CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Este trabalho aborda a influÃncia da incisÃo para-areolar no quadrante superior externo da mama, na localizaÃÃo do linfonodo sentinela em modelo canino. A BiÃpsia do linfonodo sentinela (BLS) à um mÃtodo de amostragem seletiva, minimamente invasivo, altamente sensÃvel em predizer o estado axilar, podendo evitar o esvaziamento ganglionar em pacientes sem comprometimento metastÃtico. Mulheres, com cirurgias mamÃrias previas, foram excluÃdas da realizaÃÃo da BLS por muitos cirurgiÃes por acreditar que teriam um Ãndice de falso negativo elevado, inviabilizando o mÃtodo. Outros mastologistas passaram a empregar, empiricamente, a injeÃÃo do marcador corante ou radioativo acima da borda da incisÃo prÃvia, porÃm fica a dÃvida se o gÃnglio identificado à realmente o Linfonodo Sentinela (LS). Este trabalho experimental, em modelo canino, tem como objetivo identificar a influÃncia das incisÃes para-areolares prÃvias, no quadrante superior externo (QSE) da mama na identificaÃÃo do linfonodo sentinela. à utilizado o radiocolÃide TecnÃcio99 injetado na derme sub-areolar das mamas torÃcicas craniais, para marcar o LS. Esperado o tempo de migraÃÃo do radiofÃrmaco para axila e identificado o local de marcaÃÃo com probe. Procede-se incisÃo arciforme para- areolar no QSE, entre 9 e 12h à direita e 12 e 3 h à esquerda, a 2cm do mamilo. O corante azul patente Ã, entÃo, injetado na borda superior destas incisÃes. No ponto marcado com o gama-probe à realizada a incisÃo axilar mÃnima, onde o LS à identificado com auxÃlio do probe, que capta a radiaÃÃo do gÃnglio, eou pela visualizaÃÃo direta do linfonodo impregnado com o corante. SÃo comparadas duas tÃcnicas de local de injeÃÃo e a concordÃncia entre os mÃtodos de identificaÃÃo do LS. Os experimentos da pesquisa ocorreram entre Janeiro 2008 e Maio 2009. A amostra à composta de 40 mamas torÃcicas craniais, oriundas de 23 cadelas adultas, sem raÃa definida, da espÃcie Canis familiaris. A anÃlise estatÃstica foi realizada com o auxÃlio do programa Graphpad e utilizados o Teste de McNemar e Coeficiente de ConcordÃncia de Kappa. Os resultados demonstram que em 95% das mamas estudadas (3840) obtiveram o LS identificado na axila apÃs a injeÃÃo de tecnÃcio na regiÃo subareolar e em 82% dos casos (33/40) coraram com azul patente injetado no bordo superior da incisÃo padronizada. Os resultados obtidos indicam a concordÃncia entre os mÃtodos em 82% dos casos na identificaÃÃo do LS (3340). As incisÃes para-areolares prÃvias, nos quadrantes superiores externos, das mamas torÃcicas craniais da cadela, nÃo demonstram interferir, de maneira significante, na BLS quando o corante à injetado na borda superior da incisÃo. O linfonodo encontrado a partir de injeÃÃo na borda superior da incisÃo previa, corresponde ao linfonodo sentinela da mama da cadela, em 95% dos casos (3233). / This paper discusses the influence of para-areolar incision in the upper outer quadrant of the breast for the location of the sentinel lymph node in canine model. Sentinel lymph node biopsy (SLNB)―a minimally invasive selective sampling technique highly predictive of the condition of the armpit―can spare metastasis-free patients from unnecessary axillary dissection. The high incidence of false-negative results has led many surgeons to no longer indicate SLNB to women with previous breast surgery. Some mastologists prefer to empirically inject a dye or radio-labelled marker above the border of the previous incision, though it is not always clear if the identified ganglion is in fact the sentinel lymph node. The objective of the present study was to evaluate the influence of previous para-areolar incisions in the upper outer quadrant (UOQ) of the breast upon the identification of the sentinel lymph node (SLN) in a canine model. The SLN was marked with Technetium-99m (99mTc) injected into the subareolar skin of the cranial breast. Once the marker had migrated to the axilla and the marked site had been identified with a gamma probe, an arcuate para-areolar incision was performed 2 cm from the nipple in the UOQ (between the 9 and 12 oâclock position on the right side, and between the 12 and 3 oâclock position on the left side). Patent blue dye was then injected above the upper border of the incision. At the marked site a minimal axillary incision was made and the SLN was identified by