Temporal trends and spatial clusters of gastric cancer mortality in Brazil.

Objective: To identify nationwide temporal trends and spatial patterns of gastric cancer-related mortality in Brazil. Methods: An ecological study was performed using death certificates registered from 2000 to 2019 in which gastric cancer was recorded as any cause of death (an underlying or associated cause). Trends over time were assessed using joinpoint regression models. Spatial and spatiotemporal clusters were identified by Kulldorff's space-time scan statistics to identify high-risk areas. Results: In 276 897/22 663 091 (1.22%) death certificates gastric cancer was recorded as any cause of death. Age-adjusted gastric cancer-related mortality increased significantly over time (annual percentage change [APC]: 0.7, 95% confidence interval [CI]: 0.5 to 0.8). The increase in mortality was more pronounced in the less-developed North and Northeast Regions (North Region, APC: 3.1, 95% CI: 2.7 to 3.5; Northeast Region, APC: 3.1, 95% CI: 2.5 to 3.7). Eight spatiotemporally associated high-risk clusters of gastric cancer-related mortality were identified in the North, South, Northeast and Central-West Regions, as well as a major cluster covering a wide geographical range in the South and Southeast Regions of Brazil during the first years of the study period (2000 to 2009). Conclusions: More recently, during 2010 to 2019, clusters of gastric cancer have been identified in the Northeast Region. The nationwide increase in mortality in this analysis of 20 years of data highlights the persistently high burden of gastric cancer in Brazil, especially in socioeconomically disadvantaged regions. The identification of these areas where the population is at high risk for gastric cancer-related mortality emphasizes the need to develop effective and intersectoral control measures.

oipA "on" status of Helicobacter pylori is associated with gastric cancer in North-Eastern Brazil.

BACKGROUND: Although, outer membrane protein OipA of Helicobacter pylori has been associated with gastric mucosal damage and gastroduodenal diseases, studies evaluating gastric cancer patients are scarce. We investigated whether the functional oipA "on" status was associated with gastric cancer in the North-eastern Brazil, region with high prevalence of gastric cancer. METHODS: We included samples from 95 H. pylori positive subjects (23 patients with gastritis, 24 with gastric cancer, 32 first-degree relatives of gastric cancer patients and 16 children). oipA was assayed by polymerase chain reaction (PCR) and DNA sequencing. cagA and vacA status were evaluated by PCR. RESULTS: Overall 81.1% of the H. pylori strains had functional oipA. In adults, the oipA "on" status (OR = 9.20; 95%CI = 1.45-58.48, P = 0.02) and increasing age (OR = 1.08; 95%CI = 1.03-1.14; P = 0.003) were independently associated with gastric cancer in a logistic model. The oipA "on" status (OR = 14.75; 95%CI: 2.53-86.13, P = 0.003) was also associated with first-degree relatives of gastric cancer patients when compared with gastritis. The frequency of oipA "on" status did not differ between children and adults (P = 0.87). The oipA "on" status was significantly correlated with the presence of cagA and vacA s1 m1. CONCLUSION: oipA "on" status was independently associated with gastric cancer and first-degree relatives of gastric cancer patients in North-eastern Brazil.

Unequal burden of mortality from gastric cancer in Brazil and its regions, 2000-2015.

BACKGROUND: Gastric cancer (GC) is an important cause of morbidity and mortality worldwide. However, population-based data on GC mortality dynamics in low and middle income countries are scarce. METHODS: We analyzed GC mortality in Brazil based on all GC-related deaths registered 2000-2015. RESULTS: A total of 17,374,134 deaths were recorded, with GC identified in 214,808 (1.24%) cases-203,941 (94.9%) as underlying cause, and 10,867 (5.1%) as associated cause of death. Adjusted rates for age and sex was 6.85 deaths/100,000 inhabitants [95% confidence interval (CI) 6.73-6.97]. The highest mortality rates were found in males [10.00; rate ratio (RR) 1.85; 95% CI 1.78-1.91; p < 0.0001] and patients ≥ 45 years of age (24.98; RR 3.79; 95% CI 3.55-4.05; p < 0.0001). The South (7.56; RR 1.62; 95% CI 1.50-1.76; p < 0.0001) and Southeast (7.36; RR 1.59; 95% CI 1.48-1.71; p < 0.0001) regions had the highest regional rates. Spatial and spatiotemporal high-risk mortality areas in 2004-2007 were located mainly in the South, Southeast, and Central-West regions. After 2008, the Northeast region became a high-risk area, especially Ceará State. CONCLUSION: GC remains a significant public health problem with high mortality burden and unequal distribution in Brazilian states. The new patterns in poorer regions and the high risk in some specific populations show a clear process of epidemiological transition over time. There is a need to strengthen nationwide epidemiological monitoring, surveillance, prevention, and control for GC in the country.

