Le Lymphome à Cellules du Manteau (LCM) est une entité récemment identifiée qui se caractérise par la translocation génétique t(11 ;14)(q13 ;q32) et compte pour 2 à 10 % de tous les Lymphomes non-Hodgkiniens. Avec une survie médiane entre 3 et 5 ans après le diagnostic, le LCM est une pathologie agressive et malgré les récentes avancées thérapeutiques, peu d’informations sont disponibles concernant ses facteurs pronostiques. Certaines études ont analysé le rôle des caractéristiques clinicopathologiques et des nouvelles stratégies thérapeutiques, mais on connait peut le rôle des facteurs environnementaux et du mode de vie sur le pronostic des patients atteints de LCM. Entre 2008 et 2012, le groupe LYSA a mené en France deux essais cliniques prospectifs multicentriques : LM manteau 2010 SA "RiBVD" (NCI01457144) et Manteau 2007 SJ "LyMa" (NCT00921414). Après une comparaison de ces patients avec les patients de population générale, l’effet de facteurs socioéconomiques et des habitudes de vie sur la survie des patients a été étudié à l’aide d’un questionnaire qualitatif administré à tous les volontaires après le diagnostic. Nos résultats suggèrent qu’un faible niveau d’éducation, un indice de masse corporelle élevé et de la consommation d’alcool sont associés à un risque de décès plus élevé chez les patients atteints de LCM. Toutefois, l’étude de tels facteurs et de leur influence sur un sous-type de LNH aussi rare requiert des échantillons d’étude de taille plus importante. L’élargissement des critères d’inclusion des patients dans les essais cliniques permettrait de sélectionner davantage de patients mais aussi des patients mieux représentatifs de la population générale. Enfin, l’intégration systématique de ce type de questionnaire dans les protocoles d’essais cliniques serait aussi un atout majeur. / Mantle Cell Lymphoma (MCL) is a recently defined entity, typically characterised by the genetic translocation t(11 ;14)(q13 ;q32) and counting for 2 - 10% of all non-Hodgkin Lymphomas. With a median survival between 3 and 5 years after diagnosis, MCL is an agressive disease and despite the recent therapeutic advances little in know about its prognostic factors. Some studies had investigated clinicopathological features and new treatment strategies, but there is a lack of knowledge regarding the impact of lifestyle and environnemental factors on outcome of MCL patients. From 2008 to 2012, the LYSA Group conducted in France two prospective multi center clinical trials on MCL : LM manteau 2010 SA "RiBVD" (NCI01457144) and Manteau 2007 SJ "LyMa" (NCT00921414). After a comparison of these patients with population-based data, socioeconomic factors, lifestyle factors and their influence on survival had been investigated through a qualitative survey administrated to each volunteer after diagnosis. Our findings suggest that low educational attainment, low body body mass index and alcohol consumption are associated with a higher risk of death in MCL. However, to investigate lifestyle factors in this rare NHL subtype, larger studies should be carried out. Clinical trial inclusion criteria must be widen to select more patients and patients more representative of general population. Implementation of these epidemiological studies in clinical practice should be considered.

