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ObjectiveTo investigate the diagnostic and prognostic role of gastric fluid DNA (gfDNA) in gasric cancer (GC) patients and controls submitted to upper digestive endoscopy.DesignThe concentration of gfDNA was evaluated in 941 samples, including subjects with normal gastric mucosa (n = 10), peptic diseases (n = 596), pre-neoplastic conditions (n = 99), and cancer (n = 236). gfDNA levels were evaluated according to age, gender, BMI, gastric fluid’s pH, use of proton-pump inhibitors, GC tumor subtypes, histological grades, clinical stages, and disease progression/outcome.ResultsIn the non-cancer group, we observed that gfDNA levels are increased in women as compared to men (p=7.44e-4). Remarkably, gfDNA levels are increased in GC patients as compared to non-GC (normal + peptic diseases, p=5.67e-13) and in GC versus pre-neoplastic disease (p=1.53e-6). Similar differences were also seen when more advanced tumors (T3) were compared to early stages (T2 and below) (p=5.97-4). Moreover, our results suggest the prognostic value of gfDNA as GC-patients with higher gfDNA concentrations (-3), which parallels with better disease-free survival (p= 0.014).ConclusionThese findings highlight the significance of collecting and studying stomach fluids from gastric cancer patients and reveals the potential impact of this approach as well as its diagnostic and prognostic value for disease management.What is already known on this topic-The DNA contained in biofluids that are in direct contact with tumor lesions is a valuable source of information for cancer diagnosis treatment.-Gastric fluids are in direct contact with gastric cancer (GC) lesions and immune cell infiltrates and may be a reliable source of biomarkers with multiple applications.-Liquid biopsies are usually based on the detection and analysis of cell-free DNA found in the plasma, urine or saliva.-Studies of the DNA present in the gastric fluids of patients (gfDNA), collected during routine endoscopy, are scarce and limited to assessing mutation profiles. It’s diagnostic and prognostic potential has not been studied so far.What this study adds-An analysis of gfDNA concentrations in 941 samples revealed increased DNA levels in GC patients as compared to non-GC individuals.-When tumor stages were compared, gfDNA levels are elevated in more advanced disease.-For GC subjects, increased gfDNA was positively associated with immune cell infiltrates and reduced tumor recurrence, suggesting this to be an informative and very low-cost prognostic marker.How this study might affect research, practice or policy-gfDNA collected during routine upper digestive diagnostic endoscopy can be used as an additional and very simple biomarker useful during patient follow-up and to determine cancer prognosis.-In the future gfDNA assessment has the potential to contribute to a range of applications, such as monitoring treatment response, indicating immune cell infiltration and may potentially indicate cases with progressive disease non-responsive to chemotherapy.

Background Intestinal and diffuse gastric adenocarcinomas differ in clinical, epidemiological and molecular features. However, most of the concepts related to the intestinal-type are translated to gastric adenocarcinoma in general; thus, the peculiarities of the diffuse-type are underappreciated. Results Besides its growing importance, there are many gaps about the diffuse-type carcinogenesis and, as a result, its epidemiologic and pathogenetic features remain poorly understood. Conclusions Alternative hypotheses to explain these features are discussed, including the role of the gastric microbiota, medical therapies, and modifications in the stomach’s microenvironment.

Considering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo antiinflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7) showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA‑MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.

The presence of deleterious variants of dihydropyrimidine-dehydrogenase gene (DPYD) is associated with 5-Fluorouracil toxicity. Most of the data are based on findings in Caucasian populations. The variant Y186C (rs115232898) is found almost exclusively in African populations and is related to low DPD function. Its prevalence may vary among African subpopulations and in African Americans. There is no information in other populations. Brazil has the biggest African population outside Africa. We studied for the first time the frequency of this mutation in African Brazilians. We amplified exon 6 of DPYD extracted from genomic DNA of 79 healthy volunteers of genetically defined African ancestry from Southeast Brazil and 36 self-reported African descendants from Northeast Brazil in order to determine the prevalence of the variant Y186C in Brazilians of African ancestry. The variant Y186C was found in heterozygosity in two samples from Southeast (2.53%) and one from Northeast (2.77%) Brazil. Overall, the prevalence of this mutation in the 115 African Brazilians was 2.6%. The variant Y186C is prevalent among Brazilians of African ancestry and should be taken in account in targeted genotyping for fluoropyrimidine risk variants.

