Respuesta inmunológica a varias proteínas del H. pylori en pacientes guatemaltecos / Inmune response to various H. pylori proteins in Guatemalan patients

Se determinó la respuesta inmunológica a proteínas recombinantes de Helicobacter pylori en pacientes dis-pépticos (adultos y niños), pacientes con cáncer gástrico y sus familiares asintomáticos adultos viviendo con ellos. Se utilizó la prueba recomLine® Helicobacter IgG e IgA, y con base en el reconocimiento de los factores de virulencia VacA y CagA se determinó si la cepa de H. pylori era de tipo I o II. El análisis de los datos fue descriptivo y analítico y se estimaron los intervalos de confianza de 95%, con un nivel de error de 0.05 y Odds ratio. El 58.7% (121/206) de los pacientes presentó la bacteria en tinción histológica de biopsia, positividad que disminuyó con la edad y daño histológico. La frecuencia de la respuesta a los anticuerpos IgG fue mayor que IgA, en ambos casos ésta fue menor en los niños. Las proteínas del H. pylori más reconocidas tanto por IgA como IgG fueron VacA y CagA, y la respuesta a las otras proteínas investigadas fue mayor al aumentar el daño histológi-co. La cepa tipo I fue la que predominó en la población en estudio con 66% (136/206). Se deben continuar con los estudios de prevalencia de la cepa tipo I del H. pylori y del reconocimiento de sus antígenos en la población guatemalteca a fin de determinar su utilidad en el diagnóstico y pronóstico de la infección.

The immune response to recombinant Helicobacter pylori proteins was determined in dyspeptic patients (adults and children), patients with gastric cancer and their asymptomatic adults' relatives living with them. The recomLine® Helicobacter IgG and IgA test was used and based on the recognition of the virulence factors VacA and CagA, it was determined whether the H. pylori strain was type I or II. The data analysis was descriptive and analytic, and 95% confidence intervals were estimated, with an error level of 0.05, and Odds ratio. The patients that presented the bacterium in histological biopsy were 58.7% (121/206), positivity that decreased with age and histological damage. The frecuency of response to IgG antibodies was higher than IgA, in both cases it was lower in children. VacA and CagA were the H. pylori proteins most recognized by both IgA and IgG and it was observed that the number of recognized proteins was greater with increasing histological damage. The type I strain was the one that predominated in the study population 66% (136/206). Prevalence studies of the type I strain of H. pylori ant the recognition of its antigens in the Guatemalan population should continue in order to determine its usefulness in the diagnosis and prognosis of infection.

Catheter-related infection due to Papiliotrema laurentii in an oncologic patient: Case report and systematic review

ABSTRACT Background: Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte and thought to be non-pathogenic to humans. Nevertheless, increasing number of reports of human infection have emerged in recent years, mostly in oncologic patients. Aim: To report a case of a female patient with pyloric obstructive cancer with a catheter-related Papiliotrema laurentii blood stream infection and systematically review the available evidence on P. laurentii infection in humans. Methods: Retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Library for Systematic Reviews and Opengray.eu. There was no language or date of publication restrictions. The reference lists of the studies retrieved were searched manually. Results: The search strategy retrieved 1703 references. In the final analysis, 31 references were included, with the description of 35 cases. Every patient but one had a previous co-morbidity - 48.4 % of patients had a neoplasm. Amphotericin B was the most used treatment and only a single case of resistance to it was reported. Most patients were cured of the infection. Conclusion: P. laurentii infection in humans is usually associated to neoplasia and multiple co-morbidities, and amphotericin B seems to be a reliable agent for treatment.

Infecção por Helicobacter pylori e lesões precursoras de câncer gástrico: prevalência e fatores associados em um laboratório de referência no Sudeste do Brasil / Helicobacter pylori infection and gastric cancer precursor lesions: prevalence and associated factors in a reference laboratory in southeastern brazil

