Background: Laparoscopic surgery for colorectal cancer is a novel healthcare technology, for which much research evidence has been published. The objectives of this work were to compare the oncologic outcomes of this technology across different study types, and to define patterns of adoption on the basis of the literature. Methods: A comprehensive systematic review of the literature was conducted using 1) existing systematic reviews, 2) randomized controlled trials (RCTs), and 3) observational studies. Outcomes of interest were overall survival, and total lymph node harvest. Outcomes were compared for congruence. Adoption was evaluated by means of summary expert opinions in the literature. Results: 1) Existing systematic reviews were of low to moderate quality and displayed evidence of overlap and duplication. 2) Laparoscopy was not inferior to open surgery in terms of oncologic outcomes in any study type. 3) Oncologic outcomes from RCTs and observational studies were congruent. 4) Expert opinion in the literature has been supportive of this technology, paralleling the publication of large RCTs. Conclusions: The evaluation of laparoscopic surgery for colorectal cancer in RCTs and observational studies suggests that it is not inferior to open surgery. Adoption of this technology has paralleled RCT evidence.

Introdução: o carcinoma de endométrio é uma das neoplasias ginecológicas mais comuns nos países industrializados. O tratamento desta doença é primariamente cirúrgico. Segundo a normatização da Federação Internacional de Ginecologia e Obstetrícia (FIGO), a cirurgia ideal consiste na realização de histerectomia total, anexectomia bilateral, linfadenectomia retroperitonial e coleta de citologia peritoneal. No entanto, a realização sistemática da linfadenectomia tem sido contestada. Alguns centros de referência acreditam que deva ser realizada apenas em um grupo de pacientes com alto risco para disseminação linfática da doença. O desafio é encontrar marcadores pré-operatórios que possam ser preditivos da presença de doença linfonodal e, assim , virem a ser utilizados para a definição da necessidade da linfadenectomia. Objetivos: verificar se a expressão imuno-histoquímica (IMH) positiva da p53 na amostra endometrial diagnóstica e, se o valor sérico do CA 125 obtido no tempo pré-operatório, podem ser efetivos para prever a presença de doença linfonodal. Métodos: um estudo transversal restrospectivo foi realizado. Foram incluídas 111 pacientes com carcinoma de endométrio submetidas a histerectomia com anexectomia bilateral e linfadenectomia com ou sem citologia peritoneal. Noventa pacientes apresentavam CA 125 pré-operatório e 73, a avaliação da p53. Cinquenta e quatro pacientes apresentavam as duas variáveis em combinação. Foram estabelecidas as associações entre o valor de CA 125 e da expressão IMH da p53 com o envolvimento linfonodal. Uma curva ROC foi construída para identificar o valor de CA 125 com melhor Sensibilidade (S) e Especificidade (E) para doença linfonodal. / Introduction: endometrial carcinoma is one of the most common gynecological malignancies in industrialized countries. The treatment of this disease is primarily surgical. According to the International Federation of Gynecology and Obstetrics surgery ideal consists in performing total hysterectomy, bilateral adnexectomy, retroperitoneal lymphadenectomy and peritoneal cytology. However, the systematic lymphadenectomy has been disputed, and should only be performed in a group of patients at high risk of lymphatic spread of the disease. The challenge is to find preoperative markers that may be predictive of the presence of lymph node disease and thus come to be used to determine the necessity of lymphadenectomy. Objectives: to determine whether the positive immunohistochemical expression (IMH) of p53 in diagnostic endometrial sample and, if the value of serum CA 125, obtained during pre-operative, can be effective to predict the presence of lymph node disease. Methods: a cross-sectional study was conducted. The final sample consisted of 111 patients with endometrial carcinoma undergoing hysterectomy with bilateral adnexectomy and lymphadenectomy with or without peritoneal cytology. Ninety two patients had preoperative CA 125 and 73, evaluation of p53. Fifty four patients had both variables in combination. Associations have been established between the value of CA 125 and IMH expression of p53 with lymph node involvement. A ROC curve was constructed to identify the value of CA 125 with better sensitivity (S) and specificity (E) for lymph node disease.