BACKGROUND: 13C-urea breath test (UBT) is the gold-standard, noninvasive method for H. pylori diagnosis. However, there is no uniform standardization of the test. This situation can be unpractical for laboratories running with two or more devices. OBJECTIVE: To perform a prospective comparison validation study of UBT employing one validated protocol for two different devices: BreathID Hp Lab System® (Exalenz Bioscience Ltd, Israel), here called device A and IRIS-Doc2® (Wagner Analysen-Technik, Germany, now Mayoly Spindler Group, France), here called device B, in the diagnosis of H. pylori infection. METHODS: A total of 518 consecutive patients (365 females, 153 males, mean age 53 years) referred for UBT were included. All patients received device A protocol as follow: after at least one hour fasting, patients filled two bags prior to the test, then ingested an aqueous solution containing 75 mg of 13C-urea with a 4.0 g citric acid powder and filled another two bags 15 min after ingesting the test solution. One pair of breath sample bags (before and after ingestion) was analyzed by the two different devices. A delta over baseline (DOB) ≥5‰ indicated H. pylori infection. Statistics: Wilcoxon test, kappa coefficient with 95% CI, Wilson’s method. RESULTS: Considering the device A protocol as the gold standard, its comparison with device B showed a sensitivity of 99.3% (95% CI: 96.3-99.9) and a specificity of 98.9% (95% CI: 97.3-99.6). Kappa coefficient was 0.976 (95% IC: 0.956-0.997). CONCLUSION: Correlation between the two devices was excellent and supports a uniform standardization of UBT.

Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach's high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.

Helicobacter pylori is the main etiological agent of all malignant tumors caused by an infectious disease. It is a major, at times dominant, factor in the pathogenesis of a large spectrum of diseases such as acute and chronic gastritis, gastric and duodenal ulcers, gastric carcinoma, and lymphoma. Epidemiological and experimental studies suggest that H. pylori chronic infection may be related to different extragastric diseases, including colorectal neoplasms. This concise review aims to explore the association of H. pylori infection with colorectal cancer and adenoma, including the recent epidemiological findings, the diagnostic methods employed to detect H. pylori and virulent factors, and the potentially involved mechanisms. Furthermore, is attempted to establish the current data integration for causal inference using the Bradford-Hill causality criteria. The weak, although global, strength of the epidemiological positive association between H. pylori infection and colonic neoplasms associated to new mechanisms postulated to explain this interaction, including intestinal dysbiosis, should stimulate future studies. Prospective confirmatory studies to establish the role of H. pylori eradication in the process of carcinogenic transformation of the colonic epithelium may define its eventual role in the treatment and prevention of colonic neoplasms.

This review summarizes the recent knowledge on the epidemiology of Helicobacter pylori and the potential modes of transmission. In addition to English language publications, the authors have included original full-text publications from Russia and Latin America published in the original languages. High H pylori prevalence has been reported in Russia, Jordan, Iran, China, and Latin American countries as well as in Arctic populations in Canada. Indigenous inhabitants in the Arctic were found to be infected substantially more frequently than non-indigenous inhabitants. In Amsterdam, the Netherlands, the ethnic minority groups were at a significantly higher risk of being H pylori seropositive compared to the Dutch population. For the first time, data on the prevalence from Armenia have been published indicating 41.5% H pylori prevalence. Convincing evidence on the decline of H pylori prevalence in Southeast Hungary and Taiwan was published. A study from Chile suggested high infection rates in newborns during the first month after birth. Two meta-analyses covered the potential correlation between H pylori and periodontal diseases, therefore addressing the potential oro-oral transmission rates. Periodontal disease was found to be more prevalent in H pylori-infected subjects. Other studies addressed the potential role of drinking water and food products as well as socioeconomic factors in transmitting the infection. Several studies in Asia addressed annual reinfection rates of H pylori, ranging from 1.5% in China to 3.1% in Korea. Finally, a review was published on the current evidence and future perspective of analysing H pylori in ancient human remains by a metagenomic approach.

BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries. RESUMO CONTEXTO: O Transplante de microbiota fecal (TMF) é uma importante opção terapêutica para a infecção recorrente ou refratária pelo Clostridioides difficile, sendo método seguro e eficaz. Resultados iniciais sugerem que o TMF também desempenha papel relevante em outras afecções cuja patogênese envolve a alteração da microbiota intestinal. No entanto, seu uso sistematizado é pouco difundido, especialmente no Brasil. Na última década, surgiram múltiplos relatos e séries de casos utilizando diferentes protocolos para o TMF, sem padronização de métodos e com taxas de resposta variáveis. No Brasil, poucos casos isolados de TMF foram relatados sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). OBJETIVO: O principal objetivo deste estudo foi descrever o processo de implantação de um CTMF com banco de fezes, em hospital universitário brasileiro, para tratamento de infecção recorrente e refratária pelo C. difficile. MÉTODOS: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o Food and Drug Administration, Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. RESULTADOS: Foi estabelecida toda uma plataforma envolvida na estruturação de um centro de transplante com fezes congeladas. Determinou-se os critérios para seleção de doadores, processamento e armazenamento de amostras, manejo dos receptores antes e após o procedimento, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção dos doadores foi conduzida em três etapas: pré-triagem, avaliação clínica e exames laboratoriais. Boa parte dos candidatos foram excluídos na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (IMC ≥25 kg/m2) e distúrbios gastrointestinais crônicos. Quatro dos 134 candidatos foram selecionados após a triagem completa, com taxa de detecção de doadores de 3%. CONCLUSÃO: A implantação de um CTMF, inédito no nosso meio, possibilita o acesso de pacientes com infecção recorrente e refratária pelo C. difficile a tratamento inovador, seguro, com elevada taxa de sucesso e pouco disponível no Brasil. A seleção apropriada de doadores qualificados é vital no processo de implantação de um CTMF. A avaliação clínica rigorosa dos doadores permitiu o uso racional de recursos para realização de exames laboratoriais. Um CTMF possibilita tratamento sob demanda, em maior escala, menos personalizados, com mais segurança e rastreabilidade. Este protocolo fornece subsídios para a realização de TMF em países emergentes.

Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings.

Background - Antimicrobial resistance is the major factor leading to eradication failure in H. pylori treatment. Molecular tests are useful to detect genetic mutations predictive of clarithromycin and fluoroquinolones resistance. Knowledge of the local prevalence rate of resistance is important to define the best recommended treatment. Objective - To assess the prevalence of primary resistance of H. pylori to clarithromycin and fluoroquinolones, using a molecular test, in a Southeastern urban Brazilian population. Methods - A total of 72 H. pylori seropositive patients [65% female, mean age 39 (19-73) years] never treated before for this infection were studied. All patients underwent gastroscopy in addition to antrum and corpus biopsies and molecular test GenoType HelicoDR (Hain Life Science, Germany) to detect H. pylori and point mutations in genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from biopsy samples, a multiplex amplification with biotinylated primers and a reverse hybridization. The most frequent point mutations involved in resistance to the two antibiotics were evaluated. Results - Resistance to clarithromycin was detected in nine (12.5%) patients and to fluoroquinolones in eight (11.1%) patients. The point mutation A2147G was the most common (77.8%) among resistant strains to clarithromycin. In 50% of the resistant strains to fluoroquinolones, the mutant codon couldn't be identified. Conclusion - The resistance rates to clarithromycin and fluorquinolones in a large urban population in the Southeast of Brazil were acceptable, suggesting that these drugs remain appropriate options to first and second-line of H. pylori treatment. The molecular test represents an adequate diagnostic tool for monitoring H. pylori resistance. RESUMO Contexto - A resistência aos antimicrobianos é o principal fator associado à falha terapêutica no tratamento do H. pylori. Testes moleculares são úteis na detecção das mutações genéticas associadas ao desenvolvimento de resistência à claritromicina e fluorquinolonas. O conhecimento da taxa de prevalência local de resistência é importante na definição do melhor esquema terapêutico. Objetivo - Estimar a prevalência de resistência primária do H. pylori à claritromicina e fluorquinolonas, empregando-se um teste molecular, em uma capital do Sudeste do Brasil. Métodos - Setenta e dois pacientes com sorologia positiva para H. pylori [65% mulheres, idade média 39 (19-73) anos], nunca tratados previamente para essa infecção, foram selecionados. Todos os pacientes submeteram-se à endoscopia digestiva com biópsias de antro e corpo e realização do teste molecular GenoType HelicoDR (Hain Life Science, Alemanha) para a detecção do H. pylori e das mutações pontuais dos genes responsáveis pela resistência à claritromicina e fluorquinolonas. O procedimento molecular constituía-se de três etapas: extração do DNA a partir das amostras endoscópicas, amplificação multiplex com primers biotinilados e hibridização reversa. As mutações pontuais mais frequentemente envolvidas com resistência aos dois antibióticos foram avaliadas. Resultados - Resistência à claritromicina foi detectada em nove (12,5%) pacientes e às fluorquinolonas em oito (11,1%) pacientes. A mutação pontual A2147G foi a mais comum (77,8%) entre as cepas resistentes à claritromicina. Em 50% das cepas resistentes à fluorquinolonas, o códon mutante não pôde ser identificado. Conclusão - As taxas de resistência à claritromicina (12,5%) e às fluorquinolonas (11,1%), em uma importante capital do Sudeste do Brasil, mostraram índices aceitáveis, sugerindo que essas drogas permanecem opções apropriadas para o tratamento de primeira e segunda linha do H. pylori. O teste molecular constitui uma ferramenta diagnóstica adequada para monitorar a resistência do H. pylori.

Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next-generation deep sequencing of TP53-a highly mutated and informative gene in GAC-to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash-GW). We evaluated their potential to reveal tumor-derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon-capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post-treatment (196 samples), with high vertical coverage >8,000×. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW- (15.2%) and 6/46 PL-samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW-exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene-panel designed for this malignancy.

This edition contemplates two articles about different aspects on Helicobacter pylori (HP) infection: the daily medical practice challenges on its management and the search for comprehension of still obscure points among functional interaction of the infection and human immune system, on the development of gastroduodenal diseases.

OBJECTIVE: The 13C-urea breath test is the main non-invasive test for the diagnosis of Helicobacter pylori infection. The availability of this test throughout the country is limited, mainly due to the difficulty in obtaining the labeled isotope from abroad. Recently, researchers from the Nuclear Energy Center in Agriculture at the University of São Paulo (CENA/USP) succeeded in synthesizing 13C-enriched urea for Helicobacter pylori diagnosis. The aim of the study was to compare the performance of the 13C-urea breath test using 13C-urea acquired abroad with that of a test using 13C-urea synthesized in Brazil. METHOD: Sixty-four dyspeptic patients participated in the study (24 men and 40 women). Initially, the patients performed the 13C-urea breath test using the imported substrate (Euriso-Top, France). Seven to fourteen days later, all the patients repeated the test using the Brazilian substrate. The samples from both examinations were processed in an infrared isotope analyzer (IRIS, Wagner Analisen Technik, Germany), and all delta over baseline (DOB) [%] values above four were considered positive results. RESULTS: Twenty-seven patients (42%) exhibited negative results for Helicobacter pylori infection, and thirty-seven patients (58%) exhibited positive results when tested using the foreign substrate (gold standard). There was a 100% concordance regarding the presence or absence of infection when the gold standard results were compared with those obtained using the Brazilian substrate. CONCLUSIONS: Similar performance in the diagnosis of Helicobacter pylori infection was demonstrated when using the 13C-urea breath test with the Brazilian 13C-urea substrate and the test with the substrate produced abroad. This validation represents an important step toward increasing the availability of the 13C-urea breath test throughout the country, which will have a positive influence on the management of Helicobacter pylori infection.

Os avanços significativos ocorridos desde o III Consenso Brasileiro sobre H. pylori realizado em 2012, em Bento Gonçalves, justificam este quarto consenso. O evento foi organizado pelo Núcleo Brasileiro para Estudo do Helicobacter e Microbiota, associação vinculada à Federação Brasileira de Gastroenterologia, tendo sido realizado novamente em Bento Gonçalves, RS, nos dias 25 a 27 de agosto de 2017. Participaram 26 delegados provenientes das cinco regiões brasileiras incluindo gastroenterologistas, endoscopistas e patologistas, além de um convidado internacional (EUA). Os participantes foram convidados pelo conhecimento e contribuição ao estudo da infecção por H. pylori. O encontro buscou rever diferentes aspectos relacionados ao tratamento da infecção, suas inter-relações com a dispepsia, microbiota e outras afecções, com ênfase especial ao câncer gástrico, além de promover uma reavaliação dos aspectos epidemiológicos e diagnósticos desta infecção. Os participantes foram alocados em quatro grupos, a saber: 1) Epidemiologia e diagnóstico, 2) Dispepsia, microbiota e outras afecções, 3) Neoplasias gástricas, e 4) Tratamento. Previamente à reunião do Consenso, os participantes receberam um tema a ser discutido e elaboraram texto com uma revisão recente da literatura, contendo uma assertiva de sua revisão. Todas as assertivas foram avaliadas em dois turnos de votação. Inicialmente, cada participante apresentava sua compilação e assertiva ao seu grupo, para eventuais modificações e votação. Posteriormente, em uma segunda votação, agora em sessão plenária, as assertivas eram novamente votadas e eventualmente modificadas. As votações obedeceram a cinco alternativas: 1) concorda fortemente; 2) concorda com reservas; 3) indeciso; 4) discorda e; 5) discorda fortemente. O índice de consenso adotado para cada afirmativa foi de 80% dos votantes respondendo que concorda fortemente ou concorda com reservas. As recomendações aqui apresentadas foram baseadas nas evidências científicas mais relevantes para o manuseio da infecção por H. pylori na população adulta no Brasil. Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil. ASSUMPÇÃO, P. P. Universidade Federal do Pará

