L’endométriose est définie comme la présence de tissu endométrial et de stroma en dehors de la cavité utérine. Ses localisations les plus fréquentes sont le péritoine pelvien et les ovaires. L’endométriose infiltrante est classiquement décrite comme la présence de tissu endométriotique plus de cinq millimètres sous le péritoine pelvien ou la séreuse d’un organe. Histologiquement il s’agit d’une lésion endométriotique mais qui contrairement aux lésions ovariennes ou péritonéales contient significativement plus de muscle lisse et de fibrose et est davantage associée à la douleur. Les lésions infiltrantes peuvent être responsables de dysménorrhée, dyspareunie profonde et douleurs pelviennes chroniques sévères ayant un charactère hyperalgique tel qu’on peut le retrouver dans les douleurs neuropathiques. Ces douleurs nécessitent souvent la prise de quantités importantes d’antalgiques et ont des répercussions importantes sur la vie professionnelle, quotidienne et sexuelle des femmes atteintes. L’endométriose infiltrante présente un rapport histologique étroit avec les structures nerveuses du rétropéritoine ou les nerfs des organes atteints. Dans sa localisation rectovaginale il existe une relation histologique étroite entre les lésions d’endométriose et les nerfs ainsi qu’une correlation entre l’intensité de la douleur et le nombre de structures nerveuses envahies par l’endometriose ou engaînées dans la fibrose. Ces lésions infiltrantes expriment le «nerve growth factor» (NGF), une neurotrophine qui joue un rôle clé dans la genèse de l’hyperalgie et de la douleur. Les structures nerveuses du rétropéritoine pelvien expriment quant à elles le récepteur spécifique pour la neurotrophine NGF. Le système «NGF-récepteur spécifique» peut être responsable d’un chimiotactisme tissulaire entre les tissus sécrétant du NGF et les nerfs qui expriment le récepteur pour le NGF. Le système «NGF- récepteur spécifique» au sein de la relation endométriose-nerfs pourrait rendre compte du caractère hyperalgique des lésions endométriotiques infiltrantes ainsi, qu’expliquer pourquoi les lésions nodulaires n’apparaissent que dans les sites anatomiques richement innervés (ligaments utérosacrés, lame rectovaginale, paroi du rectum ou du côlon…) et pas ailleurs. Le traitement de première intention est chirurgical. Il convient d’être suffisamment agressif sur les lésions tout en engendrant le moins de séquelles postopératoires possibles sachant que nombre de ces femmes sont stériles. En cas d’atteinte digestive basse, les modalités de l’intervention sont dictées par l’extension et le degré d’infiltration de la paroi digestive. Dans le but de réaliser dans la majorité des cas une chirurgie minimalement invasive (laparoscopique) avec des cicatrices de petites tailles, nous avons développé une stratégie de traitement basée sur le degré d’infiltration de la paroi digestive. Dans ce cadre nous avons développé une technique laparo-assistée de résection colique segmentaire et de résection antérieure du rectum. / Doctorat en sciences médicales / info:eu-repo/semantics/nonPublished

Objetivo:Existemevidências crescentes na literatura da participação do estresseoxidativonaprogressão e agressividade da endometriose. Nesse estudoprospectivo e controlado, foram medidos seis marcadores de estresse oxidativo com a finalidade de relacioná-los com a severidade e progressão da endometriose além debuscarum marcador diagnóstico para a doença. Pacientes e Métodos:Entre Julho de 2010 e Agosto de 2011, 62 pacientes consecutivas com diagnóstico histológico de endometriose foram identificadas como elegíveis para esse estudo. Após os critérios de exclusão, 44 pacientes foram alocadas em três grupos: Grupo A (estádios I/II da ASRM/1996), (n=14), grupo B (estádios III/IV da ASRM/1996),(n=16) e grupo controle (n=14). Os seguintes marcadores foram avaliados no fluido peritoneal e no tecido com endometriose: 8-hidroxi-2- deoxiguanosina (8-OHdG), 8-oxo-guaninaglicosilase (OGG1),proteínacarbonil (PC), oxidação lipídica (LPO), espécies reativas de oxigênio (ROS); capacidade totalantioxidante (TAC). Resultados: Observou-se elevação estatisticamente significante do 8 OhdG e da PC. Notou-se diminuição significativa na expressão do reparo de DNA (OGG1) em estádios avançados de endometriose. (p<0.001, p=0.001, p=0.033 respectivamente). Não notamos significância estatística entre os três grupos estudados nos marcadores ROS,CAT e LPO. Utilizando-se um modelo estatístico multivariável e as curvas ReceiverOperatingCharacteristics(ROC) construiu-se um modelo