Afin d'accélérer et automatiser l'analyse par ultrasons quantitatifs de ganglions lymphatiques de patients atteints d'un cancer, plusieurs segmentations automatiques des trois milieux rencontrés (le parenchyme du ganglion, la graisse périnodale et le sérum physiologique) sont étudiées. Une analyse statistique du signal d'enveloppe a permis d'identifier la distribution gamma comme le meilleur compromis en termes de qualité de la modélisation, simplicité du modèle et rapidité de l'estimation des paramètres. Deux nouvelles méthodes de segmentation basées sur l'approche par ensemble de niveaux et la distribution gamma sont décrites. Des statistiques locales du signal d'enveloppe permettent de tenir compte des inhomogénéités du signal dues à l'atténuation et la focalisation des ultrasons. La méthode appelée LRGDF modélise les statistiques du speckle dans des régions dont la taille est contrôlable par une fonction lisse à support compact. La seconde, appelée STS-LS, considère des coupes transverses, perpendiculaires au faisceau, pour gagner en efficacité. Une troisième méthode basée sur la classification par forêt aléatoire a été conçue pour initialiser et accélérer les deux précédentes. Ces méthodes automatiques sont comparées à une segmentation manuelle effectuée par un expert. Elles fournissent des résultats satisfaisants aussi bien sur des données simulées que sur des données acquises sur des ganglions lymphatiques de patients atteints d'un cancer colorectal ou du sein. Les paramètres ultrasonores quantitatifs estimés après segmentation automatique ou après segmentation manuelle par un expert sont comparables. / This work investigates approaches to obtain automatic segmentation of three media (i.e., lymph node parenchyma, perinodal fat and normal saline) in lymph node (LN) envelope data to expedite quantitative ultrasound (QUS) in dissected LNs from cancer patients. A statistical modeling study identified a two-parameter gamma distribution as the best model for data from the three media based on its high fitting accuracy, its analytically less-complex probability density function (PDF), and closed-form expressions for its parameter estimation. Two novel level-set segmentation methods that made use of localized statistics of envelope data to handle data inhomogeneities caused by attenuation and focusing effects were developed. The first, local region-based gamma distribution fitting (LRGDF), employed the gamma PDFs to model speckle statistics of envelope data in local regions at a controllable scale using a smooth function with a compact support. The second, statistical transverse-slice-based level-set (STS-LS), used gamma PDFs to locally model speckle statistics in consecutive transverse slices. A novel method was then designed and evaluated to automatically initialize the LRGDF and STS-LS methods using random forest classification with new proposed features. Methods developed in this research provided accurate, automatic and efficient segmentation results on simulated envelope data and data acquired for LNs from colorectal- and breast-cancer patients as compared with manual expert segmentation. Results also demonstrated that accurate QUS estimates are maintained when automatic segmentation is applied to evaluate excised LN data.

Ziel einer Definition der Resektabilität von Pankreaskarzinomen ist die Beschreibung von Kriterien, welche eine potentielle R0-Resektion ermöglichen. Wenngleich es zur Frage der Resektion bei positiven regionären Lymphknoten keine kontrollierten Studien gibt, ist weltweit die Resektion bei regionären Lymphknotenmetastasen Standard. Positive interaortokavale Lymphknoten stellen trotz Klassifikation als Fernmetastasen (M1) keine absolute Kontraindikation zur Resektion dar. Die mesenteriko-portale Venenresektion bei Verdacht auf Tumorinfiltration ist ein sicheres Verfahren. Sie hat keinen negativen Einfluss auf Morbidität, Mortalität und Überleben. Die En-bloc-Resektion der Arteria hepatica und der Arteria mesenterica superior wird sehr kontrovers diskutiert und sollte nur in Einzelfällen erwogen werden. Bei den meist fortgeschrittenen Karzinomen des Pankreaskorpus und -schwanzes kann durch eine En-bloc-Resektion des Truncus coeliacus eine höhere R0-Resektionsrate erreicht werden. / Pancreatic Cancer: Criteria and Limits of Resectability The aim of defining the resectability of pancreatic cancer is to determine the indication for potential R0 resection. Despite the absence of controlled trials, tumor resection in patients with regional lymph node involvement is a standard procedure worldwide. The involvement of interaortocaval lymph nodes is not an absolute contraindication for resection, although they are classified as distant metastasis (M1). Major pancreatic surgery can be safely combined with en-bloc resection of mesenteric, portal and splenic veins. Postoperative morbidity and mortality and long-term survival in patients with vein resection are comparable with those of patients without vein resection. The role of arterial en-bloc resection of the hepatic artery and the superior mesenteric artery is highly controversial and should be considered only in selected patients. For patients with locally advanced cancer of the body and tail of the pancreas distal pancreatectomy with en-bloc celiac axis resection offers an improved R0 resection rate. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Introduction Axillary dissection has little diagnostic and therapeutic benefit in the node-positive breast cancer patients in whom axillary disease has been completely eradicated after neoadjuvant chemotherapy (ypN0). We sought to assess the efficacy of an algorithm used for the identification of the ypN0 patients consisting of intraoperative evaluation of sentinel and tattooed (initially positive) lymph nodes. Methods Included were T1 and T2 breast cancer patients with one to three positive axillary lymph nodes marked with carbon who were referred for neoadjuvant chemotherapy followed by a surgery. Axillary dissection was performed only in the patients with residual axillary disease after neoadjuvant chemotherapy on ultrasound or with metastases described in the sentinel or tattooed lymph nodes either intraoperatively or in the final histology. Results Out of 62 included initially node-positive patients, 15 (24%) were spared axillary dissection. The detection rate of tattooed lymph node after neoadjuvant chemotherapy was 81%. The ypN0 patients were identified with 91% sensitivity and 38% specificity using ultrasound and intraoperative assessment of both sentinel and tattooed lymph node according to the final histology. Discussion/Conclusion Lymph node marking with carbon dye is a useful and...

Background: The standard of care for mediastinal staging during endobronchial ultrasound (EBUS) is Systematic Sampling (SS) where a minimum of 3 lymph node (LN) stations are biopsied, even if they appear normal on imaging. When LNs appear normal on PET and CT, the Canada Lymph Node Score can also identify if they appear normal on EBUS. For these Triple Normal LNs, the pretest probability of malignancy is < 6%, and routine biopsy may not be required. This preliminary study introduced Selective Targeted Sampling (STS), which omits biopsy of Triple Normal LNs and compared it firsthand to SS. Methods: A prospective, feasibility RCT was conducted to determine whether the progression of a definitive trial was warranted. Primary outcomes and their progression criterium were recruitment rate (70% acceptable minimum); procedure length (no overlap between sampling methods’ 95%CIs); and missed nodal metastasis (overlap between sampling methods’ diagnostic accuracy 95%CIs and crossing of the null for the percent difference in diagnosis). cN0-N1 NSCLC patients undergoing EBUS were randomized to the STS or SS arm. Patients in the STS arm were then crossed over to the SS arm to receive standard of care. Wilson’s CI method and McNemar’s test of paired proportions were used for statistical comparison. Surgical pathology was the reference standard. Results: Thirty-eight patients met the eligibility criteria, and all were recruited (100%; 95%CI: 90.82 to 100.00%). The median procedure lengths, in minutes, for STS and SS were 3.07 (95%CI: 2.33 to 5.52) and 19.07 (95%CI: 15.34 to 20.05) respectively. STS had a diagnostic accuracy of 100% (95%CI: 74.65% to 100.00%), whereas SS was 93.75% (95%CI: 67.71% to 99.67%) with the inclusion of inconclusive results. Percent difference in diagnosis between sampling method was 5.35% (95%CI: -0.54% to 11.25%). Conclusion: With the progression criteria successfully met, a subsequent multicentered, non-inferiority crossover trial comparing STS to SS is warranted. / Thesis / Master of Science (MSc) / Before deciding on treatment for patients with lung cancer, a critical step in the investigations is finding out whether the lymph nodes in the chest contain cancer. This is best done with a needle that biopsies those lymph nodes through the walls of the airway, known as endobronchial ultrasound transbronchial needle aspiration. Guidelines require that every lymph node in the chest be biopsied through a process called Systematic Sampling. However, new research has suggested that some lymph nodes may not need a biopsy. These lymph nodes are ones with a very low chance of cancer, based on their imaging tests. In this study, Selective Targeted Sampling was introduced whereby lymph nodes that appeared normal were not initially biopsied. The study followed a feasibility design, which proved sufficient patient interest, adequate safety and possible benefits in pursuing a larger trial comparing Selective Targeted Sampling to Systematic Sampling.

