Severity Of Gastric Mucosal Atrophy Research Articles

A novel endoscopic finding of a scratch sign is useful for evaluating the Helicobacter pylori infection status.

During esophagogastroduodenoscopy, a red linear scrape-like appearance with white deposits sometimes appears on the gastric mucosa at the lower greater curvature of the gastric body, a finding we named the "scratch sign." We aimed to clarify the clinical significance of this new endoscopic finding in the endoscopic evaluation of the Helicobacter pylori infection status. Among patients who underwent esophagogastroduodenoscopy at our hospital between October 2016 and June 2017, 437 patients were included in the study. We first examined the overall scratch sign positivity rate, and then this was compared according to the H. pylori infection status. Subsequently, other variables were compared and examined between the positive and negative scratch sign groups. Overall, 437 patients were included in the analysis. The scratch sign was observed in 1.4% of 71 patients with current infections, 26.9% of 290 patients with past infections, and 31.6% of 76 uninfected patients. In the multivariate analysis, H. pylori-negative, severe gastric mucosal atrophy, and acid secretion depressant were independent factors that significantly affected the appearance of the scratch sign. A novel endoscopic finding, the scratch sign, was found to be a good endoscopic predictor of H. pylori-negative gastric mucosa. Furthermore, combined with atrophic changes and xanthomas that persisted after eradication, these findings were found to be useful in accurately diagnosing H. pylori past-infected gastric mucosa endoscopically.

Development of plasma ghrelin level as a novel marker for gastric mucosal atrophy after Helicobacter pylori eradication

Background and aim The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. Methods Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Results Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. Conclusion Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication. KEY MESSAGES Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication. Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication. Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.

MAFK Polymorphisms Located in 3'-UTR are Associated with Severity of Atrophy and CDKN2A Methylation Status in the Gastric Mucosa.

Objective: This study aimed to clarify the association of MAFK polymorphisms (rs4268033, rs3735656, and rs10226620) with the degree of gastric mucosal atrophy and CDKN2A CpG methylation status. Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Results: Either rs3735656 or rs10226620, located in the 3'-UTR of MAFK, was significantly associated with the severity of gastric mucosal atrophy using a dominant genetic model (odds ratio [OR], 2.10; p = 0.0012, and OR, 1.98; p = 0.0027, respectively). However, using a recessive genetic model, no significant association was found between three polymorphisms and gastric mucosal atrophy. The serum pepsinogen I/II ratio was significantly lower in subjects with minor alleles of rs3735656 and rs10226620 than in subjects with the wild homozygous allele (p = 0.018 and 0.013, respectively). In a subgroup including 400 of the 491 subjects, the CpG of p14ARF and p16 INK4a were methylated in 132 and 112 subjects, respectively. Fifty subjects had both CpG methylations and 206 subjects had neither methylation. When comparing the groups with both and neither methylations, there were no significant associations between three polymorphisms and CDKN2A methylation using a dominant genetic model. However, all polymorphisms investigated in this study (rs4268033, rs3735656, and rs10226620) were significantly associated with CDKN2A methylation in a recessive genetic model (OR, 3.58; p = 0.0071, OR, 4.49; p = 0.0004, and OR, 3.45; p = 0.0027, respectively). Conclusions: Our results indicate that carrying the minor allele of the MAFK polymorphisms, particularly when they are located in the 3'-UTR, has a high risk for the severity of gastric mucosal atrophy; furthermore, CDKN2A CpG methylation may develop in subjects with homozygous minor allele of these polymorphisms.

Endoscopy Is Cost-Effective for Gastric Cancer Screening After Successful Helicobacter pylori Eradication

