Argon Beam Coagulation as an Adjuvant for Extended Curettage for Giant Cell Tumors of the Bone: A Study of 50 Cases / Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: Um estudo de 50 casos

Abstract Objective Extended curettage with adjuvants of giant cell tumors of bone is associated with a lower rate of recurrence of the tumor while preserving the adjacent joint. The present study was conducted to estimate the recurrence rate and functional outcome after using argon beam as an adjuvant for extended curettage. Methods We selected 50 patients with giant cell tumors, meeting all the inclusion criteria, who underwent extended curettage using high speed burr and argon beam photocoagulation between July 2016 to January 2019. On their follow-up visit, they were assessed for any complaints of pain and signs like tenderness, locally raised temperature, and decreased range of motion of the adjacent joint. Radiologically, the patients were assessed for any increased lucency around the cement mantle and uptake of the subarticular graft. Musculoskeletal Tumor Society Score (MSTS) was administered to the patients, and range of motion of the adjacent joint was compared with the contralateral joint. Results Recurrence was found in 4 patients, that is, an 8% recurrence rate. Twenty-six out of 28 patients with a tumor in the lower limb had a grade-5 weight bearing status 6 months from the surgery, and their range of motion was comparable to contralateral healthy joint with an average MSTS score of 27 (18-30). Conclusion Extended curettage of giant cell tumors using argon beam coagulation is associated with low recurrence rates of the tumor and is an effective modality in the treatment of these tumors besides having a functional outcome comparable to the healthy limb.

Resumo Objetivo A curetagem estendida com adjuvantes de tumores de células gigantes do osso está associada a uma menor taxa de recidiva da neoplasia e à preservação da articulação adjacente. Este estudo foi feito para estimar a taxa de recidiva e o resultado funcional após o uso de plasma de argônio como adjuvante à curetagem estendida. Métodos Cinquenta pacientes com tumores de células gigantes que atendiam a todos os critérios de inclusão foram selecionados para o estudo e submetidos à curetagem estendida com broca de alta velocidade e fotocoagulação com plasma de argônio entre julho de 2016 e janeiro de 2019. À consulta de acompanhamento, os pacientes foram avaliados quanto a quaisquer queixas de dor e sinais como sensibilidade, aumento local da temperatura e diminuição da amplitude de movimento da articulação adjacente. Radiologicamente, os pacientes foram avaliados quanto à presença de qualquer aumento de radiotransparência ao redor do manto de cimento e incorporação do enxerto subarticular. O questionário Musculoskeletal Tumor Society Score (MSTS) foi administrado aos pacientes e a amplitude de movimentação da articulação adjacente foi comparada à articulação contralateral. Resultados Quatro pacientes apresentaram recidiva, o que corresponde a uma taxa de 8%. Seis meses após a cirurgia, 26 de 28 pacientes com tumor no membro inferior tinham capacidade de sustentação de peso de grau 5 e amplitude de movimento comparável à articulação saudável contralateral, com pontuação MSTS média de 27 (intervalo de 18 a 30). Conclusão A curetagem estendida de tumores de células gigantes com coagulação por plasma de argônio está associada a baixas taxas de recidiva da neoplasia; é uma modalidade eficaz no tratamento desses tumores e o resultado funcional é comparável ao do membro saudável.

Intervencionismo para el control del dolor por metástasis óseas / Interventionism for pain control due bone metastases