preditivo de severidade de doença. A habilidade do modelo de distinguir 16 entre os grupos A, B e o grupo controlefoi alta. O modelo foi capaz de diferenciar aproximadamente 9 em cada 10 pacientes incluídas (acerto/corrido foi de 87%). Conclusão:O aumento da lesão no DNA e a diminuição da atividade enzimática de reparo de DNA podem estar relacionados com a progressão da endometriose. Nossos resultados indicam que marcadores oxidativos de agressão celular podem se tornar testes valiosospara se verificar a severidade da endometriose / Objective: There is increasing evidence that oxidative stress is one of the key factors for endometriosis progression. In this prospective controlled trial, we measured six different biomarkers of oxidative stress targeting protein, lipid and DNA to quantify the severity and progression of endometriosis and establish a diagnostic marker for the disease. Methods: 62 consecutive patients were identified to be enrolled in this study. After exclusion criteria, 44 patients were allocated in three groups: Group A (Stage I/II - ASRM/1996), (n=14), Group B(Stage III/IV ASRM/1996), (n=16), and control group (n=14). Levels of 8 hydroxy- deoxyguanosine (8 OHdG), 8- oxoguanine DNA glycosylase (OGG1), protein carbonyl (PC), lipid peroxidation (LPO), reactive oxygen species (ROS); total antioxidant capacity (TAC) were accessed in peritoneal fluid and tissue. Results: 8-OhdG and PC levels were found to be significantly higher in patients with endometriosis, in addition OGG1 expression was found to be significantly lower in patients with endometriosis (p<0.001, p=0.001, p=0.033 respectively); however, stages I/II, stages III/IV, and control group showed comparable levels of ROS, TAC and LPO. A predictive model was built using multivariable analyses and receiver operating characteristics curves. The ability to predict and distinguish between groups A, B and control patients washigh. The model was corrected in proximally 9 out of 10 patients included (Model/Corrected ratio was 87%). Conclusion: Higher level of DNA damage and 19 lower expression of DNA repair activity may be related with endometriosis progression. Our results indicate that oxidative stress as a biomarker of cell injury might be a useful and reliable quantitative test of endometriosis severity

Comparar a qualidade da imagem entre a ultrassonografia transvaginal sem preparo intestinal e após preparo intestinal nas pacientes com suspeita de endometriose infiltrativa profunda do compartimento posterior e avaliar do grau de desconforto das pacientes em relação ao preparo intestinal. Estudo transversal com dados coletados prospectivamente, incluindo 39 pacientes com suspeita clínica de endometriose do compartimento posterior do ambulatório de Endometriose do Hospital Universitário Pedro Ernesto (HUPE) da Universidade do Estado do Rio de Janeiro (UERJ), no Rio de Janeiro. As pacientes foram submetidas à ultrassonografia transvaginal (USTVG) sem preparo intestinal prévio, seguido de nova USTVG uma hora após realização do enema retal. Os vídeos dos exames gravados foram editados, com ênfase na avaliação do compartimento posterior, com interesse na identificação do nódulo retrocervical e do retossigmóide. Foram graduados conforme a qualidade da imagem pelo examinador e por um radiologista (ambos mascarados), que marcaram uma nota de 0 a 10, usando a escala analógica visual. Restaram apenas 26 pacientes. Em relação ao desconforto devido a realização do enema retal, todas pacientes (100%) relataram apenas um desconforto discreto. Conforme a opção escolhida pelos avaliadores em relação ao melhor método, eles concordaram em 13 (50%) pacientes que a ultrassonografia transvaginal com preparo retal é melhor. Foi usado o teste não-paramétrico de Wilcoxon para amostras dependentes. O p-valor obtido foi de 0.042, considerado significativo (abaixo de 0.05). Isto significa que a realização do enema retal antes da realização da ultrassonografia transvaginal proporcionou uma qualidade melhor na avaliação dos nódulos. A diferença entre as avaliações com e sem preparo retal é maior nos nódulos menores que 2cm, porque encontramos a diferença de 1,1 entre os valores das medianas dos dois tipos de exames. Nos nódulos maiores que 2cm, a diferença encontrada foi de apenas 0,65. A realização do enema retal previamente à realização da ultrassonografia transvaginal no diagnóstico do nódulo endometriótico mostra uma melhora discretamente significativa na qualidade da imagem, comparativamente a não realização de preparo intestinal