Pathophysiology of cancer cachexia

Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluated individually in order to clarify the intricate alterations observed in tumor-bearing patients. The difficulties in introducing sound and effective nutritional support or metabolic manipulation to reverse cancer cachexia are outlined in this review.

Heterogeneous response of adipose tissue to cancer cachexia

Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES), retroperitoneal (RPAT), and epididymal (EAT) adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections) and EAT (nuclear bodies).

A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats

Cancer cachexia induces host protein wastage but the mechanisms are poorly understood. Branched-chain amino acids play a regulatory role in the modulation of both protein synthesis and degradation in host tissues. Leucine, an important amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A leucine-supplemented diet was used to analyze the effects of Walker 256 tumor growth on body composition in young weanling Wistar rats divided into two main dietary groups: normal diet (N, 18% protein) and leucine-rich diet (L, 15% protein plus 3% leucine), which were further subdivided into control (N or L) or tumor-bearing (W or LW) subgroups. After 12 days, the animals were sacrificed and their carcass analyzed. The tumor-bearing groups showed a decrease in body weight and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9 ± 0.6, LW = 23.1 ± 1.0 g vs N = 29.4 ± 1.3, L = 28.1 ± 1.9 g, P < 0.05). Tumor weight was similar in both tumor-bearing groups fed either diet. Western blot analysis showed that myosin protein content in gastrocnemius muscle was reduced in tumor-bearing animals (W = 0.234 ± 0.033 vs LW = 0.598 ± 0.036, N = 0.623 ± 0.062, L = 0.697 ± 0.065 arbitrary intensity, P < 0.05). Despite accelerated tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and muscle myosin maintenance, suggesting that excess leucine in the diet could counteract, at least in part, the high host protein wasting in weanling tumor-bearing rats.

Proportional cancer incidence according to selected sites: comparison between residents in the City of S. Paulo, Brazil: Japanese and Brazilian/Portuguese descent

The percentual distributions of selected sites of cancer cases according to origin, sex and age are compared. Data were obtained from the Registry of Cancer of S. Paulo (School of Public Health of the University of S. Paulo, Brazil). The reference period for inhabitants of Japanese descent was 1969/78 and for those of Brazilian descent, the period was 1969/75. Standardized Proportionate Incidence Ratios (SPIR) with approximate 95% Confidence Intervals (CI) were evaluated using age specific Incidence Ratios of S. Paulo, 1973, as standards. The results agree with findings of previous works on mortality, but show different patterns according to origin. The well known fact that some sub-groups of a population may be different from the overall group is once again brought to the fore. Attention should be drawn to the differences detected for stomach, skin and prostate, in males, and for stomach, skin, cervix and uterus in females.

Cost of diseases in Brazil: breast cancer, enteritis, cardiac valve disease and bronchopneumonia

The results from the need to develop methodologies for performing cost analysis in developing countries, principally in the region of Latin America, were studied. It, furthermore, serves to generate knowledge from an economic evaluation in order to support decision-making related to the organization of health systems, particularly in the efficient use of resources which are allocated for the provision of medical services. Two chronic diseases (breast cancer and cardiac valve disease) and two infections (enteritis and bronchopneumonia) were selected for the study. The results recommend the use of a valid methodology for economic cost analysis of any disease to be studied and the use of this information in the decision-making process.

Breast cancer in Mexican women: an epidemiological study with cervical cancer control

INTRODUCTION: In Mexico, breast cancer (BC) is one of the main causes of cancer deaths in women, with increasing incidence and mortality in recent years. Therefore, the aim of the study is identify possible risk factors related to BC. METHODS: An epidemiological study of hospital cases of BC and controls with cervical uterine cancer (CUCA) was carried out at eight third level concentration hospitals in Mexico City. The total of 353 incident cases of BC and 630 controls with CUCA were identified among women younger than 75 years who had been residents of the metropolitan area of Mexico City for at least one year. Diagnosis was confirmed histologically in both groups. Variables were analyzed according to biological and statistical plausibility criteria. Univariate, bivariate and multivariate analyses were carried out. Cases and controls were stratified according to the menopausal hormonal status (pre and post menopause). RESULTS: The factors associated with BC were: higher socioeconomic level (OR= 2.77; 95%CI = 1.77 - 4.35); early menarche (OR= 1.32; 95%CI= 0.88 - 2.00); old age at first pregnancy (>31 years: OR= 5.49; 95%CI= 2.16 - 13.98) and a family history of BC (OR= 4.76; 95% CI= 2.10 - 10.79). In contrast, an increase in the duration of the breastfeeding period was a protective factor (>25 months: OR= 0.38; 95%CI= 0.20 - 0.70). CONCLUSIONS: This study contributes to the identification of risk factors for BC described in the international literature, in the population of Mexican women. Breastfeeding appears to play an important role in protecting women from BC. Because of changes in women`s lifestyles, lactation is decreasing in Mexico, and young women tend not to breastfeed or to shorten the duration of lactation.

