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Background: Given sparse relevant data, the aim of this study was to determine whether Helicobacter pylori infection, including cytotoxin-associated gene-A (CagA) producing strains, is associated with dementia in type 2 diabetes (T2DM)., Methods: Longitudinal data from 1115 participants in the community-based Fremantle Diabetes Study Phase I (mean age 64.0 years, 48.0 % males; 38.0 % H. pylori seronegative, 24.3 % H. pylori seropositive/CagA seronegative, and 37.7 % H. pylori/CagA seropositive at baseline) were analyzed., Results: During up to 19 years of follow-up, 50.3 % and 83.5 % of participants without and with incident dementia, respectively, died. In Cox proportional hazards models, H. pylori/CagA seropositivity (hazard ratio (95 % CI) 1.68 (1.15, 2.46), P = 0.008), but not H. pylori seropositivity/CagA seronegativity (P = 0.541) was an independent predictor of incident dementia, but neither H. pylori seropositivity/CagA seronegativity nor H. pylori/CagA seropositivity were significant predictors in competing risks models (P ≥ 0.280)., Conclusions: Although CagA seropositivity in T2DM may have a contributory etiologic role in the risk of dementia, this may be through its association with reduced cardiovascular/all-cause mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, including overall survival (OS), remission, and factors associated with an aggressive disease course., Materials and Methods: Medical records of 153 patients diagnosed with gastric MALT lymphoma between 2013 and 2020 were retrospectively reviewed. Patients experiencing relapse, progression, high-grade transformation, or residual diseasewere included in the aggressive group and were compared with those in the indolent group. Additionally, the endoscopic findings of Helicobacter pylori -negative patients were reviewed., Results: Patient characteristics were as follows: mean age (56.9±11.2 years), sex (male, 51.0%), H. pylori infection (positive, 79.7%), endoscopic location (distal, 89.5%), endoscopic feature (superficial, 89.5%), clinical stage (stage I, 92.8%), invasion depth by endoscopic ultrasound (mucosa, n=115, 75.7%), and bone marrow result (no involvement, n=77, 100.0%). The median follow-up period was 59 months (mean, 61; range, 36-124) and the continuous remission period (n=149) was 51 months (mean, 50; range, 3-112). The 5-year survival rate was 97.7% while the 5-year continuous remission was 88.3%. Factors associated with the patients in the aggressive group were old age, sex(male), and clinical stage II or higher. H. pylori -negative patients' endoscopy revealed a high incidence of atrophic gastritis in the antrum., Conclusions: The long-term prognosis of gastric MALT lymphoma appears indolent and is indicated by the 5-year OS and continuous remission rates. Aggressive disease courses are associated with old age, sex (male), and clinical stage II or higher, but are not related to OS., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Gastric Cancer Association.)

Background: Antioxidant and pro-oxidant dietary patterns and lifestyle changes have been considered to play a crucial role in Helicobacter pylori (H. pylori) infection. We conducted this study to investigate the underlying association between oxidative balance score (OBS) and H. pylori infection in the US population., Methods: This was a cross-sectional study according to data from the National Health and Nutrition Examination Survey (1999-2000), and included individuals with complete information about dietary intake and H. pylori serologic testing results. In the present study, we used multivariate logistic regression analysis, smoothed curve fitting, subgroup analyses, and Cox proportional hazards modeling based on demographic and clinical variables to examine the relationship between OBS and H. pylori infection., Results: A total of 3413 individuals participated in our analysis with an average age of 32.31 years. The prevalence of H. pylori infection in the study population was 29.77%. By performing smooth curve fitting analysis, we observed an approximately linear relationship between OBS and H. pylori infection, indicating that lower OBS was associated with higher risk of H. pylori infection, especially in over 60 years of age and non-Hispanic white populations. All-cause mortality was also found lower in individuals with higher OBS levels., Conclusion: In the US population, increased levels of OBS were associated with a reduced risk of H. pylori infection and decreased all-cause mortality. More and further work is still needed to elucidate the precise mechanism of the association between OBS and H. pylori infection., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Limited research has examined the association between Oxidative Balance Score (OBS) and mortality, particularly in individuals with Helicobacter pylori (H. pylori) infection. This study investigates the correlation between OBS and H. pylori infection and their impacts on all-cause mortality within a cohort of individuals, considering both infected and uninfected individuals. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, comprising 4,532 participants, were analyzed. Logistic regression analyses assessed the relationship between H. pylori infection and relevant covariates. Cox regression and restricted cubic spline analysis evaluated the association between total OBS, lifestyle OBS, dietary OBS, and all-cause mortality in H. pylori -positive and -negative individuals. Results: Restricted cubic spline modeling revealed a linear relationship between total OBS and all-cause mortality, particularly in H. pylori -negative patients. Total OBS, dietary OBS, and lifestyle OBS inversely correlated with H. pylori infection, even after adjusting for confounders. Higher dietary OBS was associated with decreased mortality risk exclusively in H. pylori -positive individuals, while lifestyle OBS was associated with mortality only in H. pylori -negative individuals. These findings underscore the complex relationships between OBS, H. pylori infection, and mortality, stressing the importance of infection status in assessing oxidative balance's impact on health. Conclusion: In this sample, higher OBS was associated with lower H. pylori infection risks. Dietary OBS correlated significantly with all-cause mortality in H. pylori -positive individuals, while lifestyle OBS was notably associated with mortality in H. pylori -negative participants. Further research is necessary to elucidate the underlying mechanisms and clinical implications of these findings., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The Blue Iguana Recovery Programme maintains a captive breeding and head-starting program for endangered Grand Cayman blue iguanas (Cyclura lewisi) on Grand Cayman, Cayman Islands. In May 2015, program staff encountered two lethargic wild Grand Cayman blue iguanas within the Queen Elizabeth II Botanic Park (QEIIBP). Spiral-shaped bacteria were identified on peripheral blood smears from both animals, which molecular diagnostics identified as a novel Helicobacter species (provisionary name Helicobacter sp. GCBI1). Between March 2015 and February 2017, 11 Grand Cayman blue iguanas were identified with the infection. Two of these were found dead and nine were treated; five of the nine treated animals survived the initial infection. Phylogenetic analysis of the 16S rRNA gene suggests Helicobacter sp. GCBI1 is most closely related to Helicobacter spp. in chelonians. We developed a Taqman qPCR assay specific for Helicobacter sp. GCBI1 to screen tissue and/or blood samples from clinical cases, fecal and cloacal samples from clinically healthy Grand Cayman blue iguanas, including previously infected and recovered iguanas, and iguanas housed adjacent to clinical cases. Fecal and/or cloacal swab samples were all negative, suggesting that Grand Cayman blue iguanas do not asymptomatically carry this organism nor shed this pathogen per cloaca post infection. Retrospective analysis of a 2014 mortality event affecting green iguanas (Iguana iguana) from a separate Grand Cayman location identified Helicobacter sp. GCBI1 in two of three cases. The source of infection and mode of transmission are yet to be confirmed. Analysis of rainfall data reveal that all infections occurred during a multi-year dry period, and most occurred shortly after the first rains at the end of seasonal drought. Additionally, further screening has identified Helicobacter sp. GCBI1 from choanal swabs of clinically normal green iguanas in the QEIIBP, suggesting they could be asymptomatic carriers and a potential source of the pathogen., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: One author (ISP) was commercially employed through the duration of the study and manuscript preparation (Island Veterinary Services and Newmarket Vets4Pets); funding from these businesses was limited to salary support. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy is still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group 1 carcinogenic agents in humans by the International Agency for Research on Cancer. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to the 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was 8.7% of all cancer deaths registered yearly, on average. Approximately 60% of deaths occurred in men, and almost the whole burden was due to four infectious agents ( Helicobacter pylori , hepatitis C virus, high-risk human papillomavirus, and hepatitis B virus). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Objective: Helicobacter pylori (HP) is known to play an important role in the development of gastric cancer (GC). The aim of this study was to analyze the effect of HP eradication on the survival rate and cancer recurrence in patients who underwent subtotal gastrectomy for GC., Design: Totally 1,031 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital from 2003 to 2017 and positive for HP infection were analyzed. The overall and GC-related survival according to HP eradication were compared; risk factors for GC-specific death and cancer recurrence were analyzed, and propensity score matching (PSM) was performed., Results: Statistically significant benefits of overall and GC-specific survival were observed in the eradicated group compared to the non-eradicated group (P < 0.001), and these benefits were maintained after PSM (P < 0.001) in both of early and advance stage. In Cox proportional hazards multivariate analyses, cancer stage (stage II, adjusted hazard ratio [aHR] = 9.33, P < 0.001; stage III or IV, aHR = 26.17, P < 0.001), and HP positivity (aHR = 3.41, P = 0.001) were independent risk factors for GC-specific death; cancer stage (cancer stage II, aHR = 7.08, P < 0.001; cancer stage III or IV, aHR = 19.64, P < 0.001) and HP positivity (aHR = 2.70; P = 0.005) were independent risk factors for cancer recurrence., Conclusion: Our results suggest that HP needed to be conducted more intensively in patients who are surgically treated for GC, regardless of cancer stage.

