Mortalidade por neoplasias no Brasil (1980/1983/1985): agrupamento dos Estados, comportamento e tendências

Examinou-se a mortalidade por neoplasias no Brasil, utilizando-se dados oficiais do Ministério da Saúde, abrangendo 26 Unidades da Federação e 13 diferentes localizações neoplásicas, para os anos de 1980, 1983 e 1985. As Análises de Agrupamento e de Componentes Principais revelaram comportamento heterogêneo entre regiões do país, com relação às 13 variáveis estudadas, sendo que os principais elementos discriminantes foram as neoplasias malignas da traquéia/brônquio/pulmão, seguidas das do estômago, esôfago, cólon e pâncreas. Análises complementares evidenciaram tendência de crescimento das taxas de mortalidade para as neoplasias malignas da próstata (17,74%), da traquéia/brônquio/pulmão(15,22%), da mama (11,32%), do pâncreas (10,23%), do cólon (8,08%), do colo uterino (6,45%) e da laringe (6,36%). Houve redução da mortalidade por neoplasias benignas/carcinoma in situ/ outras (27,37%), por neoplasias malignas no reto sigmóide/ânus (7,67%), do estômago (5,31%), de outro local do útero não especificado (2,56%), por leucemia (0,70%) e por neoplasias malignas do esôfago (0,44%). As neoplasias malignas do estômago foram a principal causa de morte por câncer no Brasil, representando 21,30% do total médio, seguidas das neoplasias malignas da traquéia/brônquio/pulmão(17,49% do total médio). Destacam-se os altos índices de mortalidade por neoplasias malignas do esôfago no Estado do Rio Grande do Sul.

Clinical outcome in chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation: The experience of the Bone Marrow Transplantation Unit of FUNFARME/BRAZIL using FISH

Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units. ©FUNPEC-RP.

Análise da expressão do HER-2 no câncer de mama e sua correlação com outros fatores prognósticos

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Genes candidatos a marcadores tumorais na progressão do adenocarcinoma de próstata indentificados por análise de HR-CGH e CGH-ARRAY

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação dos efeitos antitumorais de extratos brutos produzidos por fungos endofíticos isolados de Eugenia jambolana em células de hepatocarcinoma murino (Hepa-1c1c7)

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Accuracy of Screening for Potentially Malignant Disorders of the Oral Mucosa by Dentists in Primary Care

Purpose: To examine the accuracy of a screening programme for potentially malignant disorders of the oral mucosa by visual inspection in primary health care. Materials and Methods: The study was based on secondary data from the Primary Care Information System maintained by seven units of family health in Sao Paulo City managed by a non-governmental agency. The reference population was composed of 15,072 residents 50 years old or more of both genders. The study population comprised 2,980 individuals. During screening in community settings, the oral mucosa was examined by trained dentists and distributed into two categories: (a) screen negative (b) screen positive. All participants underwent comprehensive clinical exams by a general dental practitioner supervised by a specialist. Individual records were grouped in a working dataset. Point and 95% confidence interval estimates were calculated regarding measures of sensitivity (Se), specificity (Sp) and positive and negative predictive values (PPV and NPV, respectively). Results: 18.0% of the population was considered screen positive. A total of 133 lesions (4.5%) were identified and 8 cases of oral cancer were confirmed, which corresponded to a prevalence rate of 27 cases in 10,000 people, a much higher rate than expected. The measures found were Se: 91.7% (85.3-95.6), Sp: 85.4% (84.1-86.7), PPV: 22.7% (19.3-26.5), NPV: 99.5% (99.2-99.8). The visual screen presented high accuracy. Conclusion: The test presented high sensibility and specificity values. From a public health point of view, the high accuracy levels showed the importance of oral health teams on family health strategy for more comprehensive primary care. Targeting risk groups and delegating the screening to community health agents may improve PPV and coverage.

