O objetivo do estudo foi avaliar o efeito da escuta terapêutica na ansiedade pré-operatória e nos medos relacionados à cirurgia em pacientes hospitalizados para tratamento cirúrgico de câncer colorretal. Tratou-se de um ensaio clínico aleatorizado realizado em um hospital geral. Os participantes foram aleatorizados em dois grupos: experimental (GE) (n=25) e controle (GC) (n=25). No GE era realizada a escuta terapêutica, de modo que os pacientes tinham 30 minutos para falar com a pesquisadora sobre sua experiência com a hospitalização para o tratamento da doença. No GC os pacientes eram informados que teriam alguns dados coletados, em seguida a pesquisadora se ausentaria por 30 minutos e que, após este intervalo, a mesma retornaria para a conclusão da pesquisa. As variáveis dependentes (alfa-amilase, cortisol, frequência de pulso, frequência respiratória, pressão arterial, ansiedade estado e medos relacionados à cirurgia) foram coletadas antes e após a realização da intervenção no GE e antes e após o intervalo supracitado no GC. Na comparação das variáveis dependentes no GE em relação ao GC no momento pós-intervenção, não foram identificadas diferenças significativas para nenhuma das variáveis estudadas. Na comparação das variáveis no GE e GC nos momentos pré e pós-intervenção, constatou-se diferenças significativas apenas entre os momentos no GC para as variáveis cortisol (Z=-2,023; p=0,043), frequência de pulso (FP) (Z=-2,121; p=0,034) e medos relacionados à cirurgia (Z=-2,171; p=0,030), com redução dos valores destas variáveis. Na relação entre as variáveis estudadas obteve-se significância entre a ansiedade estado e as variáveis cortisol, idade, escolaridade e religião; os medos relacionados à cirurgia foram relacionados ao sexo, tempo de confirmação do diagnóstico de câncer colorretal, nível de escolaridade, cortisol, estado civil e à pressão arterial diastólica. Apenas a variável renda familiar mensal apresentou diferença significativa em suas distribuições no GE e no GC, no entanto, esta não teve influência sobre as variáveis dependentes. A maioria dos pacientes referiu satisfação quanto ao desenvolvimento da intervenção. Conclui-se que, no momento pré-operatório, nas condições investigadas neste estudo, os dados evidenciaram que a mensuração das variáveis imediatamente após a intervenção de escuta terapêutica de 30 minutos não evidenciou a redução esperada dos valores das variáveis estudadas; estudos com medidas dessas variáveis após um tempo para o paciente processar os efeitos da intervenção poderão confirmar se a mensuração imediata ou uma hora após a intervenção, por exemplo, conduziria a resultados distintos. Contudo, houve redução dos valores de cortisol, frequência de pulso e medos relacionados à cirurgia nos participantes do GC, o que pode ser atribuído ao contato da pesquisadora com tais participantes durante os momentos de coleta de dados / The aim of the study was to evaluate the effect of therapeutic listening on preoperative anxiety and fears related to surgery in patients hospitalized for surgical treatment of colorectal cancer. This is a randomized clinical trial conducted in a general hospital. Participants were randomized in two groups: experimental (n=25) and control (n=25). In the experimental group was performed therapeutic listening. The patients had thirty minutes to talk to the researcher about their experience with hospitalization for the treatment of disease. In the control group patients were informed that they would have some data collected, then the researcher would be gone for thirty minutes and after this range, she would return to complete the research. The dependent variables (alpha-amylase, cortisol, pulse rate, respiratory rate, blood pressure, anxiety state and fears related to surgery) were collected before and after the intervention in experimental group and before and after the break in control group. In comparing the dependent variables in the experimental group compared to the control group in the post-intervention time, no significant differences were identified for any of the variables studied. In comparing the variables in the experimental group and the control group in the pre and post-intervention, there was significant differences only between times in the control group for cortisol (Z=-2,023; p=0,043), pulse rate (Z= -2,121; p=0,034) and fears related to surgery (Z= -2,171; p=0,030), with reduced of these variables. In the relationship between the studied variables, there was a significant difference between state anxiety and the variables cortisol, age, education level and religion; the fears related to the surgery were related to sex, time of confirmation of the diagnosis of colorectal cancer, education level, cortisol, marital status and diastolic blood pressure. Only the variable monthly income showed a significant difference in their distributions in the experimental group and the control group, however, this had no influence on the dependent variables. Most patients report satisfaction with the development of the intervention. It was concluded that, in the preoperative period, under the conditions investigated in this study, the data showed that the measurement of the variables immediately after the intervention of 30 minutes of therapeutic listening did not show the expected reduction of the values of the studied variables; Studies with measures of these variables after a time for the patient to process the effects of the intervention could confirm whether the immediate measurement or one hour after the intervention, for example, would lead to different results. However, there was reduction of cortisol levels, pulse rate and fears related to surgery in the control group, which can be attributed to contact the researcher with these participants during times of data collection

