Helicobacter pylori associated chronic gastritis,clinical syndromes,precancerous lesions,and pathogenesis of gastric cancer development

Helicobacter pylori(H.pylori)infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis(AG),or gastric intestinal metaplasia(GIM),and cancer.Various molecular alterations are identified not only in gastric cancer(GC)but also in precancerous lesions.H.pylori treatment seems to improve AG and GIM,but still remains controversial.In contrast,many studies,including meta-analysis,show that H.pylori eradication reduces GC.Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H.pylori eradication.This indicates that these changes may be an important factor in the identification of high risk patients for cancer development.Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC.A randomized controlled trial from Japan concluded that prophylactic eradication of H.pylori after endoscopic resection should be used to prevent the development of metachronous GC,but recent retrospective studies did not show the tendency.Patients with precancerous lesions(molecular alterations)that do not reverse after H.pylori treatment,represent the"point of no return"and may be at high risk for the development of GC.Therefore,earlier H.pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.     

Screening for and surveillance of gastric cancer

Although the prevalence of gastric cancer (GC) progressively decreased during the last decades, due to improved dietary habit, introduction of food refrigeration and recovered socio-economic level, it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs, that rises many relevant concerns taking into account its worldwide variability, natural history, diagnostic tools, therapeutic strategies, and cost-effectiveness. Intestinal-type, the most frequent GC histotype, develops through a multistep process triggered by Helicobacter pylori (H. pylori) and progressing from gastritis to atrophy, intestinal metaplasia (IM), and dysplasia. However, the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore, it remains unclear who should be screened, when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries, at high prevalence of GC and the high-risk subjects in western countries, at low prevalence of GC. As far as concern surveillance, currently, we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach, the patients at higher risk, the best timing and the cost-effectiveness. Anyway, patients with corpus atrophic gastritis, extensive incomplete IM and dysplasia should enter a surveillance program. At present, screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.     

Histological changes of gastric mucosa after Helicobacter pylori eradication:a systematic review and meta-analysis

AIM:To systematically review pathological changes of gastric mucosa in gastric atrophy(GA)and intestinal metaplasia(IM)after Helicobacter pylori(H.pylori)eradication.METHODS:A systematic search was made of PubMed,Web of Science,EMBASE,ClinicalTrials.gov,OVID and the Cochran Library databases for articles published before March 2013 pertaining to H.pylori and gastric premalignant lesions.Relevant outcomes from articles included in the meta-analysis were combined using Review Manager 5.2 software.A Begg’s test was applied to test for publication bias using STATA 11software.χ2 and I2 analyses were used to assess heterogeneity.Analysis of data with no heterogeneity(P>0.1,I2<25%)was carried out with a fixed effects model,otherwise the causes of heterogeneity were first analyzed and then a random effects model was applied.RESULTS:The results of the meta-analysis showed that the pooled weighted mean difference(WMD)with 95%CI was 0.23(0.18-0.29)between eradication and non-eradication of H.pylori infection in antral IM with a significant overall effect(Z=8.19;P<0.00001)and no significant heterogeneity(χ2=27.54,I2=16%).The pooled WMD with 95%CI was-0.01(-0.04-0.02)for IM in the corpus with no overall effect(Z=0.66)or heterogeneity(χ2=14.87,I2=0%)(fixed effects model).In antral GA,the pooled WMD with 95%CI was 0.25(0.15-0.35)with a significant overall effect(Z=4.78;P<0.00001)and significant heterogeneity(χ2=86.12,I2=71%;P<0.00001).The pooled WMD with 95%CI for GA of the corpus was 0.14(0.04-0.24)with a significant overall effect(Z=2.67;P=0.008)and significant heterogeneity(χ2=44.79,I2=62%;P=0.0003)(random effects model).CONCLUSION:H.pylori eradication strongly correlates with improvement in IM in the antrum and GA in the corpus and antrum of the stomach.     

