Sarcoma de Ewing multifocal: presentación de un caso pediátrico / Multifocal Ewing sarcoma: presentation of a pediatric case / Sarcoma de Ewing Multifocal: apresentação de um caso pediátrico

Introducción: el Sarcoma de Ewing es una neoplasia maligna de origen mesenquimático. Al momento del diagnóstico el 75% se presentan en forma localizada. Objetivo: comunicar un caso que por su presentación multifocal, generó dificultades diagnósticas. Caso clínico: niña de 6 años. Consulta por traumatismo de mano derecha tras caída de su altura 24 horas previas, constatándose en mano y puño derecho edema, calor y eritema, movilidad conservada. No fiebre. Radiografía: aumento del diámetro del tercer metacarpiano, imagen esmerilada, no trazos de fracturas. Ingresa con planteo de celulitis. Anemia leve microcítica, hipocrómica. Proteína C reactiva 82 mg/l. Recibe clindamicina intravenosa 72 horas, completa 14 días vía oral. Persistencia de alteraciones en puño y mano derecha, agrega tumoración de raíz nasal con desviación del eje, indolora. Fosfatasa alcalina, lactato deshidrogenasa, fosfatemia, calcemia normales. Resonancia magnética: alteración morfoestructural de radio, olecranon y tercer metacarpiano, fractura de olecranon y radio, reacción perióstica. Pet-Scan: lesión extensa ósea en macizo facial, tibias, cúbitos, humero derecho y clavícula. Biopsia 3er metacarpiano: tumor de células pequeñas, redondas azules, CD99 y vimentina positivo. Comienza poliquimioterapia y radioterapia sin complicaciones. Conclusiones: es frecuente que las manifestaciones clínicas iniciales sean confundidas con entidades más frecuentes, como post-traumáticas y/o inflamatorias, tal como ocurrió en este caso. Posteriormente, la aparición de nuevas lesiones y compromiso del estado general orientó el abordaje diagnóstico de la patología tumoral. La confirmación exige el estudio anatomopatológico con estudio inmunohistoquímico. La presencia de metástasis óseas constituye un factor de mal pronóstico y dificulta el abordaje terapéutico.

Introduction: Ewing's sarcoma is a malignant neoplasm of mesenchymal origin. At the time of diagnosis 75% of the cases are localized. Objective: to report a case that, due to its multifocal presentation, generated diagnostic difficulties. Clinical case: 6-year-old girl. She consulted for right hand trauma after a fall from her height 24 hours earlier, with edema, warmth and erythema in the right hand and fist, with preserved mobility. No fever. X-ray: increase in the diameter of the 3rd metacarpal, frosted image, no traces of fractures. Admitted with cellulitis. Mild microcytic anemia, hypochromic. C-reactive protein 82mg/l. Receives intravenous clindamycin 72 hours, completes 14 days orally. Persistence of alterations in fist and right hand, adds tumor of nasal root with deviation of the axis, painless. Alkaline phosphatase, lactate dehydrogenase, phosphatemia, normal calcemia. MRI: morphostructural alteration of radius, olecranon and 3rd metacarpal, fracture of olecranon and radius, periosteal reaction. Pet-Scan: extensive bone lesion in facial mass, tibiae, ulnae, right humerus and clavicle. Biopsy 3rd metacarpal: small cell tumor, blue round, CD 99 and vimentin positive. Polychemotherapy and radiotherapy were started without complications. Conclusions: it is frequent that the initial clinical manifestations are confused with more frequent entities, such as post-traumatic and/or inflammatory, as occurred in this case. Subsequently, the appearance of new lesions and compromise of the general condition guided the diagnostic approach of the tumor pathology. Confirmation requires anatomopathological study with immunohistochemical study. The presence of bone metastases constitutes a poor prognostic factor and hinders the therapeutic approach.

Introdução: O sarcoma de Ewing é um neoplasma maligno de origem mesenquimatosa. No momento do diagnóstico, 75% dos casos são localizados. Objetivo: Relatar um caso que, devido a sua apresentação multifocal, causou dificuldades diagnósticas. Caso clínico: Menina de 6 anos. Ela consultou por traumatismo à mão direita após cair de sua altura 24 horas antes, com edema, calor e eritema na mão direita e punho, com mobilidade preservada. Sem febre. Raio-X: aumento do diâmetro do 3º metacarpo, imagem fosca, sem vestígios de fraturas. Admitido com a sugestão de celulite. Anemia microcítica leve, hipocrómica. Proteína C reativa 82mg/l. Recebe clindamicina intravenosa por 72 horas, completa 14 dias por via oral. Persistência de alterações no punho e mão direita, tumor indolor da raiz nasal com desvio do eixo. Fosfatase alcalina, desidrogenase láctica, fosfataemia, calcemia normal. IRM: alteração morfo-estrutural do rádio, olecrânio e 3º metacarpo, fratura do olecrânio e do rádio, reação periosteal. Pet-Scan: extensa lesão óssea na massa facial, tíbia, ulnae, úmero direito e clavícula. Biópsia do 3º metacarpo: tumor de pequenas células, redondo azul, CD 99 e vimentina positiva. Ela iniciou a poli-quimioterapia e radioterapia sem complicações. Conclusões: É comum que as manifestações clínicas iniciais sejam confundidas com entidades mais freqüentes, tais como pós-traumáticas e/ou inflamatórias, como ocorreu neste caso. Posteriormente, o aparecimento de novas lesões e o envolvimento do quadro geral levaram a uma abordagem diagnóstica da patologia tumoral. A confirmação requer um estudo anatomopatológico com estudo imuno-histoquímico. A presença de metástases ósseas é um fator de mau prognóstico e dificulta a abordagem terapêutica.