Introdução: O câncer de localização colorretal é o terceiro tipo de câncer mais comumente diagnosticado no mundo. As taxas de incidências do câncer colorretal não são homogêneas, apresentando diferenças entre os países. Não há estudos brasileiros que investiguem a variação geográfica da incidência de câncer colorretal conjuntamente com indicadores socioeconômicos. Esta avaliação pode revelar diferenças locais importantes na ocorrência da doença. Objetivos: Descrever as taxas de incidência e de mortalidade do câncer colorretal no Município de São Paulo, segundo sexo e faixa etária, no período de 1997 a 2009 e realizar análise da distribuição espacial segundo distrito dos casos de câncer colorretal diagnosticados em residentes no Município de São Paulo entre 1997 e 2009. Material e Métodos: Foram analisados os novos casos de câncer colorretal diagnosticados em residentes no Município de São Paulo de 1997 a 2009. Estes dados foram fornecidos pelo Registro de Câncer de Base Populacional de São Paulo (RCBP-SP). A análise dos dados foi realizada em duas etapas: na primeira, com cárater exploratório/descritivo, os dados analíticos foram utilizados para descrever a incidência e mortalidade por câncer colorretal no período pesquisado. Na segunda etapa, os casos de câncer colorretal foram geocodificados, agrupados por distrito administrativo e estudados segundo a metodologia de análise para dados de área. Toda análise foi implementada no software R. Resultados: Com 7,7 por cento e 7,3 por cento dos casos respectivamente em homens e mulheres, câncer colorretal foi o segundo tipo de câncer mais frequente, sendo a quarta (9,0 por cento dos óbitos) e a segunda (11,0 por cento dos óbitos) causa de morte respectivamente em homens e mulheres. Do total de casos incidentes (39.250), 47,50 por cento são do sexo masculino e 52,50 por cento do sexo feminino. Destes, 4.784 (37,7 por cento ) evoluíram a óbito, sendo 48,1 por cento no sexo masculino e 51,9 por cento no sexo feminino. As taxas específicas por sexo e faixa etária de incidência aumentam fortemente com a idade, na faixa etária de 80 ou mais anos chega a 377,9 e 282,9 (por 100 mil hab.) para o sexo masculino e feminino respectivamente, sendo relativamente próximas em ambos os sexos até a idade de 49 anos e maiores para homens nas faixas etárias subsequentes. As taxas específicas por sexo e faixa etária de mortalidade, apresentam comportamento análogo, aumentam fortemente com a idade, na faixa etária de 80 ou mais anos chega a 206,9 e 159,9 (por 100 mil hab.) para o sexo masculino e feminino respectivamente. A taxa anual de incidência ajustada pela população de SEGI (1960) e modificada por DOLL et al. (1966) apresenta-se em torno de 30,0 (por 100 mil hab.) nos três primeiros anos observados (1997-1999), chega a 19,0 (por 100 mil hab.) em 2002, volta a crescer nos anos seguintes (2003-2005), chegando a 31,7 (por 100 mil hab.) e matem-se estável de 2007 a 2009. A taxa anual de mortalidade de câncer colorretal ajustada pela população crescente até 2004, chegando a 15,7 (por 100 mil hab.) e decrescem nos anos seguintes, chegando a aproximadamente 3,6 mortes por 100 mil habitantes em 2009. A média anual da taxa bruta de incidência e os indicadores socioeconômicos apresentam dependência forte dependência espacial, sendo o menor Índice I de Moran observado foi para o índice de exclusão/inclusão dos anos potenciais de vida perdidos (IEX apvp = 0,29), os demais são acima de 0,6. Os indicadores apresentam forte correlação linear com a média anual da taxa bruta de incidência. Conclusões: As distribuições da incidência e da mortalidade apresentam padrões semelhantes ao identificado mundialmente. O Município de São Paulo tem taxas equivalentes às encontradas nas regiões em transição econômica. Foi identificada forte dependência espacial na distribuição da incidência de câncer colorretal no Município de São Paulo, com a formação de clusters nas áreas centrais e periféricas. As maiores taxas são encontradas nas áreas centrais e nas periferias. A distribuição espacial da incidência de câncer colorretal apresenta forte associação com a distribuição dos indicadores de status socioeconômico no Município de São Paulo, em particular apresenta associação positiva com indicadores de renda e escolaridade. / Introduction: Colorectal cancer is the third most common diagnosed cancer worldwide. Colorectal cancer incidence rates are not homogeneous, with differences between countries. No Brazilian studies investigated the geographical variation of colorectal cancer incidence with socioeconomic indicators. This study may reveal important local differences in the occurrence of the disease. Objectives: To describe colorectal cancer incidence and mortality in São Paulo, by sex and age using 1997-2009 data and perform the spatial distribution analysis according to district colorectal cancer cases diagnosed in residents at Municipality of São Paulo between 1997 and 2009. Methods: Colorectal cancer cases diagnosed from 1997 to 2009 in São Paulo residents were analyzed. These data were provided by Population Based Cancer Registry of São Paulo (RCBP-SP). Data analysis was performed in two stages. First, analytical data were used to describe the incidence and mortality from colorectal cancer. Second, colorectal cancer cases were geocoded, grouped by administrative district and studied according data area analysis methodology. All analysis was implemented in software R. Results: 7.7 per cent and 7.3 per cent of observed cases was respectively in men and women, colorectal cancer was the second most common cancer, the fourth (9.0 per cent ) cause of death in men and the second (11.0 per cent ) cause in women. It was diagnosed 39,250 colorectal cancer new cases, 47.50 per cent in men and 52.50 per cent in women. And 4,784 (37.7 per cent ) died, with 48.1 per cent in male and 51.9 per cent in female. The specific incidence rates strongly increase with age, at the 80 years or more age reaches 377.9 and 282.9 (per 100,000 inhabitants) for male and female respectively. The mortality specific rates, have similar behavior, strongly increase with age and at the 80 years or more age reaches 206.9 and 159.9 (per 100,000 inhabitants), for males and female respectively. The annual age adjusted incidence rate was around 30.0 (per 100,000 inhab.) in the first observed years (1997-1999), arrives to 19.0 (per 100,000 inhab.) in 2002, grow back reaching 31.7 (per 100,000 inhab.) and kill stable from 2007 to 2009. The annual age colorectal cancer mortality rate grow reaching 15.7 (per 100,000 inhab.) and decrease in the following years, reaching approximately 3.6 deaths per 100,000 inhabitants in 2009. The average annual the crude incidence rate and the socio-economic indicators show strong spatial dependence, the lowest Moran´s I Index was observed for the exclusion/inclusion potential years of life lost index (IEX apvp = 0.29). The indicators show strong linear correlation with the average annual crude incidence rate. Conclusions: Distributions of incidence and mortality have similar worldwide patterns. The Municipality of São Paulo has equivalent rates founded in regions in economic transition. It was identified strong spatial dependence in the distribution of the incidence of colorectal cancer, with the formation of clusters in the central and peripheral areas of Municipality of São Paulo. The highest rates were found in the central areas and lowest were found in the suburbs. The spatial distribution of colorectal cancer incidence has a strong association with the socioeconomic status indicators distribution in Municipality of São Paulo. It was identified positive association between colorectal cancer incidence with income and education indicators.