After successful Helicobacter pylori eradication, patients with gastric mucosal atrophy are at high risk of gastric cancer. Endoscopy can detect early gastric cancer with high sensitivity. This study aimed to assess the cost-effectiveness of annual endoscopy versus biennial endoscopy versus no screening for gastric cancer screening in patients after successful Helicobacter pylori eradication. We developed decision trees with Markov models for a hypothetical cohort of patients aged 50years after successful Helicobacter pylori eradication over a lifetime horizon from a healthcare payer perspective. Main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs) with discounting at a fixed annual rate of 3%, and incremental cost-effectiveness ratios (ICERs). In a base-case analysis, biennial endoscopy (US$4305, 19.785QALYs, 19.938LYs) was more cost-effective than annual endoscopy (US$7516, 19.808QALYs, 19.958LYs, ICER; US$135,566/QALY gained) and no screening (US$14,326, 19.704QALYs, 19.873LYs). In scenario analyses, biennial endoscopy for patients with mild-to-moderate gastric mucosal atrophy and annual endoscopy for patients with severe gastric mucosal atrophy were the most cost-effective. Cost-effectiveness was sensitive to incidence of gastric cancer and the proportion of stage I. Probabilistic sensitivity analyses using Monte Carlo simulation demonstrated that at a willingness-to-pay level of US$100,000/QALY gained, biennial endoscopy was optimal 99.9% for patients with mild-to-moderate gastric mucosal atrophy, and that annual endoscopy was optimal 98.4% for patients with severe gastric mucosal atrophy. Based on cancer risk assessment of gastric mucosal atrophy and cost-effectiveness results, annual or biennial endoscopic surveillance could be established for patients after successful Helicobacter pylori eradication.

Endoscopic severe mucosal atrophy indicates the presence of gastric cancer after Helicobacter pylori eradication -analysis based on the Kyoto classification

BackgroundGastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site.MethodsWe analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness.ResultsPatients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura–Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer.ConclusionsEndoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.

Precision Medicine Approaches to Prevent Gastric Cancer.

Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The primary risk factor for gastric cancer is Helicobacter pylori infection. The Kyoto global consensus report recommends eradication of H. pylori in all infected patients. However, because it is difficult to stratify the risk of carcinogenesis among patients with a history of H. pylori infection, annual endoscopic surveillance is performed for everyone after eradication. This review summarizes the current approaches used to screen for novel molecules that could assist in the diagnosis of gastric cancer and reduce mortality. Most well-studied molecules are tissue protein biomarkers expressed by the gastric epithelium and associated with metaplasia-dysplasia-carcinoma sequences. Other strategies focus on the origin of cancer stem cell-related markers, such as CD44, and immune reaction-related markers, such as matrix metallopeptidases. Noninvasive methods such as blood-based approaches are more attractive. Serum pepsinogen levels predict the severity of gastric mucosal atrophy before H. pylori eradication, whereas plasma ghrelin levels are associated with atrophy even after eradication. Cell-free DNAs and RNAs are attractive tools for the early detection of cancer. These ideas could lead to the development of more personalized strategies for cancer prevention based on cutting-edge technologies.

Association of genetic polymorphisms in DNMT3A with the progression of gastric mucosal atrophy and susceptibility to gastric cancer in Japan.

The aim of the present study was to investigate whether single nucleotide polymorphisms in the DNMT3A gene are associated with susceptibility to gastric cancer in the Japanese population. The present case-control study examined the associations between single nucleotide polymorphisms (rs6733868 and rs13428812) in DNMT3A and cancer susceptibility in 343 patients with gastric cancer and 708 subjects without gastric malignancies on upper gastro-duodenal endoscopy. Of 708 controls, 409 were classified into two groups histologically: 99 cases with and 310 cases without gastric mucosal atrophy. Overall, homozygosity for the DNMT3A rs6733868 minor allele was significantly associated with a reduced risk of gastric cancer (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.402-0.958; P=0.031), especially of the intestinal type (OR, 0.494; 95% CI, 0.274-0.890; P=0.019). In subjects >60 years, rs6733868 minor allele homozygosity was significantly associated with gastric cancer susceptibility. Carriers of the rs6733868 minor allele had a reduced risk of severe gastric mucosal atrophy (OR, 0.495; 95% CI, 0.299-0.826; P=0.0069). In addition, the number of minor alleles of both rs6733868 and rs13428812 was significantly correlated with the risk of Helicobacter pylori (HP) infection (P=0.0070 and P=0.0050, respectively). However, rs13428812 was not associated with severe gastric mucosal atrophy or gastric carcinogenesis. The present results suggest that DNMT3A polymorphisms serve roles in the progression from HP infection to gastric mucosal atrophy and gastric carcinogenesis in terms of degree and manner.

Endoscopic gastric mucosal atrophy as a predictor of colorectal polyps: a large scale case-control study.

