Tumor de células gigantes del fémur / Tumor of giant cells of the femur

El tumor de células gigantes de hueso es un tumor raro de características benignas con un comportamiento agresivo localmente. Predomina en mujeres y por lo general se presenta en la epífisis y metáfisis de los huesos largos. El propósito de este estudio es presentar el caso de un paciente con una lesión tumoral de rodilla y muslo izquierdos de 2 años de evolución y señalar las características diagnósticas de este tumor al mismo tiempo que se revisan los métodos imagenológicos recientes para su confirmación. Se presenta a un paciente masculino de 19 años de edad, que comenzó con dolor, aumento de volumen de la rodilla y muslo izquierdos, acompañado de impotencia funcional. Se reportaron los hallazgos clínicos, radiográficos e histológicos. Debido a la demora entre el inicio de los síntomas y el diagnóstico se practicó el tratamiento quirúrgico del miembro afectado (amputación). Tras 10 meses de observación no se han presentado recidivas o metástasis. Se envió al Servicio de Oncología para valorar e tratamiento con radioterapia. El tumor de células gigantes del hueso es un tumor raro, de buen pronóstico, pero que puede recidivar y causar metástasis cuando se maligniza. Por la posibilidad de transformación en sarcoma requiere estudio y observación periódica. El tiempo para realizar el diagnóstico es fundamental y debe pensarse en este tumor en caso de lesiones líticas de hueso reportadas por imagenología(AU)

The giant cell tumor of bone is a rare benign tumor with a locally aggressive behavior. It predominates in women and usually occurs in the epiphysis and metaphysis of long bones. To present a patient with a tumor lesion left knee and thigh two years of evolution, also noted the diagnostic characteristics of this tumor while recent imaging methods are reviewed for confirmation. 19-year-old male who began with pain, increased volume of the knee and left thigh, accompanied by functional impotensia. clinical, radiological and histological findings were reported. Because of the delay between the onset of symptoms and diagnosis surgical treatment of the affected limb (amputation) was performed. After ten months of observation there have been no recurrences or metastases. The giant cell tumor of bone is a rare tumor with good prognosis but can recur and metastasize when it becomes malignant. The possibility of transformation in sarcoma requires periodic study and observation. The time for diagnosis is essential and should think of this tumor in case of lytic bone lesions reported by imaging(AU)

Lidocaine in oncological surgery: the role of blocking in voltage-gated sodium channels. A narrative review / Lidocaína em cirurgia oncológica: o papel do bloqueio dos canais de sódio dependentes de voltagem. Revisão narrativa

Abstract Background: The current evidence suggests that oncological surgery, which is a therapy used in the treatment of solid tumors, increases the risk of metastasis. In this regard, a wide range of tumor cells express Voltage-Gated Sodium Channels (VGSC), whose biological roles are not related to the generation of action potentials. In epithelial tumor cells, VGSC are part of cellular structures named invadopodia, involved in cell proliferation, migration, and metastasis. Recent studies showed that lidocaine could decrease cancer recurrence through its direct effects on tumor cells and immunomodulatory properties on the stress response. Objective: The aim of this narrative review is to highlight the role of VGSC in tumor cells, and to describe the potential antiproliferative effect of lidocaine during the pathogenesis of metastasis. Contents: A critical review of literature from April 2017 to April 2019 was performed. Articles found on PubMed (2000-2019) were considered. A free text and MeSH-lidocaine; voltage-gated sodium channels; tumor cells; invadopodia; surgical stress; cell proliferation; metastasis; cancer recurrence - for articles in English, Spanish and Portuguese language - was used. A total of 62 were selected. Conclusion: In animal studies, lidocaine acts by blocking VGSC and other receptors, decreasing migration, invasion, and metastasis. These studies need to be replicated in humans in the context of oncological surgery.

Resumo Justificativa: As evidências atuais sugerem que a cirurgia oncológica, usada no tratamento de tumores sólidos, aumenta o risco de metástase. Nesse sentido, uma ampla gama de células tumorais expressa Canais de Sódio Dependentes de Voltagem (CSDV), cujos papéis biológicos não estão relacionados à produção de potencial de ação. Nas células epiteliais tumorais, o CSDV é parte integrante de estruturas celulares denominadas invadópodes, que participam da proliferação, migração e metástase celular. Estudos recentes mostraram que a lidocaína pode diminuir a recorrência do câncer através de efeitos diretos nas células tumorais e de propriedades imunomoduladoras na resposta ao estresse. Objetivo: O objetivo desta revisão narrativa é analisar o papel do CSDV nas células tumorais e descrever o possível efeito antiproliferativo da lidocaína na patogênese das metástases. Conteúdo: Foi realizada uma revisão crítica da literatura de Abril de 2017 a Abril de 2019. Os artigos encontrados no PubMed (2000 − 2019) foram analisados. Pesquisamos textos de linguagem livre e descritores MeSH-lidocaína; canais de sódio dependentes de voltagem; células tumorais; invadópodes; estresse cirúrgico; proliferação celular; metástase; recorrência do câncer − em artigos publicados em inglês, espanhol e português. Foram selecionadas 62 publicações. Conclusão: Em estudos empregando animais, a lidocaína atua bloqueando o CSDV e outros receptores, diminuindo a migração, invasão e metástase. Esses estudos precisam ser replicados em humanos submetidos a cirurgia oncológica.