In February 2013, Japan became the first country in the world to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system. Now that eradication therapy is covered by NHI, its usage has increased dramatically, and gastric cancer deaths have begun to decrease. We undertook a detailed epidemiological analysis to investigate effects of expanded NHI coverage for H. pylori eradication therapy on gastric cancer deaths in specific age groups. Numbers of gastric cancer deaths were determined by referencing data from Ministry of Health, Labour and Welfare reports and "Cancer Statistics in Japan - 2018" published by the Foundation for Promotion of Cancer Research. Gastric cancer deaths across all age groups have been clearly decreasing since 2013, but deaths of people aged 80 years and older are still increasing. The number of gastric cancer deaths in people aged in their 80s was 2 times higher than in people aged in their 70s and 4 times higher than in people aged in their 60s. The number of people in their 80s who had an endoscopy was less than half that of people in their 60s and 70s. The eradication therapy has increased dramatically, and gastric cancer deaths are clearly decreasing in Japan. However, this decrease in deaths has not extended to elderly adults aged in their 80s, which suggests that measures to prevent gastric cancer in people aged 80 years and older will be critical to achieving the mission of eliminating gastric cancer in Japan., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background/Aims: A meta-analysis of randomized trials performed in healthy asymptomatic individuals suggested that overall mortality may increase after Helicobacter pylori eradication despite a significant decrease in the gastric cancer incidence and mortality rates. This retrospective population-based cohort study investigated if H. pylori treatment is associated with an increase in overall mortality in patients with hypertension. Methods: From the database of the Korean National Health Insurance Sample Cohort, we selected 198,487 patients treated for hypertension between 2002 and 2010. Those who received H. pylori treatment ( H. pylori treatment cohort, 5,541 patients) were matched to those who did not (nontreatment cohort, 11,082 patients) at the ratio of 1 to 2. The primary outcome was the risk of overall mortality. The secondary outcomes were the risks of mortality due to cardiovascular disease, cerebrovascular disease, and cancer. The outcomes were evaluated from 6 months after H. pylori treatment to December 2013. A Cox proportional hazard model was used to estimate the hazard ratios (HRs). Results: During a median follow-up period of 4.8 years, death from any cause was reported in 4.1% of the patients in the H. pylori treatment cohort and 5.5% of the patients in the nontreatment cohort. The adjusted HR (aHR) for overall mortality in the H. pylori treatment cohort was 0.70 (95% confidence interval [CI], 0.60 to 0.82; p<0.001). With regard to cause-specific mortality, compared with the nontreatment cohort, the H. pylori treatment cohort had a lower risk of mortality due to cerebrovascular disease (aHR, 0.46; 95% CI, 0.26 to 0.81; p=0.007). The risks of mortality due to cancer and cardiovascular disease were not different between the cohorts. Conclusions: H. pylori treatment is not associated with an increase in overall mortality in patients treated for hypertension.

We evaluated the role of 18-fluoro-2-deoxy-d-glucose positron emission tomography ( [18F] FDG-PET) with computed tomography (CT) (PET/CT) as a diagnostic and prognostic tool in newly diagnosed marginal zone lymphoma (MZL) patients. This is a retrospective cohort study of patients with newly diagnosed MZL, treated with immunotherapy, chemotherapy regimens, surgery, or Helicobacter pylori eradication between 2008 and 2016 in a single tertiary center. Only patients who had a pretreatment PET/CT (P-PET/CT) were included. P-PET/CT, interim (I-PET/CT), and end-of-treatment PET/CT (E-PET/CT) studies were reviewed. P-PET/CT results were reported using two methods of evaluation, qualitative and semi quantitative: visual assessment (VAS) and maximal standardized uptake value (SUVmax), and I-PET and E-PET results were reported by Deauville 5-point score (DS) evaluation as well. Avidity of PET/CT was defined as abnormal uptake in any of these methods. The primary outcome was the prognostic role of P-PET/CT, I-PET/CT, and E-PET/CT on progression-free survival (PFS) and overall survival (OS). Data of 196 patients with MZL were identified, 110 of which had P-PET/CT and were included in this analysis. Median age was 67 years (range 18-93). The median follow-up period was 63 months (range 3-278). The median OS and PFS for the whole cohort were 63 (interquartile range 39-85) and 60 (interquartile range 37-76) months, respectively. The avidity of PET at baseline for the whole cohort was 70% (77/110 patients), for MALT lymphoma, 62.5% (40/64 patients), for NMZL, 76.4% (13/17 patients), and for SMZL, 82.7% (24/29 patients). When adjusted for IPI, sex, and comorbidities, positive E-PET/CT was associated with reduced PFS with a hazard ratio (HR) of 3.4 (95% CI, 1.27-9.14, P = 0.02). Positive E-PET/CT did not correlate with OS. However, there were only three events. P-PET/CT was not predictive of PFS or OS. Our study demonstrates that above 70% of MZL are FDG avid. Positive E-PET/CT is a strong prognostic factor for PFS., (© 2019 John Wiley & Sons, Ltd.)

