Introdução: Universidades e hospitais solicitam alternativas para o uso de animais no treinamento médico sempre que possível. O custo dos manequins artificiais atualmente aprovados pelo Colégio Americano de Cirurgiões muitas vezes torna o seu uso proibitivo em países em desenvolvimento e subdesenvolvidos. Um manequim artificial de baixo custo (SurgeMan®) foi desenvolvido no Brasil. Nosso objetivo primário foi determinar se o SurgeMan® é adequado de acordo com o grau de satisfação dos alunos e instrutores do programa ATLS® quando comparado com o modelo TraumaMan® e o modelo animal, que são os atualmente aprovados para os procedimentos cirúrgicos do curso. Nosso objetivo secundário foi determinar se os índices de satisfação do usuário para SurgeMan® são superiores a 80%. Métodos: Foi realizado um estudo cruzado prospectivo com três modelos. Foram utilizados os modelos: SurgeMan® (SMan), TraumaMan® (TMan) e um modelo animal (suínos da raça Landrace). Uma amostra de conveniência de 36 estudantes candidatos a alunos do curso ATLS® foi alocada em nove grupos de quatro alunos e monitorados por um instrutor durante toda a estação de atividades cirúrgicas. Cada grupo participou de todas as atividades cirúrgicas em cada um dos três modelos. Os procedimentos realizados foram: drenagem pleural, cricotireoidostomia, pericardiocentese e lavagem peritoneal diagnóstica (DPL). Os testes psicométricos foram concluídos com os alunos e instrutores preenchendo um questionário com escala de Likert na conclusão de cada atividade. Os estudantes e instrutores também foram questionados sobre a adequação dos modelos para a realização da prática de atividades cirúrgicas do curso ATLS®, se eles substituiriam ou não o modelo animal pelo SurgeMan® ou pelo TraumaMan® e sobre suas preferencias de modelo considerando aspectos éticos e financeiros e sem levar estes em consideração. Resultados: O modelo animal e TraumaMan® tiveram desempenho melhor do que SurgeMan® para todas as habilidades, exceto pericardiocentese, onde não houve diferença estatística entre os modelos (Anova para medidas repetidas). Quando fatores éticos e financeiros não foram levados em consideração: 58% dos alunos e 66% dos instrutores escolheram o modelo animal. Quando os fatores éticos e financeiros foram considerados os modelos foram igualmente recomendados pelos alunos (SMan.33%, TMan 30%, Suínos 33%) e os instrutores escolheram o SurgeMan® como primeira opção (SMan 66%, TMan 22%, Suínos 11%). Para a adequação de cada modelo para o aprendizado de habilidades no ATLS®, os alunos consideraram todos adequados (81% S.Man; 94% T.Man; 86% suínos; p = 0,184) e os instrutores consideraram apenas o modelo animal abaixo de 80% (SMan 88%, TMan 100%, Suínos 77%). Conclusão: TraumaMan® teve desempenho melhor do que SurgeMan® na maioria dos procedimentos. Os alunos consideram que tanto TraumaMan® quanto SurgeMan® são aceitáveis para a aprendizagem das habilidades cirúrgicas do ATLS® / Introduction: Universities and hospitals require the use of suitable alternatives to animals for training wherever possible. The cost of the currently approved artificial mannequins often makes their use prohibitive in low-income countries. A low cost Brazilian artificial mannequin (SurgeMan®) has been developed. Our primary objective was to determine whether SurgeMan® would have equivalent learner and instructor satisfaction scores compared with the currently approved TraumaMan® and an animal model for the surgical procedures of Advanced Trauma Life Support ATLS®. Our secondary objective was to determine if user satisfaction scores for the SurgeMan® exceeded 80%. Methods: This was a prospective crossover cohort study with 3 models, SurgeMan® (SMan), TraumaMan® (TMan), and an animal model (Landrace pigs). A convenience sample of 36 students enrolled in ATLS® courses was divided into 9 groups, which were monitored by 1 instructor per group throughout the skills station rotations. Each group participated in all skills in each of the 3 models. The procedures performed were tube thoracostomy, cricothyroidotomy, pericardiocentesis, and diagnostic peritoneal lavage (DPL). Psychometric testing was completed by having students and instructors fill out a Likert Scale at the completion of each activity. Students and instructors were also asked about the adequacy of the models for performing the surgical skills, if they would or would not substitute the animal model for the SurgeMan® or the TraumaMan®, and about their preferred model, with and without ethical and financial issues. Results: The animal model and the TraumaMan® performed better than the SurgeMan® for all skills except pericardiocentesis, where there was no difference in the models. When no ethical or financial factors were taken in consideration, 58% of the students and 66% of the instructors chose pigs as their preferred model. When all ethical factors were considered, all students equally recommended the models (SMan 33%, TMan 30%, pigs 33%) and the SurgeMan® was the first choice for the instructors (SMan 66%, TMan 22%, pigs 11%). The students thought all models were adequate for learning ATLS® skills (SMan 81%, TMan 94%, pigs 86%). The Instructors scored only the animal model under 80% (SMan 88%, TMan 100%, pigs 77%) for learning those skills. Conclusion: The TraumaMan® performed better than the SurgeMan® in most procedures. Students and instructors found that both the TraumaMan® and the SurgeMan® are acceptable for learning and teaching ATLS® surgical skills

