Modeling the Impact of Adjustable Gastric Banding on Survival in Patients with Morbid Obesity

Objective: Morbid obesity is associated with premature death. Adjustable gastric banding may lead to substantial weight loss in patients with morbid obesity. Little is known about the impact of weight loss on survival after adjustable gastric banding. We therefore developed a mathematical model to estimate life expectancy in patients with a body mass index (BMI) ≥40 kg/m² undergoing bariatric surgery. Research Methods and Procedures: We developed a nonhomogeneous Markov chain consisting of five states: the absorbing state (“dead”) and the four recurrent states BMI ≥40 kg/m², BMI 36 to 39 kg/m², BMI 32 to 35 kg/m², and BMI 25 to 31 kg/m². Scenarios of weight loss and age‐ and sex‐dependent risk of death, as well as BMI‐dependent excess mortality were extracted from life tables and published literature. All patients entered the model through the state of BMI ≥40 kg/m². Results: In men aged either 18 or 65 years at the time of surgery, who moved from the state BMI ≥40 kg/m² to the next lower state of BMI 36 to 39 kg/m², life expectancy increased by 3 and 0.7 years, respectively. In women aged either 18 or 65 years at the time of surgery, who moved from the state BMI ≥40 kg/m² to the next lower state BMI 36 to 39 kg/m², life expectancy increased by 4.5 and 2.6 years, respectively. Weight loss to lower BMI strata resulted in further gains of life expectancy in both men and women. Discussion: Within the limitations of the modeling study, adjustable gastric banding in patients with morbid obesity may substantially increase life expectancy.     

Genetic host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms

Helicobacter Pylori is a gram negative rod shaped microaerophilic bacterium that colonizes the stomach of approximately half the world's population. Infection with c may cause chronic gastritis which via a quite well described process known as Correas cascade can progress through sequential development of atrophic gastritis, intestinal metaplasia and dysplasia to gastric cancer. H. pylori is currently the only bacterium that is classified as a class 1 carcinogen by the WHO, although the exact mechanisms by which this bacterium contributes to gastric carcinogenesis are still poorly understood. Only a minority of H. pylori-infected patients will eventually develop gastric cancer, suggesting that host factors may be important in determining the outcome of H. pylori infection. This is supported by a growing body of evidence suggesting that the host genetic background contributes to risk of H. pylori infection and gastric carcinogenesis. In particular single nucleotide polymorphisms in genes that influence bacterial handling via pattern recognition receptors appear to be involved, further strengthening the link between host risk factors, H. pylori incidence and cancer. Many of these genes influence cellular pathways leading to inflammatory signaling, inflammasome formation and autophagy. In this review we summarize known carcinogenic effects of H. pylori, and discuss recent findings that implicate host genetic pattern recognition pathways in the development of gastric cancer and their relation with H. pylori.     

Previous Helicobacter pylori infection–induced atrophic gastritis: A distinct disease entity in an understudied population without a history of eradication

Individuals with chronic atrophic gastritis who are negative for active H. pylori infection with no history of eradication therapy have been identified in clinical practice. By excluding false‐negative and autoimmune gastritis cases, it can be surmised that most of these patients have experienced unintentional eradication of H. pylori after antibiotic treatment for other infectious disease, unreported successful eradication, or H. pylori that spontaneously disappeared. These patients are considered to have previous H. pylori infection–induced atrophic gastritis. In this work, we define these cases based on the following criteria: absence of previous H. pylori eradication; atrophic changes on endoscopy or histologic confirmation of glandular atrophy; negative for a current H. pylori infection diagnosed in the absence of proton‐pump inhibitors or antibiotics; and absence of localized corpus atrophy, positivity for autoantibodies, or characteristic histologic findings suggestive of autoimmune gastritis. The risk of developing gastric cancer depends on the atrophic grade. The reported rate of developing gastric cancer is 0.31%‐0.62% per year for successfully eradicated severely atrophic cases (pathophysiologically equal to unintentionally eradicated cases and unreported eradicated cases), and 0.53%‐0.87% per year for spontaneously resolved cases due to severe atrophy. Therefore, for previous H. pylori infection–induced atrophic gastritis cases, we recommend endoscopic surveillance every 3 years for high‐risk patients, including those with endoscopically severe atrophy or intestinal metaplasia. Because of the difficulty involved in the endoscopic diagnosis of gastric cancer in cases of previous infection, appropriate monitoring of the high‐risk subgroup of this understudied population is especially important.     

