Pylori-associated Gastritis Research Articles

Strategies for eliminating death from gastric cancer in Japan.

In Japan, efforts have been directed toward improving the detection of early gastric cancer by double contrast radiography and endoscopy, since early cancer has a good prognosis, resulting in Japan having the world’s best diagnostic system for early gastric cancer. The 5-year survival rate of gastric cancer patients in Japan is much higher than in Western countries by the development of endoscopic treatment for early gastric cancer. In February 2013, Japanese national health insurance cover for H. pylori eradication therapy was expanded to patients with H. pylori-associated gastritis, a type of chronic gastritis. H. pylori-associated gastritis causes gastric and duodenal ulcers and gastric polyps, therefore, providing treatment for this gastritis is likely to substantially decrease the prevalence of both gastric and duodenal ulcer and gastric cancer. Patients with gastritis are tested for H. pylori infection and those who are positive receive eradication therapy followed by periodic endoscopic surveillance. If such an approach is pursued further in Japan, gastric cancer deaths will show a dramatic decline after 10–20 years.

New Guidelines forHelicobacter pyloriTreatment: Comparisons between Korea and Japan

Korea and Japan show the highest incidence of gastric cancer and Helicobacter pylori infection. New 2013 guidelines on H. pylori infection differ between the two countries with regard to the indications for H. pylori eradication, diagnostic methods, and treatment regimens. Indications for eradication in Korean guideline focus on specific diseases such as peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, and after resection of early gastric cancer, while Japanese guideline includes all H. pylori-associated gastritis for the prevention of dissemination. With regard to the diagnosis, either noninvasive or invasive method (except for bacterial culture) is recommended in Korea, while two noninvasive tests including serum anti-H. pylori IgG antibody level are preferred in Japan. As for the treatment regimens, second-line treatment (quadruple bismuth-containing regimen) is recommended without first-line triple therapy in areas of high clarithromycin resistance in Korea. However, there is no bismuth-based second-line treatment in Japan, and the Japanese regimen consists of a lower dose of antibiotics for a shorter duration (7 days). Such discrepancies between the two countries are based not only on the differences in the literature search and interpretation, but also on the different approvals granted by the national health insurance system, manufacturing process of the antibiotics, and diagnostic techniques in each country. Collaborations are required to minimize the discrepancies between the two countries based on cost-effectiveness.

Roadmap to eliminate gastric cancer with Helicobacter pylori eradication and consecutive surveillance in Japan.

In Japan, the annual number of deaths from gastric cancer is approximately 50,000 and there has been no change over the last 50 years. So far, all efforts have been directed toward improving the detection of early gastric cancer by barium X-ray and endoscopy, since early cancer has a good prognosis, resulting in Japan having the best diagnostic capability for early gastric cancer worldwide. The 5-year survival rate of gastric cancer patients exceeds 60 % in Japan and is much higher than that in Europe and the US (20 %) because of this superior diagnosis of early gastric cancer. In February 2013, national health insurance coverage for Helicobacter pylori eradication therapy to treat H. pylori-associated chronic gastritis became available in Japan. H. pylori-associated gastritis leads to development of gastric and duodenal ulcers and gastric polyps. Therefore, providing treatment for gastritis is likely to substantially decrease the prevalence of both gastric and duodenal ulcers and polyps. Because treatment for H. pylori-associated gastritis, which leads to atrophic gastritis and gastric cancer, is now covered by health insurance in Japan, a strategy to eliminate gastric cancer-related deaths by taking advantage of this innovation was planned. According to this strategy, patients with gastritis will be investigated for H. pylori infection and those who are positive will receive eradication therapy followed by periodic surveillance. If this strategy is implemented, deaths from gastric cancer in Japan will decrease dramatically after 10–20 years.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Primary Gastric Linitis Plastica Presenting as Severe Non-Healing Helicobacter pylori-Associated Gastritis

