京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13126号 / 論医博第2135号 / 新制||医||1024(附属図書館) / (主査)教授 湊谷 謙司, 教授 椛島 健治, 教授 岩井 一宏 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Orientador: Aristides Augusto Palhares Neto / Resumo: Introdução: A cicatriz desempenha um importante papel no resultado final de uma cirurgia. Muitos fatores são implicados no processo de cicatrização patológica, e diversos produtos e curativos foram desenvolvidos para prevenção de cicatriz hipertrófica e quelóide, porém poucos tem evidências que o suportem. Objetivos: Comparar o resultado da cicatriz cirúrgica após utilização da fita de silicone e da fita microporosa. Métodos: Realizamos um ensaio clínico controlado, cego e randomizado, onde um lado da incisão foi randomizado para receber a fita de silicone e o outro lado recebeu o tratamento controle (fita adesiva microporosa). Foram selecionadas pacientes submetidas a abdominoplastia ou mastoplastia de aumento com implantes de silicone no período de maio a outubro de 2016. A Escala de Cicatrização de Vancouver foi utilizada para avaliar as cicatrizes. Resultados: Foram selecionadas para o estudo 17 pacientes. A idade média das pacientes foi de 31,4 ± 6,7, sendo a mínima de 20 e a máxima de 45 anos. Vemos na comparação dos tipos de curativo que os valores de p foram próximos a 5%, sugerindo uma associação do uso da fita de silicone com melhores resultados estéticos e funcionais da cicatriz em relação à fita microporosa. Notamos também que os dois tipos de curativo tiveram uma redução significativa em seus escores do primeiro para o terceiro mês (traduzindo uma melhora no aspecto da cicatriz), porém a fita de silicone teve uma redução superior à fita microporosa (45,6% e 39,2%... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Submitted by ANA LUÍZA ALVES PINTO LUNA null (analualves@hotmail.com) on 2017-09-25T18:42:11Z No. of bitstreams: 1 DISSERTAÇÃO MESTRADO Ana Luiza Alves Pinto Luna.pdf: 1782319 bytes, checksum: 832d2855b5d3e28f440d7df38d89674c (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-09-27T20:31:58Z (GMT) No. of bitstreams: 1 luna_alap_me_bot.pdf: 1782319 bytes, checksum: 832d2855b5d3e28f440d7df38d89674c (MD5) / Made available in DSpace on 2017-09-27T20:31:58Z (GMT). No. of bitstreams: 1 luna_alap_me_bot.pdf: 1782319 bytes, checksum: 832d2855b5d3e28f440d7df38d89674c (MD5) Previous issue date: 2017-08-25 / Introdução: A cicatriz desempenha um importante papel no resultado final de uma cirurgia. Muitos fatores são implicados no processo de cicatrização patológica, e diversos produtos e curativos foram desenvolvidos para prevenção de cicatriz hipertrófica e quelóide, porém poucos tem evidências que o suportem. Objetivos: Comparar o resultado da cicatriz cirúrgica após utilização da fita de silicone e da fita microporosa. Métodos: Realizamos um ensaio clínico controlado, cego e randomizado, onde um lado da incisão foi randomizado para receber a fita de silicone e o outro lado recebeu o tratamento controle (fita adesiva microporosa). Foram selecionadas pacientes submetidas a abdominoplastia ou mastoplastia de aumento com implantes de silicone no período de maio a outubro de 2016. A Escala de Cicatrização de Vancouver foi utilizada para avaliar as cicatrizes. Resultados: Foram selecionadas para o estudo 17 pacientes. A idade média das pacientes foi de 31,4 ± 6,7, sendo a mínima de 20 e a máxima de 45 anos. Vemos na comparação dos tipos de curativo que os valores de p foram próximos a 5%, sugerindo uma associação do uso da fita de silicone com melhores resultados estéticos e funcionais da cicatriz em relação à fita microporosa. Notamos também que os dois tipos de curativo tiveram uma redução significativa em seus escores do primeiro para o terceiro mês (traduzindo uma melhora no aspecto da cicatriz), porém a fita de silicone teve uma redução superior à fita microporosa (45,6% e 39,2% respectivamente). Conclusão: A fita de silicone parece ser discretamente mais efetiva em promover melhoria da cicatriz cirúrgica a médio prazo, com base na Escala de Cicatrização de Vancouver, em relação à fita microporosa. Ambas as fitas apresentaram melhora no escore do terceiro mês de pós-operatório quando comparados ao primeiro mês, porém a fita de silicone apresentou uma redução superior. Os pontos de maior diferença constaram na pliabilidade, altura e vascularização. Quanto aos efeitos adversos, ambos os curativos apresentaram como intercorrência o surgimento de rash cutâneo, sendo que o surgimento foi maior com o uso da fita de silicone (RR=2). / Introduction: The scar plays an important role on result of any surgery. Many factors are implied in the pathologic scar healing process. Lots of dressings and products have been developed to prevent formation of hypertrophic scar and keloids, but few have been supported by evidence. Objective: To compare the surgical scar result after using silicone-gel sheeting and microporous tape. Methods: We’ve performed a blind and randomized clinical trial, using the silicone-gel sheeting on one side of the surgical incision and the control-treatment on the opposite site (microporous tape). Selected patients underwent abdominoplasty or augmentation mastoplasty with silicone implants from May to October of 2016. The Vancouver Scar Scale (VSS) was assessed to evaluate the scars. Results: Seventeen patients were selected for the study. The mean age was 31,4 ± 6,7, with the youngest at 20 and the oldest with 45 years-old. Comparing the two dressing types, we found that p values were close to 5%, suggesting that the siliconegel sheeting promotes better aesthetic and functional results over the microporous tape. We also noticed that both dressings had a significant reduction on the VSS score from the first to the third month of post-operative, although the silicone-gel sheeting had a superior reduction (45,6% and 39,2%). Conclusion: Silicone-gel sheeting appears to be slightly more effective in promoting mid-term improvement of surgical scar, related to the VSS, and compared to microporous tape. Both dressings provided an upgrade on VSS score from the first to the third post-operative month evaluation, but the silicone-gel sheeting was superior. Most of the difference relied on pliability, height and vascularization. As to the side effects, both dressings presented with skin rash, but the silicone-gel sheeting had a higher occurrence (RR=2).