<p>Urođeni rascep sa naborom u prednjoj srednjoj liniji vrata (UR-N PSLV) je retka anomalija sa oko 100-150 bolesnika opisanih u literaturi. Tipičan rascep se sastoji od atrofične, ružičaste kože u obliku žleba, kožne prominencije na gornjem kraju i potkožnog sinusa na donjem kraju tzv. rascepa. Ispod ovih elemenata nalazi se potkožna vezivno-mi&scaron;ićna traka koja izaziva nabor na vratu. Izolovani nabor vrata, kao jedan od tipova rascepa, ima samo potkožnu traku i podbradnu kožnu izraslinu. U radu analiziramo seriju od 11 bolesnika sa UR-N PSLV operisanih u periodu od 12 godina (jul 1998. - jun 2010.). Rezultati lečenja sagledani su u pogledu preciznosti postavljanja dijagnoze (diferencijalna dijagnoza anomalija i oboljenja PSLV) i analize posleoperativnih funkcionalnih i estetskih karakteristika (vrednost cervikomentalnog ugla-CMU, veličina ekstenzije glave i vrata-EGV i karakteristike ožiljka). Rezultati operativnog lečenja rascepa primenom multiple &bdquo;Z&rdquo; plastike sa 4-10 kožnih režnjeva poređeni su sa Sistrunkovom operacijom kod bolesnika sa cistom tiroglosnog duktusa-TGDC (ukupno 128 bolesnika u seriji). S obzirom na veliki broj bolesnika sa različitim izgledom anomalije učinjena je podela UR-N PSLV na tipove (I-IV) i podtipove. Rascep se po embriopatogenezi, izgledu i patohistolo&scaron;kim (PH) karakteristikama jasno razlikuje od TGDC. Deskriptivnom embriologijom rascep se defini&scaron;e kao poremećaj u spajanju prednjih krajeva II (nekad i I) ždrelnih lukova. Kompresija srca u razvoju i odloženo ispravljanje vrata imaju značajnu ulogu. Kožna izraslina je rabdomiomatozni mezenhimalni hamartom kod svih na&scaron;ih bolesnika. Kaudalni sinus po PH izgledu ukazuje na bronhogeno poreklo. Operacijom rascepa vrata ne postiže se normalan CMU i potpuna EGV. Operacijom TGDC vi&scaron;e se menja CMU nego EGV, ali su vrednosti bliže kontrolnoj grupi nego kod dece sa rascepom. Ožiljci, posebno kosi delovi &bdquo;Z&rdquo; plastike, posle operacije UR-N su lo&scaron;ije&nbsp; ocenjeni nego posle operacije TGDC (parametrijski testovi pokazuju manju razliku). Na estetiku i funkcionalnost vrata i glave posle operacije rascepa veoma mnogo utiču hipoplazija donje vilice i deficit mekih struktura prednje strane vrata. Nova operativna tehnika (poprečna eliptična ekscizija i incizija u dva nivoa ili <em>step incision</em>, sa dodatnom &bdquo;Z&rdquo; plastikom na platizmi) primenjena kod dva bolesnika (pri kraju analize rezultata u studiji) daje nadu u dobijanje boljih posleoperativnih rezultata.</p> / <p>Congenital midline cervical cleft and web (CMCC-W) is a rare anomaly with about 100-150 cases described in the literature. The typical CMCC consists of midline groove of atrophic, erythematous skin with a skin protuberance cranially, and a subcutaneous blind sinus tract on the lower end of so-called cleft. Subcutaneous fibro-muscular band is located underneath, causing the web. Isolated CMCW, as one of the cleft types, includes only subcutaneous band and submental skin prominence. We analyzed a series of 11 patients with CMCC-W during the 12-year period (July 1998-June 2010). Treatment outcomes were evaluated according to precisely established diagnosis (differential diagnosis of anomalies and diseases of midline neck) and analysis of postoperative functional and aesthetic features (value of cervico-mental angle (CMA), head and neck extension (HNE) and characteristics of the scar). The results of the surgical treatment using multiple Z-plasty technique with 4-10 skin flaps were compared with Sistrunk procedure in patients with thyroglossal duct cyst (TGDC) (total of 128 patients in the series). Since a great number of patients had different forms of anomaly, the cases were divided into types (I-IV) and subtypes. Regarding embryo pathogenesis, appearance and histopathology, there was a clear difference between CMCC and TGDC. A cleft is defined, due to descriptive embryology, as a failure of the second (sometimes and first) pharyngeal arches to fuse in the midline. Compression of the heart and postponed extension of the neck played an important role during development period. Skin prominence was a rhabdomyomatous mesenchymal hamartoma in all our patients. Histopathology of the caudal sinus indicated the bronchogenic origin. The normal CMA and complete HNE were not achieved by the operation of CMCC-W. TGDC operation effects more CMA than HNE, but the values are closer to control group than in children having a cleft. Scars, especially oblique parts of Z plasty, after the operation CMCC-W were worse than after TGDC (parametric tests showed lesser difference). Hypoplasia of the mandible and vertical soft-tissue deficit of the anterior neck have a great impact on aesthetics and functionality of the head and neck after cleft surgery. New operative technique (two level transverse elliptical excision and incision or step incision &ndash; with the additional Z-plasty of platysma) was applied in two patients (at the end of the analysis of the results in the study) gives a new hope regarding better postoperative results.</p>