gamma probe and/or by direct visualization of the dye. The agreement between the two injection sites and the two SLN identification methods was determined. The experiments were carried out between January 2008 and May 2009 on a sample of 40 cranial breasts of 23 adult females of the species Canis familiaris. Using the statistics software Graphpad, the data were submitted to the McNemar test and the Kappa agreement coefficient was calculated. Our findings show that in 95% (38/40) of the breasts the SLN was identified by injection of 99mTc in the subareolar region, and that in 82% (33/40) of cases the SLN was identified by injection of patent blue dye above the upper border of the incision. Thus, the methods agreed in 82% (33/40) of cases. Previous para-areolar incisions in the UOQ of the cranial breasts did not interfere significantly with the biopsy when the dye was injected above the upper border of the incision. The lymph node identified by injection above the upper border of the previous incision corresponded to the SLN in 95% (32/33) of cases.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A gastrectomia com linfadenectomia ampliada ainda à o padrÃo ouro para o tratamento curativo do cÃncer de estÃmago (CaE), embora este procedimento possa levar a alto Ãndice de morbidade ou mortalidade, principalmente nos pacientes que nÃo apresentem disseminaÃÃo linfÃtica da doenÃa. A pesquisa do linfonodo sentinela (LS), jà consagrada nos tumores iniciais de mama e nos melanomas, apresenta-se cada vez mais freqÃente no trato digestÃrio, em especial no CaE com resultados animadores. Estudos iniciados nos meados do ano 2000 retratam busca crescente e bastante prÃspera para esclarecimento desta questÃo. O objetivo deste trabalho à elaborar um modelo experimental que possa demonstrar tecnicamente, em laboratÃrio, a viabilidade da pesquisa do LS no antro gÃstrico da cadela. Foram estudadas 25 cadelas com peso aproximado de 11 Kg e idade de 01 a 02 anos, sem raÃa definida (SRD), clinicamente saudÃveis, proveniente do Centro de Controle de Zoonoses do MunicÃpio de Fortaleza (CCZ) que tinham programaÃÃo para eutanÃsia. Com escolha aleatÃria, estes animais foram estudados individualmente e semanalmente. Utilizou-se, separadamente, TecnÃcio (99mTc) com traÃador/colÃide Fitato e corante vital azul patente V Guerbert 2,5 % (AP) injetados a 01 cm do piloro, na pequena curvatura no antro gÃstrico da cadela e analisados nos tempos zero, 05, 10, 15 e 20 minutos. ApÃs este perÃodo realizou-se pesquisa âin vivoâ do local de injeÃÃo do marcador e linfonodos encontrados e âex-vivoâ destes linfonodos. Para o estudo com o 99mTc utilizou-se o aparelho Gamma Probe modelo Nuclearlab DGC-II - detector para cirurgia radioguiada e sonda captadora de irradiaÃÃo acoplada com unidade de contagem e rastreamento sonoro e para o AP, visÃo direta. Para a anÃlise estatÃstica utilizou-se o teste de McNemar e o Coeficiente de ConcordÃncia de Kappa. Foi estabelecido em 5% o nÃvel de significÃncia (p≤0,05). Com o uso do 99mTc isolado foi identificado a presenÃa do LS em 20 animais (80%). Quando se utilizou o corante AP isolado a presenÃa do LS foi identificada em 24 animais (96 %). NÃo houve significÃncia estatÃstica quanto ao uso destes marcadores para a pesquisa do LS no antro gÃstrico da cadela. Concluiu-se que (1) O estÃmago da cadela à adequado para modelo experimental de pesquisa âin vivoâ do linfonodo sentinela e (2) O tecnÃcio (99mTc) e corante vital â azul patente V Guerbert 2,5 % (AP) sÃo eficientes como marcadores de linfonodo sentinela do antro gÃstrico da cadela. / The gastrectomy with extensive lymphadenectomy still is the gold standard for the dressing treatment of the gastric cancer (GC), even so these procedures can take high index of morbidity or mortality, mainly in the patients who do not present lymphatic dissemination of the illness. The research of sentinel lymph node (SLN), already consecrated in the initial tumors of breast and the melanomas, presents each time more frequent for upper gastrointestinal cancers, specially in GC with encouraging results. Studies initiated in the middles of 2000 portray increasing and sufficiently prosperous search for clarification of this question. The objective of this work is to elaborate an experimental model that can demonstrate technically, in laboratory, the research viability of SLN in gastric