Porcine stomachs with and without gastric ulcer differ in Lactobacillus load and strain characteristics.

Although Lactobacillus species are recognized as normal inhabitants of porcine gastric mucosa, the association of these bacteria with health status or gastric ulcer disease has never been considered. We investigated the bacterial load of Lactobacillus isolated from the antrum, corpus, and pars esophagea of stomachs with (n = 13) and without (n = 10) ulcer of the pars esophagea of slaughtered pigs. We also evaluated in vitro antagonistic properties against typical pathogens of strains isolated from stomachs without ulcer. To quantify Lactobacillus, gastric mucosa samples obtained with 5 mm biopsy punches were smeared on MRS agar and colonies were counted after 48 h of incubation under anaerobic conditions. The score of Lactobacillus was significantly greater in the antrum and corpus of stomachs without ulcer (P < 0.001 for both) when compared with stomachs with ulcer. Fingerprint profiles, obtained by repetitive sequence-based PCR using (GTG)5 primers, showed that the isolates were highly diverse. The reduction of Lactobacillus load in porcine stomachs may be a contributing factor for gastric ulcer. Strains isolated from healthy stomachs, which showed a wide spectrum of antagonistic activity against pathogens, may be viewed as an untapped source of bacteria with potential beneficial properties that deserve to be further investigated.

STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer.

BACKGROUND: Because to date there is no available study on STAT3 polymorphism and gastric cancer in Western populations and taking into account that Helicobacter pylori CagA EPIYA-C segment deregulates SHP-2/ERK-JAK/STAT3 pathways, we evaluated whether the two variables are independently associated with gastric cancer. METHODS: We included 1048 subjects: H. pylori-positive patients with gastric carcinoma (n = 232) and with gastritis (n = 275) and 541 blood donors. Data were analyzed using logistic regression model. RESULTS: The rs744166 polymorphic G allele (p = 0.01; OR = 1.76; 95 % CI = 1.44-2.70), and CagA-positive (OR = 12.80; 95 % CI = 5.58-19.86) status were independently associated with gastric cancer in comparison with blood donors. The rs744166 polymorphism (p = 0.001; OR = 1.64; 95 % CI = 1.16-2.31) and infection with H. pylori CagA-positive strains possessing higher number of EPIYA-C segments (p = 0.001; OR = 2.28; 95 % CI = 1.41-3.68) were independently associated with gastric cancer in comparison with gastritis. The association was stronger when host and bacterium genotypes were combined (p < 0.001; OR = 3.01; 95 % CI = 2.29-3.98). When stimulated with LPS (lipopolysaccharide) or Pam3Cys, peripheral mononuclear cells of healthy carriers of the rs744166 GG and AG genotypes expressed higher levels of STAT3 mRNA than those carrying AA genotype (p = 0.04 for both). The nuclear expression of phosphorylated p-STAT3 protein was significantly higher in the antral gastric tissue of carriers of rs744166 GG genotype than in carriers of AG and AA genotypes. CONCLUSIONS: Our study provides evidence that STAT3 rs744166 G allele and infection with CagA-positive H. pylori with higher number of EPIYA-C segments are independent risk factors for gastric cancer. The odds ratio of having gastric cancer was greater when bacterium and host high risk genotypes were combined.

CagA phosphorylation EPIYA-C motifs and the vacA i genotype in Helicobacter pylori strains of asymptomatic children from a high-risk gastric cancer area in northeastern Brazil.

