Gastric cancer remains a significant global health challenge,causing a substantial number of cancer-related deaths,particularly in China.While the exact causes of gastric cancer are still being investigated,Helicobac-...Gastric cancer remains a significant global health challenge,causing a substantial number of cancer-related deaths,particularly in China.While the exact causes of gastric cancer are still being investigated,Helicobac-ter pylori(H.pylori)infection has been identified as the primary risk factor,which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time.Since the 1990s,numerous efforts have focused on assessing the effectiveness of H.pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment.This body of work,including several community-based interventions and meta-analyses,has shown a reduction in both the incidence of and mortality from gastric cancer following H.pylori treatment,alongside a decreased risk of metachronous gastric cancer.In this review,we seek to consolidate current knowledge on the effects of H.pylori treatment on gastric cancer prevention,its systemic consequences,cost-effectiveness,and the influence of antibiotic resistance and host characteristics on treatment outcomes.We further discuss the potential for precision primary prevention of H.pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.展开更多
BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-imm...BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could b...BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and th...BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.展开更多
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 pylo...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.展开更多
Gastric cancer is a global public health burden, nearly one million new cases are diagnosed per year worldwide, of which 44% of cases occur in China. The prognosis of gastric cancer varies remarkably by the stage of c...Gastric cancer is a global public health burden, nearly one million new cases are diagnosed per year worldwide, of which 44% of cases occur in China. The prognosis of gastric cancer varies remarkably by the stage of cancer, and most of the patients in China are diagnosed at advanced stages, resulting in poor prognoses. Effective strategies to reduce the burden of gastric cancer include primary prevention through testing and treatment of Helicobacter pylori(H. pylori) and secondary prevention by screening and early detection. Although many countries have issued management guidelines and consensus reports concerning these strategies, the limited availability of healthcare resources often precludes their widespread implementation. Therefore, assessing the costs, benefits, and harms of population-based intervention measures through health economic evaluation is necessary for informed health policy decisions. Accordingly, we synthesize management approaches from different countries on H. pylori eradication and endoscopic screening, and also summarize recent advancements in health economic evaluations on population-based preventive strategies. The goal of the review is to provide empirical evidence supporting optimal resource allocation, maximizing benefits for the population, and ultimately reducing the burden of gastric cancer.展开更多
BACKGROUND Gastric cancer(GC)is the fourth leading cause of cancer-related deaths worldwide.Diagnosis relies on histopathology and the number of endoscopies is increasing.Helicobacter pylori(H.pylori)infection is a ma...BACKGROUND Gastric cancer(GC)is the fourth leading cause of cancer-related deaths worldwide.Diagnosis relies on histopathology and the number of endoscopies is increasing.Helicobacter pylori(H.pylori)infection is a major risk factor.AIM To develop an in-silico GC prediction model to reduce the number of diagnostic surgical procedures.The meta-data of patients with gastroduodenal symptoms,risk factors associated with GC,and H.pylori infection status from Holy Family Hospital Rawalpindi,Pakistan,were used with machine learning.METHODS A cohort of 341 patients was divided into three groups[normal gastric mucosa(NGM),gastroduodenal diseases(GDD),and GC].Information associated with socioeconomic and demographic conditions and GC risk factors was collected using a questionnaire.H.pylori infection status was determined based on urea breath test.The association of these factors and histopathological grades was assessed statistically.K-Nearest Neighbors and Random Forest(RF)machine learning models were tested.RESULTS This study reported an overall frequency of 64.2%(219/341)of H.pylori infection among enrolled subjects.It was higher in GC(74.2%,23/31)as compared to NGM and GDD and higher in males(54.3%,119/219)as compared to females.More abdominal pain(72.4%,247/341)was observed than other clinical symptoms including vomiting,bloating,acid reflux and heartburn.The majority of the GC patients experienced symptoms of vomiting(91%,20/22)with abdominal pain(100%,22/22).The multinomial logistic regression model was statistically significant and correctly classified 80%of the GDD/GC cases.Age,income level,vomiting,bloating and medication had significant association with GDD and GC.A dynamic RF GC-predictive model was developed,which achieved>80%test accuracy.CONCLUSION GC risk factors were incorporated into a computer model to predict the likelihood of developing GC with high sensitivity and specificity.The model is dynamic and will be further improved and validated by including new data in future research studies.Its use may reduce unnecessary endoscopic procedures.It is freely available.展开更多
