Esophagogastroduodenal endoscopy (EGDE) is the most commonly performed endoscopic procedure in Canada and represents 51--65% of all gastrointestinal procedures performed in teaching hospitals. The routine use of conscious sedation during EGDE has facilitated its diffusion, ensured patient and physician satisfaction and has increased the potential risk of cardiorespiratory morbidity. It remains unclear if all adult ambulatory patients require routine conscious sedation prior to diagnostic EGDE, as the efficacy and safety of such a policy has not been rigorously studied in a North American population. / Patients were randomly assigned to sedation or placebo in a double-blind trial. / So far 360 patients of the anticipated patients have been enrolled, (182 randomized to sedation, 178 randomized to placebo). Groups were similar for all baseline characteristics. Eighty-one percent of patients randomized to placebo were able to complete EGDE without sedation. The major determinant of "successful endoscopy" was the use of sedation (OR = 7.52; 95% CI: 4.61--12.26). Preliminary subgroup analysis suggested that among patients greater than 55 yrs and with decreased pharyngeal sensitivity, there was a greater likelihood of successful unsedated endoscopy, when compared to other subsets (45% successful vs. 39% successful among the unstratified placebo population; 98% power). / The use of sedation does not improve technical adequacy. However, the use of sedation in the performance of EGDE is the strongest predictor of a successful endoscopy, patient self-reported satisfaction and willingness to repeat the procedure.

Obesity is an ever-growing problem of our society and, therefore, understanding the underlying endocrine causes is vital to both the prevention and treatment of this disease. This present thesis work was undertaken to better understand the impact of Acylation Stimulating Protein (ASP), an adipokine, on the physiology and pathophysiology of the adipose tissue. I have demonstrated, for the first time, that ASP participates in the recruitment of preadipocytes to become adipocytes (differentiation process). Although, the ASP effects were comparable to those of insulin, preliminary microarray analysis indicates that the early intracellular signaling pathways are likely quite different for both hormones. Furthermore, I have identified and begun to characterize an ASP receptor initially identified as C5L2. I have demonstrated that binding affinity of ASP and C3a (immediate ASP precursor) to C5L2 is similar to that observed in cells that are responsive to ASP (triglyceride synthesis stimulation, TGS). I have also shown, for the first time, that C5L2 is expressed in human adipose tissue, human skin fibroblasts and 3T3-L1 preadipocytes. Finally, the ASP signaling pathway resulting in increased TG synthesis has began to be explored using a "shot gun" approach. This initial phase of research has provided evidence of the involvement of phospholipase C and phosphoinositide 3-kinase in ASP signaling. Overall, the data presented in this thesis defines more clearly ASP-cell interaction and reveals potential targets for pharmacological agents that may prevent or slow down development of obesity in the future.

Human carcinoembryonic antigen (CEA), a well-known clinical tumor marker, belongs to the CEACAM family of cell surface intercellular adhesion molecules that represent a subset of the immunoglobulin superfamily. The glycophosphatidyl inositol-anchored family members, CEA and CEACAM6, are over-expressed in as many as 70% of all human cancers. This correlation suggested their role in tumor progression, which was supported by extensive results obtained with several systems in vitro and ex vivo. But their contribution and relevance in vivo remains uncertain without further validation. Since mice do not possess homologs of the CEA and CEACAM6 genes, transgenic mice harboring a 187 kb portion of the human CEACAM family gene locus contained in a bacterial artificial chromosome (CEABAC) that includes CEA, CEACAM3, CEACAM6, and CEACAM7 genes were constructed in this study. The spatiotemporal expression pattern of these genes is very similar to that in humans. The expression levels of these genes are gene dosage dependent. Moreover, these CEABAC mice are more susceptible to develop carcinogen-induced colon tumors and spontaneous lung tumors. At low to moderate expression levels of CEA/CEACAM6, a partial block in cell differentiation and a mild to moderate hyperproliferation were evident in the transgenic colon; however, these mice develop normally. At higher or tumor-like expression levels, a complete block in cell differentiation, an extreme hyperproliferation and an inhibition of apoptosis were observed. These mice showed reduced survival, growth retardation and chronic diarrhea, and showed massively enlarged colons comprising continuous non-focal cytological and architectural abnormalities, including a dysplastic and serrated adenomatous morphology, by only 3 months of age. These results suggested that, while moderate expression levels of CEA/CEACAM6 cause an imbalance of tissue homeostasis leading to increased tumor susceptibility, tumor-like exp