prévio. Somente nos casos onde o nódulo era menor que 2 cm, foram encontrados valores estatisticamente significativos com o preparo retal. O enema retal causa discreto desconforto, porém isto não parece ser um fator limitante na realização da ultrassonografia com preparo intestinal. / To compare image quality between the transvaginal ultrasound without bowel preparation and after bowel preparation in patients with suspected deep infiltrating endometriosis of the posterior compartment and evaluate the degree of discomfort of patients in relation to bowel preparation. Cross sectional data collected prospectively, including 39 patients with clinical suspicion of endometriosis of the posterior compartment of the endometriosis clinic of the Hospital Universitário Pedro Ernesto (HUPE) State University of Rio de Janeiro (UERJ), in Rio de Janeiro . The patients underwent transvaginal sonography (USTVG) without prior bowel preparation, followed by new USTVG one hour after completion of the rectal enema. The recorded videos of the tests were published, with emphasis on evaluation of the posterior compartment, with interest in the identification of the nodule retrocervical and rectosigmoid. Were graded according to the quality of the image by the examiner and by a radiologist (both masked), which marked a score from 0 to 10, using the visual analog scale. That left only 26 patients. Regarding the realization of discomfort due to rectal enema, all patients (100%) reported only mild discomfort. Depending on the option chosen by the evaluators regarding the best method, they agreed in 13 (50%) patients with transvaginal ultrasound rectal preparation is better. We used the nonparametric Wilcoxon test for dependent samples. The p-value obtained was 0042 and considered significant (less than 0.05). This means that the completion of rectal enema prior to the transvaginal ultrasound provided a better quality in the evaluation of nodules. The difference between evaluations with and without rectal preparation is higher in nodules smaller than 2 cm, because we found a difference of 1.1 between the median values of the two types of tests. In nodules larger than 2cm, the difference was only 0.65. The performance of the rectal enema prior to the performance of transvaginal sonography in the diagnosis of endometriotic nodule shows a slightly significant improvement in image quality, compared to non-completion of bowel preparation prior. Only in cases where the lump was less than 2 cm were found statistically significant values with rectal preparation. The rectal enema cause mild discomfort, but this does not seem to be a limiting factor in the performance of ultrasound with bowel preparation

Endometriosis affects 5-10% of women and is characterized by the growth of endometrial tissue outside of the uterus. Treatment for endometriosis primarily focuses on symptom relief, is short term with severe side effects and often leads to recurrence of the condition. Establishing new blood supply is a fundamental requirement for endometriosis lesions growth. This has led to the idea that antiangiogenic therapy may be a successful approach for inhibiting endometriosis. Recent evidence indicates that endothelial progenitor cells (EPCs) contribute to neoangiogenesis of endometriotic lesions. These EPCs are recruited to the lesion site by stromal cell-derived factor-1 (SDF-1). We hypothesize that SDF-1 is central to the neoangiogenesis and survival of endometriotic lesions and that administration of SDF-1 blocking antibody will inhibit lesion growth by inhibiting angiogenesis in a murine model of endometriosis. Immunohistochemistry for SDF-1 and CD34 was performed on human endometriosis and normal endometrial samples. Quantification of SDF-1 and EPCs was performed in the blood of endometriosis patients and controls using ELISA and flow cytometry, respectively. A new mouse model of endometriosis was developed using BALB/c-Rag2-/-/IL2rg-/- mice to investigate role of SDF-1 in neoangiogenesis. Either SDF-1 blocking antibody or an isotype control was administered on a weekly basis for four weeks. Weekly samples of peripheral blood from mice were analyzed for SDF-1, other cytokines of interest and EPCs. Mice were euthanized at seven weeks to observe lesion growth and blood vessel development. Our results indicate overabundance of SDF-1 and CD34+ progenitor cells in human endometriotic lesions compared to eutopic endometrium. In the mouse model, SDF-1 and circulating EPC levels decreased from pre-treatment levels after one week, and remained constant over the course of the treatment in both SDF-1 blocking antibody and isotype control groups. In the SDF-1 blocking group, reduced vascularity of lesions, identified by immunofluorescence staining for CD31, was revealed compared to isotype controls. These findings suggest that SDF-1 may be responsible for CD34+ progenitor cell recruitment to the neoangiogenic sites in endometriosis. Blocking of SDF-1 reduces neovascularization of human endometriotic lesions in a mouse model. Further studies on blocking SDF-1 in combination with other antiangiogenic agents are needed. / Thesis (Master, Anatomy & Cell Biology) -- Queen's University, 2011-12-21 19:34:43.054