Yes / Recently a sub-population of cells with stem cell characteristics, reported to be associated with initiation, growth, spread and recurrence, has been identified in several solid tumors including oral tongue squamous cell carcinoma (OTSCC). The aim of our pilot study was to isolate CD44+ cancer stem cells from primary cultures of OTSCC and neck node Level I (node-I) biopsies, grow cell spheres and observe their characteristics in primary cultures. Parallel cultures of hyperplastic lesions of tongue (non-cancer) were set up as a control. Immunohistochemistry was used to detect CD44/CD24 expression and magnetic activated cell sorting to isolate CD44+ cell populations followed by primary cell culturing. Both OTSCC and node-I biopsies produced floating spheres in suspension, however those grown in hyperplastic and node-I primary cultures did not exhibit self-renewal properties. Lymph node metastatic OTSCC, express higher CD44/CD24 levels, produce cancer cell spheres in larger number and rapidly (24 hours) compared to node negative OTSCC (1 week) and non-cancer specimens (3 weeks). In addition, metastatic OTSCC have the capacity for proliferation for up to three generations in primary culture. This in vitro system will be used to study cancer stem cell behavior, therapeutic drug screening and optimization of radiation dose for elimination of resistant cancer cells. / SKMCH&RC, Yorkshire Cancer Research

Introdução: A metástase linfonodal tem impacto significativo não somente no prognóstico do carcinoma espinocelular (CEC) de laringe, como também na sobrevivência. O índice de densidade linfonodal (IDL) combina a análise da extensão e a qualidade do esvaziamento cervical, com a habilidade na análise anatomopatológica. Objetivo: Avaliar o IDL como fator prognóstico no CEC de laringe. Métodos: Foi realizado um estudo retrospectivo com 186 pacientes submetidos a tratamento cirúrgico da laringe com esvaziamento cervical entre janeiro de 2009 a dezembro de 2016. Variáveis clínico-patológicas foram avaliadas, assim como o ponto de corte de IDL para determinar fatores prognósticos. Resultados: Foram calculados dois valores de IDL no estudo: considerando os pacientes N0 (IDL= 0,018) e considerando pN+ (IDL= 0,06). A curva de Kaplan-Meier (log-rank) em relação à sobrevivência acumulada mostrou que tanto os pacientes com IDL > 0,018 quanto considerando o IDL >= 0,06 tiveram maior taxa de mortalidade do que os pacientes com IDL <= 0,018 ou IDL < 0,06, mostrando uma forma mais agressiva da doença, com recidiva mais precoce. Entretanto, apenas o IDL > 0,06 mostrou impacto tanto no intervalo livre de doença quanto na sobrevivência global. Conclusão: O IDL mostrou ser um índice importante na avaliação prognóstica dos pacientes com CEC de laringe, tendo relação direta com recidiva da doença. Pacientes com IDL > 0,060 provavelmente têm doença mais agressiva e devem ser candidatos à terapia adjuvante / Introduction: Lymph node metastasis has a significant impact not only on the prognosis for laryngeal squamous cell carcinoma (SCC), but also on survival. The index of lymph node density (LND) combines the analysis of the extension and quality of the neck dissection with the skill in analyzing the pathology. Objective: To evaluate LND as a prognostic factor in patients with laryngeal SCC. Methods: A retrospective study was carried out with 186 patients submitted to laryngeal surgical treatment with neck dissection between January 2009 and December 2016. Clinical-pathological variables were assessed, as well as the cut-off point for LND, to determine prognostic factors. Results: Two LND values were calculated in the study: one considering N0 patients (LND=0.018) and the other considering pN+ (LND=0.060). The Kaplan-Meier curve (log-rank) related to cumulative survival demonstrated that not only patients with LND > 0.018 but also those with LND >= 0.060 had a higher mortality rate than those with LND <= 0.018 or LND < 0.060, presenting a more aggressive form of the disease, with earlier recurrence. However, only the LND >= 0.060 group had impact on both disease-free survival, and overall survival. Conclusion: The LND proved to be an important index in the prognostic evaluation of larynx SCC patients, having a direct relationship with disease recurrence. Patients with LND >= 0.060 are likely to have a more aggressive form of the disease and should be considered for adjuvant therapy