Purpose: Gastric linitis plastica (GLP) is a rigid and constrictive thickening of the stomach secondary to diffuse infiltration of poorly differentiated adenocarcinoma. The risk factors leading to GLP are poorly understood, and believed to be secondary to underlying genetic predispositions, i.e. E-cadherin mutations. In contrast to intestinal-type gastric adenocarcinomas, diffuse-type GLP is not believed to be related to environmental risk factors, and has not been described as associated with Helicobacter pylori. We describe a case of GLP associated with, and presenting as severe H.pylori-associated gastritis. A 48 year old man with no past medical history was admitted for two weeks of new abdominal fullness with nausea/vomiting. CT abdomen/pelvis demonstrated dilated stomach with H. pyloric thickening. On upper endoscopy, several antral ulcers with surrounding severe pyloric congestion and edema were noted. Antral biopsies showed moderate chronic gastritis with marked reactive changes, and serum H. pylori IgG antibodies were positive. The patient was diagnosed with, and treated for severe H. pylori gastritis with ulcerative inflammation causing partial gastric outlet obstruction. The patient demonstrated slow clinical improvement, and was taken back to endoscopy at two weeks. Persistent ulcerations and congestion was noted, and endoscopic ultrasound (EUS) exam demonstrated diffuse infiltration of the gastric wall with loss of normal five layer anatomy. Pathology from deep bite biopsies and fine needle aspiration showed diffuse poorly differentiated adenocarcinoma. The patient was taken for a subtotal gastrectomy and discharged for outpatient adjuvant chemoradiation. The diffusely infiltrative nature of GLP leads to a rigid stomach that typically manifests endoscopically with a “leather bottle” appearance, and clinically as epigastric pain with nausea/vomiting, anorexia, and weight loss. This type of gastric cancer has a very poor prognosis, occurs in relatively young patients, and has not been associated with H. pylori gastritis and other environmental risk factors. In this unique case, the patient presented with non-healing ulcers with associated partial outlet obstruction that was attributed to an underlying H. pylori infection. This case highlights a number of salient issues: 1.) the inherent difficult diagnosis of GLP due to high frequency of mucosal sparing and false negative biopsies, 2.) the need to re-evaluate non-healing ulcers or patients with H. pylori not responding to traditional therapy, and 3.) the need for re-evaluation of a possible link between H. pylori and GLP.

DC-LAMP + Dendritic Cells Are Recruited to Gastric Lymphoid Follicles in Helicobacter pylori-Infected Individuals

Infection with Helicobacter pylori is associated with development of ulcer disease and gastrointestinal adenocarcinoma. The infection leads to a large infiltration of immune cells and the formation of organized lymphoid follicles in the human gastric mucosa. Still, the immune system fails to eradicate the bacteria, and the substantial regulatory T cell (Treg) response elicited is probably a major factor permitting bacterial persistence. Dendritic cells (DCs) are professional antigen-presenting cells that can activate naive T cells, and maturation of DCs is crucial for the initiation of primary immune responses. The aim of this study was to investigate the presence and localization of mature human DCs in H. pylori-infected gastric mucosa. Gastric antral biopsy specimens were collected from patients with H. pylori-associated gastritis and healthy volunteers, and antrum tissue was collected from patients undergoing gastric resection. Immunohistochemistry and flow cytometry showed that DCs expressing the maturation marker dendritic cell lysosome-associated membrane glycoprotein (DC-LAMP; CD208) are enriched in the H. pylori-infected gastric mucosa and that these DCs are specifically localized within or close to lymphoid follicles. Gastric DC-LAMP-positive (DC-LAMP(+)) DCs express CD11c and high levels of HLA-DR but little CD80, CD83, and CD86. Furthermore, immunofluorescence analyses demonstrated that DC-LAMP(+) DCs are in the same location as FoxP3-positive putative Tregs in the follicles. In conclusion, we show that DC-LAMP(+) DCs with low costimulatory capacity accumulate in the lymphoid follicles in human H. pylori-infected gastric tissue, and our results suggest that Treg-DC interactions may promote chronic infection by rendering gastric DCs tolerogenic.

The Korean Perspective of Helicobacter pylori Infection: Lessons from Japan Policy to Prevent Gastric Cancer

The guideline of the Korean College of Helicobacter and Upper Gastrointestinal Research group for Helicobacter pylori infection was first produced in 1998. Definite indication for H. pylori eradication is early gastric cancer in addition to the previous indications of peptic ulcer (PUD) including scar lesion and marginal zone B cell lymphoma (MALT type). Though treatment regimen was similar, Japan government declared the inclusion of H. pylori eradication in patients with H. pylori-associated chronic gastritis, suggesting the treatment guideline is quite different between Korea and Japan from February 21, 2013. The prime rationale of Japanese extended treatment guideline for H. pylori infection was based on the drastic intention to prevent gastric cancer according to their beliefs that H. pylori eradication can decrease gastric cancer incidence as well as mortality. In this review, the discrepancy in treatment guideline between Korea and Japan will be explained.