Leiomiosarcoma primario de hueso en fémur distal metastásico a clavícula: reporte de un caso / Primary leiomyosarcoma of bone in the distal femur with clavicle metastasis: a case report

El leiomiosarcoma (LMS) es un tipo de tumor de células fusiformes de muy baja incidencia, que tiene un comportamiento agresivo, con alta tasa de mortalidad, por lo que el manejo debe ser quirúrgico, con una resección amplia de la lesión. No está claro el papel de la radio ni de la quimioterapia en su manejo. Presentamos a una paciente de 28 años que consultó por dolor de 2 meses en la rodilla derecha. Radiográficamente, se caracterizó como una lesión osteolítica pura en el fémur distal. La resonancia nuclear magnética (RNM) contrastada mostró áreas hipervasculares dentro del tumor. La gammagrafía mostró un marcado aumento en la captación de radiotrazadores. Se tomó una biopsia, con un informe de patología de LMS óseo bien diferenciado. Se trató con 3 ciclos de quimioterapia neoadyuvante preoperatoria con ifosfamida 1.000 mg/m2 en los días 1 a 3, además de doxorrubicina 70 mg/m2 , y resección quirúrgica de la lesión y salvamento de la extremidad con endoprótesis de rodilla. Una vez que se resecó la lesión, la paciente recibió quimioterapia adyuvante con 4 ciclos de gencitabina 1.000 mg/m2 entre los días 1 y 8, y doxetacel 70 mg/m2 el día 1. Durante los dos meses de seguimiento, la paciente presenóa una fractura en el tercio medio de la clavícula, compatible con una lesión patológica en radiografías y tomografía por emisión de positrones (TEP). La biopsia reveló una lesión metastásica de LMS óseo que fue tratada mediante resección quirúrgica de la clavícula. Este es un caso único, dado que, durante el seguimiento, recibió tratamiento adyuvante con quimioterapia y se evaluó con una TEP, con una evolución clínica satisfactoria y sin evidencia de nuevas lesiones

Leiomyosarcoma (LMS) is a type of spindle-cell tumor of very low incidence that tumor has an aggressive behavior, with high mortality rates; therefore, its management must be surgical, with a wide resection of the lesion. The role of radio and chemotherapy in its management is not clear. We present the case of a 28-year-old female patient who consulted for pain lasting 2 months in the right knee. Radiographically, it was characterized as a pure osteolytic lesion in the distal femur. Contrast magnetic resonance imaging (MRI) showed hypervascular areas within the tumor. The scintigraphy showed a marked increase in radiotracer uptake. A biopsy was taken, with a pathology report of well-differentiated osseous LMS. It was treated with 3 cycles of preoperative neoadjuvant chemotherapy with ifosfamide 1,000 mg/m2 in the first 3 days, as well as doxorubicin 70 mg/m2 , and surgical resection of the lesion and limb salvage with knee endoprosthesis. Once the lesion was resected, the patient underwent adjuvant chemotherapy, with 4 cycles of gencitabine 1,000 mg/m2 between days 1 and 8, and doxetacel 70 mg/m2 on day 1. During the 2-month follow-up, the patient presented a fracture in the middle third of the clavicle, which was compatible with a pathological lesion on radiographs and positron-emission tomography (PET) scans. The biopsy showed a metastatic lesion of bone LMS, which was treated by surgical resection of the clavicle. This is a unique case, given that, during the follow-up, the patient underwent adjuvant treatment with chemotherapy, and was evaluated with a PET scan, with a satisfactory clinical evolution and no evidence of new lesions.

Denosumab como tratamiento neoadyuvante del tumor de células gigantes del hueso. Indicaciones, resultados y efectos adversos / Denosumab as a neoadjuvant treatment for giant cell tumor of bone. Indications, results and side effects

Resumen El tumor de células gigantes óseo es una neoplasia de agresividad local intermedia, que raramente metastatiza. En los últimos años el denosumab, anticuerpo monoclonal humano, surgió como una alternativa de tratamiento para esta enfermedad, al bloquear el comportamiento lítico tumoral. El objetivo de este trabajo fue determinar sus indicaciones y efectos adversos, analizando también los resultados oncológicos, y las tasas de recurrencia local en pacientes con diagnóstico de tumor de células gigantes óseo que recibieron denosumab como tratamiento neoadyuvante. Entre 2010 y 2018 se analizaron 80 pacientes con tumor de células gigantes, de los cuales 14 recibieron denosumab como tratamiento neoadyuvante. El seguimiento mínimo fue 12 meses. En 8 pacientes se trató de un tumor primario, mientras que 6 fueron pacientes con recidiva tumoral. En todos los casos se evidenció una mejoría clínica. Trece presentaron cambios radiográficos, y 11 respuesta histológica completa. En 6 de 14 pacientes se evidenció una recurrencia local y en 7 se identificó al menos un efecto adverso relacionado con el denosumab (incluyendo una malignización tumoral). A pesar de ser una herramienta útil para el tratamiento del tumor de células gigantes, el uso de denosumab está asociado a mayor tasa de recurrencias locales y no está exento de efectos adversos.

