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Aim: To investigate the clinicopathological features of the patients testing negative for high titer serum anti- Helicobacter pylori ( H. pylori ) antibody., Methods: The antibody titers were measured using antigens derived from Japanese individuals. 13 C-urea breath test-positive individuals were defined as having H. pylori infection. We investigated the demographic characteristics, laboratory data, endoscopic findings including Kyoto classification of gastritis, and histology in negative-high titer patients without H. pylori eradication therapy. Kyoto classification consisted of scores for gastric atrophy, intestinal metaplasia, enlarged folds, nodularity, and redness., Results: Of the 136 subjects enrolled, 23 (17%) had H. pylori infection. Kyoto classification had an excellent area under the receiver operating characteristics curve (0.886, 95% confidence interval: 0.803-0.968, P = 3.7 × 10 -20 ) for predicting H. pylori infection with a cut-off value of 2. Further, Kyoto classification, H. pylori density, and neutrophil activity had high accuracies (89.7%, 96.3%, and 94.1%, respectively). Kyoto classification was independent of the demographic and laboratory parameters in multivariate analysis., Conclusion: Endoscopic Kyoto classification of gastritis is a useful predictor of H. pylori infection in negative-high titer antibody patients., Competing Interests: Conflict-of-interest statement: During the last five years, Toyoshima O received personal fees from Otsuka Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Co., Ltd. outside of the submitted work; Suzuki H received scholarship funds for the research from Astellas Pharma Inc., Astra-Zeneca K.K., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd. and received service honoraria from Astellas Pharma, Inc., Astra-Zeneca K.K., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd.

Aim: To develop a novel Helicobacter pylori ( H. pylori ) CagA antibody enzyme-linked immunosorbent assay (ELISA) suitable for detecting serum anti-CagA antibodies with high sensitivity., Methods: Recombinant East Asian-type CagA protein was purified and immobilized for ELISA. Serum samples from 217 Vietnamese individuals (110 H. pylori -infected and 107 uninfected individuals) were applied. Conventional ELISA from Western-type CagA and our East Asian-type CagA ELISA were evaluated by comparing 38 subjects with the Western-type genotype and 72 subjects with the East Asian-type cagA genotype. Histological scores of the gastric mucosa were determined using the updated Sydney System to examine the relationship with anti-CagA antibody titers., Results: Recombinant 70-100 kDa fragments were immobilized on the ELISA plate. In ROC analysis, the area under the curve of our East Asian-type CagA ELISA was comparable to that of conventional CagA ELISA. The sensitivity of the two ELISAs differed depending on the cagA genotype. The sensitivity of East Asian-type CagA ELISA was higher for subjects infected with East Asian-type cagA H. pylori ( P < 0.001), and the sensitivity of the conventional CagA ELISA tended to be higher for subjects infected with Western cagA H. pylori ( P = 0.056). The titer of anti-CagA antibody tended to correlate with monocyte infiltration scores ( r = 0.25, P = 0.058) and was inversely correlated with H. pylori density ( r = -0.26, P = 0.043)., Conclusion: The novel ELISA is useful to detect anti-CagA antibodies in East Asian countries, and the titer may be a marker for predicting chronic gastritis.

Aim: To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation., Methods: A descriptive, observational study including pediatric patients with a diagnosis of autoimmune gastritis (positive parietal cell antibody and gastric corpus atrophy) established in a 6 year period (2006-2011) in the setting of refractory iron deficiency anemia (refractoriness to oral iron therapy for at least 6 mo and requirement for intravenous iron therapy) investigation, after exclusion of other potentially contributing causes of anemia. Helicobacter pylori (H. pylori) infection and anti-secretory therapy were also excluded. Data were retrospectively collected from clinical files, including: demographic data (age, gender, and ethnic background), past medical history, gastrointestinal symptoms, familial history, laboratorial evaluation (Hb, serum ferritin, serum gastrin, pepsinogen I/ pepsinogen II, B12 vitamin, intrinsic factor autoantibodies, thyroid autoantibodies, and anti-transglutaminase antibodies), and endoscopic and histological findings (HE, Periodic Acid-Schiff/Alcian blue, gastrin, chromogranin A and immunochemistry analysis for CD3, CD20 and CD68). Descriptive statistical analysis was performed (mean, median, and standard deviation)., Results: We report a case-series concerning 3 girls and 2 boys with a mean age of 13.6 ± 2.8 years (3 Caucasian and 2 African). One girl had type I diabetes. Familial history was positive in 4/5 cases, respectively for autoimmune thyroiditis (2/5), sarcoidosis (1/5) and multiple myeloma (1/5). Laboratorial evaluation on admission included: Hb: 9.5 ± 0.7 g/dL; serum ferritin: 4.0 ± 0.9 ng/mL; serum gastrin: 393 ± 286 pg/mL; low pepsinogen I/ pepsinogen II ratio in 1/5 patients; normal vitamin B12 levels (analyzed in 3 patients). Endoscopy findings included: duodenal nodularity (2/5) and gastric fold softening (2/5), and histological evaluation showed corpus atrophic gastritis with lymphocytic infiltration (5/5), patchy oxyntic gland mononuclear cell infiltration (5/5), intestinal and/or pseudo-pyloric metaplasia in corpus mucosa (4/5), and enterochromaffin cell hyperplasia (4/5). Immunochemistry for gastrin on corpus biopsies was negative in all cases. Duodenal histology was normal. All biopsies were negative for H. pylori (Giemsa staining and cultural examination)., Conclusion: We highlight autoimmune gastritis as a diagnosis to be considered when investigating refractory iron deficiency anemia in children, particularly in the setting of a personal/familial history of autoimmune disease, as well as the diagnostic contribution of a careful immunohistological evaluation.

