Increased 5-hydroxymethylcytosine is a favorable prognostic factor of Helicobacter pylori-negative gastric cancer patients

BACKGROUND Most gastric cancer(GC)patients are diagnosed at middle or late stage because the symptoms in early stage are obscure,which causes higher mortality rates of GC.Helicobacter pylori(H.pylori)was identified as a class I carcinogen and leads to aberrant DNA methylation/hydroxymethylation.5-hydroxymethylcytosine(5-hmC)plays complex roles in gene regulation of tumorigenesis and can be considered as an activating epigenetic mark of hydroxymethylation.AIM To explore the association between 5-hmC levels and the progression and prognosis of GC patients with or without H.pylori infection.METHODS A retrospective cohort study was conducted to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H.pylori infection status.A total of 144 GC patients were recruited.RESULTS The levels of 5-hmC were significantly decreased in tumor tissues(0.076±0.048)compared with the matched control tissues(0.110±0.057,P=0.001).A high level of 5-hmC was an independent significant favorable predictor of overall survival in GC patients(hazard ratio=0.61,95% confidence interval:0.38-0.98,P=0.040),the H.pylori-negative GC subgroup(hazard ratio=0.30,95% confidence interval:0.13-0.68,P=0.004)and the GC patients with TNM stage Ⅰ or Ⅱ(hazard ratio=0.32,95% confidence interval:0.13-0.77,P=0.011).CONCLUSION Increased 5-hmC is a favorable prognostic factor in GC,especially for H.pylori-negative subgroups.

Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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.

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

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.

Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions

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.

Curative resection with endoscopic submucosal dissection of early gastric cancer in Helicobacter pylori-negative Ménétrier’s disease:A case report

BACKGROUND Adult-onset Ménétrier’s disease is strongly associated with Helicobacter pylori(H.pylori)infection and an elevated risk of carcinogenesis.Cases of early-stage gastric cancer developed in H.pylori-negative Ménétrier’s disease are extremely rare.We report a case of early gastric cancer in H.pylori-negative Ménétrier’s disease that was curatively resected with endoscopic submucosal dissection(ESD).CASE SUMMARY A 60-year-old woman was referred to our hospital after her medical examination detected anemia.Contrast-enhanced upper gastrointestinal(UGI)radiography revealed translucency of the nodule-aggregating surface with giant rugae.Blood tests showed hypoproteinemia and were negative for serum H.pylori immunoglobulin G antibodies.The 99mTc-DTPA-human serum albumin scintigraphy showed protein loss from the stomach.UGI endoscopy showed a 40-mm protruding erythematous lesion on giant rugae of the greater curvature of lower gastric body,suggesting early-stage gastric cancer due to Ménétrier’s disease.En bloc resection with ESD was performed for diagnosis and treatment.Histology of ESD showed well-differentiated tubular adenocarcinoma.The cancer was confined to the mucosa,and complete curative resection was achieved.Foveolar hyperplasia and atrophy of the gastric glands were observed in non-tumor areas,histologically corresponding to Ménétrier’s disease.Three years after ESD,gastric cancer had not recurred,and Ménétrier’s disease remained in remission with spontaneous regression of giant gastric rugae.CONCLUSION Complete curative resection was achieved through ESD in a patient with earlystage gastric cancer and H.pylori-negative Ménétrier’s disease.

Health economic evaluation on population-based Helicobacter pylori eradication and endoscopic screening for gastric cancer prevention

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.

Risk factor profiles for gastric cancer prediction with respect to Helicobacter pylori:A study of a tertiary care hospital in Pakistan

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.

Predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis

BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive system.According to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant tumors.More than 60%of GC are linked to infection with Helicobacter pylori(H.pylori),a gram-negative,active,microaerophilic,and helical bacterium.This parasite induces GC by producing toxic factors,such as cytotoxin-related gene A,vacuolar cytotoxin A,and outer membrane proteins.Ferroptosis,or iron-dependent programmed cell death,has been linked to GC,although there has been little research on the link between H.pylori infection-related GC and ferroptosis.AIM To identify coregulated differentially expressed genes among ferroptosis-related genes(FRGs)in GC patients and develop a ferroptosis-related prognostic model with discrimination ability.METHODS Gene expression profiles of GC patients and those with H.pylori-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus(GEO)databases.The FRGs were acquired from the FerrDb database.A ferroptosis-related gene prognostic index(FRGPI)was created using least absolute shrinkage and selection operator–Cox regression.The predictive ability of the FRGPI was validated in the GEO cohort.Finally,we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.RESULTS Four hub genes were identified(NOX4,MTCH1,GABARAPL2,and SLC2A3)and shown to accurately predict GC and H.pylori-associated GC.The FRGPI based on the hub genes could independently predict GC patient survival;GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk group.The FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease progression.Moreover,the gene expression levels of common immune checkpoint proteins dramatically increased in the highrisk subgroup of the FRGPI cohort.The hub genes were also confirmed to be highly overexpressed in GC cell lines and tissues and were found to be primarily localized at the cell membrane.The ferroptosis inducer FIN56 inhibited GC cell proliferation in a dose-dependent manner.CONCLUSION In this study,we developed a predictive model based on four FRGs that can accurately predict the prognosis of GC patients and the efficacy of immunotherapy in this population.

