Association of oxidative balance score with helicobacter pylori infection and mortality in the US population.

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.

Systemic Helicobacter infection and associated mortalities in endangered Grand Cayman blue iguanas (Cyclura lewisi) and introduced green iguanas (Iguana iguana).

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.

Estimates of Cancer Mortality Attributable to Carcinogenic Infections in Italy.

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.

Gastric cancer deaths by age group in Japan: Outlook on preventive measures for elderly adults.

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.

Effect of Helicobacter pylori eradication after subtotal gastrectomy on the survival rate of patients with gastric cancer: follow-up for up to 15 years.

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.

Effect of Helicobacter pylori Treatment on Long-term Mortality in Patients with Hypertension.

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.

FDG PET/CT as a diagnostic and prognostic tool for the evaluation of marginal zone lymphoma.

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.

The prognostic role of Helicobacter pylori in gastric cancer patients: A meta-analysis.

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.

Cancers Due to Infection and Selected Environmental Factors.

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.

Multiple bacterial infections increase the risk of hepatic encephalopathy in patients with cirrhosis.

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.

Factors Associated with Rebleeding in Patients with Peptic Ulcer Bleeding: Analysis of the Korean Peptic Ulcer Bleeding (K-PUB) Study.

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.

MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses tumor growth, migration and invasion by directly targeting AKT2.

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.

Postoperative Helicobacter pylori Infection as a Prognostic Factor for Gastric Cancer Patients after Curative Resection.

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.

Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters.

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.

Is It a Protective Factor of Helicobacter pylori Infection in Overall Survival of All Gastric Cancer? Evidence from Meta-Analysis.

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.

Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma.

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.

Serological response to Helicobacter pylori infection among Latin American populations with contrasting risks of gastric cancer.

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.

Hypergastrinemia is associated with adenocarcinomas in the gastric corpus and shorter patient survival.

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.