Multiple organ dysfunction is the most common cause of late mortality in trauma patients. Despite adequate resuscitation, hemorrhagic shock may progress to a state of profound systemic inflammation where the polymorphonuclear neutrophil (PMN) plays a key role. Resuscitation with hypertonic saline (HTS) may modulate the host inflammatory response in hemorrhagic shock. / A murine hemorrhagic shock model evaluated by cremaster intravital microscopy demonstrated significant in vivo attenuation of neutrophil rolling and adhesion to endothelium (EC) immediately after resuscitation with HTS, as compared to Ringer's lactate (RL). Concurrently, macromolecular leakage from the same post capillary venules was 45% lower in HTS animals. / To better simulate clinical conditions, the model was transformed to recreate two-hit conditions by subjecting resuscitated animals to a subsequent mimicked pulmonary infection. Attenuated neutrophil adhesion to endothelium in HTS animals persisted 5 and 22 hours after resuscitation. Additionally, compared to RL, HTS resuscitation reduced neutrophil lung sequestration (by the myeloperoxidase assay) and neutrophil lung transmigration (by histologic analysis) one day after resuscitation. HTS resuscitation also tended to improve cremaster and lung histologic injury a day after resuscitation conferring a 50% survival advantage for that time interval. / To determine if reductions in tissue injury were due to the ability of HTS to functionally block neutrophil adhesion to endothelium, another variation to the two-hit model was developed. Two additional groups were added to evaluate if supplementation of standard fluid resuscitation with anti adhesion monoclonal antibodies (anti-CD11b and anti-ICAM-1) would reproduce the effects of HTS alone. Although early EC/PMN interactions and 24-hour lung PMN accumulation were similarly attenuated by either HTS alone or RL with anti adhesion blockade, only HTS alone definitely reduced early in vivo macromolecule leakage, and one day lung histologic injury. / Hemorrhagic shock resuscitation with hypertonic saline reduces neutrophil activation and interactions with microvascular endothelium resulting in diminished lung PMN sequestration persisting well beyond the initial resuscitation phase. Yet the anti-adhesive effects of HTS are not essential for HTS-mediated reductions in tissue injury and organ dysfunction. Hypertonic resuscitation may prove to be an immunomodulatory therapy useful in critically ill trauma victims, the precise mechanisms of which need further elucidation.

Immunotherapy of cancer aims at achieving systemic anticancer responses capable of eradicating disseminated malignant cells. The disappointing outcomes associated with several immune-based clinical trials have highlighted the need to improve upon existing therapeutic strategies. The main objective of my thesis was to develop novel means in order to improve current cytokine-based anticancer strategies. The delivery of cytokines, or their encoding cDNA sequences, can induce antitumor immune responses. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most potent cytokines able to induce tumor-specific systemic immunity, both in experimental models and clinical trials. Paradoxically, the combination of GM-CSF and IL-2 has been reported to downregulate certain immune functions, highlighting the unpredictability of dual cytokine use. In the first section of my thesis, I hypothesized that a GM-CSF and IL-2 fusion transgene (GIFT) could circumvent the limitations associated with dual cytokine expression yet preserve synergistic features. B16 mouse melanoma cells were gene modified to express GIFT (B16GIFT) and GIFT gene product was characterized in vitro. When injected into syngeneic mice, B16GIFT cells were unable to form tumors. When used as a whole cell tumor vaccine, irradiated B16GIFT could induce absolute protective immunity against wild type B16 tumors. In mice with established melanoma, B16GIFT therapeutic cellular vaccine significantly improved tumor-free survival when compared to B16 expressing both IL-2 and GM-CSF. Mechanistically, GIFT induced a significantly greater tumor site recruitment of macrophages and NK cells than combined GM-CSF and IL-2. I thus demonstrated that a fusion between GM-CSF and IL-2 can invoke greater antitumor effect than both cytokines in combination and that novel immunobiological properties can arise from such chimeric constructs. / Another means to improve current cytokine-based strategies