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 gast...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.展开更多
Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related fac...Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors,leading to inflammatory changes,dysbiosis and eventually gastric cancer.The normal gastric microbiota shows diversity,with Proteobacteria[Helicobacter pylori(H.pylori)belongs to this family],Firmicutes,Actinobacteria,Bacteroides and Fusobacteria being the most abundant phyla.Most studies indicate that H.pylori has inhibitory effects on the colonization of other bacteria,harboring a lower diversity of them in the stomach.When comparing the healthy with the diseased stomach,there is a change in the composition of the gastric microbiome with increasing abundance of H.pylori(where present)in the gastritis stage,while as the gastric carcinogenesis cascade progresses to gastric cancer,the oral and intestinal-type pathogenic microbial strains predominate.Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself.Successful H.pylori eradication is suggested to restore gastric microbiota,at least in primary stages.It is more than clear that Hp-I,gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll.Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H.pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.展开更多
BACKGROUND Persistent Helicobacter pylori(H.pylori)infection causes chronic inflammation,atrophy of the gastric mucosa,and a high risk of developing gastric cancer.In recent years,awareness of eradication therapy has ...BACKGROUND Persistent Helicobacter pylori(H.pylori)infection causes chronic inflammation,atrophy of the gastric mucosa,and a high risk of developing gastric cancer.In recent years,awareness of eradication therapy has increased in Japan.As H.pylori infections decrease,the proportion of gastric cancers arising from H.pylori uninfected gastric mucosa will increase.The emergence of gastric cancer arising in H.pylori uninfected patients though rarely reported,is a concern to be addressed and needs elucidation of its clinicopathological features.AIM To evaluate the clinicopathological features of early gastric cancer in H.pyloriuninfected patients.METHODS A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019.Of these,30 lesions in 30 patients were diagnosed as H.pylori-uninfected gastric cancer(Hp UIGC).We defined a patient as H.pylori-uninfected using the following three criteria:(1)The patient did not receive treatment for H.pylori,which was determined by investigating medical recordsand conducting patient interviews;(2)Lack of endoscopic atrophy;and(3)The patient was negative for H.pylori after being tested at least twice using various diagnostic methods,including serum anti-H.pylori-Ig G antibody,urease breath test,rapid urease test,and microscopic examination.RESULTS The frequency of Hp UIGC was 1.2%(30/2462)for the patients in our study.The study included 19 males and 11 females with a mean age of 59 years.The location of the stomach lesions was divided into three sections;upper third(U),middle third(M),lower third(L).Of the 30 lesions,15 were U,1 was M,and 14 were L.Morphologically,17 lesions were protruded and flat elevated type(0-I,0-IIa,0-IIa+IIc),and 13 lesions were flat and depressed type(0-IIb,0-IIc).The median tumor diameter was 8 mm(range 2-98 mm).Histological analysis revealed that22 lesions(73.3%)were differentiated type.The Hp UIGC lesions were classified into fundic gland type adenocarcinoma(7 cases),foveolar type welldifferentiated adenocarcinoma(8 cases),intestinal phenotype adenocarcinoma(7 cases),and pure signet-ring cell carcinoma(8 cases).Among 30 Hp UIGCs,24 lesions(80%)were limited to the mucosa;wherein,the remaining 6 lesions showed submucosal invasion.One of the submucosal invasive lesions showed more than 500μm invasion.The mucin phenotype analysis identified 7 Hp UIGC with intestinal phenotype and 23 with gastric phenotype.CONCLUSION We elucidated the clinicopathological characteristics of Hp UIGC,revealing recognition not only undifferentiated-type but also differentiated-type.In addition,intestinal phenotype tumors were also observed and could be an important tip.展开更多
AIM: To detect and evaluate the antibodies against Helicobacter pylori (H pylori) neutrophil-activating protein (HP-NAP) in patients with gastric cancer and other gastroduodenal diseases.METHODS: Recombinant HP-...AIM: To detect and evaluate the antibodies against Helicobacter pylori (H pylori) neutrophil-activating protein (HP-NAP) in patients with gastric cancer and other gastroduodenal diseases.METHODS: Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coll. Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 (IL-8) and growth-related oncogene (GROα) cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected.RESULTS: The serum positivity and mean absorbancevalue of HP-NAP-specific antibodies in the gastriccancer group (97.7% and 1.01 ± 0.24) were significantly higher than those in the chronic gastritisgroup (85.7% and 0.89 ± 0.14, P 〈 0.005) and healthy control group (27.7% and 0.65 ± 0.18, P 〈 0.001). The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly upregulate IL-8 production in gastric epithelial cell lines but had no effect on GROα production.CONCLUSION: Infection with virulent H py/ori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma, rHP-NAP- based ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.展开更多