Characterization of PAR1 and FGFR1 expression in invasive breast carcinomas: Prognostic significance

Breast cancer is the most common cause of cancer mortality among women worldwide. Among the several factors associated with breast cancer development, angiogenesis plays an essential role and has currently emerged as a potential diagnostic, prognostic and therapeutic target. Protease-activated receptor 1 (PAR1) and fibroblast growth factor receptor 1 (FGFR1) have important activities in tumor angiogenesis and progression. The aim of this study was to investigate the prognostic significance of these two receptors, hypothesising significant correlations between receptor expression in tumor angiogenesis and clinicopathological parameters customarily used in breast cancer prognosis and prediction. Formalin-fixed and paraffin-embedded samples of ductal invasive breast carcinomas were used to analyze the expression of PAR1 and FGFR1, in the tumor cells as well as in the tumor stroma, and further determine intratumoral microvessel density (iMVD) to quantify intratumoral angiogenesis. Correlations between PAR1 and FGFR1 expression in tumor cells and stroma, iMVD and several clinicopathological parameters and molecular markers used in breast cancer diagnosis have been addressed. The correlation between PAR1 and FGFR1 suggests an association of the two receptors with a more aggressive breast cancer phenotype and, consequently, a potential role during tumor progression. The results reported in the present study also emphasize the importance of microenvironmental factors in tumor progression, while precluding the positive association between iMVD and breast cancer aggressiveness.

Outcome analysis of breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) flaps

QUESTIONS UNDER STUDY: With the reduction in breast cancer mortality in recent years the aesthetic outcome after treatment has gained increasing attention. The aim of this study was to assess the outcome quality of our single institution concept of free TRAM flap breast reconstruction with the aim of providing data to assist the patient's decision-making when breast reconstruction is an option. PRINCIPLES/METHODS: Thirty-two consecutive patients receiving immediate (n = 14) or delayed (n = 18) breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) flaps were included. The selection of patients was based on their own wish and the availability of abdominal tissue, without excluding patients at risk for wound healing complications. Patient data were assessed prospectively and the aesthetic outcome was rated after the final result had been achieved. RESULTS: Ten patients sustained wound healing complications (4 of 9 smokers, 8 of 16 patients with a BMI over 25 kg/m2), 8 of them requiring revisional surgery. An average of 1.06 corrective procedures were performed per patient. The aesthetic outcome was judged to be good by 20 patients, fair by 5 and poor by 1 patient who sustained severe tissue loss. CONCLUSIONS: Our results revealed that a large measure of satisfaction is achievable from breast reconstruction with free TRAM flaps, in spite of the invasive nature of the procedure and the inclusion of patients at risk for wound healing complications. These data may be used in the decision-making process by patients eligible for breast reconstruction after mastectomy.

Mammografie-Screening

Nur wenige Vorsorgeuntersuchungen sind so umfassend in randomisiert-kon- trollierten Studien (RCTs) untersucht worden wie das Screening auf Brustkrebs mit Hilfe der Mammografie. Es liegen derzeit acht große randomisiert-kontrol- lierte Studien und mehrere Meta-Analysen vor. Letztere kommen mehrheitlich zum Schluss, dass sich die Brustkrebssterblichkeit durch Mammografie-Screening um etwa 20 % senken lässt. Dies bedeutet im Schweizer Kontext, dass etwa 1 von 1'000 Frauen weniger an Brustkrebs stirbt, wenn Frauen ab dem 50. Lebensjahr zehn Jahre lang gescreent werden. Andererseits führt das Screening auch zu Überdiagnosen und Übertherapien. So nimmt die Zahl der Brustkrebsdiagnosen um etwa 20 % zu, was zu einer entsprechenden Zunahme an chirurgischen Ein- griffen, Strahlen- und Chemotherapien führt. Über zehn Jahre gerechnet, erhal- ten etwa 4 von 1'000 Frauen eine Brustkrebsdiagnose, die sie ohne Screening nicht erhalten hätten. Etwa 200 von 1'000 Frauen sind im Verlaufe von zehn Jahren (fünf Screening-Runden) mit abklärungsbedürftigen Befunden konfron- tiert, wobei es sich dabei mehrheitlich um falsch positive Befunde handelt. Gleichzeitig werden auch mit einem Screening-Programm 20 bis 30 % der Brust- krebse nicht im Screening erfasst. Die Information der Bevölkerung bezüglich des Mammografie-Screenings ist derzeit noch mangelhaft. Dies führt dazu, dass der mögliche Nutzen von den betroffenen Frauen überschätzt und der Schaden unterschätzt wird. Die Aufklärung der Bevölkerung im Hinblick auf Nutzen und Risiken des Mammografie-Screenings muss daher verbessert werden, denn Frau- en haben einen Anspruch auf evidenzbasierte Informationen und eine „infor- mierte Entscheidung“.

