<p>Focus of Thesis This thesis focuses on the initial stages of developing the Ontario Decision Aid in Rectal Cancer for Stage II and III patients (ODARC). The ODARC is a DA meant to facilitate relevant information exchange among physicians and patients. Such a tool should enhance patient knowledge and accuracy of treatment expectations by effectively conveying to patients relevant information on treatment options and associated benefits and risks. The ODARC is designed for use during a physician-patient consultation. The ODARC prototype development was guided by a workbook on developing & evaluating patient DAs published by O’Connor & Jacobsen (for efficiency we will call this the Workbook).24 This latter document provides detailed instructions for a 7-step DA development process including: 1) assess patient and provider need 2) assess DA feasibility 3) define objectives of the DA 4) identify the framework to guide DA development 5) select tailored methods of decision support to be used in the DA 6) select the designs and measures to evaluate the aid and, 7) plan dissemination.24 In this thesis we have created a prototype ODARC as informed by Steps 1 to 5 of the Workbook. The last two steps covering evaluation and dissemination are beyond the scope and available resources of this current research effort, and can be considered as future research endeavours. This will be reviewed in the final chapter.</p> / Master of Science (MSc)

No description available.

No description available.

No description available.

Alors que le traitement standard du cancer du rectum (traitement néoadjuvant avec chirurgie d’exérèse et stomie temporaire) n’épargne ni la psyché ni le corps, peu d’études se sont intéressées à l’ajustement psycho-social des patients qui y sont confrontés. Le corps est bien souvent perçu, à la suite des traitements, comme dérivant de la norme et générant un sentiment de honte. Ainsi le premier travail de cette thèse a été de valider un outil, en population française, permettant de mesurer la honte liée à l’image du corps. Dans un deuxième travail, nous avons pu comparer la honte liée à l’image du corps ainsi que la qualité de vie, l’image du corps, et la détresse psychologique des patients ayant reçu un traitement standard à ceux traités par excision locale (nouvelle approche proposée aux patients présentant une bonne réponse clinique aux traitements néoadjuvants). Le traitement standard entraînant des difficultés psycho-sociales plus marquées, nous avons évalué plus spécifiquement ses conséquences sur la détresse psychologique et l’image du corps dans un troisième travail. La période avec la stomie temporaire représente un temps spécifique durant lequel les patients semblent mettre leur vie entre parenthèses. Ainsi, dans un quatrième travail, nous avons investigué le rôle du temps comme un déterminant possible de la qualité de vie de ces sujets. Nos résultats ont montré qu’il conviendrait de considérer, dans le parcours de soin du patient, la façon dont celui-ci perçoit le temps, en vue de prévenir une altération de sa qualité de vie. Cette altération persiste plusieurs mois après la fin des traitements mais peu d’études s’y sont, à ce jour, intéressées. Ainsi, dans un cinquième travail, nous avons exploré la qualité de vie, deux ans après le diagnostic de cancer, chez des survivants du cancer du côlon-rectum traités par chirurgie avec ou sans stomie temporaire. Nous avons alors constaté que la qualité de vie physique était significativement plus altérée chez les patients qui ont eu une stomie. Face à ces difficultés, il convenait de proposer une intervention psycho-sociale répondant aux besoins émotionnels de ces patients. Peu d’interventions ont été développées en ce sens. Dans un sixième travail, nous avons développé et mis à l’épreuve une intervention psycho-sociale qui semble s’inscrire davantage dans une approche préventive. L’ensemble de ces travaux pourrait contribuer à améliorer l’accompagnement proposé à ces patients, même s’il est nécessaire de souligner l’importance de promouvoir la recherche dans ce domaine pour mieux comprendre encore les enjeux psycho-sociaux de ce traitement. / While the standard treatment for rectal cancer (neoadjuvant treatment with rectal excision) has spared neither the psyche nor the body, few studies have focused on psychosocial adjustment of patients who have received this treatment. Following treatment, the body is often perceived as deviating from the norm, generating feelings of shame. The first objective of this thesis was to adapt, and validate, for the French population, a body image shame scale. The second step consisted in comparing body image shame, quality of life, body image, and psychological distress between rectal cancer patients treated by surgery with temporary stoma or local excision (a new treatment approach proposed for patients with rectal cancer after a good clinical response to neoadjuvant therapy). Since standard treatment leads to more psychosocial problems, in a third study, we examined the effects of standard treatment on psychological distress and body image. The temporary stoma period represents a specific time during which patients seem to temporarily suspend their lives. Thus, the fourth study of this thesis investigated how the role of time perspective might act as a determinant of quality of life for rectal cancer patients. The time perspective construct provides keys in order to improve quality of life of rectal cancer patients. Quality of life alterations persist several months after the end of treatments but, to date, few studies have focused on this topic. The fifth goal was to assess colorectal cancer survivors’ quality of life two years after diagnosis of colorectal cancer according to their stoma status (reversed or never formed). Participants with a reversed stoma score lower on the physical quality of life scale than participants without stoma. Patients with rectal cancer experience psychosocial challenges. To deal with these challenges, psychosocial interventions focused on emotional needs of rectal cancer patients treated by standard treatment should be proposed. There is a lack of this type of intervention for this population. The sixth purpose was to develop and test a psychosocial intervention which seems to be more in line with a preventive approach. Taken together, these works may contribute to improve the support offered to these patients, even though the importance of promoting research to deal with the psychosocial challenges of this treatment must be underlined.