AB0645 Sarcoid / granulomatous disease in association with helicobacter pylori

BackgroundHelicobacter Pylori (HP) has been studied in several autoimmune disorders but definite causality is perhaps restricted to MALT Lymphoma and some cases of ‘idiopathic’ immune thrombocytopenia (1,2). HP may suppress...

Chemokine receptors in gastric MALT lymphoma: loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma

Chemokine receptors have a crucial role in the development and progression of lymphoid neoplasms. To determine the chemokine receptor expression profile in gastric mucosa-associated lymphoid tissue (MALT) lymphoma, we performed an expression analysis of 19 chemokine receptors at mRNA levels by using real-time RT-PCR, as well as of five chemokine receptors—CCR8, CCR9, CXCR4, CXCR6 and CXCR7—by immunohistochemistry on human tissue samples of Helicobacter pylori-associated gastritis, gastric MALT lymphoma and gastric extranodal diffuse large B-cell lymphoma originating from MALT lymphoma (transformed MALT lymphoma). Following malignant transformation from H. pylori-associated gastritis to MALT lymphoma, an upregulation of CCR7, CXCR3 and CXCR7, and a loss of CXCR4 were detected. The transformation of gastric MALT lymphomas to gastric extranodal diffuse large B-cell lymphoma was accompanied by upregulation of CCR1, CCR5, CCR7, CCR8, CCR9, CXCR3, CXCR6, CXCR7 and XCR1. Remarkably, CXCR4 expression was exclusively found in nodal marginal B-cell lymphomas and nodal diffuse large B-cell lymphomas but not at extranodal manifestation sites, ie, in gastric MALT lymphomas or gastric extranodal diffuse large B-cell lymphomas. Furthermore, the incidence of bone marrow infiltration (16/51 with bone marrow involvement vs 35/51 with bone marrow involvement; Spearman ρ=0467 P<0.001) positively correlated with CXCR4 expression. CXCL12, the ligand of CXCR4 and CXCR7, was expressed by epithelial, endothelial and inflammatory cells, MALT lymphoma cells and was most strongly expressed by extranodal diffuse large B-cell lymphoma cells, suggesting at least in part an autocrine signaling pathway. Our data indicate that CXCR4 expression is associated with nodal manifestation and a more advanced stage of lymphomas and hence, might serve as useful clinical prognostic marker.

Outcome of screening endoscopy in common variable immunodeficiency disorder and X-linked agammaglobulinemia

Gastrointestinal symptoms are common in patients with common variable immunodeficiency disorders (CVID) and less frequent in X-linked agammaglobulinemia (XLA) although the exact prevalence is not well established. In this study, endoscopic screening was performed in 30 patients with CVID and four patients with XLA. Endoscopic and/or histological abnormalities were detected in 25 of 30 patients with CVID (83 %), regardless of symptoms, and in nine of these patients the results prompted medical treatment. Helicobacter pylori-associated gastritis, adenomatous polyps, and lymphoid hyperplasia were most frequently encountered; no malignancies were detected. Adenomatous polyps were found in two of the four patients with XLA at a relative young age. In conclusion, gastrointestinal pathology is frequent in patients with CVID regardless of symptoms. Patients with XLA seem to be at risk for colorectal adenomas at a young age.

Does Helicobacter Pylori Infection Increase the Levels of Exhaled Nitric Oxide?

It has been suggested that H. pylori infection upregulates iNOS expresion and synthesis of nitric oxide (NO). In order to extend the scope, exhaled NO in H. pylori-infected patients with chronic gastritis was investigated. Exhaled oral NO level was measured with Niox Mino® analyzer, twice before and six-seven months after successful H. pylori eradication therapy in 26 patients with gastritis and in 16 healthy non-atopic subjects. Exhaled NO was significantly increased in H. pylori-infected patients with chronic gastritis as compared with the healthy subjects. Following eradication the levels were significantly reduced compared to the basal level before the therapy and did not differ significantly from those of the healthy subjects. It seems that H. pylori-associated gastritis is accompanied by an increased level of exhaled NO, resulting probably from the locally increased NO production.