Metástasis: un hito para el conocimiento, un reto para la ciencia / Metastasis: a milestone for knowledge, a challenge for science

Introducción: La metástasis del cáncer es la transferencia de células tumorales de un órgano a otro mediante una serie de multipasos secuenciales interrelacionados. Este proceso es uno de los principales retos en el tratamiento del cáncer debido a su heterogeneidad biológica. El proceso de metástasis es considerado la principal causa de muerte en esta enfermedad, reportándose que más de 90 por ciento de las muertes por cáncer son debidos a esta etapa. Objetivo: Actualizar los conocimientos sobre metástasis en tumores sólidos y su asociación con transición epitelial-mesenquimal (EMT) en relación a la evolución y emergencia del cáncer. Método: Se realizó una revisión, no sistemática, de los estudios más significativos sobre el tema, publicados en la Web of Science, Pubmed, Ebsco, Scopus e Infomed. Conclusiones: La metástasis es la principal causa de muerte del cáncer, por lo que entender las bases del mecanismo de la formación de tumores metastásicos permitirá realizar terapias más eficaces para tratar el cáncer(AU)

Introduction: Cancer metastasis is the transfer of tumor cells from one organ to another through a series of interrelated sequential multi-steps. This process is one of the main challenges in cancer treatment due to the biological heterogeneity. The metastasis process is considered the main cause of death in this disease, accounting for more than 90 percent of cancer deaths. Objective: To identify the most recent advances on solid tumor metastasis and the association with epithelial-mesenchymal transition (EMT) in relation to the evolution and emergence of cancer. Method: A non-systematic review was carried out of the most significant studies on the subject, published in Web of Science, Pubmed, Ebsco, Scopus and Infomed. Conclusions: Metastasis is the main cause of cancer death, so understanding the bases of the mechanism for metastatic tumor formation will allow for more effective therapies(AU)

A novel hydrazide compound exerts anti-metastatic effect against breast cancer

BACKGROUND: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics. METHODS: 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5-7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells. RESULTS: Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control. CONCLUSION: This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.

Metástasis de carcinoma diferenciado de tiroides en localizaciones infrecuentes: serie de 30 pacientes / Unusual metastases from differentiated thyroid carcinoma: series of 30 patients and review of literature

RESUMEN Introducción Las metástasis son la principal causa de mortalidad específica en carcinoma diferenciado de tiroides (CDT). Las localizaciones más frecuentes son el pulmón y el hueso. El compromiso de otros sitios es inusual. Se desconoce el impacto que tienen en la evolución y sobrevida de los pacientes. Objetivos Evaluar la prevalencia de metástasis infrecuentes (MI) en pacientes con CDT, sus características clínico-patológicas y el impacto en la mortalidad. Material y métodos: Estudio multicéntrico retrospectivo. Se incluyeron pacientes con CDT y MI (diferentes de pulmón y hueso). Se analizaron las características basales, las localizaciones de las MI, el subtipo histológico, el tiempo de aparición desde el diagnóstico inicial (sincrónicas o metacrónicas), sintomatología asociada. Resultados La localización más frecuente fue el sistema nervioso central (31%). El 76,6% fueron metacrónicas, y presentaron criterios de refractariedad al yodo en 76,6% de los casos. La mitad de los pacientes presentó síntomas específicos. En 73,28% de los casos implicaron cambios en la conducta terapéutica. 19 pacientes (63,3%) fallecieron a causa de la enfermedad, con una mediana de sobrevida desde el diagnóstico de la MI de 11 meses. La sobrevida fue menor en pacientes con MI yodorefractarias y sintomáticas. Conclusiones: Las MI tuvieron una prevalencia baja, y se presentaron en forma metacrónica. Determinaron cambios en la estrategia terapéutica y se relacionaron con la mortalidad específica en más de la mitad de los casos, lo que resalta la importancia de una estadificación precisa en pacientes con enfermedad avanzada.

ABSTRACT Introduction Complications related to metastatic disease are the main cause of specific mortality in differentiated thyroid cancer (DTC.) The most common sites of metastses are lung and bone. Other localizations are infrequent and they have been reported as isolated cases or small series. The impact of unusual metastases (UM) in patient management and prognosis remains largely unknown. Objectives To retrospectively evaluate the prevalence of UM in DTC patients, define their clinical-pathological characteristics and analyze its relevance in management and mortality. Patients and methods: We retrospectively reviewed file records from 7 databases. DTC patients who had metastatic disease in sites different from lung or bone were included. UM were diagnosed by: i) biopsy and/or ii) radioiodine (RAI) bone uptake + elevated thyroglobulin (Tg) levels and/or c) bone uptake of 18-FDG in the PET-CT scan + elevated Tg levels. We analyzed histopathologic characteristics, clinical presentation, localization, time of diagnosis (synchronic vs. metachronic presentation), diagnostic and therapeutic modalities and final outcome of patients. Results UM were diagnosed in 30 out of 2986 DTC patients (1%). The most common site of UM was the central nervous system (CNS 31%). Twenty percent of the patients had more than one UM. In 93% of the cases, UM coexisted with either lung and/or bone metastases and/or locoregional disease. Papillary histology was found in 75% of cases; 76.6% were metachronic with DTC diagnosis, and 76.6% fulfilled radioiodine refractoriness criteria. Half of the patients reported symptoms related to the UM. In 73.2% of the cases, therapeutic decisions were influenced by the diagnosis of the UM. Nineteen patients (63.3%) died of DTC related causes, with a mean survival of 11 months. The most frequent cause of death was CNS progression. Survival was shorter in patients with radioiodine refractory and symptomatic lesions. Conclusions Prevalence of UM was low; they were predominantly metachronic and iodine refractory. UM were found in patients with widespread disease, however, treatment strategies were modified by their diagnosis. UM were associated with poor survival and disease specific mortality.