antrum of the dog. 25 female dogs had been studied with approach weight of 11 kg and age of 01/02 years, without definite race (WDR), healthful clinically, proceeding from the Control Center of Zoonosis of Fortaleza City with programming for euthanasia. With random choice, these animals had been studied individually and weekly. It was used, separately, radioisotopic 99mtechnetium labeled phytate and patent blue dye (V Guerbert 2.5%) injected at 01 cm above the piloro, on the small bending in the antrum gastric of the dog and analyzed in the times zero, 05, 10, 15 and 20 minutes. After this period, the injection place of the markers and gastric lymph nodes were appraised âin vivoâ (in the animal) and the gastric lymph nodes âex vivoâ (out of the animal). For the study with the 99mtechnetium it was used the device Gamma Probe model Nuclearlab DGC-II (radioguiada surgery with sounding lead of irradiation connected to unit of counting and sonorous tracking) and for the patent blue dye, direct vision. For the analysis statistics were used the test of McNemar and the Quantify agreement with Kappa. The level of significance was established in 5% (p≤0,05). When the radioisotopic 99mtechnetium labeled phytate was used single, the LS was identified in 20 animals (80%). With the patent blue dye single, in 24 animals (96%). There is no statistic significance with the use of those markers for the LS research in the gastric antrum of the dog. The conclusions are (1) The stomach of the dog is adjusted for experimental model in alive research of the sentinel lymph node (2) The radioisotopic 99mtechnetium labeled phytate and patent blue dye (V Guerbert 2.5%) are efficients as markers of sentinel lymph node of the dogâs gastric antrum.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / O cÃncer de vulva corresponde a aproximadamente 1% das neoplasias malignas da mulher e de 3% a 5% de tumores genitais femininos. 90% destes sÃo carcinomas espino-celulares, curÃveis quando diagnosticado precocemente. O tratamento radical inclui o esvaziamento inguinal bilateral na maioria dos casos. Aproximadamente 30% das pacientes operÃveis tÃm disseminaÃÃo linfonodal, as 70% restantes tÃm mutilaÃÃo desnecessÃria. A possibilidade de aplicar o conceito de linfonodo sentinela, na conservaÃÃo dos linfonodos regionais da vulva, ainda nÃo à consenso. O modelo experimental na vulva da cadela à um passo importante no reconhecimento das peculiaridades da drenagem linfÃtica deste ÃrgÃo pela similaridade com a drenagem em humanos. Este trabalho experimental, em modelo canino tem como objetivo apresentar o modelo para a pesquisa do linfonodo sentinela na vulva da cadela usando o Azul Patente e Fitato de TecnÃcio; avaliar o Azul Patente como marcador do linfonodo sentinela da vulva da cadela; avaliar o Fitato de TecnÃcio como marcador do linfonodo sentinela na vulva da cadela, comparar os mÃtodos obtidos pelas duas tÃcnicas. Foram utilizados nos procedimentos 25 cadelas, adultas, sadias, com peso variando entre 10 e 12kg. InjeÃÃo de 5ÂCI de TecnÃcio na regiÃo vulvar, com espera de 30â. Rastreamento com probe das regiÃes de drenagem vulvar, injeÃÃo de 0,5mL de azul patente na regiÃo vulvar, com espera de 15â. Definidos os pontos âquentesâ com o probe, por incisÃes inguinais abordou-se o linfonodo, avaliando-se com o probe o linfonodo sentinela in-vivo e ex-vivo, anotando-se os valores; registrados os linfonodos corados e nÃo corados com azul patente; comparados os dois mÃtodos. Em 88% dos linfonodos houve presenÃa da lateralidade, tal diferenÃa foi significante (&#61539; = 28.88 e p<0,0001). NÃo houve diferenÃa significante (p>0,05) entre os lados direito e esquerdo, quanto à intercessÃo dos dois mÃtodos. Os nÃveis de radiaÃÃo detectados foram idÃnticos em ambos os lados (p>0,05), tambÃm nÃo foi verificada diferenÃa significante (p>0,05) em ambos os lados, nas contagens in vivo e ex vivo, e no nÃmero de linfonodo corado com azul patente. O modelo experimental apresentado foi capaz de definir o linfonodo sentinela utilizando o Azul Patente e TecnÃcio(99mTc). A identificaÃÃo do linfonodo sentinela à exequÃvel com Azul Patente no mapeamento da cadeia linfÃtica; o mapeamento linfÃtico com TecnÃcio(99mTc), permite identificar com detalhes o sistema de drenagem linfÃtica; nÃo houve diferenÃa significante entre os dois mÃtodos (p=1,0), Azul Patente e TecnÃcio(99mTc).

