O câncer de mama é uma doença complexa que envolve alterações genéticas e epigenéticas junto com fatores ambientais. Dentre os tipos de câncer o de mama é o de maior incidência e mortalidade na população feminina, portanto a caracterização desta doença tem sido um desafio continuo para a comunidade cientifica. Numerosos biomarcadores moleculares tem sido associados com o câncer de mama e seus subtipos; no entanto, existe uma boa quantidade que tem sido pouco explorado. Este é o caso dos genes da família PHLDA (pleckstrin homology like domain family A), identificados repetidamente em vários estudos de perfil transcripcional em câncer de mama. Esta família compreende três genes: o gene PHLDA1 expresso em diferentes tecidos e com papel na regulação da apoptose, o gene PHLDA2 localizado em uma importante região de localização de genes supressores de tumor que sofrem regulação por imprinting, e o gene PHLDA3 envolvido na apoptose mediada por p53. Diversos estudos têm mostrado que os genes da família PHLDA estão frequentemente alterados em diferentes tipos de tumores, incluindo o câncer de mama, no entanto, o papel desses genes no desenvolvimento e progressão do câncer de mama ainda não está bem estabelecido. Na atualidade há uma enorme quantidade de dados experimentais integrados e disponibilizados em bancos de dados públicos para análise de dados genéticos e epigenéticos em diferentes tipos de tumores. Muitos dos estudos depositados nesses bancos tem facilitado a identificação de novos subtipos intrínsecos de câncer de mama, a predição de sobrevida e a resposta a drogas. Nosso objetivo é fazer uma busca em bases de dados públicos, para avaliar o padrão de expressão da família PHLDA em tumores e em linhagens celulares de mama, do perfil de metilação, mutação e do potencial valor prognóstico da expressão desses genes em câncer de mama. Para isso foram utilizadas as plataformas TCGA, GEO e GOBO para a busca de dados de expressão de mRNA, TCGA e GEO para extração de dados de metilação de DNA, TCGA e COSMIC para análise de dados de mutação e CNA, mIRTarBASE e GEO para dados de microRNA em câncer de mama, Netdecoder para a construção das redes e KMplotter para a busca de dados de sobrevida. Os resultados mostraram que PHLDA1 se encontra com baixa expressão em tumor e em linhagens celulares de mama e mais expresso nos tumores ER negativos. Os tumores ER negativos também mostraram um baixo nível de metilação quando comparados com amostra normal. Adicionalmente nos encontramos que PHLDA1 é alvo do microRNA miR-181a-5p cujos altos níveis de expressão em tumores foram associados com baixa sobrevida. PHLDA2 foi mais expresso nos tumores do que em amostra normal de mama, principalmente nos subtipos her2+; estes níveis elevados de expressão foram associados com baixa sobrevida em quase todos os subtipos moleculares; por outro lado, nenhuma diferença foi encontrada no perfil de metilação por receptor de estrógeno. O microRNA miR-193b-3p foi identificado como regulador de PHLDA2. O gene PHLDA3 foi encontrado menos expresso nos tumores ER negativos, e esses tumores também se encontravam com hipermetilação. Pacientes com todos os subtipos moleculares apresentaram um aumento de sobrevida livre de recorrência quando os níveis de PHLDA3 foram altos. Nenhum membro da família apresentou mutações nos dados analisados, enquanto que alterações no número de cópia foram encontradas nos três genes. Os dados obtidos até o momento mostram que a expressão dos membros da família PHLDA é alterada em câncer de mama e tem impacto na sobrevida dos pacientes. Processos como metilação do DNA, alterações no número de cópia e a participação de microRNAs podem ser os mecanismos implicados na desregulação desses genes / Breast cancer is a complex disease involving genetic and epigenetic alterations together with environmental factors. Among the cancer types, breast cancer is the most incident and deadliest in women population worldwide in both developed and developing countries, therefore, characterization of this disease has been a continuous challenge for the scientific community. A large quantity of molecular biomarkers has been associated with breast cancer development and their subtypes. However, there is a good amount that has been little explored. This is the case of the genes of the PHLDA family (pleckstrin homology-like domain family A) previously identified in a series of transcriptional profiling studies and recognized for their role in apoptosis. This family comprises three members; PHLDA1 is expressed in different tissues and has an important role in apoptosis regulation; PHLDA2 is located in a region harboring important tumor suppressor genes and is regulated by imprinting process. PHLDA3 gene is involved in p53-mediated apoptosis. Several studies have shown that the genes of the PHLDA family are frequently altered in different types of tumors including breast cancer. However, the role of these genes in breast cancer progression and development is not well established yet. Currently, there is a vast amount of genomic, transcriptomic, proteomic and epigenetic data generated by new high-performance technologies available in public databases. Many of the studies deposited in these banks have facilitated the identification of new intrinsic subtypes of breast cancer, prediction of survival and drug responses. Regarding the potential role of PHLDA family as biomarkers and the limited information in breast cancer, we pretend in this study to take advantage of these platforms downloading information about expression, methylation, of PHLDA family and correlating it with prognosis in breast cancer. We used TCGA, GEO and GOBO platforms to look for mRNA expression data, TCGA and GEO to extract methylation data, TCGA and COSMIC to analyze mutation and CNA, miRTarBase and GEO for microRNA analysis, KMplotter to assess prognosis and NetDecoder to construct the networks. The results showed that PHLDA1 is downregulated in tumors and breast cell line compared with breast tissue and it was more expressed in ER negative tumors. These tumors also showed a low level of methylation when compared to normal tissue. Additionally, the mining of miRNA revealed that PHLDA1 is target of two microRNAs, miR-181a-5p, whose high levels of expression in tumors were associated with low survival. On the other hand, the transcripts of PHLDA2 were more expressed in tumors than in normal sample, mainly in HER2+ subtype, and PHLDA2 high expression was associated with poor outcome in almost all the subtypes. PHLDA2 is methylated only on ER tumors and was found to be target of the microRNA has-miR-193b-3p. PHLDA3 was less expressed in ER-negative tumors, and these tumors also exhibited DNA hypermethylation. Patients with tumors expressing high levels of PHLDA3 showed better recurrence-free survival than patients with low levels of PHLDA3. No family member had mutations in the analysed data, while copy number changes were found in the three genes. The data obtained so far show that the expression of PHLDA1 family members is altered in breast cancer and has an impact on the survival of patients. Processes such as DNA methylation, copy number changes and the involvement of microRNAs may be the mechanisms involved in the deregulation of these genes

