Colorectal cancer (CRC) remains a significant burden in contemporary society due to an aging population, unhealthy dietary choices and an increasingly sedentary lifestyle. While the underlying defects for many hereditary forms of CRC have been determined, many genetic and epigenetic changes promoting common sporadic CRCs have yet to be identified. The Mutated in Colorectal Cancer (MCC) gene, identified in 1991, was initially thought to be responsible for the hereditary form of CRC, familial adenomatous polyposis, before the discovery of the susceptibility gene Adenomatous Polyposis Coli (APC), which then became the focus of intense research. Recent data, however, suggests that MCC may also be important in the development of CRC. I have investigated the mechanism of MCC gene silencing, the putative structure, and multiple functions of MCC. MCC was frequently silenced by promoter hypermethylation in CRC cell lines and primary tumours. MCC methylation showed strong molecular and clinicopathological associations with hallmarks of the serrated neoplasia pathway. Furthermore, MCC methylation was more frequent in serrated precursor lesions compared with adenomas, thus occurring early during carcinogenesis. MCC is highly conserved in complex multicellular organisms. Re-introduction of MCC in CRC cell lines resulted in partial G1 to S phase, and G2/M phase cell cycle blocks, potentially by upregulating cell cycle inhibitor gene transcription and interfering with the process of mitotic checkpoints and division, respectively. Changes in MCC levels also modulated NF?B pathway signalling, the pathway required for maintaining cell viability and proliferation in colonic epithelial cells. In particular, MCC overexpression suppressed both TNF? and LPS-induced NF?B activation, decreasing both the magnitude and rate of cellular responses. Overexpression also resulted in downregulation of proteins involved in canonical NF?B pathway signalling, while increasing the transcription of non-canonical NF?B genes. Therefore, MCC may direct activation of this pathway to a specific subset of NF?B-regulated genes. These data provide a molecular basis for the role of MCC as a tumour suppressor gene in CRC. MCC may have multiple functions, regulating cell cycle progression and modulating NF?B pathway signalling, either through direct involvement in pathway signalling cascades, or by providing a scaffold on which signalling events can occur.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

Dans quelle mesure le concept de genre constitue-t-il une clé de lecture pertinente aux rapports entre dynamiques territoriales et dynamiques sanitaires ? Cette thèse propose de répondre à cette interrogation en analysant la participation au dépistage organisé du cancer colorectal et sa promotion dans les Hauts-de-Seine (92). Les villes de Boulogne-Billancourt et de Gennevilliers, ainsi que deux quartiers populaires de chacune d’elles sont comparés à partir de données quantitatives (taux de participation au dépistage) et qualitatives (observations, entretiens semi-directifs). Il apparaît que les disparités spatiales (inter ou infra-communale) et sexuées de participation au dépistage du cancer colorectal se déclinent différemment selon les territoires étudiés et ne reflètent pas l’inégale répartition spatiale des classes sociales. L’analyse des trajectoires de recours au médecin généraliste, acteur clé du programme, révèle des représentations et pratiques territoriales spécifiques aux contextes gennevillois et boulonnais, mais aussi aux hommes et aux femmes de ces espaces. L’étude de la promotion de ce dépistage permet de mieux comprendre les modes d’organisations et de développement des communes et quartiers ciblés (types et réseaux d’acteurs politiques, professionnels ou associatifs). Elle révèle également la nécessité de prendre en compte le genre dans l’analyse des déclinaisons locales d’une politique nationale de santé publique. Enfin, les représentations et les pratiques des médecins généralistes s’ancrent dans des parcours professionnels, des normes sociales dominantes et des dynamiques territoriales originales. / To which extent does the concept of gender can be a strategic concept to understand links between health and territorial dynamics? The following study aims to investigate this topic by analyzing the attendance at colorectal cancer screening sessions and its promotion in the Hauts-de-Seine (Paris region). We draw a comparison between the towns of Boulogne-Billancourt and Gennevilliers, and two of their popular districts, based on quantitative (attendance rates to screening sessions) and qualitative data (observations, semi-directive interviews). Among the findings, it appears that spatial and gendered disparities regarding colorectal cancer screening vary depending on the places studied and do not reflect the unequal distribution of social classes. The analysis of health-seeking behaviors to a general practitioner – a key actor of this screening program – highlights spatial representations and practices which are specific to the contexts in Boulogne-Billancourt and in Gennevilliers, as well as to women and men. The study of the promotion of colorectal cancer screening also enables us to better understand the ways these towns and districts are developed and organized (type and network of political, professional and associative stakeholders). In addition, the study stresses on the necessity to take gender into account when it comes to the analysis of local implementations of a national public health policy. Lastly, professional backgrounds, dominant social norms and spatial dynamics are an integral part of general practitioner’s representations and practices.