Objetivo: El dolor óseo por cáncer óseo o metástasis es un dolor de difícil manejo asociado a dolor incidental. Hay distintas estrategias quirúrgicas para su tratamiento, sin embargo, no todos los pacientes con metástasis óseas pueden beneficiarse de un tratamiento quirúrgico. La presente revisión bibliográfica tiene como objetivo identificar terapias intervencionales mínimamente invasivas para el control del dolor por metástasis óseas. Métodos: Revisión bibliográfica acerca de terapias intervencionales para el control del dolor por metástasis óseas utilizando la base de datos PubMed (www.pubmed.gov) y el motor de búsqueda Google (www.google.cl). Tipos de participantes: Pacientes con metástasis óseas dolorosas de cualquier tumor primario. Tipos de intervenciones: Bloqueos anestésicos, bloqueos neurolíticos, terapias ablativas, cementoplastías. Resultados: Se obtuvieron 384 resultados que incluyeron revisiones sistemáticas, revisiones bibliográficas, ensayos clínicos controlados, series de casos y reporte de casos. Todos los artículos relevantes en inglés y español se incluyeron para su análisis. Conclusión: Las metástasis óseas son un evento común en los pacientes con cáncer, y el dolor óseo es un dolor de difícil manejo asociado a dolor incidental. Se han desarrollado terapias intervencionales no invasivas o mínimamente invasivas para tratar el dolor, mejorar la calidad de vida y la funcionalidad, disminuir el consumo de fármacos, y reducir el tamaño del tumor. La gran mayoría ha demostrado ser terapias seguras y eficaces, con pocos eventos adversos y de rápida resolución, y que si son combinadas mejoran los resultados.

Objective: Bone pain from bone cancer or metastasis is a pain that is difficult to manage associated with incidental pain. There are different surgical strategies for its treatment, however, not all patients with bone metastases can benefit from a surgical treatment. This literature review aims to identify minimally invasive interventional therapies for the control of pain due to bone metastasis. Methods: Literature review of interventional therapies for the control of pain due to bone metastases was done using the PubMed database (www.pubmed.gov) and the Google search engine (www.google.cl). Types of participants: Patients with painful bone metastases from any primary tumor. Types of interventions: Anesthetic blocks, neurolytic blocks, ablative therapies, cementoplasties. Results: We obtained 384 results that included systematic reviews, literature reviews, controlled clinical trials, case series and case reports. All relevant articles in English and Spanish were included for analysis. Conclusion: Bone metastases are a common event in cancer patients, and bone pain is a difficult-to-manage pain associated with incidental pain. Non-invasive or minimally invasive interventional therapies have been developed to treat pain, improve quality of life and functionality, decrease drug use, and reduce tumor size. The vast majority therapies have been shown to be safe and effective ones, with few adverse events and rapid resolution, and that if combined they improve the outcomes.

Reconstruction with Unconventional Endoprostheses after Resection of Primary Distal Femoral Bone Tumors: Implant Survival and Functional Outcomes / Reconstrução com endoprótese não convencional após ressecção de tumores ósseos primários de fêmur distal: sobrevida do implante e resultados funcionais

Abstract Objective To evaluate the survival time, the failure rate and its causes, and the functional results of cemented endoprostheses, with a polyethylene body, used after resection of primary bone tumors of the distal femur. Methods A retrospective study including 93 primary and 77 review procedures performed between 1987 and 2014. Survival was obtained by the Kaplan Meyer analysis, and the risk factors for implant failure were assessed through the Cox proportional risk model. The causes of endoprosthesis failure were classified according to Henderson et al. into five types: soft-tissue failure, aseptic loosening, structural fracture, infection, and tumor recurrence. The functional evaluation was performed using the functional classification system of the Musculoskeletal Tumor Society (MSTS) of bone sarcomas of the lower extremity, Brazilian version (MSTS-BR). Results Osteosarcoma was the most common diagnosis; 64.5% of the patients were younger than 20 years of age; the mean follow-up was of 124.3 months. The failure rate of the primary implant was of 54.8%, and the mean survival was of 123 months. The estimated survival of the primary implant was of 63.6%, 43.5%, 24.1%, and 14.5% in 5, 10, 15, and 20 years respectively. The most common cause of failure was type 2 (37.3%). Age ≤ 26 years and right side were risk factors for failure. The mean MSTS-BR score was of 20.7 (range: 14 to 27). Conclusion The results obtained for the failure rate and survival of the implant are in accordance with those of the literature, so the procedure herein studied is adequate and yields satisfactory functional results, even in the long term.