Background Gastric carcinoma (GC) is the third leading cause of death among malignant tumors worldwide, causing approximately 900,000 deaths/year. Changes in oncogenes that encode tyrosine kinase receptors play an important role in the pathogenesis of GC. MET gene is a proto-oncogene that encodes a tyrosine kinase receptor c-MET and it is required for embryonic development and tissue repair. The hepatocyte growth factor (HGF) is the only known ligand for c-Met receptor. The MET oncogene activation suppresses apoptosis and promotes the survival, proliferation, migration, differentiation and angiogenesis of cells. Among the angiogenic factors, VEGF is the main regulator. Its biological function includes the promotion of endothelial cells mitosis to stimulate cells proliferation. These biomarkers expression in GC is relatively recent and population-based studies are required to define the expression pattern. The aim of this study was to determine qPCR technical standardization to evaluate quantitatively, in paraffin tissue samples, the presence of gene 23 expression of the MET, HGF and VEGF in diffuse and intestinal GC types. Methods Twenty GC patients were studied, 10 patients were intestinal-type GC (average age 72.1 years) and 10 diffuse-type (average age 50.1 years). In all patients, tissue samples were analyzed from the tumor and distant areas of the tumor tissue. The relative expressions of the tumor markers c-Met, HGF and VEGF were performed by qPCR technique by comparing tumor and non-tumoral samples and they were normalized with the GAPDH constitutive gene. Statistical analysis was performed through T-test. Results For c-Met, 18/20 (90%) patients expressed the marker and 9/20 (45%) overexpressed this gene, in which three were intestinal-type GC and six were diffuse-type GC. For HGF, only 7/20 (35%) patients expressed this gene and it was overexpressed in 4/20 (20%), in which two were intestinal-type GC and two were diffuse-type GC. For VEGF, 20/20 (100%) patients expressed this marker and in 12/20 (60%) were observed overexpression, in which eight patients had diffuse-type GC and four had intestinal-type GC. Conclusions qPCR technique was standardized and suitable for expression analysis of the three biomarkers using paraffin embedded tissue samples. Further studies should be carried out to characterize the expression pattern of these biomarkers in GC in the Brazilian population.

In most South American countries, Helicobacter pylori infection prevalence is high, affecting over 70% in populations with precarious living conditions. It is worth pointing out that there is initial evidence of a decline in prevalence of H. pylori infection at least in some more privileged fragments of the population. It is estimated that gastric cancer, the main clinical sequela of H. pylori infection, has an average incidence rate of 12.4 cases per 100,000 inhabitants (8.4 cases per 100,000 inhabitants for women and 17.3 cases per 100,000 for men) in the region. Classical triple therapy [proton pump inhibitor (PPI), amoxicillin and clarithromycin] is still the most used regimen with eradication rates around 80%. The rates of resistance to clarithromycin range from 2 to 24%. Recurrence rates of the infection are described as 2.9% in Argentina, 4.2% in Chile, 2-7% in Brazil, and 11.5% in a trial involving 7 Latin American countries. After failure of clarithromycin-containing regimens, second- and third-line therapies using PPI, amoxicillin and levofloxacin and quadruple therapy with PPI, colloidal bismuth subcitrate, tetracycline hydrochloride and metronidazole are recommended. Due to the high rates of primary resistance to metronidazole in the Latin American countries, use of the quadruple therapy, replacing metronidazole for furazolidone, is a frequent option. Rescue triple therapy regimens using furazolidone in association with levofloxacin and PPI have also been used. Most recommended rescue therapies reach eradication rates close to 80%.