is to limit the severe side-effects associated with their systemic administration. In view of that, I tested the hypothesis that primary marrow stromal cells (MSCs) can be used as a cellular vehicle for the tumor-localized delivery of immunostimulatory cytokines. Specifically, I investigated whether IL-2 gene-modified MSCs can be used to mount an effective immune response against the poorly immunogenic B16 melanoma model. My research demonstrated that primary mouse MSCs can be efficiently gene-modified to secrete IL-2. Remarkably, IL-2 secreting MSCs embedded in a collagen-like matrix and injected in the vicinity of pre-established B16 tumors led to absence of tumor growth in 90% of treated mice. Injection of IL-2 secreting MSCs induced CD8 mediated tumor specific immunity and was dependent upon CD8 and NK cells, but not CD4 cells. / Therefore, despite their previously reported immunosuppressive effects on allogeneic immune responses, I provided evidence that primary MSCs can be used as transgenic delivery vehicles to enhance immune responses in syngeneic hosts. In order to further characterize the effect of MSCs on autologous immunity, I investigated the immunomodulatory properties of MSCs during syngeneic antigen-specific immune responses. I provide experimental evidence that syngeneic MSCs behave as conditional antigen-presenting cells. My research demonstrated that IFNgamma can induce mouse MSCs to process and present antigenic peptides derived from a soluble xenoprotein (i.e. ovalbumin) and activate in vitro antigen-specific T cells. When injected in vivo into syngeneic mice, ovalbumin-pulsed IFNgamma-treated MSCs induced potent ovalbumin-specific cellular immune responses and protected mice against ovalbumin-expressing tumors. My studies further showed that human MSCs can also acquire antigen-presenting functions upon IFNgamma stimulation, thereby activating antigen-specific T cell hybridomas. Taken together, my results strongly suggest that in syngeneic conditions, IFNgamma-stimulated MSCs behave as conditional antigen presenting cells able to activate antigen-specific immune responses. / Overall, my research opens the door for the development of new immunotherapeutic strategies based on (i) the improvement of cytokine potency by molecular fusion and (ii) the improvement of cytokine delivery by the use of gene modified somatic MSCs, and may reveal MSCs as previously unrecognized cellular regulators of physiological immune responses.

Diabetes is characterized by a complete (type 1) or partial (type 2) loss of pancreatic beta cells. Regeneration of beta-cell mass is an important goal of diabetes research. Development of strategies to induce beta-cell regeneration in situ involves identification of candidate molecules with islet regenerating activity. Islet Neogenesis Associated Protein (INGAP), identified in our laboratory, has been shown to stimulate neo-islet formation. INGAP, an endogenous pancreatic protein, is a member of the Reg3 family of proteins. We have previously shown that INGAP expression is regulated by inflammatory cytokines, more specifically by interleukin (IL)-6. It would be of interest to identify other factors, preferably of non-inflammatory nature, that upregulate INGAP expression and subsequently induce islet neogenesis. Here, using an in vitro hamster cell model and real time qRT-PCR, we show that INGAP gene expression is induced by 1,25(OH)2 D3, the hormonally active form of vitamin D. Our data indicate that 1,25(OH)2 D3 upregulates INGAP mRNA (up to 2.14 (± 0.59)) in a dose- and time-dependent manner. We also show that nicotinamide, the amide derivative of vitamin B3, potentiates the effect of 1,25(OH)2 D3 resulting in a 12-fold increase in INGAP mRNA. A computer analysis of the INGAP promoter region identified five candidate vitamin D responsive elements (VDREs), which may bind the ligand-activated nuclear vitamin D receptor (VDR). The role of this classic mechanism of vitamin D signaling in the upregulation of INGAP expression, as well as a potential involvement of rapid, membrane-linked signal transduction or calcium signaling pathways are also investigated here. / This is the first study to provide evidence for regulation of INGAP, and possibly, of other Reg proteins by vitamin D3. Interestingly, vitamin D3 can be partially activated in beta cells and is implicated in cell growth and differentiation. Given the presence of VDRs in endocrine and exocrine pancreatic tissue, the potential role of vitamin D3 in islet neogenesis should be further investigated. Taken together, these data suggest an important role for vitamin D3 in beta-cell regeneration, which may prove to be a cost-effect, natural and safe treatment for type-1 and type-2 diabetes. / Le diabète est caractérisé par la perte totale (type 1) ou partielle (type 2) des cellules beta. La régénération