Introdução: A curva de aprendizado em cirurgia é um período de sedimentação de habilidades onde procedimentos são realizados com maior dificuldade e lentidão, maior risco de complicações intra-operatórias e menor eficácia clínico-funcional devido à inexperiência do cirurgião. Nós analisamos a curva de aprendizado inicial da prostatectomia radical retropúbica realizada por médicos residentes do Setor de Uro-Oncologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Método: estudo prospectivo, envolvendo 184 prostatectomias radicais retropúbicas, realizadas por cinco residentes consecutivamente, entre 02/06/2006 e 31/01/2008. Foram considerados: o tempo operatório, sangramento transoperatório, necessidade de transfusão sanguínea, taxa de margens cirúrgicas comprometidas, complicações intra-operatórias e avaliação funcional precoce. Resultados: cada residente realizou em média 37 cirurgias. O PSA mediano foi de 9,3 ng/mL e o estágio clínico T1c em 71% dos pacientes. O estágio patológico foi pT2 (73%), pT3 (23%), pT4 (4%); o escore de Gleason na peça cirúrgica foi de 54% (Gleason <7), 33% (Gleason 7) e 13% (Gleason >7). O tempo cirúrgico mediano foi de 140 minutos, o sangramento mediano de 488 mL e a necessidade de transfusão sanguínea de 7,2%. A taxa de margens cirúrgicas positivas de 23% foi constante nos 30 primeiros casos. A avaliação funcional precoce (até 6 meses de pós-operatório) mostrou 89% de continência, 57% de disfunção erétil e 7% de recidiva bioquímica. Conclusão: Durante a curva de aprendizado da prostatectomia radical, ocorre redução significativa do tempo operatório após 20 cirurgias e tendência de redução do sangramento e da necessidade de transfusão sanguínea após 29 cirurgias. As margens cirúrgicas permanecem estáveis em 23%. / Introduction: The learning curve is a period of skills improvement. Procedures are carried through with longer operating time, high risk of surgical complications and sub optimal functional outcomes. We have analyzed the residents\' initial learning curve in open radical prostatectomy in our institution. Method: Between June of 2006 and January of 2008, 184 open radical prostatectomies have been performed in our service by five senior residents in Urology. We prospectively evaluated: operating time, blood loss, blood transfusion rate, positive surgical margins, intra-operative complications and early functional outcomes. Results: an average of 37 open radical prostatectomies was performed by each resident. Medium PSA was 9,3ng/mL; clinical stage T1c in 71% of the patients. The pathological stage was pT2 (73%), pT3 (23%), pT4 (4%) and Gleason score was 54% (Gleason <7), 33% (Gleason 7) and 13% (Gleason >7). The medium operating time was 140 minutes, medium blood loss of 488 mL and positive margins were found in 23% during the first 30 cases. Early functional outcomes (less than 6 months after surgery) revealed 89% of urinary continence, 43% of normal erectile function and 7% of biochemical recurrence. Conclusion: During the initial learning curve significant reduction in operating time occurs after first 20 procedures, blood loss and transfusion improves after 29 prostatectomies and positive margins remain stable during the first 30 patients (23%).

Introdução: o câncer de rim corresponde a aproximadamente 3% de todos os casos novos de câncer no mundo, sendo o carcinoma de células renais o tipo histológico mais frequente nos Estados Unidos da América, correspondendo a 85% das neoplasias renais malignas. A nefrectomia é o tratamento cirúrgico padrão para os pacientes diagnosticados com neoplasias renais e pode ser utilizada de forma radical ou parcial, dependendo do tamanho e localização do tumor. Alguns estudos recentes têm tentado demonstrar que diferenças no acesso ao tratamento entre pacientes com classes socioeconômicas díspares podem agravar a evolução da doença e até mesmo a sobrevida de pacientes menos favorecidos. No entanto esses dados ainda são controversos e não existem números concretos definindo qual a influência real da classe socioeconômica na evolução dos pacientes com neoplasias renais. Objetivos: 1) Verificar as chances de recorrência da neoplasia e mortalidade câncer-específica dos pacientes tratados cirurgicamente com carcinoma de células renais em instituições com perfis de pacientes socioeconômico diferentes, sendo uma pública, que atende pacientes com níveis socioeconômicos inferiores e outra privada, que atende pacientes com níveis socioeconômicos mais elevados. 2) Verificar também as características da neoplasia e as formas de tratamento de pacientes tratados em instituições públicas e privadas, supostamente influenciadas pelos diferentes níveis socioeconômicos. Métodos: foi realizado estudo retrospectivo não controlado com 398 pacientes portadores de neoplasia de rim, que foram tratados com nefrectomia radical ou parcial e acompanhados por pelo menos 5 anos. Os pacientes foram divididos em dois grupos de acordo com as instituições nas quais foram submetidos ao tratamento, sendo 300 pacientes de instituição pública (ICESP) e 98 pacientes de instituição privada (Hospital SírioLibanês). Foram realizadas comparações entre os dois grupos, incluindo as seguintes variáveis: recorrência local tumoral, mortalidade câncer-específica, dados demográficos como sexo, tipo de cirurgia realizada e aspectos anátomo-clínicos como estadiamento tumoral, tipo histológico, grau de Fuhrman e tamanho do tumor. Resultados: o tipo de cirurgia, tanto nefrectomia radical como parcial, realizada em ambas as instituições foi numericamente semelhante (p = 0,782). No que tange ao tipo histológico, houve diferença estatística significativa entre os grupos, sendo que, em ambas as instituições houve predominância do carcinoma de células claras, entretanto, com número mais elevado na instituição pública do que na instituição privada, respectivamente, 83,0% e 56,1%, observando-se, contudo, maior prevalência de tumores com componente sarcomatoide na instituição privada (6,1% versus 1%, p < 0,001). Em relação ao estágio patológico da neoplasia houve uma maior frequência de casos avançados pT3-pT4 na instituição pública, comparada à privada, respectivamente, 26,0% e 14,3% (p < 0,001). O grau de Fuhrman e o volume tumoral foram mais elevados nos pacientes submetidos ao tratamento na instituição pública, quando comparada à privada, respectivamente, 28,0% versus 24% em relação ao grau de Fuhrman (p = 0,048) e 6,7 cm versus 5,8 cm em relação ao volume tumoral (p = 0,016). Com respeito a mortalidade câncerespecífica (públicas 10,4% versus privadas 8,2%, p = 0,4250) e recorrência tumoral (públicas 15,0% versus privadas 11,2%, p = 0,304), os resultados foram semelhantes nas duas instituições estudadas. Conclusões: os riscos de recorrência tumoral e mortalidade câncer-específica foram semelhantes em pacientes tratados em instituição pública e privada no Brasil, indicando que diferentes níveis socioeconômicos não influenciam a evolução oncológica de pacientes com câncer renal localizado tratados cirurgicamente. Os resultados do presente estudo demonstraram também que pacientes tratados em instituição pública e possivelmente de nível socioeconômico mais baixo, são diagnosticados com carcinoma de células renais mais avançado, quando comparados aos pacientes tratados em hospital