The Relevance of Ultrastructural Studies of Metastatic Cells from Women with Breast Cancer History.

The interaction between cancer cells and the surrounding microenvironment is determinant for metastasis success. In this study, the ultrastructural relevance of cells in the malignant pleural effusion (MPE) of women with breast cancer history was investigated. In MPE, it is possible to observe single cells and clusters. Women whose MPE presents carcinomas in aggregates have a better prognosis when compared to cases in which metastatic single cells are found. Samples were collected via fine-needle aspiration puncture (US-FNA). Subsequent to the material preparation and ultrathin cuts, they were observed using light and transmission electron microscopy (LM/TEM). LM and TEM images served as a basis for the creation of a digital sculpture using ZBrush® software. Clusters exhibited structural stability, en route vesicles allowing exocytosis of electron-dense fibrous elements, and cytoplasmic protrusions contributing to migratory and invasive skills. Single cells presented different necrotic phenotypes and many displayed leukocyte-like characteristics. Cluster cooperative relationships seem to be related to a long-term permanence in MPE. The absence of a collaborative network presumably triggers a more aggressive behavior of single cells. Its putative fusion with leukocytes can maximize the efficiency for transendothelial migration, increasing chances of metastatic success and, unfortunately, reducing survival of women with recidivism.

Follow-Up of Women with Cervical Cytological Abnormalities: Progression and Regression Events

Abnormalities in the cervix, when identified early by Pap smear, can be treated in the early stages or in the precursor stages of the neoplasia, which may increase the chances of regression of the lesion. The aim to verify the rate of cervical abnormalities and to evaluate the risk of progression or regression associated with age and cytological diagnosis. Methods: The study was conducted in a referral hospital in Southern Brazil, based on the results of pathology and cytopathology laboratory tests of uterine cervix. The historical cohort included patients with an abnormal cytology diagnosis in the period from January 2010 to December 2014, followed until July 2016. Results: A total of 42,389 cervical smears were analyzed, 4,427 of which were eligible for analysis of the evolution of cervical abnormalities. In progression and regression events analysis, we observed that patients with a cytological diagnosis of atypical glandular cells presented a higher risk of cervical abnormality progression (Hazard Ratio: 2.0 and 95% confidence intervals 1.36­3.48). We also observed that patients younger than 25 years old were more likely to regress the cervical lesions (Hazard Ratio:1.4 and 95% confidence intervals 1.20­1.74). Conclusions: The associations found between the events (progression and regression), age and cytological diagnosis, highlights the importance of cytological screening in populations at risk of precursor of cervical cancer lesions, especially in women older than 25 years.

Impact of Her-2 Overexpression on Survival of Patients with Metastatic Breast Cancer

Introduction: Breast cancer is a complex and heterogeneous disease which is increasingly important as a public health problem. In Brazil, 57,960 new cases have been estimated to be the burden in 2016 and 2017. Despite advances in early diagnosis and therapy, approximately 20-30% of patients, even with early stage lesions, will develop distant metastatic disease. Tumors with similar clinical and pathological presentations may have differing behavior, so it is important to understand specific biological characteristics. Objective: To investigate tumor markers of primary tumors featuring pleural metastasis to identify organ-specific characteristics of metastatic breast cancer. Methods: In a historical cohort study, immunohistochemistry was performed on cell blocks of neoplastic pleural effusions and results were compared with clinicopathological data. Results: The median survival time with Her-2 overexpression in malignant pleural effusions was 2.2 months, whereas cases without overexpression survived, on average, for seven months (p = 0.02). Conclusions: We emphasize that metastases may behave independently of primary tumors, but the present results indicate that therapeutic agents targeting Her-2 overexpression could increase survival in metastatic breast cancer cases.

LACK OF ASSOCIATION BETWEEN HELICOBACTER PYLORI'S VIRULENCE AND INCREASED SERUM C-REACTIVE PROTEIN LEVELS IN FUNCTIONAL DYSPEPTIC PATIENTS.