Helicobacter pylori infection‐induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications

Background

Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori‐induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication.

Materials and Methods

Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low‐grade intraepithelial neoplasia, high‐grade intraepithelial neoplasia, and intestinal‐type gastric cancer groups. Helicobacter pylori infection was determined by either ¹³C‐urea breath test or immunohistochemistry staining.

Results

In Helicobacter pylori‐negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low‐grade intraepithelial neoplasia, and declined in high‐grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori‐infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori‐negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori‐negative control. Labeling index of Ki67 in Helicobacter pylori‐negative groups was higher in gastric cancer than chronic atrophic gastritis and low‐grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori‐positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress.

Conclusions

These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori‐induced gastric cancer.     

树突状细胞对胃癌前病变的免疫保护分析

摘要 目的：探究树突状细胞(Dendritic cells,DC)对胃癌的免疫保护作用。方法：选择2016年1月至2018年1月于我院接受治疗的145例胃癌、39例慢性萎缩性胃炎、21例不典型增生、27例肠上皮化生以及20例正常对照组患者为研究对象,分别采集其胃粘膜标本进行染色,记录和比较其胃粘膜中S100⁺、CD4⁺和CD8⁺细胞的数量、平均面积以及平均吸光度,并将胃癌患者分为中分化腺癌(49例)、低分化腺癌(53例)和未分化癌(43例)进行对比。结果：(1)胃癌组、慢性萎缩性胃炎组、不典型增生、肠上皮化生组的胃粘膜S100⁺阳性细胞计数明显高于正常对照组（P<0.05）,胃癌组平均吸光度低于对照组,其他3组平均吸光度显著高于对照组,(P<0.05);胃癌组平均面积与正常对照组相比无差异(P>0.05),其他三组平均面积显著高于对照组（P<0.05）;(2)慢性萎缩性胃炎组、肠上皮化生组、不典型增生组患者CD4⁺细胞数均低于对照组(P<0.05);胃癌组、慢性萎缩性胃炎组、肠上皮化生组患者平均面积均低于对照组(P<0.05);胃癌组、慢性萎缩性胃炎组、不典型增生、肠上皮化生组平均吸光度均低于对照组(P<0.05);(3)慢性萎缩性胃炎组、肠上皮化生组、不典型增生组患者CD8⁺细胞数明显高于对照组(P<0.05),胃癌组稍低于对照组(P>0.05);胃癌组患者平均面积低于对照组(P<0.05);胃癌组患者平均吸光值低于对照组,慢性萎缩性胃炎组、肠上皮化生组患者高于对照组(P均<0.05);(4)随着胃癌分化程度的降低,胃癌患者DC细胞数有降低趋势。结论：胃癌前病变患者胃粘膜中DC数量会显著增多,免疫功能加强,DC细胞数量会随胃癌分化程度的降低而减少,分析其原因与DC细胞能够抑制癌前病变有关。     

Obesity in the Elderly and Its Relationship with Cardiovascular Risk Factors in Taiwan**

Objectives: The obese elderly are at increased risk of mortality, morbidity, and functional disability. In this study, we examined the prevalence of obesity and relationship between various anthropometric indices (AI) and cardiovascular disease (CVD) risk factors in the elderly. Research Methods and Procedures: A stratified multistage clustered sampling scheme was used in the Elderly Nutrition and Health Survey in Taiwan during 1999 to 2000. 2432 non‐institutionalized subjects (age, 72.8 ± 9.4 years; BMI, 23.6 ± 6.4 kg/m²) were recruited. The receiver operating characteristic analysis was used to compare predictive validity of CVD risk factors among various AI, including BMI, waist circumference (WC), and waist‐to‐hip ratio (WHR). Results: The prevalence of obesity was 29.0% in men and 36.8% in women by obesity criteria for Asians (BMI ≥ 25 kg/m²) and 13.3% in men and 21.0% in women by the Taiwanese definition (BMI ≥ 27 kg/m²). Odds ratios of acquiring various CVD risk factors increased significantly with increment of WC, WHR, and BMI. The areas under the curve predicting metabolic syndrome were all <0.8. The cut‐off values of WC corresponding to the highest sensitivity and the highest specificity in predicting various CVD risk factors were 86.2–88.0 cm in men and 82.0–84.0 cm in women, respectively. Discussion: Obesity was prevalent in the Taiwanese elderly. WC was related to CVD risk factors to a greater extent than BMI and WHR. However, none of them alone was a good screening tool for CVD risk factors. Therefore, how to apply AI prudently to screen elderly for CVD risk factors needs further research.     