Aim: To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis., Methods: One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) by gastrogavage; model control group and 2 model therapy groups that underwent gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups, while the same amount of NS, instead of geranylgeranylacetone was used in that model control group. The rats were then sacrificed and stomachs were removed. The injury level of the gastric mucosa was observed by light and electron microscopy, and the levels of prostaglandin 2 (PGE₂), endothelin-1 (ET-1) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method., Results: The gastric mucosal epidermal damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group were significantly higher than that of the normal control group (0 and 0 respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than that of the model control group (all P < 0.01). There was no statistically significant difference between the low-dose and high-dose model therapy groups. The expression value of plasma ET-1 of the model control group was higher than that of the normal control group (P < 0.01) and the 2 model therapy groups (all P < 0.01). The expression values of gastric mucosal PGE₂ and serum NO of the model control group were lower than those of the normal control group (all P < 0.05) and the 2 model therapy groups (all P < 0.05). The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group (all P < 0.01) and the 2 model therapy groups (all P < 0.05). Scanning and transmission electron microscopy observation showed that in the model control group, the epithelial junctions were vague, the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group. However, in the 2 model therapy groups, damage to the intercellular joints and organelles was ameliorate relative to the model control group., Conclusion: Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion. The mechanism could be related to regulation of ET-1, NO and PGE₂.

Aim: To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa: i.e. those with Helicobacter pylori (H pylori) gastritis or atrophic gastritis, who have a high risk of gastric cancer or peptic ulcer diseases., Methods: Among 162 Japanese outpatients, pepsinogen I (Pg I) and II (Pg II) were measured using a conventional Japanese technique, and the European GastroPanel examination (Pg I and Pg II, gastrin-17 and H pylori antibodies). Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa, H pylori non-atrophic gastritis or atrophic gastritis., Results: Pg I and Pg II assays with the GastroPanel and the Japanese method showed a highly significant correlation. For methodological reasons, however, serum Pg I, but not Pg II, was twice as high with the GastroPanel test as with the Japanese test. The biomarker assays revealed that 5% of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies. GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis. When compared to the endoscopic biopsy findings, the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy, 95% sensitivity and 93% specificity., Conclusion: Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

Aim: To elucidate the influences of H pylori infection on oral iron treatment for iron deficiency anemia (IDA)., Methods: A total of 86 patients were divided into two groups: group A, receiving ferrous succinate combined with triple therapy for H pylori eradication, and group B (control), treated with ferrous succinate only. During treatment of IDA, dynamic changes in hemoglobin (Hb) level, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), serum iron (SI), and serum ferritin (SF) were compared between the groups., Results: Hb was slightly higher in group A at d 14 after the start of triple therapy for H pylori eradication (P > 0.05). After the therapy, the increase of Hb in group A became significantly faster than that in group B (P < 0.05). At d 56, the mean Hb in group A returned to the normal level, however, in group B, it was lower than that in group A (P < 0.05) although it had also increased compared with that before oral iron treatment. The MCV and MCH in group A recovered to the normal level, and were much higher than those in group B (P < 0.05) at d 21. In Group B, the MCV and MCH remained at lower than normal levels until d 42 after the start of therapy. And then, they reached a plateau in both groups and the differences disappeared (P > 0.05). The SF in group A was higher than that in group B (P < 0.05) 28 d after the treatment and its improvement was quicker in group A (P < 0.05) , and the difference between the two groups was even more significant (P < 0.01) at d 56. The SI in group A was higher than that in group B (P < 0.05) at d 14 and this persisted until d 56 when the follow-up of this research was finished., Conclusion: Treatment of H pylori can enhance the efficacy of ferrous succinate therapy in IDA patients with H pylori-positive chronic gastritis.