Predictores de detección del tumor primario en pacientes que comienzan con metástasis / Detection predictors of primary tumor in patients presenting with metastasis

Introducción: aproximadamente 15 por ciento de los pacientes con cáncer comienzan con metástasis. La búsqueda de un tumor primario resulta compleja y, en muchos casos, infructuosa. El carcinoma de primario oculto define una enfermedad neoplásica maligna diseminada, demostrada mediante estudio anatomopatológico de una de sus metástasis, sin que se consiga identificar el tumor primario a pesar de un estudio considerado óptimo en vida del paciente. Objetivo: identificar predictores de detección del tumor primario en pacientes que comienzan con metástasis. Métodos: se realizó un estudio observacional, de tipo caso-control retrospectivo. Se obtuvo información de la base de datos del protocolo de carcinoma de primario oculto. Incluyó 99 pacientes atendidos de modo consecutivo en el servicio de medicina interna entre 2010-2013 tras debutar con metástasis. Se evaluó si las variables: sitio, número de metástasis, condición física según escala del Eastern Cancer Oncology Group (ECOG) y variedad histológica podían ser predictores o no de detección del tumor primario. Resultados: no se encontraron diferencias estadísticamente significativas entre pacientes con (47,5 por ciento del total) y sin tumor primario identificado (p< 0,05) respecto a sitio, número de metástasis y puntuación del ECOG. El odds ratio para detección de tumor primario en adenocarcinoma bien y moderadamente diferenciado fue 5 veces mayor que para carcinoma pobremente diferenciado y 11 veces mayor que para carcinoma neuroendocrino. El odds ratio de detectar tumor primario fue 8 veces mayor en metástasis por tumor escamoso respecto a carcinoma pobremente diferenciado y 15 veces superior respecto al carcinoma neuroendocrino. Conclusiones: no se identificó al puntaje en la escala ECOG, sitio y número de metástasis como variables independientes en la detección del tumor primario. La probabilidad de detectarlo en quienes debutan con metástasis por carcinoma escamoso y adenocarcinoma fue superior al resto de los tejidos. La menor probabilidad fue para aquellos con carcinoma neuroendocrino. (AU)

Introduction: Approximately 15 percent of patients with cancer debut with metastasis. The search for a primary tumor is complex and in many cases unsuccessful. The carcinoma of unknown primary tumor defines a disseminated malignant neoplastic disease, demonstrated by anatomopathological study of one of its metastases, without being able to identify the primary tumor despite a study considered "optimal" during the patient's life. Objective: To identify detection predictors of primary tumor in patients presenting metastasis. Methods: A retrospective case-control observational study was conducted. The information was obtained from the database of the occult primary carcinoma protocol. It included 99 patients consecutively treated in the internal medicine service from 2010 to 2013 after debuting with metastasis. We assessed whether or not the variables site, number of metastases, physical condition according to Eastern Cancer Oncology Group (ECOG) scale and histological variety could be detection predictors of primary tumor. Results: No statistically significant differences were found between patients with (47.5 percent of the total) and no primary tumor identified (p< 0.05) regarding site, number of metastases and ECOG score. The odds ratio for detection of primary tumor in adenocarcinoma was moderately differentiated and well. It was 5 times higher than for poorly differentiated carcinoma and 11 times higher than for neuroendocrine carcinoma. The odds ratio of detecting a primary tumor was 8 times higher in squamous cell metastasis compared to poorly differentiated carcinoma and 15 times higher than in neuroendocrine carcinoma. Conclusions: The score on the ECOG scale, site and number of metastases were not identified as independent variables in the detection of the primary tumor. The probability of detecting it was higher than the rest of the histologies, in those who debuted with metastasis due to squamous cell carcinoma and adenocarcinoma. The lowest probability was for those with neuroendocrine carcinoma(AU)

Resistencia concomitante antitumoral: un posible mecanismo de control de las metástasis / 1 CONCOMITANT TUMOR RESISTANCE: A POSIBLE CONTROL MECHANISM OF THE GROWTH OF METASTASES

La Resistencia Concomitante Antitumoral (RC) es el fenómeno según el cual un individuo portador de un tumor inhibe o retarda el crecimiento de implantes tumorales secundarios. Este fenómeno ha sido descripto en animales y en seres humanos y puede ser inducido tanto por tumores inmunogénicos como no-inmunogénicos. El estudio de la RC puede darnos indicios sobre mecanismos de control de las metástasis desde que las metástasis son, de hecho, implantes secundarios naturales desarrollados espontáneamente durante el crecimiento de un tumor primario. En este sentido la experiencia clínica y numerosos datos experimentales han revelado que la extirpación quirúrgica de un tumor puede ser seguida por una abrupta aceleración del crecimiento metastásico sugiriendo que, bajo ciertas circunstancias, un tumor puede ejercer un control inhibitorio sobre sus propias metástasis. En nuestro laboratorio hemos estudiado la RC asociada al crecimiento de numerosos tumores de ratón de diferente origen, tipo histológico e inmunogenicidad. Nuestros resultados demostraron que durante el crecimiento de un tumor primario se generan dos eventos temporalmente separados de RC. El primer evento es producido sólo por tumores inmunogénicos de pequeño tamaño (<500 mm3 ), es específico de tumor y es producido por mecanismos inmunológicos dependientes del timo. Por otro lado, el segundo evento de RC es inducido tanto por tumores inmunogénicos como no-inmunogénicos de gran tamaño (≥ 2000 mm3 ), no es específico de tumor, es timo independiente y correlaciona con la presencia de un factor sérico de bajo peso molecular que demostró tener capacidad para inhibir la proliferación de células tumorales tanto in vitro como in vivo. Cuando esta actividad antitumoral no estaba presente en el suero ­en nuestros modelos, los dos únicos casos estuvieron asociados a tumores altamente metastásicos­ el segundo evento de RC no se producía. Estos resultados sugieren una correlación directa entre la actividad sérica antitumoral, el segundo evento de RC y la capacidad para restringir el crecimiento metastásico.Aunque el primer evento de RC es producido, como dijimos arriba, por una respuesta inmunológica convencional mediada por células T, la naturaleza química del factor sérico asociado a la más universal manifestación de la RC (esto es, el segundo evento de RC), permaneció siendo un enigma por muchos años. En un trabajo reciente, identificamos ese factor sérico antitumoral como una mezcla de metatirosina y orto-tirosina, dos isómeros de tirosina que no están presentes en proteínas normales. Ambos isómeros fueron capaces de inhibir el crecimiento de diferentes tumores murinos que generan RC y restringieron el crecimiento de metástasis establecidas producidas por tumores que no generan RC pero son sensibles a la RC generada por otros tumores. A su vez, y tan significativo como lo anterior, estos efectos antitumorales se lograron sin ningún efecto colateral indeseado Una comprensión más profunda de los mecanismos moleculares asociados con el efecto antitumoral de estos isómeros de tirosina podría, eventualmente, ayudar a desarrollar métodos nuevos y menos tóxicos para combatir las enfermedades malignas; en particular para limitar el crecimiento acelerado de las metástasis después de la extirpación quirúrgica del tumor primario o después del padecimiento de traumas o estresores que pudieran ­despertar­ metástasis de su estado de ­tumor dormido­.

Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants. This phenomenon has been described in human and animal systems and it can be generated by both immunogenic and non-immunogenic tumors. The relevance of CR to the mechanisms of metastases control has been highlighted by numerous observations showing that the removal of human and murine tumors may be followed by an abrupt increase in metastatic growth, suggesting that, upon certain circumstances, a primary tumor exerts a controlling action on its metastases which could be considered as secondary tumor implants developed spontaneously during the primary tumor growth. In our laboratory we have studied the CR induced by many murine tumors widely different in origin, histologic type and immunogenicity. Our results support the idea that during the primary tumor growth, there exist two temporally separate events of CR: the first one was exhibited only by small (<500 mm3 ) immunogenic tumors, it was tumor-specific and mediated by classical T-dependent immunological mechanisms. The second event was induced by both im munogenic and nonimmunogenic large (≥ 2000 mm3 ) tumors; it was non-tumor specific, thymus independent and correlated with the presence of a serum factor of low molecular weight that inhibited the in vitro and in vivo proliferation of tumor cells. When this anti-tumor serum activity was absent ­ in our hands, the only two cases were associated with highly metastatic tumors ­ the second event of CR did not exist, suggesting a direct correlation between the anti-tumor serum activity, the second event of CR and the ability to restrain metastatic growth. Although the mechanism associated with the first event of CR has, as said above, been elucidated as T cell­dependent, the molecular nature of the antitumor serum factor(s), which is at the root of the most universal manifestation of CR (that is, the second event of CR), remained an enigma for many years. In a recently published paper, we identified that antitumor serum factor(s) as a mixture of meta-tyrosine and ortho-tyrosine, two isomers of tyrosine that are not present in normal proteins. Both meta- and ortho-tyrosine inhibited the growth of different murine models of cancer that generate CR and could also block established spontaneous metastases produced by other murine models that do not generate CR but are very sensitive to the CR induced by other tumors. In addition, and most importantly, these anti-tumor effects were achieved without any collateral damage to the organism. A more profound understanding of the molecular mechanisms associated with the anti-tumor effects mediated by meta- and ortho-tyrosine could contribute to develop new and more harmless means to manage malignant diseases, especially by limiting the development of metastases that arise after resection of primary tumors or after other stressors that may promote the escape of metastases from dormancy.

Redução das desigualdades no uso de consultas médicas no Brasil: análise das regiões Nordeste e Sudeste entre 2003 e 2008 / Reduction of inequalities in medical visits in Brazil: analysis of the Northeastern and Southeastern regions between 2003 and 2008

OBJETIVO: Analisar as desigualdades socioeconômicas na utilização de consultas médicas (CM) no último ano no Brasil. MÉTODOS: Dados da Pesquisa Nacional por Amostra de Domicílios (≥ 20 anos de idade) das Regiões Nordeste (2003, n = 75.652 e 2008, n = 79.779) e Sudeste (2003, n = 76.029 e 2008, n = 79.356) foram analisados segundo CM. Compararam-se as prevalências de CM segundo as variáveis exploratórias demográficas e de saúde no primeiro (D1) e último (D10) decil de renda familiar per capita. As análises consideraram o desenho amostral complexo. RESULTADOS: A proporção de pessoas com CM aumentou no período na Região Nordeste (61,2 para 66,9%) e Sudeste (67,9 para 73,5%). A diferença absoluta de CM, segundo D1 e D10 no período, foi de 6,4 pontos percentuais (pp) no Nordeste e 4,2 pp no Sudeste. Houve importante redução das desigualdades entre os homens; naqueles sem doenças crônicas; naqueles que tinham uma percepção positiva da sua saúde e naqueles sem plano de saúde com direito a CM. A Região Sudeste ainda apresentou redução entre aqueles com apenas uma morbidade autorreferida (8 pp) e com percepção negativa da saúde (6 pp). CONCLUSÃO: Houve aumento de CM no Brasil. Observa-se ainda persistente desigualdade entre os mais pobres e os mais ricos, maior no Nordeste do que no Sudeste. Políticas para a redução da desigualdade em saúde mais eficazes e equânimes devem ser adotadas no Brasil. .