Although some studies have indicated a correlation between Helicobacter pylori infection and the risk of colorectal neoplasms, these findings have not been consistent and are controversial. This case-control study aimed to investigate the association between endoscopic gastric mucosal atrophy and colorectal polyp occurrence. Records of 7,394 participants who underwent colonoscopy examinations from August 2008 to July 2018 were reviewed retrospectively. A total of 2,404 subjects were registered; 1,565 (65.1%) were in the gastric mucosal atrophy-positive group and 1,138 (47.3%) had colorectal polyps. The multivariate analysis adjusted by age, sex, smoking habits, alcohol habits, hemoglobin A1c, and systolic blood pressure indicated that patients in the gastric mucosal atrophy-positive group more frequently had colorectal polyps compared with patients in the gastric mucosal atrophy-negative group (odds ratio, 3.27; 95% confidence interval, 2.68-4.01; p<0.001). An analysis of the association between gastric mucosal atrophy degree and colorectal polyp status indicated that, compared with mild gastric mucosal atrophy, severe gastric mucosal atrophy was associated with a higher risk of proximal colon polyps (odds ratio, 1.47; 95% confidence interval, 1.05-2.07; p=0.024) and two or more colorectal polyps (odds ratio, 1.80; 95% confidence interval, 1.30-2.49; p<0.001). In conclusion, gastric mucosal atrophy found during esophagogastroduodenoscopy may be an indication for complete colon screening.

Gender Differences in Plasma Ghrelin Levels in Hemodialysis Patients.

Ghrelin is an orexigenic hormone mainly secreted by the stomach, and it decreases according to the severity of gastric atrophy. Ghrelin has multiple favorable functions, including protein anabolism enhancement, anti-inflammatory activity, and cardiovascular protection, and is associated with survival in hemodialysis (HD) patients. Although the plasma level and role of ghrelin may be different depending on gender, they have not been completely assessed in HD patients. We enrolled 80 (male/female: 51/29) maintenance HD patients. An upper gastrointestinal endoscopic examination was performed for all patients to determine the severity of gastric mucosal atrophy and Helicobacter pylori infection. We measured plasma acyl and desacyl ghrelin levels and assessed the association between ghrelin levels and relevant clinical parameters, including nutrition, inflammation, atherosclerosis, and bone metabolism, by gender. Both acyl and desacyl ghrelin levels in female HD patients were significantly higher than those in male HD patients. When stratified by gastric mucosal atrophy, these gender differences were observed only in patients without gastric atrophy. In female patients, acyl ghrelin level was negatively correlated with age. In male patients, both acyl and desacyl ghrelin levels were positively correlated with bone mineral density. Multiple regression analysis showed significant positive correlations between both ghrelin levels and female gender after adjusting for confounding factors. Plasma ghrelin levels were higher in female HD patients than in male HD patients. The gender difference was more evident in patients without gastric atrophy.

Eradication therapy for Helicobacter pylori infection improves nutrition status in Japanese hemodialysis patients: a pilot study.

Plasma ghrelin level is influenced by Helicobacter pylori (H. pylori) status and the severity of gastric mucosal atrophy, and the ghrelin level is associated with nutrition status in hemodialysis patients. Here, we investigated the efficacy of H. pylori eradication therapy in improving nutrition status in relation to the ghrelin level in H. pylori-positive hemodialysis patients. Of H. pylori-positive patients receiving hemodialysis at 8 dialysis center, 21 patients underwent gastroduodenoscopy for evaluation of the severity of gastric atrophy, and nutrition markers and plasma ghrelin levels before and 1 year after H. pylori eradication therapy were evaluated. Serum cholinesterase level was significantly increased after H. pylori eradication compared with the level before eradication (303.2 ± 76.0 vs 287.3 ± 68.1 IU/L, p = 0.029). In particular, cholesterol (before, 196.6 ± 23.2 mg/dl; after, 206.1 ± 25.9 mg/dl, p = 0.042) and cholinesterase levels (before, 296.9 ± 70.8 IU/L; after, 316.4 ± 73.8 IU/L, p = 0.049) increased more strongly in patients with mild–moderate atrophy than those with severe atrophy, irrespective of improvement of plasma acyl-ghrelin and desacyl-ghrelin levels after eradication therapy. In conclusion, H. pylori eradication may improve nutrition status by increasing serum cholinesterase and cholesterol levels in hemodialysis patients, especially those with mild and moderate gastric mucosal atrophy.