Age-Dependent Influence of Gender on the Association Between Obesity and a Cluster of Cardiometabolic Risk Factors

BackgroundObesity is a main risk factor in metabolic syndrome. Gender is known to influence the risk of obesity and other cardiovascular risk factors. However, it remains to be determined whether there is a gender-specific difference in the relationship between obesity and accumulation of other cardiometabolic risk factors such as hypertension, dyslipidemia, and diabetes.ObjectiveThe aim of this study was to determine whether the association between obesity and a cluster of other cardiometabolic risk factors is modified by gender.MethodsThe subjects were 17,791 Japanese men and women who were divided into younger (35–40 years) and older (60–70 years) age groups. The relationships between obesity (body mass index [BMI] ≥25 kg/m² or waist-to-height ratio [WHtR] ≥0.5) and multiple cardiometabolic risk factors (≥2 of the risk factors of high blood pressure, dyslipidema, and hyperglycemia) were compared between men and women in each age group.ResultsIn the younger group, the crude odds ratios (ORs) for multiple cardiometabolic risk factors in obese versus nonobese subjects were significantly higher in women than in men (BMI: 6.23 [range, 5.53–7.02] in men vs 16.63 [range, 12.37–22.37] in women, P < 0.01; WHtR: 6.04 [range, 5.36–6.81] in men vs 9.77 [range, 7.14–13.37] in women, P < 0.01), whereas this difference was not found in the older group (BMI: 3.03 [range, 2.69–3.42] in men vs 2.92 [range, 2.33–3.67] in women P = 0.076; WHtR: 3.11 [range, 2.78–3.47] in men vs 2.50 [range, 2.02–3.09] in women, P < 0.05). On multivariate logistic regression analysis, the ORs for multiple cardiometabolic risk factors after adjusting for age, smoking, alcohol consumption, and regular exercise in subjects with versus subjects without a large waist circumference tended to be higher in women than in men in the younger group but not in the older group. The ORs of the interaction term consisting of gender and each adiposity index for multiple cardiometabolic risk factors were significantly higher than a reference level of 1.00 in the younger group (BMI: 2.68 [range, 1.95–3.69], P < 0.01; WHtR: 1.62 [range, 1.16–2.27], P < 0.01) but not in the older group (BMI: 0.95 [range, 0.74–1.23], P = 0.712; WHtR: 0.80 [range, 0.63–1.02], P = 0.066).ConclusionThe results suggest that the association between obesity and a cluster of cardiometabolic risk factors is stronger in women than in men, and this gender-specific difference exists in younger (35–40 years) but not in older (60–70 years) individuals.     

Obesity,physical activity and cancer risks: Results from the Cancer,Lifestyle and Evaluation of Risk Study (CLEAR)

IntroductionPhysical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers.MethodsWe estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression.ResultsFor women, BMI was positively associated with UC risk; specifically, obese women (BMI ≥30 kg/m²) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (<25 kg/m²) (OR = 1.99;CI:1.31–3.03). For men, BMI was also positively associated with the risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR = 1.37;CI:1.11–1.70), 113% (OR = 2.13;CI:1.55–2.91) and 51% (OR = 1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMI<25 kg/m²).Among women, PA was inversely associated with the risks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR = 0.60;CI:0.44–0.84) and UC (OR = 0.47;CI:0.27–0.80). Reduced risks of BC were associated with low (OR = 0.66;CI:0.51–0.86) and moderate (OR = 0.72;CI:0.57–0.91) levels of PA. There was no association between PA levels and cancer risks for men.We found no evidence of an interaction between BMI and PA in the CLEAR study.ConclusionThese findings suggest that PA and obesity are independent cancer risk factors.     

Waist circumference and BMI cut-off based on 10-year cardiovascular risk: evidence for "central pre-obesity"