INTRODUÇÃO: O câncer de endométrio é a sexta neoplasia maligna mais frequente nas mulheres no mundo. Com o crescimento mundial da obesidade, fator associado ao desenvolvimento do câncer de endométrio, estima-se que haja avanço no número de casos da doença. O tratamento cirúrgico do câncer de endométrio inclui a linfadenectomia pélvica e para-aórtica para o conhecimento do status linfonodal utilizado para determinação do tratamento adjuvante segundo a FIGO. Este é um procedimento que requer profissionais com treinamento cirúrgico avançado e não é isento de complicações. Algumas pacientes não se beneficiam da realização sistemática da linfadenectomia. O estudo das características clínicas, laboratoriais, radiológicas e anatomopatológicas das pacientes com câncer de endométrio em nossa população é fundamental para entendermos quais pacientes poderiam prescindir da linfadenectomia. MÉTODOS: Foram avaliadas 408 pacientes atendidas no Instituto do câncer do Estado de São Paulo entre janeiro de 2009 a março de 2015 com diagnóstico de carcinoma de endométrio submetidas ao tratamento cirúrgico. Foram avaliados parâmetros clínicos, laboratoriais, radiológicos e anatomopatológicos e sua capacidade de predizer metástases linfonodais. Foram construídas curvas Kaplan Meyer de sobrevivência. Além disso, as complicações relacionadas à realização da linfadenectomia também foram avaliadas. RESULTADOS: Das 405 pacientes elegíveis para o estudo 236(58,3%) foram submetidas à linfadenectomia pélvica e para-aórtica e não foi obtida amostra linfonadal em 73(18%). Os parâmetros significativos predição de acometimento linfonodal obtido através de regressão logística foram infiltração miometrial > 50%, presença de invasão linfovascular, presença de acometimento linfonodal pélvico por exame de imagem e CA125 > 21,5U/mL. A ausência dos quatro parâmetros implica em um risco de acometimento linfonodal de 2,7% enquanto que na presença de todos os quatro parâmetros o risco é de 82,3%. Nas curvas de sobrevida global (p=0,0001) e livre de doença (p=0,0004), a realização da linfadenectomia teve impacto positivo nas pacientes submetidas à linfadenectomia quando comparadas as não submetidas a este procedimento. CONCLUSÕES: A avaliação do risco de metástases linfonodais em pacientes com carcinoma do endométrio, baseadas em parâmetros clínicos, laboratoriais, radiológicos e anatomopatológicos foi capaz de identificar quatro variáveis com significativo valor preditivo de acometimento linfonodal que foram: linfonodos pélvicos pela imagem, CA125 com valor de corte 21,5U/mL, infiltração miometrial e invasão linfovascular. Na presença desses quatro parâmetros a probabilidade de acometimento linfonodal é de 82,3% / BACKGROUND: Endometrial cancer is the sixth most common malignancy in women worldwide. Obesity is a factor associated with this type of cancer development. Thus, the increase of obesity among women leads to a higher number of endometrial cancer cases. The surgical treatment of endometrial cancer includes pelvic lymphadenectomy and para-aortic to the knowledge of lymph node status used for determining the adjuvant treatment according to FIGO. This procedure requires professionals with advanced surgical training and is associated to complication. Moreover, some patients do not benefit from systematic lymphadenectomy. The study of clinical, laboratory, radiological and pathological data of patients with endometrial cancer in our population is critical to understand which patients could dispense lymphadenectomy. METHODS: This study analyzed 408 patients with the diagnosis of endometrial carcinoma undergoing surgical treatment at the Sao Paulo Cancer Institute between January 2009 and March 2015. Clinical, laboratory, radiologic and pathologic parameters were used to test the ability to predict lymph node metastasis. In addition, Kaplan Meyer survival curves were constructed. Complications related to lymphadenectomy were also evaluated. RESULTS: Out of 405 patients eligible for the study, 236 (58.3%) underwent pelvic and para-aortic lymphadenectomy and 73 (18%) had no lymph node samples. Significant parameters prediction of lymph node involvement obtained through logistic