Helicobacter pylori Eradication Therapy Improves Chronic Defecatory Dysfunction

Introduction: Defecatory dysfunction is one of the most common gastrointestinal disorders. Recently, dysbiosis in the gut microbiota are well known to be associated with the development of defecatory dysfunction. Helicobacter pylori infection and its eradication therapy are possible factors leading to dysbiosis. In this study, we investigated the effects of H. pylori eradication on defecatory dysfunction using questionnaires and examined the relationship between the severity of gastric mucosal atrophy and the reversibility of defecatory dysfunction after eradication therapy. Methods: We recruited a total of 166 H. pylori—positive patients who performed H. pylorieradication therapy from August 2015 to June 2017. We evaluated severity of defecatory dysfunction between before therapy and after 2 months post—therapy using the gastrointestinal symptom rating scale (GSRS) and the Izumo scale. Patients were divided into two groups based on the outcome of H. pylori eradication treatment, a successful group (n = 142) and a failed group (n = 24). The severity of endoscopic atrophy was graded according to the Kimura—Takemoto classification. Results: The constipation—related and diarrhea—related cores in the GSRS before treatment were significantly improved after treatment, from 5.8 ± 3.3 and 5.2 ± 3.2 to 5.1 ± 2.7 (P < 0.01) and 4.6 ± 2.6 (P = 0.04), respectively. In patients with constipation before eradication, the constipation—related score in the Izumo scale improved from 5.1±2.7 to 3.4±2.5 (P=0.013). In the failed eradication group, scores of constipation—related symptoms before and after treatment were similar. In contrast, those in the successful group significantly improved after treatment, from 5.63 ± 3.06 to 5.11 ± 2.71 (P=0.02). The constipation—related score in patients with mild and moderate atrophy significantly decreased from 5.5±2.8 to 4.9±2.2 (P=0.024), but not in patients with severe atrophy. Conclusion: H. pylori eradication therapy has the potential to improve defecatory dysfunction in H. pylori—infected patients without severe gastric atrophy. We hypothesize that this difference is due to eradication—induced changes in the secondary gastrointestinal tract environment, such as improved gastric acid secretion, and in the homeostatic gut microbiota. Merits of H. pylori eradication therapy lie not only in the effect it has as a preventer of gastric cancer, but also in its potential to improve defecatory dysfunction.

Eradication Therapy for Helicobacter pylori Improves Nutrition Status Depended on Severity of Gastric Mucosal Atrophy and Plasma Ghrelin Level in Japanese Hemodialysis Patients

Introduction: The state of metabolic and nutritional derangement, called protein—energy wasting (PEW), has a major impact on mortality in hemodialysis (HD) patients. Ghrelin has multiple favorable functions and associates with the pathogenesis of PEW in HD patients. Plasma and gastric ghrelin levels are affected in H pylori status. Here, we investigated relationships among nutrition status, ghrelin level, H. pylori and severity of atrophy in HD patients and investigated the efficacy of H. pylori eradication therapy for improvement of nutrition status related with ghrelin in H. pylori—positive HD patients. Methods: H. pylori&#x2014;IgG and pepsinogen levels of 500 HD patients at 8 dialysis centers were measured. We classified H. pylori infectionstatus into three groups: present infection, past infection and non—infection. Plasma ghrelin levels were measured and we investigated above relationship among three groups. H. pylori—positives underwent endoscopy for evaluation of the severity of atrophy, and eradicated by PPI, amoxocollin and clarithromycin for 7days. We evaluated nutrition markers and ghrelin levels before and 1 year after eradication. Results: Acyl— and desacyl—ghrelin levels were 29.7±21.3 fmol/mland 279.2±168.5 fmol/ml, respectively. Acyl—ghrelin in the non—infection group was significantly higher than in the present and past infection groups. Acyl—ghrelin level was positively correlated with serum PG I level and PG I/II ratio and was significantly lower in patients with severe atrophy than in those with no atrophy (20.9±14.6and 40.4±21.9, p<0.001). Cholinesterase level was significantly increased after eradication compared with before eradication (303.2±76.0 vs. 287.3±68.1, p=0.029). In particular, cholesterol(before, 196.6±23.2; after, 206.1±25.9, p=0.042) and cholinesterase levels(before, 296.9±70.8; after, 316.4±73.8, p=0.049) increased more strongly in patients with mild-moderate atrophy than those with severe atrophy. Conclusion: Plasma ghrelin level was associated with endoscopic and serological severity of atrophy related with H. pylori infection in HD patients. Eradication improved nutrition status by increasing serum cholinesterase and cholesterol levels, especially those with mild and moderate gastric mucosal atrophy. In HD patients, eradication therapy may contribute to an improvement in prognosis associated with PEW.