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains.

Helicobacter pylori infection in infants and toddlers in South America: concordance between [13C]urea breath test and monoclonal H. pylori stool antigen test.

Accurate noninvasive tests for diagnosing Helicobacter pylori infection in very young children are strongly required. We investigated the agreement between the [(13)C]urea breath test ([(13)C]UBT) and a monoclonal ELISA (HpSA) for detection of H. pylori antigen in stool. From October 2007 to July 2011, we enrolled 414 infants (123 from Brazil and 291 from Peru) of ages 6 to 30 months. Breath and stool samples were obtained at intervals of at least 3 months from Brazilian (n = 415) and Peruvian (n = 908) infants. [(13)C]UBT and stool test results concurred with each other in 1,255 (94.86%) cases (kappa coefficient = 0.90; 95% confidence interval [CI] = 0.87 to 0.92). In the H. pylori-positive group, delta-over-baseline (DOB) and optical density (OD) values were positively correlated (r = 0.62; P < 0.001). The positivity of the tests was higher (P < 0.001; odds ratio [OR] = 6.01; 95% CI = 4.50 to 8.04) in Peru (546/878; 62.2%) than in Brazil (81/377; 21.5%) and increased with increasing age in Brazil (P = 0.02), whereas in Peru it decreased with increasing age (P < 0.001). The disagreement between the test results was associated with birth in Brazil and female gender but not with age and diarrhea. Our results suggest that both [(13)C]UBT and the stool monoclonal test are reliable for diagnosing H. pylori infection in very young children, which will facilitate robust epidemiological studies in infants and toddlers.

Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases.

Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR) was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31). Patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%). In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.

Helicobacter pylori Infection Is Associated With Thyroid Dysfunction in Children With Congenital Hypothyroidism.

Helicobacter pylori (H. pylori) infection leads to a systemic low-grade inflammatory state and has been associated causally with a diverse spectrum of extra-gastric disorders. Among them, the infection has been involved in the pathogenesis of autoimmune thyroid disease (ATD), but only one study had evaluated children. Therefore, a cross-sectional study was conducted in a cohort of 142 children and adolescents, randomly assessed among those followed up for thyroid diseases in a university pediatric endocrinology service: 106 with congenital hypothyroidism (CH) and 36 with ATD. All children were asymptomatic, under strict control on levothyroxine replacement, and reported no other diseases or use of drugs. Helicobacter pylori status was evaluated by the 13C-Urea Breath Test (13C-UBT). Antithyroid antibodies (ATPO, antiTg, and TRAb) and serum thyroid hormones (TSH, free T4, and T3) were assessed by standard assays. Data were analyzed in logistic models by the SPSS statistical software package, and a p-value ≤ 0.05 was considered statistically significant. The prevalence of H. pylori infection was 19.44% in children with ATD. Neither the gender nor the serum levels of thyroid hormones and antithyroid antibodies were associated with the H. pylori-positive status. Thirty-seven (34.90%) children with CH were infected with H. pylori. The mean T3 serum level (3.59 ± 0.84) was significantly lower (p = 0.001) in the infected children than in those free from the infection (3.95 ± 0.89), association that remained after adjustment for the other variables in the multivariate analysis. Because no difference was observed in the levels of TSH and T4, the results indicate that the infection may lead to impairment in the thyroid hormonal balance, but not in the hypothalamic-pituitary-thyroid axis function. In as much as H. pylori infection is highly widespread and the prevalence of CH is also not negligible, additional studies are required to confirm our results and to identify the involved mechanisms.

Clarithromycin-resistant H. pylori primary strains and virulence genotypes in the Northeastern region of Brazil.