Helicobacter pylori and gastric cancer: Indian enigma

Helicobacter pylori(H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade Ⅰ carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.     

Helicobacter pylori eradication for preventing gastric cancer

Helicobacter pylori(H.pylori)infection is a major riskfactor for gastric cancer(GC)development,which isone of the most challenging malignant diseases worldwide with limited treatments.In the multistep pathogenesis of GC,H.pylori infection slowly induces chronicactive gastritis,which progresses through the premalignant stages of atrophic gastritis,intestinal metaplasia,and dysplasia,and then finally to GC.Although eradication of H.pylori is a reasonable approach for the prevention of GC,there have been some contradictory reports,with only some long-term follow-up data showingefficacy of this approach.The inconsistencies are likely due to the insufficient number of participants,relatively short follow-up periods,poor quality of study designs,and the degree and extent of preneoplastic changes atthe time of H.pylori eradication.This review analyzesrecent high-quality studies to resolve the discrepancies regarding the eradication of H.pylori for GC prevention.The relationship between H.pylori eradication and GC/precancerous lesions/metachronous GC is examined,and the cost-effectiveness of this strategy in the prevention of GC is assessed.Although it is assumed that eradication of H.pylori has the potential to prevent GC,the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined.As a result,additional well-designed trials with longer followup periods are needed to clarify this issue.     

Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication

The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori(H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection(ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies.The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy(NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a "gastritislike"appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H.pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection.     

Helicobacter pylori infection following partial gastrectomy for gastric cancer

Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer.The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer.Helicobacter pylori(H.pylori)infection is also a well-known characteristic of gastric carcinogenesis.H.pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis;however,the H.pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis.For instance,H.pylori infection of the gastric stump produced controversial results in several recent studies.The prevalence of H.pylori infection in the gastric stump has varied among recent reports.Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ.Bilerefluxate also has a significant influence on the colonization of the stomach stump,with several studies reporting mixed results as well.In contrast,the elimination of H.pylori from the gastric stump has shown a dramatic impact on eradication rate.H.pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers.To overcome the current discrepancies in the literature regarding the role of H.pylori in the gastric stump,further research is required.     

Neutrophil infiltration and the distribution of intestinal metaplasia is associated with metachronous gastric cancer following endoscopic submucosal dissection

BACKGROUND:

Endoscopic submucosal dissection (ESD) of early gastric cancer is a minimally invasive procedure. However, the risk for metachronous cancers after successful cancer treatment remains high and the risk factors for metachronous cancers have not been elucidated.

OBJECTIVE:

To evaluate the risk factors for metachronous gastric cancers after ESD with a long-term follow-up.

METHODS:

A total of 155 consecutive patients (119 men, 36 women, mean age 68.9 years) were treated with ESD between September 2000 and September 2009. Biopsy specimens were obtained from the greater curvature of the antrum and middle corpus to evaluate gastric mucosal status, including Helicobacter pylori, intestinal metaplasia (IM) and neutrophil infiltration (NI) before ESD. Follow-up endoscopy after ESD was scheduled at two and six months, one year and annually thereafter. H pylori eradication was recommended when possible.

RESULTS:

The median follow-up period was 4.2 years. Metachronous gastric cancers were found in 23 of 155 patients (3.5% per year). No local recurrences were observed. The cumulative incidence of metachronous gastric cancer was significantly high in IM and NI in the corpus (P=0.0093 and P=0.0025, respectively [log-rank test]). The ORs for IM and NI in the corpus were 2.65 and 3.06, respectively, according to the Cox proportional hazards model (P=0.024 and P=0.0091, respectively).

CONCLUSIONS:

The presence of IM and NI in the corpus was closely related to the development of metachronous gastric cancer after ESD.     