Abstract Giant cell tumor of bone is an intermediate, locally aggressive and rarely metastasiz ing, primary bone neoplasia. In recent years denosumab emerged as a treatment alternative for this pathology. The objective of this work was to analyze its indications as well as the clinical outcomes, side effects and local recurrence rates in patients diagnosed with giant cell tumor of bone, who received denosumab as neoadjuvant treatment. Between 2010 and 2018, 80 patients with giant cell tumor were analyzed, of whom 14 received deno sumab as a neoadjuvant treatment. The minimum follow-up was 12 months. In 8 patients it was a primary tumor, while 6 showed tumor recurrence. In all cases, clinical improvement was evident. Thirteen patients presented radiographic changes, and 11 showed complete histological response. A local recurrence was evidenced in 6 of 14 patients, and at least one adverse effect related to denosumab (including tumor malignancy) was identified in 7. Despite being a useful tool for treating giant cell tumor, the use of denosumab is associated with a higher rate of local recurrences and is not free of adverse effects.

Expert consensus on diagnosis and treatment of renal cell cancer bone metastasis (2021 edition) / 中华肿瘤杂志

Bone is a common metastatic site of renal cell carcinoma (RCC), with about 30% of metastatic RCC patients are suffering from bone metastasis. More than 70% of RCC patients with bone metastasis may experience skeletal related events (SREs), which may severely impair patients' quality of life and even shorten their survival time. Therefore, SREs prevention has become one of the treatment objectives of RCC bone metastasis. Bone-modifying agents are the basic treatment of bone metastases in addition to anti-tumor therapy. The treatment of RCC bone metastasis also requires multi-disciplinary team and individualized comprehensive treatment strategies. To standardize the diagnosis and treatment of RCC bone metastasis in China, the expert group of Genitourinary Oncology Committee, Chinese Anti-cancer Association has formulated the expert consensus for the reference of clinical practice, to improve the general therapeutic level of RCC with bone metastasis and benefit more patients.

Avaliação do Efeito do Laser Preventivo na Mucosite Oral Quimioinduzida em Pacientes Submetidos a Altas Doses de Metotrexato / Evaluation of the Effect of Preventive Laser on Chemo-induced Oral Mucositis in Patients Submitted to High Doses of Methotrexate / Evaluación del Efecto del Láser Preventivo em la Mucositis Oral Inducida por Quimioterapia en Pacientes Sometidos a Altas Dosis de Metotrexato

Introdução: A quimioterapia, uma das formas de tratamento de neoplasias malignas, tem sua administração associada a inúmeras drogas, sendo uma delas o metotrexato (MTX), de alta toxicidade, responsável por inúmeros fatores agravantes para a saúde e bem-estar do paciente. Uma das principais complicações é a mucosite oral, manifestação clínica resultante do tratamento oncológico que pode interferir no tratamento e na cura. Objetivo: Avaliar, comparativamente, por meio de um estudo retrospectivo, o efeito do laser preventivo na ocorrência da mucosite oral quimioinduzida em pacientes com osteossarcoma não metastático submetidos a altas doses de MTX, bem como a intensidade da mucosite oral, utilizando o laser preventivo após os ciclos quimioterápicos contendo o medicamento MTX nos pacientes atendidos no Hospital de Câncer infantojuvenil de Barretos/SP. Método: Estudo de coorte com coleta retrospectiva em prontuários. Os pacientes foram divididos em dois grupos, um submetido à terapia profilática com laser de baixa intensidade após infusão do MTX e outro grupo não submetido a essa terapia. Resultados: Os dados obtidos mostraram que houve redução da gravidade da mucosite oral com o uso da laserterapia preventiva, com resultados estatisticamente significativos (p<0,001), corroborando os resultados encontrados na literatura. Conclusão: O uso da laserterapia é uma terapêutica auxiliar importante na prevenção e na redução da severidade da mucosite oral em pacientes submetidos a altas doses de MTX, diminuindo o número de internações por mucosite e os atrasos no protocolo terapêutico, o que reduz gastos e melhora o prognóstico para o paciente.

Introduction: Chemotherapy, one of the treatments for malignant neoplasms, is associated to innumerous drugs, one of them methotrexate (MTX), of high toxicity, responsible for several health damages and impact on the patient's well-being. One of the main complications is oral mucositis, a clinical manifestation resulting from the oncologic treatment that can interfere in the treatment and cure. Objective: To evaluate comparatively through a retrospective study, the effect of preventive laser in the occurrence of chemo-induced oral mucositis in patients with non-metastatic osteosarcoma submitted to high doses of methotrexate (MTX), and the intensity of oral mucositis, using the preventive laser after the chemotherapy cycles containing the drug methotrexate (MTX) in the patients treated at the Child and Adolescent Cancer Hospital of Barretos/SP. Method:Retrospective cohort study with charts review. The patients were divided in two groups, one submitted to low-intensity laser prophylaxis therapy after infusion of MTX and another group not submitted to prophylactic therapy. Results: The data obtained showed that preventive laser-therapy reduced the severity of oral mucositis with statistically significant results (p<0.001), corroborating the results found in the literature. Conclusion: The use of laser therapy is an important auxiliary therapy in the prevention and reduction of severity of oral mucositis in patients submitted to high doses of MTX, reducing the number of hospitalizations and delays in therapeutic protocol, which reduces costs and improves the patient prognosis.