We conducted a comprehensive literature review and meta-analysis study on the efficacy of Helicobacter pylori(H. pylori) eradication in preventing metachronous gastric cancer after endoscopic resection among an East A...We conducted a comprehensive literature review and meta-analysis study on the efficacy of Helicobacter pylori(H. pylori) eradication in preventing metachronous gastric cancer after endoscopic resection among an East Asian population. Our results showed that the eradication of this pathogen significantly reduced the risk of susceptibility to metachronous gastric cancer in these patients. However, based on the available evidence, several factors such as increasing age, severe atrophy in the corpus and antrum, and intestinal metaplasia all may increase the risk of metachronous gastric cancer in H. pylori eradicated patients.展开更多
Background: Many studies documented an association between a Helicobacter pylori infection and the development of human gastric cancer. None of these studies were able to identify Helicobacter pylori as a cause or as ...Background: Many studies documented an association between a Helicobacter pylori infection and the development of human gastric cancer. None of these studies were able to identify Helicobacter pylori as a cause or as the cause of human gastric cancer. The basic relation between gastric cancer and Helicobacter pylori still remains uncertain. Objectives: This systematic review and re-analysis of Naomi Uemura et al. available long-term, prospective study of 1526 Japanese patients are performed so that some new and meaningful inference can be drawn. Materials and Methods: Data obtained by Naomi Uemura et al. who conducted a long-term, prospective study of 1526 Japanese patients with a mean follow up about 7.8 years and endoscopy at enrolment and in the following between one and three years after enrolment were reanalysed. Statistical Analysis Used: The method of the conditio sine qua non relationship was used to proof the hypothesis without a Helicobacter pylori infection no development of human gastric cancer. The mathematical formula of the causal relationship was used to proof the hypothesis, whether there is a cause effect relationship between a Helicobacter pylori infection and human gastric cancer. Significance was indicated by a p-value of less than 0.05. Results: Based on the data published by Uemura et al. we were able to make evidence that without a Helicobacter pylori infection no development of human gastric cancer. In other words, a Helicobacter pylori infection is a conditio sine qua non of human gastric cancer. In the same respect, the data of Uemura et al. provide significant evidence that a Helicobacter pylori infection is the cause of human gastric cancer. Conclusions: Without a Helicobacter pylori infection of human stomach no development of human gastric cancer. Helicobacter pylori is the cause of human gastric cancer (k = +0.07368483, p-value = 0.00399664).展开更多
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. Variou...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.展开更多
Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infecti...Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.展开更多
Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal...Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20<sup>th</sup> century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19<sup>th</sup> century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17<sup>th</sup> to 19<sup>th</sup> centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19<sup>th</sup> century. The environment before the 20<sup>th</sup> century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19<sup>th</sup> century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20<sup>th</sup> century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for “surgical disease” or for “Sippy” diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.展开更多
Helicobacter pylori(H.pylori)plays an important role in gastric carcinogenesis,as the majority of gastric cancers develop from H.pylori-infected gastric mucosa.The rate of early gastric cancer diagnosis has increased ...Helicobacter pylori(H.pylori)plays an important role in gastric carcinogenesis,as the majority of gastric cancers develop from H.pylori-infected gastric mucosa.The rate of early gastric cancer diagnosis has increased in Japan and Korea,where H.pylori infection and gastric cancer are highly prevalent.Early intestinal-type gastric cancer without concomitant lymph node metastasis is usually treated by endoscopic resection.Secondary metachronous gastric cancers often develop because atrophic mucosa left untreated after endoscopic treatment confers a high risk of gastric cancer.The efficacy of H.pylori eradication for the prevention of metachronous gastric cancer remains controversial.However,in patients who undergo endoscopic resection of early gastric cancer,H.pylori eradication is recommended to suppress or delay metachronous gastric cancer.Careful and regularly scheduled endoscopy should be performed to detect minute metachronous gastric cancer after endoscopic resection.展开更多
BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression ...BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated;it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17(G-17)and pepsinogens(PGs)during clinical practice.AIM To explore the prevalence of type I and type II H.pylori infection status and their impact on G-17 and PG levels in clinical practice.METHODS Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined,and 523 patients were enrolled in this study.H.pylori infection was confirmed by both 13C-urea breath test and serological assay.Patients were divided into non-atrophic gastritis(NAG),nonatrophic gastritis with erosion(NAGE),chronic atrophic gastritis(CAG),peptic ulcers(PU)and gastric cancer(GC)groups.Their serological G-17,PG I and PG II values and PG I/PG II ratio were also measured.RESULTS A total H.pylori infection rate of 3572 examined patients was 75.9%,the infection rate of 523 enrolled patients was 76.9%,among which type I H.pylori infection accounted for 72.4%(291/402)and type II was 27.6%;88.4%of GC patients were H.pylori positive,and 84.2%of them were type I infection,only 11.6%of GC patients were H.pylori negative.Infection rates of type I H.pylori in NAG,NAGE,CAG,PU and GC groups were 67.9%,62.7%,79.7%,77.6%and 84.2%,respectively.H.pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio.Both types of H.pylori induced higher G-17 level,but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG,NAGE and CAG groups over uninfected controls.Overall PG I levels showed no difference among all disease groups and in the presence or absence of H.pylori;in stratified analysis,its level was increased in GC and PU patients in H.pylori and type I H.pylori-positive groups.CONCLUSION Type I H.pylori infection is the major form of infection in this geographic region,and a very low percentage(11.6%)of GC patients are not infected by H.pylori.Both types of H.pylori induce an increase in G-17 level,while type I H.pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease.The data provide insights into H.pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.展开更多
Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to familie...Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to families and societies;it is also a heavy economic and healthcare burden for countries that having high infection rates.Eradication of H.pylori is recommended for all infected individuals.Traditionally,"test and treat"and"screen and treat"strategies are available for various infected populations.However,clinical practice has noticed that these strategies have some shortfalls and may need refinement,mostly due to the fact that they are not easily manageable,and are affected by patient compliance,selection of treatment population and cost-benefit estimations.Furthermore,it is difficult to control infections from the source,therefore,development of additional,compensative strategies are encouraged to solve the above problems and facilitate bacteria eradication.H.pylori infection is a family-based disease,but few studies have been performed in a whole family-based approach to curb its intra-familial transmission and the development of related diseases.In this work,a third,novel whole family-based H.pylori eradication strategy is introduced.This approach screens,identifies,treats and follows up on all H.pylori-infected individuals in entire families to control H.pylori infection among family members,and reduce its long-term complications.This strategy is high-risk population-oriented,and able to reduce H.pylori spread among family members.It also has good patient-family compliance and,importantly,is practical for both high and low H.pylori-infected communities.Future efforts in these areas will be critical to initiate and establish healthcare policies and management strategies to reduce H.pylori-induced disease burden for society.展开更多
Gastric cancer is a leading cause of cancer death worldwide,and significant effort has been focused on clarifying the pathology of gastric cancer.In particular,the development of genome-wide analysis tools has enabled...Gastric cancer is a leading cause of cancer death worldwide,and significant effort has been focused on clarifying the pathology of gastric cancer.In particular,the development of genome-wide analysis tools has enabled the detection of genetic and epigenetic alterations in gastric cancer;for example,aberrant DNA methylation in gene promoter regions is thought to play a crucial role in gastric carcinogenesis.The etiological viewpoint is also essential for the study of gastric cancers,and two distinct pathogens,Helicobacter pylori(H.pylori)and Epstein-Barr virus(EBV),are known to participate in gastric carcinogenesis.Chronic inflammation of the gastric epithelium due to H.pylori infection induces aberrant polyclonal methylation that may lead to an increased risk of gastric cancer.In addition,EBV infection is known to cause extensive methylation,and EBV-positive gastric cancers display a high methylation epigenotype,in which aberrant methylation extends to not only Polycomb repressive complex(PRC)-target genes in embryonic stem cells but also non-PRC-target genes.Here,we review aberrant DNA methylation in gastric cancer and the association between methylation and infection with H.pylori and EBV.展开更多
基金supported by the National Natural Science Founda-tion of China(grant number:82273704)the Beijing Hospitals Author-ity Clinical Medicine Development of Special Funding Support(grant number:ZLRK202325)+6 种基金Beijing Hospitals Authority’s Ascent Plan,Na-tional Key R&D Program of China(grant number:2018YFA0507503)Peking University Medicine Fund for world’s leading discipline or disci-pline cluster development(grant number:BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(grant number:2022-27)and Science Foundation of Peking University Cancer Hospital(grant number:XKFZ2410)he funding sources had no role in study designin the collection,analysis,and interpretation of datain the writing of the reportor in the decision to submit the article for publication.The funders had no role in study design,data collection,data analysis,data interpretation,or writing of the report.