A avaliação de linfonodos é parte importante do estadiamento das neoplasias mamárias, muito comum em cadelas, podendo auxiliar no estabelecimento do prognóstico e na escolha da melhor conduta terapêutica. Neste trabalho, dentre as várias técnicas de exame que permitem a avaliação de linfonodos, foi utilizada a ultra-sonografia. A avaliação ultra-sonográfica em modo B possibilitou avaliar tamanho, contorno, borda, forma, arquitetura, ecotextura e ecogenicidade do parênquima dos linfonodos e, em modo Doppler, a quantidade e distribuição dos seus vasos internos. Os objetivos deste trabalho foram identificar as características ultra-sonográficas mais importantes utilizadas para classificar os linfonodos em metastáticos e não-metastáticos, estabelecer elementos de confiabilidade do ultra-som como ferramenta para diferenciar linfonodos metastáticos de não-metastáticos e estabelecer procedimentos que permitam ao exame ultra-sonográfico de linfonodos, para essa classificação, ser reprodutível. Foram examinados 63 linfonodos inguinais superficiais de 30 cadelas com tumor em pelo menos uma das mamas inguinais ou abdominais caudais. Após o exame, cada linfonodo foi classificado como metastático ou não-metastático. A impressão diagnóstica do exame ultra-sonográfico foi associada aos resultados do exame histopatológico dos linfonodos obtendo-se uma taxa de concordância de 92,5%, índice de sensibilidade de 94,1%, índice de especificidade de 92%, valor preditivo positivo de 0,8 e valor preditivo negativo de 0,9787. As principais características ultra-sonográficas que classificaram um linfonodo inguinal superficial como metastático foram o contorno irregular, forma arredondada com razão C/E menor que dois, arquitetura desorganizada, ecotextura homogênea ou heterogênea, ecogenicidade alterada, vascularização elevada e de localização periférica. Quanto aos linfonodos não-metastáticos, as principais características ultra-sonográficas identificadas foram contorno regular, forma ovalada com razão C/E maior que dois, arquitetura preservada, ecotextura preservada, ecogenicidade normal, vascularização discreta a pequena e de localização hilar. O exame ultra-sonográfico dos linfonodos regionais constitui importante ferramenta na detecção de metástase e sugere-se incluí-lo como rotina do estadiamento de neoplasias mamárias em cadelas. / The evaluation of lymph nodes is an important part of the staging in case of mammary tumors, which are very common in female dogs. It can help in establishing a prognosis and chosing the best therapeutic procedures. In this study we used ultrasonography to assess lymph nodes within a variety of imaging techniques. B mode ultrasonography was used to provide information on size, edge, nodal borders, shape, architecture, echotexture and echogenivity of lymph nodes and Doppler ultrasonography to evaluate the quantity and distribution of the intranodal vessels. The objectives of this work were to identify which features in an ultrasound image can be associated to the metastatic or non-metastatic character of a lymph node; to establish the accuracy of the ultrasound as a tool to differentiate between metastatic and non-metastatic behavior and to establish procedures that permit the reproducibility of the results. Sixty three lymph nodes in thirty female dogs with mammary tumors were examined. We chose female dogs that had involvement of at least one of the inguinal or caudal abdominal mammary glands. Ultrasound imaging and histopathological exams were performed for each lymph node. Based on its ultrasound imaging, each lymph node was classified as metastatic or non-metastatic. When the ultrasound diagnostic was matched to the results of the histopathologic exam it was found that the classification of the lymph nodes using ultrasound imaging was correct in 92.5% of the cases, with sensibility of 94.1%, specificity of 92%, positive predictive value of 0.8 and negative predictive value of 0.9787. The main features in an ultrasound image associated with a metastatic superficial inguinal lymph node were irregular edge, round shape with long to short axis ratio lower than 2, loss of internal structure, homogeneous or heterogeneous echotexture, alteration of the echogenicity and high and peripheral vascularity. Relating to non metastatic lymph nodes, the main ultrasonographic characteristics were regular edge, oval shape with long to short axis ratio higher than 2, maintenance of internal structure, normal echo genetics and low hilar vascularity. The ultrasound imaging of regional lymph nodes is an important tool to detect metastasis and it is suggested that it becomes a regular procedure in the staging of canine mammary tumors.