Introducción: La quimioterapia, es uma de las formas de tratamiento de las neoplasias malignas, tiene su administración asociada a numerosas drogas siendo una de ellas el metotrexato (MTX), de alta toxicidad, responsable de numerosos factores agravantes para la salud y bienestar del paciente. Una de las principales complicaciones es la mucositis oral, manifestación clínica resultante del tratamiento oncológico que puede interferir en el tratamiento y cura. Objetivo: Evaluar, comparativamente, a través de um estudio retrospectivo, el efecto del láser preventivo em la aparición de la mucositis oral quimio inducida em pacientes com osteosarcoma no mestastásico sometido a altas dosis de MTX, bien como la intensidade de la mucositis oral, utilizando el láser preventivo después de los ciclos quimioterápicos que contiene el medicamento MTX en los pacientes antendidos en el Hospital del Cáncer Infantojuvenil de Barretos/SP. Método: Estudio de coorte con colección retrospectiva en prontuários. Los pacientes fueron divididos em dos grupos, uno sometido a terapia profiláctica con láser de baja intensidade después de la infusión de MTX y otro grupo no sometido a terapia profiláctica. Resultados: Los dados obtenidos mostraron que hubo una reducción en la severidad de la mucositis oral con el uso de la terapia láser preventiva, con resultados estáticamente significativos (p<0,001), corroborando los resultados encontrados em la literatura. Conclusión: El uso de la terapia con láser es una terapia auxiliar importante en la prevención y reducción de la severidad de la mucositis oral em pacientes sometidos a altas dosis de MTX, diminuendo el número de internaciones por mucositis y retrasos en el protocolo terapéutico, lo que reduce los gastos y mejora el pronóstico para el paciente.

Retinal ischemia following mandible tumor treatment with steroid injection / Isquemia de retina após tratamento de tumor de mandíbula com injeção de esteroide

ABSTRACT Central giant cell granuloma is a rare osseous tumor affecting young patients with anatomical and functional compromise of the maxilla and mandible. Steroid injection therapy constitutes a less invasive treatment modality for disease control in selected cases. Retinal ischemia is a reported complication of multiple medical procedures, including dental interventions, and may lead to loss of vision with poor prognosis. We report a case of retinal arteriolar ischemic disease following central giant cell granuloma management with local injected corticosteroids.

RESUMO O granuloma central de células gigantes é um tumor ósseo raro que afeta pacientes jovens com comprometimento anatômico e funcional da maxila e mandíbula. A terapia com injeção de esteroides constitui uma modalidade de tratamento menos invasiva para o controle da doença em casos selecionados. A isquemia retiniana é uma complicação relatada em vários procedimentos médicos, incluindo intervenções odontológicas, e pode levar à perda da visão com mau prognóstico. Relatamos um caso de doença isquêmica arteriolar da retina após o tratamento com granuloma central de células gigantes com corticosteroides injetados locais.

Mechanism of the Notch signaling pathway in enhancing the efficacy of chemotherapy drugs in osteosarcoma / 中南大学学报(医学版)

Osteosarcoma is the most common malignant tumors of bone. Since 1970s, researchers had used chemotherapy drugs to treat osteosarcoma. However, multidrug resistance is a major adverse reaction that affects the efficacy of chemotherapy drugs, leading to the reduced survival rate of osteosarcoma patients. The Notch signaling pathway plays an important role in osteosarcoma proliferation, which affects tumor resistance by reducing intracellular drug accumulation, regulating epithelial-mesenchymal transition, dysregulating microRNA, disrupting the expression of apoptosis genes, and regulating tumor stem cells.

Ginger-partitioned moxibustion in prevention of vomiting induced by chemotherapy in advanced malignant bone tumors: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of ginger-partitioned moxibustion on digestive tract reaction, quality of life and white blood cell count after chemotherapy in advanced malignant bone tumors patients.@*METHODS@#A total of 64 patients were randomly divided into an observation group and a control group, 32 cases in each group. Both groups were treated with adriamycin combined with cisplatin (AP) chemotherapy. The patients in the control group were treated by tropisetron hydrochloride intravenous on preventing the vomiting 1 h before receiving chemotherapy. On the basis of the control group, the patients in the observation group were treated with ginger-partitioned moxibustion at Neiguan (PC 6), Zusanli (ST 36), Shenque (CV 8), and Zhongwan (CV 12) 2 h after chemotherapy, once a day, 30 min each time. The course of chemotherapy, ginger-partitioned moxibustion and tropisetron hydrochloride intravenous was 5 days. The digestive tract reaction rating, quality of life score and white blood cell count were compared 1 d before chemotherapy, 2 d after chemotherapy and 7 d after chemotherapy between the two groups.@*RESULTS@#The number of 0 grade in digestive tract reaction 2 d and 7 d after chemotherapy in the observation group was significantly higher than that in the control group (@*CONCLUSION@#Ginger-partitioned moxibustion can prevent and treat vomiting after chemotherapy in advanced malignant bone tumors, and improve the quality of life and white blood cell count of patients.