ABSTRACT BACKGROUND: Helicobacter pylori infection is the most important risk factor for gastric atrophy and intestinal metaplasia, both considered gastric cancer precursor lesions. Therefore, the investigation of the occurrence of H. pylori infection, precursor lesions and associated factors guides the adoption of specific strategies for the control this type of cancer. OBJECTIVE: To evaluate the prevalence of H. pylori infection in patients undergoing upper digestive endoscopy, as well as the prevalence of intestinal metaplasia, atrophy and chronic inflammation and their association with H. pylori infection. METHODS: A retrospective study was performed based on reports of gastric endoscopic biopsies performed in a private laboratory affiliated to the Brazilian Public Health System (SUS). Patients were evaluated for age, gender and type of health service. The samples were evaluated for the presence of H. pylori, and also of chronic inflammation, intestinal metaplasia and glandular atrophy. RESULTS: Of a total of 4,604 patients (mean age 51±16.6), 63.9% were female and 63.1% coming from private health care service. The prevalence of H. pylori infection was 31.7% (n=1,459), and the percentage of infection was significantly higher in patients from public health service (42.0%) in relation to patients from private health service (25.6%). Among H. pylori (+) patients, a higher percentage of intestinal metaplasia (17.7% vs 13.3%) and glandular atrophy (17.6% vs 6.9%) were observed when compared to those H. pylori (-) (P<0.01). From the patients H. pylori (+) with at least one type of precursor lesion (n=418), 161 (38.5%) had metaplasia and chronic inflammation, 160 (38.3%) had atrophy and chronic inflammation and finally 97 (23.2%) presented metaplasia, atrophy and chronic inflammation simultaneously. CONCLUSION: The present study reinforces the association of H. pylori infection with gastric cancer precursor lesions in a Brazilian population, emphasizing the importance of infection prevention measures, as well as the treatment of infected patients, especially in regions with lower socioeconomic levels that show a higher prevalence of infection by H. pylori.

RESUMO CONTEXTO: A infecção por Helicobacter pylori é o fator de risco mais importante para atrofia gástrica e metaplasia intestinal, ambas consideradas lesões precursoras do câncer gástrico. Portanto, a investigação da ocorrência de infecção por H. pylori, das lesões precursoras e dos fatores associados orienta a adoção de estratégias específicas para o controle deste tipo de câncer. OBJETIVO: Avaliar a prevalência de infecção por H. pylori em pacientes submetidos à endoscopia digestiva alta, bem como a prevalência de metaplasia intestinal, atrofia e inflamação crônica e a associação destas com a infecção por H. pylori. MÉTODOS: Foi realizado um estudo retrospectivo com base em laudos de biópsias endoscópicas gástricas realizadas em laboratório privado afiliado ao Sistema Único de Saúde (SUS). Os pacientes foram avaliados quanto à idade, sexo e tipo de serviço de saúde. As amostras foram avaliadas quanto à presença de H. pylori e também de inflamação crônica, metaplasia intestinal e atrofia glandular. RESULTADOS: Do total de 4.604 pacientes (idade média de 51±16,6), 63,9% eram do sexo feminino e 63,1% provenientes de serviços de saúde privado. A prevalência de infecção por H. pylori foi de 31,7% (n=1.459) e o percentual de infecção foi significativamente maior nos pacientes do serviço público de saúde (42,0%) em relação aos pacientes do serviço privado de saúde (25,6%). Entre os pacientes com H. pylori (+), foi observado maior percentual de metaplasia intestinal (17,7% vs 13,3%) e atrofia glandular (17,6% vs 6,9%) quando comparados aos H. pylori (-) (P<0,01). Dos pacientes H. pylori (+) com pelo menos um tipo de lesão precursora (n=418), 161 (38,5%) apresentaram metaplasia e inflamação crônica, 160 (38,3%) apresentaram atrofia e inflamação crônica e, finalmente, 97 (23,2%) apresentaram metaplasia, atrofia e inflamação crônica simultaneamente. CONCLUSÃO: O presente estudo reforça a associação da infecção por H. pylori com lesões precursoras de câncer gástrico em uma população brasileira, enfatizando a importância de medidas de prevenção de infecção, bem como o tratamento de pacientes infectados, principalmente em regiões com níveis socioeconômicos mais baixos que apresentam maior prevalência de infecção por H. pylori.

Gênero, idade, achados endoscópicos, urease e Helicobacter pylori: ausência de correlação dentro de uma amostra de população com alta prevalência de câncer gástrico na Amazônia / Gender, age, endoscopic findings, urease and helicobacter pylori: all uncorrelated within a sample of a high gastric cancer prevalence population in amazon

ABSTRACT BACKGROUND: It is widely assumed that gender, age, gastritis and Helicobacter pylori , all have some degree of correlation and, therefore, can synergistically lead to the development of gastric cancer. OBJECTIVE: In this cross-sectional study, we expected to observe the above mentioned correlation in the analysis of medical records of 67 patients of both sexes (female, n=44), mean age ± standard deviation: 41±12 years old, all from Belém (capital of Pará State, Brazilian Amazon), a city historically known as one with the highest gastric cancer prevalence in this country. METHODS: All patients were submitted to upper gastrointestinal endoscopy for gastric biopsy histopathological analysis and rapid urease test. All diagnoses of gastritis were recorded considering its topography, category and the degree of inflammatory activity, being associated or not associated with H. pylori infection. RESULTS: The results show that no statistically relevant associations were found among the prevalences of the observed variables. CONCLUSION: The authors hypothesize that observed risk factors associated to gastric cancer might be lesser synergistic than is usually expected.