Background: Patient reports of pain and function are used to inform the need for and timing of total knee replacement (TKR) and evaluate TKR outcomes. This dissertation compared measurement properties of commonly-used patient surveys in TKR and explored ways to develop more efficient knee-specific function measures. Methods: 1,179 FORCE-TJR patients (mean age=66.1, 61% female) completed questionnaires before and 6 months after TKR. Patient surveys included the knee-specific Knee injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and generic SF-36 Health Survey. Tests of KOOS and WOMAC measurement properties included evaluations of scaling assumptions and reliability. Item response theory methods were used to calibrate 22 KOOS function items in one item bank; simulated computerized adaptive tests (CAT) then were used to evaluate shorter function scores customized for each patient. Validity and responsiveness of measures varying in attributes (knee-specific versus generic, longer versus shorter, CAT versus fixed-length) were compared. Results: KOOS and WOMAC scales generally met tests of scaling assumptions, although many pain items were equally strong measures of pain and physical function. Internal consistency reliability of KOOS and WOMAC scales exceeded minimum levels of 0.70 recommended for group-level comparisons across sociodemographic and clinical subgroups. Function items could be calibrated in one item bank. CAT simulations indicated that reliable knee-specific function scores could be estimated for most patients with a 55-86% reduction in respondent burden, but one-third could not achieve a reliable (≥ 0.95) CAT score post-TKR because the item bank did not include enough items vi measuring high function levels. KOOS and WOMAC scales were valid and responsive. Short function scales and CATs were as valid and responsive as longer KOOS and WOMAC function scales. The KOOS Quality of Life (QOL) scale and SF-36 Physical Component Summary discriminated best among groups evaluating themselves as improved, same or worse at 6 months. Conclusions: Results support use of the KOOS and WOMAC in TKR. Improved knee-specific function measures require new items that measure higher function levels. TKR outcomes should be evaluated with a knee-specific quality of life scale such as KOOS QOL, as well as knee-specific measures of pain and function and generic health measures.

Costimulation blockade protocols are promising alternatives to the use of chronic immunosuppression for promoting long-term allograft survival. However, the efficacy of costimulation blockade-based protocols is decreased by environmental insults such as viral infections. For example, lymphocytic choriomeningitis virus (LCMV) infection at the time of costimulation blockade treatment abrogates skin allograft survival in mice. In this dissertation, we test the hypothesis that viruses shorten allograft survival by activating the innate immune system through pattern-recognition receptors (PRRs), such as toll-like receptors (TLRs). To investigate the role of innate immunity in shortening allograft survival, costimulation blockade-treated mice were co-injected with TLR2 (Pam3Cys), TLR3 (polyinosinic:polycytidylic acid, poly(I:C)), TLR4 (lipopolysaccharide, LPS), or TLR9 (CpG DNA) agonists, followed by transplantation with skin allografts 7 days later. Costimulation blockade prolonged skin allograft survival that was shortened in mice coinjected with TLR agonists. To investigate the underlying mechanisms of this observation, we used synchimeric mice, which circulate trace populations of anti-H2b transgenic alloreactive CD8+ T cells. In synchimeric mice treated with costimulation blockade, co-administration of all four TLR agonists prevented deletion of alloreactive CD8+ T cells. These alloreactive CD8+ T cells 1) expressed the proliferation marker Ki-67, 2) upregulated CD44, and 3) failed to undergo apoptosis. We also demonstrate that costimulation blockade-treated CD8α-deficient mice exhibit prolonged allograft survival when co-injected with LPS. These data suggest that TLR agonists shorten allograft survival by impairing the apoptosis of alloreactive CD8+T cells. We further delineate the mechanism by which TLR agonists shorten allograft survival by demonstrating that LPS and poly(I:C) fail to shorten allograft survival in IFNRI- deficient mice. Interestingly, the ability of poly(I:C) to more potently induce IFN-α/β than LPS correlates with its superior abilities to shorten islet allograft survival and induce allo-specific CTL activity as measured by an in vivo cytotoxicity assay. The ability to shorten allograft survival and induce IFN-α/β is a TLR-dependent process for LPS, but is a TLR-independent process for poly(I:C). Strikingly, the injection of IFN-β impairs alloreactive CD8+T cell deletion and shortens allograft survival, similar to LPS and poly(I:C). These data suggest that LPS and poly(I:C) shorten allograft survival by inducing IFN-α/β through two different mechanisms. Finally, we present data showing that viruses (LCMV, Pichinde virus, murine cytomegalovirus and vaccinia virus) impair alloreactive CD8+T cell deletion and shorten allograft survival, in a manner comparable to LPS and poly(I:C). Similar to LPS, LCMV and MCMV exhibit an impaired ability to shorten allograft survival in MyD88-deficient mice. These data suggest that the MyD88 pathway is required for certain viruses and TLR-agonists to shorten allograft survival. In this dissertation, we present data supporting an important role for TLRs and IFN- α/β in shortening allograft induced by costimulation blockade. Our findings suggest that targeting these pathways during the peri-transplant period may enhance the efficacy of costimulation blockade protocols in the clinic.