Submitted by Rosangela Silva (rosangela.silva3@unioeste.br) on 2018-05-24T20:10:40Z No. of bitstreams: 2 Bruna Brasil Rodrigues Furtado.pdf: 1803735 bytes, checksum: 07becc4d75752532c49c5275ef0cabb9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-05-24T20:10:40Z (GMT). No. of bitstreams: 2 Bruna Brasil Rodrigues Furtado.pdf: 1803735 bytes, checksum: 07becc4d75752532c49c5275ef0cabb9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-01 / Increased longevity, poor eating habits and genetic predisposition are some of the factors related to the increase of chronic diseases, such as cancer. Colorectal cancer is a neoplasia related to diets rich in fats and refined carbohydrates, with poor fiber and protein. This situation has increased the number of researches that evaluate the anticancer activity of several bioactive compounds, aiming at foods and pharmaceuticals. Probiotic bacteria have been researched in action studies on several cancer cell lines, being proposed different mechanisms. Lactobacillus acidophilus, among the probiotics is lactic acid bacteria, with well-defined probiotic capacity. Objectives: This study aimed at evaluating the effect of Lactobacillus acidophilus in patients with colorectal cancer by means of clinical studies administered individually or in association with other substances and probiotic bacteria through food or pharmaceuticals. Methodology: A systematic review of the literature was carried out in the following databases: Medline, Embase, Elsevier, Cochrane Central Register of Controlled Trials, Scopus, Web of Science and Scielo. The search strategies were composed of the terms "colorectal cancer", oxidative stress, "antioxidant activity", "Lactobacillus acidophilus", "probiotics" and "randomized controlled trial" associated with boolean operators AND or OR, being adjusted according to the base of data. Manual search was also carried out on the bibliographic references of the articles included. There were no restrictions on time, but language was limited to articles published in English, Spanish and Portuguese. We included all clinical studies that used L. acidophilus alone or associated with other probiotic bacteria and fibers in colorectal cancer patients. Articles that included yeasts, which the evaluation parameters did not show clinical data or that had patients with diseases other than colorectal cancer and whose data were not separated and that they had probiotic bacteria but did not have L. acidophilus, were not included in the study. We also did not include articles with languages other than those stipulated, nor those in which the inclusion of L. acidophilus was not clear in the study by lack of probiotic strains. Handling and data management were done through the Microsoft Office Excel 2013® and Endnote Web® X8 programs for data management. The evaluation of quality and risk of bias were performed through the Review Manager 5.3® program. Results and Discussion: 1028 articles were retrieved from the databases, eight of which met the necessary requirements and were used in the study. As limitations, it is important to note the impossibility of accessing the query in the Embase database; in the same way, considering that five of the eight articles included come from China (three from the same study group), laying uncertainty about the application of results found in Western diets. The evaluation resulted in a total of 616 individuals, 297 with colorectal cancer in the probiotic group, 286 colorectal cancer patients who were in the control and / or placebo group, and 33 healthy individuals. All the included studies presented the association of the L. acidophilus with other probiotic bacteria. Two articles associated with prebiotic fibers (inulin and fructooligosaccharides). All studies were randomized to seven double-blind studies and one study with a control group without placebo. The administration of the probiotic mixture was by pharmaceutical forms (capsules in 04 articles, sachets in 03 articles and tablets in one article). The main outcomes analyzed were the integrity of the intestinal barrier, microbiological culture, microbiota alteration, postoperative clinical observations and only one article was analyzed indirectly antioxidant capacity. Three outcomes (intestinal barrier integrity, microbiota alteration and microbiological culture) depicted that the intervention of probiotic bacteria was statistically significant (P< 0.05) compared to placebo. In the analysis of postoperative clinical observations, through meta-analysis, it was evidenced that the administration of probiotics decreased the incidence of operative infections in comparison to the placebo group, a result related to the improvement of intestinal barrier integrity. The antioxidant activity was verified only in one article, through the measurement of ALT and AST liver enzymes, but further studies are needed to prove this antioxidant capacity in human individuals with colorectal cancer. Conclusions: The study highlighted that there are no studies involving Lactobacillus acidophilus individually in humans with colorectal cancer, which may allow more direct studies with the use of this bacterium in this pathology, allowing a better understanding of its behavior and mechanisms of action and, in this way, clarifying in fact the actions that their use have in this pathological condition. It has also pinpointed that few analyzes of the antioxidant capacity are made in humans, showing that it is an significant area of study although it is palliative to the oxidative stress that cancer patients possess; Thus, studies with antioxidant enzymes, such as glutathione and superoxide dismutase, may be the object of analysis in future studies, as well as the measurement of metabolites related to oxidative stress, biomarkers and substances that protect the intestinal mucosa, showing that the possibilities of studies of the biological activities of this bacterium are quite broad. The main effects of administration of strains of L. acidophilus with other probiotic bacteria are the reduction of bacterial translocation, followed by effects related to this outcome, such as: qualitative and quantitative alteration of the intestinal microbiota and reduction of postoperative complications; which results in a better quality of life for the individual who received the intervention and decrease hospital costs due to shortening stay and infections related to surgical procedure. / O aumento da longevidade, hábitos alimentares inadequados e predisposição