Orientadores: Luiz Carlos Zeferino, Fernando Carlos de Landér Schmitt / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T10:11:46Z (GMT). No. of bitstreams: 1 Alvarenga_CesarAugusto_D.pdf: 4979947 bytes, checksum: 8da78ad01d29e47c7c97bb4d231ee04b (MD5) Previous issue date: 2011 / Resumo: A maioria dos carcinomas invasivos da mama são classificados como carcinoma ductal invasivo, sem outras especificações (CDI-SOE), enquanto que cerca de 25% são definidos como tipos especiais histológicos (TEH). Esses TEH de carcinomas da mama são categorizados em pelo menos 17 entidades patológicas distintas. Como a maioria dos estudos realizados na literatura em relação à classificação molecular (luminais A e B, sobre expressão de HER2, "basal-like") tenham utilizado somente CDI-SOE e lobulares invasivos, um estudo com mais TEH seria necessário. A CK19 pode ser utilizada como método de avaliação do linfonodo sentinela através de uma técnica molecular chamada de OSNA (amplificação de ácido nucléico de um passo). A expressão de sua positividade foi avaliada somente nos carcinomas ductais, lobulares, medulares e de pequenas células. Realizado tissue microarray (TMA) no IPATIMUP (Porto-Portugal) de 157 casos selecionados dos arquivos do Instituto de Patologia de Campinas. Obtido um total de 121 e 116 casos no TMA do perfil molecular e da CK19, respectivamente, estes incluíram carcinomas tubulares, mucinosos, papilares encapsulados e invasivo, lobulares, micropapilares, medulares, metaplásicos, apócrinos e mistos. Foram utilizados marcadores imunoistoquímicos tais como: RE, RP, RA (somente nos apócrinos), HER2, Ki67, P-caderina, CK5, EGFR e p63 para classificá-los quanto à classificação molecular e CK19 para avaliar sua expressão na mama antes da realização da técnica de OSNA em linfonodo sentinela. Tubulares, papilares e mucinosos foram todos luminais A e B, dado semelhante ao perfil de expressão genética; medulares e metaplásicos foram quase todos "basais-like" (76.2% e 90%, respectivamente), enquanto que ao nível transcriptômico, todos os casos pertencem ao subtipo "basallike"; micropapilares foram luminais A e B e sobre-expressão de HER2, sendo que ao nível transcriptômico são praticamente todos luminais B devido à alta expressão de HER2; apócrinos foram os mais heterogêneos de todos com casos luminais A e B, sobre-expressão de HER2 e "basais-like", dado diferente ao nível transcriptômico que revela o subtipo "molecular apócrino" (RE-/RA+/HER2- ou +). O risco relativo do Ki67 aumentou entre os TEH, sendo que o carcinoma medular teve 110 vezes mais risco de aumento do Ki-67 em relação ao tubular. A CK19 foi expressa em 98.2% dos TEH de carcinomas da mama, dado idêntico ao estudo anterior de Chu et al, sendo que sua positividade aumentou nos casos em que o bloco de parafina foi inteiramente estudado, pois sua marcação foi focal em muitos casos avaliados no TMA. Isso pode produzir eventualmente resultados falso-negativos nas "corebiopsies" / Abstract: Most invasive breast carcinomas are classified as invasive ductal carcinoma, not otherwise specified (IDC-NOS), while approximately 25% are defined as special histological types (HST). These HST of breast carcinomas are categorized into at least 17 distinct pathological entities. Most studies in the literature regarding the molecular classification (luminal A and B, HER2- overexpression, "basal-like") were evaluated only in IDC-NOS and in lobular invasive carcinoma, a study with more HST of breast carcinoma would be necessary. The CK19 can be used as a method of evaluation of sentinel lymph node using a molecular technique called OSNA (one step acid nucleic amplification). The expression of CK19 positivity was assessed only in ductal, lobular, medullary and small cell carcinomas. It was performed tissue microarray (TMA) in IPATIMUP (Porto-Portugal) of 157 cases selected from the archives of the Instituto de Patologia de Campinas, a private laboratory. A total of 121 and 116 TMA cases in the molecular profiling and in the CK19 studies was obtained, respectively, including tubular, mucinous, papillary encapsulated and invasive, lobular, micropapillary, medullary, metaplastic, apocrine and mixed carcinomas. It was used immunohistochemical markers such as ER, PR, RA (only in apocrine carcinomas), HER2, Ki67, P-cadherin, CK5, EGFR and p63 to classify them as the molecular classification and as the CK19 expression in the breast before performing the technique of OSNA in sentinel lymph node. Tubular, papillary and mucinous