CpG island methylator phenotype and Helicobacter pylori infection associated with gastric cancer

AIM:To investigate the association between the CpG island methylator phenotype(CIMP) and serum Helicobacter pylori(H.pylori) levels for clinical prediction of gastric cancer(GC) progression.METHODS:We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction.Serum samples from 40 healthy persons were examined at the same time.The genes examined were APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad.H.pylori infection in serum was assayed with an anti-H.pylori immunoglobulin G antibody test and a rapid urease test.RESULTS:The frequencies of high-level methylation in GC tissues for the seven genes were:48% for APC,57.33% for WIF-1,56% for RUNX-3,50.67% for DLC-1,52% for SFRP-1,54.67% for DKK,and 48% for E-cad.The frequencies in GC serum were 30.67% for APC,34.67% for WIF-1,37.33% for RUNX-3,29.33% for DLC-1,33.33% for SFRP-1,32% for DKK,and 26.67% for E-cad.CIMP+(defined as ≥ 3 methylated genes) was associated with 47(62.67%) GC tissue samples and 44(58.67%) GC serum samples.CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons.Of the 75 GC cases,51(68%) were H.pylori +,and 24(32%) were H.pylori-.Of the 51 H.pylori + cases,36 were CIMP+ and 15 were CIMP-.In contrast,for the 24 H.pylori-cases,11 were CIMP+,and 13 were CIMP-.The difference was significant between the H.pylori + and H.pylori-groups(χ 2 = 4.27,P 0.05).Of the 51 H.pylori + GC patients,34 were CIMP+ and 17 were CIMP-,while among the 24 H.pylori-GC cases,10 were CIMP+ and 14 were CIMP-.The difference was significant between the H.pylori+ and H.pylori-groups(χ 2 = 4.21,P 0.05).A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H.pylori +/CIMP+ cases and the H.pylori +/CIMP-cases or CIMP-cases associated with H.pylori assayed in serum(P 0.05).However,there were no significant differences in survival rates between the two groups.CONCLUSION:H.pylori +/CIMP+ cases are associated with higher rates of metastasis and recurrence than H.pylori +/CIMP-cases.Serum may be useful for examining CIMP status.     

Helicobacter pylori and interleukin-8 in gastric cancer

Helicobacter pylori(H.pylori)is a major etiological factor in the development of gastric cancer.Large-scale epidemiological studies have confirmed the strong association between H.pylori infection and both cancer development and progression.Interleukin-8(IL-8)is overexpressed in gastric mucosa exposed to H.pylori.The expression of IL-8 directly correlates with a poor prognosis in gastric cancer.IL-8 is multifunctional.In addition to its potent chemotactic activity,it can induce proliferation and migration of cancer cells.In this review,we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer.The relationship between IL-8 and H.pylori is discussed.We also summarize the current therapeutics against IL-8 in gastric cancer.     

Helicobacter pylori infection,gastrin and cyclooxygenase-2 in gastric carcinogenesis

Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori(H. pylori) infec-tion and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demon-strated that expression of cyclooxygenase-2(COX-2) is elevated in gastric carcinomas and in their precursor le-sions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.     

Relationship between β-catenin expression and epithelial cell proliferation in gastric mucosa with intestinal metaplasia

AIM: To investigate beta-catenin expression in patients with intestinal metaplasia, and to look for a possible relationship between beta-catenin expression and either epithelial proliferation values or Helicobacter pylori (H pylori) infection. METHODS: Twenty patients with complete type intestinal metaplasia were studied. beta-Catenin expression and epithelial cell proliferation in antral mucosa were assessed using an immunohistochemical analysis. H pylori infection was detected by histology and a rapid urease test. RESULTS: Reduced beta-catenin expression on the surface of metaplastic cells was detected in 13 (65%) out of 20 patients. Moreover, in eight (40%) patients intranuclear expression of beta-catenin was found. When patients were analyzed according to H pylori infection, the prevalence of both beta-catenin reduction at the cell surface and its intranuclear localization did not significantly differ between infected and uninfected patients. Cell proliferation was higher in patients with intranuclear beta-catenin expression as compared to the remaining patients, although the difference failed to reach the statistical significance (36+/-8.9 vs 27.2+/-11.4, P = 0.06). On the contrary, a similar cell proliferation value was observed between patients with reduced expression of beta-catenin on cell surface and those with a normal expression (28.1+/-11.8 vs 26.1+/-8.8, P = 0.7). H pylori infection significantly increased cell proliferation (33.3+/-10.2% vs 24.6+/-7.4%, respectively, P = 0.04). CONCLUSION: Both cell surface reduction and intranuclear accumulation of beta-catenin were detected in intestinal metaplasia. The intranuclear localization of beta-catenin increases cell proliferation. H pylori infection does not seem to play a direct role in beta-catenin alterations, whilst it significantly increases cell proliferation.     