genética são alguns dos fatores relacionados ao aumento de doenças crônicas, como o câncer. O câncer de cólon e reto, também denominado câncer colorretal, é uma neoplasia relacionada às dietas ricas em gorduras e carboidratos refinados, com pobreza de fibras e proteínas. Essa situação aumentou o número de pesquisas que avaliam a atividade anticancerígena de diversos compostos bioativos, com o objetivo de aplicação em alimentos e produtos farmacêuticos. As bactérias probióticas têm demonstrado, em alguns estudos, ação sobre diversas linhagens de células cancerígenas, sendo propostos diferentes mecanismos de ação a partir de sua atividade antioxidante. Destaca-se, entre as bactérias probióticas, o Lactobacillus acidophilus, uma bactéria ácido-lática com capacidade probiótica bem definida, de forma cepa-dependente. Objetivos: O objetivo do trabalho foi avaliar, com auxílio da metodologia de Medicina Baseada em Evidências, o efeito da administração de cepas de Lactobacillus acidophilus em pacientes com câncer colorretal por meio de estudos clínicos administrado individualmente ou em combinação com outras substâncias e cepas probióticas, por meio de alimentos ou de formas farmacêuticas. Metodologia: Foi realizada uma revisão sistemática da Literatura nas seguintes bases de dados: Medline, Embase, Elsevier, Cochrane Central Register of Controlled Trials, Scopus, Web of Science e Scielo. As estratégias de busca foram compostas dos termos “colorectal cancer”, “oxidative stress”, “antioxidant activity”, “Lactobacillus acidophilus”, “probiotics” e “randomized controlled trial” associados aos operadores booleanos AND ou OR, sendo ajustados de acordo com a base de dados. Também foi realizada busca manual a partir das referências bibliográficas dos artigos incluídos. Não houve restrições quanto ao tempo, contudo, limitou-se o idioma em artigos publicados em inglês, espanhol e português. Foram incluídos todos os estudos clínicos que utilizaram cepas de L. acidophilus, exclusivamente ou em associação com outras cepas probióticas, e fibras em pacientes com câncer colorretal. Artigos que incluíam leveduras, dos quais os parâmetros de avaliação não demonstravam dados clínicos, como artigos que utilizaram questionários para avaliar a qualidade de vida, em que os pacientes apresentavam outras doenças além de câncer colorretal, ou, cujos dados não estavam separados e que tinham bactérias probióticas, isentos de L. acidophilus, não foram incluídos no estudo. Também não foram incluídos artigos com idiomas diferentes dos estipulados, nem aqueles onde não estava clara a inclusão de L. acidophilus no estudo por omissão de cepas probióticas. O gerenciamento dos dados foi feito por meio dos programas Microsoft Office Excel 2013®e Endnote Web® X8. A avaliação da qualidade e de risco de viés foram realizadas com o programa Review Manager 5.3®. Resultados e Discussão: Foram recuperados das bases de dados 1028 artigos, sendo que oito se enquadraram nos requisitos necessários e foram utilizados no estudo. Como limitações destacam-se a impossibilidade de acesso a consulta na base de dados Embase; da mesma forma, considerando-se que cinco dos oito artigos incluídos são provenientes da China (três do mesmo grupo de estudo), dando incerteza sobre a aplicação dos resultados encontrados em dietas ocidentais. A avaliação resultou num total de 616 indivíduos, 297 com câncer colorretal no grupo com probióticos, 286 pacientes com câncer colorretal que estavam no grupo controle e/ou placebo e 33 indivíduos saudáveis. Todos os estudos incluídos apresentavam associação do L. acidophilus com outras bactérias probióticas. Dois artigos associaram as fibras prebióticas (inulina e frutooligossacarídeos). Todos os estudos foram randomizados com sete estudos duplo-cegos e um estudo com grupo controle sem placebo. A administração da mistura probiótica foi por meio de formas farmacêuticas (cápsulas em 04 artigos, sachês em 03 artigos e tabletes em um artigo). Os principais desfechos analisados se referiram a integridade da barreira intestinal, cultura microbiológica, alteração da microbiota, observações clínicas pós-operatórias e encontrou-se apenas um artigo que analisou de forma indireta capacidade antioxidante. Três desfechos (integridade da barreira intestinal, alteração da microbiota e cultura microbiológica) demonstraram que a intervenção de bactérias probióticas foi estatisticamente significativa (P < 0.05) em comparação ao placebo. Na análise de observações clínicas pós-operatórias, por meio de de metanálise ficou evidenciado que a administração de probióticos diminuiu a incidência de infecções operatórias em comparação ao grupo placebo, resultado relacionado com a melhora da integridade da barreira intestinal. A atividade antioxidante foi verificada apenas em um artigo, por meio da mensuração das enzimas hepáticas alanina transferase e aspartato transferase, contudo, são necessários mais estudos que comprovem essa capacidade antioxidante em indivíduos humanos com câncer colorretal. Conclusões: O estudo ressaltou que não há artigos envolvendo Lactobacillus acidophilus individualmente em seres humanos com câncer colorretal, o que pode permitir estudos mais direcionados com a utilização de tal bactéria nessa patologia, permitindo conhecer melhor seu comportamento e mecanismos de ação e, desse modo, esclarecer, de fato, as ações que sua utilização têm nessa condição patológica. Considerou-se, também, que poucas análises da capacidade antioxidante são feita em humanos, configurando-se em uma área interessante para estudo, ainda que seja como paliativo ao estresse oxidativo que pacientes com câncer possuem; dessa forma, estudos com enzimas antioxidantes, como glutationa e superóxido dismutase, podem ser objetos de análise em estudos futuros, da mesma forma que a mensuração de metabólitos relacionados ao estresse oxidativo, biomarcadores e substâncias de proteção da mucosa intestinal são possibilidades bastante amplas de estudos das atividades biológica dessa bactéria. Ressaltam-se como principais efeitos da administração de cepas de L. acidophilus com outras bactérias probióticas, a diminuição da translocação bacteriana, seguida de efeitos relacionados a tal desfecho, como: alteração qualitativa e quantitativa da microbiota intestinal e diminuição das complicações pós-operatórias, resultando em melhor qualidade de vida para o indivíduo que recebeu a intervenção e na diminuição de custos hospitalares por diminuição de estadia e de infecções relacionadas a procedimento cirúrgico.