were all luminal A and B, as similar as the geneexpression profiling; medullary and metaplastic were almost all "basal-like" (76.2% and 90%, respectively), while at transcriptome level, all cases belong to subtype "basal-like"; micropapillary was luminal A and B and HER2- overexpression and in the transcriptomic level was virtually all luminal B due to high expression of HER2; apocrine was the most heterogeneous tumours of our study with luminal A and B, HER2-overexpression and "basal-like" cases. This data was different from transcriptomic level that revealed the "molecular apocrine" subtype (RE-/ RA+/ HER2- or +). The relative risk of Ki67 increased between HST, because medullary carcinomas had 110 times more risk of increased Ki-67 than tubular carcinomas. The CK19 was expressed in 98.2% of HST of breast carcinomas, data identical to the Chu et al study, and the positivity increased in cases where the entire paraffin block had been fully studied, because its labeling was focal in many cases evaluated on TMA. This CK19 focal expression can produce false-negative results in the breasts "corebiopsies" / Doutorado / Oncologia Ginecológica e Mamária / Doutor em Ciências da Saúde

Orientador: Antônio José Maria Cataneo / Resumo: Introdução: No melanoma primário, a aplicabilidade da biópsia de linfonodo sentinela (BLS), seguida ou não de esvazimento linfonodal (EL) é conhecida. Na recidiva locorregional (RL) de melanoma, alguns serviços tendem a indicá-la, buscando estadiamento mais acurado para embasar condutas individualizadas aos pacientes, ainda que as evidências sejam insuficientes. Objetivo: Avaliar o sucesso da BLS no encontro do linfonodo sentinela (LNS) e sua positividade na RL. Comparar a sobrevida entre os pacientes com LNS positivo e negativo. Verificar diferença na sobrevida pós EL. Métodos: Revisão sistemática, através das bases MEDLINE via PUBMED, LILACS, SCOPUS, EMBASE e CENTRAL, buscando estudos experimentais e observacionais sobre BLS na RL de melanoma. Desfechos avaliados: sucesso na BLS pelo encontro do LNS, positividade para melanoma no LNS; sobrevida no subgrupo LNS positivo comparado com o negativo; sobrevida livre de doença no subgrupo LNS positivo comparada com o negativo; sobrevida dos pacientes submetidos ao EL. Para metanálises, utilizaram-se RevMan 5.3 e StatsDirect 3.0.121. Resultados: Foram identificados 1872 estudos, destes, seis estudos observacionais foram incluídos, totalizando 449 pacientes. O LNS foi encontrado em 98% das BLS (IC 95-100%, I2=53,7% - seis estudos). LNS com 32% de positividade para melanoma (IC 19-47%, I2= 84,6% - seis estudos). A chance de sobrevida global em cinco anos foi 2,49 vezes maior no subgrupo com LNS negativo (IC 95% 1,41-4,38, I2=0% - qua... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: In primary melanoma, the applicability of sentinel lymph node biopsy (SLB), followed or not by complete lymph node dissection (CLND) is known. In locoregional recurrence (LR) of melanoma, some groups may indicate it for more accurate staging to support individualized management, even with scarce evidence. Objective: To evaluate success in SLB and its positivity in LR. Compare survival between patients with positive and negative sentinel lymph node (SLN). Check for survival modification after CLND. Methods: Systematic review through databases such as MEDLINE via PUBMED, LILACS, SCOPUS, EMBASE and CENTRAL, searching for experimental and observational studies on SLB in melanoma LR. Outcomes assessed: success in SLB by finding the SLN, positivity for melanoma in the SLN; survival in the positive SLN subgroup compared to the negative one; disease-free survival in the positive versus negative SLN subgroup; survival of patients undergoing CLND. For meta-analyzes, RevMan 5.3 and StatsDirect 3.0.121 were used. Results: The total number of patients in six observational studies was 449, over 1872 studies indentified. The SNL was found in 98% of SLB (95-100% CI, I2 = 53.7%, 6 studies). SLB detected 32% positivity for melanoma on SNL (CI 19-47%, I2 = 84.6%, 6 studies). The chance of five year overall survival was 2,49 higher in the negative SNL subgroup (95% CI 1.41-4.38, I2 = 0%, 4 studies). Meta-analyzes were not performed due to lack of objective data for disease-free survi... (Complete abstract click electronic access below) / Doutor