Le vieillissement de la population associé à un nombre croissant de cancers constituent une réalité épidémiologique qui soulève des interrogations sur l’accès aux soins et le pronosticdes sujets âgés avec un cancer, pour lesquels des disparités ont été mises en évidence. Toutefois, les études présentent plusieurs limites dont l’absence de facteurs spécifiques aux personnes âgées (PA). L’objectif de ce travail était d’étudier les déterminants sociodémographiques, socioéconomiques et cliniques de l’accès aux soins (stade de cancer, traitement) et du pronostic (déclin fonctionnel, survie) chez des PA atteintes d’un cancer. Les travaux ont été réalisés à partir de données issues de registres de cancers et de troiscohortes de PA en Gironde (486 patients de 65 ans et plus, période 2005-14). Les cohortes ont permis de disposer de données telles que le niveau d’éducation, le revenu, la prise demédicaments, la dépendance ou la démence. Selon l’objectif (accès/pronostic), nous avons utilisé différentes méthodes pour prendre en compte le type de données et de critères (régression logistique, modèles multiniveaux, modèles multi-état et de Cox). Notre population était composée pour plus de la moitié de PA de 80 ans et plus, de sexe masculin et ayant un niveau d’éducation supérieur au niveau primaire. Nous nous sommes d’abord intéressés aux déterminants de l’accès aux soins. Aucun déterminant d’un stade avancé de cancer au diagnostic n’a pu être mis en évidence, un niveau d’éducation faible était proche de la significativité pour les cancers avec un stade avancé (p=0,0671). Pour l’accès à un traitement du cancer, nous avons mis en évidence qu’un stade avancé (p=0,003) et la présence d’une démence (p=0,0109) étaient associés à un risque plus faible de recevoir un traitement. Nous avons ensuite étudié les déterminants du pronostic. Les sujets les plus âgés présentaient toujours un risque plus élevé de déclin fonctionnel (p<0,005), quel que soit le critère analysé. Les sujets ayant un faible niveau d’éducation (p=0,027), prenant plus de six médicaments par jour (p=0,047), présentant une démence (p<0,001) ou diagnostiqués à un stade avancé (p<0,001) avaient une probabilité de déclin fonctionnel plus importante, les résultats variant selon le critère. Enfin, à 12, 24 et 36 mois, la probabilité de survie globale était respectivement de 66, 57 et 48%. Le risque de décès était plus élevé chez les hommes (p=0,019), diagnostiqués à un stade avancé de cancer (p<0,001) et sans traitement du cancer (p<0,001), mais aussi chez les fumeurs (actuels et anciens) (p=0,019) et les PA dépendantes (p<0,001). En sus de déterminants classiques de l’accès aux soins ou du pronostic des cancers, nous avons mis en évidence pour les PA, le rôle des déficits cognitifs pour l’accès à un traitement ou sur le pronostic fonctionnel et celui de la dépendance sur la survie. Chez les PA avec un cancer, les facteurs spécifiques aux PA semblent donc essentiels à analyser. L’analyse des liens de causalité entre les déterminants de santé reste un sujet particulièrement intéressant dans cette population de PA comme pour les patients avec un cancer. / The growing incidence of cancer associated to an aging population represents an epidemiologic reality that requires questioning access to care and prognosis in elderly with cancer, for which disparities have been highlighted. However, generally speaking, studies are limited in that they overlook geriatric-specific factors. The aim of this work was to study sociodemographic, socioeconomic and clinical determinants of access to care (cancer stage, cancer treatment) and prognosis (functional decline, survival) in elderly cancer patients. This research project has relied on data from cancer registries and three elderly cohort studies in the French department of Gironde (486 patients aged 65 and over from 2005 to 2014). The cohorts provided data such as education level, income, medication, dependency and dementia. Depending on the aim, we used different statistical methods to analyze different types of data and outcomes (logistic regression, multi-level model, multi-state model, Cox model). More than half of our population was aged 80 and over, male and had high education degrees. First, we studied determinants of access to care. No determinant of advance stage at diagnosis was found, but low education was close to significance for advanced stage (p=0.067). Concerning cancer treatment administration, advanced stage at diagnosis (p=0.003) and diagnosis of dementia (p=0.011) were associated with a lower risk of treatment administration. Second, we studied determinants of prognosis. Older old had higher risk of functional decline (p<0.001), regardless of the outcome. Subjects with low education (p=0.027), taking more than six daily drugs (0.047), presenting diagnosed dementia (p<0.001) or those with advanced cancer stage at diagnosis had higher risk of functional decline, results depending on outcome. At last, overall survival at 12, 24 and 36 months was 66, 55 and 48%, respectively. Risk of death was higher in men (p=0.019), in patients with advanced stage at diagnosis (p<0.001) or without treatment (p<0.001) in current and former smokers (p=0.019) and in dependent elderly patients (p<0.001). In addition to classical determinants of access to care and prognosis in cancer, we demonstrated the impact of cognitive impairment on treatment administration or functional prognosis, and that of dependency on survival. . It appears essential to consider geriatric specific factors in studies on the elderly with cancer population. The causality between health determinants is particularly interesting in the elderly as well as in the cancer populations.

<p>Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. </p><p>Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.</p><p>Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.</p><p>A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.</p><p>Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.</p>

<p>The aim the thesis was to investigate, the prevalence of Lower Urinary Tract Symptoms (LUTS). Moreover, we examine symptom severity and different levels of distress and describe how different symptoms from the lower urinary tract affect the self-assessed health, sadness, happiness and the quality of life in men. </p><p>The studies are based on two data collections. In the first data collection, all men aged 40 – 80 years (n=2571) living in the Swedish community received a postal questionnaire. Twelve months later, 504 men who had earlier reported LUTS and 504 who had not reported symptoms were asked to complete the DAN-PSS and the SF-36 questionnaires. </p><p>The overall prevalence of LUTS was 24%. Post-micturition dribbling (21%) was the most frequent symptom, and stress incontinence (2%) was the least frequent symptom. Urge incontinence, stress incontinence and “other” incontinence cause a high level of distress, even if the symptoms do not occur very often. Men experiencing mild, moderate or severe urge, stress or “other incontinence” had lower mean scores for all of the eight dimensions measured by the SF-36 than men without the same symptoms. Men experiencing a moderate/severe degree of weak stream or nocturia reported a poorer quality of life in all dimensions compared to men with a mild level of the same symptoms. The total burden of moderate/severe LUTS is related to self-assessed health, sadness and happiness. For each of the 12 specific LUTS, men with mild, moderate or severe symptoms had lower scores for self-assessed health and happiness, and higher scores for self-assessed sadness, than men without the same symptoms. </p><p>In conclusions, one of every four men reports LUTS. Urinary incontinence causes high level of distress even to men who experience this symptom rarely. LUTS have a negative impact on quality of life, health, sadness and happiness. </p>