Comparar a qualidade da imagem entre a ultrassonografia transvaginal sem preparo intestinal e após preparo intestinal nas pacientes com suspeita de endometriose infiltrativa profunda do compartimento posterior e avaliar do grau de desconforto das pacientes em relação ao preparo intestinal. Estudo transversal com dados coletados prospectivamente, incluindo 39 pacientes com suspeita clínica de endometriose do compartimento posterior do ambulatório de Endometriose do Hospital Universitário Pedro Ernesto (HUPE) da Universidade do Estado do Rio de Janeiro (UERJ), no Rio de Janeiro. As pacientes foram submetidas à ultrassonografia transvaginal (USTVG) sem preparo intestinal prévio, seguido de nova USTVG uma hora após realização do enema retal. Os vídeos dos exames gravados foram editados, com ênfase na avaliação do compartimento posterior, com interesse na identificação do nódulo retrocervical e do retossigmóide. Foram graduados conforme a qualidade da imagem pelo examinador e por um radiologista (ambos mascarados), que marcaram uma nota de 0 a 10, usando a escala analógica visual. Restaram apenas 26 pacientes. Em relação ao desconforto devido a realização do enema retal, todas pacientes (100%) relataram apenas um desconforto discreto. Conforme a opção escolhida pelos avaliadores em relação ao melhor método, eles concordaram em 13 (50%) pacientes que a ultrassonografia transvaginal com preparo retal é melhor. Foi usado o teste não-paramétrico de Wilcoxon para amostras dependentes. O p-valor obtido foi de 0.042, considerado significativo (abaixo de 0.05). Isto significa que a realização do enema retal antes da realização da ultrassonografia transvaginal proporcionou uma qualidade melhor na avaliação dos nódulos. A diferença entre as avaliações com e sem preparo retal é maior nos nódulos menores que 2cm, porque encontramos a diferença de 1,1 entre os valores das medianas dos dois tipos de exames. Nos nódulos maiores que 2cm, a diferença encontrada foi de apenas 0,65. A realização do enema retal previamente à realização da ultrassonografia transvaginal no diagnóstico do nódulo endometriótico mostra uma melhora discretamente significativa na qualidade da imagem, comparativamente a não realização de preparo intestinal prévio. Somente nos casos onde o nódulo era menor que 2 cm, foram encontrados valores estatisticamente significativos com o preparo retal. O enema retal causa discreto desconforto, porém isto não parece ser um fator limitante na realização da ultrassonografia com preparo intestinal. / To compare image quality between the transvaginal ultrasound without bowel preparation and after bowel preparation in patients with suspected deep infiltrating endometriosis of the posterior compartment and evaluate the degree of discomfort of patients in relation to bowel preparation. Cross sectional data collected prospectively, including 39 patients with clinical suspicion of endometriosis of the posterior compartment of the endometriosis clinic of the Hospital Universitário Pedro Ernesto (HUPE) State University of Rio de Janeiro (UERJ), in Rio de Janeiro . The patients underwent transvaginal sonography (USTVG) without prior bowel preparation, followed by new USTVG one hour after completion of the rectal enema. The recorded videos of the tests were published, with emphasis on evaluation of the posterior compartment, with interest in the identification of the nodule retrocervical and rectosigmoid. Were graded according to the quality of the image by the examiner and by a radiologist (both masked), which marked a score from 0 to 10, using the visual analog scale. That left only 26 patients. Regarding the realization of discomfort due to rectal enema, all patients (100%) reported only mild discomfort. Depending on the option chosen by the evaluators regarding the best method, they agreed in 13 (50%) patients with transvaginal