RESUMO CONTEXTO: É amplamente assumido que gênero, idade, gastrite e Helicobacter pylori , todos têm algum grau de correlação e, portanto, podem sinergicamente levar ao desenvolvimento de câncer gástrico. OBJETIVO: Neste estudo transversal, esperamos observar a correlação acima mencionada na análise de prontuários de 67 pacientes de ambos os sexos (sexo feminino, n=44), média de idade ± desvio padrão: 41±12 anos, todos de Belém (capital do Estado do Pará, Amazônia Brasileira), uma cidade historicamente conhecida como sendo uma das que apresenta maior prevalência de câncer gástrico no país. MÉTODOS: Todos os pacientes foram submetidos à endoscopia digestiva alta para análise histopatológica da biópsia gástrica e teste rápido da urease. Todos os diagnósticos de gastrite foram registrados considerando sua topografia, categoria e grau de atividade inflamatória, sendo associada ou não associada à infecção por H. pylori . RESULTADOS: Os resultados mostram que não foram encontradas associações estatisticamente relevantes entre as prevalências das variáveis observadas. CONCLUSÃO: Os autores levantam a hipótese de que os fatores de risco associados ao câncer gástrico podem ser menos sinérgicos do que o esperado.

Morfología y repercusiones diagnóstico-terapéuticas de las lesiones preneoplásicas gástricas / Morphology and diagnostic determinants of gastric precancerous conditions

El carcinoma gástrico (CG) de tipo intestinal se origina en un epitelio displásico, que a su vez se desarrolla en medio de una atrofia gástrica (AG) y metaplasia intestinal (MI). La infección por Helicobacter pylori (HP) es la causa más frecuente de AG, causando una pangastritis atrófica multifocal. Entre otras condiciones que producen inflamación crónica de la mucosa gástrica se encuentran también la gastritis autoinmune y la anemia perniciosa. El marco conceptual sobre el cual descansa gran parte de la investigación actual y nuestra comprensión de los cambios que ocurren en la mucosa gástrica se debe a la denominada "cascada de Correa"; quien planteó que la mucosa gástrica crónicamente inflamada, da paso a la AG, que va adquiriendo focos de MI y en dicho epitelio se desarrollará finalmente una displasia (DIS). Se ha acuñado el término lesiones preneoplásicas gástricas (LPG), para referirse a: AG, MI y DIS.Después de la erradicación de HP, se ha demostrado una reducción general de la incidencia de CG; efecto que no es tan claro, cuando la pangastritis por HP ha evolucionado a AG extensa. De tal modo que el efecto de la erradicación de HP medido a través de EC, ha sido poco consistente. La AG grave diagnosticada por histología representa la condición de mayor riesgo. Por otra parte, la MI puede ser de tipo intestinal (delgado-entérica ó incompleta) y la colónica (colónica ó completa) considerándose a esta última, como la variedad de peor pronóstico. El diagnóstico histológico de este tipo de lesiones determina que quien las padece, debe someterse a vigilancia endoscópica. El objetivo de este manuscrito fue resumir la evidencia existente respecto de las LPG, en términos de su caracterización morfológica y sus repercusiones diagnóstico-terapéuticas (significado patológico, graduación del riesgo, vigilancia recomendada; y factores de riesgo).

Gastric carcinoma (GC) of intestinal type, originates from a dysplastic epithelium, which in turn develops in the midst of gastric atrophy (GA) and intestinal metaplasia (IM). Helicobacter pylori (HP) infection is the most frequent cause of GA, causing a multifocal atrophic pangastritis. Among other conditions that produce chronic inflammation of gastric mucosa are also autoimmune gastritis and pernicious anemia. The conceptual framework on which much of current research rests and our understanding of the changes that occur in the gastric mucosa is due to the so-called "Correa waterfall"; who stated that gastric mucosa chronically inflamed, gives way to the GA, which is acquiring foci of IM and in said epithelium a dysplasia (DIS) will eventually develop. The term precancerous conditions (PCC) of the gastric mucosa have been coined to refer to: GA, IM and DIS. After HP eradication, a general reduction in the incidence of GC has been demonstrated; effect that is not so clear, when pangastritis by HP has evolved to extensive GA. Thus, the effect of HP eradication measured through clinical trials has been inconsistent. Severe GA diagnosed represents the highest risk condition. On the other hand, IM can be enteric (grade I), enterocolic (grade II) or colonic (grade III); considering IM III as the variety with the worst prognosis. Histological diagnosis of gastric PCC, determines that the one who suffers them, must undergo endoscopic surveillance. The aim of this manuscript was to update morphological aspects and diagnostic-therapeutic scope of gastric PCC.