<p>Colorectal cancer is one of the most common malignancies in Sweden, with more than 5000 new cases annually. Median age at time of diagnosis is approximately 75 years. Owing to the ageing population, the incidence of colorectal cancer is increasing. The improvement in surgical technique and the introduction of adjuvant radio- and chemotherapy increased the 5-year survival rate from approximately 30-40% in the early 1960s to almost 60% in the late 1990s. The cost of public health care has risen considerably, and case-costing systems are increasingly demanded. Linked to clinical guidelines and quality registers, such control systems form a proper basis for quality assurance projects and improvement. The aim of this thesis is to describe the efficiency and cost effectiveness of colorectal cancer treatment in a defined Swedish population. Emergency surgery for colon cancer, constituting 25% of the cases, increased both mortality and cost. Among emergency cases there was not only an increase in postoperative mortality but also a stage specific decrease in long-term survival rate. Correct staging is decisive for further treatment of patients after colon cancer surgery and influences long-term survival. The number of lymph nodes examined varied between different pathology departments and could be used as a quality measurement. The proportion of tumour stage III increased the more nodes examined. A prognostic estimation of stage III cases that is less sensitive to the number of nodes examined is proposed. A case-control study aimed at identifying risk factors for anastomotic leakage after rectal cancer surgery confirmed previously known risk factors but failed to identify further steps during the perioperative course that were amenable to improvement. This research has confirmed that population-based quality and case-costing registers, linked to clinical guidelines, constitute a proper source for projects of quality improvement and decisions about distribution of resources in health care.</p>

Colorectal cancer is one of the most common malignancies in Sweden, with more than 5000 new cases annually. Median age at time of diagnosis is approximately 75 years. Owing to the ageing population, the incidence of colorectal cancer is increasing. The improvement in surgical technique and the introduction of adjuvant radio- and chemotherapy increased the 5-year survival rate from approximately 30-40% in the early 1960s to almost 60% in the late 1990s. The cost of public health care has risen considerably, and case-costing systems are increasingly demanded. Linked to clinical guidelines and quality registers, such control systems form a proper basis for quality assurance projects and improvement. The aim of this thesis is to describe the efficiency and cost effectiveness of colorectal cancer treatment in a defined Swedish population. Emergency surgery for colon cancer, constituting 25% of the cases, increased both mortality and cost. Among emergency cases there was not only an increase in postoperative mortality but also a stage specific decrease in long-term survival rate. Correct staging is decisive for further treatment of patients after colon cancer surgery and influences long-term survival. The number of lymph nodes examined varied between different pathology departments and could be used as a quality measurement. The proportion of tumour stage III increased the more nodes examined. A prognostic estimation of stage III cases that is less sensitive to the number of nodes examined is proposed. A case-control study aimed at identifying risk factors for anastomotic leakage after rectal cancer surgery confirmed previously known risk factors but failed to identify further steps during the perioperative course that were amenable to improvement. This research has confirmed that population-based quality and case-costing registers, linked to clinical guidelines, constitute a proper source for projects of quality improvement and decisions about distribution of resources in health care.