Background: The prognostic value of Helicobacter pylori (H. pylori) infection in gastric cancer patients has been investigated over many years; however, the results remain inconclusive. Thus, we performed a comprehensive review of currently available evidence via a systemic meta-analysis to evaluate the effects of H. pylori infection on the prognosis of gastric cancer patients., Methods: Studies that evaluated the prognostic value of H. pylori infection in gastric cancer were extracted in March 2016 by searching PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We obtained or calculated hazard ratios (HRs) and the associated 95% confidence intervals (CIs) from the identified studies, and conducted random-effects model analyses of overall survival and progression-free survival. Twenty-four studies with a cumulative sample size of 7191 patients were included in our analysis., Results: Our meta-analysis revealed that H. pylori infection is an indicator of improved overall survival in gastric cancer patients (HR, 0.79; 95% CI, 0.64-0.99); however, this was only true for European patients. The benefits of H. pylori infection were not detected in Asian gastric cancer patients (HR, 1.01; 95% CI, 0.91-1.12) or those in the United States (HR, 0.88; 95% CI, 0.73-1.05). Subgroup analyses revealed that the prognostic significance of H. pylori infection differed with respect to the year of study publication, number of patients, H. pylori detection method, tumor stage, H. pylori-positive rate, and risk of bias. The prognostic value of H. pylori infection on progression-free survival was unclear (HR, 0.84; 95% CI, 0.70-1.01)., Conclusions: These data provide limited, moderate-quality evidence that H. pylori infection is an indicator of good prognosis in European gastric cancer patients. However, this is not necessarily true for other populations., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Causal relationships with the occurrence of cancer have been established for a number of infections and environmental risk factors., Methods: Numbers and proportions (population-attributable fractions, PAF) of cancer cases attributable to these factors in Germany were calculated by sex and age groups for ages 35 to 84 years based on population projections, national cancer incidence, exposure data, and published risk estimates., Results: For 2018, more than 17 600 cancer cases (4.0% of all incident cancers) were estimated to be attributable to infections. The largest contributions come from Helicobacter pylori (n = 8764) and human papillomavirus (n = 7669) infections. Infection with hepatitis B and C, human immunodeficiency virus, and human herpesvirus 8 were estimated to cause 983 cases, 144 cases, and 116 cases, respectively. More than 5400 cancer cases (1.2% of all incident cancers) were estimated to be attributable to selected environmental factors, of which the largest contributor is indoor radon (n = 3185), followed by particulate matter (n = 1049), sunbed use (n = 892), and secondhand smoke (n = 309)., Conclusion: Of all cancers expected in 2018 in Germany, at least 5% are attributable to potentially avoidable infections and environmental factors. Further research should be directed towards more comprehensive identification and quantification of environmental risks as a basis for targeted cancer prevention.

Background/aims: Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB., Methods: The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding., Results: In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations., Conclusions: The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.

Objective: Patients with liver cirrhosis (LC) are at increased risk for bacterial infections. It is not fully understood how exposure to infections induces further development of hepatic encephalopathy (HE). This study estimated risks of infection associated with HE among patients with LC., Methods: A nested case-control study of 14,428 adult patients with LC was performed using the population-based Longitudinal Health Insurance Database 2000 in Taiwan. Cases were cirrhotic patients who developed HE during follow-up. Controls were matched to each case by age at LC diagnosis (±2 years), sex, Charlson Comorbid index score, year of LC, and follow-up time with a 1:1 ratio. A multivariate logistic regression model was used to determine and compare the odds of developing HE based on exposure to various risk factors, including site of infection, cirrhosis-related complications, Helicobacter pylori eradication therapy, and peptic ulcer bleeding. Patient survival was evaluated using the time-dependent Cox regression model., Results: Cirrhotic patients with HE (n = 714) and without HE (n = 714) were matched to compare risks. Infections and more frequent yearly infections were significantly associated with increased risk of HE. Independent predictors of HE included spontaneous bacterial peritonitis (aOR, 5.13; 95% CI, 3.03-8.69), sepsis (aOR, 2.54; 95% CI, 1.82--3.53), and biliary tract infection (aOR, 2.03; 95% CI, 1.2-3.46), controlling for confounders., Conclusion: Frequent infections are associated with increased risk of HE in cirrhotic patients. More frequent exposure to infection increases the risk of HE and mortality rates. Appropriate prevention of infection and the use of antibiotics for cirrhotic patients at risk for HE are needed.

Background/aims: Few studies have evaluated the effect of Helicobacter pylori infection on the prognosis of patients diagnosed with gastric cancer (GC) after curative surgery. We investigated the association between the H. pylori infection status and clinical outcome after surgery., Methods: We assessed the H. pylori status of 314 patients who underwent curative resection for GC. The H. pylori status was examined using a rapid urease test 2 months after resection. Patients were followed for 10 years after surgery., Results: An H. pylori infection was observed in 128 of 314 patients. The median follow-up period was 93.5 months. A Kaplan-Meier analysis indicated that patients with H. pylori had a higher cumulative survival rate than those who were negative for H. pylori . Patients with stage II cancer who tested negative for H. pylori were associated with a poor outcome. In a multivariate analysis, H. pylori -negative status was a significant independent prognostic factor for poor overall survival., Conclusions: Having a negative H. pylori infection status seems to indicate poor prognosis for patients with GC who have undergone curative resection. Further prospective controlled studies are needed to evaluate the mechanism by which H. pylori affects GC patients after curative surgery in Korea.

Our previous studies have suggested a protective role for H. pylori infection in the prognosis of gastric cancer. Based on those findings, we hypothesized that H. pylori-positive and -negative gastric cancers may exhibit different growth patterns and pathobiological behaviors, indicating different mechanisms of cancer progression. By microarray analysis, we studied miRNAs expression profiles in 42 gastric cancer patients, comparing 21 H. pylori-positive and 21 H. pylori-negative groups. Luciferase reporter assay and western blot were used to examine the potential target genes of the interested miRNA. In the present study, 53 miRNAs were significantly differentially expressed in H. pylori-positive and -negative gastric cancer tissues. We investigated the expression and function of one candidate, miR-143-3p, which was the most significantly increased miRNA in H. pylori-positive gastric cancer tissues. We observed that miR-143-3p expression was significantly decreased in gastric cancer tissues and cells, which correlated with late stage and lymph node metastasis. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-143-3p negatively regulated cell growth, apoptosis, migration and invasion. We further characterized AKT2 as a novel direct target of miR-143-3p. Knockdown of AKT2 expression mimicked the effects of miR-143-3p restoration. In conclusion, our data suggest that miR-143-3p acts as a novel tumor suppressive miRNA by regulating tumor growth, migration and invasion through directly targeting AKT2 gene. Further investigation is warranted to characterize the mechanisms underlying gastric cancer progression and may eventually contribute to its therapy.