BACKGROUND: Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C-reactive protein, with the pathogen. OBJECTIVE: The objective of this study was to evaluate the presence of H. pylori, bacterial virulence and C-reactive protein serum levels in individuals diagnosed with functional dyspepsia. METHODS: Were prospectively included in this study 489 dyspeptic individuals. They fulfill Rome III clinical criteria for the diagnosis of functional dyspepsia with no organic disease at endoscopy. The bacterial infection was established by histology and urease rapid test. The levels of serum C-reactive protein were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined through an imunoenzimatic assay. RESULTS: Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. In addition, it has been noticed an association between Ilex paraguariensis (yerba maté) consumption and pathogen's prevalence. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. CONCLUSION: No systemic response to the pathogen, measured through C-reactive protein levels, was observed, regardless of CagA status. Otherwise, the intake of yerba maté should be considered as a cultural factor possibly related to H. pylori's transmission.

Lack of association between helicobacter pylori's virulence and increased serum c-reactive protein levels in functional dyspeptic patients

ABSTRACT Background Recently, a great variety of studies aimed to investigate and even suggestHelicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C-reactive protein, with the pathogen. Objective The objective of this study was to evaluate the presence of H. pylori, bacterial virulence and C-reactive protein serum levels in individuals diagnosed with functional dyspepsia. Methods Were prospectively included in this study 489 dyspeptic individuals. They fulfill Rome III clinical criteria for the diagnosis of functional dyspepsia with no organic disease at endoscopy. The bacterial infection was established by histology and urease rapid test. The levels of serum C-reactive protein were obtained by immunonefelometry and CagA status ofH. pylori positive individuals was determined through an imunoenzimatic assay. Results Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. In addition, it has been noticed an association between Ilex paraguariensis(yerba maté) consumption and pathogen's prevalence. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. Conclusion No systemic response to the pathogen, measured through C-reactive protein levels, was observed, regardless of CagA status. Otherwise, the intake of yerba maté should be considered as a cultural factor possibly related toH. pylori's transmission.

RESUMO Contexto Recentemente, uma grande variedade de estudos tem investigado e até mesmo sugerido a presença de Helicobacter pylori como um importante fator no desenvolvimento de eventos restritos ou não ao trato gastrointestinal. A relação já bem estabelecida entre virulência bacteriana e risco aumentado para úlcera péptica ou adenocarcinoma gástrico não parece estar tão elucidada quando se comparam alterações de marcadores inflamatórios, como a proteína C-reativa, com a presença do patógeno. Objetivo O objetivo deste estudo foi avaliar a presença da infecção por H. pylori, a virulência bacteriana e os níveis séricos de proteína C-reativa em indivíduos diagnosticados com dispepsia funcional. Métodos Foram incluídos neste estudo, prospectivamente, 489 indivíduos dispépticos. Os pacientes deveriam preencher os critérios clínicos de Roma III para o diagnóstico de dispepsia funcional sem apresentar doença orgânica evidenciada a partir da endoscopia. A infecção bacteriana foi estabelecida por histologia e pelo teste rápido da urease. Os níveis de proteína C-reativa foram quantificados através de imunonefelometria e o status para a presença da CagA dos indivíduos infectados por H. pylorifoi determinado por ensaio imunoenzimático. Resultados A taxa de prevalência de H. pylori foi de 66.3% e o fator de virulência CagA foi detectado em aproximandamente 43% das amostras positivas. Adicionalmente, denotou-se uma associação entre o consumo deIlex paraguariensis (chimarrão) e a prevalência do patógeno. Um importante efeito da infecção bacteriana na inflamação apenas foi observado localmente, no epitélio gástrico. Conclusão Não foi evidenciada resposta sistêmica ao patógeno aferido através dos níveis de proteína C-reativa, independentemente do status para CagA. Por outro lado, o consumo de chimarrão pode ser sugerido como um fator cultural possivelmente relacionado à transmissão de H. pylori.

Immunosuppression and the occurrence of HPV in kidney transplant patients verified by urinary cytology / Imunossupressão e ocorrência de HPV em pacientes transplantados renais a partir de exame citológico urinário