Condrosarcoma costal con diseminación intraperitoneal / Costal Chondrosarcoma with Intraperitoneal Dissemination

RESUMEN El condrosarcoma es definido como un tumor maligno con diferenciación de cartílago hialino puro que puede presentar cambios mixoides, calcificación y osificación. El objetivo es mostrar el resultado del tratamiento de una diseminación peritoneal a partir de un condrosarcoma costal. Se realizó una revisión de la literatura, las indicaciones y técnicas en el tratamiento de la diseminación peritoneal del condrosarcoma y se presentan los resultados en una paciente diagnosticada e intervenida en el Hospital Clínico Quirúrgico "Hermanos Ameijeiras", entre enero de 2014 y diciembre de 2017. Paciente femenina de 46 años, que 7 años antes presentó un aumento de volumen en región costal baja izquierda y fue intervenida quirúrgicamente. Con el diagnóstico de condrosarcoma, se realizó una resección costal en la primera ocasión y luego, en dos oportunidades más por recidiva tumoral, en la última intervención se coloca una prótesis de polipropileno. Dos años después de la última cirugía, acude de nuevo con un aumento de volumen en la parte baja (región tóraco-abdominal, línea axilar), salvo este síntoma, exhibía un estado general excelente. La diseminación peritoneal del condrosarcoma es excepcional, muy poco reportado a nivel mundial y con pocas experiencias en su tratamiento. Se realizó técnica de resección multivisceral y peritonectomía con quimioterapia adyuvante posoperatoria. No hubo complicaciones relacionadas con el proceder y se realizó una segunda intervención extensa por recidiva a los 2 años(AU)

ABSTRACT Chondrosarcoma is defined as a malignant tumor with pure hyaline cartilage differentiation and that may be accompanied with myxoid changes, calcification, and ossification. The objective is to show the treatment outcome for peritoneal dissemination from a rib chondrosarcoma. A review of the literature was carried out, as well as the indications and techniques corresponding to the treatment of chondrosarcoma peritoneal dissemination. The outcomes are presented in a patient diagnosed and operated on at Hermanos Ameijeiras Clinical-Surgical Hospital, between January 2014 and December 2017. Female patient, 46 years old, who, seven years earlier, had presented increased volume in the left lower rib region and undergone surgery. With the diagnosis of chondrosarcoma, a rib resection was performed the first time, and then, on two more occasions due to tumor recurrence, a polypropylene prosthesis was placed in the last intervention. Two years after the last surgery, she returned with increased volume in the lower part (thoracoabdominal region, axillary line), except for the following symptom: she exhibited an excellent general condition. Theperitoneal dissemination of chondrosarcoma is exceptional, very little reported worldwide, and with little treatment experience. A multivisceral resection and peritonectomy technique was performed with postoperative adjuvant chemotherapy. There were no complications related to the procedure and a second extensive intervention was performed after two-year relapse(AU)

Zoledronic acid effect on bone of growing rats / Efecto del ácido zoledrónico en el hueso de ratas en crecimiento

Zoledronic acid (ZA) is an antiresorptive drug used in children with bone diseases like osteogenesis imperfecta, juvenil osteoporosis, fibrous dysplasia and primary bone tumors. The aim of the present study was to evaluate the effects of ZA dose accumulation on growing bone during different periods of treatment in normal rats. Methods: A 4x2 factorial design was used to study the effect of the dose of ZA (D: 0-2.5-12.5-25 µg Z/kg body weight/s.c. weekly) and the length of treatment (T: 15-30 days) in normal female Sprague Dawley rats. Bone morphometric, histomorphometric, densitometric and biomechanical studies were performed. Results: Femoral length and cross-sectional area were affected by both D and T. A significant interaction between D and T was observed in length with a lower value at higher dose and 30 days of treatment. Growth plate of the tibia showed a decrease in total thickness with D and T. Histomorphometric and connectivity parameters of trabecular bone were significantly increased with D and several parameters were also affected by T. Cortical bone strength was increased only with T. Biomechanical parameters of trabecular bone showed significant interaction with greater effect at higher D and T. Conclusion: Even though a mild negative effect of the highest dose of ZA on linear and appositional growth was observed, the other bone parameters evaluated were improved. A careful risk/benefit analysis would lead us to conclude that the mild deleterious effects of ZA during growth are outweighed by the benefit obtained with treatment. (AU)

El ácido zoledrónico (AZ) es un fármaco antirresortivo utilizado en niños con enfermedades óseas como osteogénesis imperfecta, osteoporosis juvenil, displasia fibrosa y tumores óseos primarios. El objetivo del presente estudio fue evaluar los efectos de las dosis acumuladas de AZ en el hueso en crecimiento de ratas hembras normales durante diferentes períodos de tratamiento. Métodos: se utilizó un diseño factorial de 4x2 para estudiar el efecto de la dosis de AZ (D: 0-2,5-12,5-25 µg Z / kg de peso corporal /sc semanalmente) y el período de tratamiento (T: 15-30 días) en ratas Sprague Dawley. Se realizaron estudios óseos morfométricos, histomorfométricos, densitométricos y biomecánicos. Resultados: la longitud y el área de sección transversal del fémur se vieron afectadas tanto por D como por T. Se observó una interacción significativa entre D y T en la longitud obteniéndose un valor más bajo a la dosis más alta y a 30 días de tratamiento. El cartílago de crecimiento de la tibia mostró una disminución en el espesor total con D y T. Los parámetros histomorfométricos y de conectividad del hueso trabecular aumentaron significativamente con D y varios parámetros también se vieron afectados por T. La fortaleza ósea cortical aumentó solo con T. Los parámetros biomecánicos del hueso trabecular mostraron una interacción significativa con un mayor efecto a mayor D y T. Conclusión: a pesar que se observó un leve efecto negativo de la dosis más alta de AZ sobre el crecimiento lineal y aposicional, el resto de los parámetros óseos evaluados mejoraron. Un análisis cuidadoso del riesgo /beneficio permite concluir que los efectos negativos leves del AZ durante el crecimiento son superados por el beneficio obtenido con el tratamiento. (AU)