O Câncer Colorretal (CCR) consiste no terceiro tipo de câncer mais comum em homens e o segundo em mulheres. O tratamento, na maioria dos casos, implica na cirurgia geradora de estoma, que constitui um procedimento invasivo, com grande impacto em todas as áreas na vida da pessoa. O presente estudo teve por objetivos investigar prospectivamente variáveis relacionadas à imagem corporal, sintomas ansiosos e depressivos, domínios da Qualidade de Vida Relacionada a Saúde (QVRS) e as cognições, emoções e comportamentos diante do processo de adaptação ao estoma. Trata-se de um estudo exploratório, longitudinal e de abordagem quanti qualitativa. A amostra foi composta por pacientes adultos (n=122), de ambos os sexos, atendidos no Ambulatório de Estomaterapia do Hospital de Câncer de Barretos (SP). A avaliação quantitativa foi realizada em todos os pacientes e a qualitativa em 26 dos pacientes, sorteados aleatoriamente. Os participantes foram avaliados em quatro momentos (pré-operatório, três, seis e quinze meses após a cirurgia) e foram subdivididos de acordo com o tipo de procedimento cirúrgico realizado (Anastomose Primária, Estomia Intestinal Temporária e Estomia Intestinal Definitiva). Para a coleta de dados, foram utilizados os instrumentos: questionário de dados sociodemográficos; Critério de Classificação Econômica Brasil; ficha de condições clínicas; Escala de Figura de Silhuetas (EFS); Escala de Ansiedade e Depressão para Hospital Geral (HADS); Questionários para avaliação da QVRS (EORTC QLQ-C30/ QLQ-CR38); Medida subjetiva de pensamentos e emoções e Roteiro de entrevista semiestruturada. Os resultados demonstraram que a amostra foi constituída por pacientes mais velhos, de baixa renda e escolaridade. Os valores médios encontrados na avaliação da imagem corporal indicaram uma superestimação desta. Apesar dos participantes não terem apresentado sintomatologias graves para ansiedade e depressão, de acordo com a escala HADS, as comparações estatísticas infere-se que, quanto pior a sintomatologia para ansiedade e depressão, pior a saúde global. Segundo o EORTC QLQ-C30 e QLQ-CR38 a maioria dos domínios de QVRS apresentaram níveis moderados, sendo que os piores sintomas foram os sexuais. A depressão influenciou de forma direta e negativa na saúde global, assim como na acurácia da imagem corporal. Foram encontradas diferenças significantes entre os grupos na comparação das variáveis nos diversos momentos de avaliação, sugerindo que o nível dos sintomas variou de acordo com o tempo. Não foram encontradas altas frequências para as distorções cognitivas nesses pacientes, entretanto, observou-se pela entrevista semiestruturada que na primeira avaliação existia grande preocupação quanto às limitações ocasionadas pela estomia intestinal em detrimento da percepção de normalidade, frequentemente reportada na última avaliação. Conclui-se que a entrevista qualitativa complementou os resultados encontrados na abordagem quantitativa, sendo que a análise de conteúdo reforçou que os pacientes, em geral, apresentaram boa adaptação à estomia. O suporte social foi apontado como uma das principais estratégias utilizadas no processo de adaptação. Neste sentido, orientações psicoeducativas aos pacientes e familiares devem ser realizadas desde o diagnóstico, a fim de contribuir para adaptação ao estoma. / The Colorectal Cancer (CRC) is the third most common type in men and the second in women. The treatment in most cases implies a surgery with a stoma, which is an invasive procedure, with a great impact in all areas in a person\'s life. This study aimed to prospectively investigate variables related to body image, depression and anxiety symptoms, areas of Health Related Quality of Life (HRQoL) and cognitions, emotions and behaviors related to the adaptation process to the stoma. It is an exploratory study, longitudinal, with quantitative and qualitative approach. The sample consisted of adult patients (n = 122), of both sexes, attended in Stomatherapy Clinic of Barretos Cancer Hospital. The quantitative evaluation was performed in all patients and the qualitative evaluation was performed in 26 patients randomly selected. Participants were assessed at four time points (preoperative, three, six and fifteen months after surgery) and were subdivided according to the type of surgical procedure performed (Primary Anastomosis, Temporary Intestinal Ostomy and Definitive Intestinal Ostomy). For data collection, the follow instruments were used: socio-demographic questionnaire; Brazilian Economic Classification Criteria; clinical conditions record; Figures of Silhouettes Scale (FSS); Hospital Anxiety and Depression Scale (HADS); Questionnaires to assess the HRQoL (EORTC QoL-C30 / QoL-CR38); Subjective measure of thoughts and emotions and Semi-structured interviews. The results showed that the sample was composed of older patients, with low income and low education level. The mean values found in the evaluation of body image showed an overestimation of it. Although the participants did not show servere symptomatology for anxiety and depression, according to the HADS, statistical comparisons inferred that, the worse the symptoms for anxiety and depression, worse overall health. According to the EORTC QoL-C30 and QoL-CR38 most HRQoL domains showed moderate levels in which the worst symptoms were sexual. Depression had a direct and negative impact on global health, as well as the accuracy of body image. Significant differences were found between groups when comparing the variables in the different time points, suggesting that the level of symptoms varied according to the time. There were no high frequencies for cognitive distortions in these patients; however, the semi-structured interview shows that in the first assessment there was great concern about the limitations caused by intestinal ostomy at the expense of perceived \"normal\" often reported in the last assessment. We conclude that the qualitative interview complemented the findings in quantitative approach, and the content analysis emphasized that patients generally showed good adaptation to the stoma. Social support was considered one of the main strategies used in the adjustment process. In this sense, psychoeducational guidance to patients and their families must be carried out from diagnosis, in order to contribute to the adaptation to the stoma.