Factors associated with mammography utilization in Sao Paulo and Mexico city elderly females

Introduction. Breast cancer has the highest incidence and mortality rates of all cancers in Sao Paulo and Mexico City women with rates expected to rise due to increasing elderly populations. While mammograms could reduce the breast cancer burden, little information exists about screening behavior factors in these areas. The primary objective of this study is testing the association of socio-demographic, geographic, and health access/health status variables on mammogram screenings in elderly females in both cities. Studying the regions' healthcare systems and their screening impact is the ancillary objective. ^ Methods. Accounting for the complex sample design (weights, stratification, and clusters) of the 1999-2000 SABE study, analysis of mammogram utilization in the past two years was performed. The sample consisted of 1239 women from Sao Paulo and 1349 women from Mexico City. ^ Results. Having private insurance in Sao Paulo (OR = 5.86) and Mexico City (OR = 4.09) increased the chance of having a mammogram in the targeted women. In both cities, women with higher levels of education had higher likelihoods of screening (Sao Paulo OR = 4.56 and Mexico City OR = 3.04). Age, regular medical care, and health status were significant in Sao Paulo; however, the factors showed no significance in Mexico City. ^ Discussion. Mammogram utilization can reduce mortality from breast cancer, and understanding screening factors is crucial to screening adherence. Addressing key variables may lead to increased screening and decreased breast cancer mortality in elderly women in Sao Paulo, Mexico City, and similar regions. ^

The effect of obesity on mammography utilization in African American women

Breast cancer continues to reign as a common cause of death for women in the United States, claiming the lives of more than an estimated 40,000 women in 2009 alone (Ries et al., 2009). A mammogram, an x-ray of the breast, can aid in early detection of breast cancer and thus more successful treatment. Screening patterns indicate African American women are less likely to utilize mammography technology when compared to their Caucasian counterparts. Additionally, the obesity epidemic in the United States remains a major public health problem. Obesity trends indicate that African American women are likely to be more obese when compared to Caucasian women. Pischon, Nöthlings, & Boeing (2008) concluded there was sufficient evidence linking breast cancer and obesity. Many researchers have identified obesity as a risk factor for breast cancer. As African American women are disproportionately burdened by both breast cancer mortality and obesity, more extensive research is needed to gain more knowledge about their association. The purpose of this study was to identify the role obesity plays in lessening an African American woman’s usage of mammography technology. Data from the 2005 National Health Interview Study were analyzed using SPSS to evaluate the relationship between body mass index (BMI) and mammography utilization in the two aforementioned populations.^ After excluding respondents from the sample who did not meet the set criteria, there were 17,666 women remaining. Of the 17,666 women, 6,156 (34.8%) had a healthy weight, 6,024 (34.1%) were overweight, and 4,285 (24.3%) were obese. About 70% of the sample population reported having had a mammogram in the last two years. Another 27.6% of women reported not receiving a mammogram within this same two year time frame. Within ethnic categories, the majority of the sample was Caucasian (64.2%) while only 15.1% of the sample was African American. The relationship between mammography usage and body mass index was not statistically significant within any body mass index categories. When analyzing the relationship between mammography usage and BMI, adjusting for ethnicity, there was also no significant difference between obese African American and obese Caucasian women. The study did find significant relationships between mammography usage and body mass index when adjusting for cancer risk OR = .79 (95% CI .72 - .85), and marital status OR = 1.18 (95% CI 1.05 - 1.34). Due to insignificant findings, there was no evidence to support the hypothesis regarding differences in mammography usage based on weight or ethnicity. Mammography screening differences based on ethnicity are widely cited. Unfortunately it is still unclear exactly where these differences lie. Obesity has been widely documented in the literature as a risk factor for many chronic diseases, including certain forms of cancer. Understanding the relationship between screening behaviors and weight can assist in the development of health promotion programs aimed at high risk groups. In order to change screening behavior and reduce mortality from breast cancer, more research is needed to identify similarities within low screening populations.^