ABSTRACT Introduction: Human papillomavirus (HPV) is the main cause of cervical cancer, and immunosuppression is recognized as a risk factor for HPV infection and its persistence. After renal transplantation, immunosuppressive agents are used to prevent rejection, but predispose recipients to chronic infections and malignancies. Objective: This study aimed to verify, based on urinary cytology (UC), the prevalence of HPV in immunosuppressed kidney transplant patients. Material and method: In this cross-sectional study, the population was composed of kidney transplant patients that had undergone routine UC from August 2012 to August 2014. Results: There were 2,305 urine cytopathological tests. Thirteen patients with presence of koilocytes in such examination were observed. Therefore, the relative frequency of patients with HPV detected in urine was 0.56%. In the interval until the first post-transplant year, 10 (76.92%) patients presented koilocytes (p < 0.0001) in the UC. The dosages of immunosuppressive agents until the first post-transplant consultation, which showed correlation with the period between transplantation and the first UC test with the presence of koilocytes (p < 0.0001), were prednisone 10.5-20 mg/day, mycophenolate sodium 901-1,440 mg/day, and tacrolimus 4.5-12 mg/day. Conclusion: This study showed immunosuppression as an important risk factor for infection by HPV or its reactivation. Screening UC tests after transplantation may evidence HPV infection.

RESUMO Introdução: O papilomavírus humano (HPV) é a principal causa de câncer de colo do útero, e a imunossupressão é reconhecida como fator de risco para infecção pelo HPV e sua persistência. Após o transplante renal, agentes imunossupressores são usados para evitar rejeição, mas predispõem o receptor a infecções crônicas e doenças malignas. Objetivo: Este trabalho teve como objetivo verificar, a partir do exame citológico urinário, a prevalência do HPV em pacientes transplantados renais imunossuprimidos. Material e método: Neste estudo transversal, a população foi composta por pacientes transplantados renais que fizeram o exame de rotina citológico urinário no período de agosto de 2012 a agosto de 2014. Resultados: Realizaram-se 2.305 exames citopatológicos de urina. Foram observados 13 pacientes com presença de coilócitos no referido exame. A frequência relativa de pacientes com HPV detectado na urina foi de 0,56%. No intervalo até o primeiro ano pós-transplante, 10 (76,92%) pacientes apresentaram coilócitos (p < 0,0001) no exame citológico urinário (ECU). As dosagens de imunossupressores até a primeira consulta pós-transplante, que demonstraram correlação com o período entre o transplante e o primeiro ECU com presença de coilócito (p< 0,0001), foram prednisona 10,5-20 mg/dia, micofenolato de sódio 901-1.440 mg/dia e tacrolimo 4,5-12 mg/dia. Conclusão: Este estudo mostrou a imunossupressão como um fator de risco importante para infecção pelo HPV ou sua reativação. O acompanhamento por meio do ECU pós-transplante pode evidenciar a infecção por HPV.

Erratum: CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families.

This corrects the article DOI: 10.1590/S0004-28032012000400008.

Impact of cell arrangement of pleural effusion in survival of patients with breast cancer.

OBJECTIVE: This study was performed to evaluate the potential influence of cytological differences between pleural effusions on the survival of women with metastatic breast cancer during 30 months of follow-up. STUDY DESIGN: A hospital-based cohort study was performed. Pleural fluid cytology slides from patients with breast cancer were examined. Cases were grouped according to the pattern of tumor cells (spheroid and isolated), in order to access their prognostic value. RESULTS: The study comprised 87 patients. An isolated cell pattern was associated with higher mortality 30 months after the pleural effusion when compared to a spheroid pattern (p = 0.038). Patients with an isolated cell pattern showed higher risk of dying than patients with spheroid formations. The relative risk after adjustment of intervening variables was 5.336 (95% CI 1.054-27.020). The presence of a triple-negative immunohistochemical pattern significantly increased the risk of mortality before 30 months. CONCLUSION: Pleural effusion with isolated malignant cells is associated with worse prognosis after 30 months of follow-up.

Resistance to amoxicillin, clarithromycin and ciprofloxacin of Helicobacter pylori isolated from Southern Brazil patients.

INTRODUCTION: Helicobacter pylori is a bacteria which infects half the world population and is an important cause of gastric cancer. The eradication therapy is not always effective because resistance to antimicrobials may occur. The aim of this study was to determine the susceptibility profile of H. pylori to amoxicillin, clarithromycin and ciprofloxacin in the population of Southern Brazil. MATERIAL AND METHODS: Fifty four samples of H. pylori were evaluated. The antibiotics susceptibility was determined according to the guidelines of the British Society for Antimicrobial Chemotherapy and the Comité de l'Antibiogramme de la Société Française de Microbiologie. RESULTS: Six (11.1%) H. pylori isolates were resistant to clarithromycin, one (1.9%) to amoxicillin and three (5.5%) to ciprofloxacin. These indices of resistance are considered satisfactory and show that all of these antibiotics can be used in the empirical therapy. CONCLUSION: The antibiotics amoxicillin and clarithromycin are still a good option for first line anti-H. pylori treatment in the population of Southern Brazil.