文摘Gastric cancer remains a significant global health challenge,causing a substantial number of cancer-related deaths,particularly in China.While the exact causes of gastric cancer are still being investigated,Helicobac-ter pylori(H.pylori)infection has been identified as the primary risk factor,which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time.Since the 1990s,numerous efforts have focused on assessing the effectiveness of H.pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment.This body of work,including several community-based interventions and meta-analyses,has shown a reduction in both the incidence of and mortality from gastric cancer following H.pylori treatment,alongside a decreased risk of metachronous gastric cancer.In this review,we seek to consolidate current knowledge on the effects of H.pylori treatment on gastric cancer prevention,its systemic consequences,cost-effectiveness,and the influence of antibiotic resistance and host characteristics on treatment outcomes.We further discuss the potential for precision primary prevention of H.pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.
基金Supported by Ministerio de la Produccion de Peru,No.317-PNICP-EC-2014,and No.430-PNICP-PIAP-2014Consejo Nacional de Ciencia Tecnologia e Innovacion Tecnologica,No.196-2015-FONDECYT,No.197-2015-FONDECYT,and No.204-2015-FONDECYT.
文摘BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.
基金All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Southwest Medical University(Protocol No.SWMU20230818).
文摘BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.
文摘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.
基金supported in part by the Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (No. ZLRK202325)a grant from National Key R&D Program of China (No. 2018YFC 1313105)。
文摘Gastric cancer is a global public health burden, nearly one million new cases are diagnosed per year worldwide, of which 44% of cases occur in China. The prognosis of gastric cancer varies remarkably by the stage of cancer, and most of the patients in China are diagnosed at advanced stages, resulting in poor prognoses. Effective strategies to reduce the burden of gastric cancer include primary prevention through testing and treatment of Helicobacter pylori(H. pylori) and secondary prevention by screening and early detection. Although many countries have issued management guidelines and consensus reports concerning these strategies, the limited availability of healthcare resources often precludes their widespread implementation. Therefore, assessing the costs, benefits, and harms of population-based intervention measures through health economic evaluation is necessary for informed health policy decisions. Accordingly, we synthesize management approaches from different countries on H. pylori eradication and endoscopic screening, and also summarize recent advancements in health economic evaluations on population-based preventive strategies. The goal of the review is to provide empirical evidence supporting optimal resource allocation, maximizing benefits for the population, and ultimately reducing the burden of gastric cancer.
文摘BACKGROUND Gastric cancer(GC)is the fourth leading cause of cancer-related deaths worldwide.Diagnosis relies on histopathology and the number of endoscopies is increasing.Helicobacter pylori(H.pylori)infection is a major risk factor.AIM To develop an in-silico GC prediction model to reduce the number of diagnostic surgical procedures.The meta-data of patients with gastroduodenal symptoms,risk factors associated with GC,and H.pylori infection status from Holy Family Hospital Rawalpindi,Pakistan,were used with machine learning.METHODS A cohort of 341 patients was divided into three groups[normal gastric mucosa(NGM),gastroduodenal diseases(GDD),and GC].Information associated with socioeconomic and demographic conditions and GC risk factors was collected using a questionnaire.H.pylori infection status was determined based on urea breath test.The association of these factors and histopathological grades was assessed statistically.K-Nearest Neighbors and Random Forest(RF)machine learning models were tested.RESULTS This study reported an overall frequency of 64.2%(219/341)of H.pylori infection among enrolled subjects.It was higher in GC(74.2%,23/31)as compared to NGM and GDD and higher in males(54.3%,119/219)as compared to females.More abdominal pain(72.4%,247/341)was observed than other clinical symptoms including vomiting,bloating,acid reflux and heartburn.The majority of the GC patients experienced symptoms of vomiting(91%,20/22)with abdominal pain(100%,22/22).The multinomial logistic regression model was statistically significant and correctly classified 80%of the GDD/GC cases.Age,income level,vomiting,bloating and medication had significant association with GDD and GC.A dynamic RF GC-predictive model was developed,which achieved>80%test accuracy.CONCLUSION GC risk factors were incorporated into a computer model to predict the likelihood of developing GC with high sensitivity and specificity.The model is dynamic and will be further improved and validated by including new data in future research studies.Its use may reduce unnecessary endoscopic procedures.It is freely available.