regression were myometrium infiltration > 50%, lymphovascular space invasion, pelvic lymph node involvement by imaging and CA125 > 21,5U/mL. The absence of the four parameters implies a risk of lymph node metastasis of 2.7%, whereas in the presence of all four parameters the risk is 82.3%. The overall survival curves (p = 0.0001) and the disease-free survival curves (p = 0.0004), had a positive impact on patients undergoing lymphadenectomy compared to the subject without lymphadenectomy. CONCLUSIONS: The assessment of lymph node metastasis in patients with carcinoma of the endometrial, based on clinical, laboratorial, radiologic and pathologic parameters was able to identify four variables with significant predictive value of lymph node metastasis. Those were pelvic lymph nodes by the image, CA125 > 21,5U/ml, myometrium infiltration > 50% and lymphovascular space invasion. In the presence of these four parameters, the probability of lymph node involvement is 82.3%

Dentre tantas complicações do diabetes mellitus (DM), a infecção por bactérias comuns da microbiota superficial da pele como, por exemplo, a bactéria Gram-positiva Staphylococcus aureus, causadora de infecções como a peritonite, com altos índices de hospitalização e morte. A hipótese deste trabalho é a que o efeito da insulina na ativação das vias de sinalização MAPK, PKC e PI3K em peritonite induzida por S. aureus em animais diabéticos e não diabéticos possa regular a produção de citocinas. Foram utilizadas amostras de fígado, rim, linfonodos peritoniais e baço de animais oriundos de estudo anterior (Projeto FCF/USP-375), no qual animais diabéticos (aloxana, 42 mg/kg, i.v., 10 dias) e não-diabéticos com peritonite decorrente da infecção por S. aureus receberam uma dose de 4 UI e 1 UI de insulina NPH, respectivamente, por via subcutânea, 2 horas antes da infecção com S. aureus, e outras 3 doses de 2 UI e 0,5 UI às 17h00\', respectivamente. A glicemia foi determinada no dia anterior, 10 dias após a injeção de aloxana e após os tratamentos com insulina. Em amostras de fígado, rim, linfonodo e baço dos animais supra citados foram avaliados a dosagem de citocinas (IL-1&#946;, IL-4, IL-10, TNF-&#945;, CINC-1, CINC-2 e CINC-3) por ensaios de enzima-imunoensaio (ELISA); em homogenato de fígado foram avaliadas a expressão das moléculas das vias MAPK (fosfo P-38, fosfo ERK p42/44), PKC (fosfo PKC-&#945;, fosfo PKC-&#948;) e PI3K (fosfo-AKT) pelo método de Western Blotting. Na avaliação do fígado, a insulina foi capaz de aumentar a concentração das citocinas IL-4 e TNF-&#945; que apresentavam-se diminuídas em animais não diabéticos, em relação aos animais não diabéticos e não infectados, mas nos animais diabéticos, na infecção pela cepa N315, a insulina diminuiu a concentração de IL-4, que não estava alterada pela infecção, e não foi capaz de aumentar a concentração de IL-1&#946; que estava diminuída na infecção, em relação aos animais diabéticos e não infectados. Em linfonodos peritoniais de animais não diabéticos infectados pela cepa N315, a insulina diminuiu a produção de IL-1&#946; e IL-10, que não estavam alteradas na infecção, e diminuiu a concentração de IL-4, que estava aumentada na infecção, em relação aos animais não diabéticos e não infectados; em animais diabéticos, a insulina diminuiu a produção das citocinas IL-1&#946; e CINC-1, que estavam aumentadas, e aumentou a concentração de IL-10, que estava diminuída na infecção com a cepa N315, mas baixou a concentração de IL-4, em relação aos animais infectados, e na infecção pela cepa ATCC, a insulina aumentou a produção de IL-1&#946;, CINC-1 e CINC-3 dos animais tratados, em relação aos infectados e não tratados. Em baço, a insulina diminuiu a produção de IL-10 na infecção pela cepa ATCC tanto em animais não diabéticos quanto em animais diabéticos e, nesse último grupo, também aumentou a produção de CINC-3 em relação aos animais diabéticos não infectados; na infecção com a cepa N315, a insulina não aumentou a concentração de IL-1&#946; e TNF-&#945;, que estavam diminuídas na infecção. Em rim, não houveram alterações significativas na produção de citocinas na infecção com nenhuma das cepas estudadas, nem para os grupos diabéticos, nem para os não diabéticos. Verificou-se que os animais diabéticos apresentam maior alteração tanto nas vias de