Astragalus polysaccharides decrease proliferation, migration, and invasion but increase apoptosis of human osteosarcoma cells by up-regulation of microRNA-133a

Osteosarcoma (OS) has a high incidence, malignity, and frequency of recurrence and metastasis. In this study, we aimed to explore the potential anti-cancer effects of Astragalus polysaccharides (APS) on human OS MG63 cells as well as underlying mechanisms. Viability of MG63 cells was assessed by CCK-8 assay to determine the adequate concentration of APS. Then, effects of APS on MG63 cell proliferation, cell cycle distribution, apoptosis, and migration and invasion were analyzed by BrdU incorporation, PI staining, flow cytometry, and transwell assays, respectively. The expression levels of proteins involved in these physiological processes were assessed by western blot analysis. Afterwards, miR-133a level in APS-treated cells was determined by qRT-PCR, and whether APS affected MG63 cells through regulation of miR-133a was determined. Finally, the activation of c-Jun N-terminal protein kinase (JNK) pathway was detected. We found that APS treatment suppressed the viability, proliferation, migration, and invasion of MG63 cells, as well as induced cell apoptosis. Moreover, APS enhanced the expression of miR-133a in MG63 cells. Knockdown of miR-133a reversed the APS treatment-induced MG63 cell proliferation, migration and invasion inhibition, as well as cell apoptosis. Furthermore, APS inactivated JNK pathway in MG63 cells. Knockdown of miR-133a reversed the APS treatment-induced inactivation of JNK pathway in MG63 cells. To conclude, APS repressed proliferation, migration, and invasion while induced apoptosis of OS MG63 cells by up-regulating miR-133a and then inactivating JNK pathway.

MicroRNA-340-5p modulates cisplatin resistance by targeting LPAATβ in osteosarcoma

MicroRNAs (miRNAs) play an important role in drug resistance and modulate the efficiency of chemotherapy. A recent study indicated that miR-340 functions as a tumor suppressor in various types of cancer. However, the role of miR-340 in chemotherapy has not been reported yet. In this study, we found that miR-340 enhanced cisplatin (CDDP)-induced cell death. Induction of miR-340-5p expression decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells. Moreover, miR-340-5p decreased the accumulation of MRP1 and MDR1. We further explored the mechanism underlying the promoting effects of miR-340-5p on CDDP-induced cell death. We identified a potential target of miR-340 in the 3′ untranslated region of lysophosphatidic acid acyltransferase (LPAATβ) using the online program Targetscan (http://www.microrna.org). Luciferase reporter assays showed that miR-340 binds to the 3′UTR of LPAATβ. Enforced expression of miR-340-5p decreased the accumulation of LPAATβ in both MG-63 and Saos-2 cells. Silencing LPAATβ decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells, which is consistent with the effect of miR-340-5p on CDDP-induced cell death. Moreover, induced expression of LPAATβ compromised the effects of miR-340-5p on CDDP-induced cell death and accumulation of MRP1 and MDR1. Taken together, our data indicated that miR-340-5p enhanced the sensitivity to CDDP by targeting LPAATβ.

Eficacia y seguridad de denosumab para el tratamiento de tumor óseo de células gigantes, en pacientes con enfermedad localmente avanzada e irresecable / Efficacy and safety of denosumab for the treatment of giant cell bone tumor in patients with locally advanced and unresectable disease