d'une masse fonctionnelle de cellules beta est un objectif important de la recherche sur le diabète. Le développement de stratégies pour induire la régénération des cellules beta in situ implique l'identification de molécules candidates ayant une activité néogénique sur les îlots de Langerhans. La protéine Islet Neogenesis Associated Protein (INGAP), identifiée dans notre laboratoire, stimule la néogenèse des îlots de Langerhans. INGAP, protéine pancréatique endogène, est membre de la famille de protéines Reg3. Nous avons montré précédemment que l'expression d'INGAP est régulée par les cytokines inflammatoires, plus particulièrement par l'interleukine (IL) -6. Il serait intéressant d'interfier d'autres facteurs, préférablement de nature non-inflammatoire, ayant la capacité d'agumenter l'expression d'INGAP et par conséquent la néogenèse des îlots de Langerhans. Ici, en utilisant un modèle in vitro de cellules de hamster et la technique de RT-PCR quantitative (real-time), nous montrons que l'expression d'INGAP est induite par 1,25(OH)2D3, la forme hormonalment active de la vitamine D. Nos données indiquent que 1,25(OH)2D3 induit l'expression de INGAP (ARNm) d'un facteur 2.14 (± 0.59) de façon dose-dépendante et en suivant une cinétique bien precise. Nous montrons également que la nicotinamide, un dérivé amidique de la vitamine B3, potentialise l'effect de la 1,25(OH)2D3, ce qui a pour résultat une augmentation de 12 fois de l'expression de INGAP (ARNm). / En utilisant une analyse informatique de la séquence du promoteur d'INGAP, nous avons identifié 5 éléments de réponse a la vitamine D (VDREs) qui pourraient lier le récepteur a la vitamin D (VDR) activé par la fixation de son ligand. Le rôle de ce mécanisme classique de la signalisation de la vitamine D dans l'induction de l'expression d'INGAP, ainsi que la participation potentielle d'une transduction rapide via liaison à la membrane ou encore l'implication de la voie de signalisation du calcium sont également étudiées ici. / Cette étude est la première à démontrer la regulation de l'expression de INGAP, et probablement d'autre proteins Reg, par la vitamine D3. De façon intéressante, la vitamine D3 peut être partiellement activée dans les cellules beta et est impliquée dans la croissance cellulaire et la différenciation. Compte-tenu de la présence de VDR dans le le pancreas endocrine et exocrine, le rôle potentiel de vitamine D3 dans la néogenèse d'îlot devrait être étudié plus avant. L'ensemble de ces données suggère un rôle important pour la vitamine D3 dans la régénération des cellules beta, qui pourrait donc constituer un traitement naturel, sécurataire, et peu coûteux pour le diabète type-1 et type 2.

Quality of life (QOL) optimization is an important issue during the process of care for patients suffering from a life-threatening illness such as cancer. The Quality of Life in Life-Threatening Illness-Patient questionnaire (QOLLTI-P) is a self-administered questionnaire based on the McGill Quality of Life questionnaire (MQOL) with domains added to enhance content validity. This study's main objective was to assess the construct validity of QOLLTI-P in cancer patients. Cancer outpatients were asked to complete a set of questionnaires including QOLLTI-P and the Functional Assessment of Chronic Illness Therapy- Spiritual well-being scale (FACIT-Sp). An 8-factor structure was suggested for QOLLTI-P. In general, QOLLTI-P Total and subscale scores are highly correlated with their corresponding FACIT-Sp scores. In conclusion, QOLLTI-P is a valid instrument to assess the QOL of cancer patients. / L'optimisation de la qualité de vie (QOL, quality of life) est un enjeu important lorsqu'on donne des soins aux patients atteints d'une maladie grave telle que le cancer. Le Questionnaire de qualité de vie pour patient gravement malade (QOLLTI-P, Quality of Life in Life-Threatening Illness – Patient) est un questionnaire auto-administré basé sur le Questionnaire de qualité de vie de McGill (MQOL, McGill Quality of Life), avec des domaines supplémentaires ajoutés pour augmenter la validité du contenu. Le but principal de cette étude était d'évaluer la validité conceptuelle du QOLLTI-P pour les patients atteints de cancer. On a demandé aux patients des cliniques externes en oncologie de compléter une série de questionnaires comprenant le QOLLTI-P et le Bilan fonctionnel de la thérapie pour une maladie chronique – Échelle de bien-être spirituel (FACIT-Sp, Functional Assessment of Chronic Illness Therapy – Spiritual well-being scale). Une structure de 8 facteurs a été suggérée pour le QOLLTI-P. En général, les cotes des sous-échelles et les cotes totales du QOLLTI-P sont fortement corrélées avec les cotes du FACIT-Sp correspondantes. En conclusion, le QOLLTI-P est, un instrument valable pour évaluer la qualité de vie des patients atteints de cancer.