ultrasound rectal preparation is better. We used the nonparametric Wilcoxon test for dependent samples. The p-value obtained was 0042 and considered significant (less than 0.05). This means that the completion of rectal enema prior to the transvaginal ultrasound provided a better quality in the evaluation of nodules. The difference between evaluations with and without rectal preparation is higher in nodules smaller than 2 cm, because we found a difference of 1.1 between the median values of the two types of tests. In nodules larger than 2cm, the difference was only 0.65. The performance of the rectal enema prior to the performance of transvaginal sonography in the diagnosis of endometriotic nodule shows a slightly significant improvement in image quality, compared to non-completion of bowel preparation prior. Only in cases where the lump was less than 2 cm were found statistically significant values with rectal preparation. The rectal enema cause mild discomfort, but this does not seem to be a limiting factor in the performance of ultrasound with bowel preparation

Objetivo:Existemevidências crescentes na literatura da participação do estresseoxidativonaprogressão e agressividade da endometriose. Nesse estudoprospectivo e controlado, foram medidos seis marcadores de estresse oxidativo com a finalidade de relacioná-los com a severidade e progressão da endometriose além debuscarum marcador diagnóstico para a doença. Pacientes e Métodos:Entre Julho de 2010 e Agosto de 2011, 62 pacientes consecutivas com diagnóstico histológico de endometriose foram identificadas como elegíveis para esse estudo. Após os critérios de exclusão, 44 pacientes foram alocadas em três grupos: Grupo A (estádios I/II da ASRM/1996), (n=14), grupo B (estádios III/IV da ASRM/1996),(n=16) e grupo controle (n=14). Os seguintes marcadores foram avaliados no fluido peritoneal e no tecido com endometriose: 8-hidroxi-2- deoxiguanosina (8-OHdG), 8-oxo-guaninaglicosilase (OGG1),proteínacarbonil (PC), oxidação lipídica (LPO), espécies reativas de oxigênio (ROS); capacidade totalantioxidante (TAC). Resultados: Observou-se elevação estatisticamente significante do 8 OhdG e da PC. Notou-se diminuição significativa na expressão do reparo de DNA (OGG1) em estádios avançados de endometriose. (p<0.001, p=0.001, p=0.033 respectivamente). Não notamos significância estatística entre os três grupos estudados nos marcadores ROS,CAT e LPO. Utilizando-se um modelo estatístico multivariável e as curvas ReceiverOperatingCharacteristics(ROC) construiu-se um modelo preditivo de severidade de doença. A habilidade do modelo de distinguir 16 entre os grupos A, B e o grupo controlefoi alta. O modelo foi capaz de diferenciar aproximadamente 9 em cada 10 pacientes incluídas (acerto/corrido foi de 87%). Conclusão:O aumento da lesão no DNA e a diminuição da atividade enzimática de reparo de DNA podem estar relacionados com a progressão da endometriose. Nossos resultados indicam que marcadores oxidativos de agressão celular podem se tornar testes valiosospara se verificar a severidade da endometriose / Objective: There is increasing evidence that oxidative stress is one of the key factors for endometriosis progression. In this prospective controlled trial, we measured six different biomarkers of oxidative stress targeting protein, lipid and DNA to quantify the severity and progression of endometriosis and establish a diagnostic marker for the disease. Methods: 62 consecutive patients were identified to be enrolled in this study. After exclusion criteria, 44 patients were allocated in three groups: Group A (Stage I/II - ASRM/1996), (n=14), Group B(Stage III/IV ASRM/1996), (n=16), and control group (n=14). Levels of 8 hydroxy- deoxyguanosine (8 OHdG), 8- oxoguanine DNA glycosylase (OGG1), protein carbonyl (PC), lipid peroxidation (LPO), reactive oxygen species (ROS); total antioxidant capacity (TAC) were accessed in peritoneal fluid and tissue. Results: 8-OhdG and PC levels were found to be significantly higher in patients with endometriosis, in addition OGG1 expression was found to be significantly lower in patients with endometriosis (p<0.001, p=0.001, p=0.033 respectively); however, stages I/II, stages III/IV, and control group showed comparable levels of ROS, TAC and LPO. A predictive model was built using multivariable analyses and receiver operating characteristics curves. The ability to predict and distinguish between groups A, B and control patients washigh. The model was corrected in proximally 9 out of 10 patients included (Model/Corrected ratio was 87%). Conclusion: Higher level of DNA damage and 19 lower expression of DNA repair activity may be related with endometriosis progression. Our results indicate that oxidative stress as a biomarker of cell injury might be a useful and reliable quantitative test of endometriosis severity