OBJECTIVE: To analyze the socioeconomic inequalities in medical visits (MV) in the past year in Brazil. METHODS: Data from adults aged ≥ 20 years old who participated in the Brazilian National Household Surveys and living in the Northeastern (2003; n = 75,652 and 2008, n = 79,779) and Southeastern (2003; n = 76,029 and 2008; n = 79,356) regions were analyzed according to MV. We compared MVs according to demographic and health variables in the first (D1) and last (D10) per capita family income deciles. All analyses considered the complex cluster design. RESULTS: The proportion of people who had MV during this period increased in the Northeastern (from 61.2 to 66.9%) and the Southeastern (from 67.9 to 73.5%) regions. The absolute difference (AD) in the use of MV, according to D1 and D10 in this period, was equal to 6.4 percentage points (pp) in the Northeastern and 4.2 pp in the Southeastern regions. Significant reduction in inequalities was observed among men without chronic diseases, in those who had a positive perception of their health, and among those without health insurance which included MV. The Southeastern region has also showed significant reduction among those with chronic disease (8 pp) and with negative health self-perception (6 pp). CONCLUSION: The increasing number of MVs was found in Brazil. However, persistent inequalities were observed between the poorest and the richest, higher in the Northeastern than in the Southeastern region. More effective and equitable policies to reduce health inequalities should be adopted in Brazil. .

effect of surveillance on the outcome of breast cancer patients

The beginning of metastasis poorly affects the prognosis of breast cancer patients. Lung is the most frequent site of visceral metastasis, and the rate of recurrence is 10-30%. We have tried to find out if the routine Chest X Ray [CXR] could play a role for early detection of lung metastasis, during the prognosis of these patients. The files of the breast cancer patients between 1996 to 2006 [1739 patients] have reviewed. Clinical characteristics of patients with pulmonary metastasis have recorded. Patients, who lacked imaging files or lacked an appropriate follow-up, have excluded. Data have analyzed by SPSS 11.5. The survival analyses have performed by using the Kaplan-Meier method. Fifty-six patients, median age 46, have entered into this retrospective study. Median tumor size was 4cm; median number of Lymphadenopathy [LAP] was 4. The intermediate grade has detected in 74% of patients. All patients have received adjuvant treatment. Median time from cancer diagnosis to pulmonary metastasis was 22 months. Pulmonary metastasis has detected by control CXR in 77.4% and patients' symptoms in 22.6%. Forty eight patients have received chemotherapy in metastatic phase. In 28 patients [50%], other sites of metastasis [bone, liver, and brain] have discovered. The most frequent pattern of lung recurrence was pulmonary nodule [44.6%], followed by pleural effusion [28.6%]. Median survival was 27.5; median survival from pulmonary metastasis was 8 m; Early detection of pulmonary metastasis by CXR did not affect patients' endpoints. None of the probable prognostic factors have shown a significant effect on patients' outcome. Despite systemic treatment, survival after metastasis is low

Optimización del tratamiento y seguimiento del cáncer de tiroides / Optimizing treatment and follow-up of thyroid cancer

Se describe una creciente incidencia de carcinoma de tiroides en todo el mundo, pero la mayor parte de estos casos corresponde a cánceres de bajo riesgo. Se necesita comprender con precisión la patología tumoral y su comportamiento biológico, para aprovechar estos parámetros en una terapia rentable con utilización adecuada de recursos. La apreciación de la importancia y el significado de los factores pronósticos y la estratificación por grupos de riesgo es esencial para el enfoque actual del carcinoma tiroideo. Se requiere discreción para la selección del tratamiento quirúrgico y la indicación de terapias adyuvantes, así como para las estrategias de vigilancia

Análise de expressão do gene ADAM23 em tumores do sistema nervoso central (SNC) e estudo de sua função em gliomas e em melanomas / Analysis of ADAM23 gene expression in tumors of the central nervous system (CNS) and study of its function in melanoma and glioma

O gene ADAM23 está epigeneticamente silenciado em tumores de mama de estágios mais avançados e o seu silenciamento nesses tumores confere ao paciente um maior risco de desenvolvimento de metástases e um pior prognóstico. O silenciamento do gene ADAM23 na linhagem tumoral de mama MDA-MB-435 reduz a capacidade proliferativa e aumenta a capacidade migratória e invasiva das células em modelo tridimensional de cultura. No entanto, paradoxalmente, o silenciamento do gene ADAM23 nessa linhagem reduz a capacidade tumorigênica e metastática das células em ensaios in vivo utilizando animais imunodeficientes. Ensaios subsequentes utilizando misturas de células positivas e negativas para a expressão de ADAM23 revelaram que as células negativas estimulam a proliferação, migração e invasão das células positivas e que a heterogeneidade tumoral em relação à expressão de ADAM23 é importante para a disseminação e colonização metastática. Este trabalho teve como objetivo validar a associação entre o silenciamento do gene ADAM23 em tumores primários e a progressão tumoral, e também encontrar um modelo celular alternativo para a realização de ensaios funcionais que comprovassem o papel do gene ADAM23 na proliferação, migração, e invasão celular, bem como a existência de interação celular entre células ADAM23 positivas e negativas. A análise da expressão do gene ADAM23 em amostras de gliomas de diferentes estágios através de PCR em Tempo Real revelou que a expressão desse gene diminui ao longo da progressão tumoral e está bastante reduzida em tumores de grau avançado. Porém, ao contrário do observado em tumores de mama, o silenciamento do gene ADAM23 em gliomas não é causado por hipermetilação de sua região promotora nem por mutações em sua região codificante, ou perda de heterozigose. Infelizmente, não foi possível selecionar clones derivados da linhagem celular de glioblastoma U87MG com silenciamento estável do gene ADAM23 para a realização de ensaios funcionais. Aparentemente, o silenciamento de ADAM23 nessa linhagem resulta na parada do ciclo celular na fase G0/G1, impedindo a seleção de clones com silenciamento estável do gene. O mesmo fenômeno não foi observado na linhagem de melanoma SKmel-37, permitindo a seleção de clones com silenciamento estável de ADAM23 e a realização de ensaios funcionais. Curvas de proliferação em monocamada e ensaios de incorporação de MTT em modelo tridimensional in vitro demonstraram que o silencimento de ADAM23 na linhagem SKmel-37 diminui sua taxa de proliferação em 20-50%. Ensaios de citometria de fluxo demonstraram que o silenciamento de ADAM23 interfere na expressão das integrinas αvß3 e αvß5 na membrana celular, resultando em diminuição de 50% na afinidade aos ligantes de matriz e aumento significativo na capacidade de migração e invasão no colágeno. Ensaios in vitro e in vivo utilizando misturas de células SKmel-37 ADAM23 positivas e negativas também confirmaram a existência de interação entre os dois subtipos celulares. Ensaios in vitro de migração e invasão no colágeno revelaram que células ADAM23 negativas induzem a migração e a invasão de células positivas e, em ensaios de tumorigienese in vivo, observamos que os tumores formados a partir da injeção de uma mistura de células positivas e negativas apresentam crescimento semelhante ao dos tumores formados a partir da injeção de células ADAM23 positivas