Tissue injury related to liver surgery stimulates the release of stress hormones and proinflammatory cytokines to produce the necessary elements needed for healing. An exaggerated stress response compounded by preoperative fasting limits the liver's capacity to regenerate by depleting its energy stores. This change in metabolism leads to an insulin resistant state in the patient and associated hyperglycaemia. Dextrose supplementation coupled with intravenous insulin given perioperatively affords superior surgical outcomes through preservation of liver glycogen and strict glycaemia control.The goal of this research was to investigate the benefits of a metabolic support protocol involving carbohydrate loading and insulin infusion provided by a hyperinsulinemic normoglycaemic clamp (HNC), for patients undergoing hepatic resection. Studies were performed in the context of a randomized-controlled clinical trial registered at clinicaltrial.gov NCT00774098. Initially, 5 patients including 1 with diabetes mellitus were given the HNC protocol while undergoing a major hepatectomy. This feasibility study helped fine-tune the protocol towards improving its safety and reproducibility, and prompted expansion and randomization of the trial to include sixty patients. The goal of the expanded trial was to study the benefits of the protocol in augmenting liver glycogen and reducing postoperative complications. The patients were randomly assigned to either intervention or control groups. Intervention patients received a 24-hour oral carbohydrate-load, followed by an IV dextrose infusion (2 mg/kg/min) in the 24 hours leading to surgery, followed by insulin therapy given intra- and postoperatively. Controls adhered to routine management. Blood and tissue samples were taken at various time points for monitoring liver glycogen content and function. In the final stage of the project a subset of patients was selected for genetic expression testing. Blood and liver tissue samples were analyzed to identify specific inflammatory, metabolic and cell cycles pathways stimulated by the protocol.Carbohydrate loading combined with intra- and postoperative use of the HNC protocol augmented liver glycogen and reduced postoperative complications. Diabetic and nondiabetic patients alike benefited from this therapy. / Les tissus traumatiques chirurgicaux stimulent la libération d'hormones de stress et de cytokines pro-inflammatoires afin de créer les éléments nécessaires pour la cicatrisation. Une réponse au stress aggravée par le jeune préopératoire limite la capacité du foie à se régénérer en puisant dans ses réserves d'énergie. Ce changement de métabolisme conduit à un état de résistance insulinémique et d'hyperglycémie chez le patient. Un supplément de dextrose et d'insuline par voie intraveineuse durant la période périopératoire offre des résultats post-chirurgicaux supérieurs tout en laissant le foie préserver son glycogène et maintenir un contrôle glycémique stricte. Le but de cette étude était d'étudier les avantages reliés à l'utilisation d'un protocole de soutien métabolique impliquant la perfusion de glucides et d'insuline par le biais d'une pince hyperinsulinémique normoglycémiques (HNC) sur des patients cédulés pour une résection hépatique. Cette étude a été réalisée dans le cadre d'une étude clinique randomisé-contrôlées enregistré sous NCT00774098 sur clinicaltrial.gov. Au départ, 5 patients, dont 1 atteint de diabète Type I, ont été randomisés sur le protocole HNC durant l'hépatectomie majeure. Cette étude de faisabilité nous a aidés à affiner le protocole afin de le reproduire, tout en sécurité, sur un plus grand échantillon. Nous avons généré un essai clinique randomisé incluant 60 patients afin d`étudier les effets bénéfiques reliés à ce type de protocole au niveau de l'accroissement du niveau de glycogène dans le foie et la réduction des complications post opératoires. Les patients ont été randomisés soit sur le protocole HNC ou le groupe de contrôle. Les patients randomisés sur l'étude recevaient, en plus du HNC durant la période intra et post opératoire, des suppléments élevés de glucide par voie orale, suivie d'une perfusion de dextrose par voie intraveineuse à 2 mg / kg / min dans les 24 heures précédant l'intervention chirurgicale. Le groupe de contrôle était gérer en suivant le protocole standard de l'hôpital. Des échantillons de sang et de foie ont été prélevés à divers moments afin de suivre de près la fonction hépatique et la teneur de glycogène dans le foie. En plus, des tests d'expression génétique ont été faits sur certains de ces échantillons. Les échantillons de sang et de foie étaient analysés pour étudier le cycle métabolique, inflammatoire et cellulaire. Une surcharge de glucide combiné avec l'utilisation du HNC durant l'opération et la période post-opératoire a augmenté le niveau de glycogène dans le foie et a réduit les complications post-opératoires. Les diabétiques et les non-diabétiques ont bénéficié d'une telle thérapie.