Análise comparativa do polimorfismo genético da glutationa transferase, do Helicobacter pylori e do vírus Epstein-Barr entre a área do tumor e as margens de ressecção proximal e distal do câncer gástrico / Comparative analysis of glutathione transferase genetic polymorphism, Helicobacter pylori and Epstein-Barr virus between the tumor area and the proximal and distal resection margins of gastric cancer

RESUMO Objetivo: comparar o polimorfismo dos genes Glutationa S-transferase teta 1 (GSTT1) e Glutationa S-transferase mu 1 (GSTM1) da área do tumor com as margens proximal e distal de espécimes de estômago ressecados de pacientes com câncer gástrico, e investigar a presença do DNA do vírus Epstein-Barr (EBV) e Helicobacter pylori. Métodos: coletamos prospectivamente amostras teciduais da área do tumor e das margens de ressecção proximal e distal dos estômagos de dez pacientes com adenocarcinoma gástrico submetidos à gastrectomia com linfadenectomia D2 e submetemos esses espécimes à extração de DNA. Comparamos a área do tumor com as margens proximal e distal dos estômagos ressecados para o polimorfismo dos genes GSTT1 e GSTM1 e investigamos a presença de DNA do EBV e H. pylori. Utilizamos o exon 5 do gene p53 como controle interno da reação de PCR multiplex. Resultados: em um paciente, detectamos genótipos GSTT1 e GSTM1 nulos na área do tumor, em contraste com a presença de ambos os genes nas margens proximal e distal. Encontramos DNA do EBV e H. pylori na área do tumor e também nas margens proximal e distal. Em outro paciente, a margem proximal foi negativa para GSTT1 e o DNA do EBV foi negativo na margem distal. Em três pacientes, o EBV-DNA foi negativo apenas na margem distal. Conclusão: este é o primeiro relato em que diferentes genótipos, infecção por EBV-DNA e H. pylori foram observados no mesmo paciente, indicando provável deleção desses genes em resposta à progressão tumoral e heterogeneidade intratumoral.

ABSTRACT Objective: to compare the polymorphism of the Glutathione S-transferase theta 1 (GSTT1) and Glutathione S-transferase mu 1 (GSTM1) genes from the tumor area with the proximal and distal margins of stomach specimens resected from patients with gastric cancer, and to investigate the presence of Epstein-Barr virus (EBV) DNA and Helicobacter pylori. Methods: we prospectively collected tissue specimens from the tumor area and from the proximal and distal resection margins of the stomachs of ten patients with gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy, and submitted these specimens to DNA extraction. We compared the tumor area with the proximal and distal margins of the resected stomachs for polymorphism of GSTT1 and GSTM1 genes and investigated the presence of EBV-DNA and H. pylori. We used the p53 exon 5 gene as an internal control of the multiplex PCR reaction. Results: in one patient, we detected null GSTT1 and GSTM1 genotypes in the tumor area, in contrast to the presence of both genes in the proximal and distal margins. We found EBV-DNA and H. pylori in the tumor area and also in the proximal and distal margins. In another patient, the proximal margin was negative for GSTT1, and EBV-DNA was negative in the distal margin. In three patients, EBV-DNA was negative only in the distal margin. Conclusion: this is the first report where different genotypes, EBV-DNA and H. pylori infection were observed in the same patient, indicating a probable deletion of these genes in response to tumor progression and intratumoral heterogeneity.

Infecção pelo Helicobacter pylori e perfil imunológico em pacientes com diferentes doenças gastroduodenais / Helicobacter pylori infection and immune profile of patients with different gastroduodenal diseases

ABSTRACT BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.