Colorectal cancer (CRC) is a common malignancy which develops due to old age and lifestyle factors, low percent of patients afflicted by a genetic disorders. Half of all colorectal cancer patients are diagnosed after metastasis. The high rate of the late detection, emphasizes on the requirement of convenient and inexpensive diagnostic methods for comprehensive screening programs. The aim of this study was to discover proto-oncogenes mutation and assessment of tumor suppressor genes expression. Formalin fixed paraffin embedded (FFPE) histologically verified colorectal cancer samples were used. APC, KRAS and BRAF mutations were investigated using polymerase chain reaction (PCR) fragments and direct sequencing. Gene expression assessment of MLH1, MGMT and CDKN2A were achieved via quantitative polymerase chain reaction (qPCR). In the present study we could detect a novel transversion heterozygous mutation in APC gene codon 1365 in three patients. BRAF codon 600 mutation were detected in one patient. KRAS codon 12 mutation was discovered in one sample and also a novel transition mutation in codon 15 was detected in 6 patients. In 80% of cases, MLH1 and MGMT expression were undetectable, in remaining 20%, MLH1 expression were reduced, but MGMT showed both reduced and increased expression compared to control. In 100% of patients CDKN2A expression was undetectable. The rate of mutations in predetermined hotspot codons and amount of uncommon mutations into APC, BRAF and KRAS in Nepalese patients indicates the requirement of further investigation in CRC patients from that part of the world. Also, the expression rate of MLH1, MGMT, CDKN2A and deficiency of an information source emphasizes the necessity of whole genome CRC expression profiling data to comparison and conclusion. / <p>-</p> / -

Les polyphénols sont un groupe de métabolites secondaires communément trouvés dans l’alimentation et plus de 500 composés différents sont retrouvés dans plus de 450 denrées alimentaires. Au cours des 30 dernières années, de nombreuses études in vitro et chez l’animal ont suggéré un rôle bénéfique des polyphénols dans des maladies chroniques comme le cancer 1-3. Les études épidémiologiques basées majoritairement sur des questionnaires alimentaires sont cependant plus contradictoires 4-6. De nouvelles méthodes sont requises pour quantifier un plus grand nombre de composés dans une même série afin de réaliser des études épidémiologiques à grande échelle. Le but de cette thèse est de développer des méthodes de quantification d’une large gamme de polyphénols représentatifs des principales classes et sous-classes de polyphénols dans le sang et urine, d’évaluer les excrétions urinaires de polyphénols et leurs associations avec la consommation d’aliments source dans une population Européenne, d’évaluer les concentrations dans le sang dans une étude cas-témoin sur cancer colorectal dans l’étude prospective européenne sur le cancer et la nutrition (EPIC). Après une brève présentation des polyphénols et du cancer colorectal dans le chapitre II, une méthode originale basée sur la dilution isotopique différentielle et l’analyse en spectrométrie de masse est développée pour quantifier 38 polyphénols dans l’urine et présentée dans le chapitre III. Cette méthode est basée sur un marquage différentiel en 12C et 13C des polyphénols grâce à une dérivatisation par les isotopes du chlorure de dansyl. Différentes conditions pour l’hydrolyse des polyphénols conjugués, l’extraction et la dérivatisation des aglycones ont été évaluées et la méthode a été validée pour la mesure de 37 polyphénols. Les niveaux d’excrétion urinaire de ces 37 polyphénols mesurés chez 475 individus de la cohorte EPIC issues de quatre pays européens sont présentés dans le chapitre IV. Une grande variabilité d’excrétion urinaire dans les quatre pays Européens a pu être montrée et des corrélations significatives avec la consommation de certains aliments source de ces composés ont été observées suggérant l’utilisation possible de plusieurs de ces