Objective: The objective was to assess the waist circumference (WC) cut‐off point that best identifies a level of 10‐year cardiovascular disease (CVD) risk with optimal balance of sensitivity and specificity in Chinese subjects according to their predicted 10‐year CVD risk. Research Methods and Procedures: A community‐based cross‐sectional observational study involving 14,919 Hong Kong Chinese subjects. The 10‐year CVD risk based on various prediction models was calculated. The projected WC cut‐off points were then determined. Results: There were 4837 (32.4%) men and 10,082 (67.6%) women (mean age ± standard deviation, 47.3 ± 13.5 years; age range, 18 to 93 years; median age, 45.0 years). The mean optimal WC or BMI predicting a 15% to 30% 10‐year CVD risk were 83 to 88 cm and 25 kg/m² for men, and 76 cm and 23 kg/m² for women, respectively. With WC ≥90 cm in men and ≥80 cm in women, the likelihood ratio at various WC cut‐off points to develop a ≥20% 10‐year CVD risk is 1.5 to 2.0 in men and 3.0 in women. The likelihood ratio was 1.5 in men with WC at 84 cm and in women at 70 cm. Discussion: Our results agree with the present guidelines on the definition of general and central obesity in Asia‐Pacific regions. We propose the creation of an intermediate state of high WC, the “central pre‐obesity” for Chinese men with WC ≥84 to 90 cm (≥33 to 36 inches) and women with WC ≥74 to 80 cm (≥29 to 32 inches). People with central pre‐obesity, similar to those with overweight (BMI ≥23 to 25 kg/m²), already have an increased risk of co‐morbidities.     

BMI vs. waist circumference for identifying vascular risk

Objective: Current guidelines recommend measurement of both BMI and waist circumference (WC) in individuals with BMI between 25.0 and 34.9 kg/m². We investigated the relative contributions of BMI and WC toward identifying risk of adverse vascular events in a community‐based sample. Methods and Procedures: We evaluated Framingham Study participants (n = 4,195 person‐examinations, 53% women) using pooled logistic regression to assess the incremental prognostic utility of WC in predicting risk of a first cardiovascular disease (CVD) event in the three BMI categories (normal, <25 kg/m²; overweight, 25 to <30 kg/m²; obese, ≥ 30 kg/m²) and to assess the incremental prognostic utility of BMI and WC separately for predicting risk of a first cardiovascular event. Results: On follow‐up (16 years), 430 participants (158 women) had experienced a first CVD event. In overweight women, but not in overweight men, larger WC was found to be an independent predictor of CVD incidence, longitudinally (in women, multivariable‐adjusted odds ratio (OR) per s.d. increment in WC 1.86, 95% confidence interval (CI) = 1.03–3.36, P = 0.04; in men adjusted OR per s.d. increment in WC 0.91, 95% CI 0.60–1.38, P = 0.66). In obese individuals and in those with normal BMI, WC was not associated independently with incident CVD. When BMI and WC were analyzed separately for predicting risk of a first cardiovascular event, the c statistics associated with the multivariable CVD models incorporating BMI vs. WC were nearly identical in men and women. Discussion: Knowledge of WC aids identification of vascular risk among overweight women. Among normal weight or obese women and men (regardless of BMI category) WC did not appear to substantially add to prediction of risk of vascular events.     

Associated Factors of Atrophic Gastritis Diagnosed by Double-Contrast Upper Gastrointestinal Barium X-Ray Radiography: A Cross-Sectional Study Analyzing 6,901 Healthy Subjects in Japan

Background

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection.

Methods

We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach.

Results

Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H₂-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects.

Conclusions

The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.     

First nationwide survey of prevalence of overweight, underweight, and abdominal obesity in Iranian adults

Objective: The goal was to estimate the prevalence of overweight, obesity, underweight, and abdominal obesity among the adult population of Iran. Research Methods and Procedures: A nationwide cross‐sectional survey was conducted from December 2004 to February 2005. The selection was conducted by stratified probability cluster sampling through household family members in Iran. Weight, height, and waist circumference (WC) of 89,404 men and women 15 to 65 years of age (mean, 39.2 years) were measured. The criteria for underweight, normal‐weight, overweight, and Class I, II, and III obesity were BMI <18.5, 18.5 to 24.9, 25 to 29.9, 30 to 34.9, 35 to 39.9, and ≥40 (kg/m²), respectively. Abdominal obesity was defined as WC ≥102 cm in men and ≥88 cm in women. Results: The age‐adjusted means for BMI and WC were 24.6 kg/m² in men and 26.5 kg/m² in women and 86.6 cm in men and 89.6 cm in women, respectively. The age‐adjusted prevalence of overweight or obesity (BMI ≥25) was 42.8% in men and 57.0% in women; 11.1% of men and 25.2% of women were obese (BMI ≥30), while 6.3% of men and 5.2% of women were underweight. Age, low physical activity, low educational attainment, marriage, and residence in urban areas were strongly associated with obesity. Abdominal obesity was more common among women than men (54.5% vs. 12.9%) and greater with older age. Discussion: Excess body weight appears to be common in Iran. More women than men present with overweight and abdominal obesity. Prevention and treatment strategies are urgently needed to address the health burden of obesity.     