OBJETIVO: avaliar a eficácia da complementação por coagulação com plasma de argônio para reduzir a taxa de neoplasia residual ou recorrente após ressecção endoscópica completa fragmentada de grandes adenomas sésseis colorretais. MÉTODOS: critérios de inclusão: pacientes com grandes adenomas colorretais sésseis, > 20mm, sem sinais morfológicos de infiltração profunda, submetidos à ressecção endoscópica completa fragmentada estudada com cromoendoscopia e magnificação de imagens. Os pacientes foram randomizados em dois grupos: grupo 1 - nenhum procedimento adicional e, grupo 2 - complementação por coagulação com plasma de argônio. O seguimento por colonoscopia foi realizado em três, seis e 12 meses de pós-operatório. Foi avaliada a taxa de neoplasia residual ou recidiva local. RESULTADOS: foram incluídos no estudo um total de 21 lesões. Onze lesões no grupo 1 e dez no grupo 2. Ocorreram duas neoplasias residuais ou recorrências locais em cada grupo, detectadas em três meses de acompanhamento. CONCLUSÃO: a complementação por coagulação com plasma de argônio após uma aparente ressecção endoscópica completa em fragmentos de grandes adenomas sésseis colorretais não parece reduzir a ocorrência de lesão adenomatosa residual ou recidiva local. OBJECTIVE: To evaluate the efficacy of complement by argon plasma coagulation to reduce the rate of residual or recurrent tumor after complete endoscopic piecemeal resection of large sessile colorectal adenomas. METHODS: Inclusion criteria: patients with large sessile colorectal adenomas (e" 20 mm), without morphological signs of deep infiltration, submitted to complete endoscopic piecemeal resection studied with chromoendoscopy and magnification of images. Patients were randomized into two groups: group 1 - no additional procedure, and group 2 - complementation by argon plasma coagulation. follow-up colonoscopy was performed at three, six and 12 months postoperatively. We evaluated the rate of local recurrence or residual malignancy. RESULTS: The study included 21 patients, eleven in group 1 and ten in group 2. There were two local recurrences or residual tumors in each group, detected at three months follow-up. CONCLUSION: Complementation by argon plasma coagulation after apparent complete endoscopic piecemeal resection of large sessile colorectal adenomas does not seem to reduce the occurrence of residual adenomatous lesions or local recurrence.

Background In cystic fibrosis (CF) patients a duodenal impaired bicarbonate secretion and unbuffered gastric acid are always described and the development of duodenal ulceration is uncommon (CF paradox). Helicobacter pylori (HP) infection is the main cause for duodenal ulceration and its prevalence in CF patients is controversial. Aim The objective of this study is to evaluate HP prevalence, gastric histology, and duodenal ulceration in adult FC patients. Methods 32 adult CF patients were submitted to 13 C-urea breath test and serum immunoblotting test for HP diagnosis. Among them, 20 patients were submitted to endoscopy. Results 19/32 (68%) patients showed positive serology. Endoscopy showed erosive duodenitis (15%), and duodenal ulcer scar in 10%. On duodenal histology, 94.5%, showed active inflammation and 66.7% gastric metaplasia. Conclusion HP infection prevalence in adult CF patients was similar to that of general Brazilian population. CF patients have all the duodenal spectrum of alterations, including duodenal ulcer. CF paradox may not exist.

Transnasal endoscopy (TNE) has been proposed to screen for esophageal squamous cell cancer (ESCC) in Asia. This study aimed to assess the feasibility and tolerance of Brazilian patients to undergo unsedated TNE for screening, the prevalence of ESCC in this population, and the effectiveness of white-light endoscopy (WLE) and digital chromoendoscopy [flexible spectral imaging color enhancement (FICE)] to diagnose esophageal neoplasia.This was a diagnostic test study that enrolled patients with head and neck squamous cell cancer (HNSCC) referred to ESCC screening. Patients' tolerance was rated by a numeric pain intensity scale. Interventions included unsedated TNE with WLE and FICE examination of the esophagus, in a tandem manner with blinded operators, followed by lugol chromoscopy. Performance of WLE and FICE for neoplasia detection was compared with the reference standard (lugol chromoscopy plus histology).A total of 106 patients were recruited. TNE was feasible in 99.1%, and 92% of the patients rated the discomfort as absent or minimal. Thirteen ESCC were detected (12.3%), with 10 early cancers (77%). The tests showed an excellent performance and there was no difference between WLE (sensitivity 92.3%, specificity 98.9%, accuracy 98.1%, area under curve 0.995) and FICE (sensitivity 100%, specificity 98.9%, accuracy 99%, area under curve 0.956) for esophageal neoplasia detection.Unsedated TNE is a feasible, well accepted, and efficient diagnostic tool for the screening of ESCC. The elevated rate of esophageal neoplasia strengthens the recommendations to screen patients with HNSCC. The yields of WLE and FICE were similar for ESCC detection.