Severity of gastric mucosal atrophy affects the healing speed of post-endoscopic submucosal dissection ulcers.

AIMTo investigate factors associated with the healing of endoscopic submucosal dissection (ESD)-induced ulcers.METHODSWe enrolled 132 patients with gastric tumors scheduled for ESD. Following ESD, patients were treated with daily lansoprazole 30 mg or vonoprazan 20 mg. Ulcer size was endoscopically measured on the day after ESD and at 4 and 8 wk. The gastric mucosa was endoscopically graded according to the Kyoto gastritis scoring system. We assessed the number of patients with and without a 90% reduction in ulcer area at 4 wk post-ESD and scar formation at 8 wk, and looked for risk factors for slower healing.RESULTSThe mean size of gastric tumors and post-ESD ulcers was 17.4 ± 12.1 mm and 32.9 ± 13.0 mm. The mean reduction rates in ulcer area were 90.4% ± 0.8% at 4 wk and 99.8% ± 0.1% at 8 wk. The reduction rate was associated with the Kyoto grade of gastric atrophy at 4 wk (A0: 97.9% ± 0.6%, A1: 93.4% ± 4.1%, and A2: 89.7% ± 1.0%, respectively). In multivariate analysis, the factor predicting 90% reduction at 4 wk was gastric atrophy (Odds ratio: 5.678, 95%CI: 1.190-27.085, P = 0.029).CONCLUSIONThe healing speed of post-ESD ulcers was associated with the degree of gastric mucosal atrophy, and Helicobacter pylori eradication therapy is required to perform at younger age.

Nutrition status and Helicobacter pylori infection in patients receiving hemodialysis.

Chronic kidney disease (CKD) patients receiving hemodialysis (HD) often develop gastrointestinal abnormalities over their long treatment period. In general, prognosis in such patients is poor due to the development of protein-energy wasting (PEW). Therefore, it is important to clarify the etiology of PEW and to establish better strategies to deal with this condition. Chronic Helicobacter pylori (H. pylori) infection in the gastric mucosa has a close association with not only the development of peptic ulcer disease and gastric cancer, but is also associated with abnormal plasma and gastric mucosal ghrelin levels that are seen in malnutrition. It is unclear whether H. pylori infection of the gastric mucosa is directly associated with prognosis in HD patients by affecting ghrelin levels. Recent studies show that the prevalence of H. pylori infection in HD patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in HD patients, the prevalence of infection decreases as the length of time on HD increases. The severity of gastric mucosal atrophy has been suggested as the major determinant of ghrelin levels in these patients, and eradication therapy of H. pylori improves nutritional status by increasing serum cholinesterase and cholesterol levels, especially in patients with mild-to-moderate gastric mucosal atrophy. Prompt H. pylori eradication to inhibit the progress of gastric atrophy may be required to prevent this decrease in ghrelin levels and subsequent PEW and improve the prognosis of HD patients by improving their nutritional status.

Submitted, Not Presented: Stomach.