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian populationby comparison with a Japanese population.METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age(± 5 years), sex, and endoscopic diagnosis were matched between the two countries.RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, where as 73.9 % of advanced can cersdisplayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients(75.9% vs 4 8. 3 %, P0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian Cag Aspecific antibody was negative in 99.4% of H. pyloripositive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients(P 0.0001), with the exception of the intestinal metaplasia score of specimen from the greater curvature of the upper body. The type of gastritis changed from antrumpredominant gastritis to corpus-predominant gastritis with age in both populations.CONCLUSION: Gastric cancer was located in the upper part of the stomach in half of the Mongolian patients; Mongolian patients were infected with non-East-Asiantype H. pylori.     

Relatedness of Helicobacter pylori populations to gastric carcinogenesis

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrica1, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and possibly result from geographical separation of the bacterium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different populations of H. pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H. pylori. Further studies are indicated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals.     

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     

Eradication rate and histological changes after Helicobacter pylori eradication treatment in gastric cancer patients following subtotal gastrectomy

AIM: To investigate the eradication rate and histological changes after Helicobacter pylori(H. pylori) eradication treatment following subtotal gastrectomy for gastric cancer.METHODS: A total of 610 patients with H. pylori infection who had undergone surgery for either early or advanced gastric adenocarcinoma between May 2004 and December 2010 were retrospectively studied. A total of 584 patients with proven H. pylori infection after surgery for gastric cancer were enrolled in this study. Patients received a seven day standard triple regimen as first-line therapy and a 10 d bismuthcontaining quadruple regimen as second-line therapy in cases of eradication failure. The patients underwent an esophagogastroduodenoscopy(EGD) between six and 12 mo after surgery, followed by annual EGDs. A further EGD was conducted 12 mo after confirming the result of the eradication and the histological changes. A gastric biopsy specimen for histological examination and Campylobacter-like organism testing was obtained from the lesser and greater curvature of the corpus of the remnant stomach. Histological changes in the gastric mucosa were assessed using the updated Sydney system before eradication therapy and at follow-up after 12 mo.RESULTS: Eradication rates with the first-line and second-line therapies were 78.4%(458/584) and 90%(36/40), respectively, by intention-to-treat analysis and 85.3%(458/530) and 92.3%(36/39), respectively, by per-protocol analysis. The univariate and multivariate analyses revealed that Billroth Ⅱ surgery was an independent factor predictive of eradication success in the eradication success group(OR = 1.53, 95%CI: 1.41-1.65, P = 0.021). The atrophy and intestinal metaplasia(IM) scores 12 mo after eradication were significantly lower in the eradication success group than in the eradication failure group(0.25 ± 0.04 vs 0.47 ± 0.12, P = 0.023; 0.27 ± 0.04 vs 0.51 ± 0.12, P = 0.015, respectively). The atrophy and IM scores 12 mo after successful eradication were significantly lower in the Billroth Ⅱ group than in the Billroth I group(0.13 ± 0.09 vs 0.31 ± 0.12, P = 0.029; 0.32 ± 0.24 vs 0.37 ± 0.13, P = 0.034, respectively).CONCLUSION: Patients with H. pylori following subtotal gastrectomy had a similar eradication rate to patients with an intact stomach. H. pylori eradication is recommended after subtotal gastrectomy.     