Polymorphism of IL-1RA and TNF-alpha genes in patients with Helicobacter pylori associated gastritis and duodenal ulcer

The goal of this work was to determine the frequency of major types of polymorphism in the genes of interleukin-1 receptor antagonist (IL-1RA) and TNF-alpha in patients with Helicobacter pylori-associated gastritis and duodenal ulcer and elucidate its correlation with clinical manifestation of the disease. A total of 126 patients were selected for the study with different gastroduodenal pathologies and H. pylori detected in biopsy material. The obtained data indicate a possible correlation between the risk of developing duodenal ulcer and the presence of the allele A in the TNF-alpha gene at the −308 position in the patients. Polymorphism analysis of the IL-1RA gene revealed a statistically significant difference in the availability of the 2/L genotype in the studied groups of patients. The conducted research demonstrates that a parallel typing of the H. pylori virulence genes and determination of the cytokine gene polymorphism in the biopsy material taken from the patient is required for characterization of the bacterium-host interaction.

Effect of Bifidobacterium bifidum BF-1 on gastric protection and mucin production in an acute gastric injury rat model

Homeostasis in the stomach environment is maintained by the balance of protective factors such as gastric mucus and aggressive factors such as gastric acid, stress, alcohol, and drugs. An overload of aggressive factors that upsets this balance can induce gastric injury. Fermented milk that contains Bifidobacterium bifidum BF-1 (BF-1), a probiotic strain, and Streptococcus thermophilus YIT 2021 (ST) is known to improve Helicobacter pylori-associated gastritis in humans. Here, we investigated the gastroprotective potential of BF-1 in a rat model of acid-ethanol-induced acute gastric injury to fully elucidate its potential compared with ST. Living BF-1, ST, or vehicle was orally administrated to rats, and acid-ethanol gastric injury was induced 2h later. The gastric injury rate was determined and shown to be significantly lower in the BF-1 group than in the vehicle group, which showed a similar level to the ST group. The production of gastric mucin and the expression of several target genes associated with protection and inflammation were examined before and after induction of gastric injury. Interestingly, mucin 5ac (muc5ac) gene expression in gastric corpus samples and gastric mucin production in stomach samples from the BF-1 group, but not the ST group, were significantly higher than those in the respective samples from the vehicle group. These findings indicate that BF-1 has the potential to provide gastroprotection, alleviating acute gastric injury by enhancing the production of gastric mucin in a rat model.

Elevated risk of recurrent colorectal neoplasia with Helicobacter pylori-associated chronic atrophic gastritis: A follow-up study of patients with endoscopically resected colorectal neoplasia

In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33-5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.

A clinicopathological study of dyspeptic subjects in Lagos, Nigeria

The clinicopathological and endoscopic features of dyspepsia have not been well studied in Nigeria due to the high cost of gastroscopes and lack of the relevant expertise. This study was designed to highlight these features and possible risk factors. This prospective study was conducted on adult dyspeptic patients who fulfilled the study criteria from November 2007 to December 2008 at a University hospital in Lagos, Nigeria. Demographic and clinical presentation including possible risk factors were obtained through a questionnaire administered by an interviewer followed by an upper gastrointestinal endoscopy and gastric biopsy. Of the 123 subjects who took part in the study, 100 gave their consent to an upper gastrointestinal endoscopy and biopsy. The male:female ratio was 1:1, mean age was 44.98 (SD 15.4) years and the modal age group was 38-47years. The prevalence of dyspepsia was 29% and epigastric pain was the most common presentation. Endoscopic findings were superficial mucosal lesion (21%), peptic ulcer (16%), features of gastroesophageal reflux disease (10%), and gastric cancer (2%), as well normal findings (44%). Non-steroidal antiinflammatory drug (NSAID) use as a risk factor had a significant association with positive endoscopic findings; relative risk for development of positive endoscopic findings was 1.5% (P =0.03). Histology showed rates of chronic gastritis to be 91% and normal values 9%. The most common type of gastritis was the non-specific form (59.3%), followed by H. Pylori-associated gastritis (36.3%). The topography of gastritis was mainly pangastritis (68.1%) and antral predominant in 23.1%. The prevalence of H. pylori by histology was 41%. The presence of H. pylori was not associated with severity, location or duration of symptoms. H. pylori was, however, found to be a significant contributor to the development of positive endoscopic findings (P=0.01; OR 2.92 95% CI 1.50-3.17). Alarm symptoms were found to be important markers of malignancy. Dyspeptic illness is common,with peak incidence in the 4th decade of life and no gender predilection. Epigastric pain has the most discriminatory value with alarm symptoms in cases of gastric cancer. Risk factors such as NSAID use and H. pylori infection had a very significant impact on endoscopic findings while presence of H. pylori, smoking and alcohol consumption were associated with increased risk of developing chronic gastritis.