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación de eficacia y seguridad del uso de denosumab en el manejo de pacientes con tumor óseo de células gigantes con enfermedad localizada \r\nno metastásica. Aspectos Generales: El tumor óseo de células gigantes (TOCG) es considerado un tumor benigno. Sin embargo, este tipo de tumor puede ser agresivo y localmente recurrente hasta en el 50% de los casos. Asimismo, el 5% de las veces este tipo de tumor hace metástasis hacia los pulmones, transformándose en un tumor altamente maligno en 1 a 3% de los casos. Tecnología Sanitaria de Interés: Denosumab (Prolia, Xgeva) es un anticuerpo monoclonal totalmente humano, el cual se une específicamente al ligando del receptor activador para el factor nuclear kappa (RANKL, por sus siglas en inglés). El hueso está formado principalmente por dos tipos de células: los osteoblastos, los cuales se encargan de la formación y mineralización regulando la masa ósea y los osteoclastos, los cuales se encargar de la absorción de la masa ósea; a su vez dichos osteoclastos provienen de un proceso mediado por los osteoblasto. METODOLOGIA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de \r\ndenosumab para el tratamiento de tumor ósea de células gigantes con enfermedad localmente avanzada e irresecable. Esta búsqueda se realizó utilizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE) y National Library of Medicine (Pubmed-Medline). Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas (RS), \r\nevaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como la Cochrane Group, The National lnstitute for Health and Care Excellence (NICE), the Agency for Health care Research and Quality (AHRQ), The Canadian Agency forDrugs and Technologies in Health (CADTH) y The Scottish Medicines Consortium (SMC). RESULTADOS: Sinop´sis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica hasta agosto 2016 para el sustento del uso de denosumab en el tratamiento de tumor ósea de células gigantes con enfermedad localmente avanzada e irresecable. Se presenta la evidencia \r\ndisponible según el tipo de publicación priorizada en los criterios de inclusión (i.e., GP, ETS, RS y ECA fase III). CONCLUSIONES: El presente documento evaluó la evidencia científica publicada hasta agosto \r\ndel 2016 para el uso de denosumab en el tratamiento de tumor óseo de células gigantes (TOCG), en pacientes con enfermedad localizada e irresecable. En la actualidad el petitorio farmacológico de EsSalud cuenta con bifosfonatos el cual es mencionado como alternativa de tratamiento en algunas revisiones sobre TOCG. Sin embargo, los bisfosfonatos no se mencionan dentro de las guías de práctica clínica internacionales revisadas y hasta la fecha no existe evidencia sólida de que dicho tratamiento haya probado un beneficio clínico en pacientes con TOCG. Los resultados presentados en los tres ensayos de fase II, parecen promisorios y la proporción de eventos adversos serios es relativamente baja. Asimismo, la \r\nincidencia de TOCG dentro del sistema de EsSalud es de alrededor de 10 pacientes por año, lo que supone un costo anual de tratamiento de aproximadamente 127,459.20 soles. El Instituto de evaluación de Tecnologías en Salud e Investigación (IETSI) decide aprobar el uso de denosumab para el tratamiento \r\nde tumor óseo de células gigantes (TOCG), en pacientes con enfermedad localizada e irresecable. El periodo de vigencia de este dictamen es de un año y la continuación de dicha aprobación estará sujeta a los resultados obtenidos de os pacientes que se beneficien con dicho tratamiento y a nueva evidencia que \r\npueda surgir en el tiempo. Asimismo, debido a la alta incertidumbre del efecto de este medicamento, es estrictamente necesario un monitoreo cercano para evaluar la respuesta al tratamiento y detectar eventos tóxicos asociados.

Metástasis pulmonares en osteosarcoma neoadyuvancia, tratamiento quirúrgico y supervivencia

La supervivencia global a 5 años de los pacientes con osteosarcoma no-metastásico es del 60-70%, mientras que la misma se reduce a 10-30% en los pacientes con enfermedad diseminada. El objetivo de nuestro estudio fue determinar supervivencia y factores pronósticos en un grupo de pacientes con metástasis pulmonares por osteosarcoma tratados quirúrgicamente. Se realizó una búsqueda retrospectiva en nuestra base de datos oncológica entre 1992-2006, y 38 pacientes fueron incluidos en el estudio. La edad media al momento del diagnóstico fue de 18 ± 9.4 años (3-45) y el seguimiento promedio de 57 ± 53.8 meses (12-231). Todos fueron tratados con quimioterapia, resección oncológica del tumor primario y de las metástasis pulmonares. Se analizó la supervivencia a 5 y 10 años de la serie y los siguientes factores pronósticos: edad, sexo, localización del tumor primario, metástasis de inicio, recidiva local, número de metástasis extirpadas y la respuesta al tratamiento de quimioterapia (necrosis tumoral). La supervivencia global fue de 29% a los 5 años (IC95%:14.5-43.5) y de 26% a los 10 años (IC95%:12-40). Se encontró una diferencia estadísticamente significativa entre los buenos y malos respondedores a la quimioterapia: 53% (IC95%: 28-78) vs. 8% (IC95%: 0-20) (p = 0.0008). No se observó relación estadísticamente significativa entre los demás factores pronósticos analizados. La supervivencia a 5 y 10 años de los pacientes con osteosarcoma y metástasis pulmonares tratados con quimioterapia y resección quirúrgica continúa siendo pobre. Los pacientes con buena respuesta a la quimioterapia neoadyuvante presentan un mejor pronóstico oncológico.

Five years overall survival in osteosarcoma patients is around 70%, although in patients with metastatic disease it is only 10-30%. The objective of this study was to analyze overall survival and prognostic factors in a group of patients with metastatic osteosarcoma treated with surgical removal of the lung metastases. A retrospective review from our oncology data base revealed 38 patients treated between 1992 and 2006. The mean age at diagnosis was 18 ± 9.4 years (3-45) and mean follow-up was 57 ± 53.8 months (12-231). All patients were treated with chemotherapy and oncologic resection of the primary tumor and surgical removal of the lung metastases. We analyzed overall survival and prognostic factors: age, gender, site, time of metastasis, local recurrences, number of lung metastasis and chemotherapy response (necrosis). Overall survival of the entire series was 29% at 5 years (CI95%: 14.5-43.5) and 26% at 10 years (CI95%: 12-40). Significant difference in 5 year overall survival was found between good and bad responders to chemotherapy, 53% (IC95%: 28-78) vs. 8% (IC95%: 0-20) (p = 0.0008). No statistically significant relationship between other prognostic factors analyzed was observed. Five and ten years overall survival rates in osteosarcoma patients with lung metastasis treated with chemotherapy and surgically resection is poor. Patients with good response to chemotherapy have better prognosis.