BACKGROUND A liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation of endogenous uracil (U) and dihydrouracil (UH2) was developed and tested in a Brazilian population of patients with gastrointestinal cancer previously exposed to 5-fluorouracil (5FU). METHODS The analytes were extracted by a liquid-liquid method using 5-clorouracil as internal standard. The separation was performed on a reversed-phase XTerra C18 column with a mobile phase composed of methanol and aqueous 0.1% ammonium hydroxide (15:85). Mass spectrometry detection was carried out using negative electrospray ionization and selected reaction monitoring. Bovine serum albumin was employed as an alternative matrix to prepare the calibration standards, aiming to avoid the measurement of physiologic U and UH2. Calibration curves were constructed over the range of 5-200 ng/mL for U and 10-500 ng/mL for UH2. RESULTS The mean RSD values in the intrarun precision were 6.5% and 10.0% and in the interrun precision were 7.8% and 9.0% for U and UH2, respectively. The mean accuracy values were within the range of 90%-110% for both analytes. The analytes were stable in plasma under different conditions of temperature and time. The validated method was successfully applied to determine the plasma concentrations of U and UH2 in patients with gastrointestinal cancer (n = 32) previously treated with 5FU and for whom clinical toxicity was well documented. U concentrations varied from 21.8 to 56.6 ng/mL, whereas UH2 concentrations varied from 57.7 to 271.5 ng/mL. UH2/U ratio ranged from 1.56 to 6.18. CONCLUSIONS The method has proved to provide a quick, reliable, and reproducible quantitation of the plasma concentrations of U and its metabolite UH2. The UH2/U ratios did not discriminate patients previously exposed to 5FU with and without severe toxicities, possibly due to the small sample. Further studies in a larger population are desirable.

Aims The objective of this work was to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), after their intraperitoneal administration in male and female mice. Main methods After single administration of free CDDP (5,10,and 20 mg/kg) or SpHL-CDDP (7,12,30,45 and 80 mg/kg), the body weight was recorded and the LD 50 was calculated. Blood samples were collected for biochemical and hematological analysis. Kidneys, liver, spleen and bone marrow were removed to histopathological examination. Key findings Mice treated with high doses of free CDDP showed a greater loss of body weight and more delayed recovery time than those treated with SpHL-CDDP. The LD 50 values for SpHL-CDDP treatment for male and female mice groups were 2.7 and 3.2 fold higher, respectively, than that obtained for free CDDP. The red and white blood cells counts and quantification of hemoglobin and hematocrit presented no change upon administration of SpHL-CDDP treatment. Free CDDP treatment, however, did lead to an appearance of mild anemia and a reduction in total white blood cell counts. As regards nephrotoxicity, it was observed that free CDDP treatment caused pronounced alterations in the blood urea and creatinine levels of mice. In contrast, these parameters were slightly altered only after SpHL-CDDP treatment at a dose of 30 mg/kg. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed no morphological alteration. Concerning hepatotoxicity, no histopathological alteration was observed after both treatments. Significance These findings reveal that SpHL-CDDP can eliminate CDDP-induced toxicity and is thus a promising candidate for intraperitoneal chemotherapy.

Failure of Helicobacter pylori treatment is a growing problem in daily practice. Aim: To evaluate the efficacy of two new regimes as second-line options in a randomized and prospective study. Methods: Patients in whom a first eradication regime containing clarithromycin had failed were included. After performing gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg (two tablets) of furazolidone administered once daily for 10 days (RLF) or the combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate, 100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for 10 days (RBDF). Clinical examinations and new UBT were performed 60 days after therapy. Results: Sixty patients were included (mean age, 46 years, 57% females). Two patients were excluded: one because of adverse effects and another as a result of protocol violation. Compliance was similar in both groups (90% took all medications correctly). Side-effects (96% mild) were observed in 87% of the patients and were comparable between groups, except diarrhea, which was more frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95% confidence interval (CI): 62–93%) in the RLF group and 83% (95% CI: 68–97%) in the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65–95%) in the RLF group and 82% (95% CI: 67–96%) in the RBDF group (p= 1.0). Conclusions: Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes.