The increase of H. pylori resistance to clarithromycin is a concern. This study evaluated the prevalence of H. pylori's primary resistance to clarithromycin and its association with virulence factors in adult dyspeptic patients and asymptomatic children. The gastric mucosa from patients (153 gastritis, 24 gastric cancer, 21 peptic ulcer) and gastric juice obtained by string test from 24 H. pylori and 23S rRNA positive asymptomatic children were included. The clarithromycin resistance was assessed by TaqMan RT-PCR 23S rRNA point mutations, A2142G and/or A2143G, and H. pylori virulence markers by PCR. Overall, the clarithromycin resistance was 14.4% (32/222), 14.2% in adults, and 12% in children, whereas origin, gender, and disease were not distinctive factors. The most prevalent point mutation was A2143G (62.5%). The point mutation was significantly less frequent in cagA-positive (11.4%) than in cagA-negative (23.6%) strains (p=0.03 OR = 0.4 95%CI = 0.19 - 0.91) as well as in cagE-positive (10.2%), cagE-negative (21.2%) (p=0.03 OR: 0.4 I.C:0.20-0.91). No difference was found in iceA or vacA alleles genotypes. Primary resistance to clarithromycin was lower than that reported in Southeast Brazil. The cagA and cagE positive H. pylori samples have few point mutations suggesting that individuals infected with virulent strains may be more susceptible to anti-H. pylori treatment.

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia.

Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-ß were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia.

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient.

The hypothesis that Helicobactermight be a risk factor for human liver diseases has arisen after the detection of Helicobacter DNA in hepatic tissue of patients with hepatobiliary diseases. Nevertheless, no explanation that justifies the presence of the bacterium in the human liver has been proposed. We evaluated the presence of Helicobacterin the liver of patients with hepatic diseases of different aetiologies. We prospectively evaluated 147 patients (106 with primary hepatic diseases and 41 with hepatic metastatic tumours) and 20 liver donors as controls. Helicobacter species were investigated in the liver by culture and specific 16S rDNA nested-polymerase chain reaction followed by sequencing. Serum and hepatic levels of representative cytokines of T regulatory cell, T helper (Th)1 and Th17 cell lineages were determined using enzyme linked immunosorbent assay. The data were evaluated using logistic models. Detection of Helicobacter pylori DNA in the liver was independently associated with hepatitis B virus/hepatitis C virus, pancreatic carcinoma and a cytokine pattern characterised by high interleukin (IL)-10, low/absent interferon-γ and decreased IL-17A concentrations (p < 10(-3)). The bacterial DNA was never detected in the liver of patients with alcoholic cirrhosis and autoimmune hepatitis that are associated with Th1/Th17 polarisation. H. pylori may be observed in the liver of patients with certain hepatic and pancreatic diseases, but this might depend on the patient cytokine profile.

IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia.

Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1ß were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.

Variation rhythms of lymphocyte subsets during healthy aging.

Immunological alterations associated with aging (immunosenescence) do not represent a simple unidirectional decline in all functions but develop as a complex remodeling of the immune system, involving multiple reorganization and developmentally regulated changes. In general, most data available about aging were obtained at particular age intervals and most of them come from Caucasian individuals from either Europe or the United States. Here, we report the frequencies of major lymphocyte subsets in healthy Brazilian individuals from 2 distinct geographic regions (Southeast and South) at several age intervals spanning a lifetime period (0-86 years). Overall, we demonstrated that changes in the frequencies of cells related to both innate and adaptive immunity clearly occur with aging in these individuals. These changes were not progressive and equally steady for all cell populations tested but instead showed an oscillatory or rhythmic behavior that was distinctive of each population at different age intervals. We also observed that abrupt changes in the frequencies of immune cells may occur in healthy individuals over 75 years old, suggesting there is an impaired flexibility of the immune system at late stages of life to sustain homeostasis via immune mechanisms. We presented reference ranges for healthy Brazilian individuals at all ages. The knowledge of these parameters in further detail will allow interventions to optimize immune function in advanced age and to improve the quality of life in the elderly.

Bioelectrical Impedance Analysis-Derived Measurements in Chronic Hepatitis C: Clinical Relevance of Fat-Free Mass and Phase Angle Evaluation.