RESISTANCE TO AMOXICILLIN, CLARITHROMYCIN AND CIPROFLOXACIN OF Helicobacter pylori ISOLATED FROM SOUTHERN BRAZIL PATIENTS / Resistência à amoxicilina, claritromicina e ciprofloxacina de Helicobacter pylori isolados de pacientes do Sul do Brasil

Introduction: Helicobacter pylori is a bacteria which infects half the world population and is an important cause of gastric cancer. The eradication therapy is not always effective because resistance to antimicrobials may occur. The aim of this study was to determine the susceptibility profile of H. pylori to amoxicillin, clarithromycin and ciprofloxacin in the population of Southern Brazil. Material and methods: Fifty four samples of H. pylori were evaluated. The antibiotics susceptibility was determined according to the guidelines of the British Society for Antimicrobial Chemotherapy and the Comité de l'Antibiogramme de la Société Française de Microbiologie. Results: Six (11.1%) H. pylori isolates were resistant to clarithromycin, one (1.9%) to amoxicillin and three (5.5%) to ciprofloxacin. These indices of resistance are considered satisfactory and show that all of these antibiotics can be used in the empirical therapy. Conclusion: The antibiotics amoxicillin and clarithromycin are still a good option for first line anti-H. pylori treatment in the population of Southern Brazil.

Introdução: Helicobacter pylori é uma bactéria que infecta metade da população mundial e é considerada importante causa de câncer gástrico. A terapia de erradicação nem sempre é eficaz, pois pode ocorrer a resistência aos antimicrobianos. Este estudo determinou a sensibilidade de H. pylori frente à amoxicilina, claritromicina e ciprofloxacina na população do Sul do Brasil. Material e métodos: Foram avaliadas 54 amostras de H. pylori. A sensibilidade aos antibióticos foi determinada segundo as orientações da British Society for Antimicrobial Chemotherapy e do Comité de l'Antibiogramme de la Société Française de Microbiologie. Resultados e discussão: Sete (13%) isolados de H. pylori foram resistentes à claritromicina, um (1,9%) à amoxicilina e três (5,5%) à ciprofloxacina. Estes índices são satisfatórios e demonstram que esses antibióticos podem ser utilizados na terapia empírica. Conclusão: Os antibióticos amoxicilina e claritromicina ainda são uma boa opção no tratamento de primeira linha anti-H. pylori na população do Sul do Brasil.

No evidence of HPV DNA in esophageal squamous cell carcinoma in a population of Southern Brazil.

AIM: To investigate the association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in southern Brazil. METHODS: We studied 189 esophageal samples from 125 patients from three different groups: (1) 102 biopsies from 51 patients with ESCC, with one sample from the tumor and another from normal esophageal mucosa distant from the tumor; (2) 50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma (HNSCC); and (3) 37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients, not exposed to smoking or alcohol consumption. Nested-polymerase chain reaction (PCR) with the MY09/11 and GP5/6 L1 primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks. All PCR reactions were performed with a positive control (cervicovaginal samples), with a negative control (Human Genomic DNA) and with a blank reaction containing all reagents except DNA. We took extreme care to prevent DNA contamination in sample collection, processing, and testing. RESULTS: The histological biopsies confirmed the diagnosis of ESCC in 52 samples (51 from ESCC group and 1 from the HNSCC group) and classified as well differentiated (12/52, 23.1%), moderately differentiated (27/52, 51.9%) or poorly differentiated (7/52, 13.5%). One hundred twenty-eight esophageal biopsies were considered normal (51 from the ESCC group, 42 from the HNSCC group and 35 from dyspeptic patients). Nine had esophagitis (7 from the HNSCC and 2 from dyspeptic patients). Of a total of 189 samples, only 6 samples had insufficient material for PCR analysis: 1 from mucosa distant from the tumor in a patient with ESCC, 3 from patients with HNSCC and 2 from patients without cancer. In 183 samples (96.8%) GAPDH, G3PDH and/or ß-globin were amplified, thus indicating the adequacy of the DNA in those samples. HPV DNA was negative in all the 183 samples tested: 52 with ESCC, 9 with esophagitis and 122 with normal esophageal mucosa. CONCLUSION: There was no evidence of HPV infection in different ESCC from southern Brazil.

CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families / Mutação germinativa 1100delC no gene CHEK2: estudo da frequência em famílias brasileiras com câncer de mama e cólon hereditários

CONTEXT: CHEK2 encodes a cell cycle checkpoint kinase that plays an important role in the DNA damage repair pathway, activated mainly by ATM (Ataxia Telangiectasia Mutated) in response to double-stranded DNA breaks. A germline mutation in CHEK2, 1100delC, has been described as a low penetrance allele in a significant number of families with breast and colorectal cancer in certain countries and is also associated with increased risk of contralateral breast cancer in women previously affected by the disease. About 5%-10% of all breast and colorectal cancers are associated with hereditary predisposition and its recognition is of great importance for genetic counseling and cancer risk management. OBJECTIVES: Here, we have assessed the frequency of the CHEK2 1100delC mutation in the germline of 59 unrelated Brazilian individuals with clinical criteria for the hereditary breast and colorectal cancer syndrome. METHODS: A long-range PCR strategy followed by gene sequencing was used. RESULTS: The 1100delC mutation was encountered in the germline of one (1.7%) individual in this high risk cohort. This indicates that the CHEK2 1100delC is not commonly encountered in Brazilian families with multiple diagnoses of breast and colorectal cancer. CONCLUSION: These results should be confirmed in a larger series of families and further testing should be undertaken to investigate the molecular mechanisms underlying the hereditary breast and colorectal cancer phenotype.

INTRODUÇÃO: CHEK2 codifica uma proteína quinase envolvida em um ponto de checagem do ciclo celular que desempenha um papel importante na via de reparação do DNA, danos ativados principalmente por ATM (Ataxia Telangiectasia Mutado) em resposta a danos na dupla hélice do DNA. A mutação germinativa 1100delC no gene CHEK2 tem sido descrita como um alelo de baixa penetrância em um número significativo de famílias com câncer de mama e cólon em certos países e também está associada com risco aumentado de câncer de mama contralateral em mulheres previamente afetadas pela doença. Cerca de 5%-10% de todos os cânceres de mama e colorretais estão associados a predisposição hereditária e o seu reconhecimento é de grande importância para o aconselhamento genético e gestão do risco de câncer. OBJETIVOS: Neste estudo foi avaliada a frequência da mutação germinativa 1100delC no gene CHEK2 em 59 diferentes indivíduos brasileiros com critérios clínicos para a síndrome de câncer de mama e cólon hereditários. MÉTODO: Utilizamos como estratégia a realização do PCR de longo alcance seguido de sequenciamento. RESULTADOS: A mutação 1100delC foi encontrada em um indivíduo (1,7%), indicando que esta mutação germinativa não é comumente encontrada em famílias brasileiras com múltiplos diagnósticos de câncer de mama e câncer colorretal. CONCLUSÃO: Estes resultados devem ser confirmados em uma série maior de famílias, e estudos adicionais devem ser realizados para investigar a patologia molecular do fenótipo HBCC.

The role of urine cytology for 'decoy cells' as a screening tool in renal transplant recipients.

OBJECTIVE: To determine the role of urine cytology for 'decoy cells' as a screening tool for polyomavirus type BK (BKV) infection in renal transplant recipients. STUDY DESIGN: This was a prospective cohort study of patients undergoing renal transplantation between 2006 and 2010. RESULTS: A total of 442 patients underwent urine cytology for decoy cells, 27.8% underwent 1 examination only and 72.2% more than one. Of the 1,713 examinations reviewed, 426 (24.9%) were positive and 785 (45.8%) were negative for 'decoy' cells, 380 (22.2%) showed degenerated tubular cells and 122 (7.1%) were unsatisfactory for analysis. Urine cytology was found to have a specificity of 68.5%, a sensitivity of 84.6%, a positive predictive value of 21.2%, a negative predictive value of 97.8% and an overall accuracy of 69.9%. The incidence of polyomavirus nephropathy among the patients investigated was 11.8%. Of the 442 patients, 32 (7.2%) had graft loss, which was attributed to BKV nephropathy in 2 (6.2% of the 32). CONCLUSIONS: Urine cytology is an effective screening method for monitoring renal transplant patients, with high sensitivity and a high negative predictive value, and can therefore be used routinely in the follow-up of renal transplant patients.