文摘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.
文摘Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors,leading to inflammatory changes,dysbiosis and eventually gastric cancer.The normal gastric microbiota shows diversity,with Proteobacteria[Helicobacter pylori(H.pylori)belongs to this family],Firmicutes,Actinobacteria,Bacteroides and Fusobacteria being the most abundant phyla.Most studies indicate that H.pylori has inhibitory effects on the colonization of other bacteria,harboring a lower diversity of them in the stomach.When comparing the healthy with the diseased stomach,there is a change in the composition of the gastric microbiome with increasing abundance of H.pylori(where present)in the gastritis stage,while as the gastric carcinogenesis cascade progresses to gastric cancer,the oral and intestinal-type pathogenic microbial strains predominate.Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself.Successful H.pylori eradication is suggested to restore gastric microbiota,at least in primary stages.It is more than clear that Hp-I,gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll.Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H.pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.
文摘BACKGROUND Persistent Helicobacter pylori(H.pylori)infection causes chronic inflammation,atrophy of the gastric mucosa,and a high risk of developing gastric cancer.In recent years,awareness of eradication therapy has increased in Japan.As H.pylori infections decrease,the proportion of gastric cancers arising from H.pylori uninfected gastric mucosa will increase.The emergence of gastric cancer arising in H.pylori uninfected patients though rarely reported,is a concern to be addressed and needs elucidation of its clinicopathological features.AIM To evaluate the clinicopathological features of early gastric cancer in H.pyloriuninfected patients.METHODS A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019.Of these,30 lesions in 30 patients were diagnosed as H.pylori-uninfected gastric cancer(Hp UIGC).We defined a patient as H.pylori-uninfected using the following three criteria:(1)The patient did not receive treatment for H.pylori,which was determined by investigating medical recordsand conducting patient interviews;(2)Lack of endoscopic atrophy;and(3)The patient was negative for H.pylori after being tested at least twice using various diagnostic methods,including serum anti-H.pylori-Ig G antibody,urease breath test,rapid urease test,and microscopic examination.RESULTS The frequency of Hp UIGC was 1.2%(30/2462)for the patients in our study.The study included 19 males and 11 females with a mean age of 59 years.The location of the stomach lesions was divided into three sections;upper third(U),middle third(M),lower third(L).Of the 30 lesions,15 were U,1 was M,and 14 were L.Morphologically,17 lesions were protruded and flat elevated type(0-I,0-IIa,0-IIa+IIc),and 13 lesions were flat and depressed type(0-IIb,0-IIc).The median tumor diameter was 8 mm(range 2-98 mm).Histological analysis revealed that22 lesions(73.3%)were differentiated type.The Hp UIGC lesions were classified into fundic gland type adenocarcinoma(7 cases),foveolar type welldifferentiated adenocarcinoma(8 cases),intestinal phenotype adenocarcinoma(7 cases),and pure signet-ring cell carcinoma(8 cases).Among 30 Hp UIGCs,24 lesions(80%)were limited to the mucosa;wherein,the remaining 6 lesions showed submucosal invasion.One of the submucosal invasive lesions showed more than 500μm invasion.The mucin phenotype analysis identified 7 Hp UIGC with intestinal phenotype and 23 with gastric phenotype.CONCLUSION We elucidated the clinicopathological characteristics of Hp UIGC,revealing recognition not only undifferentiated-type but also differentiated-type.In addition,intestinal phenotype tumors were also observed and could be an important tip.