GM1 gangliosidosis is an autosomal recessive lysosomal storage disease, caused by a deficiency in the enzyme β-galactosidase. The disease affects the CNS, liver, kidney, heart and skeletal system, leading to severe neurodegeneration and death. We propose to treat this disorder using ex vivo hematopoietic stem cell therapy. The effectiveness of this therapy requires the recruitment of transduced donor cells to the CNS. This is only found to occur after mice are conditioned with total body irradiation, due to the increase in CNS cytokine production and blood brain barrier permeability that occurs. As the use of total body irradiation in pediatric patients has been linked to future developmental problems, this myeloablation approach is often avoided in younger patients in favor of a conditioning regimen using the chemotherapy drugs, busulfan and cyclophosphamide. Whether donor cells can enter the CNS when a busulfan and cyclophosphamide conditioning regimen is used has not been determined. In this study we plan to quantify the cytokine and blood-brain barrier permeability increases necessary for donor cells to be recruited to the CNS after total body irradiation. We will then investigate whether busulfan and cyclophosphamide conditioning and/or the chronic neuroinflammation present in GM1 mice can produce similar conditions and facilitate the recruitment of donor hematopoietic stem cells to the CNS. Finally we will assess whether ex vivo hematopoietic stem cell gene therapy is still an effective therapy when busulfan and cyclophosphamide are used for myeloablative conditioning.

Breast cancer is one of the most prevalent cancers in the world. Each year, over 400,000 women die from breast cancer world wide and metastasis is the main cause of their mortality. Tumor cell invasion into the adjacent tissue is the first step in the multistep process of cancer metastasis and it involves multiple protein changes. The α6β4 integrin, a transmembrane heterodimeric laminin receptor is associated with poor prognosis in many tumor types, including breast cancer. Src family kinase (SFK) activity is elevated in many cancers and this activity also correlates with invasive tumor behavior. The α6β4 integrin can stimulate SFK activation and promote cancer invasion, however the mechanism by which it does so is not known. In the current study, I provide novel mechanistic insight into how the α6β4 integrin selectively activates the Src family kinase member Fyn in response to receptor engagement. Specifically, the tyrosine phosphatase SHP2 is recruited to α6β4 and its catalytic activity is stimulated through a specific interaction of its N-terminal SH2 domain with pY1494 in the β4 subunit. Importantly, both catalytic and non-catalytic functions of SHP2 are required for Fyn activation by α6β4. Fyn is recruited to the α6β4/SHP2 complex through an interaction with phospho-Y580 in the C-terminus of SHP2. In addition to activating Fyn, this interaction with Y580-SHP2 localizes Fyn to sites of receptor engagement, which is required for α6β4-dependent invasion. Moreover, the selective activation of Fyn, but not Src, requires the palmitoylation modification of Fyn on its N-terminus. Of clinical relevance, phospho-Y580-SHP2 and phospho-Y418-SFK could be used as potential biomarkers of invasive breast cancer because their expression are elevated in high-grade breast tumors.

Estudos baseados em parâmetros fisiológicos tem mostrado que a fisioterapia tem papel imperativo na assistência de pacientes pré e pós-operatórios. Os efeitos da assistência fisioterapêutica na unidade de terapia intensiva (UTI) sobre o tempo de ventilação mecânica invasiva (VMI), tempo de internação e mortalidade do paciente crítico não foram elucidados. Tampouco, estudos sobre o impacto do turno diário da assistência fisioterapêutica nestes desfechos tem sido realizados. A despeito disto, e, possivelmente, baseadas na experiência clínica, as UTIs brasileiras adotarão turnos de 18 horas de assistência fisioterapêutica na UTI para atender a uma regulamentação governamental. O objetivo deste estudo foi comparar o efeito da assistência fisioterapêutica na UTI em turno diário de 24 horas (Fisio-24) ao turno diário de 12 horas (Fisio-12), sobre o tempo de VMI, tempo de internação na UTI, frequência de complicações respiratórias relacionadas a VMI e custos indiretos de pacientes pós-operatórios. Este estudo observacional, prospectivo, de coorte incluiu 114 pacientes de UTIs com Fisio-12 e 152 pacientes de UTIs com Fisio-24 em condição pós-operatória, idade 18 anos, submetidos a VMI por 24 horas e admitidos na UTI para rotina pós-operatória. Foram coletados dados demográficos e cirúrgicos. Os desfechos primários deste estudo foram tempo de VMI, tempo de internação na UTI, complicações respiratórias relacionadas a VMI e custos indiretos. O desfecho secundário foi o dia-livre de ventilação (VFD). Os custos foram avaliados através do Omega French Score que compreende três categorias (Omega 1, 2 e 3). Um modelo de regressão linear múltipla (MRL) foi construído para verificar a associação entre o turno diário de assistência fisioterapêutica na UTI e o tempo de VMI. A despeito dos pacientes Fisio-24 serem mais velhos (p=0,002), possuírem maior número de comorbidades (p=0,001), maior frequência de risco cirúrgico moderado a alto (p=0,003), maior frequência de complicações intra operatórias (p=0,012) e insuficiência renal aguda dialítica (p<0,001), comparados aos pacientes Fisio-12, apresentaram melhores desfechos clínicos, tais quais, menor mediana de tempo de VMI (4 dias versus 6 dias; p=0,002), maior mediana de VFD (24 dias versus 21 dias; p=0,004) e menor mediana de tempo de internação na UTI (10 dias versus 15 dias; p=0,015). Não foi encontrada diferença na frequência de complicações respiratórias relacionadas à VMI entre os dois grupos (p=0,704), embora pacientes Fisio-24 tenham recebido mais sessões de fisioterapia