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion

A bibliometric analysis of studies dedicated to autoimmune gastritis(AIG)recently published demonstrated a noteworthy surge in publications over the last three years.This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition.Follow-up studies and retrospective analyses showed that the risk of gastric cancer(GC)in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori(H.pylori)were excluded.The low prevalence of precancerous lesions,such as the incomplete type of intestinal metaplasia,may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion.However,changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric microbiome,stimulating the growth of bacterial species such as streptococci,which may promote the development of precancerous lesions and GC.Thus,Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice,reproducing the wellestablished process for carcinogenesis associated with H.pylori.Prospective studies in H.pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts,which has been reported in economically developed countries.

Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia

Heliobacter pylori(H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer.Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia(IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia(SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals.There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H.pylori infection.

Tumor infiltrating lymphocytes in gastric cancer:Unraveling complex interactions for precision medicine

This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment.The role of tumor infiltrating lymphocytes(TILs)will also be discussed in detail,including the types,mechanism of action,and role.Gastric cancer(GC)often presents in the advanced stage and has various factors predicting the outcomes.The interplay of these factors and their correlation with the TILs is discussed.A literature review revealed high intratumoral TILs associated with higher grade,HER2-,and Helicobacter pylori negativity.Moreover,stromal(ST)TILs correlated with lower grade and lesser recurrence risk in GC.High TILs in ST and invasive border also correlated with mismatch repair deficiency status.Further characterization of the CD3+,CD8+,and other cells is also warranted.In the future,this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.

Characteristics and predictors of gastric cancer after Helicobacter pylori eradication

Helicobacter pylori(H. pylori) eradication can reduce gastric cancer. However, gastric cancer still develops after eradication, and cases who received eradication therapy are increasing. In this study, we have reviewed the characteristics and predictors of primary gastric cancer developing after H. pylori eradication. In terms of the characteristics, endoscopic, histologic, and molecular characteristics are reported. Endoscopically, gastric cancer after eradication is often depressedtype and shows a gastritis-like appearance, which sometimes makes the diagnosis difficult. Histologically, most gastric cancer after eradication is intestinal type, and non-neoplastic epithelium, also called epithelium with low-grade atypia, is frequently seen over the tumor, which is presumably the cause of the endoscopic gastritis-like appearance. As for molecular characteristics, some markers, such as Ki67, MUC2, and Wnt5a expression, are lower in cancer from patients in whom H. pylori has been eradicated. In terms of predictors, several Japanese studies have reported that severe endoscopic atrophy at eradication is a risk factor for gastric cancer development. Histologic intestinal metaplasia, especially in the corpus, and long-term use of proton pump inhibitors, are also reported as risk factors for gastric cancer after H. pylori eradication. These studies on the characteristics and predictors of gastric cancer development will become the cornerstone for establishing a novel surveillance program based on the gastric cancer risk stratification specific to H. pylori-eradicated patients.

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.

Gastric cancer, Helicobacter pylori infection and other risk factors

Gastric cancer incidence is declining. However, it is too early to consider this neoplastic disease as rare and the worldwide mortality rate still remains high. Several risk factors have been identif ied for non-cardia gastric cancer and primary prevention is feasible since most of the risk factors can be removed. Helicobacter pylori eradication treatment reduces but does not abolish gastric cancer risk. Indeed, gastric cancer is a multifactorial disease and removing one factor does not therefore prevent all cases. Endoscopic surveillance is still needed, especially in subjects at higher risk. The def inition of high-risk patients will be the future challenge as well as identifying the best surveillance strategy for such patients.

Role of Helicobacter pylori in gastric cancer:Updates

Helicobacter pylori(H. pylori) infection is highly prevalent in human,affecting nearly half of the world's population; however,infection remains asymptomatic in majority of population. During its co-existence with humans,H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side,presence of H.pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer(GC). A complex combination of host genetics,environmental agents,and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world,they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis,the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC.

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 &#x0201c;point of no return&#x0201d; 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.

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.

Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis

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.

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

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 20th 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 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th 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 19th 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 20th 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.

Efficacy of Helicobacter pylori eradication for the prevention of metachronous gastric cancer after endoscopic resection for early gastric cancer

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.