The ADAM23 gene is epigenetically silenced in breast tumors of more advanced stages and its silencing in these tumors gives the patient a greater risk of developing metastasis and a worse prognosis. The ADAM23 gene silencing in the MDA-MB-435 breast tumor cell line reduces the proliferative capacity and increases migratory and invasive abilities of cells in three-dimensional culture models. Yet, paradoxically, the ADAM23 gene silencing in this line reduces tumorigenic and metastatic abilities of cells in in vivo assays using immunodeficient animals. Subsequent tests using ADAM23 positive and negative cells mixtures revealed that negative cells stimulate proliferation, migration and invasion of positive cells and the heterogeneity of ADAM23 expression in tumors is important for the spreading and metastatic colonization. This study aimed to validate the association between ADAM23 gene silencing in primary tumors and tumor progression as well as find an alternative cellular model for performing functional tests to prove the role of the ADAM23 gene in proliferation, migration and cell invasion, and to prove the existence of cell interaction between ADAM23 positive and negative cells. The analysis of ADAM23 gene expression in samples from different stages of gliomas by RT-PCR revealed that the expression of this gene decreases over tumor progression and is greatly reduced in tumors of advanced degree. However, unlike that observed in breast tumors, the ADAM23 gene silencing in gliomas is not caused by hypermethylation of its promoter region or by mutations in its coding region, or by loss of heterozygosity. Unfortunately, it was not possible to select clones derived from the U87MG glioblastoma cell line with stable silencing of the gene ADAM23 for the functional testing. Apparently, the silencing of ADAM23 in this cell line results in cell cycle arrest in G0/G1 phase, preventing the selection of clones with stable gene silencing. The same phenomenon was not observed in SKmel-37 melanoma cell line, allowing selection of clones with stable silencing of ADAM23 and functional testing. Monolayer proliferation curves and in vitro MTT incorporation assays in three-dimensional models showed that ADAM23 silencing in the SKmel-37 cell line reduces their rate of proliferation by 20-50%. Flow cytometry assays demonstrated that ADAM23 silencing interferes with the expression of αvß3 and αvß5 integrins in the cell membrane, resulting in a 50% decrease in binding afinity to the matrix and a significant increase in migratory and invasive abilities on collagen. In vitro and in vivo assays using ADAM23 positive and negative SKmel-37 cell mixtures also confirmed the existence of interaction between the two cell subsets. In vitro invasion and migration on collagen assays revealed that ADAM23 negative cells induce migration and invasion of positive cells. Furthermore, in in vivo tumorigenic tests we found that tumors formed from injection of a mixture of positive and negative cells exhibit growth similar to the tumors formed after injection of ADAM23 positive cells

Intravenous KITENIN shRNA Injection Suppresses Hepatic Metastasis and Recurrence of Colon Cancer in an Orthotopic Mouse Model

KITENIN (KAI1 C-terminal interacting tetraspanin) promotes invasion and metastasis in mouse colon cancer models. In the present study, we evaluated the effects of KITENIN knockdown by intravenous administration of short hairpin RNAs (shRNAs) in an orthotopic mouse colon cancer model, simulating a primary or adjuvant treatment setting. We established orthotopic models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). In the primary therapy model, treatment with KITENIN shRNA substantially delayed tumor growth (P = 0.028) and reduced the incidence of hepatic metastasis (P = 0.046). In the adjuvant therapy model, KITENIN shRNA significantly reduced the extent of tumor recurrence (P = 0.044). Mice treated with KITENIN shRNA showed a better survival tendency than the control mice (P = 0.074). Our results suggest that shRNA targeting KITENIN has the potential to be an effective tool for the treatment of colon cancer in both adjuvant and metastatic setting.

