical for development of atrophy in relation to the severity of inflammation. However, it is interesting to note that, H pylori does not show any additive effect on development of atrophy.     

Does gastric atrophy exist in children？

INTRODUCTION The discovery of H pylori in adult patients by Warren and Marshall[1] was a major event in modern gastroenterology, rewarded with the Nobel Prize in 2005, and strongly stimulated paediatric studies focused on gastroduodenal pathology. The pre…     

H pylori and gastric cancer： Shifting the global burden

INTRODUCTION Since the discovery of H pylori in 1983, intensive research has led to the conclusion that infection with this bacterium is the major cause for the development of distal gastric cancer. Infection with the bacterium leads to a chronic inflamma…     

Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis

Many epidemiological reports indicate that Helicobacterpylori(H pylori)infection plays an important role ingastric carcinogenesis.Several genetic and epigeneticalterations contribute to the initiation,promotion,andprogression of the cancer cells in a multi-step manner.H pylori is known to induce chronic inflammation in thegastric mucosa.Its products,including superoxides,participate in the DNA damage followed by initiation,andthe inflammation-derived cytokines and growth factorscontribute to the promotion of gastric carcinogenesis.By eradicating H pylori,gastric inflammation can becured; the therapy diminishes the levels not onlyof inflammatory cell infiltration,but also atrophy/intestinal metaplasia in part.A randomized controlledtrial revealed that the eradication therapy diminishedthe gastric cancer prevalence in cases without pre-cancerous conditions.In addition,recent epidemiologicalstudies from Japanese groups demonstrated thatthe development of gastric cancer,especially of theintestinal type,was decreased by successful eradicationtherapy,although these were designed in a non-randomized manner.However,it should be mentionedthat endoscopic detection is the only way to evaluate thedegree of gastric carcinogenesis.We have reported thatthe endoscopic and histological morphologies could bemodified by eradication therapy and it might contributeto the prevalence of gastric cancer development.Considering the biological nature of cancer cellproliferation,it is considered that a sufficiently long-termfollow-up would be essential to discuss the anticancereffect of eradication therapy.     

Serum anti-Helicobacter pylori antibody titer and its association with gastric nodularity,atrophy, and age: A cross-sectional study

AIM To clarify the role of serum anti-Helicobacter pylori(H. pylori) antibody titers in gastric cancer.METHODS In this cross-sectional study, the effect of patients' baseline characteristics and endoscopic findings on their serum antibody titers were assessed. We evaluated consecutive patients who underwent esophagogastroduodenoscopy and their first evaluation for H. pylori infection using a serum antibody test. We excluded patients with a history of eradication therapy. The participants were divided into four groups according to their E-plate serum antibody titer. Patients with serum antibody titers 3, 3-9.9, 10-49.9, and ≥ 50 U/m L were classified into groups A, B, C, and D, respectively. RESULTS In total, 874 participants were analyzed with 70%, 16%, 8.7%, and 5.1% of them in the groups A, B, C, and D, respectively. Patients in group C were older than patients in groups A and B. Gastric open-type atrophy, intestinal metaplasia, enlarged folds, diffuse redness, and duodenal ulcers were associated with a high titer. Regular arrangements of collecting venules, fundic gland polyps, superficial gastritis, and gastroesophageal reflux disease were related to a low titer. Multivariate analysis revealed that nodularity(P = 0.0094), atrophy(P = 0.0076), and age 40-59 years(vs age ≥ 60 years, P = 0.0090) were correlated with a high serum antibody titer in H. pylori-infected patients. Intestinal metaplasia and atrophy were related to age ≥ 60 years in group C and D.CONCLUSION Serum antibody titer changes with age, reflects gastric mucosal inflammation, and is useful in predicting the risk of gastric cancer.     

Eradication of H pylori for the prevention of gastric cancer

Infection with H pylori is the most important known etiological factor associated with gastric cancer. While colonization of the gastric mucosa with H pylori results in active and chronic gastritis in virtually all individuals infected, the likelihood of developing gastric cancer depends on environmental, bacterial virulence and host specific factors. The majority of all gastric cancer cases are attributable to H pylori infection and therefore theoretically preventable. There is evidence from animal models that eradication of H pylori at an early time point can prevent gastric cancer development. However, randomized clinical trials exploring the prophylactic effect of H pylori eradication on the incidence of gastric cancer in humans remain sparse and have yielded conflicting results. Better markers for the identification of patients at risk for H pylori induced gastric malignancy are needed to allow the development of a more efficient public eradication strategy. Meanwhile, screening and treatment of H pylori in first-degree relatives of gastric cancer patients as well as certain high-risk populations might be beneficial.     