Oxidative stress in inflammation‐based gastrointestinal tract diseases: Challenges and opportunities

Oxygen free radicals in excessively high amounts are all very reactive chemically and can impose a detrimental influence on living organisms by provoking "oxidative stress" that can damage major cellular constituents. The latter includes the cell membrane, cytoplasmic proteins, and nuclear DNA. Conversely, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) when present in low amounts play an important role as regulatory mediators in signaling processes, through which, paradoxically, many ROS-mediated responses can protect the cells against oxidative stress by induction of "redox homeostasis." Therefore, diseases associated with free radical overproduction are provoked by "blazed ROS productions" far beyond the host's capacity to quench. Free radicals have been implicated in the pathogenesis of diverse gastrointestinal (GI) diseases including gastroesophageal reflux disease (GERD), gastritis, enteritis, colitis and associated cancers as well as pancreatitis and liver cirrhosis. This article provides an overview of the role of oxidative stress in inflammation-based GI tract diseases, including reflux esophagitis, Helicobacter pylori-associated gastritis, non-steroidal anti-inflammatory drug-induced enteritis, ulcerative colitis, and associated colorectal cancer. The challenging issue that ROS can contribute to diverse gastrointestinal dysfunction, or manifest dual roles in cancer promotion or cancer suppression will also be discussed for the opportunity to enhance understanding of inflammation-based GI diseases.

501 Evaluation of specific biochemical indicators of Helicobacter pylori-associated gastric cancer in Egypt

The aim of the study was to assess the accuracy of some specific biochemical indicators in discriminating between Helicobacter pylori-associated gastritis and H. pylori-associated stomach cancer (serum gastrin level, serum soluble E-cadherin and tissue COX-2 activity, as well as serodiagnostic markers for H. pylori infection) in order to find a simple diagnostic test that can reasonably predict the development of gastric cancer. The study participants comprised 20 patients with gastric carcinoma, 20 patients with positive H. pylori-associated gastritis and 20 individuals as the control group. Standard procedures and quality control measures were followed. Using cut-off values and ROC analysis to assess the diagnostic abilities of the biochemical indicators, E-cadherin showed the highest sensitivity (100%). We suggest that close follow-up together with periodic endoscopic examination for all patients with persistent H. pylori infection and serum soluble E-cadherin level above 5 microg/mL is essential.

Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng

Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide (H2S) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating H2S generation. Because the incubation of endothelial cells with H2S has been known to enhance their angiogenic activities, we hypothesized that the amelioration of H2S-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the H2S generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine β-synthase and cystathionine γ-lyase, enzymes that are essential for H2S synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this H2S-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate H2S-induced angiogenesis, implying that antagonistic action against H2S-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.

Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis

This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤ 3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach.

Comparison of sequential and 7-, 10-, 14-d triple therapy forHelicobacter pyloriinfection

To compare the effectiveness of sequential therapy for Helicobacter pylori (H. pylori) infection with that of triple therapy of varying durations. The 460 patients enrolled in this study had H. pylori-associated gastritis or a gastric or duodenal ulcer. After screening, H. pylori-infected patients were randomly assigned to receive either conventional triple therapy for 7, 10 or 14 d, or a new 10-d sequential therapy. Each of the 4 treatment groups included 115 patients. The outcomes of eradication therapy were assessed 4 wk after treatment by the urea breath test and histology. The overall eradication rate was 81.0%, and eradication rates were 75.7% for 7-d conventional triple therapy, 81.9% for 10-d conventional triple therapy, 84.4% for 14-d conventional triple therapy, and 82.0% for 10-d sequential therapy. Neither intention-to-treat analysis nor per protocol analysis showed significant differences in eradication rates using sequential therapy or the standard triple therapy (P = 0.416 and P = 0.405, respectively). There are no significant differences between 10-d sequential eradication therapy for H. pylori and any duration of standard triple treatment in Korean patients.