Cancer incidence in eighteen cities of the State of São Paulo, Brazil

OBJECTIVE: As in Brazil cancer registries are mostly based on large cities, there are no estimates per state or per region and information on the disease incidence in the vast in-land areas is very scarce. An incidence survey was conducted in 18 major cities of the state of São Paulo, excluding the capital, aiming to collect information about cancer incidence in the state of São Paulo. METHODS: Of the 18 cities in state of São Paulo included in the survey, all had available resources for cancer management. Data from the year of 1991 were collected by the personnel of the Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Statistics), who were especially trained by the study coordinators at the Fundação Oncocentro de São Paulo (Cancer Center of São Paulo). The collected data were processed and analyzed at the Oncocentro. Data collection, processing, and analyses were performed according to the recommendations of the International Agency for Research on Cancer. RESULTS: Although some discrepancies were observed in cancer incidence rates between the cities, results obtained for all 18 cities combined were remarkably close to those recently found for the city of São Paulo in the year 1993. One remarkable finding was the relatively high cancer incidence rates in both sexes in the city of Santos. CONCLUSIONS: The very similar all-sites cancer incidence rates found in the year 1991, when compared to those for the city of São Paulo in the year 1993, are suggestive that all regions have common cancer-related factors. Nevertheless, other explanations, such as the inclusion in the study of prevalent cases, as well as of non-residents, may have occurred in both studies, biasing the results. There is a need of further studies to confirm the high cancer incidence in Santos.

Modern cancer epidemiological research: genetic polymorphisms and environment

Individual cancer susceptibility seems to be related to factors such as changes in oncogenes and tumor suppressor genes expression, and differences in the action of metabolic enzymes and DNA repair regulated by specific genes. Epidemiological studies on genetic polymorphisms of human xenobiotics metabolizing enzymes and cancer have revealed low relative risks. Research considering genetic polymorphisms prevalence jointly with environmental exposures could be relevant for a better understanding of cancer etiology and the mechanisms of carcinogenesis and also for new insights on cancer prognosis. This study reviews the approaches of molecular epidemiology in cancer research, stressing case-control and cohort designs involving genetic polymorphisms, and factors that could introduce bias and confounding in these studies. Similarly to classical epidemiological research, genetic polymorphisms requires considering aspects of precision and accuracy in the study design.

Dietary patterns and risk of oral cancer: a case-control study in São Paulo, Brazil

OBJECTIVE: To analyze the association between dietary patterns and oral cancer. METHODS: The study, part of a Latin American multicenter hospital-based case-control study, was conducted in São Paulo, Southeastern Brazil, between November 1998 and March 2002 and included 366 incident cases of oral cancer and 469 controls, frequency-matched with cases by sex and age. Dietary data were collected using a food frequency questionnaire. The risk associated with the intake of food groups defined a posteriori, through factor analysis (called factors), was assessed. The first factor, labeled "prudent," was characterized by the intake of vegetables, fruit, cheese, and poultry. The second factor, "traditional," consisted of the intake of rice, pasta, pulses, and meat. The third factor, "snacks," was characterized as the intake of bread, butter, salami, cheese, cakes, and desserts. The fourth, "monotonous," was inversely associated with the intake of fruit, vegetables and most other food items. Factor scores for each component retained were calculated for cases and controls. After categorization of factor scores into tertiles according to the distribution of controls, odds ratios and 95% confidence intervals were calculated using unconditional multiple logistic regression. RESULTS: "Traditional" factor showed an inverse association with cancer (OR=0.51; 95% CI: 0.32; 0.81, p-value for trend 0.14), whereas "monotonous" was positively associated with the outcome (OR=1.78; 95% CI: 1.78; 2.85, p-value for trend <0.001). CONCLUSIONS: The study data suggest that the traditional Brazilian diet, consisting of rice and beans plus moderate amounts of meat, may confer protection against oral cancer, independently of any other risk factors such as alcohol intake and smoking.