Les cancers sont l’une des causes majeures de mortalité dans le monde. Les mécanismes en jeu dans la croissance tumorale sont qualitativement connus, mais on se sait pas à l’heure actuelle prédire précisément quel sera le développement d’une tumeur donnée, ni estimer de façon certaine le protocole thérapeutique optimal pour chaque patient. Il est entendu que la modélisation mathématique pourrait apporter des éléments de réponse à ces questions. Durant cette thèse on s'est alors intéressé à la construction de formalismes mathématiques pour décrire la croissance tumorale et l’action de traitement anti-cancéreux. En particulier, on s'est intéressé à la prise en compte des mécanismes aussi bien moléculaires que cellulaires et tissulaires, par la construction d’un modèle continu, multi-échelles, de croissance de tumeur solide et d’angiogenèse. A partir de ce modèle, nous a pu envisager de façon qualitative un protocole optimal de combinaison entre un anti-angiogénique et une chimiothérapie.Le modèle multi-échelles inclut une représentation mathématique des voies de signalisation du VEGF dont on détaille la construction.Dans une autre approche, on a considéré un modèle discret, cellule-centré, reproduisant le développement de sphéroïdes de cellules épithéliales mammaires telles qu’observées lorsque ces cellules sont cultivées in vitro. On a pu mettre en évidence les différents mécanismes cellulaires impliqués dans la morphogenèse de structures composées de cellules saines, et celles composées de cellules mutées.Ces contributions montrent l’intérêt du formalisme multi-échelles adopté pour intégrer les connaissances et données sous-jacentes à l’étude du traitement des tumeurs. / Cancer is one of the leading causes of death in Europe. The mechanisms involved in tumour growth are qualitatively known, but we are still unable to precisely predict how a given tumour will evolve, nor estimate with certainty the optimal therapeutic protocol for each patient.It is well understood that mathematical modelling could give part of the answer to these questions. That is why during this thesis we considered the building of mathematical formalisms to describe tumour growth and the action of anti-cancer treatments. In particular, we investigated the molecular to tissular mechanisms of cancer development and angiogenesis through the building of a continuous multi-scale model. We were able to reproduce the effect of anti- angiogenesis treatments on tumour growth, and qualitatively study an optimal therapeutic protocol of anti-angiogenic combined with cytotoxic drugs. This multi-scale model integrates a mathematical representation of the signalling pathways of VEGF (Vascular Endothelial Growth Factor). We detail the development of this model which is based solely on information available in the literature and dedicated databases. In another approach, we considered a discrete, cell-based model to reproduce the development of spheroid structures of mammary epithelial cells. This model considers the behaviour of these cells when observed while grown in vitro in an appropriate medium. We were able to highlight the different mechanisms involved in the morphogenesis of wild and mutated cells structures.This work shows the importance of the multi-scale formalism we used to integrate the knowledge and data related to the study of cancer treatment.

Contexte: Le cancer colo-rectal est la deuxième cause de décès, par ordre de fréquence. L’utilisation de l’imagerie dans la stadification du cancer colo-rectal est un élément important de la prise en charge de la maladie. L’échographie endoscopique est une modalité qui permet de préciser la profondeur de l’atteinte néoplasique. Les données probantes concernant la performance diagnostique dans l’identification de cancers peu avancés sont variables. Objectif : Effectuer une revue systématique sur la performance diagnostique de l’échographie endoscopique dans l’identification de cancer de stade T1 et T2. Devis : Revue systématique. Sources bibliographiques : PubMed, EMBASE, Ovid and Cochrane library Méthodes: Dans un premier temps, une recherche de revue systématique publiée dans les 15 dernières années fût effectuée sur la précision diagnostique de l’échographie endoscopique dans les banques PubMed, Cochrne et trip database. Deux revues systématiques, publiées en 2008 et 2009 fûrent identifiées. Une deuxième recherche portant sur des études primaires a été effectuée pour la période 2009 à 2016, dans les mêmes banques bibliographiques. La qualité des études primaires a été évaluée à l’aide de la grille QUADAS2. Les mots clés utilisés étaient échographie endoscopique, EUS, cancer rectal, histo-pathologie, staging. Sélection d’études : Les critères d’inclusion : population adulte avec diagnostic de cancer du rectum pas avancé, articles complets publiés dans des revues avec comité de pairs, articles en anglais. Critères d’exclusion : population pédiatrique, cancers avancés avec atteinte métastatique, patients évalués avec d’autres modalités (CT ou IRM) sans échographie endoscopique, absence de confirmation histologique. Résultats : Dix articles, publiés depuis 2009, répondaient aux critères d’inclusion. Ces articles furent ajoutés aux articles retenus dans les revues systématiques déjà publiées. Au total,49 articles sont inclus dans cette revue systématique. La performance diagnostique de l’échographie endoscopique a été évaluée en calculant la sensitivité et la spécificité des études regroupées. Pour le stade T1, les valeurs de sensitivité et spécificité étaient 0.84 (CI 0.75-0.91) et 0.93 (CI 0.86–0.97), respectivement. Pour le stade T2 les valeurs de sensitivité et spécificité étaient 0.83 (CI 0.74–0.90) et 0.93 (CI 0.86–0.97), respectivement. Conclusion: L’échographie endoscopique présente une performance diagnostique pour l’identification de cancers de stade T1 et T2. Ceci permet d’orienter des patients vers des chirurgies moins invasives avec une survie égale et un taux de complications inférieures comparativement à des chirurgies plus invasives. / Background: Colorectal cancer (CRC) is the second leading cause of death. The use of preoperative imaging in the staging of (CRC) plays a major role in the management. Endorectal ultrasound (ERUS) is a precise imaging modality to determine the depth of penetration. The data on the precision of (ERUS) to predict early stage of rectal cancer has been variable Objectives: To conduct a systematic review, on the diagnostic performance of (ERUS) in the staging of T1 and T2 CRC. Design: Systematic review. Data sources: A literature search via PubMed, EMBASE, Ovid and Cochrane library. METHODS: An initial search for systematic review articles published in the last 15 years on the diagnostic accuracy of EUS in the staging of CRC using PubMed, Cochrane library, and trip database was conducted. After finding two systematic reviews that were published in 2008 and 2009, a second search of original studies published since the systematic reviews were conducted using the same databases from 2009 to 2016. The primary studies included in the systematic reviews and the primary studies published afterwards were included in the review. Methodological quality was applied using a modified version of the quality assessment of diagnostic accuracy studies (QUADAS2) tool. Terms used for search were endoscopic ultrasound, EUS, rectal cancer, histo-pathological finding, and staging. Study selection: Inclusion criteria includes adult people diagnosed with early stage CRC, all articles in english language and must be a full manuscripts published in peer-reviews journals. Exclusion criteria includes any recurrent or metastasis cancer and children with rectal cancer. Patients who were staged preoperatively by other imaging modality (MRI or CT) and no comparison with post operative pathology. Results: The search identified 420 articles, 97 articles were duplicate and excluded, and 232 refined articles were screened for title and abstract, reviewed. Thirty-two full text studies were assessed for eligibility, and ten published as full text and met the inclusion criteria; they were added to the articles identified in the earlier systematic reviews a total of 49 articles. Results of the evaluation of the accuracy of ERUS analyzed according to the diagnostic measures of sensitivities and specificities calculated for each study. The pooled sensitivity and specificity of EUS for stage T1 CRC was 0.84 (CI 0.75-0.91) and 0.93 (CI 0.86–0.97), and for T2 was 0.83 (CI 0.74–0.90) and 0.93(CI 0.86–0.97) respectively. Conclusion: The range of sensitivity and specificity values suggest that EUS performs well in accurately staging T1 and T2 cancers. Further advancement in this technology will lead to an improved diagnosis, clinical decision-making, and reduce the over staging drawback.