privado, supostamente de nível socioeconômico mais alto / Introduction: kidney cancer corresponds to approximately 3% of all new cancer cases in the world, and kidney cell carcinoma being the most frequent histological type in the United States of America, corresponding to 85% of the malignant kidney cancer. More than 60% of kidney tumors have been incidentally diagnosed between the sixth and seventh decade of life with predominance for the male gender, and the proportion of patients under 65 had varied in the last few years. Nephrectomy has been the standard surgical treatment for patients diagnosed with kidney cancer, and it can be used in a radical or partial manner, depending on the size and the location of the tumor. Some worldwide studies have attempted to demonstrate that differences in the access to the treatment among different socioeconomic classes can contribute to the outcome of the disease, leading to a worse survival rate of the less privileged patients. However, studies are still controversial, and in fact there is no firm knowledge as to the real influence of the socioeconomic class in the evolution of patients affected by kidney cancer. Objectives: 1) to evaluate the chances of local disease local recurrence and cancer specific mortality of the patients with renal cancer treated surgically in institutions with different socioeconomic patients\' profile, one public institution attending lower socioeconomic levels, and another private taking care of higher socioeconomic level patients. 2) In addition we evaluated disease characteristics and forms of treatment of patients dealt with in both public and private institutions. Methods: a non-controlled retrospective study was carried out involving 398 patients treated with radical or partial nephrectomy for kidney cancer treatment. All patients were followed for at least 5 years and were divided in two groups in accordance with the institutions where treatment was provided, 300 of whom in a public institution and 98 in a private one. Comparisons between the two groups included the following data: tumor recurrence, cancer-specific mortality, sex, type of surgery performed, tumor staging, histologic type, Fuhrman grade and size of the tumor. Results: The type of surgery performed in both institutions was similar, showing no statistical difference (p = 0.782). Regarding the histological type, there was a statistically significant difference between the groups, and in both institutions there was a predominance of clear cell carcinoma, however, with a higher number in the public institution than in the private institution, respectively, 83.0% and 56.1%. Sarcomatoid features were prevalent in the private institution (6,1% versus 1%, p < 0,001). There was a higher frequency of pT3-pT4 advanced cases in the public institution, compared to the private one, respectively, 26.0% and 14.3% (p < 0.001). Fuhrman grade and tumor volume were higher in patients submitted to treatment at the public institution and in both variables there was a significant statistical difference (tumor grade, respectively, 28.0% and 20.4%, p = 0.048 and tumor volume, respectively, 6.7 cm and 5.8 cm, p = 0.016). In relation to cancer-specific mortality (public 10.4% and private 8.2%, p = 0.4250) and tumor recurrence (public 15.0% and private 11.2%, p = 0.304), the results were similar in the two studied institutions. Conclusions: the risks of tumor recurrence and cancer specific mortality were similar in patients treated in a public and private institution in Brazil. The results of the present study also demonstrated that patients treated at a public institution and possibly of a lower socioeconomic level are diagnosed with higher volume renal cell carcinoma and with a more advanced nuclear grade when compared to patients treated at a private hospital, supposedly of a higher socioeconomic level

O objetivo desta pesquisa foi estabelecer uma metodologia para avaliar carcinomas espinocelulares (CEC) de cabeça e pescoço, identificando e distinguindo áreas de maior atividade metabólica dentro da neoplasia, associando dados simultaneamente adquiridos, obtidos por diferentes modalidades de aquisição de imagens, combinando informações metabólicas e anatômicas num único exame. A população estudada consistiu de 17 pacientes com carcinoma espinocelular (CEC) de cabeça e pescoço pertencentes aos arquivos do Departamento de Imagem do Hospital do Câncer, São Paulo. As imagens de TC (tomografia computadorizada) e do 18 F-FDG-PET (tomografia por emissão de pósitrons) foram simultaneamente adquiridas utilizando um aparelho não dedicado. Os dados originais foram transferidos para uma estação de trabalho independente com programa de computação gráfica para o processamento dos grupos individuais e fusão em um único grupo, contendo os dados fisiológicos e metabólicos. Os achados foram definidos como positivos na presença de focos com aumento da concentração do radiofármaco em áreas não relacionadas à distribuição normal do mesmo. Em 77% dos casos (n=13), a hipercaptação foi detectada ao centro da lesão e em 23% (n=4) dos casos houve comportamento diferente, com hipercaptação excêntrica. A fusão de imagens simultaneamente adquiridas num único exame ( 18 F- FDG PET e TC) possibilitou o mapeamento topográfico metabólico das lesões estudadas e foi possível localizar áreas de maior atividade metabólica dentro do próprio 13 tumor, verificando recidivas ou metástases, possibilitando aumentar as opções quanto ao planejamento radioterápico ou cirúrgico a serem seguidos. / The aim of this study is to propose a methodological approach to evaluate head and neck squamous cell carcinoma (SCCA) in order to identify and to distinguish areas of higher metabolic activity inside the lesion combining the functional metabolic and morphological data simultaneously acquired in a non dedicated PET-CT device. The study population consisted of 17 patients, with SCCA of the head and neck carcinoma. These patients were submitted to a non-dedicated 18 F- FDG- PET imaging using a system with low dose CT and Positron emission coincidence acquisition capabilities. The image acquisition was then transferred to an ENTEGRA 2 NT workstation to generate groups of individual images (metabolic and anatomical data) and image fusion (CT + PET). In those patients with anomalous concentrations of 18 F-FDG, the lesion was depicted on three planes (axial, coronal and sagittal) in CT, PET, and the image fusion at the computer screen. The findings were defined as positive in the presence of well-defined focal area of increased uptake in regions unrelated to the normal biodistribution of the tracer on visual inspection. Two examiners interpreted the images in different sessions, in order to get an agreement. Subsequently, the sites of higher metabolic activity inside the tumor were identified and classified in centric or eccentric, according to their relative location. Observing the images, we found 77.00% of the patients with the site of higher activity at the center of lesion. In 23.00% of the patients a different 15 behavior, with the tracer increased eccentrically to the lesion. This technique gave a realistic view of the functional metabolism, locating the anatomical tumor area and helping in future treatment planning.