Resumo Objetivo Avaliar o tempo de sobrevida, a taxa de falha e suas causas, e os resultados funcionais de endopróteses cimentadas, com corpo em polietileno, empregadas após ressecção de tumores ósseos primários do fêmur distal. Métodos Estudo retrospectivo, que incluiu 93 procedimentos primários e 77 de revisão, realizados entre 1987 e 2014. A sobrevida foi obtida pela análise de Kaplan Meyer, e os fatores de risco para falha do implante foram avaliados por meio do modelo de riscos proporcionais de Cox. As causas de falha da endoprótese foram classificadas segundo Henderson et al. em cinco tipos: falha de partes moles, soltura asséptica, fratura estrutural, infecção e recorrência do tumor. A avaliação funcional foi realizada por meio do sistema de classificação funcional da Musculoskeletal Tumor Society (MSTS) para sarcomas ósseos da extremidade inferior, versão brasileira (MSTS-BR). Resultados Osteossarcoma foi o diagnóstico mais comum; 64,5% dos pacientes tinham menos de 20 anos; e o seguimento médio foi de 124,3 meses. A taxa de falha do implante primário foi de 54,8%, e a sobrevida média foi 123 meses. A estimativa de sobrevida do implante primário foi de 63,6%, 43,5%, 24,1%, 14,5% em 5, 10, 15 e 20 anos, respectivamente. A causa de falha mais comum foi a do tipo 2 (37,3%). Idade ≤ 26 anos e lado direito foram fatores de risco para falha. A pontuação média no MSTS-BR foi de 20,7 (variação: 14 a 27). Conclusão Os resultados obtidos para a taxa de falha e o tempo de sobrevida do implante estão de acordo com os da literatura, de forma que o procedimento estudado é adequado e apresenta resultados funcionais satisfatórios, inclusive em longo prazo.

Sarcoma de Ewing mesencefálico: reporte de caso / Mesencephalic Ewing sarcoma: Case report

El sarcoma de Ewing es una neoplasia de origen más frecuentemente óseo; otras localizaciones son excepcionales. En el caso de las presentaciones primarias intracraneales, resulta imprescindible descartar que se trate de un secundarismo así como también de otros tumores neuroectodérmicos que puedan requerir distintos abordajes diagnósticos y terapéuticos. Se presenta a una paciente de 14 años que consultó por ptosis palpebral de ojo izquierdo asociado a diplopía de 2 meses de evolución; los estudios por imágenes mostraron una lesión tumoral extraaxial situada a nivel de la cisterna interpeduncular. Se realizó la exéresis completa, con diagnóstico anatomopatológico de sarcoma de Ewing de ubicación mesencefálica

Ewing's sarcoma is a malignant neoplasm mainly occurring in the bone, with other locations being exceptional. In the case of primary intracranial presentations, it is essential to rule out metastatic lesions as well as other neuroectodermal tumors that may require different diagnostic and therapeutic approaches. We present a 14-year-old patient who consulted for upper eyelid ptosis of left eye associated with a 2-month history of diplopia, with imaging evidence of extra-axial tumor lesion, located at the level of the interpeduncular cistern. Complete excision was performed, with a pathological diagnosis of Ewing's sarcoma of midbrain location.

Estudio clínico, radiológico y derivación en tumores musculoesqueléticos / Diagnosis and referral of musculoskeletal tumors

Musculoskeletal tumors are uncommon. However, the true burden of all bone and soft tissue tumors of extremities is underestimated. Usually, the diagnosis of sarcomas is missed or delayed. Therefore, an adequate clinical and radiological assessment, along with the awareness and application of simple guidelines for referral to a specialized center, are of utmost importance. These are critical steps for an appropriate diagnosis and treatment of sarcomas, improving their prognosis.

Treatment of Metastasis in the Appendicular Skeleton / Tratamento das metástases no esqueleto apendicular

Abstract Bone metastases may evolve with events (pain, fractures and compression) that the orthopedic surgeon will encounter regardless of his subspecialty. Accumulated surgical knowledge is predictive for the prevention of impending fractures, as well as of pathological fractures. We will present a guide to properly evaluate and conduct a patient with bone implant for surgeons who are not specialists in this area.