慢性胃炎、胃癌组织中幽门螺杆菌基因分型的临床研究

目的 探讨幽门螺杆菌(HP)基因分型与慢性胃炎、胃癌的关系。方法 应用PCR—RFLP方法对36例慢性胃炎及45例胃癌组织中的幽门螺杆菌菌株进行检测。并用HindⅡ酶切尿毒酶B(UreB)扩增基因产物进行多态性分析。结果 36例慢性胃炎HP阳性24例(66．7％)，45例胃癌组织中HP阳性23例(51．1％)。二者差异无显著性。47例HP阳性标本均显示不同的RFLP图谱。胃癌组织中未发现特异性条带。结论 慢性胃炎、胃癌与HP感染密切相关。HP基因具有多态性，HP菌株存在基因型差异。PCR—RFLP方法可对HP菌株进行鉴定并将其分型。     

Helicobacterpylori infection and gastropathy： A comparison between Indonesian and Japanese patients

AIM: To compare the effects of Helicobacter pylori ( H pylori) infection on gastropathy between Indonesian and Japanese patients.METHODS: Biopsy specimens were obtained during upper gastrointestinal endoscopy from 167 subjects (125 Indonesians and 42 Japanese) with uninvestigated symptoms of dyspepsia. The specimens were analyzed for the presence of H pylori using urease analysis, histopathology, and cell culture. The grade and activity of gastritis was assessed using the updated Sydney system.RESULTS: The percentages of Indonesian and Japanese patients who were H pylori-positive at the antrum or body of the stomach were similar (68% and 59.5%, respectively; P = 0.316). Of those who were H pylori-positive, more Japanese patients than Indonesian patients had high levels of polymorphonuclear cells ( P = 0.001), mononuclear cells ( P = 0.013), glandular atrophy ( P = 0.000), and intestinal metaplasia ( P = 0.011) in both the antrum and body of the stomach.CONCLUSION: The grade of gastritis and prevalence of mucosal atrophy and intestinal metaplasia were higher in Japanese patients. The difference between Indonesian and Japanese patients was significant.     

Nucleotide-binding oligomerization domain 1 and Helicobacter pylori infection: A review

Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.     

幽门螺杆菌相关性胃炎和胃癌前期病变的发病机制

幽门螺杆菌（H．pylori）感染诱发胃黏膜的炎症反应是引起一切病变的基础，并且它在慢性胃炎→萎缩性胃炎→胃黏膜肠上皮化生→不典型增生→胃癌的演变过程中至始至终起作用，因此H．priori相关性胃炎是H．priori致病的启动因子。H．priori感染可引起胃黏膜局部固有和获得性免疫异常，炎症介质的释放、ROS和NO含量的异常，胃上皮细胞增殖与凋亡失衡，端粒酶及相关基因表达异常。这些因素综合作用引起胃黏膜炎症，并且由其发展为胃癌前病变，最终导致胃癌发生。     

幽门螺杆菌感染对Fas/FasL表达的影响在胃癌发生中的作用

目的：观察幽门螺杆菌（Hp）及其不同毒力株（cagA阳性与cagA阴性株）感染对胃黏膜上皮细胞Fas/FasL表达的影响，进而探讨胃癌的发生机制。方法：胃镜下取胃窦黏膜标本，将研究对象按病理结果分为黏膜萎缩组，黏膜萎缩伴轻度不典型增生组，黏膜萎缩伴中度不典型增生组，胃腺癌组，黏膜大致正常组为对照组，再根据Hp感染情况为分Hp阳性组与阴性组，并将Hp阳性组进一步成cagA阳性组及阴性组，共9组80例。以快速尿素酶试验，PCR及组织学第三种方法检测Hp，用PCR方法对Hp进行分型。用免疫组化法检测Fas、FasL等表达情况。结果Hp感染率为60．0％，cagA阳性率为90．47％，非腺癌病人Hp阳性组Fas/FasL表达明显高于Hp阴性组（P＜0．05），腺癌组Fas/FasL表达明显高于大致正常组及黏膜萎缩，黏膜萎缩伴轻度不典型增生，黏萎缩伴中度不典型增生组（P＜0．01）。cagA阳性组Fas/FasL表达与cagA阴性组差异无显著性（P＞0．05）。结论：幽门螺杆菌感染后早期即黏 萎缩阶段已出现Fas、FasL等的表达增加，随细胞凋亡的增加，黏膜上皮细胞萎缩加重，细胞DNA不稳定性增加，并出现不典型增生加重， Fas、FasL的表达随之增强，一旦肿瘤细胞形成，Fas/FasL表达进一步增加，形成局部免疫豁免区，导致肿瘤的浸润生长。cagA阳性的菌株在促成肿瘤的发生过程中无明显作用。     