Health significance of chlorination byproducts in drinking water: The Houston experience: A continuation study

Background. Houston, Texas, once obtained all its drinking water from underground sources. However, in 1853, the city began supplementing its water from the surface source Lake Houston. This created differences in the exposure to disinfection byproducts (DBPs) in different parts of Houston. Trihalomethanes (THMs) are the most common DBP and are useful indicators of DBPs in treated drinking water. This study examines the relationship between THMs in chlorinated drinking water and the incidence of bladder cancer in Houston. ^ Methods. Individual bladder cancer deaths, from 1975 to 2004, were assigned to four surface water exposure areas in Houston utilizing census tracts—area A used groundwater the longest, area B used treated lake water the longest, area C used treated lake water the second longest, and area D used a combination of groundwater and treated lake water. Within each surface water exposure area mortality rates were calculated in 5 year intervals by four race-gender categories. Linear regression models were fitted to the bladder cancer mortality rates over the entire period of available data (1990–2004). ^ Results. A decrease in bladder cancer mortality was observed amongst white males in area B (p = 0.030), white females in area A (p = 0.008), non-white males in area D (p = 0.003), and non-white females in areas A and B (p = 0.002 & 0.001). Bladder cancer mortality differed by race-gender and time (p ≤ 0.001 & p ≤ 0.001), but not by surface water exposure area (p = 0.876). ^ Conclusion. The relationship between bladder cancer mortality and the four surface water exposure areas (signifying THM exposure) was insignificant. This result could be attributable to Houston controlling for THMs starting in the early 1980’s by using chloramine as a secondary disinfectant in the drinking water purification process.^

Expression of p53, {\it * ras\/} and PCNA in human colonic neoplasms: Possible biomarkers of malignant potential

Colorectal cancer is a leading cause of cancer mortality and early detection can significantly improve the clinical outcome. Most colorectal cancers arise from benign neoplastic lesions recognized as adenomas. Only a small percentage of all adenomas will become malignant. Thus, there is a need to identify specific markers of malignant potential. Studies at the molecular level have demonstrated an accumulation of genetic alterations, some hereditary but for the most occurring in somatic cells. The most common are the activation of ras, an oncogene involved in signal transduction, and the inactivation of p53, a tumor suppressor gene implicated in cell cycle regulation. In this study, 38 carcinomas, 95 adenomas and 20 benign polyps were analyzed by immunohistochemistry for the abnormal expression of p53 and ras proteins. An index of cellular proliferation was also measured by labeling with PCNA. A general overexpression of p53 was immunodetected in 66% of the carcinomas, while 26% of adenomas displayed scattered individual positive cells or a focal high concentration of positive cells. This later was more associated with severe dysplasia. Ras protein was detected in 37% of carcinomas and 32% of adenomas mostly throughout the tissue. p53 immunodetection was more frequent in adenomas originating in colons with synchronous carcinomas, particularly in patients with familial adenomatous polyposis and it may be a useful marker in these cases. Difference in the frequency of p53 and ras alterationbs was related to the location of the neoplasm. Immunodetection of p53 protein was correlated to the presence of a mutation in p53 gene at exon 7 and 5 in 4/6 carcinomas studied and 2 villous adenomas. Thus, we characterized in adenomas the abnormal expression of two proteins encoded by the most commonly altered genes in colorectal cancer. p53 alteration appears to be more specifically associated with transition to malignancy than ras. By using immunohistochemistry, a technique that keeps the architecture of the tissue intact, it was possible to correlate these alterations to histopathological characteristics that were associated with higher risks for transformation: villous content, dysplasia and size of adenoma. ^