Resumo As metástases ósseas podem evoluir com eventos (dor, fraturas e compressão) com os quais o cirurgião ortopédico irá se depararar independentemente da sua subespecialidade. Os conhecimentos cirúrgicos acumulados são predicativos para a prevenção de fraturas iminentes, assim como de fraturas patológicas. Apresentaremos um guia para avaliar e conduzir de forma adequada um paciente com implante ósseo para cirurgiões que não sejam especialistas na área.

Manejo del dolor óseo en pacientes cancerosos / Bony pain management in cancerous patients

Las metástasis óseas se desarrollan en aproximadamente 30 a 70% de todos los pacientes con cáncer. El dolor es una experiencia de la condición humana universal, y es común que las personas busquen atención médica a raíz de ello. El presente estudio tuvo como objetivo describir la eficacia y el papel de diferentes estrategias en el control del dolor óseo en pacientes cancerosos metastásicos. Se trata de un estudio observacional realizado entre el 1 de diciembre de 2018 y el 30 de diciembre de 2019. Se inscribieron exactamente 100 pacientes cancerosos. Los pacientes fueron evaluados antes de recibir las modalidades de control del dolor, al principio y al final del tratamiento. La puntuación del dolor óseo se utilizó de 0 (sin dolor) a 10 (el peor dolor). Nuestros hallazgos con respecto al sexo, hubo 51 (51%) hombres y 49 (49%) mujeres. La edad media fue de 57,3 ± 11,2 años y el grupo de edad más frecuente fue de 41-50 años, 37 (37%). Entre los tipos de cáncer, el cáncer de mama ocupa el primer lugar entre los casos estudiados en nuestra investigación 37 (37%), seguido del cáncer de próstata 24 (24%). Las vértebras de la columna fueron el sitio más representado en un 52%, seguido de los huesos pélvicos en un 36%. La mayoría de los pacientes no requirieron cirugía. Mientras que el 15% de los pacientes se sometieron a descompresión del cordón, el 13% requirió fijación interna y solo cuatro pa- LA PRENSA MÉDICA ARGENTINA Bony pain management in cancerous patients 117 V.107/Nº 2 cientes se sometieron a vertebroplastia. El dolor agudo se describió comúnmente en un 40%, seguido de naturaleza punzante en un 15%. El dolor frecuente fue más prevalente en el 60% de los pacientes, mientras que el dolor constante se presentó en el 40%. La noche fue el momento más común de sentir dolor en el 55%. Después de recibir el tratamiento, varias modalidades provocan un desplazamiento de la puntuación del dolor hacia abajo. Combinación de más de estrategias más eficientes que utilizar una opción para el manejo del dolor óseo con un mejor resultado y pronóstico.

Bone metastases develop in approximately 30­70% of all cancer patients. Pain is a universal human experience condition, and it is a common question for people to seek health care. The study aimed to describe the efficacy and roles of different strategies in the control of bony pain in metastatic cancerous patients. This is an observational study carried out, from the 1st of December 2018 to the 30th of December 2019. Exactly 100 cancerous patients were enrolled. Patients were assessed before received of pain control modalities, in the beginning, and at the end of treatment. Bone pain scoring was used from 0 (no pain) to 10 (the worst pain). Our findings regarding sex, there were 51(51%) male and 49(49%) female. The mean age was 57.3±11.2 years, and the most frequent age group was 41-50 years as 37(37%). Among cancer types, breast cancer comes in 1st rank cases studied in our research 37(37%), followed by prostate cancer 24(24%). Spine vertebrae were the most site figured 52%, followed by pelvic bones in 36%. Most patients did not require surgery. Whereas 15% of patients underwent cord decompression, 13% required internal fixation and only four patients performed for vertebroplasty. The sharp pain was commonly described by 40%, followed by stabbing nature in 15%. Frequent pain was more prevalent in 60% of patients, whereas constant pain presented in 40%. The night was the commonest timing of feeling pain in 55%. After receiving treatment, several modalities cause shifting of the pain scoring downward. Combination of more than strategies more efficient than of use one option for manage of bone pain with a better outcome, and prognosis.