Expression of macrophage migration inhibitory factor is associated with enhanced angiogenesis and advanced stage in gastric carcinomas

AIM: Macrophage migration inhibitory factor (MIF) was reported to inactivate p53 and play an essential role in the growth and angiogenesis of tumors that arise at sites of chronic inflammation. Gastric inflammation is a prerequisite for the development of gastric carcinoma (GC), which has recently been linked to Helicobacter pylori (H pylori) infection. This study aimed to investigate dinicopathological significance of MIF expression in GCs. METHODS: We selected 90 consecutive patients with GCs for investigation of the relation among MIF status, clinicopathological parameters, p53 expression and angiogenesis. MIF and p53 expression was assessed by immunohistochemistry as positive and negative groups. Tumor vascularity was evaluated by counting microvessel density on anti-CD34 stained sections. Expression status of MIF was correlated with determined dinicopathological data, p53 immunoreactivity and microvessel counts. RESULTS: Strong immunostainings of MIF were observed in the cytoplasm of cancerous cells in 40% (36/90) of cases but not in normal or metaplastic epithelia. There was no statistically significant correlation between MIF expression and age, gender, H pylori infection, tumor location, histological subtypes, lymph node metastasis or p53 expression. Early GC less frequently overexpressed MIF as compared to advanced GCs (4/20 vs 32/70, P= 0.04). A remarkably increased microvessel count was noted in GCs with MIF expression than those without MIF expression (55.1±30.1 vs 31.3±28.8, P= 0.0001). CONCLUSION: Our results suggest that expression of MIF may contribute to the progression and enhanced angiogenesis in a substantial portion of GCs.     

Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and Helicobacter pylori associated gastric diseases

AIM: To investigate the relationship between the expression of pepsinogen C (PGC) and gastric cancer, precancerous diseases, and Helicobacter pylori (H pylori) infection. METHODS: The expression of PGC was determined by immunohistochemistry method in 430 cases of gastric mucosa. H3 Pylori infection was determined by HE staining, PCR and ELISA in 318 specimens. RESULTS: The positive rate of PGC expression in 54 cases of normal gastric mucosa was 100%. The positive rates of PGC expression in superficial gastritis or gastric ulcer or erosion, atrophic gastritis or gastric dysplasia and gastric cancer decreased significantly in sequence (P<0.05; 100%/89.2% vs 14.3%/15.2% vs 2.4%). The over-expression rate of PGC in group of superficial gastritis with H pyloriinfection was higher than that in group without H pylori infection (P<0.05; x2= 0.032 28/33 vs 15/25). The positive rate of PGC expression in group of atrophic gastritis with H pylori infection was lower than that in group without H pylori infection (P<0.01; x2 = 0.003 4/61 vs9/30), and in dysplasia and gastric cancer. CONCLUSION: The level of PGC expression has a close relationship with the degree of malignancy of gastric mucosa and development of gastric lesions. There is a relationship between H pylori infection and expression of antigen PGC in gastric mucosa, the positive rate of PGC expression increases in early stage of gastric lesions with H pylori infection such as gastric inflammation and decreases during the late stage such as precancerous diseases and gastric cancer. PGC-negative cases with H py/ori-positive gastric lesions should be given special attention.     

NEW DIAGNOSTIC METHODS FOR HELICOBACTER PYLORI INFECTION

Recently, some studies revealed that gastric cancer and precancer, were more frequent in individuals with H. pylori antibodies. Histological studies, found that the relationship between H. pylori infection and gastric cancer were in wide range (19% ‐ 80%). In our department, from 1999 Jan 1^st to 1999 Dec 31^th No biopsy, showed severe atrophic/dysplasia, or lymphoid follicle. Age, ethnic and location were also studied, correlated to malignant and premalignant lesions.     

根除幽门螺杆菌感染对慢性胃炎疗效影响的多中心临床研究

目的 探讨根除幽门螺杆菌(Hp)对慢性胃炎患者临床症状、内镜表现及病理改变的影响.方法 采用多中心、前瞻性、随机化对照研究,观察2009年1月至2010年12月间入组的慢性胃炎患者,分为Hp阳性根除组、Hp阳性不根除组和Hp阴性组,均予以8周的胃黏膜保护剂治疗,对比各组治疗前后临床症状、内镜下表现及病理炎症的变化.结果...     