respiratória durante a internação na UTI (25 versus 20 sessões; p=0,014). Pacientes Fisio-24 apresentaram menor pontuação do Omega 2 (p=0,007). O MRL manteve como variáveis explicativas o número de sessões de fisioterapia respiratória, APACHE II, realização de Neurocirurgia e o turno diário de assistência fisioterapêutica na UTI. Mantidas constantes as outras variáveis explicativas, a presença de Fisio-24 na UTI reduziu o tempo de VMI em 2,80 unidades. Concluí-se que pacientes pós-operatórios admitidos em UTIs com Fisio-24 apresentaram menores tempo de VMI e tempo de internação na UTI, maior VFD, contudo, não foi encontrada diferença na frequência de complicações respiratórias relacionadas à VMI entre Fisio-12 e Fisio-24. A redução da pontuação de Omega 2 nos pacientes Fisio-24 não foi suficiente para promover diferenças no custo indireto entre os grupos / According to studies based on physiologic parameters, physiotherapy plays an imperative role on pre and postoperative patients. The effects of physiotherapy assistance (PTA) in the intensive care unit (ICU) on length of invasive mechanical ventilation (IMV), length of ICU stay, frequency of ventilator-associated pneumonia and mortality remain unclear. Moreover, studies about impact of PTA shifts have not been conducted. Despite this fact, and possibly based on clinical experiences, Brazilian ICUs are going to adopt 18 hours of PTA shifts in order to attend a governmental regulation. The objective of this study was to compare the effects of 24-hour PTA (Physio-24) to 12-hour PTA (Physio-12) daily shifts in the ICU on length of IMV, length of ICU stay, frequency of respiratory complications related to IMV and indirect costs of postoperative patients. This observational, prospective and cohort study included 114 patients from ICUs with Physio-12 and 152 patients from ICU with Physio-24. Patients presented postoperative conditions, were aged 18 years, who underwent IMV 24 hours and were admitted on ICU for postoperative routine. We collected demographical and surgical data. Our primaries end-points were duration of IMV, length of ICU stay, frequency of respiratory complications related to IMV and indirect costs. The secondary end-point was ventilator-free days (VFD). Indirect costs were assessed by Omega French Score which comprises three categories (Omega 1, 2 and 3). In addition, a multiple linear regression model (MLR) was constructed to verify the association between daily shifts of PTA in ICU and length of IMV. Despite of the fact that Physio-24 patients were older (p=0.002), with more severe conditions such as higher number of co morbidities (p<0.001), higher presence of moderate to severe surgical risk (p=0.003), higher frequency of intraoperative complications (p=0.012) and dialytic acute renal failure in ICU (p<0.001), compared to Physio-12 patients, they presented better clinical outcomes such as fewer median days spent in IMV (4 versus 6 days; p=0.002), higher median of VFD (24 versus 21 days; p=0.004) and shorter median of ICU stay (10 versus 15 days; p=0.015). No differences were found concerning respiratory complications related to IMV between groups (p=0.704), although Physio-24 patients had received more sessions of chest physiotherapy during ICU stay (25 versus 20 sessions; p=0.014). Physio-24 patients presented lower scores of Omega 2 (p=0.007). The number of chest physiotherapy sessions, APACHE II, Neurosurgery, and daily shifts of PTA in ICU remained as independent variables to length of IMV in the MLR model. According to this model, Physio-24 may reduce 2.80 units from length of IMV if the other independent variables are constant. We concluded that postoperative patients admitted in ICUs with daily shifts of 24-hour PTA showed shorter length of IMV and length of ICU stay and increased VFD; however, no reduction in frequency of respiratory complications related to IMV was found between groups. Despite the fact that Physio-24 patients had lower score of Omega 2, it was not enough to provoke a difference on indirect costs between Physio-12 and Physio-24 patients

Os desfechos clínicos e oncológicos dos pacientes submetidos à ressecção endoscópica do câncer gástrico precoce (CGP), considerando os critérios de indicação, comparados à cirurgia, não foram relatados em revisões sistemáticas. A pesquisa foi desenvolvida para estabelecer os desfechos de curto e longo prazos da ressecção endoscópica comparada à cirurgia no tratamento do CGP, elevando as informações para o nível de evidência 2a, melhor respaldando a prática clínica. A revisão sistemática com metanálises foi procedida utilizando-se as bases Medline, Embase, Cochrane, LILACS, Scopus e CINAHL. Onze coortes retrospectivas foram selecionadas para análise qualitativa e quantitativa. Todos os estudos incluem pacientes com CGP e comparam os desfechos nos dois braços. Os dados envolveram 2654 pacientes que preenchiam os critérios absolutos ou expandidos para ressecção endoscópica. Diferentes modalidades de tratamento endoscópico foram avaliadas, principalmente os procedimentos de ressecção, como endoscopic mucosal resection (EMR) e endoscopic submucosal dissection (ESD). As informações basearam-se nas características dos participantes, critérios de inclusão e exclusão, tipos de intervenções e desfechos (diferentes taxas de sobrevida, eventos adversos, ressecção completa, recorrência e mortalidade). As análises dos riscos absolutos dos desfechos foram feitas com o software RevMan, computando-se as diferenças de risco (DR) das variáveis dicotômicas. Dados de DR e intervalo de confiança de 95% (IC) foram calculados utilizando-se o teste de Mantel-Haenszel e a inconsistência foi qualificada e reportada em ?2 e método Higgins (I2). A análise de sensibilidade foi feita quando a heterogeneidade era maior que 50%. Todas as análises basearam-se inicialmente no modelo de efeito fixo. Dados de sobrevida de 3 anos estavam disponíveis em seis estudos (n = 1197). Não houve DR após os dois tratamentos (DR = 0,01, IC 95% = -0,02 a 0,05). A sobrevida de 5 anos (n = 2310) não demonstrou diferença significativa entre os grupos analisados (DR = 0,01, IC 95% = -0,01 a 0,03). A avaliação de 551 pacientes não evidenciou desigualdade na sobrevida de 10 anos entre as diferentes abordagens (DR = -0,02, IC 95% = -0,15 a 0,10). Dados de complicação estavam presentes em oito estudos (n = 2439), e diferença significativa foi detectada (DR = -0,08, IC 95% = -0,10 a -0,05), demonstrando melhores resultados com a endoscopia. As taxas de ressecção completa foram analisadas em 536 pacientes. Evidenciou-se diferença significativa entre o tratamento endoscópico e cirúrgico (DR = -0,13, IC 95% = -0,17 a -0,09), validando melhores resultados no último grupo. A recorrência foi avaliada em cinco pesquisas (n = 1331) e não houve diferença entre as duas formas de terapêutica (DR = 0,01, IC 95% = -0,00 a 0,02). As taxas de mortalidade foram obtidas de quatro estudos (n = 1107), e não se evidenciou diferença entre os grupos envolvidos (DR = -0,01, IC 95% = -0,02 a 0,00). Conclui-se que as taxas de sobrevida de 3, 5 e 10 anos, recorrência e mortalidade são semelhantes em ambos os grupos. Considerando-se as taxas de complicação, a abordagem endoscópica confere resultados mais apropriados e, analisando-se as taxas de ressecção completa, ela é inferior à cirurgia / Clinical and oncological outcomes of endoscopic resection of early gastric cancer (EGC), considering the indication criteria, compared to surgery, have not been reported in systematic reviews. To address the short- and long-term outcomes of endoscopic resection compared to surgery in the treatment of EGC, a systematic review was performed, establishing the available data to an unpublished 2a strength of evidence, better handling clinical practice. A systematic review and meta-analysis using Medline, Embase, Cochrane, LILACS, Scopus and CINAHL databases were done. Eleven retrospective cohort studies were selected to quantitative and qualitative synthesis. All studies included patients diagnosed with EGC that compared outcomes considering endoscopic treatment and surgery. The included records involved 2654 patients with EGC that filled the standard or expanded indications for endoscopic resection. Different endoscopic treatment modalities were analyzed, mainly mucosal resection procedures such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), compared to surgery. Information of the selected studies was extracted on characteristics of trial participants, inclusion and exclusion criteria, types of interventions and outcomes (different survival rates, adverse events, complete resection, recurrence and mortality rates). The analysis of the absolute risks of the outcomes was performed using the software RevMan, by computing risk differences (RD) of dichotomous variables. Data on RD and 95% confidence interval (CI) for each outcome were calculated using the Mantel-Haenszel test and inconsistency was qualified and reported in X2 and the Higgins method (I2). Sensitivity analysis was performed when heterogeneity was higher than 50%. All pooled analyses were initially based on fixed-effects model. Three-year survival data were available for six studies (n = 1197). There were no RD in 3-year survival data after endoscopic and surgical treatment of EGC (RD = 0.01, 95% CI = -0.02 to 0.05). Five-year survival data (n = 2310) showed no evidence of a difference between the two groups (RD = 0.01, 95% CI = -0.01 to 0.03). The data analysis, in 551 patients, showed no difference in 10-year survival rates between the approaches (RD = -0.02 and 95% CI = -0.15 to 0.10). Complication data were identified in eight studies (n = 2439). A significant difference was detected (RD = -0.08, 95% CI = -0.10 to -0.05), demonstrating better results with endoscopic approach. Complete resection data was analyzed in 536 patients. It showed significant difference in complete resection rates between endoscopic and surgical treatment of EGC (RD = -0.13, 95% CI = -0.17 to -0.09), exhibiting improved results in the surgical group. Recurrence data were analyzed in five studies (n = 1331) and there was no difference between the approaches (RD = 0.01, 95% CI = -0.00 to 0.02). Mortality data were obtained in four studies (n = 1107), and there was no difference between treatment modalities (RD = -0.01, 95% CI = -0.02 to 0.00). This systematic review concludes that 3-, 5- and 10-year survival, recurrence and mortality rates are similar for both groups. Considering procedure-related complication rates, endoscopic approach achieves significantly better results and, analyzing complete resection data, it is considered worse than surgery

Made available in DSpace on 2016-01-26T12:51:37Z (GMT). No. of bitstreams: 1 eumildodecampos junior_tese.pdf: 1761590 bytes, checksum: 07f0e6564f9169c180cc6baf09d6de84 (MD5) Previous issue date: 2011-12-16 / Dysphagia caused by chagasic megaesophagus compromises the clinical status and quality of life of patients. In this context, the Serra Dória s operation is a useful procedure in cases of advanced or recurrent disease. Little is known about the cardiovascular complications related to this surgery. Objective: This study aim to identify preoperative risk factors associated with cardiovascular complications after Serra Dória s operation in patients with megaesophagus caused by Chagas disease at the hospital period to document the data in order to better preoperative evaluating of these of these patients. Methods: This is a retrospective study evaluating patients who underwent the Serra Dória s operation at the General Surgery Service of Hospital de Base (FUNFARME), Faculty of Medicine of Sao Jose do Rio Preto (FAMERP) from 1998 to 2010. Initially, we assessed 103 medical records and excluded from the study 16 patients with idiopathic achalasia and 11 incomplete charts; therefore, the