CD44 Plays a Functional Role in Helicobacter pylori-induced Epithelial Cell Proliferation

The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat). Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylorithat was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique approach to study H. pylori interaction with the human gastric epithelium. Here, we show that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation.     

Helicobacter pylori induces direct activation of the lymphotoxin beta receptor and non-canonical nuclear factor-kappa B signaling

The pathogen Helicobacter pylori, which infects half of the world's population, is a major risk factor for the development of gastric diseases including chronic gastritis and gastric cancer. Among H. pylori's virulence factors is the cytotoxin-associated gene pathogenicity island (cagPAI), which encodes for a type IV secretion system (T4SS). The T4SS induces fast canonical nuclear factor-kappa B (NF-κB) signaling, a major factor increasing inflammation, supressing apoptotic cell death and thereby promoting the development of neoplasia. However, H. pylori's capability to mediate fast non-canonical NF-κB signaling is unresolved, despite a contribution of non-canonical NF-κB signaling to gastric cancer has been suggested.We analyzed signaling elements within non-canonical NF-κB in response to H.?pylori in epithelial cell lines by immunoprecipitation, immunoblot, electrophoretic mobility shift assay and RNA interference knockdown. In addition, tissue samples of H. pylori-infected patients were investigated by immunohistochemistry.Here, we provide evidence for a T4SS-dependent direct activation of non-canonical NF-κB signaling. We identified the lymphotoxin beta receptor (LTβR) to elicit the fast release of NF-κB inducing kinase (NIK) from the receptor complex leading to non-canonical NF-κB signaling. Further, NIK expression was increased in human biopsies of H. pylori-associated gastritis. Thus, NIK could represent a novel target to reduce Helicobacter pylori-induced gastric inflammation and pathology.     

Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice

Background

Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined.

Methodology/Principal Findings

By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion.

Conclusions/Significance

These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.     

Cancers in France in 2015 attributable to high body mass index

BackgroundOverweight, as defined by high body mass index (BMI), is an established risk factor for various morbidities including cancer. Globally, its prevalence has increased markedly over the past decades. The aim of this study was to estimate the proportion and number of cancers that were attributable to high BMI in France in 2015.MethodsPopulation attributable fractions (PAFs) and numbers of cancer cases attributable to high BMI (a population mean BMI above the optimum of 22 kg/m²) were estimated by age and sex, for cancer sites with convincing or probable evidence of an established causal link. Assuming a 10-year lag-period, PAFs were calculated using mean BMI estimates from a cross-sectional French population survey, and relative risk estimates from published meta-analyses.ResultsAn estimated 18,639 cancer cases diagnosed in France in 2015 were attributable to high BMI, corresponding to 5.3% of all cancer cases (6.7% in women and 4.1% in men). This included 4507 cases of postmenopausal breast and 3380 cases of colon cancer. The highest estimated PAFs were for oesophageal adenocarcinoma and corpus uteri cancer (37% and 34%, respectively).ConclusionHigh BMI is associated with a substantial number of cancer cases in France, a country with a low but increasing prevalence of overweight and obesity when compared to other European countries. Assuming that the association between high BMI and cancer is causal, these results highlight the need to prioritise the prevention of this risk factor as part of cancer control planning in France and elsewhere in Europe.     

Clinical Profile and Management of Patients With Hypertension and Chronic Ischemic Heart Disease According to BMI

Obesity is associated with numerous risk factors and comorbidities such as hypertension, metabolic syndrome, type 2 diabetes, and cardiovascular diseases. However, numerous studies have reported an obesity paradox; the overweight and obese patients with established cardiovascular disease have better prognosis than those with a BMI <25 kg/m². This study was designed to assess potential differences in the clinical profile and management of hypertensive outpatients with chronic ischemic heart disease in obese and lean patients that could explain these two apparently contradictory points. Overweight and obesity were defined as a BMI 25–29.9 kg/m² and ≥30 kg/m², respectively. Cardiovascular risk factors goals were considered according to European Society of Hypertension‐European Society of Cardiology 2003, National Cholesterol Education Program Adult Treatment Panel III and American Diabetes Association 2005 guidelines. A sample of 2,024 patients (66.8 ± 10.1 years; 31.7% women) was included. Of these, 0.1% had a BMI <20 kg/m²; 17.1% BMI 20–24.9 kg/m²; 53.7% BMI 25–29.9 kg/m²; 23.7% BMI 30–34.9 kg/m²; 4.3% BMI 35–39.9 kg/m²; and 1.1% BMI ≥40 kg/m². The subgroup of patients with BMI ≥30 kg/m² had a higher proportion of women, diastolic dysfunction, diabetes, dyslipidemia, left ventricular hypertrophy, and heart failure. There was an inverse relationship between risk factors control rates and BMI (all comparisons BMI 20–24.9 kg/m² vs. 25–29.9 kg/m² vs. ≥30 kg/m²): blood pressure (BP) control (51.7% vs. 42.4% vs. 29.2%, P < 0.001); low‐density lipoprotein cholesterol (LDL‐C) control (35.2% vs. 30.5% vs. 27.9%, P = 0.03) and diabetes control (38.6% vs. 27.6% vs. 22.2%, P = 0.023). In conclusion, in patients with hypertension and chronic ischemic heart disease, as BMI increases, the clinical profile worsens as well as risk factors control rates.     