Si les connaissances anatomiques supportent l’élaboration des techniqueschirurgicales, peu d’informations étaient disponibles sur l’anatomie et la physiologie del’innervation pelvi-périnéale. La détermination précise de l’origine, du trajet péri-viscéral, desrapports anatomiques avec les organes et les vaisseaux de voisinage et de la terminaison deces nerfs au niveau d’organes dont ils commandent la fonction était jusqu’alors peu accessibleaux techniques anatomiques classiques de dissection macroscopique sur sujet cadavérique.Dans le domaine de la chirurgie pelvienne pour cancer, l’amélioration de la qualité de vie desmalades passe par la préservation de ces structures nerveuses, la dimension fonctionnelle étantdésormais indissociable des impératifs carcinologiques. En effet, l’intégrité de ces nerfs estindispensable aux fonctions de continence sphinctérienne et de sexualité. Par ailleurs, lamajorité des travaux s’intéressant aux séquelles fonctionnelles postopératoires sont réaliséschez l’homme et très peu de travaux concernent exclusivement les femmes dont les troublessexuels sont plus difficiles à identifier. La réduction de ces troubles fonctionnelspostopératoires passe donc par une meilleure compréhension de l’anatomie nerveuse pelvipérinéale,qui peut être éclaircie par de nouvelles techniques d’étude / Anatomical knowledge is required for the development of surgical techniques,but little is known about the anatomy and physiology of innervation in the pelvic/perinealarea. The origin, perivisceral trajectory, anatomical relationships to organs and neighbouringvessels and of the endings of these nerves in the organs they control has not, to date, beeneasy to determine precisely by classical anatomical techniques based on the macroscopicdissection of cadavers. In the domain of pelvic cancer surgery, improvements in the quality oflife of patients are dependent on the preservation of these nervous system structures; themaintenance of function cannot be dissociated from oncological imperatives. Indeed, theintegrity of these nerves is essential for sphincter continence and sexual functions. Moststudies have focused on the functional sequelae of surgery in men. Very few studies havefocused exclusively on women, in whom sexual problems are more difficult to identify. Thereduction of such postsurgical functional problems thus requires a more completeunderstanding of the anatomy of the pelvic/perineal nervous system. This may be possiblethrough the use of new investigative techniques