Functional Assessment of Cancer Therapy Bone Marrow Transplantation: tradução e validação

OBJETIVO: Traduzir para o português e validar o questionário de qualidade de vida Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) em pacientes transplantados de medula óssea. OBJETIVO: O estudo foi realizado em Ribeirão Preto, SP, em 2005. O FACT-BMT (versão 3) traduzido e a versão em português do Short Form-36 Health Survey (SF-36) foram aplicados simultaneamente em 55 pacientes consecutivos com leucemia, submetidos ao transplante e em seguimento. Dois parâmetros clínicos foram utilizados para testar a sensibilidade do questionário: tempo decorrido do transplante e presença ou não de doença do enxerto contra o hospedeiro. Foi utilizada a análise de variância (ANOVA) com o teste post hoc de Tukey. Aplicou-se o coeficiente alfa de Cronbach, padronizado para todas as questões, escore final e domínios. RESULTADOS: A média de idade dos pacientes foi 34,8±8,1 anos, com escolaridade média de 10,8±4,7 anos, sendo 78,1% do sexo feminino. A duração média de tempo pós-transplante foi de 29,8±32,19 meses. Nenhuma alteração do formato original do questionário foi observada no final do processo de tradução e adaptação cultural. A consistência interna foi alta (0,88). A correlação entre o questionário traduzido e o SF-36 variou de 0,35 a 0,57, considerada de moderada a boa para a maioria dos domínios de qualidade de vida. A avaliação das validades de construto e concorrente foi satisfatória e estatisticamente significativa. CONCLUSÕES: A versão para o português do FACT-BMT foi validada satisfatoriamente para a aplicação em pacientes brasileiros de ambos os sexos submetidos ao transplante de medula óssea.

Oral health, hygiene practices and oral cancer

OBJECTIVE: To assess the association between oral health and hygiene practices and oral cancer. METHODS: Hospital-based case-control study in the metropolitan area of São Paulo, southeastern Brazil, from 1998 to 2002. A total 309 patients with squamous cell carcinoma of the mouth and the pharynx and 468 controls matched by sex and age were included in the study. Cases were recruited in seven reference hospitals and controls were selected in five out of the seven participating hospitals. Detailed information on smoking, alcohol consumption, schooling, oral health status and hygiene practices were obtained through interviews. Odds ratios (OR) and 95% confidence intervals (95% CI), adjusted by sex, age, schooling, smoking, alcohol consumption as well as the variables oral health status and hygiene practices were estimated using unconditional logistic regression analyses. RESULTS: The use of complete dental prosthesis was not associated with oral cancer but regular gum bleeding showed a strong association (OR 3.1; 95% CI 1.2-7.9). Those who never attended a dental visit were more likely to have oral cancer (OR 2.5; 95% CI 1.3-4.8). Daily mouthwash use showed a stronger association to pharynx (OR 4.7; 95% CI 1.8-12.5) than mouth cancer (OR 3.2; 95% CI 1.6-6.3). CONCLUSIONS: Gum bleeding, no dental care, and daily mouthwash use were factors associated with oral cancer regardless of tobacco and alcohol consumption.

Factors related to inadequate cervical cancer screening in two Brazilian state capitals

OBJECTIVE:To analyze factors associated with cervical cancer screening failure. METHODS:Population-based cross-sectional study with self-weighted two-stage cluster sampling conducted in the cities of Fortaleza (Northeastern Brazil) and Rio de Janeiro (Southeastern Brazil) in 2002. Subjects were women aged 25-59 years in the last three years prior to the study. Data were analyzed through Poisson regression using a hierarchical model. RESULTS: The proportion of women who did not undergo the Pap smear test in Fortaleza and Rio de Janeiro was 19.1% (95% CI: 16.1;22.1) and 16.5% (95% CI: 14.1;18.9), respectively. Higher prevalence ratios of cervical cancer screening failure in both cities were seen among women with low education and low per capita income, old age, unmarried, who never underwent mammography, clinical breast examination, and blood glucose and cholesterol level testing. Smokers also had lower screening rates compared to non-smoker women and this difference was only statistically significant in Rio de Janeiro. CONCLUSIONS:The study findings point to the need of intervention focusing particularly women in worse socioeconomic conditions and access to healthcare, old-aged and unmarried. Education activities must prioritize screening of asymptomatic women and early diagnosis for symptomatic women and access to adequate diagnostic methods and treatment should be provided.