OBJECTIVE: Because cirrhotic patients are at high risk of malnutrition and sarcopenia, we evaluated the prevalence of low fat-free mass index (FFMI) and low phase angle (PhA) among patients with chronic hepatitis C (CHC). METHODS: In total, 135 subjects with CHC (50.4% males; mean age, 52.4 ± 11.8 years; 65.9% noncirrhotic and 34.1% compensated cirrhotic patients) were prospectively included and evaluated by bioelectrical impedance analysis. Subjective global assessment was used to evaluate malnutrition. RESULTS: Low FFMI and low PhA were identified in 21.5% and 23.7% of the patients, respectively. Compensated cirrhotic patients had lower PhA values than those without cirrhosis. Low FFMI was associated with male sex (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.00-7.01; P = .04) and malnutrition (OR, 4.27; 95% CI, 1.42-12.90; P = .01). Low PhA was associated with cirrhosis (OR, 3.92; 95% CI, 1.56-9.86; P = .004), malnutrition (OR, 5.52; 95% CI, 1.73-17.62; P = .004), and current alcohol use (OR, 2.77; 95% CI, 1.01-7.58; P = .05). Reactance (Xc) normalized for height (H), an indicator of muscle strength, was independently associated with male sex, age, hypertension, and serum albumin. CONCLUSION: Host factors, including clinical comorbidities, lifestyle, and nutrition status, are associated with low FFMI and low PhA in noncirrhotic and in compensated cirrhotic patients with CHC. These findings highlight the relevance of evaluating body composition in patients chronically infected by hepatitis C virus independently of the stage of liver disease.

Temporal trends and spatial clusters of gastric cancer mortality in Brazil

[ABSTRACT]. Objective. To identify nationwide temporal trends and spatial patterns of gastric cancer–related mortality in Brazil. Methods. An ecological study was performed using death certificates registered from 2000 to 2019 in which gastric cancer was recorded as any cause of death (an underlying or associated cause). Trends over time were assessed using joinpoint regression models. Spatial and spatiotemporal clusters were identified by Kulldorff’s space–time scan statistics to identify high-risk areas. Results. In 276 897/22 663 091 (1.22%) death certificates gastric cancer was recorded as any cause of death. Age-adjusted gastric cancer–related mortality increased significantly over time (annual percentage change [APC]: 0.7, 95% confidence interval [CI]: 0.5 to 0.8). The increase in mortality was more pronounced in the less-developed North and Northeast Regions (North Region, APC: 3.1, 95% CI: 2.7 to 3.5; Northeast Region, APC: 3.1, 95% CI: 2.5 to 3.7). Eight spatiotemporally associated high-risk clusters of gastric cancer–related mortality were identified in the North, South, Northeast and Central–West Regions, as well as a major cluster covering a wide geographical range in the South and Southeast Regions of Brazil during the first years of the study period (2000 to 2009). Conclusions. More recently, during 2010 to 2019, clusters of gastric cancer have been identified in the Northeast Region. The nationwide increase in mortality in this analysis of 20 years of data highlights the persistently high burden of gastric cancer in Brazil, especially in socioeconomically disadvantaged regions. The identification of these areas where the population is at high risk for gastric cancer–related mortality emphasizes the need to develop effective and intersectoral control measures.

[RESUMEN]. Objetivo. Identificar las tendencias temporales y los patrones espaciales de la mortalidad relacionada con el cáncer gástrico a nivel nacional en Brasil. Métodos. Se realizó un estudio ecológico, empleando certificados de defunción registrados entre los años 2000 y 2019 en los que se notificó cáncer gástrico como cualquier causa de muerte (subyacente o asociada). Se evaluaron las tendencias con el transcurso del tiempo mediante modelos de regresión de punto de inflexión (joinpoint). Se identificaron los conglomerados espaciales y espaciotemporales mediante la técnica estadística de exploración espaciotemporal de Kulldorff para determinar cuáles eran las áreas de alto riesgo. Resultados. En 276 897 de 22 663 091 certificados de defunción (1,22%), se registró cáncer gástrico como cualquier causa de muerte. La mortalidad relacionada con el cáncer gástrico ajustada por edad aumentó significativamente con el tiempo (cambio porcentual anual: 0,7; intervalo de confianza [IC] del 95%: 0,5 a 0,8). El aumento de la mortalidad fue más acusado en la regiones Norte y Noreste, menos desarrolladas, (región Norte, cambio porcentual anual: 3,1, IC del 95%: 2,7 a 3,5; región Noreste, cambio porcentual anual: 3,1, IC del 95%: 2,5 a 3,7). Durante los primeros años del período de estudio (del 2000 al 2009), se identificaron ocho conglomerados de alto riesgo de mortalidad relacionada con el cáncer gástrico y con asociación espacial y temporal en las regiones Norte, Sur, Noreste y Centro-Oeste, así como un conglomerado importante que cubría un amplio rango geográfico en las regiones Sur y Sureste de Brasil. Conclusiones. Más recientemente, del 2010 al 2019, se han identificado conglomerados de cáncer gástrico en la región noreste. El aumento nacional de la mortalidad en este análisis de veinte años de datos destaca la carga persistentemente alta del cáncer gástrico en Brasil, especialmente en las regiones socioeconómicamente desfavorecidas. La identificación de estas áreas en que la población presenta un alto riesgo de mortalidad relacionada con el cáncer gástrico subraya la necesidad de elaborar medidas de control intersectoriales y efectivas.