study population consisted of 76 patients with chagasic megaesophagus who underwent Serra Dória s procedure. The study was approved by the Ethics in Research Committee No. 254/2011. The following preoperative variables were included in the multivariate stepwise regression analysis: the model: age, sex, degrees of megaesophagus, operation for recurrence of symptoms, need for transfusion of red blood cells, blood pressure, electrolytes, comorbidities, electrocardiographic findings and degree of surgical risk. Cardiovascular complications were as follows: levels of hypotension and hypertension and cardiac arrhythmias without hemodynamic instability observed during the surgery and in the postoperative period. Student s t test was used in the comparison of continuous variables, whereas the chi-squared test was used in the comparison of categorical variables. Variables associated with the presence of cardiovascular complications at the p<0.05 were included in multivariate logistic stepwise regression. Those that remained associated with the presence of cardiovascular complications were considered independent variables to predict the appearance of cardiovascular complications. Results: The mean age was 61 ±10 years with male predominance (42, 55%). Most patients were classified as advanced megaesophagus (65, 86%); 36(47%) of them had relapsed megaesophagus. In 22(29%) of cases there was at least one comorbidity, with hypertension being the most frequently found (25, 30%). In 34(45%) patients the surgical risk was classified as moderate to severe. Among the electrocardiographic findings found preoperatively, sinus rhythm was found in 68(89%) patients, and right bundle-branch block in 28(37%). Cardiovascular complication was observed in 29(38%) patients, with prevalence of hypotension in various levels (14, 41%), followed by cardiac arrhythmias in 12(35%). The largest number of cardiovascular complications occurred during the immediate postoperative period. Variables associated with the presence of complications in the univariate model were age (p=0.003) and left bundle-branch block (p= 0.02). However, only the aged above 61 years of age was an independent predictor of cardiovascular complications in the postoperative Serra Dória s operation. Conclusion: Age is an independent predictor of cardiovascular complications following the Serra Dória s procedure. / A disfagia causada pelo megaesôfago chagásico compromete o estado geral e a qualidade de vida dos pacientes. Neste contexto, a cirurgia de Serra Dória é um procedimento útil nos casos avançados ou de recidiva da doença. Pouco se sabe a respeito das complicações cardiovasculares relativas a esta cirurgia. Objetivo: O estudo buscou identificar fatores de risco pré-operatórios associados às complicações cardiovasculares após a cirurgia de Serra Dória no período hospitalar para documentar os dados visando melhorar a avaliação pré-operatória destes pacientes. Casuística e Métodos: Estudo retrospectivo que analisou pacientes submetidos à cirurgia de Serra Dória no Serviço de Cirurgia Geral do Hospital de Base (FUNFARME) da Faculdade de Medicina de São Jose do Rio Preto (FAMERP) no período de 1998 a 2010. Inicialmente foram analisados 103 prontuários e excluídos do estudo 16 portadores de acalasia idiopática e 11 prontuários incompletos; portanto, a amostra consistiu de 76 pacientes portadores de megaesôfago chagásico submetidos à cirurgia de Serra Dória. O estudo foi aprovado pelo Comitê de Ética e Pesquisa parecer nº 254/2011. As seguintes variáveis pré-operatórias foram incluídas na análise de regressão logística multivariada passo-a-passo: idade, sexo, graus do megaesôfago, operação por recidiva dos sintomas, necessidade de transfusão de hemácias, níveis de pressão arterial, eletrólitos, comorbidades, achados eletrocardiográficos e grau de risco cirúrgico. As complicações cardiovasculares consideradas foram: níveis de hipotensão e hipertensão arterial e arritmias cardíacas com ou sem instabilidade hemodinâmica, observadas durante o período transoperatório, pós-operatório imediato e enfermaria. Para análise das variáveis contínuas utilizou-se o Test t de student não pareado, e para as variáveis descontínuas, o teste de qui-quadrado. Variáveis associadas à presença de complicações cardiovasculares com p <0,05 foram incluídas no modelo multivariado de regressão logística passo-a-passo. Aquelas que se mantiveram associadas à presença de complicações cardiovasculares foram consideradas variáveis de predição independente para o aparecimento dessas complicações. Resultados: A idade média da amostra foi de 61 ± 10 anos com predomínio do sexo masculino (42, 55%). A maioria dos pacientes apresentou megaesôfago avançado (65, 86%), e 36(47%) com recidiva dos sintomas que necessitaram de novo procedimento. Em 22(29%) dos casos houve pelo menos uma comorbidade, sendo a hipertensão arterial a mais frequente (25, 30%). O risco cirúrgico em 34(45%) pacientes foi considerado como moderado a grave. Nos achados eletrocardiográficos do pré-operatório, os mais frequentemente encontrados foram 68(89%) com ritmo sinusal seguido pelo bloqueio completo do ramo direito do feixe de His em 28(37%). Observou-se complicação cardiovascular em 29(38%) pacientes, com predomínio de hipotensão arterial em vários níveis (14, 41%), seguida de arritmias cardíacas em 12(35%). O maior número de complicações cardiovasculares ocorreu no período pós-operatório imediato. As variáveis associadas à presença de complicações no modelo univariado foram a idade (p=0,003) e o bloqueio de ramo esquerdo do feixe de His (p=0,02). No modelo multivariado, apenas a idade igual ou superior a 61 anos mostrou-se variável de predição independente para o aparecimento de complicações cardiovasculares no pós-operatório da cirurgia de Serra Dória. Conclusão: A idade é um fator de predição independente de complicações cardiovasculares após a cirurgia de Serra Dória.