Astrocitomas constituem o tipo mais comum de tumor cerebral neuroepitelial primário apresentando grande heteogeneidade. De acordo com a Organização Mundial de Saúde, os astrocitomas podem ser histologicamente divididos em graus I- IV. Astrocitomas pilocíticos (grau I) são tumores circunscritos, de crescimento lento e bom prognóstico. Astrocitomas difusos (grau II) apresentam hipercelularidade, crescimento relativamente lento e propensão para invadir o tecido cerebral normaladjacente. Astrocitomas anaplásicos (grau III) apresentam aumento da celularidade, atipia nuclear e figuras mitóticas. Glioblastomas (GBMs - grau IV) representam o mais frequente e maligno tumor cerebral humano com crescimento extremamente agressivo, anaplasia, células altamente proliferativas, com frequente neoangiogênese e necrose. O comportamento altamente invasivo dos GBMs, caracterizado pela infiltração difusa para o parênquima cerebral normal adjacente, inviabiliza a remoção cirúrgica total do tumor. Além disso, as células dos GBMs são relativamente resistentes às terapias disponíveis. Analogamente a outros tipos de câncer, os GBMs demonstram comportamentos semelhantes às de células trofoblásticas, sugerindo vias de sinalização compartilhadas no controle dos processos tumorigênicos e de implantação da placenta. Em ambos os casos, o estabelecimento de um fenótipo invasivo compreende processos celulares que incluem aumento da proliferação, expressão ou repressão de moléculas de adesão celular específicas, produção de enzimas que digerem a matriz extracelular, expressão de produtos de proto-oncogenes, ativação da telomerase, evasão ou edição da resposta imune do hospedeiro e angiogênese. Com base nas características comuns entre células tumorais e trofoblastos, o presente trabalho teve como objetivo a busca in silico de genes expressos em placenta e tecidos tumorais e que podem contribuir para o estabelecimento e manutenção do fenótipo maligno, utilizando os bancos de dados de MPSS e SAGE. Dentre os 12 genes avaliados, CD99 foi o que apresentou o maior valor de expressão média nas amostras de GBM em comparação a amostras de tecido cerebral não neoplásico. Em uma casuística ampliada de astrocitomas , observou-se uma maior expressão relativa de CD99 em todos os graus de malignidade, sendo que os GBMs apresentaram os valores mais elevados. Esses achados foram confirmados em nível proteico por western blot e imunoistoquímica. Além disso, foi realizada a análise de imunolocalização de CD99 em amostras de tumores astrocíticos, com localização restrita a membrana ou citoplasma, em contraste ao tecido cerebral não neoplásico ou astrocitomas pilocíticos não infiltrantes, que não apresentaram marcação nestas estruturas. Ao compararmos três linhagens celulares derivadas de GBM, CD99 apresentou maior expressão na membrana e maior capacidade migratória nas linhagens A172 e U87MG, enquanto que a linhagem T98G apresentou menor expressão da proteína e ausência de capacidade migratória. O silenciamento da expressão de CD99 por siRNA diminuiu significativamente a migração das linhagens celulares A172 e U87MG. Além disto, anticorpo anti-CD99 apresentou maior marcação por em lamelipódios das células U87MG, possivelmente por reorganização do citoesqueleto de actina. Os resultados integrados de expressão gênica e proteica sugerem que a expressão de CD99 em astrocitomas de diferentes graus de malignidade pode contribuir para a capacidade infiltrativa destes tumores, ressaltando a importância desta proteína como um potencial alvo para a redução da capacidade infiltrativa dos astrocitomas nos processsos de migração e invasão / Astrocytomas are the most common type of primary neuroepithelial brain tumour and show great heterogeneity. According to World Health Organization criteria, astrocytomas can be histologically separated into grades I through IV. Pilocytic astrocytomas (grade I) are circumscribed, slow growing tumours with a good prognosis and mainly occur in children or young adults. Low-grade astrocytomas (grade II) show hypercellularity, relatively slow growth, and a propensity to invade surrounding normal brain tissue. Anaplastic astrocytomas (grade III) have increased cellularity, nuclear atypia, and mitotic figures. Glioblastomas (GBMs - grade IV), are the most common malignant and aggressive of all brain malignancies, exhibiting anaplastic, highly proliferative cells, with frequent neoangiogenesis and necrosis. GBM cells can escape complete resectability and are relatively resistant to the available therapies (radiation and chemotherapy). Similar to other cancer types, GBMs demonstrates behaviours that are analogous to trophoblastic cells, suggesting shared pathways to control tumourigenic processes and placental implantation. In both cases, the establishment of an invasive phenotype comprises cellular processes that include increased proliferation, the expression or repression of specific cell adhesion molecules, the production of enzymes that digest the extracellular matrix, the expression of proto-oncogene products, telomerase activation, evasion or edition of the host immune response, and angiogenesis. Based on the shared characteristics of tumour cells and trophoblasts, we searched in silico for genes that are in both placenta and tumour tissues using MPSS and SAGE databases and that could contribute to the establishment and maintenance of a malignant phenotype. Among 12 selected genes, CD99 exhibited the highest relative mRNA expression in GBM compared to non-neoplastic brain tissues. In a larger cohort of astrocytic tumours, we further demonstrated increased CD99 expression in all malignant grades, with GBMs showing the highest values. These findings were confirmed at the protein level by Western blotting and immunohistochemistry. Additionally, we demonstrated the CD99 localisation profile in astrocytic tumours. Interestingly, CD99 expression was confined to the cytoplasm or membrane in more malignant astrocytomas, in contrast to non-neoplastic brain tissue or non-infiltrative pilocytic astrocytoma, which showed no obvious staining in these structures. Comparison of three GBM cell lines revealed higher CD99 expression at the membrane and higher migratory capacity in the A172 and U87MG lines, but lower CD99 expression and no migratory ability in the T98 line. Knocking down CD99 expression by siRNA decreased significantly the migration of both A172 and U87MG cell lines. Additionally, a higher anti-CD99 antibody staining was observed in lamellipodia of U87MG, probably because of actin citoskeletal reorganization. These integrated CD99 gene and protein expression results suggest that CD99 expression in astrocytomas of different malignant grades might contribute to the infiltrative ability and support the importance of CD99 as a potential target to reduce infiltrative astrocytoma capacity in migration and invasion.