[RESUMO]. Objetivo. Identificar tendências temporais e padrões espaciais de mortalidade relacionada ao câncer gástrico em todo o Brasil. Métodos. Realizou-se um estudo ecológico a partir de declarações de óbito registradas de 2000 a 2019 em que o câncer gástrico foi indicado como qualquer causa de morte (causa básica ou associada). As tendências ao longo do tempo foram avaliadas a partir de modelos de regressão por pontos de inflexão (joinpoint). Os aglomerados espaciais e espaço-temporais foram identificados por estatística de varredura espaçotemporal de Kulldorff para detectar áreas de alto risco. Resultados. O câncer gástrico foi registrado como qualquer causa de morte em 276.897/22.663.091 (1,22%) declarações de óbito. A mortalidade relacionada ao câncer gástrico ajustada por idade aumentou significativamente ao longo do tempo [variação percentual anual (VPA): 0,7, intervalo de confiança (IC) de 95%: 0,5 a 0,8]. O aumento da mortalidade foi mais acentuado no Norte e Nordeste, regiões menos desenvolvidas (região Norte, VPA: 3,1, IC 95%: 2,7 a 3,5; região Nordeste, VPA: 3,1, IC 95%: 2,5 a 3,7). Identificaram-se oito aglomerados de alto risco de mortalidade relacionada ao câncer gástrico em associação espaço-temporal nas regiões Norte, Sul, Nordeste e Centro-Oeste, além de um grande aglomerado que abrangia uma larga faixa geográfica nas regiões Sul e Sudeste do Brasil durante os primeiros anos do período de estudo (2000 a 2009). Conclusões. Mais recentemente, no período de 2010 a 2019, identificaram-se aglomerados de câncer gástrico na região Nordeste. O aumento da mortalidade em todo o país nesta análise de dados relativos a 20 anos evidencia a persistência da alta carga de câncer gástrico no Brasil, sobretudo em regiões desfavorecidas do ponto de vista socioeconômico. A identificação dessas áreas em que a população corre alto risco de morte relacionada ao câncer gástrico enfatiza a necessidade de desenvolver medidas de controle efetivas e intersetoriais.

Temporal trends and spatial clusters of gastric cancer mortality in Brazil / Tendencias temporales y conglomerados espaciales de mortalidad por cáncer gástrico en Brasil / Tendências temporais e aglomerados espaciais de mortalidade por câncer gástrico no Brasil