Persistent infection with Opisthorchis viverrini causes hepatobiliary abnormalities, predisposing infected individuals to cholangiocarcinoma (CCA). In addition, Helicobacter pylori is highly prevalent in most countries and is a possible risk factor for CCA; however, its role in enhancing hepatobiliary abnormality is unclear. Here, we investigated the effects of coinfection with H. pylori and O. viverrini on hepatobiliary abnormality. Hamsters were divided into four groups: (i) normal, (ii) H. pylori infected (HP), (iii) O. viverrini infected (OV), and (iv) O. viverrini and H. pylori infected (OV+HP). At 6 months postinfection, PCR and immunohistochemistry were used to test for the presence of H. pylori in the stomach, gallbladder, and liver. In the liver, H. pylori was detected in the following order: OV+HP, 5 of 8 (62.5%); HP, 2 of 5 (40%); OV, 2 of 8 (25%). H. pylori was not detected in normal (control) liver tissues. Coinfection induced the most severe hepatobiliary abnormalities, including periductal fibrosis, cholangitis, and bile duct hyperplasia, leading to a significantly decreased survival rate of experimental animals. The greatest thickness of periductal fibrosis was associated with a significant increase in fibrogenesis markers (expression of alpha smooth muscle actin and transforming growth factor beta). Quantitative reverse transcription-PCR revealed that the highest expression levels of genes for proinflammatory cytokines (interleukin-1 [ IL-1 ], IL-6 , and tumor necrosis factor alpha) were also observed in the OV+HP group. These results suggest that coinfection with H. pylori and O. viverrini increased the severity of hepatobiliary abnormalities to a greater extent than either single infection did., (Copyright © 2017 American Society for Microbiology.)

Purpose - We aimed to assess whether Helicobacter pylori infection influences prognosis in gastric cancer patients (GC). Methods - We systematically searched MEDLINE, PubMed, EBSCO, EMBASE, and the Cochrane Library (CENTRAL) Register from inception to June 1, 2017. Overall survival (mean OS) or disease-free survival (mean DFS) in GC patients were calculated using the hazard ratio (HR) and 95% confidence intervals (95% CIs). Results - In total, 19 articles with 4,321 GC patients were enrolled. Helicobacter pylori infection is associated with longer OS (HR 0.73; 95% CI 0.60-0.89; P < 0.001) and DFS (HR 0.75; 95% CI 0.53-1.07; P = 0.002) in GC patients overall. For our subgroup analysis, the pooled HRs and 95% CIs were as follows: China (OS: HR 0.95; 95% CI 0.63-1.42; P = 0.804 and DFS: HR 0.88; 95% CI 0.50-1.56; P = 0.658), Europe (OS: HR 0.69; 95% CI 0.52-0.92; P = 0.010 and DFS: HR 0.62; 95% CI 0.32-1.17; P = 0.141), United States (OS: HR 0.77: 95% CI 0.56-1.06; P = 0.105), Korea (OS: HR 0.45; 95% CI 0.27-0.75; P = 0.002 and DFS: HR 0.45; 95% CI 0.24-0.83, P = 0.011), and Turkey (OS: HR 0.94; 95% CI 0.52-1.70; P = 0.839 and DFS: HR 0.95; 95% CI 0.53-1.71, P = 0.864). Moreover, for R0 or M0 patients, H. pylori infection is associated with better OS and DFS (P all values < 0.05). Conclusions - Helicobacter pylori infection has a better prognosis in GC patients from Korea and Europe. Helicobacter pylori infection has no association with prognosis for China, the United States, or Turkey. Also, H. pylori infection has a better prognosis in R0 resection or M0 GC patients.

Background: Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC)., Methods: Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS)., Results: Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034)., Conclusions: Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited.

Gastric cancer is a rare outcome of chronic Helicobacter pylori infection. Serologic profiles may reveal bacterial, environmental and/or host factors associated with cancer risk. We therefore compared specific anti-H. pylori antibodies among populations with at least twofold differences in gastric cancer mortality from Mexico, Colombia and Chile. Our study included 1,776 adults (mean age 42 years) from three nationally representative surveys, equally divided between residents of high- and low-risk areas. Antibodies to 15 immunogenic H. pylori antigens were measured by fluorescent bead-based multiplex assays; results were summarized to identify overall H. pylori seropositivity. We used logistic regression to model associations between antibody seroreactivity and regional cancer risk (high vs. low), adjusting for country, age and sex. Both risk areas had similar H. pylori seroprevalence. Residents in high- and low-risk areas were seroreactive to a similar number of antigens (means 8.2 vs. 7.9, respectively; adjusted odds ratio, OR: 1.02, p = 0.05). Seroreactivities to Catalase and the known virulence proteins CagA and VacA were each significantly (p < 0.05) associated with residence in high-risk areas, but ORs were moderate (1.26, 1.42 and 1.41, respectively) and their discriminatory power was low (area under the curve < 0.6). The association of Catalase was independent from effects of either CagA or VacA. Sensitivity analyses for antibody associations restricted to H. pylori-seropositive individuals generally replicated significant associations. Our findings suggest that humoral responses to H. pylori are insufficient to distinguish high and low gastric cancer risk in Latin America. Factors determining population variation of gastric cancer burden remain to be identified., (© 2015 UICC.)

Rationale: Chronic systemic infections such as those with Helicobacter pylori (H. pylori) may contribute to the evolution and progression of chronic obstructive pulmonary disease (COPD). Using data from the Lung Health Study (LHS), we determined the relationship of H. pylori infection with the severity and progression of COPD., Methods: Using an immunoassay, we measured H. pylori immunoglobulin G (IgG) antibody titres in serum samples of 4765 patients with mild-to-moderate COPD. We then determined their relationship with the individual's FEV1 and the rate of decline in FEV1 and mortality over 11 years using multiple regression analysis., Results: Approximately 18% of the patients were seropositive to H. pylori and these individuals demonstrated lower FEV1 (L) values at every study visit compared with individuals who were seronegative for H. pylori (p value=0.00012). However, patients with seropositivity to H. pylori were on average 0.012 m shorter than those with seronegativity (p value=0.0015). The significant relationship between FEV1 and H. pylori seropositivity disappeared when FEV1 per cent predicted (FEV1pp) was used (p value=0.45). H. pylori seropositive individuals had greater circulating C reactive protein (CRP) levels compared with H. pylori seronegative individuals (p value=0.012), and had increased risk of cardiovascular mortality (relative risk 1.61, p=0.05)., Conclusions: H. pylori infection was associated with reduced lung function that is most likely due to the effect of the bacterium on lung growth earlier in life. It is also associated with systemic inflammation and increased risk of cardiovascular mortality in patients with COPD., Trial Registration Numbers: NCT00000568 and NCT00000569., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

A 'black box' paradigm has prevailed in which researchers have focused on the association between the total number of pathogens for which individuals are seropositive (i.e. total pathogen burden) and various chronic diseases, while largely ignoring the role that seropositivity for specific combinations of pathogens may play in the aetiology of such outcomes and consequently mortality. We examined the association between total pathogen burden as well as specific pathogen combinations and all-cause mortality in the United States. Data were from individuals aged ⩾25 years tested for cytomegalovirus (CMV), herpes simplex virus (HSV)-1, HSV-2 and Helicobacter pylori, with mortality follow-up to 31 December 2006 in the National Health and Nutrition Examination Survey (NHANES) III (N = 6522). We did not observe a statistically significant graded relationship between total pathogen burden level and all-cause mortality. Furthermore, compared to those seronegative for all four pathogens, the greatest statistically significant rate of all-cause mortality was for those CMV+/HSV-2+ (hazard ratio 1·95, 95% confidence interval 1·13-3·35) adjusting for age, gender, race/ethnicity, education level, body mass index (kg/m2) and smoking status. Interventions targeting prevention or treatment of particular pathogens may be more effective for reducing mortality than those focused solely on reducing overall pathogen burden.