By using the acridine orange (AO) staining method to examine the release of contents from lysosomes, it was found that PD released AO into the cytosol in both cell lines. However, the releasing pattern of HepG2 and RHepG2 was quite different. Upon PD treatment, the release of AO in HepG2 cells was graduate and slow while that in RHepG2 was sudden and sharp. / Cancer is one of the leading causes of death in the world. During cancer treatment, development of multidrug resistance (MDR) is always the major cause of failures of chemotherapy in human cancers. In our project, hepatocarcinoma HepG2 and its drug-resistant derivatives RHepG2 with MDR towards doxorubicin (Dox), fenretinide and Taxol were used to examine the differences in their response towards various anti-cancer agents. / From the AO staining, most of the lysosomes were found in the cytosol near the nucleus. However, some lysosomes were found inside the nucleus occasionally. When we double stained the HepG2 cells with DiOC6(3), it was found that the lysosomes were actually located inside the nuclear tubules. However, no such lysosome migration was observed after treating the HepG2 cells with PD. Thus, lysosomes inside the nuclear tubules might not be involved in the PD-induced lysosomal pathway. The mechanism that leads to the migration of lysosomes into the nuclear tubules is still unclear. / From the Western blot analysis, cathepsin D (Cat D) and cathepsin L (Cat L) were both released from the lysosomes after treating the two cell lines with PD. Also, it seemed likely that Cat L was released earlier than that of cyt c. This implies that lysosomal permeabilization is an early event in apoptosis. With the use of siRNA technology, it was found that RHepG2 with the knockdown of Cat D and Cat L were more tolerant and vulnerable towards PD, respectively. These suggest that Cat D and Cat L might act oppositely in the apoptotic pathway. Furthermore, the addition of Cat D inhibitor, pepstatin A, blocked the PD-mediated cell death in RHepG2 cells further confirms that Cat D is a pro-apoptotic protein that is involved in the apoptotic pathway. / In conclusion, PD was a potent anti-cancer agent that could reverse the MDR properties of RHepG2 and kill more RHepG2 cells through lysosomal and mitochondrial apoptotic pathway. / Next, we investigated the underlying killing mechanism and found out that PD switched on both the mitochondrial and lysosomal apoptotic pathway in both cell lines. Our results indicate that PD was able to depolarize mitochondrial membrane potential and release apoptosis inducing factor (AIF) and cytochrome c (cyt c) from the mitochondria to cytosol. Also, PD was able to act on isolated mitochondria directly, causing a stronger mitochondrial membrane permeabilization and more AIF release from the RHepG2 than that of the parental cells. / Polyphyllin D (PD) is a saponin found in a tradition Chinese herb, Paris polyphylla, which has been used to treat liver cancers in China for many years. Interestingly, from the MTT assays, we found out that RHepG2 (IC50: 2.0 muM) was more sensitive towards PD when compared to that of its parental cells (IC50: 3.9 muM). To keep the MDR properties, RHepG2 cells were routinely cultured with 1.2 muM of Dox. When we cultured RHepG2 in the absence of Dox but with 1.2 muM of PD for 28 days, the Pgp expression could not be maintained. However, such high expression level of Pgp was maintained when RHepG2 cells were treated with vincristine (1.2 muM) in the absence of Dox. This indicates that vincristine was a substrate of Pgp to keep the Pgp expression in RHepG2 cells while PD was not. / When incubated with different concentrations of Dox, RHepG2 accumulated less Dox than that of its parental HepG2 cells. When probed by the antibody against P-glycoprotein (Pgp), RHepG2 showed a strong Pgp expression. With the addition of Pgp modulator, verapamil, RHepG2 accumulated more Dox. All these findings indicate that Pgp is a mediator giving rise the MDR in RHepG2 cells. However, RHepG2 had a higher resistance to Dox than its parental line even co-cultured with verapamil. RHepG2 remained viable at the intracellular Dox concentration that was toxic to HepG2 cells. These observations suggest that the MDR properties of RHepG2 involved multiple mechanisms in addition to the effect of Pgp. / Lee, Kit Ying Rebecca. / "August 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4735. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 241-253). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Li Ka Wai Kay. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references. / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT (ENGLISH/CHINESE) --- p.ii / TABLE OF CONTENTS --- p.viii / LIST OF FIGURES --- p.xii / LIST OF APPENDICES --- p.xiii / Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Gastric carcinomas --- p.1 / Chapter 1.1a --- Epidemiology --- p.1 / Chapter 1.1b --- Classification --- p.2 / Chapter 1.1c --- TNM staging --- p.3 / Chapter 1.1d --- Prognosis --- p.4 / Chapter 1.1e --- Etiology --- p.6 / Chapter 1.1f --- Genetic alteration in gastric cancer --- p.10 / Chapter 1.2 --- Treatment --- p.16 / Chapter 1.2a --- "Surgery, chemotherapy, and others" --- p.16 / Chapter 1.2b --- Response rate of treatments in previous studies --- p.18 / Chapter 1.2c --- Chemotherapeutic Drugs --- p.21 / Chapter 1.2c (1) --- 5-fluorouracil (5-FU) --- p.22 / Chapter 1.2c (2) --- cis-diamminedichloroplatinum (Cisplatin) --- p.23 / Chapter 1.2c (3) --- Doxorubicin (Adriamycin) --- p.23 / Chapter 1.2c (4) --- Daunorubicin --- p.25 / Chapter 1.2c (5) --- Epirubicin --- p.25 / Chapter 1.2d --- Toxicity of chemotherapeutic drugs --- p.26 / Chapter 1.2d (1) --- Side effects of 5-FU --- p.26 / Chapter 1.2d (2) --- "Side effects of anthracyc lines (adriamycin, daunobicin, epuirbicin)" --- p.27 / Chapter 1.2d (3) --- Side effects of cisplatin --- p.28 / Chapter 1.3 --- Mechanisms of drug resistance --- p.28 / Chapter 1.3a --- Drug resistance --- p.28 / Chapter 1.3b --- P-glycoprotein (MDR1 gene) --- p.29 / Chapter 1.3c --- p53 tumor suppressor gene --- p.35 / Chapter 1.4 --- Chemosensitivity testing --- p.40 / Chapter 1.4a --- Original of chemosensitivity testing --- p.40 / Chapter 1.4b --- Non-clonogentic assay --- p.40 / Chapter 1.4c --- Clonogenic assay --- p.42 / Chapter 2 --- AIM OF MY STUDY --- p.44 / Chapter 3 --- MATERIALS AND METHODS --- p.45 / Chapter 3.1 --- Patients --- p.45 / Chapter 3.2 --- Tumor collection and handling procedure --- p.46 / Chapter 3.2a --- Large tumor tissue from gastrectomy --- p.46 / Chapter 3.2b --- Pseudo-biopsies --- p.47 / Chapter 3.3 --- Chemosensitivity testing --- p.48 / Chapter 3.3a --- Cell Plating --- p.48 / Chapter 3.3b --- Drug testing --- p.49 / Chapter 3.4 --- Chemosensitivity analysis --- p.50 / Chapter 3.5 --- Conformational sensitive gel electrophoresis analysis (CSGE) and single strand conformational polymorphism (SSCP) --- p.51 / Chapter 3.5a --- Preparation of genomic DNA --- p.51 / Chapter 3.5b --- PCR condition for CSGE analysis --- p.51 / Chapter 3.5c --- Scanning PCR products by CSGE --- p.52 / Chapter 3.5d --- PCR condition for SSCP analysis --- p.53 / Chapter 3.5e --- Scanning PCR products by SSCP --- p.53 / Chapter 3.6 --- Reverse transcription-polymerase chain reaction (RT-PCR) for multi-drug drug resistance (MDR1) gene --- p.54 / Chapter 3.6a --- Isolation of RNA --- p.54 / Chapter 3.6b --- cDNA synthesis --- p.55 / Chapter 3.6c --- PCR primers --- p.55 / Chapter 3.6d --- Optimalization of PCR condition for MDR1 gene expression --- p.56 / Chapter 3.6e --- PCR of β2-m gene --- p.57 / Chapter 3.6f --- PCR of MDR1 gene and analysis of its expression --- p.57 / Chapter 3.7 --- Immunohistochemistry --- p.58 / Chapter 3.7a --- Immunostaining by DO-7 --- p.58 / Chapter 3.7b --- lmmunohistochemistochemical analysis of p53 protein expression --- p.59 / Chapter 3.8 --- Statistics --- p.59 / Chapter 4. --- RESULTS --- p.60 / Chapter 4.1 --- Chemosensitivity testing --- p.60 / Chapter 4.1a --- Tests completed --- p.60 / Chapter 4.1b --- Number of cases tested for each drug --- p.60 / Chapter 4.1c --- 〇D reading of the background samples --- p.60 / Chapter 4.1d --- Dose-dependent response curve --- p.61 / Chapter 4.1e --- Unique IC50 for each tumor in each drug test --- p.61 / Chapter 4.1f --- Wide distribution of ic50 for anti-tumor drugs --- p.61 / Chapter 4.1g --- Chemosensitivity and tumor histologic type --- p.63 / Chapter 4.1h --- Correlation of ic50 with tumor stage --- p.63 / Chapter 4.2 --- Immunohistochemical staining of p53 protein (DO-7) --- p.64 / Chapter 4.2a --- p53 protein accumulation in samples --- p.64 / Chapter 4.2b --- Correlation of p53 IHC expression and chemosensitivity --- p.64 / Chapter 4.3 --- SSCP and CSGE --- p.65 / Chapter 4.3a --- Detection of abnormal band movement --- p.65 / Chapter 4.3b --- Correlation of p53 mutations with chemosensitivity --- p.66 / Chapter 4.3c --- Concordance between IHC and SSCP/CSGE --- p.66 / Chapter 4.4 --- MDR1 gene expression --- p.67 / Chapter 4.4a --- MDR1 gene expression in normal and tumors --- p.67 / Chapter 4.4b --- Correlation of MDR1 expression and chemosensitivity --- p.68 / Chapter 4.5 --- Pseudobiopsies --- p.68 / Chapter 5 --- DISCUSSION --- p.70 / Chapter 5.1 --- p53 analysis of the tumors --- p.70 / Chapter 5.1a --- Immunohistochemistry versus mutational analysis --- p.70 / Chapter 5.1b --- Methods of mutational analysis --- p.73 / Chapter 5.1c --- Comparing IHC results with previous findings --- p.77 / Chapter 5.1d --- Comparing SSCP/ CSGE results with previous findings --- p.78 / Chapter 5.1e --- Correlation of IHC and SSCP/CSGE results --- p.81 / Chapter 5.2 --- MDR1 expression --- p.85 / Chapter 5.2a --- Methods for detecting MDR1 expression --- p.85 / Chapter 5.2b --- Comparing MDR1 expression results with published data --- p.88 / Chapter 5.2c --- Correlation between chemosensitivity and MDR1 gene expression --- p.92 / Chapter 5.3 --- Chemosensitivity testing --- p.94 / Chapter 5.3a --- Chemosensitivity testing method --- p.94 / Chapter 5.3b --- The chemosensitivity results --- p.102 / Chapter 5.3c --- Chemosensitivity and MDR1 expression --- p.108 / Chapter 5.3d --- Chemosensitivity and p53 immunohistochemical expression… --- p.110 / Chapter 5.3e --- Chemosensitivity and p53 mutations --- p.112 / Chapter 5.3f --- Limitation of this study --- p.115 / Chapter 5.3g --- Pseudobiopsies and large tumor samples --- p.118 / Chapter 6. --- conclusions --- p.121 / figures / appendices / references

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2019-01-23T19:10:52Z No. of bitstreams: 1 Adriana Duarte M. Queiroz.pdf: 895696 bytes, checksum: 1f1af189f22327c9526a39e8514a1ccc (MD5) / Made available in DSpace on 2019-01-23T19:10:52Z (GMT). No. of bitstreams: 1 Adriana Duarte M. Queiroz.pdf: 895696 bytes, checksum: 1f1af189f22327c9526a39e8514a1ccc (MD5) Previous issue date: 2018-11-12 / Atualmente o carcinoma de tireoide (CT) vem apresentado um crescimento da taxa de incidência na maioria dos países (cerca de 1% ao ano). A incidência anual varia entre as populações, mas encontra-se entre 2-3 casos/100 mil homens e 4-9 casos/100 mil mulheres. Para a Paraíba, a estimativa do Instituto Nacional do Câncer para o biênio 2018-2019 é de 5,88/100.000 para mulheres e 2,08/100.000 em homens. Objetivo: Verificar a relação entre fatores clínico-epidemiológicos dos pacientes com carcinoma diferenciado da tireoide (CDT) atendidos em um hospital de referência no Estado da Paraíba e risco de recorrência da doença. Métodos: Tratou-se de um estudo transversal, realizado através da coleta de dados obtidos de prontuários