基金Supported by Grants from Guangdong Natural Science Foundation Project,5004750National Key Development Project,973 Program 2002CB513206
文摘AIM: To detect and evaluate the antibodies against Helicobacter pylori (H pylori) neutrophil-activating protein (HP-NAP) in patients with gastric cancer and other gastroduodenal diseases.METHODS: Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coll. Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 (IL-8) and growth-related oncogene (GROα) cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected.RESULTS: The serum positivity and mean absorbancevalue of HP-NAP-specific antibodies in the gastriccancer group (97.7% and 1.01 ± 0.24) were significantly higher than those in the chronic gastritisgroup (85.7% and 0.89 ± 0.14, P 〈 0.005) and healthy control group (27.7% and 0.65 ± 0.18, P 〈 0.001). The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly upregulate IL-8 production in gastric epithelial cell lines but had no effect on GROα production.CONCLUSION: Infection with virulent H py/ori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma, rHP-NAP- based ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.
文摘We conducted a comprehensive literature review and meta-analysis study on the efficacy of Helicobacter pylori(H. pylori) eradication in preventing metachronous gastric cancer after endoscopic resection among an East Asian population. Our results showed that the eradication of this pathogen significantly reduced the risk of susceptibility to metachronous gastric cancer in these patients. However, based on the available evidence, several factors such as increasing age, severe atrophy in the corpus and antrum, and intestinal metaplasia all may increase the risk of metachronous gastric cancer in H. pylori eradicated patients.
文摘Background: Many studies documented an association between a Helicobacter pylori infection and the development of human gastric cancer. None of these studies were able to identify Helicobacter pylori as a cause or as the cause of human gastric cancer. The basic relation between gastric cancer and Helicobacter pylori still remains uncertain. Objectives: This systematic review and re-analysis of Naomi Uemura et al. available long-term, prospective study of 1526 Japanese patients are performed so that some new and meaningful inference can be drawn. Materials and Methods: Data obtained by Naomi Uemura et al. who conducted a long-term, prospective study of 1526 Japanese patients with a mean follow up about 7.8 years and endoscopy at enrolment and in the following between one and three years after enrolment were reanalysed. Statistical Analysis Used: The method of the conditio sine qua non relationship was used to proof the hypothesis without a Helicobacter pylori infection no development of human gastric cancer. The mathematical formula of the causal relationship was used to proof the hypothesis, whether there is a cause effect relationship between a Helicobacter pylori infection and human gastric cancer. Significance was indicated by a p-value of less than 0.05. Results: Based on the data published by Uemura et al. we were able to make evidence that without a Helicobacter pylori infection no development of human gastric cancer. In other words, a Helicobacter pylori infection is a conditio sine qua non of human gastric cancer. In the same respect, the data of Uemura et al. provide significant evidence that a Helicobacter pylori infection is the cause of human gastric cancer. Conclusions: Without a Helicobacter pylori infection of human stomach no development of human gastric cancer. Helicobacter pylori is the cause of human gastric cancer (k = +0.07368483, p-value = 0.00399664).
基金Supported by Grant,NIDDK,RO1DK63618 to KMD from the National Institutes of Health,Bethesda,MD
文摘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.
文摘Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.
基金Supported by In part by the Office of Research and Development Medical Research Service Department of Veterans Affairs,Public Health Service grants No.DK062813 and No.DK56338 which funds the Texas Medical Center Digestive Diseases Center
文摘Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20<sup>th</sup> century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19<sup>th</sup> century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17<sup>th</sup> to 19<sup>th</sup> centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19<sup>th</sup> century. The environment before the 20<sup>th</sup> century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19<sup>th</sup> century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20<sup>th</sup> century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for “surgical disease” or for “Sippy” diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.
文摘Helicobacter pylori(H.pylori)plays an important role in gastric carcinogenesis,as the majority of gastric cancers develop from H.pylori-infected gastric mucosa.The rate of early gastric cancer diagnosis has increased in Japan and Korea,where H.pylori infection and gastric cancer are highly prevalent.Early intestinal-type gastric cancer without concomitant lymph node metastasis is usually treated by endoscopic resection.Secondary metachronous gastric cancers often develop because atrophic mucosa left untreated after endoscopic treatment confers a high risk of gastric cancer.The efficacy of H.pylori eradication for the prevention of metachronous gastric cancer remains controversial.However,in patients who undergo endoscopic resection of early gastric cancer,H.pylori eradication is recommended to suppress or delay metachronous gastric cancer.Careful and regularly scheduled endoscopy should be performed to detect minute metachronous gastric cancer after endoscopic resection.
基金Supported by National Natural Science Foundation of China,No.U1604174Henan Provincial Government-Health and Family Planning Commission,No.20170123+1 种基金Henan Provincial Government-Health and Family Planning Commission Research Innovative Talents Project,No.51282Henan Provincial Government-Science and Technology Bureau,No.142300410050.