Histological analysis antimetastatic effect of intera-venus injection of staphylococcal enterotoxin b and monophosphoryl lipid a against fibrosarchoma in lung tissue

Staphylococcal enterotoxin B [SEB] is a potent inducer of cytotoxic T-cell activity, cytokine production and necrosis induction in vivo. Monophosphoryl lipid A [MPL] is an adjuvant derived from the lipopolysaccharide of E.coli, Salmonella Minnesota Re595 and other gram negative bacteria. In this research, The antitumor and antimetastatic effect of intra-venus injection of Monophosphoryl Lipid A [MPL], Staphylococcal enterotoxin B [SEB] and SEB+ MPL was evaluated using Balb/C male mice bearing inoculable mice Fibrosarcoma. The anti tumor effect of SEB+ MPL, SEB and MPL in mice with inoculated fibrosarchoma tumor [Wehi-164] was examined by IV injection and the sizes of the inoculated tumors were determined. The inoculated tumors were also examined histologically. Moreover, histophatologic study in lung tissue didn't showed any metastasis. In the mice IV injected group with SEB4- MPL, reduction of tumor size show a significant difference compared with mice in the SEB and MPL injected and negative control group. A significantly higher frequency of necrosis in tumor tissues was also observed in mice in the IV [SEB+ MPL]-injected group in comparison with other group. Moreover, histophatologic study in lung tissue didn't show any metastasis Our findings suggest that tumor cell death and the prevention of metastasis be caused by increased Cytotoxic T-cell activity in response to IV injection of SEB+ MPL that need to more investigation

Lapatinib for treatment of advanced or metastasized breast cancer: systematic review / Lapatinib no tratamento do câncer de mama avançado ou metastático: revisão sistemática

Context and objective: Around 16 percent to 20 percent of women with breast cancer have advanced, metastasized breast cancer. At this stage, the disease is treatable, but not curable. The objective here was to assess the effectiveness of lapatinib for treating patients with advanced or metastasized breast cancer. Design and setting: Systematic review of the literature, developed at Centro Paulista de Economia da Saúde (CPES), Universidade Federal de São Paulo (Unifesp). Method: Systematic review with searches in virtual databases (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science) and manual search. Results: Only one clinical trial that met the selection criteria was found. This study showed that lapatinib in association with capecitabine reduced the risk of cancer progression by 51 percent (95 percent confidence interval, CI: 0.34-0.71; P < 0.001), compared with capecitabine alone, without any increase in severe adverse effects. Conclusion: The combination of lapatinib plus capecitabine was more effective than capecitabine alone for reducing the risk of cancer progression. Further randomized clinical trials need to be carried out with the aim of assessing the effectiveness of lapatinib as monotherapy or in association for first-line or second-line treatment of advanced breast cancer.

Contexto e objetivo: Aproximadamente 16 por cento a 20 por cento das mulheres com câncer de mama têm doença avançada com metástases. Neste estágio, a doença é tratável, porém incurável. O objetivo foi avaliar a efetividade do lapatinib no tratamento de pacientes com câncer de mama avançado ou metastático. Tipo de estudo e local: Revisão sistemática da literatura desenvolvida no Centro Paulista de Economia da Saúde (CPES), Universidade Federal de São Paulo (Unifesp). Método: Revisão sistemática com busca em bases de dados virtuais (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science) e busca manual. Resultados: Foi encontrado apenas um ensaio clínico que preencheu os critérios de seleção. Este estudo mostrou que o lapatinib em associação com a capecitabina reduziu em 51 por cento o risco de progressão da doença (intervalo de confiança, IC 95 por cento: 0,34-0,71; P < 0,001) quando comparado com a capecitabina isolada, sem aumento de efeitos adversos graves. Conclusão: A combinação de lapatinib e capecitabina foi mais efetiva do que a capecitabina isolada na redução do risco de progressão da doença. Ensaios clínicos aleatórios devem ser realizados com o objetivo de avaliar a efetividade do lapatinib como monoterapia ou em associação no tratamento primário ou secundário do câncer de mama avançado.

O impacto, na sobrevida, dos exames bioquímicos e de imagem utilizados no seguimento a pacientes com câncer de mama / The impact on survival of biochemical and imaging examinations performed during the follow-up of patients with breast cancer

O seguimento às pacientes tratadas de câncer de mama é um aspecto de extrema importância, mas ainda muito controverso devido à falta de consenso sobre o significado clínico da detecção precoce da recorrência das metástases. Os exames de seguimento utilizados têm escassa probabilidade de detectar metástases na ausência de sintomas ou sinais clínicos e não contribuem para aumentar o tempo de sobrevivência. O uso rotineiro de exames bioquímicos de sangue, radiografia de tórax, cintilografia óssea, ultra-sonografia hepática, tomografias, ressonância magnética, PET scan e marcadores tumorais (CEA,CA-15,3,CA 27,29) não é recomendado para o seguimento às pacientes portadoras de câncer de mama assintomáticas e sem evidência clínica da doença. A anamnese, o exame clínico minucioso e o exame mamográfico regular bastam para orientar a paciente, sendo esses os únicos exames suficientes, apropriados e recomendados para a detecção das recorrências do câncer de mama.

[Expression of Nm23 marker in benign and malignant thyroid neoplasms immunohistochemical]

Several prognostic factors affect the outcome of thyroid carcinomas including tumor stage and distant metastases. Nm23 is a metastasis suppressor gene and has a crucial role in the control of metastatic potential of several carcinomas. The aim of our study is to evaluate expression of nm23 marker in benign and malignant thyroid neoplasms using the immunohistochemistry method and to elucidate its relationship with tumor size, vascular or capsular invasion and lymph node involvement. In a descriptive study, 200 paraffin blocks comprising of 38 benign and 162 malignant thyroid neoplasms stained with nm23 marker were studied. Cytoplasmic staining in more than 10% of cells was considered as positive. The relationship between nm23 and tumor size, vascular or capsular invasion, lymph node involvement was analysed using SPSS 11.5 software [p=0.05]. There was 40% positive incidence of nm23 in follicular adenoma, 87.5% in hurthle cell adenoma, 67.2% in papillary carcinoma, 66.7% in follicular carcinoma, and 64.7% in medullary carcinoma. In follicular adenoma, frequency of nm23 positive tumors was directly correlated to tumor size [p=0.04]. There are no statistically significant correlation between nm23 and tumor size, vascular or capsular invasion or lymph node involvement in malignant thyroid neoplasms. In papillary and medullary carcinoma, negative predictive value of nm23 for lymphnode involvement was over 80%. Also in follicular carcinoma, sensitivity and negative predictive value of nm23 for vascular invasion were approximately 90%. Lack of significant correlation between nm23 and tumor invasiveness [and probably metastasis] factors, demonstrate that although nm23 is a potentially metastasis suppressor gene, whereas in many other tumors it may play a different role in thyroid neoplasms, a role which necessitates further studies to be conducted

Effect of homeopathic medicines on transplanted tumors in mice.