Introduction: Osteoporosis is often regarded as the disease specific to female, whereas male patients with osteoporosis are increasing as well. Although the main factor of osteoporosis in female is the decrease of estrogen production, the etiology is not clear for men. In Western countries, infection of H. pylori, particularly CagA-positive strain, has been shown as a possible risk for osteoporosis in male. The absorption of calcium is affected by acidity of gastrointestinal tract. In Japan, most H. pylori strains are CagA-positive and severe gastric mucosal atrophy is often observed in infected patients causing the reduction of gastric acid secretion. Thus, there could be more clear relationship between H. pylori infection and loss of bone density in Japan comparing with Western populations. The aim of this study was to examine whether H. pylori infection associates with loss of bone density in Japanese healthy males. Methods: 295 healthy male adults who attended the mass survey in 2014 were enrolled into the study (mean age: 50.2 ± 15.4 years old). We measured H. pylori stool antigen and the titer of serum antibodies to H. pylori. H. pylori status was defined as positive or negative when both tests showed concordant results. The bone density was examined calcaneal osteo sono-assessment index (OSI) using quantitative ultrasound. Osteopenia was defined when measured OSI was less than 1.0 SD from the mean OSI of the young age (20-44 years old) according to WHO diagnostic criteria. We performed logistic regression models and calculated the adjusted odds ratio (OR) for having osteopenia as a dependent variable. The independent variables were age, BMI, serum level of estradiol, the intake of calcium per day, smoking, drinking, periodical exercise, last educational background and H. pylori infection. Results: Bivariate and multivariate analyses revealed that only age was significantly different between subjects with or without osteopenia. In multivariate analysis, the adjusted OR of age for osteopenia was 2.88 (95%CI: 1.46-5.68, p < 0.001). On the other hand, the adjusted OR of H. pylori infection for osteopenia was 0.92 (0.47-1.81; p=0.81). Conclusion: Age was a significant risk for developing osteopenia in Japanese males. Unlike Western populations, no significant association was found between H. pylori infection and osteopenia in this series of adult males.

Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients

Background: Ghrelin, an orexigenic hormone, has multiple favorable functions including protein anabolism enhancement, anti-inflammatory actions, and cardiovascular protection. A low plasma ghrelin level is associated with increased mortality in patients treated with hemodialysis (HD). However, it is unclear whether the plasma ghrelin level in HD patients correlates with the severity of gastric mucosal atrophy and Helicobacter pylori status. Methods: Seventy-eight maintenance HD patients and 51 non-dialysis patients with chronic kidney disease were evaluated for severity of gastric mucosal atrophy by gastroduodenoscopy and for H. pylori status using an anti-H. pylori-antibody and rapid urease test. Plasma acyl and des-acyl ghrelin levels were measured and their associations with relevant clinical parameters were investigated. Results: Des-acyl ghrelin level in HD patients was significantly higher than that in patients with kidney function preserved. Although acyl and des-acyl ghrelin levels were similar between current H. pylori positive and negative HD patients, both levels decreased significantly with the progress of endoscopic gastric mucosal atrophy in HD patients. Serum pepsinogen (PG) I level and PG I/II ratio decreased significantly according to the severity of atrophy in HD patients and positively significantly correlated with both ghrelin levels. Multiple regression analysis showed significant positive correlations between acyl ghrelin and PG I levels (β = 0.738, p < 0.001) and significant negative correlations between ghrelin and age, albumin, and creatinine levels. Conclusions: Gastric atrophy is the major determinant of ghrelin level in HD patients. Management practices, such as H. pylori eradication, before advanced atrophy may be required to prevent the decrease of ghrelin levels and improve the prognosis of HD patients.

Lower Serum Level of Iron and Ferritin in Patients with H. pylori Infection Is not Associated With Serological Atrophic Gastritis and Intake of Iron and Vitamin C

Introduction: In Western countries, gastric mucosal inflammation caused by H. pylori infection has been associated iron metabolism. In Japan, patients with H. pylori infection develop severe gastric mucosal atrophy resulting in the decrease of gastric acid, which is an important factor for absorption of iron. However, in Japan, association between H. pylori infection and iron metabolism has not been well studied. We examined the influence of H. pylori infection on iron metabolism considering nutritional intake and serum pepsinogen (PG) in a Japanese population. Methods: 639 healthy adults who received health survey in May 2012 were entered into the study. We measured H. pylori stool antigen, titer of serum antibody to H. pylori (E-plate), serum level of PG I and II, iron and ferritin. Subjects were considered as H. pylori-infected when positive stool antigen test or serum antibody titer >10 U/mL were observed. Non-infected subjects were defined when stool antigen was negative, serum antibody titer was < 3 U/mL and without past history of eradication therapy. Subjects who were taking PPI and had previous history of gastric surgery were excluded. Daily intake of iron and vitamin C during the previous 1 month of the survey was calculated using a brief-type comprehensive self-administered diet history questionnaire. Regression coefficient between level of PGs and serum level of iron and ferritin was calculated in both males and females adjusted by age. Results: Daily intake of iron and vitamin C was not different between H. pylori-infected patients and non-infected subjects in all age groups in both male and female. In male with age of 30-39 years old, mean serum level of iron was 84.4±33.7 μg/dL in infected patients and 124.5±40.5 μg/dL in non-infected subjects (p < 0.05). Lower level of ferritin was also observed in 50-59 years male patients (132.8±103.7 ng/mL) comparing with non-infected subjects (251.9±25.0 ng/mL) (p < 0.05). In female, significantly lower level of ferritin was observed in infected patients in age of 30-39, 60-69 and 70-79 years old. Serum level of PG II was negatively correlated with serum level of iron in male infected patients (r = - 0.21, p < 0.05). However, presence of serological atrophic gastritis (PG I < 70 ng/mL and PG I/II < 3.0) was not associated with serum level of iron and ferritin. Conclusion: Lower serum level of iron and ferritin was observed in Japanese patients with H. pylori infection. Modulation of iron metabolism would be associated with gastric mucosal inflammation but not progress of glandular atrophy or intake of iron and vitamin C.