Hypergastrinemia causes carcinoids or carcinomas in the gastric corpus in animal models. Helicobacter pylori (HP) infection in patients causes atrophy, hypergastrinemia and promotes gastric carcinogenesis. Many patients with gastric cancer have hypergastrinemia and it has therefore been hypothesized that hypergastrinemia promotes carcinogenesis. We have examined the associations between serum gastrin, the anatomical localization of gastric cancer, histological classification and patient survival. Patients with non-cardia gastric adenocarcinomas were included prospectively (n = 80). Tumour localization, histological classification according to Laurén and disease stage were recorded. Preoperative fasting serum gastrin was analysed by radioimmunoassay and HP serology by ELISA. Patient survival was determined after a median postoperative follow-up of 16.5 years. Hypergastrinemic patients had carcinomas located in the gastric corpus more often compared to normogastrinemic patients (81.8 vs 36.2%, p = 0.002). Patients with disease stage 2-4 and hypergastrinemia had shorter survival than normogastrinemic patients [5.0 (1.1-8.9) vs 10.0 (6.4-13.6) months (p = 0.04)]. There was no significant difference in serum gastrin or survival between patients with intestinal and diffuse type carcinomas. Hypergastrinemia was associated with adenocarcinomas in the gastric corpus and shorter survival. The findings support the hypothesis that hypergastrinemia promotes carcinogenesis and affects biological behaviour., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

Background: The incidence of gastric cancer varies both within and among populations and can change rapidly without a corresponding decline in Helicobacter pylori prevalence. Here, we describe the changes in gastric cancer mortality in Japan in relation to age-period-cohort effects as well as the decline in H. pylori prevalence., Methods: We used data from Japanese for men and women aged 30-94 for birth years 1875-1970 (calendar time 1950-2000) to observe the age, period and cohort effects on gastric cancer mortality rates. Additionally, we used Poisson regression to simultaneously adjust for concurrent age, period and cohort effects as well as for declining H. pylori prevalence in the Japanese population., Results: There was an approximate 60 % decline in gastric cancer mortality between 1965 and 1995. Detailed age, period and cohort analyses and Poisson regression analysis showed these factors interact in complex ways, analyses focused on one or two of these effects, such as birth cohort without considering concurrent age and period would obscure important interactions that affected different age groups at different times to produce this composite effect., Conclusion: The underlying complexity in population-disease dynamics requires population-specific descriptions of trends using multiple methods to provide an in-depth analysis while simultaneously allowing for necessary statistical adjustments as well as identification of interactions. More thorough descriptions of the population-specific general trends in relation to changes in the population structure (age-period-cohort) enable better prevention and health care policy planning, and further, the descriptions enable hypothesis generation regarding causes of population-specific disease patterns.

Clinical trials performed in populations at high GC risk have demonstrated that eradication of Helicobacter pylori from the stomach with a course of combination antimicrobials helps prevent gastric carcinogenesis when they are administered before precancerous lesions have yet developed. In this review, we consider the insights into H. pylori-associated gastric carcinogenesis that have been gained from these and many other clinical studies in the field to highlight priority areas for basic research and clinical investigation. Among these are defining the magnitude of the risk reduction that may be achieved in clinical practice and at a population level by H. pylori eradication and investigating when, during the slow multistep progression to GC, intervention will be of the most benefit. Additional strategies to prevent GC induced by H. pylori, including chemoprevention, dietary modification, and close endoscopic surveillance, may also have value in augmenting the risk reduction. Why only a small subpopulation of those infected by H. pylori go on to develop GC may be partially explained by genetic susceptibility related to SNPs in several genes regulating the intensity of the gastric inflammatory response to H. pylori. Investigation of the basic mechanisms underlying the promotion of GC by H. pylori and the associated inflammatory response will likely continue to improve clinical strategies for the prevention of one of the most common causes of cancer death globally. See related review, At the Bench: H. pylori, dysregulated host responses, DNA damage, and gastric cancer., (© 2014 Society for Leukocyte Biology.)

Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. Given that ∼50% of the global population is infected with this pathogen, there is great impetus to elucidate underlying causes that mediate progression from infection to cancer. Recent evidence suggests that H. pylori-induced chronic inflammation and oxidative stress create an environment conducive to DNA damage and tissue injury. DNA damage leads to genetic instability and eventually, neoplastic transformation. Pathogen-encoded virulence factors induce a robust but futile immune response and alter host pathways that lower the threshold for carcinogenesis, including DNA damage repair, polyamine synthesis and catabolism, antioxidant responses, and cytokine production. Collectively, such dysregulation creates a protumorigenic microenvironment within the stomach. This review seeks to address each of these aspects of H. pylori infection and to call attention to areas of particular interest within this field of research. This review also seeks to prioritize areas of translational research related to H. pylori-induced gastric cancer based on insights garnered from basic research in this field. See related review by Dalal and Moss, At the Bedside: H. pylori, dysregulated host responses, DNA damage, and gastric cancer., (© 2014 Society for Leukocyte Biology.)

Previous reports clearly demonstrated that Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA) use significantly and independently increased the risk for the development of peptic ulcer disease. Today, the presence of H. pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications. Whether NSAID intake in the presence of H. pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate. Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years. In addition, the interaction between H. pylori infection and low-dose ASA remains even more controversial. In real clinical practice, we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors. These huge variety of possible combinations greatly hinder the decision making process of physicians.

Gastric cancer (GC) is the fourth most common cancer in the world with more than 70% of cases occur in the developing world. More than 50% of cases occur in Eastern Asia. GC is the second leading cause of cancer death in both sexes worldwide. In Asia, GC is the third most common cancer after breast and lung and is the second most common cause of cancer death after lung cancer. Although the incidence and mortality rates are slowly declining in many countries of Asia, GC still remains a significant public health problem. The incidence and mortality varies according to the geographic area in Asia. These variations are closely related to the prevalence of GC risk factors; especially Helicobacter pylori (H. pylori) and its molecular virulent characteristics. The gradual and consistent improvements in socioeconomic conditions in Asia have lowered the H. pylori seroprevalence rates leading to a reduction in the GC incidence. However, GC remains a significant public health and an economic burden in Asia. There has been no recent systemic review of GC incidence, mortality, and H. pylori molecular epidemiology in Asia. The aim of this report is to review the GC incidence, mortality, and linkage to H. pylori in Asia.