L'augmentation de l'incidence et de la mortalité du cancer colorectal nécessitent la découverte de nouvelles méthodes de prévention et de traitement. Les chalcones ont été identifiées comme des composés intéressants ayant des propriétés chimiopreventives et antitumorales. Dans cette étude, nous avons étudié les effets de la 3-hydroxy-3', 4, 4', 5'-tétra-méthoxy-chalcone (3-HTMC), une chalcone synthétisée par notre laboratoire, sur la prolifération, la distribution du cycle cellulaire, l'apoptose et son mécanisme d'action sur les cellules cancéreuses colorectales humaines HT-29 (COX-2 sauvage) et HCT116 (déficientes en COX-2). Nous avons montré que la 3-HTMC diminue la viabilité cellulaire d'une façon dose dépendante avec un effet antiprolifératif plus puissant sur les cellules HCT116 que les cellules HT-29. L'analyse par cytométrie en flux a révélé une accumulation des cellules en phase G2/M du cycle cellulaire pour les cellules HT-29 et un arrêt significatif en G2/M pour les cellules HCT116 avec une apparition du pic sub-G1 caractéristique de l'apoptose. Nous avons démontré que le traitement des deux lignées cellulaires par la 3-HTMC induit un processus apoptotique associé à la surexpression du récepteur de mort DR5, l'activation des caspase-8 et -3, le clivage de la PARP et la fragmentation de l'ADN. De plus, la 3-HTMC induit l'activation des voies de survie PI3K/Akt et MEK/ERK qui sont impliquées dans la résistance à l'apoptose. De même, la 3-HTMC induit une surexpression de la COX-2 dans les cellules HT-29 qui contribue aussi à la résistance à l'apoptose, ceci expliquant la différence de sensibilité entre les cellules HT-29 et HCT116 traitées par la 3-HTMC. Donc, malgré l'activation des voies de résistance à l'apoptose, la 3-HTMC peut être un agent chimiopréventif ou thérapeutique prometteur pour le traitement du cancer colorectal. / Increasing incidence and mortality of colorectal cancer brings the necessity to uncover new possibilities in its prevention and treatment. Chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. In this study, we investigated the effects of the synthetic chalcone derivative 3-hydroxy-3',4,4',5'-tetra-methoxy-chalcone (3-HTMC) on proliferation, cell cycle distribution, apoptosis and its mechanism of action in human colorectal HT-29 (COX-2 sufficient) and HCT116 (COX-2 deficient) cancer cells. We showed that 3-HTMC decreased cell viability in a dose-dependent manner with a more potent antiproliferative effect on HCT116 than HT-29 cells. Flow cytometric analysis revealed G2/M cell cycle accumulation in HT-29 cells and significant G2/M arrest in HCT-116 cells with a subsequent apoptosis shown by appearance of Sub-G1 peak. We demonstrated that 3-HTMC treatment on both cell lines induced apoptotic process associated with overexpression of death receptor DR5, activation of caspase-8 and -3, PARP cleavage and DNA fragmentation. In addition, 3-HTMC induced activation of PI3K/Akt and MEK/ERK principal survival pathways which delay 3-HTMC-induced apoptosis in both cell lines. Furthermore, COX-2 overexpression in HT-29 cells contributes to apoptosis resistance which explains the difference of sensitivity between HT-29 and HCT116 cells to 3-HTMC treatment. Even if resistance mechanisms to apoptosis reduced chalcone antitumoral potential, our results suggest that 3-HTMC may be considered as an interesting compound for colorectal cancer therapy or chemoprevention.

Several malignant diseases, such as colorectal, pancreatic, breast or ovarial cancers, are primarily treated with cytostatics 5-fluorouracil (5-FU). 5-FU undergoes biotransformation in human body and arising metabolites induce the damage and subsequent apoptosis in the target cells. The main aim of this diploma Thesis was the determination of methylation in promoter regions of 14 candidate genes participating on 5-FU biotransformation: TK1, PPAT, RRM1, RRM2, UCK2, UCK1, UMPS, TYMP, UPP1, UPP 2 SLC29A1, UPB1, DPYS and DPYD. We hypothesize that the methylation in promoter regions regulates mRNA transcription of the above candidate genes. We have conducted appropriate analyses in 128 colorectal cancer patients, for whom both tumor and nonmalignant adjacent tissues were available. Sample processing and analysis involved DNA isolation, bisulfite conversion of unmethylated cytosines to corresponding uracils, methylation-specific analysis of melting curves with high resolution for theproper methylation analysis and gel electrophoresis to separate PCR products. For the majority of the studied genes (TK1, PPAT, RRM1, RRM2, UCK2, UCK1, UMPS, TYMP, UPP1, SLC29A1 and DPYD) we did not detect any aberrant methylation in promoter regions. In genes DPYS, UPB1 and UPP2 we recorded various degree of promoter...