Helicobacter pylori and gastric mucin expression: A systematic review and meta-analysis

AIM: To investigate the relationship between Helicobacter pylori (H. pylori) and mucin expression in gastric mucosa.METHODS: English Medical literature searches were conducted for gastric mucin expression in H. pylori infected people vs uninfected people. Searches were performed up to December 31^th 2014, using MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Studies comparing mucin expression in the gastric mucosa in patients positive and negative for H. pylori infection, were included. Meta-analysis was performed by using Comprehensive meta-analysis software (Version 3, Biostat Inc., Englewood, NJ, United States). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated compared mucin expression in individual studies by using the random effects model. Heterogeneity between studies was evaluated using the Cochran Q-test, and it was considered to be present if the Q-test P value was less than 0.10. I² statistic was used to measure the proportion of inconsistency in individual studies, with I² > 50% representing substantial heterogeneity. We also calculated a potential publication bias.RESULTS: Eleven studies, which represent 53 sub-studies of 15 different kinds of mucin expression, were selected according to the inclusion criteria. Every kind of mucin has been considered as one study. When a specific mucin has been studied in more than one paper, we combined the results in a nested meta-analysis of this particular mucin: MUC2, MUC6, STn, Paradoxical con A, Tn, T, Type 1 chain mucin, LeA, SLeA, LeB, AB-PAS, MUC1, and MUC5AC. The odds ratio of mucin expression in random analysis was 2.33, 95%CI: 1.230-4.411, P = 0.009, higher expression in H. pylori infected patients. Odds ratio for mucin expression in H. pylori positive patients was higher for MUC6 (9.244, 95%CI: 1.567-54.515, P = 0.014), and significantly lower for MUC5AC (0.447, 95%CI: 0.211-0.949, P = 0.036). Thus, H. pylori infection may increase MUC6 expression and decrease MUC5AC expression by 924% and 52%, respectively.CONCLUSION: H. pylori inhibits MUC5AC expression in the gastric epithelium, and facilitates colonization. In contrast, increased MUC6 expression may help inhibiting colonization, using MUC6 antibiotics properties.     

Effect of Helicobacter pylori on gastric epithelial cells

The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world’s population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori’s avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori.     

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。     

Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection

AIM:To evaluate the incidence and clinical characteristics of gastric cancer(GC) in peptic ulcer patients with Helicobacter pylori(H.pylori) infection.METHODS:Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed.Those with previous gastric ulcer(GU) and H.pylori infection were assigned to the Hp GU-GC group(n = 86) and those with previous duodenal ulcer(DU) disease and H.pylori infection were assigned to the Hp DUGC group(n = 35).The incidence rates of GC in the Hp GU-GC and Hp DU-GC groups were analyzed.Data on demographics(age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren's classification, atrophy of surrounding mucosa and intestinal metaplasia(IM)], outcome of eradication therapy for H.pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed.Univariate and multivariate analyses were performed to identify factors influencing GC development.The relative risk of GC was evaluated using a Cox proportional hazards model.RESULTS:The incidence rates of GC were 3.60%(86/2387) in the Hp GU-GC group and 1.66%(35/2098) in the Hp DU-GC group.The annual incidence was 0.41% in the Hp GU-GC group and 0.11% in the Hp DUGC group.The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the Hp GU-GC group than in the Hp DU-GC group(86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P 0.05).In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H.pylori infection were significantly associated with the development of GC(P 0.05).There was no significant difference in the prognosis of GC patients between the Hp GU-GC and Hp DU-GC groups(P = 0.347).The relative risk of GC development in the Hp GUGC group compared to that of the Hp DU-GC group,after correction for age and gender,was 1.71(95%CI:1.09-2.70;P=0.02).CONCLUSION:GU patients with H.pylori infection had higher GC incidence rates and relative risks.Atrophy of surrounding mucosa,IM and eradication therapy were associated with GC.