The regenerating (Reg) genes have been associated with tissue repair and have been directly implicated in pancreatic beta-cell regeneration. Peptide administration of INGAP, a hamster Reg3, can reverse hyperglycaemia in rodents and stimulate new beta-cell growth in human epithelial cultures. / New Reg genes in rats and hamsters were identified using homology reverse transcription polymerase chain reaction (RT-PCR) with degenerate Reg3 primers and selected products were further sequenced using rapid amplification of cDNA ends (RACE). This method resulted in no novel rat Regs, although a putative rat INGAP with 65% identity to the mouse INGAP protein was discovered by a BLAST homology search of the rat genome. The putative rat INGAP protein was shorter than both mouse and hamster INGAP and a mRNA transcript could not be amplified by PCR. It is thus concluded that this rat homologue of INGAP is a pseudogene. / Homology RT-PCR did, however, result in the discovery of a new hamster Reg3 gene of 765 nucleotides (nt) that encodes a 174 amino acid (aa) protein. This protein sequence was identified as a novel hamster Reg3gamma with 78% and 75% identity to the rat Reg3gamma and mouse Reg3gamma protein, respectively. The hamster Reg1 gene coding region was fully sequenced from a reported partial sequence using RACE to yield a 756 nt transcript that encodes a deduced 173 aa protein. This protein was identified as hamster Reg2, rather than Reg1 as was initially reported, with an 81% identity to mouse Reg2. / Mice and hamsters are the only species known to carry either of the functional INGAP or Reg2 genes. It remains to be determined whether these genes bestow mice and hamsters with special regenerative abilities in the pancreas.

Background: As breast reconstruction evolves, plastic surgeons continue to find ways to improve their reconstruction' outcomes. The aim of our study is to demonstrate how plastic surgery research impacts and improves current surgical practices. For instance, we designed three clinical studies which illustrate how research can affect current popular surgical practices, not only during the pre-operative period, but also intra-operative and post-operative periods. Methods: In the first study, we performed a meta-analysis to evaluate first the safety and efficacy of Thoracic ParaVertebral Block (TPVB) for breast surgery, and then to compare TPVB to General Anesthesia (GA) with regards to postoperative pain, nausea and vomiting, opioid consumption and length of hospital stay. To do so, an electronic and manual search of English- and French- language articles on TPVB in breast surgery (published up to June 2010) was performed. Two levels of screening were used to identify relevant articles. The Mantel-Haenszel method (fixed effect) was used to perform the meta-analysis.In the second study, we performed a systematic review to evaluate the existing literature, comparing the use of drains or not in reduction mammaplasty. We assessed first, if there is enough evidence to reach a conclusion regarding the routine use of drains after reduction mammaplasty, and then, if there is a need for more randomized control trials. To do so, we searched PubMed, EMBASE, the Cochrane Central Database of Clinical Trials (CENTRAL) on the Cochrane Library and Science Citation Index Expanded for original articles and reviews from January 1980 to June 2009. Finally, in the third study, we are presenting our clinical experience of using subcutaneous breast tissue expansion prior to reconstruction with Deep Inferior Epigastric Perforator (DIEP) flaps, and we are showing how our new technique eliminates the patch-like appearance of the skin paddle. We developed this technique; surgical technique that was never described or presented before. Over the past 2 years (January 2008 – January 2010), five patients underwent breast reconstruction using this three-stage approach. Retrospective analysis of patients' characteristics, breast history, surgical stay, complications and outcomes were performed. Results: Our first study demonstrated that pre-operative TPVB provides effective anesthesia for ambulatory / same-day breast surgery and can result in significant benefits over GA. However further studies are required to determine if these advantages would still persist if an optimal technique for outpatient GA is employed. Adjunctive ultrasonography may contribute to improve the safety of TPVB in breast surgery and requires further investigation.Our second study, we demonstrated that although placement of intra-operative drains after reduction mammaplasty is common practice, it should not be used routinely in reduction mammaplasty. Further randomized controlled trials are not warranted. Finally, our third study demonstrated