Abstract In the Western world, colorectal cancer (CRC) is one of the most common cancers and causes of cancer deaths. It is estimated that up to a third of CRCs represent a recently defined subtype, serrated adenocarcinoma (SAC), which develops via the serrated pathway and differs from conventional cancer by molecular, histological, and clinicopathological characteristics. The oncogenic mutation of BRAF V600E is characteristic to the serrated pathway lesions, and VE1 is a novel antibody that has been reported to recognize this mutated BRAF protein. In these studies, two independent cohorts of CRCs and a cohort of 922 colorectal polyps (545 patients) consecutively removed in Oulu University Hospital were utilized to study potential immunohistochemical markers (annexin A10 and VE1) as markers for the serrated pathway lesions, to investigate the presence of ectopic crypt foci (ECF) in different colorectal polyps and CRCs, and to study the network of determinants and the clinical impact of tumor necrosis with special regard to SAC. VE1 immunohistochemistry was found a sensitive and accurate method in the detection of BRAF V600E mutation with potential applications in the recognition of the BRAF V600E-mutated SACs. Annexin A10 immunohistochemistry was indicated to be a marker with high specificity for the serrated pathway lesions. ECF were found to be frequently encountered in addition to traditional serrated adenomas also in the tubular, tubulovillous and villous adenomas. Tumor necrosis in CRC was associated with high tumor stage and inversely associated with the serrated histology. High tumor necrosis percentage correlated with poor survival in CRC independently of other clinicopathological factors. In conclusion, these studies add to the knowledge of the molecular and histological features of SAC and its precursors. The results suggest that VE1 and ANXA10 immunohistochemistry may help in the recognition of the serrated pathway lesions. ECF can be found in other colorectal polyps in addition to traditional serrated adenomas. Tumor necrosis represents a relevant histomorphological prognostic indicator in CRC. / Tiivistelmä Paksu-peräsuolisyöpä on yksi yleisimmistä syövistä länsimaissa. Arviolta kolmasosaa kaikista paksu-peräsuolisyövistä edustava sahalaitainen adenokarsinooma eroaa tavallisesta adenokarsinoomasta molekulaaristen muutostensa sekä histologisten ja kliinispatologisten piirteidensä perusteella. BRAF-onkogeenin V600E-mutaatiota tavataan vain paksu-peräsuolisyövän sahalaitaisen kehittymisreitin muutoksissa ja VE1-immunohistokemian on todettu tunnistavan tämän mutatoituneen BRAF-proteiinin. Tutkimuksessa käytettiin kahta itsenäistä paksu-peräsuolisyöpäaineistoa sekä polyyppiaineistoa, joka käsitti 922 Oulun yliopistollisessa sairaalassa peräkkäisissä kolonoskopioissa poistettua paksu-peräsuolen polyyppia (545 potilasta). Tutkimuksen tarkoituksena oli selvittää kahden immunohistokemiallisen merkkiaineen (VE1 ja annexin A10) spesifisyyttä sahalaitaiselle adenokarsinoomalle ja sen esiastemuutoksille, ektooppisten kryptafokusten esiintymistä paksu-peräsuolen polyypeissa sekä kasvaimen nekroosiin yhteydessä olevia tekijöitä ja nekroosin ennustevaikutusta. VE1-immunohistokemia oli sekä sensitiivinen että spesifinen BRAF V600E-mutaation toteamisessa, minkä vuoksi sitä voidaan käyttää BRAF V600E-mutatoituneiden sahalaitaisten adenokarsinoomien tunnistamisessa. Annexin A10-immunohistokemia osoittautui spesifiseksi sahalaitaisen kehittymisreitin muutosten toteamissa. Ektooppisia kryptafokuksia havaittiin traditionaalisen sahalaita-adenooman lisäksi myös tubulaarisissa, tubulovillooseissa ja villooseissa adenoomissa. Kasvaimen nekroosi oli vähäisempää sahalaitaisessa adenokarsinoomassa sekä matalan levinneisyysasteen kasvaimissa. Runsas nekroosin määrä oli kasvaimen levinneisyydestä riippumatta yhteydessä huonompaan ennusteeseen. Tutkimus lisää tietoa sahalaitaisesta adenokarsinoomasta ja sen esiastemuutoksista. Tulokset osoittavat, että VE1 ja annexin A10 -immuno¬histokemia auttaa sahalaitaisen kehittymisreitin muutosten tunnistamisessa; ektooppisia kryptafokuksia voidaan nähdä traditionaalisten sahalaita-adenoomien lisäksi myös muissa paksu-peräsuolen polyypeissa; lisäksi todettiin, että kasvaimen nekroosin määrällä on vaikutusta paksu-peräsuolisyövän ennusteen arvioinnissa.

Tumors are one of the leading causes of death worldwide. Generally, the prognosis is better if the treatment begins at an early stage. Nowadays, the conventional chemotherapy treatment of cancer, known for its limited efficacy and side effects, is being gradually replaced by targeted biological treatment, which is used when specific genetic mutations are found. A part of the treatment is a detection of a potential progression, which is mainly based on the tumor biomarkers monitoring. Currently, further investigation of a so-called liquid biopsy method are ongoing, on which this thesis is focused. The main aim of this work was the experimental development and validation of the method for detection of the ctDNA in the plasma samples based on the somatic mutations presence. For the development and optimization of the system on the principle of denaturation capillary electrophoresis, the samples of cancer patients with KRAS mutation were used. Subsequently, a clinical part of the research was performed on a pilot set of 21 plasma samples. Finally, the method was optimized for the detection of BRAF and EGFR markers. A partial objective was to improve the detection sensitivity and increase the capture of the ctDNA in patients with advanced stage of the disease. The results of this work suggest the...

Avec l'amélioration de la prise en charge du cancer colorectal (CCR), on constate une augmentation croissante du nombre de personnes en longue rémission de ce cancer. Cependant, le CCR et ses traitements peuvent avoir des répercussions physiques et psychologiques à long terme. L'objectif était d'évaluer la QdV et la réinsertion de patients en longue rémission d'un CCR, 5, 10 et 15 ans après le diagnostic, comparées à des témoins de population générale. Etude constituée de cas de CCR tirés au sort à partir des 3 registres des tumeurs et de témoins tirés au sort à partir des listes électorales. Les participants ont complété 5 auto-questionnaires : le SF-36 et le QLQC30, le MFI-20 et le STAI, et un questionnaire de conditions de vie. Au total, 542 cas de CCR et 1181 témoins ont été inclus. Globalement, la QdV des patients était comparable à celle des témoins 15 ans après le diagnostic. Les patients atteints du cancer du rectum ont été plus affectés physiquement et ont ressenti davantage de fatigue. Quant à la réinsertion, les patients ont reporté des changements positifs tels que l'an1élioration de leur relation conjugale. Cependant les patients ont noté plus de difficultés lors de démarches de souscription à un prêt. En terme de QdV, cette étude a démontré qu'elle était globalement satisfaisante chez les patients en longue rémission de leur CCR. Ils ont reporté dans leur vie sociale et familiale plus de changements positifs que les témoins, signe d'une adaptation à la maladie. Mais il persiste encore des difficultés d'ordre professionnel et financier. Il parait nécessaire de maintenir la prise en charge médico-psycho-sociale des personnes en longue rémission d'un CCR / Given enhancing managing of colorectal cancer (CRC), we note an increasing number of long term cancer survivors. However, CRC and its treatment can cause long term physical and psychological effects. The goal was to evaluate quality of life and reintegration in long term CRC survivors, 5, 10, and 15 years after diagnostic, in comparison with population controls. Study consisted of CRC cases, randomly selected from files of three cancer registries and controls randomly selected from electoral rolls. Participants completed five self-administrated questionnaires: SF-36 and QLQC30, MFI-20 and ST Al, and a life conditions questionnaire. Five hundred forty two CRC cases and l, 181 controls were included. Globally, survivors QOL was comparable with that of controls, 15 years after diagnosis. Rectal cancer survivors were more affected in physical field and perceived more fatigue. In reintegration analyses, cancer survivors reported more positive changes than controls, as strengthening in marital relationships. However, survivors met more difficulties in loan and insurance requests. In term of QOL, this study demonstrated it was globally satisfactory in long term CRC survivors. In term of reintegration they reported positive changes and less negative changes in social and marital life, sign of an adaptation to cancer. However, they still met difficulties in professional and financial position. lt seems to be necessary to strength medical and psychosocial follow-up of CRC survivors.

Les plantes médicinales Diplotaxis harra et Diplotaxis simplex occupent une place importante dans la pharmacopée traditionnelle grâce à leurs compositions variées en métabolites secondaires tels que les flavonoïdes. Ces derniers jouent un rôle important dans plusieurs activités biologiques, notamment anti-inflammatoires et anti-cancéreuses. Dans ce contexte, et à la recherche de molécules bioactives dans D. harra et D. simplex, nous avons mis au point un nouveau modèle d'étude in vitro des cellules souches à l'origine des pathologies inflammatoires et cancéreuses coliques où leur survie dépend de l'activation de la Glycogène Synthase Kinase 3beta (GSK3beta) en aval du récepteur de protéases inflammatoires PAR2. Ce modèle a permis la purification bioguidée de glucoflavonoïdes à partir d'un extrait méthanolique des fleurs de D. harra capables d'inhiber GSK3beta via la voie PKC. Ainsi, l'Isorhamnétine-3,7-di-O-glucoside s'est révélé cytotoxique vis à vis des cellules inflammatoires ou cancéreuses coliques tout en épargnant les cellules normales. D'autre part, en raison de l'intérêt grandissant porté aux fractions volatiles en thérapeutique, nous avons étudié les compositions chimiques et les activités antioxydantes des fractions volatiles des feuilles et des fleurs de D. simplex. En se basant sur la technique chromatographique en phase gazeuse couplée à la spectrométrie de masse (GC-MS), nous avons montré que les deux fractions volatiles contiennent des quantités importantes de composés soufrés/azotés, parmi lesquels le 5-methylthiopentanenitrile et le 1-isothiocyanatobutane pourraient être impliqués dans l'effet antioxydant des fleurs de D. simplex. En conclusion, nos travaux ont permis de révéler l'axe PAR2/GSK3beta comme une nouvelle voie de survie des cellules souches coliques et l'intérêt thérapeutique des glucoflavonoïdes et des fractions volatiles de l'espèce Diplotaxis. / The medicinal plants Diplotaxis harra and Diplotaxis simplex occupy an important place in traditional medicine due to their varied compositions in secondary metabolites such as flavonoids. Flavonoids play an important role in many biological activities, including inflammation and cancer. In this context and in search of bioactive molecules in D. harra and D. simplex, we have developed a new study model, in vitro, where colonic stem cells causing inflammatory diseases and colorectal cancer survive through the activation of Glycogen Synthase Kinase 3beta (GSK3beta) downstream of inflammatory proteases PAR2 receptor. This model allowed the bio-guided purification of glucoflavonoids from a methanol extract of D. harra flowers able to inhibit GSK3beta via a PKC-dependent pathway. Thus, isorhamnetin-3,7-di-O-glucoside was found to be cytotoxic against inflammatory or colon cancer cells while sparing normal cells. On the other hand, due to the growing interest in therapeutic volatile fractions, we studied the chemical composition and antioxidant activity of volatile fractions of leaves and flowers of D. simplex. Based on the gas chromatography mass spectrometry technique (GC-MS), we have shown that both volatile fractions contain significant amounts of sulfur/nitrogen compounds, including 5-methylthiopentanenitrile and 1-isothiocyanatobutane, which might be involved in the antioxidant effect of flowers from D. simplex. In conclusion, our work revealed the axis PAR2/GSK3beta as a new survival pathway for colon stem cells and the therapeutic value of glucoflavonoids and volatile fractions of Diplotaxis species.