<p>The overall aim was to study factors that affect behaviour related to CVD (cardiovascular diseases). Study I tested whether gender, education and so-cioeconomic status correlated to knowledge about risk factors, and Study II studied knowledge and risk behaviour from a national perspective (Sweden versus Poland). Furthermore, Study III examined whether obese people dif-fered from people of normal weight regarding knowledge about risk factors, and Study IV examined whether risk behaviour is affected by personal ex-perience of illness and family history of CVD. </p><p>The studies are population-based with cross-sectional design. Data were obtained by questionnaires and by screening results of risk factors related to CVD. The studies were carried out among 50-year old men and women in Västmanland, Sweden (n=1011) and in Wroclaw, Poland (n=1043).</p><p>The results show that women are more knowledgeable than men about the risk factors for CVD, and that low education is associated with insufficient knowledge about CVD (Study I). The discrepancy between knowledge and behaviour was greater among the Poles than it was among the Swedes (Study II). Obese individuals did not differ significantly from individuals with a normal weight regarding knowledge of cardiovascular risk factors when education was controlled for (Study III). Individuals with a personal experience of illness may be more inclined to change smoking behaviour than the average person (Study IV).</p><p>In conclusion, knowledge about risk factors for CVD varies with education, gender and, to a certain degree, nationality. However, knowledge does not only consist of the conditions of behaviour change. The results in the thesis substantiate theories suggesting that change in risk behaviour is a process over time. Predictors of risk behaviours on the individual level as well as national level are of importance, and needs to be considered in the every day practice of health care professionals.</p>

Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease. Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor. A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions. Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.

The aim the thesis was to investigate, the prevalence of Lower Urinary Tract Symptoms (LUTS). Moreover, we examine symptom severity and different levels of distress and describe how different symptoms from the lower urinary tract affect the self-assessed health, sadness, happiness and the quality of life in men. The studies are based on two data collections. In the first data collection, all men aged 40 – 80 years (n=2571) living in the Swedish community received a postal questionnaire. Twelve months later, 504 men who had earlier reported LUTS and 504 who had not reported symptoms were asked to complete the DAN-PSS and the SF-36 questionnaires. The overall prevalence of LUTS was 24%. Post-micturition dribbling (21%) was the most frequent symptom, and stress incontinence (2%) was the least frequent symptom. Urge incontinence, stress incontinence and “other” incontinence cause a high level of distress, even if the symptoms do not occur very often. Men experiencing mild, moderate or severe urge, stress or “other incontinence” had lower mean scores for all of the eight dimensions measured by the SF-36 than men without the same symptoms. Men experiencing a moderate/severe degree of weak stream or nocturia reported a poorer quality of life in all dimensions compared to men with a mild level of the same symptoms. The total burden of moderate/severe LUTS is related to self-assessed health, sadness and happiness. For each of the 12 specific LUTS, men with mild, moderate or severe symptoms had lower scores for self-assessed health and happiness, and higher scores for self-assessed sadness, than men without the same symptoms. In conclusions, one of every four men reports LUTS. Urinary incontinence causes high level of distress even to men who experience this symptom rarely. LUTS have a negative impact on quality of life, health, sadness and happiness.