polyphénols en tant que biomarqueurs de l’alimentation. Une méthode d’analyse pour les mêmes 37 polyphénols également basée sur la dilution isotopique différentielle est développée, validée et appliquée à 1618 échantillons dans la cohorte EPIC (chapitre V). Les changements majeurs en comparaison de la méthode sur la matrice urinaire sont essentiellement les difficultés d’hydrolyse des polyphénols conjugués et des effets de matrice importants mais réduits par la méthode de dilution isotopique. Enfin l’étude des associations entre l’exposition aux polyphénols mesurée à l’aide des marqueurs plasmatique avec le risque de cancer colorectal a été conduite dans une étude cas-témoin nichée dans la cohorte EPIC et est présentée dans le chapitre VI. Une association inverse entre les concentrations plasmatiques d’equol, et une association positive entre l’acide homovanillique et le risque de cancer du côlon ont été trouvées. Les résultats obtenus constituent une nouvelle base pour des applications futures dans le domaine de l’épidémiologie des polyphénols / Polyphenols are secondary plant metabolites found in diet and more than 500 different compounds are found in more than 450 foods. Along the last 30 years, many in vitro and animals studies have suggested a beneficial role of polyphenols in chronic diseases such as cancer. However, epidemiological studies based mainly on dietary questionnaires are inconsistent. New methodologies with broader polyphenol coverage are required to quantify a large diversity of compounds within large scale epidemiological studies.The goal of this thesis is to develop methods to quantify a large number of polyphenols representative of the main classes and sub-classes in blood and urine, evaluate urinary excretions of polyphenols and their association with food consumption in an European population, evaluate concentrations in blood in a nested case-control study on colorectal cancer within the European prospective investigation study on cancer and nutrition (EPIC).After a short presentation of polyphenols and colorectal cancer in chapter II, an original method based on differential isotopic dilution and analyse by tandem mass spectrometry is developed to quantify 38 polyphenols in urine and presented in chapter III. This method is based on differential 12C-/13C- isotope labelling of polyphenols through derivatisation with isotopic dansyl chloride reagents. Different conditions for enzymatic hydrolysis of conjugated polyphenols, extraction and dansylation of unconjugated aglycones have been tested, optimized and validated for the measure of 37 polyphenols.Urinary excretion levels of these 37 polyphenols in 475 subjects within EPIC cohort from 4 European countries are presented in chapter IV. Large urinary excretion variability in the 4 European countries has been shown and significant correlations with the consumption of specific food containing polyphenols have been observed suggesting the possible used of some polyphenols as biomarker for food consumption.A similar method on plasma for the 37 polyphenols, based on differential isotopic dilution, is developed, validated and applied to 1618 samples within the EPIC cohort (Chapter V). Main changes compared to the method developed on urine are essentially difficulties to hydrolyse conjugated polyphenols and huge matrix effects but reduced by the isotopic dilution method.Finally, the study on the association between polyphenols exposure measured owing to plasmatic marker with colorectal cancer risk has been driven in a nested case-control study within the EPIC cohort and is presented in chapter VI. An inverse association between plasmatic concentrations of equol, and a positive association between homovanillic acid and colon cancer risk have been found.Results obtained constitute a new approach for future applications in large scale epidemiology study on polyphenols

L’objectif de ce travail est d'explorer et comprendre les principaux freins et leviers psychologiques à la démarche de dépistage du cancer colorectal (CCR) par Hemoccult-II®. Plus particulièrement, nous cherchons à préciser le rôle spécifique du concept d’anxiété envers la santé dans le processus qui conduit à prendre la décision de participer au dépistage du CCR.Une étude qualitative exploratoire basée sur la méthodologie des focus groups, suivie d’une étude quantitative ont été menées auprès d’individus âgés de 50 à 74 ans, ayant un risque moyen de développer un CCR. Les individus ayant déjà participé au dépistage ont de meilleures connaissances concernant le test Hemoccult-II®, surestiment davantage les leviers envers le test Hemoccult-II®, sont plus anxieux envers la santé, et mobilisent davantage de stratégies d’ajustement de type vigilant que les individus n’ayant jamais participé au dépistage. Les principaux prédicteurs de la participation au dépistage du CCR sont le degré de connaissances envers le dépistage du CCR, la surestimation des leviers au test Hemoccult-II®, la peur de la maladie et les stratégies d’ajustement de type vigilant.Ces résultats suggèrent que certains facteurs psychologiques, dont l’anxiété envers la santé, jouent un rôle essentiel dans la participation au dépistage du CCR par Hemoccult-II®. / The aim of this study is to investigate and to understand the main psychological barriers to and facilitators of colorectal cancer screening (CRC) by Hemoccult-II®. More specifically, we try to clarify the specific role of the concept of health anxiety in the decision making process which influences participation in CRC screening.An exploratory qualitative study, based on the methodology of focus groups, followed by a forward-looking quantitative study were led with people from 50 to 74 years old, with an average risk of developing a CRC. People having already participated to CRC screening have better knowledge about the Hemoccult-II® test, overestimate facilitators of the Hemoccult-II® test, are more anxious about health, and use more monitoring coping strategies than individuals having never participated to CRC screening. Main predictors of the participation to CRC screening are knowledge about CRC screening, overestimation of facilitators of Hemoccult-II® test, fear of disease and monitoring coping strategies.Results suggest that psychological factors, including health anxiety, play an important role in the participation in CRC screening by Hemoccult-II®.

Le cancer colorectal est la deuxième cause de mortalité due au cancer en Europe et aux États-Unis. Etant donné l’efficacité limitée et la toxicité élevée des agents de chimiothérapie, de nouvelles approches sont nécessaires. Le flavanolignane silybine représente le principal constituant actif du chardon-marie (Silybum marianum). Les mécanismes moléculaires des propriétés anticancéreuses de la silybine ont été étudiés dans un modèle cellulaire de progression du cancer colorectal humain : les cellules SW480 issues d’un adénocarcinome, et leurs dérivées métastatiques les cellules SW620. Les effets chimiopréventifs de la silybine ont été étudiés dans un modèle de cancérogenèse colique induite par l’azoxyméthane chez le rat. La silybine induit une mort apoptotique avec activation de la caspase-3 dans les deux lignées. L’expression des récepteurs de mort TRAIL est augmentée, et la caspase-8 activée. Le potentiel mitochondrial est perturbé provoquant une libération du cytochrome c et une activation de la caspase-9. En plus de l’activation des voies apoptotiques extrinsèque et intrinsèque la silybine induit une réponse autophagique. La combinaison de la silybine et de TRAIL, un agent anti-cancéreux prometteur, provoque une mort cellulaire synergique dans les deux lignées. Un effet synergique est aussi observé avec la combinaison de la silybine et des inhibiteurs des histones déacétylases (HDAC) : TSA et SAHA. Dans le modèle chez le rat, la silybine réduit de 50% le nombre des lésions prénéoplasiques. En conclusion, la silybine est un agent naturel intéressant pour la prévention du cancer colorectal et dans le cadre d’une combinaison avec TRAIL/des inhibiteurs d’HDACs. / Colorectal cancer (CRC) is the second most common cause for cancer-related deaths in Europe and in the USA. Because of the limited efficacy and considerable toxicity of chemotherapeutic agents, new approaches are needed. The hepatoprotective flavonolignan silibinin is the major biologically active compound of the milk thistle (Silybum marianum).The molecular mechanisms of the anticancer properties of silibinin in CRC were studied in an in vitro model of cancer progression consisting of the adenocarcinoma cell line SW480 and its derived metastatic cell line SW620. Its chemopreventive effects were assessed in an in vivo model of azoxymethane-induced colon carcinogenesis in the rat. Silibinin induced apoptotic cell death with activation of caspase-3 in both cell lines. The expression of death receptors was upregulated, and caspase-8 was activated. The potential of the mitochondrial membrane was perturbed permitting the release of cytochrome c and the activation of caspase-9. Besides the activation of the extrinsic and the intrinsic apoptotic pathway, silibinin induced an autophagic response. Combination of silibinin and TRAIL, a promising anticancer agent selectively inducing apoptosis in cancer cells, induced synergistic cell death in both cell lines. Synergy in cell death induction was also observed by the combination of silibinin and the histone deacetylase (HDAC) inhibitors TSA and SAHA. In the preclinical model in the rat, silibinin administration was able to reduce by half the number of preneoplastic lesions present in the colon. In conclusion, silibinin is a promising natural agent for colon cancer chemoprevention and for combination therapy with TRAIL/HDAC inhibitors.

Le facteur de transcription homéotique Cdx2 est un suppresseur de tumeurs et son expression est réduite de manière hétérogène dans les tumeurs coliques. Or, le cancer colorectal demeure un problème de santé publique par sa fréquence et sa gravité. Au travers de 3 sous-projets, cette thèse visait à comprendre le mode d’action de Cdx2. Premièrement, la cadhérine Mucdhl a été identifiée et caractérisée en tant que nouvelle cible de Cdx2 : Mucdhl inhibe la croissance des cellules cancéreuses coliques et s’oppose à l’activité de la -caténine. Deuxièmement, un effet inattendu de Cdx2 sur le cytosquelette et la rigidité cellulaire a été montré. Ceci pourrait expliquer comment Cdx2 intervient dans l’organisation structurale des entérocytes ou la migration. En parallèle, une lignée cellulaire rapportrice de l’expression de Cdx2 a été créé qui, après validation, sera un outil précieux pour l’étude des mécanismes moléculaires qui conditionnent l’hétérogénéité tumorale. Par la mise en évidence de nouvelles fonctions et cibles de Cdx2, cette thèse permet de mieux appréhender son rôle physiologique et son action de suppresseur de tumeurs dans l’intestin. / Colorectal cancer is a major public health problem because of its frequency and propensity to metastasize. Cdx2 plays the role of a tumor suppressor and its expression is frequently but heterogeneously reduced in colon tumors. Through three sub-projects, this thesis aimed to better understand the mode of action of Cdx2. First, the Cadherin Mucdhl was identified and characterized as a new direct target gene of Cdx2. Mucdhl was also shown to inhibit the growth of colon cancer cells and to oppose -catenin activity. Second, an unexpected effect of Cdx2 on the cell cytoskeleton and rigidity of a cancer cell monolayer was uncovered. This gives new clues about how Cdx2 contributes to the structural organization and differentiation of enterocytes but also nhibits cell migration. In parallel, a reporter cell line for Cdx2 expression was created. After its validation, this cell line will be a precious tool to study the molecular mechanisms underlying tumor heterogeneity in vivo. Altogether, this thesis unraveled new functions and target genes of Cdx2 that permit to better apprehend its physiological function and its action as a tumor suppressor in the intestine.

O câncer de cólon e reto configura-se como a terceira causa mais comum de câncer no mundo, em ambos os sexos, e a segunda causa em países desenvolvidos. Estudar a qualidade de vida (QV) é fundamental para a presença de intervenções que promovam bem-estar e/ou o estar bem destes pacientes, cujo prognóstico nem sempre é o melhor. Esta dissertação tem como norte a seguinte questão: como é a qualidade de vida do paciente com câncer colorretal em quimioterapia ambulatorial? Trata-se de um estudo transversal com abordagem quantitativa descritiva, no qual buscou-se avaliar a qualidade de vida do paciente com câncer colorretal em quimioterapia ambulatorial. A pesquisa foi desenvolvida em uma Unidade de Quimioterapia Ambulatorial em um hospital do sul do Brasil, cujos pacientes eram portadores do diagnóstico de câncer colorretal e foram submetidos ao tratamento com o Protocolo 5FU. A amostra contou com 48 participantes que estavam em tratamento quimioterápico por um período de 6 meses. Utilizou-se como instrumento de levantamento de dados um questionário já validado e traduzido para o português, o WHOQOL-Bref. Nos resultados encontrados, prevaleceu a idade de 50 anos ou mais, todos os participantes estavam com estadiamento Dukes B e possuíam no mínimo um mês e no máximo 11 meses de tratamento. Os domínios do WHOQOL-Bref afetados mais significativamente foram os domínios II e III (psicológico e relações sociais), respectivamente, havendo diferença nas respostas quanto à QV geral naqueles que estavam no 1º ciclo de tratamento daqueles que já se encontravam no último ciclo (6º). A qualidade de vida é resultado da combinação de fatores subjetivos e de fatores objetivos, precisando suprir às necessidades humanas integrais, em seus aspectos físicos, psicológicos, sociais e espirituais. / Cancer of the colon and rectum appears as the third most common cancer worldwide in both sexes, and the second leading cause in developed countries. Studying the quality of life (QOL) is fundamental for the existence of interventions that promote wellness and/or well-being of these patients, whose prognosis is not always the best. This thesis is guided by the following question: how is the quality of life of patients with colorectal cancer in outpatient chemotherapy? It was a cross-sectional study with a descriptive quantitative approach, which aimed at assessing the quality of life of patients with colorectal cancer in outpatient chemotherapy. The research was conducted in an Outpatient Chemotherapy Unit at a hospital in Southern Brazil, whose patients were diagnosed with colorectal cancer and were treated with 5-FU protocol. The sample had 48 participants who were undergoing chemotherapy for a period of six months. It was used as an instrument of data collection a questionnaire, which has already been validated and translated into Portuguese, the WHOQOL-Bref. In the results found, prevailed the age of 50 years or more, all participants were in Dukes stage B, with at least a month and a maximum of 11 months of treatment. / El cáncer de colon y recto se configura como la tercera causa más frecuente de cáncer en el mundo, en ambos los sexos, y la segunda en los países desarrollados. Estudiar la calidad de vida (CV) es fundamental para la presencia de intervenciones que promueven bienestar y/o el estar bien de los pacientes cuyo pronóstico no siempre sea el mejor. Esta tesina se propone a la siguiente cuestión central: ¿cómo se presenta la calidad de vida de los pacientes con cáncer colorrectal sometidos a quimioterapia ambulatoria? Se trata de un estudio transversal con un abordaje cuantitativo descriptivo en el que se ha buscado evaluar la calidad de vida de pacientes con cáncer colorrectal sometidos a quimioterapia ambulatoria. Se ha desarrollado esta investigación en una Unidad de Quimioterapia Ambulatoria de un hospital ubicado al sur de Brasil, cuyos pacientes eran portadores de diagnóstico de cáncer colorrectal y fueran sometidos al tratamiento con el Protocolo 5-FU. La muestra dispuso de 48 pacientes en tratamiento quimioterápico por un periodo de 6 meses. Se ha utilizado como instrumento de recolección de datos un cuestionario validado y traducido al portugués, el WHOQOL-Bref. En los resultados obtenidos ha prevalecido la franja de edad de 50 años o más, todos los participantes se encontraban en el estadio Dukes B y poseían como mínimo un mes y como máximo 11 meses de tratamiento. The domains of the WHOQOLBref affected more significantly were the domains II and III (psychological and social relations), respectively, with significant differences in responses regarding overall QOL in those who were in the first cycle of treatment from those already in the last cycle (6th). Quality of life is the result of a combination of subjective and objective factors, needing help meeting human needs in full, in terms of physical, psychological, social and spiritual.

Introdução: a TC de tórax possui sensibilidade superior à do RX de tórax na detecção de metástases pulmonares do CCR. O uso rotineiro da TC de tórax préoperatória, no entanto, resulta na identificação de um alto número de lesões pulmonares indeterminadas (LPI), as quais raramente são malignas. Objetivo: nosso objetivo principal foi avaliar a eficácia da TC de tórax no estadiamento pré-operatório de pacientes com CCR. Investigamos, também, se os resultados da TC de tórax tiveram influência significativa no manejo oncológico e desfecho clínico dos pacientes. Métodos: realizamos uma revisão de todas as TCs e RXs de tórax realizados em pacientes operados eletivamente por CCR no período de 2005-2012 no serviço de coloproctologia do HCPA. Todos os exames de imagem foram analisados por um radiologista independente “cego”. Os achados dos exames foram classificados como benignos, malignos ou indeterminados. Os pacientes foram acompanhados por pelo menos 12 meses após a cirurgia para avaliar a evolução e real natureza das lesões indeterminadas. Resultados: duzentos e vinte e três pacientes foram incluídos. A TC de tórax demonstrou achados normais ou benignos em 157 (70,4%) pacientes, achados malignos em 17 (7,6%) e achados indeterminados (LPI) em 49 (22%). Dos 30 casos com metástases pulmonares comprovadas, o RX detectou as lesões em apenas 11 pacientes (36,7%). No seguimento pós-operatório (mediana de 27,5 meses), 14 pacientes (28,6%) com LPI tiveram progressão maligna das lesões. Dos 223 pacientes estudados, apenas 6 (2,7%) foram submetidos à ressecção pulmonar, 2 destes permanecendo em remissão até o fechamento do estudo. Conclusão: demonstramos que a TC é claramente superior ao RX na detecção de metástases pulmonares. Apesar das implicações médicas e financeiras do emprego da TC de tórax, apenas um número muito limitado de pacientes será eventualmente submetido à ressecção pulmonar. Nossos resultados contestam o uso da TC de tórax de rotina no estadiamento de pacientes com CCR. Sugerimos uma conduta mais seletiva, reservando a TC para aqueles pacientes com alto risco de metástases pulmonares. / Background: Chest computed tomography (CCT) has higher sensitivity than chest x-ray in detecting lung metastases from colorectal cancer (CRC). However, the routine use of pretreatment CCT results in a high number of indeterminate lung lesions (ILLs), which rarely prove to be malignant. Objective: our main goal was to evaluate the effectiveness of CCT in the preoperative staging of patients with CRC. We also tried to investigate whether the results of CCT have a significant influence on cancer management and clinical outcomes. Methods: we conducted a review of all preoperative CCTs and x-rays performed in patients submitted to an elective resection of CRC between 2005 and 2012 at our institution. All imaging tests were analyzed by a "blind" independent radiologist. Findings were classified as benign, malignant, or indeterminate. Patients were followed up for at least 12 months after surgery to assess clinical evolution of undetermined lesions and their oncological outcome. Results: Two hundred and twenty-three patients were included. CCTs showed normal or benign findings in 157 (70.4%) patients, malignant lesions in 17 (7.6%) patients, and indeterminate lung lesions (ILL) in 49 (22%) patients. Of the 30 cases with proven lung metastases, x-rays detected lesions in only 11 (36.7%) patients. During postoperative follow-up, 14 patients (28.6%) with the initial diagnosis ILL had malignant progression of their lung lesions. Of all 223 patients, only six (2.7%) underwent lung resection. Two of them remained in remission until the end of the study. Conclusion: We demonstrated that CCT is clearly superior to x-ray in the detection of lung metastases. Despite medical and financial implications of preoperative chest CT, only a very limited number of patients will eventually undergo lung resection. We call into question the role of routine chest CT in the staging of patients with CRC. A more selective approach, reserving CT for patients at high risk of lung metastases, is suggested.