D.Litt. et Phil. / Endometriosis is among the most common gynaecological maladies affecting women's reproductive health and is also known to be associated with infertility. The pathogenesis of endometriosis is however not well understood. Altered immunity has been indicated in the pathophysiology of this puzzling disease. Over the last decade or more the research evidence suggesting that stress might play a role in the pathogenesis of various illnesses has grown significantly. According to certain tenets of psychoneuroimmunology, behaviour and cognitive therapy, by changing an individual's reaction to stress and increasing the ability to cope with stress, thereby altering immune function, may have an effect on the proliferation of a specific illness, in the case of this study, endometriosis. Various behaviour patterns used by individuals to deal with personal and environmental stressors, have been identified. The incessant struggle to overcome real and imagined obstacles imposed by events, time and the actions of other people typifies the Type A behaviour pattern. The aims of this study were to detemine, whether there were, in a randomly chosen group of patients with endometriosis, persons with high indices of Type A behaviour; to determine whether the modification of Type A behaviour in these patients had a positive effect on their biopsychosocial functioning and finally, whether the modification of Type A behaviour had a positive effect on these patients' endometriosis-related infertility. Endometriosis patients being treated at an infertility clinic were invited to participate in the study. Forty-two subjects were recruited. A psychometric test battery was administered to all the participants. Based on the results of the Videotaped Structured Interview, the subjects were equally divided into three groups: a low index Type A group, a high index Type A group and a middle group. Experimental groups 1 and 2 received counseling aimed at reducing Type A behaviour, using the revised version of the SARCPP, which was originally used with coronary heart disease patients. The test battery was again administered after the intervention. It was found that a subset of endometriosis patients did show higher indices of Type A behaviour. Furthermore an intervention that was found to be successful in reducing the Type A behaviour intensity and frequency in subjects with coronary heart disease was also found to be similarly successful in a subset of women with endometriosis. The most significant finding was the increase in pregnancies among the group of subjects who had been exposed to the treatment. Type A behaviour modification was indeed found to be effective in the treatment of infertility in couples where the female experienced endometriosis-related infertility.

L’endométriose concerne 8 à 10% des femmes en âge de procréer et est responsable de douleurs pelviennes chroniques et d’infertilité. Seule l’exérèse chirurgicale des lésions permet un traitement curatif de la maladie. Dans le cas de l’endométriose profonde avec atteinte rectale la chirurgie est extensive et associée à une morbidité significative. Les traitements médicaux reposent sur une hormonothérapie visant à bloquer la fonction ovarienne dont l’effet n’est que suspensif et transitoire. Il n’existe à ce jour aucun traitement ciblant les mécanismes à l’origine de la maladie. L’objectif de notre travail était d’explorer différents mécanismes potentiellement impliqués dans le développement de la maladie et d’identifier des molécules capables d’intervenir sur ces mécanismes. Dans un premier temps nous avons exploré le phénotype hyperprolifératif des cellules endométriosiques profondes et cherché un lien avec différentes voies métaboliques impliquées dans la prolifération cellulaire telles que le stress oxydant, la voie ERK et la voie Akt. Dans un deuxième temps, nous avons exploré le recrutement des cellules endométriales au sein de la cavité péritonéale au travers de l’interaction CXCR4-CXCL12. Des cultures cellulaires ont été réalisées à partir de prélèvements humains de nodules endométriosiques profonds, d’endomètre eutopique et d’endomètre sain. Des lames histologiques ont été préparées à partir de nodules endométriosiques profonds. Des