The overall aim was to study factors that affect behaviour related to CVD (cardiovascular diseases). Study I tested whether gender, education and so-cioeconomic status correlated to knowledge about risk factors, and Study II studied knowledge and risk behaviour from a national perspective (Sweden versus Poland). Furthermore, Study III examined whether obese people dif-fered from people of normal weight regarding knowledge about risk factors, and Study IV examined whether risk behaviour is affected by personal ex-perience of illness and family history of CVD. The studies are population-based with cross-sectional design. Data were obtained by questionnaires and by screening results of risk factors related to CVD. The studies were carried out among 50-year old men and women in Västmanland, Sweden (n=1011) and in Wroclaw, Poland (n=1043). The results show that women are more knowledgeable than men about the risk factors for CVD, and that low education is associated with insufficient knowledge about CVD (Study I). The discrepancy between knowledge and behaviour was greater among the Poles than it was among the Swedes (Study II). Obese individuals did not differ significantly from individuals with a normal weight regarding knowledge of cardiovascular risk factors when education was controlled for (Study III). Individuals with a personal experience of illness may be more inclined to change smoking behaviour than the average person (Study IV). In conclusion, knowledge about risk factors for CVD varies with education, gender and, to a certain degree, nationality. However, knowledge does not only consist of the conditions of behaviour change. The results in the thesis substantiate theories suggesting that change in risk behaviour is a process over time. Predictors of risk behaviours on the individual level as well as national level are of importance, and needs to be considered in the every day practice of health care professionals.

The understanding of the mesorectal spread in rectal cancer has lead to wide acceptance of total mesorectal excision (TME) as the surgical technique of choice for carcinoma in the lower and mid rectum. While oncological results and survival have improved with TME-surgery, morbidity and mortality remain important issues. The most feared complication is symptomatic anastomotic leakage. The aim of this thesis was to focus on the role of the defunctioning stoma, risk factors, and postoperative monitoring in regard to anastomotic leakage in sphincter saving resection of the rectum. Intraoperative adverse events were analysed in a retrospective population based case-control study in which all patients who underwent elective anterior resection in Sweden between 1987 and 1995, and who died within 30 days or during the initial hospital stay (n=140), were compared with patients chosen at random (n=423) who underwent the same operation during the same period, but survived the operation. Intraoperative adverse events were more frequent in those who died, and reconstruction of an anastomosis judged unsatisfactory by the surgeon improved the outcome. In a population based retrospective case-control study, risk factors for symptomatic anastomotic leakage were investigated in randomly chosen sample of patients who underwent anterior resection in Sweden between 1987 and 1995 (n=432). Twelve per cent of the patients developed symptomatic leakage, and 25% of the patients with leakage ended up with a permanent stoma. In multivariate regression analysis, low anastomosis, preoperative radiotherapy, male gender and intraoperative adverse events were independent riskfactors for anastomotic leakage. In a randomised multicentre trial patients operated with sphincter saving TME¨surgery for rectal cancer were randomised to a defunctioning stoma (n=116) or not (n=118). The overall rate symptomatic leakage was 19%. Patienst without a defunctioning stoma leaked in 28% and patients with a defunctioing stoma in 10%, a statistically significant difference (p&lt;0.001) not previously demonstrated in any randomised trial of adequate size. Postoperative monitoring with computed tomography scan (CT-scan) on postoperative day 2 and 7, and C-reactive protein (CRP) daily in 33 patients operated on with anterior resection of the rectum, demonstrated larger pelvic fluid collections in patients with leakage before the leakage was clinically diagnosed. CRP was increased from postoperative day 2 and onwards in patients in whom clinical leakage was diagnosed on median postoperative day 8. In 23 patients who underwent anterior resection of the rectum, intraperitoneal metabolism was investigated using microdialysis technique measuring the carbohydrate metabolites lactate, pyruvate and glucose. Intraperitoneal cytokines IL-6, IL-10 and TNF-α were collected through a pelvic drain and analysed. In patients who developed leakage, the latate/pyruvate ratio was increased near the anastomosis on postoperative day 5 and 6, as well as IL-6 and IL-10 which were increased postoperatively day 1 and 2, while TNF-α was higher on day 1.

A previous population-based study of survival in Chronic Lymphocytic Leukemia (CLL) patients in the province of Manitoba demonstrated a lower five-year relative survival among CLL patients compared with the age- and gender-adjusted general population. This decreased relative survival was most pronounced among elderly male CLL patients. In this study, we have demonstrated that the reduced five-year relative survival observed in CLL patients compared to the general population of Manitoba may partially be attributed to increased risk of second cancers and non-referral to specialized CLL clinics. The increased risk of second cancers in CLL patients compared to Follicular Lymphoma (FL), a similar indolent B cell malignancy, was only observed after CLL diagnosis indicating that a CLL-specific factor may be responsible for the increased risk of second cancers in these patients. The risk of second cancers is independent of treatment and surveillance bias but is further increased with chemotherapy. A superior outcome in CLL patients who have been referred to the CancerCare Manitoba (CCMB) specialized CLL clinic was observed that was independent of age, gender, treatment and history of previous cancers. This superior outcome was most pronounced in the elderly CLL patients. We propose that CLL patients should be referred to CLL-specific hematologists and, where not possible, that guidelines created by such experts be followed. Appropriate screening for second cancers should be performed during routine follow up of CLL patients.