sinalização estudadas quando na produção de citocinas pró-inflamatórias, quando comparados aos animais não diabéticos, na infecção por ambas as cepas de S. aureus estudadas. Assim, os resultados obtidos sugerem que o tratamento com insulina possa modular parcialmente a produção das citocinas IL-1&#946;, TNF-&#945; e IL-10 no fígado e nos linfonodos peritoniais dos animais infectados principalmente pela cepa N315 de S.aureus, modulando parcialmente a expressão das moléculas da via de sinalização (MAPK e PKC), envolvidas na produção dessas citocinas. / Among so many complications of diabetes mellitus (DM), infection by common bacteria of the superficial microbiota of the skin, for example, a gram-positive bacteria Staphylococcus aureus, causing infections like peritonitis, with high rates of hospitalization and death. The hypothesis of this study is that the effect of insulin on the activation of MAPK, PKC and PI3K signaling pathways in peritonitis induced by S. aureus in diabetic and non-diabetic animals may regulate the production of proinflammatory cytokines. Liver, kidney, peritonial lymph nodes and spleen samples of animals from the previous study (FCF / USP-375 Project) were used in this project; diabetic animals (alloxan, 42 mg / kg, iv, 10 days) and non-diabetic animals with peritonitis due to S. aureus infection received one dose of 4 IU and 1 IU of NPH insulin, respectively, subcutaneously, 2 hours before infection with S. aureus, and another 3 doses of 2 IU and 0.5 IU at 5:00 p.m., respectively. Blood glucose was determined the day before, 10 days after alloxan injection and after insulin treatments. In the liver, kidney, lymph node and spleen samples of the above-mentioned animals the cytokines (IL-1&#946;, IL-4, IL-10, TNF-&#945;, CINC- 2 and CINC-3) by enzyme-immunoassay (ELISA) assays; we avaliated, by Western Blotting, the signaling pathways MAPK (phospho-P-38, phospho ERK p42 / 44), PKC (phospho PKC-&#945; and phospho PKC-&#948;) and PI3K (phospho AKT) in liver, insulin was able to increase the concentration of cytokines IL-4 and TNF-&#945; that were decreased in non-diabetic animals, in relation to non-diabetic and non-infected animals, but in diabetic animals, in strain N315, insulin decreased the concentration of IL-4, which was not altered by the infection, and was not able to increase the concentration of IL-1&#946; that was decreased in infection, relative to diabetic and uninfected animals. In peritonial lymph nodes from non-diabetic animals infected with the N315 strain, insulin decreased the production of IL-1&#946; and IL-10, which were not altered in the infection, and decreased the concentration of IL-4, which was increased in infection, in relation to non-diabetic and non-infected animals; in diabetic animals, insulin decreased IL-1&#946; and CINC-1 which were increased, and increased the concentration of IL-10, which was decreased in infection with strain N315, but decreased the concentration of IL-4 in Infected animals, and in infection by the ATCC strain, insulin increased the production of IL-1&#946;, CINC-1 and CINC-3 of treated animals over infected and untreated animals. In spleen, insulin decreased IL-10 production on infection by the ATCC strain in both non-diabetic and diabetic animals and, in this last group, also increased the production of CINC-3 in relation to uninfected diabetic animals; in infection with the N315 strain, insulin did not increased the concentration of IL-1&#946; and TNF-&#945;, which were decreased in infection. In kidney, there were no significant changes in cytokine production in infection with any of the strains studied, neither for diabetic groups nor for non-diabetics. It was verified that diabetic animals present a greater alteration both in the signaling pathways studied and in the production of pro-inflammatory cytokines, when compared to non-diabetic animals, in the infection by both strains of S. aureus studied. Thus, the results suggest that insulin treatment may partially modulate the production of IL-1&#946;, TNF-&#945; and IL-10 cytokines in the liver and in the peritonial lymph nodes of animals infected mainly with S. aureus strain N315, since they partially modulating the expression of signaling pathway molecules (MAPK and PKC), involved in the production of these cytokines.