ABSTRACT Objective. To identify nationwide temporal trends and spatial patterns of gastric cancer-related mortality in Brazil. Methods. An ecological study was performed using death certificates registered from 2000 to 2019 in which gastric cancer was recorded as any cause of death (an underlying or associated cause). Trends over time were assessed using joinpoint regression models. Spatial and spatiotemporal clusters were identified by Kulldorff's space-time scan statistics to identify high-risk areas. Results. In 276 897/22 663 091 (1.22%) death certificates gastric cancer was recorded as any cause of death. Age-adjusted gastric cancer-related mortality increased significantly over time (annual percentage change [APC]: 0.7, 95% confidence interval [CI]: 0.5 to 0.8). The increase in mortality was more pronounced in the less-developed North and Northeast Regions (North Region, APC: 3.1, 95% CI: 2.7 to 3.5; Northeast Region, APC: 3.1, 95% CI: 2.5 to 3.7). Eight spatiotemporally associated high-risk clusters of gastric cancer-related mortality were identified in the North, South, Northeast and Central-West Regions, as well as a major cluster covering a wide geographical range in the South and Southeast Regions of Brazil during the first years of the study period (2000 to 2009). Conclusions. More recently, during 2010 to 2019, clusters of gastric cancer have been identified in the Northeast Region. The nationwide increase in mortality in this analysis of 20 years of data highlights the persistently high burden of gastric cancer in Brazil, especially in socioeconomically disadvantaged regions. The identification of these areas where the population is at high risk for gastric cancer-related mortality emphasizes the need to develop effective and intersectoral control measures.

RESUMEN Objetivo. Identificar las tendencias temporales y los patrones espaciales de la mortalidad relacionada con el cáncer gástrico a nivel nacional en Brasil. Métodos. Se realizó un estudio ecológico, empleando certificados de defunción registrados entre los años 2000 y 2019 en los que se notificó cáncer gástrico como cualquier causa de muerte (subyacente o asociada). Se evaluaron las tendencias con el transcurso del tiempo mediante modelos de regresión de punto de inflexión (joinpoint). Se identificaron los conglomerados espaciales y espaciotemporales mediante la técnica estadística de exploración espaciotemporal de Kulldorff para determinar cuáles eran las áreas de alto riesgo. Resultados. En 276 897 de 22 663 091 certificados de defunción (1,22%), se registró cáncer gástrico como cualquier causa de muerte. La mortalidad relacionada con el cáncer gástrico ajustada por edad aumentó significativamente con el tiempo (cambio porcentual anual: 0,7; intervalo de confianza [IC] del 95%: 0,5 a 0,8). El aumento de la mortalidad fue más acusado en la regiones Norte y Noreste, menos desarrolladas, (región Norte, cambio porcentual anual: 3,1, IC del 95%: 2,7 a 3,5; región Noreste, cambio porcentual anual: 3,1, IC del 95%: 2,5 a 3,7). Durante los primeros años del período de estudio (del 2000 al 2009), se identificaron ocho conglomerados de alto riesgo de mortalidad relacionada con el cáncer gástrico y con asociación espacial y temporal en las regiones Norte, Sur, Noreste y Centro-Oeste, así como un conglomerado importante que cubría un amplio rango geográfico en las regiones Sur y Sureste de Brasil. Conclusiones. Más recientemente, del 2010 al 2019, se han identificado conglomerados de cáncer gástrico en la región noreste. El aumento nacional de la mortalidad en este análisis de veinte años de datos destaca la carga persistentemente alta del cáncer gástrico en Brasil, especialmente en las regiones socioeconómicamente desfavorecidas. La identificación de estas áreas en que la población presenta un alto riesgo de mortalidad relacionada con el cáncer gástrico subraya la necesidad de elaborar medidas de control intersectoriales y efectivas.

RESUMO Objetivo. Identificar tendências temporais e padrões espaciais de mortalidade relacionada ao câncer gástrico em todo o Brasil. Métodos. Realizou-se um estudo ecológico a partir de declarações de óbito registradas de 2000 a 2019 em que o câncer gástrico foi indicado como qualquer causa de morte (causa básica ou associada). As tendências ao longo do tempo foram avaliadas a partir de modelos de regressão por pontos de inflexão (joinpoint). Os aglomerados espaciais e espaço-temporais foram identificados por estatística de varredura espaço-temporal de Kulldorff para detectar áreas de alto risco. Resultados. O câncer gástrico foi registrado como qualquer causa de morte em 276.897/22.663.091 (1,22%) declarações de óbito. A mortalidade relacionada ao câncer gástrico ajustada por idade aumentou significativamente ao longo do tempo [variação percentual anual (VPA): 0,7, intervalo de confiança (IC) de 95%: 0,5 a 0,8]. O aumento da mortalidade foi mais acentuado no Norte e Nordeste, regiões menos desenvolvidas (região Norte, VPA: 3,1, IC 95%: 2,7 a 3,5; região Nordeste, VPA: 3,1, IC 95%: 2,5 a 3,7). Identificaram-se oito aglomerados de alto risco de mortalidade relacionada ao câncer gástrico em associação espaço-temporal nas regiões Norte, Sul, Nordeste e Centro-Oeste, além de um grande aglomerado que abrangia uma larga faixa geográfica nas regiões Sul e Sudeste do Brasil durante os primeiros anos do período de estudo (2000 a 2009). Conclusões. Mais recentemente, no período de 2010 a 2019, identificaram-se aglomerados de câncer gástrico na região Nordeste. O aumento da mortalidade em todo o país nesta análise de dados relativos a 20 anos evidencia a persistência da alta carga de câncer gástrico no Brasil, sobretudo em regiões desfavorecidas do ponto de vista socioeconômico. A identificação dessas áreas em que a população corre alto risco de morte relacionada ao câncer gástrico enfatiza a necessidade de desenvolver medidas de controle efetivas e intersetoriais.