Aim: To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis., Methods: Fifty consecutive patients (24 males and 26 females) with either H pylori-positive gastritis (n = 34) or H pylori-negative gastritis (n = 16) with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study. Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid, 1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d, followed by an additional 4 wk of 30 mg lansoprazol treatment. H pylori infection was eradicated in 23 of 34 (67.6%) patients. H pylori-positive patients were given eradication therapy. Gastric acidity was determined via intragastric pH catheters. Serum ghrelin was measured by radioimmunoassay (RIA)., Results: There was no significant difference in plasma ghrelin levels between H pylori-positive and H pylori-negative groups (81.10 +/- 162.66 ng/L vs 76.51 +/- 122.94 ng/L). In addition, there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy., Conclusion: H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.

Aim: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children with Helicobacter pylori (H pylori) infection and to evaluate their significance for the morphological changes found in gastric mucosa., Methods: The study included 106 children: 59 children (55.7%) with chronic gastritis and positive IgG against H pylori, 29 children (27.3%) after previous H pylori infection without the bacterium colonization but with positive IgG against H pylori, and 18 children (17%) with functional disorders of the gastrointestinal system but with normal IgG against H pylori. Endoscopic and histopathological evaluation of gastric mucosa was performed based on the Sydney System classification. The evaluation of sP-selectin, sICAM-1, sVCAM-1 levels in the sera of children was carried out using ELISA test., Results: The assessment of gastritis activity degrees indicated statistically significant values in the antrum and corpus (P<0.001) of children examined. Serum sVCAM-1 levels were higher in group with gastritis due to H pylori infection than in group without infection and differed statistically (P<0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive molecules in infected children and decreased after eradication of H pylori. Serum sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were similar in children with and without H pylori infection., Conclusion: Assessment of adhesive molecules (sP-selectin, sICAM-1, sVCAM-1) in the sera of children with active H pylori infection can show the participation of sVCAM-1 in the pathogenesis of gastric mucosal inflammation. sP-selectin and sICAM-1 concentrations in the sera of children with H pylori infection after eradication cannot reveal any significant differences as compared to healthy children.

Aim: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer., Methods: One hundred and seventy-eight consecutive Helicobacter pylori (H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests., Results: There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values., Conclusion: Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.

Aim: To determine the prevalence of Helicobacter pylori (H. pylori) infection, the serum anti-H. pylori immunoglobulin G (IgG) and IgA antibody responses, and the value of clinical presentations in diagnosis of H. pylori infection in patients with gastric atrophy, intestinal metaplasia and dysplasia., Methods: H. pylori infection was detected by histology in 209 patients with mild chronic atrophic gastritis (CAG, n=76), severe CAG (n=22), mild intestinal metaplasia (IM, n=22), severe IM (n=58), or dysplasia (DYS, n=31). Serum anti-H. pylori IgG and IgA were double sampled and evaluated by enzyme-linked immunoadsordent assays. 35 clinical presentations were observed and their relationship with H. pylori infection was analyzed by the k-means cluster method., Results: Both IgG and IgA levels in H. pylori positive patients were significantly higher than those negative for H. pylori (P<0.001-0.01). The prevalence of H. pylori was highest in severe IM (84.5 %), and lowest in mild CAG (51.3 %) (P<0.01). They were similar in severe CAG (68.2 %), mild IM (72.7 %), and DYS (67.7 %). In H. pylori positive patients, the IgG levels in severe CAG were significantly higher than those in mild CAG (P<0.01). In H. pylori negative patients, both IgG and IgA levels increased remarkably in severe IM, compared to those in mild IM (P<0.01-0.05). H. pylori infection exhibited no association with patient's gender (62.1 % in males; 71.7 % in females) and age (r=0.0814, P=0.241). The diagnostic accuracy based on 35 clinical presentations was 65.7 %. It could be improved by 5.7 % when only the assemblage of digestive symptoms were engaged, or by 8.6 % when the pathogenic factors, general status and grossoscopy were combined. The diagnostic accuracy could be decreased when only the general symptoms were engaged, or when the pathogenic factors were accompanied with some common digestive symptoms., Conclusion: H. pylori infection is a major risk factor for the process from atrophy, IM to DYS of gastric mucosa. Serum IgG and IgA are good indicators to evaluate this progress with a certain arrearage. Investigation on the effective assemblages of clinical presentations may provide a better understanding in the pathogenesis, diagnosis and treatment for H. pylori infection.