BACKGROUND: Breast cancer is the most common cancer type in women, with 276,480 women diagnosed with breast cancer in the United States in 2020.1 Death from breast cancer is usually caused by metastasis to distant sites, rather than from the primary tumor itself.2 Regional spread of breast cancer to the tumor draining lymph nodes (TDLN) often precedes further dissemination to the rest of the body, and as such is an important prognostic tool during cancer diagnosis and staging.3 During tumor growth, multiple immune cells and stromal cells in both the primary tumor microenvironment (pTME) and the TDLN undergo changes that promote tumor growth, metastasis and immune evasion in the TDLN and to the rest of the body. Among breast cancer subtypes, triple negative breast cancer (TNBC) is one of the most aggressive, and is most likely to be resistant to traditional chemotherapies, has the worst 5-year survival percentage, regardless of stage.4 Additionally, human growth factor receptor-2 (Her2) positive breast cancers are aggressive breast cancers as well, and Her2+ breast cancers are most likely to metastasize to the TDLN.5 PROBLEM: Little is known about how breast cancer cells induce genetic or transcriptomic changes in immune cells and stromal cells in the lymph node microenvironment and pTME as cancer cells metastasize to the TDLN. OBJECTIVE: To elucidate changes observed in immune and stromal cells in the TDLN via single cell sequencing, and to quantify changes in exhaustion status of lymphocytes in the metastatic TDLN microenvironment that may be causal of lymph node metastasis. METHODS: With a bioinformatics approach on single cell RNA sequencing, and with flow cytometry, we will measure changes in the transcriptomes of cells in the primary tumor microenvironment and the TDLN and compare changes in the primary site, tumor draining lymph node, and a normal lymph node. We measure changes in the expression of canonical exhaustion markers and inhibitory receptors: Tim-3, Lag-3, Tigit, CTLA-4, PD-1, and CD160 in lymphocytes in the metastatic TDLN and nonmetastatic spleens in Balb/c mice with flow cytometry. Additionally, we measured changes in myeloid and lymphoid populations in the spleens and lymph nodes with flow cytometry. RESULTS: B cell accumulation was observed in both the single cell RNA sequencing analysis and via flow cytometry in both the metastatic TDLN itself and in the spleens of mice with metastasis to the TDLN. Increased RNA of exhaustion markers in CD8+ T cells was observed in the primary tumor samples. Additionally, a trend of increased Natural Killer cells, B cells, naive and memory CD4+ and CD8+ T cells expressing canonical exhaustion markers was observed in both the metastatic TDLNs and the spleens of mice with cancer, indicating systemic immune suppression may occur as TNBCs and Her2+ breast cancers metastasize to the TDLN. / 2022-11-24T00:00:00Z

Introduction: Sentinel lymph node biopsy is an established method used to investigate the riskof lymphatic metastasis especially in breast cancer and melanoma patients. SPECT/ CT isconsidered to be an advantageous method in mapping of sentinel nodes. Aim: The aim of this systematic literature review was to investigate the clinical value ofSPECT/ CT in the detection of sentinel lymph nodes in breast cancer patients. Method: Using specific search terms the database PubMed was used to find studies of potentialrelevance for this systematic review. Criteria for inclusions and exclusion were decided todetermine article relevance. Eligibility of articles was determined according to these criteriawhich lead to the selection of the specific articles included in this study. Results: Eleven studies were included in this systematic review. Seven out of 8 studies foundhigher identification rates of sentinel lymph nodes with SPECT/ CT in comparison to planarlymphoscintigraphy. SPECT/ CT could detect additional lymph nodes in 9 out of 9 studies.SPECT/ CT detected additional extra-axillary lymph nodes in 6 out of 7 studies. SPECT/ CTdetected lymph nodes in 9 out of 9 studies where planar lymphoscintigraphy was negative.Information from additional SPECT/ CT lead to changes in surgical treatment plan in 4 out of4 studies. None of the included studies contained information about change in oncologicaltreatment plan due to findings on SPECT/ CT. Conclusion: SPECT/ CT is an imaging technique with much potential as it seems to allow amore accurate SLN mapping and more precise anatomical localization of SLN in breast cancerpatients, specifically in certain clinical situations. Despite this however, the impact of SLNmapping through SPECT/ CT on patient prognosis remains uncertain.