Alimentary factors in the development of gastric intestinal metaplasia in functional dyspeptic patients.

CONTEXT: Intestinal metaplasia of the stomach is a lesion in which metaplasia of gastric epithelial cells occurs for an intestinal phenotype. Gastric intestinal metaplasia is a lesion associated with an increase in the risk of gastric carcinoma development. Epidemiologic studies indicate a relation between dietary habits and stomach cancer development, some habits increasing the risk for it, and others have a protective effect, suggesting that antioxidants, such as vitamins A, C, and E, decrease the risk of this type of cancer. The relationship of these alimentary factors and intestinal metaplasia is unknown. METHODS: It is a case-control, observational study in which 320 patients with functional dyspepsia, divided in two groups, were assessed. The case I group (individuals with intestinal metaplasia) had their dietary pattern compared to that of the control group, constituted of individuals similar to those in the case group but without intestinal metaplasia, through a food frequency questionnaire. RESULTS: The analysis of the dietary pattern of functional dyspeptic patients with intestinal metaplasia, and its comparison with those without intestinal metaplasia, showed a higher frequency of canned and smoked foods consumption in the first group and, on the other hand, a higher consumption of fruits and vegetables in patients without intestinal metaplasia. No effect of salt consumption was detected. CONCLUSIONS: The results obtained in this study suggest changes in the diet, with a decrease in the consumption of smoked and canned foods, and an increase in the consumption of fruits and vegetables, can lead to a diminution of gastric intestinal metaplasia cases.

Clinical and pathological factors influencing the survival of breast cancer patients with malignant pleural effusion.

OBJECTIVE: The objective of this study was to identify the clinical and pathological factors that can influence the prognosis of breast cancer patients with clinical symptoms of malignant pleural effusion. METHODS: This was a clinical cohort study, in which we analyzed the medical charts of patients diagnosed with malignant pleural effusion between 2006 and 2010. By examining the charts, we identified the female patients with a history of breast cancer. For those patients, we collected pathology data related to the primary tumor and cytopathology data related to the pleural metastasis. RESULTS: We evaluated 145 patients, 87 (60%) of whom had tested positive for malignant cells in the pleural fluid. Ductal histology was observed in 119 (82%). The triple-negative breast cancer phenotype was seen in 25 cases (17%). Those patients had the worst prognosis (with a sharp decline in the survival curve), and 20 of the 25 (80%) died during the follow-up period (through June of 2011). The mean survival after the identification of malignant pleural effusion was 6 months. CONCLUSIONS: In patients with triple-negative breast cancer who test positive for malignant cells in the pleural fluid, the prognosis is poor and survival is reduced.

Alimentary factors in the development of gastric intestinal metaplasia in functional dyspeptic patients / Fatores alimentares envolvidos no desenvolvimento de metaplasia intestinal em dispépticos funcionais

CONTEXT: Intestinal metaplasia of the stomach is a lesion in which metaplasia of gastric epithelial cells occurs for an intestinal phenotype. Gastric intestinal metaplasia is a lesion associated with an increase in the risk of gastric carcinoma development. Epidemiologic studies indicate a relation between dietary habits and stomach cancer development, some habits increasing the risk for it, and others have a protective effect, suggesting that antioxidants, such as vitamins A, C, and E, decrease the risk of this type of cancer. The relationship of these alimentary factors and intestinal metaplasia is unknown. METHODS: It is a case-control, observational study in which 320 patients with functional dyspepsia, divided in two groups, were assessed. The case I group (individuals with intestinal metaplasia) had their dietary pattern compared to that of the control group, constituted of individuals similar to those in the case group but without intestinal metaplasia, through a food frequency questionnaire. RESULTS: The analysis of the dietary pattern of functional dyspeptic patients with intestinal metaplasia, and its comparison with those without intestinal metaplasia, showed a higher frequency of canned and smoked foods consumption in the first group and, on the other hand, a higher consumption of fruits and vegetables in patients without intestinal metaplasia. No effect of salt consumption was detected. CONCLUSIONS: The results obtained in this study suggest changes in the diet, with a decrease in the consumption of smoked and canned foods, and an increase in the consumption of fruits and vegetables, can lead to a diminution of gastric intestinal metaplasia cases.