Sarcoma de Ewing óseo: Enfoque multidisciplinario y resultados oncológicos en 88 pacientes / Ewing sarcoma of the bone. Multidisciplinary approach and oncological results in 88 patients

El sarcoma de Ewing óseo es un tumor poco frecuente, agresivo, que afecta principalmente a niños y adultos jóvenes. Existe ausencia de registros en nuestro país respecto de la prevalencia de esta enfermedad, los esquemas de tratamiento utilizados y sus resultados. El objetivo fue analizar, en un grupo de pacientes con sarcoma de Ewing óseo tratados con quimioterapia y cirugía de conservación de miembro, las tasas de supervivencia global, de recurrencia local y los factores de riesgo oncológicos. Se incluyó a 88 pacientes. La edad media de la serie fue de 14.5 años y el seguimiento promedio de 8.8 años. La tasa de supervivencia global fue de 79.5% a los 2 años, de 69% a 5 años y de 64% a 10 años. Los factores pronósticos negativos asociados a menor supervivencia fueron: mala respuesta a la quimioterapia, edad ≥ de 16 años, localización central, y recurrencia local. En el análisis multivariable únicamente la respuesta a la quimioterapia tuvo significancia estadística. La tasa libre de recurrencia local a 2 y 5 años fue del 87%. La mala respuesta a la quimioterapia fue el único factor significativo para la recurrencia local. Consideramos que la cirugía de conservación de miembro asociada a quimioterapia pre y postoperatoria debe ser el tratamiento para el sarcoma de Ewing óseo, alcanzando de esta manera una supervivencia global a 5 años del 69%. En nuestra serie, la respuesta a la quimioterapia ha sido el factor pronóstico más relevante para supervivencia y recurrencia local.

Ewing sarcoma of the bone is a rare, highly aggressive tumor that typically affects children and young adults. In Argentina, the lack of Ewing's sarcoma registries reflects in the absence of information regarding prevalence, treatment protocols and patient´s outcome. The purpose of this study was to analyze, in a group of patients diagnosed with Ewing sarcoma of the bone, treated with chemotherapy and limb-conserving surgery, their overall survival rate, local recurrence rate, and oncological risk factors. A retrospective research was conducted between 1990 and 2017. Eighty-eight patients with Ewing sarcoma of the bone matched the inclusion criteria. Median age was 14.5 years and median follow-up was 8.8 years. Overall survival rate was 79.5%, 69% and 64% at 2, 5 and 10 years respectively. Negative prognostic factors, associated with less survival rate after univariate analysis, were: bad response to chemotherapy (tumoral necrosis 0-89%), age > 16 years-old, central tumor localization and local recurrence. Gender and tumor size were not significant prognostic factors. After multivariate analysis, response to chemotherapy remained statistical significant. Local recurrence-free survival rate at 2 and 5 years was 87%. Tumor response to chemotherapy (0-89%) was the only significant factor for local recurrence. We consider that limb-salvage surgery, with neoadjuvant and adjuvant chemotherapy, are the mainstays of treatment for Ewing's sarcoma, with an overall survival rate, at 5 years, of 69%. In this population, response to chemotherapy is the most relevant prognostic factor, being associated with both local recurrence and overall survival.

Delays in the health care system for children, adolescents, and young adults with bone tumors in Brazil / Atrasos no sistema de saúde para crianças, adolescentes e adultos jovens com tumores ósseos no Brasil

ABSTRACT Objective: To identify delays in the health care system experienced by children and adolescents and young adults (AYA; aged 0-29 years) with osteosarcoma and Ewing sarcoma using information from the Brazilian hospital-based cancer registries. Methods: Patient data were extracted from 161 Brazilian hospital-based cancer registries between 2007 and 2011. Hospital, diagnosis, and treatment delays were analyzed in patients without a previous histopathological diagnosis. Referral, hospital, and health care delays were calculated for patients with a previous histopathological diagnosis. The time interval was measured in days. Results: There was no difference between genders in overall delays. All delays increased at older ages. Patients without a previous histopathological diagnosis had the longest hospital delay when compared to patients with a previous histopathological diagnosis before first contact with the cancer center. Patients with Ewing sarcoma had longer referral and health care delays than those with osteosarcoma who had a previous histopathological diagnosis before first contact with the cancer center. The North and Northeast regions had the longest diagnosis delay, while the Northeast and Southeast regions had the longest treatment delay. Conclusion: Health care delay among patients with a previous diagnosis was longer, and was probably associated with the time taken for to referral to cancer centers. Patients without a previous histopathological diagnosis had longer hospital delays, which could be associated with possible difficulties regarding demand and high-cost procedures. Despite limitations, this study helps provide initial knowledge about the healthcare pathway delays for patients with bone cancer inside several Brazilian hospitals.