幽门螺杆菌感染与胃癌前病变胃内分布的特点

目的：检测胃幽门螺杆菌(Hpylori)阳性患者胃癌前病变的组织病理情况和在胃内的分布特点.方法：伴有消化不良症状的门诊患者,先应用~(14)C尿素酶呼气试验检测Hpylori感染,如为阳性则行胃镜检查,于胃窦大、小弯侧及胃体大、小弯侧,分别取活检做病理检查,判断是否存在癌前病变,如：萎缩、肠化和不典型增生,并分析其分布特点.结果：在128例Hpylori阳性患者中,胃癌前病变71例,占55.5%.而阴性患者中,癌前病变的发生率仅占31.3%(10/32),两组间有显著性差并(P＜0.05).在Hpylori阳性组患者中,癌前病变在各部位所占的百分比分别为,胃窦小弯侧(58.5%)＞胃窦大弯侧(36.9%)＞胃体小弯侧(23.8%)＞胃体大弯侧(14.6%).而在Hpylori阴性对照组中,胃窦小弯侧(31.3%)＞胃窦大弯侧(18.2%)＞胃体小弯侧(15.6%)＞胃体大弯侧(12.5%).结论：Hpylori感染与胃癌前病变密切相关,胃癌前病变以胃窦小弯侧阳性率最高,其次为胃窦大弯侧.     

非幽门螺杆菌感染患者上腹部不适的可能机制

目的 探讨非幽门螺杆菌感染患者上腹部不适相关症状的可能机制.方法 收集2006年8月至11月初次行胃镜、组织学检查幽门螺杆菌呈阴性的成人患者232例,2005年9月至2009年8月门诊及住院儿童患者31例(年龄<14岁).对以上患者行胃镜取胃黏膜组织做连续切片,HE染色及WS染色观察组织学改变.结果 成人组患者组织内可观察到微、小动脉腔堵塞和(或)灶性出血病变,其中16例(8.8%)黏膜和(或)黏膜下层见微、小动脉腔部分或完全堵塞,82例(45.6%)仅有黏膜灶性出血,82例(45.6%)两种病变同时存在.微、小动脉腔堵塞病变以移行部检出率最高(65.2%,P=0.159),灶性出血病变以底体部检出率最高(65.6%,P=0.001).微、小动脉腔堵塞病变组烧心症状发生率显著低于无动脉腔堵塞/出血病变组(x2=8.564,P=0.003).儿童组中96.8%(30/31)的患者活检组织中观察到微、小动脉腔堵塞和(或)灶性出血病变.结论 胃微、小动脉堵塞引起的黏膜缺血比较常见,可发生于各个年龄段,可能是导致非幽门螺杆菌感染患者上腹部不适相关症状的重要原因.     

Kyoto classification of gastritis: Advances and future perspectives in endoscopic diagnosis of gastritis

This editorial provides an update of the recent evidence on the endoscopy-based Kyoto classification of gastritis, clarifying the shortcomings of the Kyoto classification, and providing prospects for future research, with particular focus on the histological subtypes of gastric cancer (GC) and Helicobacter pylori (H. pylori) infection status. The total Kyoto score is designed to express GC risk on a score ranging from 0 to 8, based on the following five endoscopic findings: Atrophy, intestinal metaplasia (IM), enlarged folds (EF), nodularity, and diffuse redness (DR). The total Kyoto score reflects H. pylori status as follows: 0, ≥ 2, and ≥ 4 indicate a normal stomach, H. pylori-infected gastritis, and gastritis at risk for GC, respectively. Regular arrangement of collecting venules (RAC) predicts non-infection; EF, nodularity, and DR predict current infection; map-like redness (MLR) predicts past infection; and atrophy and IM predict current or past infection. Atrophy, IM, and EF all increase the incidence of H. pylori-infected GC. MLR is a specific risk factor for H. pylori-eradicated GC, while RAC results in less GC. Diffuse-type GC can be induced by active inflammation, which presents as EF, nodularity, and atrophy on endoscopy, as well as neutrophil and mononuclear cell infiltration on histology. In contrast, intestinal-type GC develops via atrophy and IM, and is consistent between endoscopy and histology. However, this GC risk-scoring design needs to be improved.