dos pacientes com CDT atendidos na Fundação Assistencial da Paraíba (FAP) entre abril de 2011 a abril de 2018. Foram considerados fatores de risco: história de exposição ocupacional a substâncias ou à radiação ionizante, tabagismo, presença de doença autoimune da tireoide (DAT), neoplasia maligna prévia e história familiar de câncer de tireoide. Foi utilizado o teste de Qui-quadrado para associação de variáveis qualitativas e para análise dos possíveis fatores associados foram utilizados modelos de regressão logística com nível de significância de 5%. Resultados: Foram selecionados 284 pacientes, a maioria do sexo feminino (86,6%), com idade média de 46,3±14,4 anos, cerca de 40% dos indivíduos eram agricultores, 70,6% não referiam exposição ocupacional e 97,6% não referiram exposição à radiação. Quarenta e três (20%) referiam história familiar de CT e 75,7% não apresentavam DAT. A variante papilífero clássica do CDT foi a mais prevalente (69,4%) e 32,7% dos CDT eram multifocais. Na avaliação de risco de recidiva, 98 (34,5%) apresentaram com risco intermediário e 43 (15,1%) com alto risco. A análise univariada identificou ¿idade¿ (OR=1,05; IC=1,046-2,723; p=0,031), ¿zona de moradia¿ (OR=1,87; IC=1,10-3,17; p=0,02), ¿exposição à agrotóxicos¿ (OR=2,03; IC=1,135-3,618; p=0,016), ¿DAT¿ (OR=5,63; IC=1,204-26,351; p=0,045), ¿subtipos histológicos de maior agressividade¿ (OR=5,12; IC=1,037-25,28; p=0,001) e ¿tumor multifocal¿ (OR=2,56; IC=1,527-4,278; p=0,001) como fatores de risco para recidiva, contudo na análise múltipla final, apenas subtipo histológico mais agressivo, exposição ocupacional e tumor multifocal mostraram-se estatisticamente significantes. Discussão: Alguns resultados desse estudo são concordantes com os dados encontrados na literatura como idade ao diagnóstico, maior prevalência do sexo feminino e da variante papilífero clássica do CDT. Na regressão múltipla, tumores multifocais e variantes consideradas mais agressivas também foram concordantes. Apesar da exposição ocupacional mostrar associação estatisticamente significante com risco de recidiva, esse estudo apresenta limitação quanto ao desenho pois exposição e doença não são condições contemporâneas e não foi mensurado o tempo de exposição e se há presença de contato atual ou passado com as substâncias. Conclusão: Variantes histológicas mais agressivas e tumores multifocais são fatores de risco para recidiva da doença. Exposição ocupacional a agrotóxicos apresenta controvérsias quanto a esse risco, portanto novos estudos são necessários para esclarecer essa relação. / Currently thyroid carcinoma (TC) has shown an increase in the incidence rate in most countries (about 1% per year). The annual incidence varies among populations, however it is between 2-3 cases / 100,000 men and 4-9 cases / 100,000 women. In the context of Paraíba, the National Cancer Institute's estimate for the biennium 2018-2019 is 5.88 / 100,000 for women and 2.08 / 100,000 for men. Objective: To verify the relationship between clinical and epidemiological factors of patients with differentiated thyroid carcinoma (DTC) treated at a reference hospital in the state of Paraíba, and risk of recurrence of the disease. Methods: The present paper presents a cross-sectional study, carried out through the collection of data obtained from the medical records of patients with DTC attended at Fundação Assistencial da Paraíba (FAP) from April 2011 to April 2018. It were considered risk factors as: history of occupational exposure to substances or ionizing radiation, smoking, presence of autoimmune thyroid disease (AITD), previous malignant neoplasm, and family history of thyroid cancer. It was used the Chi-square test for the association of qualitative variables and it were used logistic regression models with a significance level of 5% for analysis of possible associated factors. Results: 284 patients were selected, most of them female (86.6%), with an average age of 46.3 ± 14.4 years; about 40% of the individuals were farmers; 70.6% did not report occupational exposure; and 97.6% did not report radiation exposure. Forty-three (20%) reported a family history of TC and 75.7% did not present DTC. The classical variant papillary of DTC was the most prevalent (69.4%) and 32.7% of DTCs were multifocal. In the evaluation of risk of relapse, 98 (34.5%) presented intermediate risk and 43 (15.1%) high risk. The univariate analysis identified ¿age¿ (OR=1,05; IC=1,046-2,723; p=0,031), "dwelling zone" (OR=1,87; IC=1,10-3,17; p=0,02), "pesticides exposure" (OR=2,03; IC=1,135-3,618; p=0,016), "AITD" (OR=5,63; IC=1,204-26,351; p=0,045), "histological subtypes of greate aggressiveness" (OR=5,12; IC=1,037-25,28; p=0,001) and "multifocal tumor" (OR=2,56; IC=1,527-4,278; p=0,001) as risk factors for recurrence, nevertheless in the final multiple analysis, only more aggressive histological subtype, occupational and multifocal tumor were statistically significant. Discussion: Some results of this study are consistent with the data found in the literature such as age at diagnosis, higher prevalence of females and the classical variant papillary of DTC. In the multiple regression, multifocal tumors and variants considered more aggressive were also concordant. Regardeless of occupational exposure shows a statistically significant association with risk of recurrence, this study has a limitation concerning the design since exposure and disease are not contemporary conditions, the time of exposure was not measured, and also if there is presence of current or past contact with the substances. Conclusion: More aggressive histological variants and multifocal tumors are risk factors for recurrence of the disease. Occupational exposure to agrochemicals presents controversies regarding this risk, therefore new studies are needed to clarify this relationship.