RESUMO CONTEXTO: A associação da infecção por Helicobacter pylori com diferentes doenças gastroduodenais pode estar associada a fatores bacterianos, do hospedeiro e do ambiente. Nesse contexto, estudos têm demonstrado que a diversidade genética do H. pylori, sobretudo nos genes vacA e cagA, está associada ao desenvolvimento de doenças gastroduodenais como a úlcera péptica e o câncer gástrico. Além disso, a natureza da resposta inflamatória do hospedeiro pode explicar essas diferentes manifestações da infecção por esse microrganismo. Portanto, fatores do hospedeiro que regulam as respostas imunológica e inflamatória, envolvendo a interação funcional da infecção por H. pylori com diferentes membros do compartimento imunológico, especialmente respostas imunes de células T nas doenças gastroduodenais, ainda precisam ser melhor estudados. OBJETIVO: Caracterizar a resposta imune, incluindo imunidade induzida por infecção pelo H. pylori, especialmente com cepas virulentas de H. pylori (alelos vacA e gene cagA), através da análise do perfil de citocinas e da caracterização da população de células T presentes em doenças gastroduodenais em nossa população. MÉTODOS: Em um estudo prospectivo, foram coletadas biópsias gástricas de 554 pacientes portadores das diferentes doenças gastroduodenais. Nas amostras biológicas destes pacientes foi realizada a determinação do genótipo bacteriano e a detecção das citocinas IL-4, IL-10, INF-γ e IL-12 através do método Elisa. Foram obtidas biópsias gástricas para avaliação histológica. RESULTADOS: Observamos que o genótipo predominante nas cepas de H. pylori isoladas dos pacientes estudados foi s1m1cagA positivo, sendo mais frequentes entre os pacientes com úlcera gástrica, úlcera duodenal e câncer gástrico. Houve associação significativa das cepas com o genótipo s1m1cagA positivo com maior grau de inflamação, atividade neutrofílica e desenvolvimento de metaplasia intestinal. As concentrações gástricas de INF-γ e IL-12 foram significativamente mais elevadas em pacientes infectados pelo H. pylori do que nos não infectados. Foram detectados níveis mais elevados dessas citocinas nos portadores de úlcera e câncer gástrico, sendo que nesses pacientes foram observados níveis mais baixos de IL-4 e IL-10 na mucosa gástrica. Além disso, as concentrações de INF-γ e IL-12 em biópsias gástricas, foram mais elevadas nos pacientes portadores das cepas bacterianas virulentas s1m1cagA+. Contrariamente, os níveis de IL-4 e IL-10 foram maiores em tecido infectado por cepas s2m2cagA. Pacientes com maior grau de inflamação, de atividade neutrofílica e presença de metaplasia intestinal, apresentaram níveis mais elevados de INF-γ e IL-12 e uma concentração mais baixa de IL-4 e IL-10 nas biópsias gástricas. CONCLUSÃO: Nosso estudo demonstra que a interação entre o tipo de cepa infectante e resposta imunológica com perfil Th1, podem influenciar e perpetuar a inflamação gástrica contribuindo para o desenvolvimento de diferentes manifestações clínicas na infecção pelo H. pylori.

Patrón EPIYA en cepas de Helicobacter pylori CagA positivas en pacientes del Hospital Regional de Talca / EPIYA pattern in Helicobacter pylori CagA positive strains in patients of the Regional Hospital of Talca

BACKGROUND: The clinical outcome of Helicobacter pylori (H. pylori) infection has been related to the presence of CagA protein. This protein is highly polymorphic and its oncogenic ability depends on the number and type of tyrosine phosphorylation sites in the EPIYAs repeat sequences (A, B, C and D). AIM: To determine the EPIYA patterns of the CagA gene in H. pylori strains and its relationship with gastrointestinal pathology in infected patients of the Regional Hospital of Talca. MATERIAL AND METHODS: The strains were isolated from gastric biopsies and characterized by bacteriological and molecular methods. Gastrointestinal pathology was characterized by histopathological analysis. For the determination of the presence of the cagA gene and the EPIYAs standards, the conventional PCR technique was used. RESULTS: 138 DNA samples from H. pylori strains were analyzed. 92.0% (127/138) of the isolates carried the cagA gene, of which 66 (52.0%) corresponded to the EPIYA-ABC pattern, 43 (33.8%) to the EPIYA-ABCC pattern and 21 16.5%) to the EPIYA-ABCCC phosphorylation pattern. 50.4% (64/127) of cagA positive strains isolated from dyspeptic patients in the Maule region have more than two C sites of phosphorylation. The number of EPIYAs C motifs was associated with the presence of more severe histopathological damage in the gastric mucosa.

Infecciones y alteraciones epigenéticas en cáncer / Infections and epigenetic changes in cancer

La participación de mecanismos epigenéticos, junto con infecciones en etapas tempranas de la vida, moldean lesiones premalignas del cáncer, en particular el cáncer gástrico, uno de los tumores más frecuentes en Chile, Latinoamérica y el mundo. El principal objetivo de este artículo, como parte de la serie de revisiones en torno a mecanismos epigenéticos en el desarrollo de enfermedades crónicas, es actualizar el rol de alteraciones epigenéticas (i.e. metilación del ADN) en el contexto de la infección crónica por H. pylori en las etapas precursoras del cáncer gástrico. Las investigaciones desarrolladas en esta área permiten delinear desafíos e interrogantes, en los cuales la pediatría tiene un papel preponderante en el desarrollo de estrategias de prevención y detección temprana de esta enfermedad.

The role of epigenetics and infectious diseases at early stages of life influence pre-malignant lesions of cancer, in particular, gastric cancer, one of the most frequent tumours in Chile, Latin America, and worldwide. This article examines the role of H.pylori and epigenetic alterations (i.e. DNA methylation) at early stages of gastric cancer and proposes, from the paediatric point of view, strategies for prevention and early detection.