prélèvements de liquide péritonéal de femmes endométriosiques et de témoins ont été congelés. La prolifération cellulaire a été étudiée par incorporation de thymidine tritiée. La production des FRO a été évaluée par spectrofluorimétrie. La voie ERK a été évaluée par western blot, ELISA et immunohistochimie. La voie Akt été évaluée par western blot et immunohistochimie. Nous avons montré un phénotype hyperprolifératif des cellules endométriosiques profondes en rapport avec une activation de la voie ERK par le biais du stress oxydant et à une activation de la voie Akt. Nous avons montré qu’un anti-oxydant (NAC), un inhibiteur de protéines kinases (A771726), un inhibiteur de Raf (sorafenib), un inhibiteur de mTOR (temsirolimus), un agoniste des cannabinoïdes (WIN 55212-2) et un anti-métabolite (5-FU) pouvaient contôler la prolifération des cellules endométriosiques profondes in vitro et la progression de nodules endométriosiques profonds implantés dans des souris Nudes. L’interaction CXCR4-CXCL12 a été étudiée par western blot, analyse de migration, cytométrie de flux et ELISA. Nous avons montré une attraction spécifique des cellules endométriosiques profondes sur-exprimant le CXCR4 par la chimiokine CXCL12 présente en quantité accrue dans le liquide péritonéal des femmes endométriosiques. En conclusion, nous avons montré que le traitement médical de l’endométriose pouvait être non hormonal et que le stress oxydant, la voie ERK et la voie Akt constituaient de nouvelles pistes thérapeutiques à évaluer dans le cadre d’essais cliniques. Nous avons également montré comment la modification constitutive des cellules de l’endomètre eutopique pouvait favoriser leur recrutement dans la cavité péritonéale. / Endometriosis, a common disease that affects approximately 8 to 10% of women of childbearing age, is responsible for chronic pelvic pain and infertility. There is currently no cure other than surgical removal of lesions. In the case of deep infiltrating endometriosis with rectal involvement, surgery is associated with a significant morbidity. Medical treatments are based on a hormone used to block ovarian function. Their effects are only transient and suspensive. There is currently no treatment targeting the mechanisms underlying the disease. The aim of our study was to explore different pathways potentially involved in the development of endometriosis and to identify molecules that act on these mechanisms. In a first step, we explored the hyperproliferative phenotype of deep infiltrating endometriosis cells and sought a link with different metabolic pathways involved in cell proliferation such as oxidative stress, ERK, and Akt pathways. In a second step, we explored the recruitment of endometrial cells in the peritoneal cavity through the CXCL12-CXCR4 interaction. Cell cultures were taken from deep infiltrating endometriosis nodules, eutopic endometrium and control endometrium. Histological slides were prepared from deep endometriotic nodules. Peritoneal fluid of women with deep infiltrating endometriosis, and of women without endometriosis were frozen. Cell proliferation was determined by [H3]thymidine incorporation. Cellular production of ROS was assessed by spectrofluorometry. ERK pathway was assessed by Western blot, ELISA assay and immunohistochemistry. The Akt pathway was assessed by Western blot and immunohistochemistry. We showed a hyperproliferative phenotype of deep infiltrating endometriosis cells in line with an activation of the ERK pathway through an up-regulation of oxidative stress, and activation of the Akt pathway. We have shown that an antioxidant (NAC), an inhibitor of protein kinases (A771726), a Raf inhibitor (sorafenib), an inhibitor of mTOR (temsirolimus), a cannabinoid agonist (WIN 55212-2) and an anti-metabolite (5-FU) could control the proliferation of endometriotic cells in vitro, and the growth of endometriotic nodules grafted in Nude mice. The CXCL12-CXCR4 interaction was studied by Western blot, Transwell migration assay, flow cytometry and ELISA assay. We showed a specific attraction of deep infiltrating endometriosis cells over-expressing the CXCR4 chemokine by CXCL12 present in increased amounts in the peritoneal fluid of endometriotic women. In conclusion, we have shown that medical treatment of endometriosis could be non-hormonal and that oxidative stress, ERK and Akt were new therapeutic approaches to assess in clinical trials. We also showed how the molecular changes of eutopic endometrial cells could facilitate their recruitment into the peritoneal cavity.