Background: Bcl-2 and BID play a major role in the process of apoptosis and their dysfunction underlies carcinogenesis. The study objective was to assess the expression of Bcl-2 and BID in gastric cancer cells in correlation with chosen clinicopathological parameters, presence of Helicobacter pylori infection, and patients' survival., Materials and Methods: The study involved 88 patients operated on for gastric cancer. The expressions of Bcl-2 and BID were determined immunohistochemically., Results: Positive Bcl-2 expression was found in 55.7% and, BID in 53.6% of patients. The Bcl-2 expression correlated with stage pT3 and T4 gastric cancer (P < 0.05), with the intestinal type according to Lauren (P < 0.001), ulcerated type according to Bormann's classification (P < 0.01), and with local lymph node metastases (P < 0.05)., Conclusion: The Bcl-2 protein plays a key role in the process of gastric cancer formation and is associated with the growth of definite types of gastric cancer.

Background: Acute upper gastrointestinal bleeding is a common complication of peptic ulcer disease, often caused by Helicobacter pylori and nonsteroidal anti-inflammatory drug (NSAID) use. The purpose of this study was to determine whether the cause and biologic behavior of ulcers associated with acute upper gastrointestinal bleeding might lead to divergent patient outcomes., Methods: In this Institutional Review Board-approved study, we compared clinical features and outcomes of patients with acute upper gastrointestinal bleeding due to ulcers categorized into 4 groups: Helicobacter pylori positive or negative combined with NSAID usage positive or negative. Likelihood chi-squared analyses were utilized for group comparisons and stepwise multiple logistic regression models were utilized to determine which factors were related to bleeding outcomes., Results: Of 2242 patients with upper gastrointestinal bleeding, 575 (26%) had gastroduodenal ulcer disease, and of those with appropriate diagnostic testing, approximately half (228, 10% overall) had evidence of Helicobacter pylori infection and half (216, 10% overall) had no evidence of Helicobacter pylori infection. Patients without Helicobacter pylori infection had significantly more comorbid conditions than those with Helicobacter pylori and higher Charlson Index comorbidity scores (2.6 ± 2.6 [mean and SD] vs 1.9 ± 2.3, P = .003). Hospital length of stay was significantly longer for Helicobacter pylori-negative patients (mean 11.4 ± 21.7 vs 6 ± 8.5 days and median 5.5 vs 3 days, P <.001 and <.001, respectively). Rebleeding events within 30 days were more frequent in Helicobacter pylori-negative patients than Helicobacter pylori-positive patients (11% vs 5%, P = .009). Rebleeding was most frequent in patients without Helicobacter pylori and with no reported use of NSAIDS (18%, P = .01)., Conclusions: Helicobacter pylori-negative ulcers were associated with poorer outcomes regardless of use of NSAIDs. Patients with ulcers negative for Helicobacter pylori and no history of NSAID use had the worst outcomes and had more severe systemic disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The risk factors affecting the survival rates of laryngeal carcinoma are not well understood. In this study, we investigated the expression status of mutS homolog 2 (MSH2) and mutL homolog 1 (MLH1) and examined the relationship between these two molecules and overall survival rates in laryngeal cancer. We also explored the potential reason for the altered expression of these two genes. Using real-time polymerase chain reaction and western blotting, we detected MSH2 and MLH1 expression in laryngeal cancer tissue samples. We collected a retrospective cohort with 180 laryngeal cancer patients, and inspected MSH2 and MLH1 staining with tissue microarray immunohistochemistry. Prognostic value of clinicopathological characteristics was evaluated by statistical analysis. Laryngeal carcinoma cells were co-cultured with Helicobacter pylori (H. pylori) bacteria. MSH2 and MLH1 were expressed at lower levels compared to those of adjacent tissues in 21 laryngeal carcinoma patients. Patients with negative expression of MSH2 and MLH1 tended to have a higher risk of mortality compared to patients with positive expression (HR=4.38; HR=3.0, respectively). Cigarette smoking rate was higher in the MLH1 expression positive group. H. pylori infection reduced the MSH2 and MLH1 expression levels of laryngeal carcinoma cell lines within co-culture conditions. It is suggested that the altered expression levels of MSH2 and MLH1 probably affect the overall survival of laryngeal carcinoma patients. H. pylori infection may have an effect on the expression of MSH2 and MLH1 in laryngeal carcinoma patients.

Gastroesophageal cancer (GEC), comprising proximal esophagogastric junction (EGJ) and distal gastric cancer (GC), is a significant public health concern. The epidemiology of these tumors has significantly changed over the past several decades especially in developed countries. There is a recognized decrease in incidence and mortality of distal GC and an increase in incidence and mortality of proximal EGJ cancer. The changing epidemiology is thought to be mainly due to changing trends of risk factors such as lower incidence of Helicobacter pylori infection and increasing incidence of obesity and gastroesophageal reflux. Histologically, EGJ cancers are adenocarcinoma (AC), while distal esophagus may be squamous cell carcinoma (SCC) or AC. Distal GC is predominantly AC. Following anatomical and histological distinction, tumors are staged with endoscopic ultrasound (EUS), computerized tomography (CT), and often positron emission tomography (PET) with or without diagnostic laparoscopic and peritoneal washing. Accurate staging of tumors, with emphasis on excluding occult metastasis, is imperative to avoid unnecessary surgical resection. Therefore, it is crucial to understand how these tumors are classified, the associated epidemiology, and the current standards of staging prior to selecting the appropriate course of therapy. In this review we will discuss the epidemiology, classification, and staging of locally advanced GEC.

There is a commonly held perception that Helicobacter pylori related diseases are declining, however these are still associated with a high risk of morbidity and mortality. In recent years worrying themes have emerged such as increasing levels of antibiotic resistance and falling cure rates which illustrate there is no room for complacency with respect to H. pylori. In addition there are many significant issues which have not been elucidated regarding the role played by H. pylori in very serious pathologies such as gastric and esophageal cancer and other more benign disorders common in the developed world such as gastroesophageal reflux disease, functional dyspepsia and perhaps obesity which carry a significant impact both economically and as regards to symptoms. Future guidelines aimed at European practitioners and patients will need to address the questions raised by these issues as well as the more familiar areas such as constituents and duration of therapy.

Background: The aim of the study was to evaluate the presence of cagA gene Helicobacter pylori in etiopathogenesis of initiation and development of larynx squamous cell carcinoma (LSCC) and its predictable role as a prognostic factor., Material and Methods: The prospective, controlled study involved a series of 75 patients (65 male, 10 female, mean age 59.1 years, range 43 to 79 years) with larynx cancer. Samples of larynx cancerous tissue, each of 10-15 mg, were obtained from fresh tissues and were used for nucleic acid purification. DNA was extracted from 225 samples (larynx tumor - I (75), margin of tumor and normal tissue - II (75) and normal larynx tissue from opposite side to the tumor - III). All samples were subjected to H. pylori ureA detection by the PCR H. pylori diagnostic test. Samples that were positive for ureA H. pylori gene were evaluated for cagA H. pylori gene., Results: Presence of H. pylori cagA gene was identified in 46,7% to 49,3% of 75 H. pylori ureA gene-positive larynx cancer depending of tissue location. There was a correlation of high incidence of positive cagA gene in larynx cancer tissue in supraglottic versus subglottic and glottic location. We observed a predominance of cagA gene in LSCC in patients with positive cervical lymph nodes and clinical stage T3 and T4., Conclusions: H. pylori is present in larynx tissue and may be a possible carcinogen or co-carcinogen in LSCC development, but that must be addressed by future investigations. The presence of cagA gene in larynx cancer tissues significantly decreases survival rate and increases the disease recurrence possibilities.