High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood

Early detection is an effective means of reducing cancer mortality. Here, we describe a highly sensitive high-throughput screen that can identify panels of markers for the early detection of solid tumor cells disseminated in peripheral blood. The method is a two-step combination of differential display and high-sensitivity cDNA arrays. In a primary screen, differential display identified 170 candidate marker genes differentially expressed between breast tumor cells and normal breast epithelial cells. In a secondary screen, high-sensitivity arrays assessed expression levels of these genes in 48 blood samples, 22 from healthy volunteers and 26 from breast cancer patients. Cluster analysis identified a group of 12 genes that were elevated in the blood of cancer patients. Permutation analysis of individual genes defined five core genes (P ≤ 0.05, permax test). As a group, the 12 genes generally distinguished accurately between healthy volunteers and patients with breast cancer. Mean expression levels of the 12 genes were elevated in 77% (10 of 13) untreated invasive cancer patients, whereas cluster analysis correctly classified volunteers and patients (P = 0.0022, Fisher's exact test). Quantitative real-time PCR confirmed array results and indicated that the sensitivity of the assay (1:2 × 108 transcripts) was sufficient to detect disseminated solid tumor cells in blood. Expression-based blood assays developed with the screening approach described here have the potential to detect and classify solid tumor cells originating from virtually any primary site in the body.

Efeitos do treinamento de força no músculo esquelético em ratos com caquexia induzida pelo câncer

A ausência de terapias eficazes para a caquexia permanece como um problema central para o tratamento do câncer no mundo. Em contrapartida, o treinamento de força (i.e. também conhecido como treinamento resistido) tem sido amplamente utilizado como uma estratégia não farmacológica anticatabólica, prevenindo a perda da massa e da função da musculatura esquelética. Entretanto, o papel terapêutico do treinamento de força na caquexia do câncer permanece apenas especulativo. Portanto, nesse estudo avaliamos se o treinamento de força poderia atenuar a perda da massa e da função da musculatura esquelética em um severo modelo de caquexia do câncer em ratos. Para isso, ratos machos da linhagem Wistar foram randomizados em quatro grupos experimentais: 1) ratos sedentários injetados com solução salina na medula óssea (Controle); 2) ratos injetados com solução salina na medula óssea e submetidos ao treinamento de força (Controle + T); 3) ratos sedentários injetados com células do tumor Walker 256 na medula óssea (Tumor); e 4) ratos injetados com células do tumor Walker 256 na medula óssea e submetidos ao treinamento de força (Tumor + T). Foram avaliados a massa e a área de secção transversa da musculatura esquelética, marcadores de disfunção metabólica e do turnover proteico, a função da musculatura esquelética in vivo e ex vivo, o consumo alimentar, o crescimento tumoral e a sobrevida dos grupos experimentais com tumor. O grupo Tumor apresentou atrofia muscular após quinze dias da injeção das células tumorais como pode ser observado pela redução na massa dos músculos Plantaris (- 20,5%) e EDL (-20%). A atrofia no músculo EDL foi confirmada por análises histológicas, demonstrando uma redução de 43,8% na área de secção transversa. Embora o treinamento de força tenha aumentado o conteúdo proteico da lactato desidrogenase e revertido totalmente o conteúdo da forma fosforilada de 4EBP-1 (i.e. repressor da transcrição de mRNA), ele não atuou na morfologia da musculatura esquelética nos animais com tumor. Além disso, o treinamento de força não atenuou a perda de função da musculatura esquelética, a anorexia, o crescimento tumoral ou a taxa de mortalidade. Contudo, a força muscular, avaliada pelo teste de 1RM, apresentou uma correlação negativa com a sobrevida dos animais (p = 0,02), sugerindo que a perda de força prediz a mortalidade nesse modelo experimental de caquexia do câncer. Em suma, a injeção de células do tumor Walker 256 na medula óssea induz caquexia do câncer em ratos. O treinamento de força não foi eficaz em atenuar a perda de massa e função da musculatura esquelética nesse modelo. Entretanto, a força muscular prediz a sobrevida dos animais, sugerindo que novos estudos são necessários para elucidar o possível efeito terapêutico do treinamento de força para atenuar a caquexia do câncer e a progressão tumoral