文摘BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated;it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17(G-17)and pepsinogens(PGs)during clinical practice.AIM To explore the prevalence of type I and type II H.pylori infection status and their impact on G-17 and PG levels in clinical practice.METHODS Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined,and 523 patients were enrolled in this study.H.pylori infection was confirmed by both 13C-urea breath test and serological assay.Patients were divided into non-atrophic gastritis(NAG),nonatrophic gastritis with erosion(NAGE),chronic atrophic gastritis(CAG),peptic ulcers(PU)and gastric cancer(GC)groups.Their serological G-17,PG I and PG II values and PG I/PG II ratio were also measured.RESULTS A total H.pylori infection rate of 3572 examined patients was 75.9%,the infection rate of 523 enrolled patients was 76.9%,among which type I H.pylori infection accounted for 72.4%(291/402)and type II was 27.6%;88.4%of GC patients were H.pylori positive,and 84.2%of them were type I infection,only 11.6%of GC patients were H.pylori negative.Infection rates of type I H.pylori in NAG,NAGE,CAG,PU and GC groups were 67.9%,62.7%,79.7%,77.6%and 84.2%,respectively.H.pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio.Both types of H.pylori induced higher G-17 level,but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG,NAGE and CAG groups over uninfected controls.Overall PG I levels showed no difference among all disease groups and in the presence or absence of H.pylori;in stratified analysis,its level was increased in GC and PU patients in H.pylori and type I H.pylori-positive groups.CONCLUSION Type I H.pylori infection is the major form of infection in this geographic region,and a very low percentage(11.6%)of GC patients are not infected by H.pylori.Both types of H.pylori induce an increase in G-17 level,while type I H.pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease.The data provide insights into H.pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.
基金Supported by grants to SZD from Henan Provincial GovernmentScience and Technology Bureau,No.142300410050Henan Provincial Government-Health and Family Planning Commission,No.20170123+1 种基金Henan Provincial Innovative Talents Projects of 2016and 2017National Natural Science Foundation of China,No.U1604174
文摘Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to families and societies;it is also a heavy economic and healthcare burden for countries that having high infection rates.Eradication of H.pylori is recommended for all infected individuals.Traditionally,"test and treat"and"screen and treat"strategies are available for various infected populations.However,clinical practice has noticed that these strategies have some shortfalls and may need refinement,mostly due to the fact that they are not easily manageable,and are affected by patient compliance,selection of treatment population and cost-benefit estimations.Furthermore,it is difficult to control infections from the source,therefore,development of additional,compensative strategies are encouraged to solve the above problems and facilitate bacteria eradication.H.pylori infection is a family-based disease,but few studies have been performed in a whole family-based approach to curb its intra-familial transmission and the development of related diseases.In this work,a third,novel whole family-based H.pylori eradication strategy is introduced.This approach screens,identifies,treats and follows up on all H.pylori-infected individuals in entire families to control H.pylori infection among family members,and reduce its long-term complications.This strategy is high-risk population-oriented,and able to reduce H.pylori spread among family members.It also has good patient-family compliance and,importantly,is practical for both high and low H.pylori-infected communities.Future efforts in these areas will be critical to initiate and establish healthcare policies and management strategies to reduce H.pylori-induced disease burden for society.
文摘Gastric cancer is a leading cause of cancer death worldwide,and significant effort has been focused on clarifying the pathology of gastric cancer.In particular,the development of genome-wide analysis tools has enabled the detection of genetic and epigenetic alterations in gastric cancer;for example,aberrant DNA methylation in gene promoter regions is thought to play a crucial role in gastric carcinogenesis.The etiological viewpoint is also essential for the study of gastric cancers,and two distinct pathogens,Helicobacter pylori(H.pylori)and Epstein-Barr virus(EBV),are known to participate in gastric carcinogenesis.Chronic inflammation of the gastric epithelium due to H.pylori infection induces aberrant polyclonal methylation that may lead to an increased risk of gastric cancer.In addition,EBV infection is known to cause extensive methylation,and EBV-positive gastric cancers display a high methylation epigenotype,in which aberrant methylation extends to not only Polycomb repressive complex(PRC)-target genes in embryonic stem cells but also non-PRC-target genes.Here,we review aberrant DNA methylation in gastric cancer and the association between methylation and infection with H.pylori and EBV.