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan.

A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1year after successful H. pylori eradication. Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5years after successful H. pylori eradication was 15.0%; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5years after successful H. pylori eradication. Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.

Su1973 Tamoxifen Induced Gastric Atrophy Is Regulated by the NF-κB Subunit NFKB1

Introduction Chronic Helicobacter felis infection of C57BL/6 mice results in gastric corpus atrophy. We have previously demonstrated that the outcome of H. felis infection is altered by deletion of specific NF-κB subunits. Nfkb1 -/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection, whereas, Nfkb2 -/- mice were protected. The oestrogen receptor antagonist tamoxifen (TAM) has recently been shown to cause acute, reversible gastric atrophy in mice. In wild-type mice, this is associated with an increase in proliferating epithelial cells. We therefore hypothesised that gastric atrophy and altered epithelial cell turnover induced by TAM may be regulated by signalling involving NF-κB subunits. Method Groups of 5 adult female C57BL/6 (WT), Nfkb1 -/- , Nfkb2 -/- and c-Rel -/- mice were administered 150 mg/kg TAM by IP injection. Animals were culled 72 h later and the gastric corpus underwent quantitative histological assessment. Gastric atrophy was quantified using a validated visual analogue score. Cell positional scoring was used to quantify H + /K + ATPase expressing cells and Ki67 positive cells; gastric epithelial cells expressing cleaved-caspase 3 were quantified in 10 high-powered fields (hpf) per mouse. Results Morphological scoring demonstrated that TAM induced gastric atrophy in WT mice (median composite atrophy score (MCAS) 2 vs 0 in untreated WT mice, p + /K + ATPase or active caspase 3 positive cells was however seen. Nfkb2 -/- and c -Rel -/- mice exhibited similar phenotypes to WT mice. TAM treated Nfkb1 -/- mice developed more severe gastric atrophy with marked antralisation of the corpus epithelium (MCAS 4 vs 1 in untreated Nfkb1 -/- mice, p Nfkb1 -/- mice also exhibited corpus gland elongation after TAM treatment (36.1 ± 0.9 vs 23.9 ± 1.2cph, p 2.5 fold reduction in the number of parietal cells compared with untreated Nfkb1 -/- mice (p 2.3 fold increase in proliferating cells (p Nfkb1 -/- mice. Conclusion NFKB1 mediated signalling influences the severity of gastric mucosal atrophy and cell proliferation following TAM administration. This correlates closely with our previous observations following H. felis infection. As NFKB1 signalling plays a similar role in two models of gastric atrophy, this suggests that it may have a generic role in regulating the development of this pathology. Disclosure of interest None Declared.

Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study.

Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy. PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n = 84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H. pylori-negatives (n = 266). Frequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives (19.5%) (p < .001). Compared with duodenal ulcer, having the T allele significantly increased the risk of gastric cancer (OR: 3.97, 95% CI: 2.02-7.80; p < .001), gastric ulcer (2.40, 1.13-5.10; p = .023), and gastritis (4.72, 2.26-9.86; p < .001). Mean pepsinogen (PG) I/PG II ratio in T allele carriers (2.17 ± 0.75) was significantly lower than that in C/C genotype (3.39 ± 1.27, p < .001). The PSCA rs2294008 C>T polymorphism is associated with differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer.