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<p>Diss. (sammanfattning) Umeå : Umeå universitet, 2002</p> / digitalisering@umu

Distant brain metastases from oral squamous cell carcinomas (OSCC) are extremely rare. Here we describe a case of a 53-year-old man with a primary OSCC who referred to the neurosurgical department because of epileptic seizures. MR imaging revealed an enhancing lesion in the right parietal lobe. A craniotomy with tumor removing was performed. Histopathological examination verified an invasive, minimally differentiated metastasis of the primary OSCC. The patient refused whole brain radiation therapy and died from pulmonary metastatic disease 10 months after the neurosurgical intervention without any cerebral recurrence. To the authors’ knowledge, only two similar cases have been previously reported.

The purpose of this work was to further understand nutritional status, especially body weight and composition, during colorectal cancer progression. Population-based studies of colorectal cancer patients were conducted using administrative health data (primary and co-morbid diseases, demographics), and computed tomography (CT) imaging (body composition). In cohort 1, administrative health data was used to study comorbidities and nutritional status in 574 colorectal cancer patients referred for chemotherapy. Multivariate Cox regression revealed several comorbidities, performance status and weight loss 20% predicted survival. In cohort 2, a serial CT image analysis assessed longitudinal body composition changes during the last 12 months preceding death from colorectal cancer (n=34). Body composition changes were typified by exponential increases in liver metastases with concurrent accelerations of muscle and fat loss. These results have the potential to make a difference in how colorectal cancer patients are treated and researched by dietitians, oncologists, and health services researchers. / Nutrition and Metabolism

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Les déterminants psychologiques de la qualité de vie des patients atteints de métastases cérébrales traités par des techniques de neurochirurgie sont peu connus, et en particulier la contribution du fonctionnement cognitif et émotionnel. Des auteurs encouragent la prise en compte de la temporalité pour mieux saisir le concept de qualité de vie. Zimbardo et ses collaborateurs ont développé une théorie du temps psychologique qui permet de relier la qualité de vie et la dépression, nommée la « perspective temporelle ». La thèse vise à confirmer le rôle prédicteur du fonctionnement cognitif dans la qualité de vie de patients traités chirurgicalement pour tumeur(s) cérébrale(s) métastatique(s) et à mieux comprendre les relations entre la perspective temporelle, la dépression et la qualité de vie. Une première étude a comparé le profil sociocognitif en inter-sujets (patients versus témoins) et en intra-sujets (avant traitement neurochirurgical versus après), et a exploré des déterminants de la qualité de vie (i.e., fonctionnement cognitif, symptomatologie dépressive et perspective temporelle). Les résultats principaux sont que les patients présentent un dysfonctionnement cognitif global qui impacte négativement leur autonomie fonctionnelle et qu’une symptomatologie dépressive, même légère, est un important prédicteur de leur qualité de vie globale. Les patients sont plus orientés vers le « présent fataliste » que des témoins, et les dimensions « passé » de leur perspective temporelle sont liées à leur qualité de vie, notamment à travers leur influence sur l’état émotionnel. Une deuxième étude a examiné les relations entre la dimension « passé négatif » de la perspective temporelle en particulier, la dépression et la qualité de vie chez un groupe de patients. Les résultats suggèrent que la symptomatologie dépressive des patients est un médiateur des effets de la dimension « passé négatif » sur leur qualité de vie. Une troisième recherche a exploré, via une étude de cas, les dynamiques du profil de perspective temporelle, de la symptomatologie dépressive, de « l’incertitude vers le futur » et de la qualité de vie au cours du suivi médical. Le principal résultat de cette étude est que les dynamiques des deux dimensions « présent » évoluent conjointement à celle de l’incertitude vers le futur. La thèse encourage la mise en œuvre d’études interventionnelles destinées à évaluer l’efficacité d’interventions psychologiques centrées sur la perspective temporelle chez des patients atteints de métastases cérébrales. / Little is known about the psychological determinants of quality of life in brain metastases patients treated with neurosurgical techniques, in particular the contribution of cognitive and emotional functioning. Authors encourage the consideration of temporality in order to better understand the concept of quality of life. Zimbardo and his collaborators developed a psychological time theory that links quality of life and depression, called the "time perspective". The thesis aims to confirm the predictive role of cognitive functioning in the quality of life of patients treated surgically for metastatic cerebral tumors and to better understand the relationships between time perspective, depression and quality of life. A first study compared the sociocognitive profile in inter-subjects (patients versus controls) and in intra-subjects (before neurosurgical treatment versus after), and explored determinants of quality of life (ie, cognitive functioning, depressive symptomatology and time perspective). The main results are that patients have a global cognitive dysfunction that negatively impairs their functional autonomy and that a depressive symptomatology, even minimal, is an important predictor of their overall quality of life. Patients are more oriented towards the "present-fatalistic " than the controls, and the "past" dimensions of their time perspective are related to their quality of life, notably through their influence on the emotional state. A second study examined the relationship between the "past-negative" dimension of the time perspective in particular, depression and quality of life in a group of patients. The results suggest that the depressive symptomatology of patients mediate the effects of the "past negative" dimension on their quality of life. A third study explored, through a case study, the dynamics of the time perspective profile, depressive symptomatology, "uncertainty towards the future" and quality of life during medical follow-up. The main result of this study is that the dynamics of the two "present" dimensions evolve jointly with the future uncertainty. The thesis encourages the implementation of interventional studies to evaluate the effectiveness of psychological interventions centered on the time perspective in brain metastases patients.

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.

Le carcinome à cellules rénales claires métastatique (CCC) demeure résistant aux thérapies actuelles. Les travaux précédents ont montré des similitudes mécanistiques entre tumorigenèse et néphrogenèse. Parmi les cibles de la voie oncogénique Sonic Hedgehog-Gli, le facteur développemental Lim1 a été identifié comme un nouvel oncogène dans le CCC. Les études préliminaires suggèrent que Lim1 aurait un rôle dans l’invasion cellulaire. Aucun inhibiteur de Lim1 n’est disponible; l’ARN interférence reste l’outil le plus efficace et le plus spécifique pour l’extinction des gènes. Dans le but de développer un nouvel outil d’inhibition de Lim1 applicable en clinique, basée sur des siRNAs véhiculés par des systèmes nanométriques, une nouvelle génération de véhicules de siRNAs a été étudiée. Il s’agit de polymères diacétyléniques photo-polymérisables sous forme de nanofibres (PDA-Nf). Ces travaux démontrent le rôle invasif de Lim1 dans la dissémination métastatique et identifient les PDA-Nf comme un nouvel outil de délivrance de siRNAs très prometteur en clinique. L’avantage du ciblage de Lim1 avec cette approche, est l’absence de son expression à l’âge adulte. / Clear cell renal cell carcinoma (CCC) remains resistant to current therapies, despite the development of anti-angiogenic and the new immunotherapeutic approaches. Previous work of the laboratory has shown mechanistic similarities between tumorigenesis and nephrogenesis. Among the targets of the Sonic Hedgehog-Gli pathway which is found oncogenic in CCC, the developmental factor Lim1 has been identified as a new oncogene in CCC. Preliminary studies suggest that Lim1 would have a role in cell invasion. No Lim1 inhibitors are available; RNA interference remains the most effective and specific tool for gene silencing. In order to develop a new clinically applicable inhibition tool for Lim1, based on siRNAs carried by nanoparticles, a new generation of siRNA vehicles has been investigated. These are photo-polymerizable diacetylenic polymers in the form of nanofibers (PDA-Nf). These works demonstrate the invasive role of Lim1 in metastatic dissemination and identifies PDA-Nf as a new promising siRNA delivery tool in clinical practice. The advantage of targeting Lim1 with this nano-carrier approach is that Lim1 is not expressed in adulthood.