I Sverige insjuknar 250-300 barn varje år av cancer. De cancertyper som drabbar barn är vanligtvis inte de samma som vuxna utvecklar. Olika cancerformer kräver olika typer av behandling, dessa är cytostatika, operation samt strålbehandling. Sjuksköterskan skall kunna möta föräldrar och barn samt uppfatta deras lidande för att kunna tillfredställa behovet av en god omvårdnad. För föräldrarna upplevs barnets cancerdiagnos ofta som ett svårt lidande, som kan kännas helt outhärdligt. När ett barn är svårt sjukt i cancer innebär detta en långvarig kontakt med sjukvården för hela familjen. Det är en svår och stressfull situation för familjen och deras välbefinnande påverkas av vårdarens agerande.Syftet med studien är att beskriva föräldrarnas uppfattning av vad som är god vård i samband med behandling av det cancersjuka barnet på sjukhus. Metoden är en litteraturstudie där åtta kvalitativa artiklar analyseras enligt Evans (2003) metod.Resultatet presenteras utifrån fem teman som är: Anpassad information, Kontinuerlig vårdrelation, Emotionellt stöd, Familjens delaktighet i vården samt Lugn vårdmiljö.Det mest framträdande i resultatet är att information är grunden till att föräldrarna skall uppleva att deras barn får en god vård. En adekvat given information med lyhördhet inför den enskilde förälderns behov och önskemål resulterar i en mer tillfredställd förälder. / Program: Fristående kurs

INTRODUÇÃO: As necroses de retalhos da mastectomia (RM) afetam até um terço das mulheres submetidas à reconstrução imediata de suas mamas e aumentam o risco de outras complicações e, por fim, de falha da reconstrução. A glicemia capilar (GC) tem sido usada para monitorização clínica de mudanças agudas na perfusão tecidual de retalhos livres. Nós avaliamos a acurácia diagnóstica da GC para predição de necrose de espessura total (NET) em RM após mastectomia com reconstrução imediata. MÉTODOS: Duzentos e trinta amostras de sangue para mensuração de GC foram coletadas ao longo da ferida operatória de 30 mulheres submetidas à ressecção total de suas mamas. Uma amostra de sangue periférico para mensuração da GC periférica foi colhida em cada paciente. Fotografias da mama foram capturadas no final da cirurgia e no pós-operatório (entre 7 e 14 dias). Estas fotos foram comparadas por um investigador cego aos valores das GCs para determinar a ocorrência de necrose e em que pontos de coleta ela ocorreu. A associação entre GC e a ocorrência de NET foi testada usando modelos de equações de estimação generalizadas. Nós analisamos a acurácia diagnóstica da GC como um teste intraoperatório de predição de NET usando curvas de Característica de Operação do Receptor e a estatística C (ou área sob a Curva). RESULTADOS: NET ocorreu em 21/230 (9.1%) pontos de coleta aleatória de 9/30 pacientes (30%). Cada decréscimo de 10mg/dL no valor absoluto da GC (GCA) foi associada a uma razão de chance (RC) de 1.71 (1.21-2.41; p=.002) para NET e C=.78 (.65-.92). Cada queda em 10% da razão entre a GC e a GC periférica (GCr) foi associada com uma RC=1.77 (1.23-2.55; p=.002) para NET e C=.75 (.47-.89). Para pontos de corte de GCA < 90 mg/dL ou GCR < 80%, a especificidade e sensibilidade para o teste como uma ferramenta de rastreamento para NET foi de 67% (14/21) e 86% (179/209), respectivamente. CONCLUSÕES: A performance da GC como uma ferramenta de rastreamento para NET foi sub ótima, com um poder discriminatório moderado. No entanto, sua mensuração pode ser informativa como uma ferramenta adicional para esta avaliação ainda altamente subjetiva. As associações observadas entre a GC e a ocorrência de NET pós-operatória suportam nossa hipótese de que os tecidos dos RM sob stress perfusional demonstram alterações metabólicas precoces / INTRODUCTION: Mastectomy skin flap (MSF) necrosis affects up to one-third of patients undergoing immediate breast reconstruction and increases the risk other complications rand, ultimately, reconstruction failure. Interstitial glucose level (IGL) has been used clinically to monitor acute changes in local tissue perfusion in free flaps. We evaluated the accuracy of IGL for prediction of full thickness necrosis (FTN) in MSF after mastectomy with immediate breast reconstruction. METHODS: Two hundred and thirty random blood samples for IGL measurement along the surgical wound edges of 30 women undergoing unilateral total breast resection with immediate reconstruction were collected. At the same time, a peripheral blood sample was also tested. Pictures of the breast were taken after skin closure with markings identifying the position where the samples were taken and 7 to 14 days post-operatively. These pictures were compared by an investigator blinded to IGL values to determine the occurrence of FTN and at which IGL sampling sites it occurred. The association between IGL and the occurrence of FTN was tested using generalized estimating equation models. We analyzed the diagnostic accuracy of IGL as an intraoperative test for FTN with the use of Receiver Operating Curves and their C-statistics (or Area Under the Curve). RESULTS: FTN occurred in 21/230 (9.1%) random sampling points from 9/30 patients (30%). Each 10mg/dL decrease in absolute IGL (IGLA) was associated with an OR=1.71 (1.21-2.41; p=.002) for FTN and C=.78 (.65-.92). Each 10% decrease in the ratio of IGL to peripheral glucose level (IGLR) was associated with an OR=1.77 (1.23-2.55; p=.002) for FTN, with C=.75 (.47-.89). For cut-offs of IGLA < 90 mg/dL or IGLR < 80%, the specificity and sensitivity of the test as a screening tool for FTN were 67% (14/21) and 86% (179/209), respectively. CONCLUSIONS: The performance of IGL as a screening tool for FTN was suboptimal, with a moderate discriminative power for FTN. However, it can be informative as an additional tool to the still highly subjective intraoperative evaluation of MSFs. The observed association between IGL measurements and post-operative FTN supports our hypothesis that tissues of the MSF under perfusion stress will show early metabolic alterations