L'objectif de ce travail de recherche est le développement, la mise au point et la validation d'une méthode de spectroscopie multi-modalités en diffusion élastique et autofluorescence pour caractériser des tissus cutanés cicatriciels hypertrophiques in vivo. Ces travaux sont reposés sur trois axes. La première partie des travaux présente l'instrumentation : développement d'un système spectroscopique qui permet de réaliser des mesures de multimodalités in vivo de manière automatique et efficace. Des procédures métrologiques sont mise en place pour caractériser le système développé et assurer la repétabilité les résultats de mesure. La deuxième partie présente une étude préclinique. Un modèle animal et un protocole expérimental ont été mises en place pour créer des cicatrices hypertrophiques sur lesquelles nous pouvons recueillir des spectres à analyser. La troisième partie porte sur la classification des spectres obtenus. Elle propose des méthodes algorithmiques pour débruiter et corriger les spectres mesurés, pour extraire automatiquement des caractéristiques spectrales interprétables et pour sélectionner un sous-ensemble de caractéristiques "optimales" en vue d'une classification efficace. Les résultats de classification réalisée respectivement par trois méthodes (k-ppv, ADL et RNA) montrent que la faisabilité d'utiliser la spectroscopie bimodale pour la caractérisation de ce type de lésion cutané. Par ailleurs, les caractéristiques sélectionnées par notre méthode montrent que la cicatrisation hypertrophique implique un changement de structure tissulaire et une variation de concentration de porphyrine / This research activity aims at developing and validating a multimodal system combining diffuse reflectance spectroscopy and autofluorescence spectroscopy in characterizing hypertrophic scar tissues in vivo. The work relies on three axes. The first part concerns the development of an automatic system which is suitable for multimodal spectroscopic measurement. A series of calibration procedures are carried out for ensuring the reliability of the measurement result. The second part presents a preclinical study on an animal model (rabbit ear). An experimental protocol was implemented in order to create hypertrophic scars on which we can collect spectra to analyze. The third part deals with the classification problem on the spectra obtained. It provides a series of algorithmic methods for denoising and correcting the measured spectra, for automatically extracting some interpretable spectral features and for selecting an optimal subset for classification. The classification results arched using respectively 3 different classifiers (knn, LDA and ANN) show the ability of bimodal spectroscopy in characterization of the topic skin lesion. Furthermore, the features selected my selection method indicate that the hypertrophic scarring may involve a change in tissue structure and in the concentration of porphyrins embedded in the epidermis

Hypertrophic scarring is a common occurrence for severe burn victims leading to major functional, physiological, and aesthetic effects to the patients. Limiting the hypertrophic scarring of the patients alleviates the functional, physiological, and aesthetic effects. Silicone gels, over the past decade, have been widely used to remediate and limit hypertrophic scarring but the mechanism of action is yet to be determined. One explanation has been that hydration of the outermost area of the burn is induced by the silicone gel . However, non-silicone polymers which increase hydration could not mimic the effect. An alternative interpretation is that there may be silicone species that migrate from the silicone gel into the viable tissue to mediate reactions in the extra-cellular matrix that result in a decreased deposition of excessive amounts of collagen - a central feature of the hypertrophic scar. A novel and informative technique to study these species is MALDI-TOF/MS (Matrix Assisted Laser Desorption Ionisation-Time of Flight Mass Spectrometry) in conjunction with gel permeation chromatography. MALDI-TOF/MS, which has allowed the detection of intact molecular species that were not possible with more established mass spectrometric techniques. The mobile species that may migrate from polydimethylsiloxane medical gel sheeting into skin have been identified by MALDI-MS. The bulk gel contains predominantly cyclic oligomers with a mass distribution peaking at n = 19 (number of repeating siloxane units), but in an aqueous environment the species at the surface of the silicone medical gel are predominantly methyl/methylol-terminated linear siloxanes. By using a gelatine matrix as a model substrate, the distribution of silicon after application of the silicone gel for 16 weeks was determined by Energy-dispersive X-Ray mapping of the sectioned gelatine. The association of the linear and cyclic oligomers with proteins relevant in hypertrophic scarring are considered. The mobility of silicone species across stratum corneum was confirmed by Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FT/IR). This method confirms our hypothesis that not only are the low molecular weight silicone species mobile, but also that they do traverse the natural barrier, the stratum corneum, to levels that are detectable by ATR after a continuous application over approximately 11 days. Invitro studies of the effects of LMWS on primary line fibroblast cells indicate a response that down regulates the proliferation of fibroblast cells and protein production. Preliminary results indicate that a family of pendant functional LMWS are effective in down regulating hypertrophic-derived fibroblast primary cells. Studies on hypertrophic scar tissue treated with silicone medical gel indicate that LMWS permeate across the stratum corneum into viable scar tissue. In some areas, the LMWS tend to pool as detected by SEM/EDX elemental silicon analysis. These areas of LMWS pooling tend to be composed of highly disorganised collagen nodules.