Mass Eradication of Helicobacter pylori to Prevent Gastric Cancer: Theoretical and Practical Considerations

Although the age-adjusted incidence of gastric cancer is declining, the absolute number of new cases of gastric cancer is increasing due to population growth and aging. An effective strategy is needed to prevent this deadly cancer. Among the available strategies, screen-and-treat for Helicobacter pylori infection appears to be the best approach to decrease cancer risk; however, implementation of this strategy on the population level requires a systematic approach. The program also must be integrated into national healthcare priorities to allow the limited resources to be most effectively allocated. Implementation will require adoption of an appropriate screening strategy, an efficient delivery system with a timely referral for a positive test, and standardized treatment regimens based on clinical efficacy, side effects, simplicity, duration, and cost. Within the population, there are subpopulations that vary in risk such that a "one size fits all" approach is unlikely to be ideal. Sensitivity analyses will be required to identify whether the programs can be utilized by heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations.

Análisis cualitativo del deterioro de la calidad del agua y la infección por Helicobacter pylori en una comunidad de alto riesgo de cáncer de estómago (Cauca, Colombia) / Qualitative analysis of water quality deterioration and infection by Helicobacter pylori in a community with high risk of stomach cancer (Cauca, Colombia)

Este estudio aborda aspectos de la salud ambiental de la población rural de Timbío (Cauca, Colombia) con relación al deterioro de la calidad del agua. La información se obtuvo mediante métodos de investigación participativa, relacionadas al manejo y uso del agua, fuentes de contaminación y percepción de la calidad del agua y su relación con la infección por Helicobacter pylori. Los resultados forman parte del análisis cualitativo de una primera fase de caracterización de la problemática hídrica y sanitaria y su relación con enfermedades infecciosas emergentes y soluciones comunes, llevada a cabo entre noviembre de 2013 y agosto de 2014. Los resultados de esta investigación se discuten desde un enfoque ecosistémico de la salud humana, que reconoce la complejidad de los conflictos ambientales relacionados con el recurso hídrico y su impacto en la salud de las poblaciones. A través de la metodología empleada, este estudio permitió conocer y visualizar los problemas prioritarios y las causas frecuentes de la contaminación del recurso hídrico, para postular algunas soluciones a través de una agenda compartida con los actores sociales.

This study looks at aspects of the environmental health of the rural population in Timbío (Cauca, Columbia) in relation to the deterioration of water quality. The information was obtained through participatory research methods exploring the management and use of water, the sources of pollution and the perception of water quality and its relation to Helicobacter pylori infection. The results are part of the qualitative analysis of a first research phase characterizing water and sanitation problems and their relation to emerging infectious diseases as well as possible solutions, which was carried out between November 2013 and August 2014. The results of this research are discussed from an ecosystemic approach to human health, recognizing the complexity of environmental conflicts related to water resources and their impacts on the health of populations. Through the methodology used, it is possible to detect and visualize the most urgent problems as well as frequent causes of contamination of water resources so as to propose solutions within a joint agenda of multiple social actors.

Genotipificación de los factores de virulencia vacA y cagA de Helicobacter pylori en individuos de dos regiones de Colombia con riesgo opuesto de cáncer gástrico / Genotyping of Helicobacter pylori virulence factors vacA and cagA in individuals from two regions in Colombia with opposing risk for gastric cancer

Introducción. La prevalencia de infección por Helicobacter pylori es alta en Colombia; en la zona andina las tasas de cáncer gástrico son altas mientras que en las zonas costeras son bajas. Los genotipos de H. pylori cagA positivo y vacA s1 y m1 se asocian con un mayor riesgo de cáncer gástrico. Objetivo. Determinar las diferencias en las frecuencias de los genotipos de H. pylori asociados a virulencia en dos regiones de Colombia con riesgo opuesto de cáncer gástrico. Materiales y métodos. Se analizaron 401 biopsias del antro gástrico provenientes de 401 individuos con diagnóstico de gastritis no atrófica, gastritis atrófica o metaplasia intestinal; 256 se obtuvieron en la zona de alto riesgo (Tunja y Bogotá) y, 145, en la zona de bajo riesgo (Barranquilla, Santa Marta y Cartagena). La genotipificación de los genes de virulencia cagA y vacA se hizo mediante reacción en cadena de la polimerasa (PCR). Resultados. No se observó diferencia en la frecuencia de infección por H. pylori entre las dos zonas (77,3 Vs . 77,9 %, p=no significativo, ns). La presencia de cagA fue mayor en la zona de bajo riesgo (77,9 Vs . 69,2 %, p=ns). El alelo vacA s1 también fue más prevalente en la zona de bajo riesgo (61,8 Vs . 72,0 %, p=ns). El alelo vacA m1 presentó mayor prevalencia en la zona de alto riesgo (57,2 Vs . 42,8 %, p=ns). La combinación cagA positivo s1m1 también fue más frecuente en la zona de bajo riesgo (48,9 Vs . 38,9 %, p=ns). Conclusiones. Las diferencias en el riesgo de cáncer gástrico en estas dos zonas no pueden explicarse por las diferencias en la prevalencia de infección por H. pylori o en la virulencia de las cepas circulantes.