Esophagogastroduodenoscopy (EGD) is frequently requested for patients with gastroesophageal reflux symptoms. When the distal esophagus mucosa shows no erosions, questions are posed: (1) Does the esophageal biopsy contribute to confirm reflux as the cause of the symptoms? (2) Do minimum endoscopic changes have correspondence with histology? A total of 1901 patients were prospectively interviewed by a standard questionnaire to obtain a clinical diagnosis of gastroesophageal reflux disease (GERD); 150 patients (98 males; median age, 42 years) with clinical manifestations of GERD and an intact esophageal mucosa were assigned to nonerosive reflux disease (NERD) patients, and 49 patients (24 males; median age, 46 years) with no complaints of GERD were assigned to Controls. The EGD images were documented on tape. Four biopsies were performed at the distal esophagus. Experienced endoscopists and pathologists examined twice, at different times and separately, the respective endoscopic and histological examinations. For all comparisons, kappa (K) match, 95% confidence interval, and the P value were determined. In NERD patients, the match between endoscopic and histological findings as to the aspect of the mucosa of the esophagus was poor (K = 0.08). EGD showed 17.2% sensitivity and 90.2% specificity, whereas the esophagus histological study showed 39% sensitivity and 73% specificity. NERD patients presented a greater frequency of esophagitis than Controls (38.6% vs. 22.4%), but this value was nonsignificant (P = 0.023). Agreement between patient symptoms or endoscopic findings and histological diagnosis is poor; therefore, histology of the esophageal mucosa as a diagnostic test of NERD demonstrates low sensitivity and does not justify routine use.

It has been suggested that obesity is associated with an altered rate of gastric emptying. The objective of the present study was to determine whether the rates of solid and semi-solid gastric emptying differ between morbidly obese patients and lean subjects. The Gastric-emptying time (GET) of solid and semi-solid meals were compared between lean healthy subjects and morbidly obese patients enrolled in two previously published studies. GET of solid and semi-solid meals was measured using the 13C-octanoic acid breath test and 13C-acetic acid breath test, respectively, in 24 lean and 14 morbidly obese individuals of both sexes. Student t-test was used to compare the mean data between the lean and morbidly obese groups. The influence of sex, gender, BMI and morbid obesity on the GET of solid meals was verified by linear regression analysis. Mean t(1/2) values of solid GET (± standard deviation) were 203.6 ± 76.0 min and 143.5 ± 19.1 min for lean and obese subjects, respectively (P = 0.0010). Mean t(lag) values of solid GET were 127.3 ± 42.7 min and 98.4 ± 13.0 min for lean and obese subjects, respectively (P = 0.0044). No significant difference in semi-solid GET was observed between the lean and morbidly obese groups. The present study demonstrated a significantly enhanced gastric emptying of the solid meal test in morbidly obese patients when compared to lean subjects. This finding is compatible with the hypothesis that rapid gastric emptying in morbidly obese subjects increases caloric intake due to a more rapid loss of satiety.

In 1980, an international group of pathologists and clinicians led by Basil Morson published a critical review entitled Precancerous Conditions and Epithelial Dysplasia in the Stomach. 1 This seminal article attempted to merge Eastern and Western pathological experiences in the evaluation of preneoplastic conditions into a systematic approach to the evaluation of gastric precancerous conditions. Thirty-five years after its publication, we pay homage to Professor Morson's team by revisiting their positions in light of the dramatic advances of our understanding of gastric disease that have occurred during this time. To this end, we have selected from the original article those statements that warranted reappraisal and, after reproducing them verbatim , have provided our comments. Introduction When considering problems of pre-malignancy, it is essential to define exactly what is meant by this term. A distinction can be made between a precancerous condition and a precancerous lesion . The former is best regarded as a clinical state associated with a significantly increased risk of cancer, whereas a precancerous lesion is a histopathological abnormality in which cancer is more likely to occur than in its apparently normal counterpart. In many clinical conditions with an increased risk of cancer, there is also an identifiable precancerous lesion, but this is not invariably so. Studies carried out in the last three decades have supported the multifactorial aetiology of sporadic gastric cancer and have led to the concept of a progressive ‘cascade’ of phenotypic and molecular changes that may eventually result in neoplasia.2 In 1994, Helicobacter pylori was added to the cascade, providing the hitherto missing crucial aetiological element that initiates the entire process.3 ,4 While the distinction between precancerous condition and lesion remains useful, the current understanding of gastric oncogenesis (including its early molecular disarrangements) begs an expansion of the concept of ‘lesion’, …