Bakgrund: Endometrios är en kronisk gynekologisk sjukdom som tio procent av alla kvinnor lider av. Symtomen är individuella men de vanligaste är bäckenbottensmärta, smärta vid menstruation och samlagsmärta. Kvinnor bemöts med misstro och normalisering av symtom, detta på grund av bristfällig kompetens från hälso- och sjukvården. Sjuksköterskans förhållningssätt gentemot dessa patienter bör innefatta lyhördhet, sympati och empati, ha en god kommunikation och finna mening vid varje möte med patienten.   Syfte: Syftet med litteraturstudien var att beskriva kvinnors erfarenheter i vardagen av att leva med endometrios. Vidare var syftet att beskriva de inkluderade artiklarnas datainsamlingsmetod.   Metod: Litteraturstudie med deskriptiv design. Data samlades in via PubMed och CINAHL där tio vetenskapliga artiklar med kvalitativ ansats fanns, dessa låg till grund för resultatet.   Huvudresultat: Vägen till diagnostisering var en lång process relaterat till misstro samt endometrios diffusa symtom. Endometrios begränsade kvinnornas fysiska, psykiska och sociala förmåga som sänkte livskvalitén. Smärta var det mest påtagliga symtomet, detta bidrog till ett ständigt sökande av strategier för att hantera smärtan. Strategierna varierade hos kvinnorna men den mest användbara strategin var kostförändringar. De tio inkluderade artiklarna i studien använde främst intervjuer för att beskriva kvinnors erfarenheter av att leva med endometrios.   Slutsats: Endometrios påverkar kvinnornas dagliga liv samt att relationer till andra människor blir lidande. Brister i hälso- och sjukvården sågs markant då de ej utgav adekvat  information samt en tydlig misstro relaterat till kvinnors symtom, vilket ligger till grund för den fördröjda diagnosen. För att hantera vardagen har kvinnorna själva funnit olika strategier som reducerar smärtan. / Background: Endometriosis is a chronic gynecological disease which ten percent of all women suffer from. The symptoms are individual but the most common are pelvic pain, pain during menstruation and intercourse pain. Because of insufficient competence in health care system women are treated with disbelief and normalization of symptoms. The nurse attitude towards these patients ought to include sensitivity, sympathy and empathy and also have a good communication and be able to find meaning in each meeting with patients.   Aim: The aim with this literature review was to describe womens experience in daily life of living with endometriosis. The aim was furthermore to describe the included articles data collections method.   Method: A literature review with descriptive design. Data were collected through databases PubMed and CINAHL where ten articles with a qualitative approach was found which laies to basis for the result.   Main results: The way to diagnosis was a long process that was related to disbelief and endometriosis diffuse symptoms. Endometriosis limited womens physical, psychological and social abilities that significantly reduced quality of life. Pain was the most substantial symptom and to be able to handle with the pain, they constantly search for strategies. The strategies varied slightly among the women but the most useful approach was a major dietary change. The ten articles that was included in this literature review  used interviews to collect data and supplemented with diarys and journal entries to describe womens experiences of living with endometriosis.   Conclusion: Endometriosis affects a womans daily life adversely and also her relationships with other people. Deficiencies in health care was significantly when non adequate information was given and a marked disbelief related to the womens symptom that can be one reason for a delayed diagnosis. To be able to handle everyday life women had found different strategies to reduce pain.

Endometrios är en kronisk sjukdom som drabbar en av tio kvinnor världen över. Vanliga symptom är menstruationssmärta, samlagssmärta och en nedsatt fertilitet. Diagnosen endometrios ställs oftast i samband med en titthålsoperation och kan i många fall dröja upp till flera år. Tidigare forskning på området har funnit att individer som lever med endometrios kan uppleva en minskad livskvalité, komplikationer med sociala relationer samt emotionella besvär. Syftet med föreliggande studie var att studera kvinnors upplevelse av endometrios. Åtta kvinnor intervjuades, samtliga bosatta i Stockholmsområdet. Resultatet visar på flera olika psykologiska aspekter som sjukdomen för med sig. En minskad livskvalité, komplikationer med sociala relationer och en nedsatt arbetsförmåga är aspekter som påverkas av de upplevda symptomen. En nedsatt fertilitet kan vidare skapa en reducering av individens självkänsla. Slutsatsen är att en tidigare diagnos och ökad forskning skulle kunna bidra till underlättande av endometriosdrabbades vardag och därmed förbättra deras livskvalité.