Introduction: The overall prevalence of Helicobacter pylori infection is high in Colombia; however, in the country´s Andean region, gastric cancer rates far surpass those in coastal areas. Helicobacter pylori genotypes cagA positive and vacA s1 and m1 are associated with an increased risk of gastric cancer. Objective: To compare the distribution of H. pylori genotypes associated with virulence in two regions in Colombia with opposing risk for gastric cancer. Materials and methods: Four hundred and one gastric antral biopsies were obtained and analyzed from 401 individuals diagnosed with non-atrophic gastritis, atrophic gastritis and intestinal metaplasia: 256 came from the high-risk area cities of Tunja and Bogotá, and 145 from the low-risk area cities of Barranquilla, Santa Marta and Cartagena. Genotyping of virulence genes vacA and cagA was performed by PCR. Results: No difference was observed in the frequency of H. pylori infection between the two areas (77.3% vs 77.9 %, p=non significant, ns). The presence of cagA was higher in the low-risk area (77.9% vs. 69.2 %, p=ns). The vacA s1 allele was also more prevalent in the low-risk area (61.8 % vs 72.0 %, p=ns). The vacA m1 allele was more prevalent in the high-risk area (57.2 % vs 42.8 %, p=ns). The cagA positive s1m1 combination was also more frequent in the low-risk area (48.9% vs 38.9%, p=ns). Conclusions: The differences in the risk of gastric cancer in these two geographic areas cannot be explained by differences in the prevalence of infection by H. pylori or by differences in the virulence of circulating strains.

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 AND t(11;18)(q21;q21) TRANSLOCATION IN GASTRIC MALT LYMPHOMA / Helicobacter pylori e presença de translocação t(11;18)(q21;q21) em pacientes portadores de linfoma MALT gástrico

Context Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is clearly associated with Helicobacter pylori gastritis and can be cured with anti- H pylori therapy alone. The presence of t(11;18)(q21;q21) translocation is thought to predict a lower response rate to anti- H pylori treatment. Objectives To study the presence of t(11;18)(q21;q21) genetic translocation and its clinical impact in low-grade gastric MALT lymphoma Brazilian patients. Methods A consecutive series of eight patients with gastric MALT lymphoma were submitted to gastroscopy, endoscopic ultrasound, histopathological examination, H pylori search and RT-PCR-based methodology. All patients received anti-H pylori treatment. Eradicated patients were followed-up every 3-6 months for 2 years. Results Eight patients were studied. All patients had tumor involvement restricted to the mucosa or submucosa and seven patients had low-grade gastric MALT lymphoma. All infected patients achieved H pylori eradication. Histological tumor regression was observed in 5/7 (71%) of the low-grade gastric MALT lymphoma patients. The presence of t(11;18)(q21;q21) translocation was found in 4 (57%) of these patients; among them only two had histological tumor regression following H pylori eradication. Conclusions RT-PCR is a feasible and efficient method to detect t(11;18)(q21;q21) translocation, being carried out in routine molecular biology laboratories. The early detection of such translocation can be very helpful for better targeting the therapy to be applied to gastric MALT lymphoma patients. .

Contexto A patogênese do linfoma MALT (tecido linfoide associado à mucosa) gástrico, também conhecido como linfoma de zona marginal de células B, está claramente associada à gastrite por infecção pelo Helicobacter pylori e, a maioria desses tumores pode ser curada apenas com a erradicação da bactéria. A presença da translocação t(11;18)(q21;q21) tem sido identificada como a anomalia citogenética mais comum do linfoma MALT gástrico e sua presença pode prever uma menor taxa de resposta ao tratamento anti-H pylori. Objetivos Estudo da translocação genética t(11;18)(q21;q21) e seu impacto na evolução clínica de pacientes portadores de linfoma MALT gástrico de baixo grau. Métodos Uma série consecutiva de oito pacientes com linfoma MALT gástrico foi submetida à endoscopia digestiva, ultra-sonografia endoscópica, exame histopatológico, pesquisa do H pylori e metodologia rotineira de transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR) utilizando primers específicos para API2-MALT1. Todos os pacientes receberam tratamento anti-H pylori e retratamento, quando necessário. Após a erradicação, exames endoscópicos foram realizados a cada 3-6 meses durante 2 anos para acompanhamento da evolução do tumor. Resultados Foram estudados oito pacientes (seis mulheres, idade média: 57 anos). Todos apresentavam à ecoendoscopia envolvimento tumoral restrito à mucosa ou submucosa com aparência endoscópica variável. A histologia mostrou que sete pacientes tinham linfoma MALT gástrico de baixo grau e um de alto grau. A erradicação do H pylori foi obtida em todos os pacientes, embora a bactéria não tenha sido identificada em um deles. Foi observada regressão histológica ...