In Latin America, gastric cancer is a leading cancer, and countries in the region have some of the highest mortality rates worldwide, including Chile, Costa Rica, and Colombia. Geographic variation in mortality rates is observed both between neighboring countries and within nations. We discuss epidemiological observations suggesting an association between altitude and gastric cancer risk in Latin America. In the Americas, the burden of gastric cancer mortality is concentrated in the mountainous areas along the Pacific rim, following the geography of the Andes sierra, from Venezuela to Chile, and the Sierra Madre and Cordillera de Centroamérica, from southern Mexico to Costa Rica. Altitude is probably a surrogate for host genetic, bacterial, dietary, and environmental factors that may cluster in the mountainous regions. For example, H. pylori strains from patients of the Andean Nariño region of Colombia display European ancestral haplotypes, whereas strains from the Pacific coast are predominantly of African origin. The observation of higher gastric cancer rates in the mountainous areas is not universal: the association is absent in Chile, where risk is more strongly associated with the age of H. pylori acquisition and socio-economic determinants. The dramatic global and regional variations in gastric cancer incidence and mortality rates offer the opportunity for scientific discovery and focused prevention programs.

Background: Gastro-oesophageal reflux symptoms (GERS) are common in the community. However, few studies have examined their long-term natural history, or impact on survival., Aim: To examine these issues in individuals recruited into a community-based screening programme for Helicobacter pylori in 1994., Methods: Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, gastrointestinal symptoms and quality of life were recorded at study entry. The effect of all these factors on persistent and new-onset GERS, and 10-year mortality, were examined using univariate and multivariate analysis, with results expressed as odds ratios (ORs) or hazard ratios (HR) with 99% confidence intervals (CI)., Results: Of 3967 individuals providing complete GERS data at baseline and 10 years, 549 (13.8%) had GERS at baseline. Of these, 183 (33.3%) had persistent symptoms. Among 3418 individuals asymptomatic at baseline, approximately 0.8% per year developed new-onset GERS. No predictors of persistent GERS were identified. New-onset symptoms were associated with lower quality of life or presence of irritable bowel syndrome (IBS) at baseline, and higher body mass index (BMI) at 10 years. There were 8331 (99.1%) of 8407 subjects providing complete GERS data at baseline, 1289 (15.5%) of whom were symptomatic. Presence of GERS at baseline did not affect survival (HR: 0.84; 99% CI: 0.44-1.59)., Conclusions: Gastro-oesophageal reflux symptoms persisted in one-third of individuals, whilst new-onset gastro-oesophageal reflux symptoms were associated with poor quality of life, irritable bowel syndrome and higher body mass index. Gastro-oesophageal reflux symptoms did not impact adversely on survival., (© 2012 Blackwell Publishing Ltd.)

The meta-analysis of 12 clinical research of application of antibiotics (azithromycin, roxithromycin clarithromycin, gatifloxacin) in 24 949 patients with coronary heart disease were carried out. The obtained results were shown that application of short courses of antibiotic therapy in patients with severe morphological changes in small coronary vessels were not enough effective. Contrariwise, long-term courses of antibiotic therapy could be effective in patients with initial lesions of blood vessels and presence of chronic infections.

Objective: There is debate whether infection with Helicobacter (H.) pylori, the main inducer of chronic atrophic gastritis (CAG), is a risk factor for cardiovascular disease and premature mortality., Methods: Serological measurements of H. pylori infection and pepsinogen (PG) I and II were obtained in a population-based German cohort of 9953 older adults (50-74 years). Cox regression was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for myocardial infarction, stroke, cardiovascular and all-cause mortality during five-year follow-up., Results: According to serology, 4977 participants (51.9%) were infected with H. pylori (2604 with cytotoxin-associated gene A (cagA) strains) and 541 (5.7%) had CAG (PGI<70 ng/mL and PGI/PGII<3). During follow-up, 540 participants died (163 from cardiovascular causes), 170 experienced a primary myocardial infarction and 241 had a stroke. Neither cytotoxin-associated gene A (cagA) negative nor cagA positive H. pylori infections were associated with an increased risk for myocardial infarction, stroke or all-cause mortality. Intriguingly, infection with cagA positive H. pylori strains was inversely associated with cardiovascular mortality (HR, 0.62; CI: 0.41-0.94). No statistically significant associations were observed for the small group of participants with CAG, but point estimates of adjusted HRs for myocardial infarction, stroke and cardiovascular mortality were all below 1 (0.71, 0.59 and 0.65, respectively)., Conclusions: Our results do not support the hypothesis that H. pylori infection or CAG are risk factors for cardiovascular disease or mortality and instead suggest an inverse relationship of cagA positive H. pylori infection with fatal cardiovascular events., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Context: There is some evidence that Helicobacter pylori correlates with distal gastric cancer genesis. However, few studies analyzed the survival related to H. pylori infection., Objective: To correlate gastric cancer survival and H. pylori infection., Methods: Sixty-eight patients with distal gastric cancer that underwent subtotal gastrectomy were studied. Minimal follow-up was 1 month. H. pylori infection was confirmed by biopsy., Results: Thirty-four patients (19 males (55.9%), mean age 60.9 ± 14.03, range 33-82 years) were H. pylori positive. Thirty-four patients (16 males (47.1%), mean age 57.9 ± 13.97, range 27-85 years) were H. pylori negative. Groups were comparable in regards to age (P = 0.4), gender (P = 0.5), stage [T (P = 0.2), N (P = 0.6) and M (P = 0.9)]. Survival was not different when groups were compared [P = 0.1616 (hazard ratio 0.6834, 95% CI 0.4009 to 1.1647)]., Conclusions: H. pylori infection does not affect distal gastric cancer survival.

Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura). The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season), concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials.

Peptic ulcer has frequently been associated with liver cirrhosis. The death rate for peptic ulcer in cirrhotics has been reported to be five times higher than in general population. The underlying mechanisms are poorly understood. Different factors have been claimed to be involved, such as alterations in serum gastrin level, gastric acid secretions, mucosal blood flow and decreased prostaglandin production in gastric mucosa. Moreover, Helicobacter pylori infection, when accurately assessed, is detectable in most peptic ulcer cirrhotics. Since the H. pylori infection strongly correlates with peptic ulcer in general population, it is necessary to clarify the role of H. pylori in the pathogenesis of peptic ulcer in cirrhosis before eradication can be proposed as a preventive measure.