Helicobacter pylori strain and the pattern of gastritis among first-degree relatives of patients with gastric carcinoma

Background. Relatives of gastric cancer patients have an increased risk of gastric cancer, possibly related to genetically‐related strains of Helicobacter pylori or a common environment. Methods. The pattern of gastritis and H. pylori from gastric cancer patients and their first‐degree relatives were compared using detailed DNA fingerprints and vacA, cagA, and iceA genotyping. Results. Sixteen index cases from Korea, the US, or Colombia and their 38 first‐degree relatives (brothers, sisters, sons and daughters) were studied. No definite, or consistent, relationship between the pattern of gastritis and the relatedness of the H. pylori strain was observed (i.e. relatives could have an identical or a totally different pattern of gastritis regardless if they were infected with identical or highly similar organisms). For example, three elderly siblings of an index case with atrophic pangastritis had identical H. pylori isolates and environments in childhood and yet two had antral predominant nonatrophic gastritis, which is typically associated with duodenal ulcer instead of gastric cancer. Conclusions. The results of this study are not consistent with the hypothesis that specific virulence factors or similar H. pylori strains correlate with a specific histologic pattern or outcome even among those sharing the same environment in childhood.     

血清胃蛋白酶原联合G-17对萎缩性胃炎及胃癌早期诊断价值

目的:探索检测血清胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)、胃泌素-17(G-17)在萎缩性胃炎及胃癌中的诊断价值。方法:收集医院2015年2月至12月门诊及住院的慢性非萎缩性胃炎44例(非萎缩性胃炎组),慢性萎缩性胃炎47例(萎缩性胃炎组),早期胃癌42例(胃癌组)。采用酶联免疫吸附试验(ELISA)测定各组血清PGⅠ、PGⅡ、G-17的水平,同时计算PGⅠ/PGⅡ的比值(PGR),比较各组指标间的差异,同时绘制各指标筛查萎缩性胃炎及胃癌的受试者工作曲线(ROC)曲线,分别评价其诊断价值。结果:胃癌组及萎缩性胃炎组的血清PGⅠ、PGR水平较非萎缩性胃炎组明显下降,且胃癌组下降更明显,差异均具有统计学意义(P0.05),萎缩性胃炎组血清PGⅡ显著低于非萎缩性胃炎组,差异均具有统计学意义(P0.05);胃癌组的血清G-17水平较非萎缩性胃炎组及萎缩性胃炎组均升高,差异有统计学意义(P0.05)。血清PGⅠ筛查萎缩性胃炎的最佳界值为PGⅠ90 ng/m L,其灵敏度和特异度分别为71.5%和51.0%,血清PGR筛查萎缩性胃炎的最佳界值为PGR8,其灵敏度和特异度分别为71.9%和54.0%,血清G-17筛查萎缩性胃炎的最佳界值为G-175 pmol/L,其灵敏度和特异度分别为66.1%和64.0%。血清PGⅠ筛查胃癌的最佳界值为PGⅠ73 ng/m L,其灵敏度和特异度分别为86.0%和74.9%;血清PGR筛查胃癌的最佳界值为PGR3,其灵敏度和特异度分别为90.2%和62.5%;血清G-17筛查胃癌的最佳界值为G-174 pmol/L,其灵敏度和特异度分别为62.5%和61.3%。结论:胃癌及萎缩性胃炎患者血清PGⅠ、PGR水平下降明显,且胃癌患者的血清G-17异常升高,血清PG联合GS-17测定可用于萎缩性胃炎及胃癌的早期筛查。