Infecciones por bacterias poco comunes y oncogénesis bacteriana / [Infections due to unusual bacteria and bacterial oncogenesis].

The recovery of an unusual organism in the clinical microbiology laboratory may be an indicator of an immunological abnormality in the patient. For instance, an important relationship between Clostridium septicum and colon carcinoma as well as between leukemia or lymphoma with species frequently considered contaminants (Bacillus spp., Corynebacterium spp.) or others rarely isolated from different contexts (Capnocytophaga spp.) were described. Some bacteria are almost exclusively isolated from AIDS patients (Rhodococcus equi). Campylobacter spp., Aeromonas spp., group G and mitis group streptococci were more frequently isolated in individuals suffering from any type of cancer than in other patients. Furthermore, some other bacteria can be considered markers of an undetected cancer that can be found mostly in neutropenic patients rather than in immunologically normal individuals. Possible mechanisms of bacterial oncogenesis include a modification of the inflammatory response, antigen-derived lymphoproliferation, and induction of hormones that increase epithelial cell proliferation. Typical examples of the above are: gastric adenocarcinoma induced by Helicobacter pylori, the association between group bovis bacteremia and colon carcinoma and the mucosa-associated lymphoid tissue (MALT) related to Helicobacter species (gastric MALT) and Chlamydophila spp. (ocular MALT). Isolation of any of these pathogens should require a thorough search for possible malignant diseases.

Study of the cytoxin-associated gene A [CagA Gene] in helicobacter pylori using gastric biopsies of Iraqi patients

The Helicobacter pylori CagA gene is a major virulence factor that plays an important role in gastric pathologies. The size variation of CagA gene, which is dependent on the 3' repeat region, contains one or more Glu-Pro-Ile-Tyr-Ala [EPIYA] motifs and CagA multimerization [CM] motifs. Four segments flanking the EPIYA motifs, EPIYA A, B, C, or D, were reported to play a crucial role in the pathogenesis of H. pylori infection. The aim was to determine the roles of EPIYA segments and CM motifs in gastroduodenal pathogenesis in an Iraqi population. Gastric biopsies were collected from 210 patients with gastritis, duodenal ulcer [DU], gastric ulcer [GU], and gastric cancer [GC]. The EPIYA motif genotyping was determined by polymerase chain reaction and sequencing. The differences in age, gender, and CagA EPIYA motifs of H. pylori between GC, DU, GU and gastritis patients were analyzed using a 2-test. A total of 22 [45.8%] strains had three copies of EPIYA [ABC type], 2 [4.16%] had four copies [ABCC type], 6 [12.7%] had five copies [ABCCC type], 13 [27.08%] had two copies [AB type], 3 [6.25%] had the BC, and 2 [4.17%] had AC motif. The alignment of the deduced protein sequences confirmed that there were no East Asian type EPIYA-D sequences in Iraqi strains. A significant association was found between increase in number of EPIYA-C motifs and GU [P 0.01] compared with gastritis. The structure of the 3' region of the CagA gene in Iraqi strains was Western type with a variable number of EPIYA-C and CM motifs. A significant association was found between increase in number of EPIYA-C motifs and GU compared with gastritis indicating predictive association with the severity of the disease. The GenBank accession numbers for the partial CagA nucleotide sequences determined in this study are JX164093-JX164112

Effect of Xeroderma pigmentosum complementation group F polymorphisms and H.pylori infection on the risk of gastric cancer

We conducted a case-control study by genotyping three potential functional SNPs to assess the association of Xeroderma pigmentosum complementation group F [XPF] polymorphisms with gastric cancer susceptibility, and role of XPF polymorphisms in combination with H.pylori infection in the risk of gastric cancer. A hospital case-control study was conducted. A total of 331 patients with gastric cancer and 355 controls were collected. Three SNPs of XPF, XPF rs180067, rs1799801 and rs2276466, were genotyped by Taqman real-time PCR method with a 7900 HT sequence detector system. The gastric cancer patients were more likely to have smoking habit, a family history of cancer and H.pylori infection. We did not find the significant difference in the genotype distributions of XPF rs180067, rs1799801 and rs2276466 between cases and controls. Multivariate logistic analysis showed a non-significant decreased risk in patients carrying rs180067 G allele, rs1799801 T allele or rs2276466 T allele genotypes. The stratification by H.pylori infection was not significantly different in polymorphisms of XPF rs180067, rs1799801 and rs2276466. There was no evidence that polymorphisms in rs180067, rs1799801 and rs2276466 significantly affect the risk of gastric cancer. Further large sample size studies are strongly needed to validate their association

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.