Comparative Effects of Ibandronate and Paclitaxel on Immunocompetent Bone Metastasis Model

PURPOSE: Bone metastasis invariably increases morbidity and mortality. This study compares the effects of ibandronate and paclitaxel on bone structure and its mechanical properties and biochemical turnover in resorption markers using an immunocompetent Walker 256-Sprague-Dawley model, which was subjected to tumor-induced osteolysis. MATERIALS AND METHODS: Seventy rats were divided equally into 4 groups: 1) sham group (SHAM), 2) tumor group (CANC), 3) ibandronate treated group (IBAN), and 4) paclitaxel treated group (PAC). Morphological indices [bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp)] and mechanical properties (failure load, stiffness) were evaluated after thirty days of treatment period. Bone resorption rate was analysed using serum deoxypyridinoline (Dpd) concentrations. RESULTS: Morphological indices showed that ibandronate (anti-resorptive drug) had a better effect in treating tumor-induced architectural changes in bone than paclitaxel (chemotherapeutic drug). The deterioration in bone architecture was reflected in the biomechanical properties of bone as studied with decreased failure load (F(x)) and stiffness (S) of the bone on the 30th day postsurgery. Dpd concentrations were significantly lower in the IBAN group, indicating successful inhibition of bone resorption and destruction. CONCLUSION: Ibandronate was found to be as effective as higher doses of paclitaxel in maintaining stiffness of bone. Paclitaxel treatment did not appear to inhibit osteoclast resorption, which is contrary to earlier in-vitro literature. Emphasis should be placed on the use of immunocompetent models for examining drug efficacy since it adequately reflects bone metastasis in clinical scenarios.

BK polyomavirus in Kidney transplant recipients: screening, monitoring and clinical management / BK poliomavírus em receptores do transplante renal: rastreamento, monitoramento viral e manuseio clínico

BK polyomavirus (BKPyV) is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid disease progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months. The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits. Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review.

BK Poliomavírus (BKPyV) é um agente causal de nefropatia, estenose ureteral e cistite hemorrágica em receptores de transplante renal, sendo considerado uma importante doença emergente na transplantação. Rastreamento regular para reativação do BKPyV, principalmente nos dois primeiros anos pós-transplante, com subsequente redução preemptiva da imunossupressão é considerada a melhor conduta para evitar a progressão da doença, já que a eliminação ou redução da viremia é alcançada na grande maioria dos pacientes dentro de 6 meses. O uso de drogas com propriedades antivirais para os pacientes com viremia persistente tem sido tentado, embora sem benefícios claros. As manifestações clínicas da nefropatia por BKPyV, as estratégias para o diagnóstico e monitoramento da infecção por BKPyV, o manejo do regime de imunossupressão após a detecção da reativação do BKPyV e o uso de drogas antivirais são discutidas nesta revisão.

Askin tumour: A rare thoracopulmonary tumour in adults.

Askin tumour, a primitive neuroectodermal tumour of the thoracopulmonary region, is a rare tumour presenting in childhood. Its presentation in adults is rare. We report a case of an Askin tumour in an adult patient who presented to us with worsening breathlessness and vague chest pain. Investigations including immunohistochemistry confirmed the diagnosis of Askin tumour.

Tratamiento multimodal del condrosarcoma mesenquimal del hueso temporal: reporte de un caso / Multimodal handling of mesenchymal chondrosarcoma in temporal bone: case report

Se presenta una paciente de 15 años de edad con el diagnóstico de condrosarcoma mesenquimal de hueso temporal derecho con infiltración del músculo temporal y de la duramadre de la fosa media, desplazamiento del lóbulo temporal sin infiltración de parénquima cerebral, diagnosticada en enero del 2010, la cual recibió tratamiento quirúrgico con resección total de la lesión mediante craneotomía temporal, radioterapia de intensidad modulada y quimioterapia como tratamiento coadyuvante.

A 15 year-old patient is present with the diagnostic of a mesenchymal chondrosarcoma of the temporal bone with infiltration of the temporal muscle and with to scroll up of the temporal lobe on January 2010. She had got a temporal craniotomy a radical insensitive modulate radiotherapy and chemotherapy as adjuvant treatment.

What is the best treatment option in postmenopausal, hormone responsive breast cancer patients with isolated bone metastases.

Background: Bone is the most common metastatic site for breast cancer. Aim: To determine the effectiveness of addition of chemotherapy to hormonal therapy in postmenopausal hormone receptor-positive breast cancer patients with isolated bone metastases. Materials and Methods: Between June 2001 and January 2007, 101 patients were classified into two groups according to initial treatment modalities; patients who received hormonotherapy only (group I) and chemotherapy followed by hormonotherapy (group II). The effect of treatment choice on clinical course, time to progression, and overall survival were evaluated. Results: There were 70 patients in group I and 31 patients in group II. Bone metastases in 27 patients (26.7%) were synchronous and the remainder were metachronous. The median follow-up time was 41 months. The two groups showed similar results when patients' tumor characteristics were compared. However, 81% of synchronous cases had upfront chemotherapy following hormonotherapy, whereas this ratio was only 12% in the metachronous group. All patients received systemic antiresorptive bisphosphonates whereas only 24 patients required palliative radiotherapy at some time during the course of their disease. In groups I and II, the median time to progression was 12 and 16 months (P: 0.96) and median overall survival was 41 and 40 months (P: 0.79), respectively. In HER-2-positive patients, a trend of prolongation of overall survival was observed in group II, but it was not statistically significant (P: 0.12). Conclusions: Anti-hormonal therapy still seems to be considered as the ideal treatment of choice for postmenapousal breast cancer patients with isolated bone metastases.

Prognostic Factors for Patients with Bone-Only Metastasis in Breast Cancer

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.