how innovation in plastic surgery research can improve the final, post-operative aesthetic outcome. Subcutaneous breast tissue expansion followed by DIEP flap reconstruction can be performed safely, offering patients a completely autologous breast reconstruction with low morbidity, as well as eliminating the classical patch-like appearance of flap reconstructions.Conclusion:These three different studies illustrate how plastic surgery research can have an impact on breast reconstruction outcomes. The first two studies demonstrate with a strong level of evidence (meta-analysis and systematic review, respectively) that established pre-operative and post-operative factors can be changed for the benefit of the patient. Finally, we demonstrated how surgical technique innovation can improve the post-operative outcome. / Contexte: Avec l'évolution de la chirurgie reconstructive du sein, les chirurgiens plasticiens continuent de trouver des moyens d'améliorer leurs reconstructions. Le but de notre étude est de démontrer, à travers trois études cliniques, comment la recherche en chirurgie plastique peut améliorer les pratiques chirurgicales courantes, durant les périodes pré-, intra- et postopératoires. Méthodes: Lors de notre première étude, nous avons effectué une méta-analyse afin d'évaluer la sécurité d'utilisation et l'efficacité des Blocs Thoraciques Para-Vertébraux (BTPV) pour la chirurgie du sein, en comparaison à l'Anesthésie Générale (AG). Pour cela, nous avons effectué une recherche électronique et manuelle d'articles écrits en anglais et français sur les BTPV en chirurgie du sein (publiés jusqu'en Juin 2010). Deux niveaux de sélection d'articles ont été utilisés. La méthode de Mantel-Haenszel (effets fixes) a été utilisée pour effectuer la méta-analyse. Lors de notre seconde étude, nous avons effectué une revue systématique afin d'évaluer la littérature existante qui compare l'utilisation de drains ou non lors des réductions mammaires. Pour cela, nous avons cherché Pub Med, EMBASE, le "Cochrane Central Database of Clinical Trials (CENTRAL) on the Cochrane Library" et le "Science Citation Index Expanded" pour les articles et revues de Janvier 1980 à Juin 2009. Finalement, lors de notre troisième étude, nous présentons notre expérience sur l'utilisation d'expanseurs sous cutanés de seins avant une reconstruction avec un lambeau basé sur la perforante de l'artère inferieure épigastrique profonde (lambeau DIEP). Nous démontrons comment notre nouvelle technique élimine l'apparence de patch du lambeau DIEP sur le sein. Nous avons développé cette technique; technique chirurgicale qui n'a jamais été décrite ou présentée auparavant. Au courant des deux dernières années (Janvier 2008 – Janvier 2010), cinq patients ont bénéficié de cette approche à trois étapes. Une analyse rétrospective des caractéristiques médicales des patients, de leur pathologie mammaire, de leurs hospitalisations, des complications et de leurs résultats, a été effectuée. Résultats: Notre première étude a démontré que les BTPV en préopératoire permettent une anesthésie effective pour les cas-de-jour de chirurgie du sein et démontrent des bénéfices supérieurs à l'AG. Cependant, plus d'études sont à faire afin de déterminer si ces avantages perdurent si une technique optimale pour une AG pour patients non-hospitalises est employée. L'échographie pourrait contribuer à améliorer la morbidité possible associée avec les BTPV en chirurgie du sein et devrait être étudiée en profondeur. Notre seconde étude a démontré que même si le placement routinier de drains en intra-opératoire après réduction mammaire est une pratique très populaire, cela ne devrait pas être utilisé de manière routinière après les réductions mammaires. Plus d'études randomisées contrôlées ne sont pas requises. Finalement, notre troisième étude a démontré comment l'innovation en recherche en chirurgie plastique peut améliorer le résultat final, postopératoire. L'expansion mammaire sous-cutanée suivie par reconstruction avec lambeau DIEP peut être effectuée en toute sécurité et offre aux patients une reconstruction mammaire totalement autologue, avec une faible morbidité, tout en éliminant l'apparence en forme de patch des reconstructions mammaires autologues classiques. Conclusion: Ces trois différentes études illustrent bien comment la recherche en chirurgie plastique peut affecter les résultats en reconstruction mammaire. Nos deux premières études démontrent avec un niveau d'évidence très élevé (méta-analyse puis revue systématique) que des pratiques préopératoires et intra-opératoires établies peuvent être modifiées au bénéfice des patients. Finalement, nous avons démontré comment une technique chirurgicale innovatrice peut améliorer les résultats postopératoires.