Ultra low doses used in homeopathic medicines are reported to have healing potential for various diseases but their action remains controversial. In this study we have investigated the antitumour and antimetastatic activity of selected homeopathic medicines against transplanted tumours in mice. It was found that Ruta graveolens 200c and Hydrastis canadensis 200c significantly increased the lifespan of Ehrlich Ascites Carcinoma and Dalton's Lymphoma Ascites induced tumour-bearing animals by 49.7%, and 69.4% respectively. Moreover there was 95.6% and 95.8% reduction of solid tumour volume in Ruta 200c and Hydrastis 200c treated animals on the 31st day after tumour inoculation. Hydrastis 1M given orally significantly inhibited the growth of developed solid tumours produced by DLA cells and increased the lifespan of tumour bearing animals. Some 9 out of 15 animals with developed tumors were completely tumour free after treatment with Hydrastis 1M. Significant anti-metastatic activity was also found in B16F-10 melanoma-bearing animals treated with Thuja1M, Hydrastis 1M and Lycopodium1M. This was evident from the inhibition of lung tumour nodule formation, morphological and histopathological analysis of lung and decreased levels of gamma-GT in serum, a cellular marker of proliferation. These findings support that homeopathic preparations of Ruta and Hydrastis have significant antitumour activity. The mechanism of action of these medicines is not known at present.

Tumores estromales colorrectales. A propósito de un caso y revisión de la literatura / Colorectal stromal tumors. Case report and literature review

Introducción: En la última década los tumores estromales gastrointestinales (GIST) han sido redefinidos como una entidad propia y se caracterizan por presentar aspectos diagnósticos, clínicos e histológicos casi específicos. El tratamiento actual consiste en un abordaje multifactorial en el cual la cirugía tiene un rol principal. Objetivo: poner en consideración un tumor de recto de presentación poco frecuente y analizar la literatura con respecto a dicho caso. Diseño: Presentación de un caso. Revisión de la literatura. Paciente y Método: Tratamos un paciente de sexo masculino de 65 años que consultó por pujos y tenesmo rectal. Examen proctológico: tumoración duro-elástica de 7 cm que no compromete la mucosa a 3 cm del margen anal. Se realizó punción biopsia guiada por ecografía. El resto del colon no presentó lesiones. Se completó con resonancia magnética y marcadores histológicos específicos por inmunohistoquímica para el diagnóstico diferencial. El CD117 fue negativo. Se realizó operación de Miles asistida por vía laparoscópica. Cursó un postoperatorio favorable egresando al 5° día. El resultado histológico definitivo mostró tumor estromal mesenquimático gastrointestinal de bajo potencial maligno. La inmunomarcación fue CD117 positivo. Conclusiones: Los tumores estromales colorrectales son los menos frecuentes dentro de los GIST gastrointestinales. El diagnóstico preoperatorio no siempre es posible y debe realizarse su diferenciación con los sarcomas. La cirugía debe ser en lo posible resectiva con intención curativa. Otras tácticas terapéuticas son consideradas, en particular el imatinib. Esta droga provee las mayores expectativas en cuanto al tratamiento de estos tumores y es motivo de múltiples ensayos clínicos actualmente.

Cáncer de labio inferior: reconstrucción con técnica de Karapandjic / Lower lip cancer: reconstruction with the Karapandjic technique

La técnica de Karapandjic fue inicialmente descripta en el año 1974 y se indica en resecciones del labio inferior, donde la pérdida de sustancia no es muy importante. La característica principal es su fácil realización y los resultados son aceptables, tanto en estética como en funcionalidad. En este trabajo se presenta la aplicación de la misma en un caso de carcinoma espinocelular

Radioquimioterapia neoadyuvante en cáncer gástrico T4 localmente irresecable: resultados preliminares / Chemoradiotherapy in patients with non resectable gastric cancer: report of 10 patients

En el caso de pacientes con cáncer gástrico T4, puede estar indicada la quimiorradioterapia si no es posible la resección de las estructuras infiltradas. Analizamos 10 pacientes con cáncer gástrico irresecable (8 hombres, 2 mujeres) tratados por nosotros en el periodo 2003-2005. Después de la laparotomía exploradora, los pacientes con cáncer gástrico localmente avanzados e irresecables son tratados con RT-QT concomitante 2 semanas después de la laparotomía. El tratamiento consistió en radioterapia a dosis de 45 Gy en 25 fracciones de 1.8 Gy, 5 veces por semana por 5 semanas sobre estómago y linfáticosregionales, y 5 FU en 1ª y 5º semana (425mg/m2) o Capecitabina 825 mg/m2 diarios, en dos dosis, cada12 hrs. Un mes después se realiza la segunda laparotomía con resección del estómago y linfadenectomía en casos de remisión total o parcial de la enfermedad. Todos los carcinomas fueron proximales. Nueve pacientes se reintervinieron, un paciente tuvo progresión de la enfermedad. Un paciente fue nuevamente irresecable y ocho fueron sometidos a una gastrectomía total D2. Se logró respuesta patológica completa en tres casos (no había cáncer residual en el estómago ni en los ganglios) y parcial en cinco. Creemos que en cáncer gástrico T4 localmente irresecable la RT-QT seguida de cirugía es una buena alternativa terapéutica.