Survival of a cohort of women with cervical cancer diagnosed in a Brazilian cancer center

OBJECTIVE: To assess overall survival of women with cervical cancer and describe prognostic factors associated. METHODS: A total of 3,341 cases of invasive cervical cancer diagnosed at the Brazilian Cancer Institute, Rio de Janeiro, southeastern Brazil, between 1999 and 2004 were selected. Clinical and pathological characteristics and follow-up data were collected. There were performed a survival analysis using Kaplan-Meier curves and a multivariate analysis through Cox model. RESULTS: Of all cases analyzed, 68.3% had locally advanced disease at the time of diagnosis. The 5-year overall survival was 48%. After multivariate analysis, tumor staging at diagnosis was the single variable significantly associated with prognosis (p<0.001). There was seen a dose-response relationship between mortality and clinical staging, ranging from 27.8 to 749.6 per 1,000 cases-year in women stage I and IV, respectively. CONCLUSIONS: The study showed that early detection through prevention programs is crucial to increase cervical cancer survival.

Efeito idade-periodo-coorte na mortalidade por cancer do colo uterino

OBJETIVO: Estimar o efeito da idade, período e coorte de nascimento na mortalidade por câncer do colo do útero. MÉTODOS: Foram analisados dados de mortalidade por câncer do colo do útero em mulheres ≥ 30 anos nos municípios do Rio de Janeiro, RJ, e São Paulo, SP, de 1980 a 2009. Os dados foram extraídos do Sistema de Informação Sobre Mortalidade. A variação percentual anual estimada foi calculada para os períodos de 1980-1994 e 1995-2009. O efeito da idade, período e coorte de nascimento foi calculado pelo modelo de regressão de Poisson, utilizando funções estimáveis: desvios, curvaturas e drift , por meio da biblioteca Epi do programa estatístico R versão 2.7.2. RESULTADOS: A taxa de mortalidade média do período por 100.000 mulheres foi 15,90 no Rio de Janeiro e 15,87 em São Paulo. Houve redução significativa na mortalidade por câncer do colo do útero nos dois períodos: no Rio de Janeiro, -1,20% (IC95% -2,20;-0,09) e -1,46% (IC95% -2,30;-0,61), e em São Paulo, -2,58% (IC95% -3,41;-1,76) e -3,30% (IC95% -4,30;-2,29). A análise da curvatura dos efeitos indicou tendência de redução do risco de morte nas sucessivas coortes (RR < 1 nas mulheres nascidas após a década de 1960). Observou-se redução acentuada no risco relativo (RR) a partir dos anos 2000. CONCLUSÕES: O estudo evidenciou efeito de período na redução das taxas de mortalidade por câncer do colo do útero no período analisado, tendo em vista que houve efeito de proteção (RR < 1) a partir dos anos 2000 e nas mulheres nascidas após a década de 1960.

Assistencia ao cancer entre criancas e adolescentes: mapeamento dos fluxos origem-destino no Brasil

OBJETIVO: Analisar os fluxos de viagens de crianças e adolescentes com câncer, entre os locais de residência e serviço de saúde. MÉTODOS: Foram analisados os fluxos de viagens de crianças e adolescentes com câncer entre os locais de residência e de serviço de saúde atendidos no Sistema Único de Saúde (SUS), de 2000 a 2007. A unidade de análise foi a regional de saúde. Utilizou-se o sistema de informações geográficas e metodologia de redes por tipo de tratamento recebido (quimioterapia e radioterapia) e internações hospitalares. RESULTADOS: Foram emitidas 465.289 autorizações de quimioterapia, 29.151 de radioterapia e 383.568 de internações hospitalares de crianças e adolescentes com diagnóstico de câncer para tratamento no SUS. O fluxo dominante formou 48 redes para quimioterapia, 53 para radioterapia e 112 para internações hospitalares. A maior parte do volume de atendimento ocorreu nas regionais de saúde das 12 maiores metrópoles do País com grande relacionamento entre elas e extensa área de influência direta acompanhando a estrutura da rede urbana brasileira. CONCLUSÕES: A identificação das redes estabelecidas no âmbito do SUS para o atendimento de crianças e adolescentes com câncer mostra que a maioria dos pacientes está contemplada pelas redes estruturadas. Cerca de 10% das viagens ocorrem fora do fluxo dominante, indicando a necessidade de regionalização alternativa. Os resultados evidenciam a importância do planejamento da distribuição dos serviços de acordo com as necessidades da população usuária.