Objectives: There is cross-sectional evidence that CagA antigen produced by Helicobacter pylori is associated with coronary heart disease, stroke, atrial fibrillation (AF) and microalbuminuria, but no large-scale longitudinal studies have been conducted in diabetic patients. We aimed to determine whether cytotoxin-associated gene-A (CagA) seropositivity is independently associated with important vascular outcomes in type 2 diabetes., Methods: We studied 1179 type 2 patients from a well characterized community-based cohort who had available sera from baseline assessment between 1993 and 1996, and follow-up for incident events to end-June 2007. H. pylori IgG and CagA antibodies at baseline were measured by validated ELISA. Multiple logistic/linear regression analysis and Cox proportional hazards modelling were used to determine independent baseline associates of prevalent and incident complications, respectively, including H. pylori/CagA serostatus., Results: At baseline, 62.0% of patients were H. pylori seropositive and 37.7% were both H. pylori and CagA seropositive. CagA seropositivity was not independently associated with prevalent coronary heart disease (CHD), cerebrovascular disease (CVD), peripheral arterial disease or AF at baseline (P > 0.41), but there was a significant inverse association with ln(urinary albumin:creatinine) (P = 0.033). There were no independent associations between CagA seropositivity and incident CHD/CVD or progression to microalbuminuria (P > 0.20). During follow-up, 480 patients (40.7%) died, 246 (50.2%) from cardiovascular causes. After adjustment for other variables,CagA seropositivity was weakly protective against cardiovascular death (P = 0.024)., Conclusion: CagA seropositivity is not a risk factor for chronic vascular complications of type 2 diabetes. Assay of CagA antibodies does not contribute significantly to clinical management outside gastroenterological indications.

Background: Endoscopic surveillance of presumed-benign gastric ulcers may detect missed malignancy, but its impact on long-term outcomes is uncertain., Objective: To estimate the clinical benefits and cost-effectiveness of follow-up surveillance., Design: State-transition model., Setting: To simulate the clinical course of presumed-benign gastric ulcers, we estimated prevalence and incidence of undetected gastric cancer, surveillance effectiveness, stage-specific disease mortality rates, and costs from clinical studies and databases., Patients: This study involved 60-year-old men diagnosed with presumed-benign gastric ulcers., Intervention: Follow-up endoscopic surveillance., Main Outcome Measurements: Lifetime gastric cancer risk, life expectancy, quality-adjusted life expectancy, lifetime costs, and incremental cost-effectiveness ratios., Results: For a cohort of 60-year-old men with presumed-benign gastric ulcers and a 2.6% prevalence of undetected malignancy, the lifetime gastric cancer risk was 4.4%. Surveillance improved (undiscounted) life expectancy by 10.0 days and increased discounted quality-adjusted life expectancy by 3.4 days at a cost of $146,700 per quality-adjusted life year (QALY). Surveillance cost less than $50,000 per QALY if the undetected gastric cancer prevalence was 6.5%, and it cost less than $100,000 per QALY if the prevalence was greater than 3.5%, endoscopy costs were 40% lower, or the disutility associated with gastric cancer was 30% lower. Probabilistic sensitivity analysis suggested that at a willingness-to-pay threshold of $100,000 per QALY, the probability that surveillance was cost effective was 25.2%., Limitations: Data from multiple sources with varied study designs were used., Conclusion: Endoscopic surveillance of presumed-benign gastric ulcers may improve overall survival. However, unless the prevalence of having undetected malignancy exceeds 6%, surveillance is unlikely to be cost-effective., (Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background & Aims: In the province of Cadiz (Spain), the adjusted mortality rate for gastric cancer in the coastal town of Barbate is 10/100.000 inhabitants, whereas in the inland town of Ubrique, the rate is twice as high. The rate of Helicobacter pylori (H. pylori) infection (H. pylori antibodies) in the normal population was 54% in Ubrique, but only 32% in Barbate. In the two decades since its original discovery, p53 has found a singularly prominent place in our understanding of human gastric cancer and H. pylori cause accumulation of reactive oxygen species in the mucosa compartment. This study was designed to compare serum levels of p53 in a population characterized by high mortality due to stomach cancer and a high prevalence of H. pylori infection and another population in which mortality from this cause and the prevalence of H. pylori infection are low., Materials and Methods: 319 subjects from the low mortality population and 308 from the high mortality population were studied, as were 71 patients with stomach cancer. We measured serum immunoglobulin G antibody to H. pylori and serum mutant p53 protein and ceruloplasmin., Results: The difference between the two populations in the prevalence of H. pylori infection was significant (p < 0.001). Of the seropositive, 81% had elevated values of mutant p53, in comparison with 11% of the seronegative (p < 0.0001). Serum concentration of ceruloplasmin was significantly higher in seropositive with elevated mutant p53 protein than in seronegative with normal levels of p53 (p < 0.05)., Conclusions: There is a significant association between infection with H. pylori, elevated titers of H. pylori antibodies, and positivity for serum mutant p53 protein. Such information can significantly increase our basic knowledge in molecular pathology of gastric cancer and protection against H. pylori infection.

Objectives: To examine whether treatment with clarithromycin was associated with an increased risk of death in patients with preexisting ischemic heart disease (IHD)., Methods: Employing nationwide registers, all patients with IHD events from 1997 to 2007 who subsequently claimed prescriptions for dual antibiotic treatment for eradication treatment were identified. The primary endpoint was all-cause mortality., Results: The study included 214,330 individuals with IHD; 5,265 (2.5 %) of these claimed prescriptions for dual antibiotics. Compared with IHD patients not undergoing eradication therapy, no increase in the risk of all-cause mortality was demonstrated (HR 1.02; 95% CI 0.84-1.23, p = 0.87) after 5 years., Conclusions: The use of clarithromycin in the setting of eradication treatment for Helicobacter pylori in patients with IHD was not associated with an increased risk of death., (Copyright 2010 S. Karger AG, Basel.)

Gastric infection with Helicobacter Pylori in end-stage renal disease patients is of relevance because of its potential impact on the quality of life as well as morbidity and mortality of patients. Existed data on the issue are controversial, and we attempt in this article to evaluate the available data to approach extended perception of the current knowledge on the epidemiology, relevance, and optimum therapeutic strategies.

Goals and Background: Little is still known regarding the clinical features and prognosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma without Helicobacter pylori (H. pylori) infection., Study: From January 1996 to April 2006, a total of 185 patients with gastric MALT lymphoma were enrolled at Seoul National University Hospital. To assess the differences in clinical characteristics and long-term outcomes between H. pylori-negative (n=29, 15.7%) and H. pylori-positive (n=156, 84.3%) cases, we compared these 2 types of lymphoma., Results: The overall median follow-up period was 39 months. There were no significant differences between the 2 groups in terms of age, macroscopic phenotype, or histologic grade. H. pylori-negative group showed male predominancy (72.4%) and higher percentage of proximal stomach location (62.1%). Although H. pylori-negative lymphomas were more frequently presented as advanced disease (stage IIE or IV, 37.9%), no significant differences in both the overall complete response and overall survival rates were observed between the 2 groups., Conclusions: Our results suggest that H. pylori-negative gastric MALT lymphoma shows a favorable long-term outcome, which is comparable to that of H. pylori-positive lymphoma.