CONTEXTO: A metaplasia intestinal do estômago é uma lesão onde ocorre a metaplasia das células epiteliais gástricas para um fenótipo intestinal. A metaplasia intestinal gástrica é considerada uma lesão associada ao aumento do risco de desenvolvimento de carcinoma gástrico. Estudos epidemiológicos indicam uma relação entre hábitos alimentares e o risco de desenvolvimento de câncer de estômago: tanto podendo ter efeito carcinogênico gástrico, como fator protetor, sugerindo que os antioxidantes como as vitaminas A, C e E diminuem o risco desse tipo de câncer. Não se conhece a influência desses fatores alimentares na metaplasia intestinal gástrica. MATERIAL: Trata-se de estudo caso-controle, observacional, para o qual foram avaliados 320 pacientes com dispepsia funcional, separados em dois grupos, um grupo de casos I (indivíduos com metaplasia intestinal) teve seus hábitos alimentares comparados aos do grupo de casos-controle (sem metaplasia intestinal), através de um questionário de frequência de consumo alimentar. RESULTADOS: Ao analisarmos o padrão alimentar dos pacientes dispépticos funcionais com metaplasia intestinal e compará-lo com o padrão daqueles que não possuem metaplasia intestinal, constatou-se que os pacientes com metaplasia intestinal consomem mais alimentos como os enlatados e defumados, enquanto os pacientes sem metaplasia intestinal apresentam consumo expressivamente maior de frutas em geral e vegetais. Diferença no padrão de consumo de sal não foi identificada. CONCLUSÕES: Através dos resultados obtidos no presente estudo podemos supor que a modificação da dieta, por meio da diminuição na ingestão de alimentos como defumados e enlatados e acréscimo na ingestão de frutas e vegetais pode levar a diminuição de casos de metaplasia intestinal.

Fatores clínicos e anatomopatológicos que influenciam a sobrevida de pacientes com câncer de mama e derrame pleural neoplásico / Clinical and pathological factors influencing the survival of breast cancer patients with malignant pleural effusion

OBJETIVO: O objetivo deste estudo foi identificar os fatores clínicos e anatomopatológicos que possam influenciar o prognóstico de pacientes com câncer de mama e sintomas clínicos de derrame pleural neoplásico. MÉTODOS: Trata-se de um estudo clínico de coorte, no qual foram analisados os prontuários médicos de pacientes que receberam diagnóstico de derrame pleural neoplásico entre 2006 e 2010. Por meio da análise dos prontuários, identificamos as pacientes com história de câncer de mama. Para essas pacientes, coletamos dados anatomopatológicos relacionados ao tumor primário e dados citopatológicos relacionados à metástase pleural. RESULTADOS: Das 145 pacientes avaliadas, 87 (60%) apresentaram, no exame citológico, resultado positivo para células neoplásicas no líquido pleural; além disso, 119 (82%) apresentaram tipo histológico ductal. O fenótipo triplo-negativo foi observado em 25 pacientes (17%), as quais apresentaram o pior prognóstico, com queda acentuada na curva de sobrevida. Das 25 pacientes, 20 (80%) evoluíram a óbito durante o período de seguimento (até junho de 2011). A sobrevida média após a identificação de derrame pleural neoplásico foi de 6 meses. CONCLUSÕES: Em pacientes com câncer de mama triplo-negativo e exame citológico com resultado positivo para células neoplásicas no líquido pleural, o prognóstico é ruim e a sobrevida é menor.

OBJECTIVE: The objective of this study was to identify the clinical and pathological factors that can influence the prognosis of breast cancer patients with clinical symptoms of malignant pleural effusion. METHODS: This was a clinical cohort study, in which we analyzed the medical charts of patients diagnosed with malignant pleural effusion between 2006 and 2010. By examining the charts, we identified the female patients with a history of breast cancer. For those patients, we collected pathology data related to the primary tumor and cytopathology data related to the pleural metastasis. RESULTS: We evaluated 145 patients, 87 (60%) of whom had tested positive for malignant cells in the pleural fluid. Ductal histology was observed in 119 (82%). The triple-negative breast cancer phenotype was seen in 25 cases (17%). Those patients had the worst prognosis (with a sharp decline in the survival curve), and 20 of the 25 (80%) died during the follow-up period (through June of 2011). The mean survival after the identification of malignant pleural effusion was 6 months. CONCLUSIONS: In patients with triple-negative breast cancer who test positive for malignant cells in the pleural fluid, the prognosis is poor and survival is reduced.

CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families.

CONTEXT: CHEK2 encodes a cell cycle checkpoint kinase that plays an important role in the DNA damage repair pathway, activated mainly by ATM (Ataxia Telangiectasia Mutated) in response to double-stranded DNA breaks. A germline mutation in CHEK2, 1100delC, has been described as a low penetrance allele in a significant number of families with breast and colorectal cancer in certain countries and is also associated with increased risk of contralateral breast cancer in women previously affected by the disease. About 5%-10% of all breast and colorectal cancers are associated with hereditary predisposition and its recognition is of great importance for genetic counseling and cancer risk management. OBJECTIVES: Here, we have assessed the frequency of the CHEK2 1100delC mutation in the germline of 59 unrelated Brazilian individuals with clinical criteria for the hereditary breast and colorectal cancer syndrome. METHODS: A long-range PCR strategy followed by gene sequencing was used. RESULTS: The 1100delC mutation was encountered in the germline of one (1.7%) individual in this high risk cohort. This indicates that the CHEK2 1100delC is not commonly encountered in Brazilian families with multiple diagnoses of breast and colorectal cancer. CONCLUSION: These results should be confirmed in a larger series of families and further testing should be undertaken to investigate the molecular mechanisms underlying the hereditary breast and colorectal cancer phenotype.

Helicobacter pylori eradication in functional dyspepsia: HEROES trial.

BACKGROUND: Eradication of Helicobacter pylori in patients with functional dyspepsia continues to be a matter of debate. We studied eradication effects on symptoms and quality of life of primary care patients. METHODS: Helicobacter pylori -positive adult patients with functional dyspepsia meeting the Rome III International Consensus criteria were randomly assigned to receive omeprazole, amoxicillin trihydrate, and clarithromycin, or omeprazole plus placebo for 10 days. Endoscopy and H pylori tests were performed at screening and at 12 months. Outcome measures were at least 50% symptomatic improvement at 12 months using a validated disease-specific questionnaire (primary end point), patient global assessment of symptoms, and quality of life. RESULTS: We randomly assigned 404 patients (78.7% were women; mean age, 46.1 years); 201 were assigned to be treated with antibiotics (antibiotics group) and 203 to a control group. A total of 389 patients (96.3%) completed the study. The proportion of patients who achieved the primary outcome was 49.0% (94 of 192) in the antibiotics group and 36.5% (72 of 197) in the control group (P = .01; number needed to treat, 8). In the patient global assessment of symptoms, 78.1% in the antibiotics group (157 of 201) answered that they were better symptomatically, and 67.5% in the control group (137 of 203) said that they were better (P = .02). The antibiotics group had a significantly larger increase in their mean (SD) Medical Outcomes Study 36-Item Short Form Health Survey physical component summary scores than the control group did (4.15 [8.5] vs 2.2 [8.1]; P = .02). CONCLUSION: Helicobacter pylori eradication provided significant benefits to primary care patients with functional dyspepsia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00404534.

Relationship between cagA-positive Helicobacter pylori infection and risk of gastric cancer: a case control study in Porto Alegre, RS, Brazil.

CONTEXT: Gastric cancer is the second most common cause of cancer related death worldwide. Although Helicobacter pylori has been classified as a class I carcinogen, the presence of infection is not a factor that alone is able to lead to gastric cancer, and one of the possible explanations for this is the existence of different strains of H. pylori with different degrees of virulence. OBJECTIVES: To investigate the association between cagA-positive H. pylori and gastric cancer, using polymerase chain reaction (PCR) for the detection of this bacterial strain. METHODS: Twenty-nine patients with gastric cancer were matched by sex and age (± 5 years) with 58 patients without gastric cancer, submitted to upper gastrointestinal endoscopy. All patients were evaluated for the status of infection by H. pylori (through urease test, histological analysis and PCR for the genes ureA and 16SrRNA) and by cagA-positive strain (through PCR for cagA gene). RESULTS: Evaluating the presence of infection by cagA-positive H. pylori, it was verified that the rate of infection was significantly higher in the group with gastric cancer when compared with the matched controls, occurring in 62.1% and 29.3%, respectively (OR = 3.95; CI 95% 1.543-10.096). CONCLUSIONS: There is an association between cagA-positive H. pylori strain and risk of gastric cancer.