Einteilung:Das Lungenkarzinom ist eine der häufigsten Krebstodesursachen der Welt. Die chirurgische Therapie mit onkologischer Resektion des Tumors bietet bessere Chancen für einen dauerhaften Therapieerfolg. Die Bedeutung der systematischen Lymphadenektomie im Sinne eines akkuraten Stagings und einer besseren Lokalkontrolle des Tumors ist unumstritten. In der Literatur wurden verschiedene LK-Befallsmuster bei den operierten NSCLC anhand verschiedener histomorphologischer Parameter beschrieben, um letztendlich eine passende Technik der Lymphadenektomie zu entwickeln. Patienten und Methoden: In unserer retrospektiven Studie wurde ein Kollektiv von 111 Patienten mit operierten nicht kleinzelligen Lungenkarzinome zwischen 2008 und 2013 untersucht. Das LK-Metastasierungsmuster wurde anhand verschiedener histomorphologischer Parameter untersucht. Ergebnisse: Eine zentrale Tumorlage, L1-Kategorie, sowie die zunehmende Tumorgröße zeigten eine signifikante Neigung zur LK-Metastasierung. Anhand der Tumorlokalisation im Lungenlappen ließ sich jedoch kein bestimmtes LK- Befallmuster sichern. Schlussfolgerung: Diese Daten unterstützen die Angaben der Literatur, in der eine systematische Lymphadenektomie unabhängig von den anderen Parametern weiter gefordert wird, um ein akkurates Staging zur erreichen und so eine optimale Therapie durchzuführen.fi

Objective: Background: Rare disease An epithelial inclusion cyst within a lymph node denotes a heterotopic phenomenon. Nodal epithelial inclusion cysts have been reported in a variety of anatomical locations including pelvic, abdominal, mediastinal, and axillary regions. While nodal melanocytic nevus (also known as nevus cell aggregates) is the most common heterotopic phenomena involving the axillary lymph nodes, the presence of benign epithelial inclusion cysts in axillary lymph nodes is a rare but well-reported finding. Such documentation is in part due to assessment of sentinel lymph nodes in breast cancer becoming standard of care. These epithelial inclusion cysts offer a diagnostic pitfall in evaluation of sentinel lymph node in the setting of breast carcinoma. They also complicate assessment of sentinel lymph node during intraoperative frozen sections analysis. Case Report: We report a case of co-existent of benign squamous-type and glandular-type epithelial inclusions cysts in 2 sentinel lymph nodes in a patient with grade III invasive ductal carcinoma involving the left breast. There have been at least 4 cases reported in literature in which benign epithelial inclusion cysts in sentinel lymph nodes were first mistakenly diagnosed as metastatic carcinoma both during intraoperative frozen section analysis and during review of permanent sections. The missed diagnosis could potentially occur intraoperatively during frozen section sentinel lymph node analysis secondarily due to lack of availability of the primary tumor for comparison and inability to use immunohistochemical stains. Conclusions: Pathologists should be aware of this pitfall especially in frozen section analysis of sentinel lymph node to avoid misdiagnosis and its associated potential grave consequences.