INTRODUÇÃO: A Moléstia de Dupuytren (MD) é uma doença crônica progressiva fibroproliferativa caracterizada por contraturas em flexão dos dedos. A origem deste processo está na proliferação de miofibroblastos e na síntese de matriz extracelular. Diversas técnicas já foram descritas no tratamento da MD. A falta de uma técnica capaz de associar altas taxas de sucesso com baixos índices de complicações e recidivas estimulou a procura por novas técnicas. Acredita-se que a propriedade totipotente das células-tronco presentes no tecido adiposo seria capaz de atuar na proliferação e na diferenciação dos fibroblastos em miofibroblastos, interrompendo a formação da fibrose e consequentemente a progressão da deformidade dos dedos. OBJETIVO: O objetivo primário deste estudo foi avaliar o efeito do enxerto de gordura, rico em células-tronco, nos pacientes com MD, submetidos a fasciectomia parcial aberta, por meio de avaliação funcional e goniométrica, e comparar com a técnica convencional (sem adição de enxerto de gordura). MÉTODO: Dois grupos totalizando 45 pacientes (24 pacientes no Grupo Controle e 21 no Grupo com gordura) foram operados pela técnica da fasciectomia parcial aberta. No Grupo controle era realizada apenas a fasciectomia parcial aberta. No Grupo com gordura, era realizada a fasciectomia parcial aberta e injetado, no local da corda ressecada, o enxerto de gordura, após o processamento do lipoaspirado de adipócitos proposto por Coleman (2006). O estudo foi prospectivo, randomizado e terapêutico. Os desfechos foram avaliados pela medida goniométrica do Déficit de Extensão Passiva Total (DEPT) e pelo escore funcional Brief Michigan Hand Questionnaire (BMHQ). As avaliações eram feitas no pré-operatório, com 6 semanas, 6 meses, 1 ano e 2 anos de seguimento. RESULTADOS: Na comparação com 6 semanas de pós-operatório, houve um aumento significativo da dor no Grupo com Gordura [mediana 2 ± 2,82 versus 0 ± 1,86 no grupo Controle (p=0,045)]. Os resultados do DEPT, não mostraram diferença significativa entre os grupos. Observamos piores resultados do escore funcional BMHQ com 6 meses e 1 ano de pós-operatório no Grupo com gordura (p=0,040 e p=0,047, respectivamente). Observamos ainda 9 casos (43%) de complicações no Grupo com gordura e 2 (8%) no Grupo Controle (p=0,019). CONCLUSÃO: O uso do enxerto de gordura associado à fasciectomia parcial aberta promoveu piores resultados funcionais comparado com a fasciectomia parcial aberta convencional, no curto prazo (um ano de seguimento pós-operatório). No entanto, resta a dúvida de qual seriam os resultados a longo prazo e, se as células-tronco, presentes no enxerto de gordura, poderiam interferir na recidiva da doença futuramente / BACKGROUND: Dupuytren\'s disease (DD) is a progressive chronic fibroproliferative disease characterized by flexion contractures of the fingers. The origin of this process is the proliferation of myofibroblasts and extra-cellular matrix synthesis. Several techniques have been described to treat the DD. The lack of a technique capable to associate high success rates with low rates of complications and recurrence stimulated the search for new techniques. It is believed that the totipotent property of the adipose-derived stem cells present in the processed lipoaspirate tissue would be able to inhibit the proliferation and differentiation of fibroblasts in myofibroblasts, interrupting the formation of fibrosis and consequently the progression of finger deformity. The primary objective of this study was to evaluate the effect of adipose-derived stem cells in patients with DD who underwent to open limited fasciectomy and compare with the conventional technique of limited fasciectomy. METHODS: A total of 45 patients were assigned in two groups in a single blind, prospective, randomized, controlled trial. All the patients were treated by the limited fasciectomy technique. In the control group (24 patients), only limited fasciectomy was performed. In the study group (21 patients), after the limited fasciectomy procedure, autologous lipoaspirate was injected at the site of the resected cord. Outcomes were assessed by the Total Passive Extension Deficit (TPED) and by the Brief Michigan Hand Questionnaire (BMHQ) functional score. The evaluations were performed by occupational therapists in the preoperative and at 6 weeks, 6 months, 1 year and 2 years. RESULTS: The study group presented higher rates of pain at 6 weeks postoperative (median 2 ± 2,82 versus 0 ± 1,86 on control group, p=0,045). TPED showed no significant differences between groups. BMHQ score, at 6 months and 1 year after surgery, were significantly inferior in the study group (p=0,040 e p=0,047, respectively). Patients in the study group had higher incidence of complications (9 patients, 43% versus 2, 8% in the control group, p=0,019). CONCLUSIONS: The autologous lipoaspirate associated to limited fasciectomy demonstrates inferior results regarding to functional score and pain compared to conventional limited fasciectomy, in short-term. Further long-term analysis is required to observe the effect of adipose-derived stem cells in the recurrences rates