Clarithromycin-resistant H. pylori primary strains and virulence genotypes in the Northeastern region of Brazil

ABSTRACT The increase of H. pylori resistance to clarithromycin is a concern. This study evaluated the prevalence of H. pylori's primary resistance to clarithromycin and its association with virulence factors in adult dyspeptic patients and asymptomatic children. The gastric mucosa from patients (153 gastritis, 24 gastric cancer, 21 peptic ulcer) and gastric juice obtained by string test from 24 H. pylori and 23S rRNA positive asymptomatic children were included. The clarithromycin resistance was assessed by TaqMan RT-PCR 23S rRNA point mutations, A2142G and/or A2143G, and H. pylori virulence markers by PCR. Overall, the clarithromycin resistance was 14.4% (32/222), 14.2% in adults, and 12% in children, whereas origin, gender, and disease were not distinctive factors. The most prevalent point mutation was A2143G (62.5%). The point mutation was significantly less frequent in cagA-positive (11.4%) than in cagA-negative (23.6%) strains (p=0.03 OR = 0.4 95%CI = 0.19 - 0.91) as well as in cagE-positive (10.2%), cagE-negative (21.2%) (p=0.03 OR: 0.4 I.C:0.20-0.91). No difference was found in iceA or vacA alleles genotypes. Primary resistance to clarithromycin was lower than that reported in Southeast Brazil. The cagA and cagE positive H. pylori samples have few point mutations suggesting that individuals infected with virulent strains may be more susceptible to anti-H. pylori treatment.

CagA-positive Helicobacter pylori strain containing three EPIYA C phosphorylation sites produces increase of G cell and decrease of D cell in experimentally infected gerbils (Meriones unguiculatus).

PURPOSE: Human infection by Helicobacter pylori is associated with an increase in the number of gastrin-producing G cells and a concomitant decrease of somatostatin-producing D cells. However, to our knowledge, changes in G and D cell numbers in response to infection with H. pylori CagA-positive strains containing different number of EPIYA-C phosphorylation sites have not been analyzed to date. Therefore, the aim of this study was to perform a quantitative analysis of the number of G and D cells in Mongolian gerbils challenged with H. pylori strains with different numbers of EPIYA-C motifs. MATERIALS AND METHODS: Mongolian gerbils were inoculated with isogenic H. pylori strains containing one to three phosphorylation sites. Mucosal fragments were evaluated by morphometry and immunohistochemistry using primary polyclonal rabbit anti-gastrin and anti-somatostatin antibodies. Positive cells were counted using an image analyzer. RESULTS: Forty-five days after infection, there was a decrease in the number of D cells and an increase in the G/D cell ratio in the group with three EPIYA-C. Six months after infection, there was a progressive and significant increase in the number of G cells and in the G/D cell ratio, with a concomitant decrease in the number of D cells, especially in the three EPIYA-C group. CONCLUSIONS: CagA-positive H. pylori strains containing a large number of EPIYA-C phosphorylation sites induce a decrease in D cell number and an increase in G cell number and G/D ratio, which were correlated with the number of inflammatory cells of the lamina propria.