RESUMO Objetivo: Identificar atrasos no sistema de saúde em crianças e adolescentes e adultos jovens (AAJ; até 29 anos) com osteossarcoma e sarcoma de Ewing com informações dos registros de câncer de base hospitalar do Brasil. Métodos: Os dados dos pacientes foram extraídos de 161 registros de câncer de base hospitalar brasileiros entre 2007 e 2011. Os atrasos no hospital, no diagnóstico e no tratamento foram analisados em pacientes sem um diagnóstico histopatológico anterior. Os atrasos no encaminhamento, no hospital e no sistema de saúde foram calculados para pacientes com diagnóstico histopatológico anterior. O intervalo de tempo foi medido em dias. Resultados: Não houve diferença entre os sexos nos atrasos em geral. Todos os atrasos aumentaram na faixa etária mais velha. Os pacientes sem um diagnóstico histopatológico anterior apresentaram o atraso hospitalar mais longo em comparação com os pacientes com diagnóstico histopatológico anterior antes do primeiro contato com o centro de câncer. Os pacientes com sarcoma de Ewing apresentaram atrasos no encaminhamento e no sistema de saúde mais longos do que os com osteossarcoma, que apresentaram diagnóstico histopatológico anterior antes do primeiro contato com o centro oncológico. As regiões Norte e Nordeste apresentaram o atraso mais longo no diagnóstico, ao passo que as regiões Nordeste e Sul apresentaram o atraso mais longo no tratamento. Conclusão: O atraso no sistema de saúde entre os pacientes com diagnóstico anterior foi maior e provavelmente associado ao tempo de encaminhamento para os centros oncológicos. Os pacientes sem um diagnóstico histopatológico anterior apresentaram atrasos mais longos no hospital, o que pode ser associado a possíveis dificuldades com relação à demanda e aos procedimentos de alto custo. Apesar das limitações, nosso estudo ajuda a fornecer um conhecimento inicial sobre os atrasos no sistema de saúde para tratamento de pacientes com câncer em vários hospitais brasileiros.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Manejo expectante de osteocondroma solitario interóseo de la tibia distal: reporte de un caso y revisión de la literatura / Non-surgical management of an interosseous solitary osteochondroma of the distal tibia: a case report and review of the literature

La localización del osteocondroma en la tibia distal es poco frecuente y su crecimiento con compromiso y deformidad del peroné distal es aún más raro, haciéndolo una condición más sintomática que en otras ubicaciones. Factores como la severidad de los síntomas, deformidad progresiva del tobillo, complicaciones sindesmóticas, riesgo de fractura patológica o transformación maligna, junto con nuevas y mejores técnicas quirúrgicas, han llevado a que el manejo expectante de esas lesiones sea excepcional y escasamente reportado. Presentamos el caso de un joven de 17 años con osteocondroma solitario interóseo tibio distal sintomático y compromiso fibular, que fue exitosamente manejado en forma expectante. A los 5 años de seguimiento clínico-radiológico no presenta complicaciones y la lesión se mantiene estable.

Osteochondromas located in the distal tibia are a rare condition, and the involvement of the distal fibula with deformity is even more uncommon. Factors such as the severity of symptoms, progressive deformity of the ankle, syndesmotic complications, the risk of pathological fracture or malignant transformation, together with new and safer surgical techniques, have led to scarce reports of non-surgical management. We present a case report of a 17-year-old male with a symptomatic interosseous solitary osteochondroma in the distal tibia with fibular involvement, which was successfully managed non surgically. After 5 years of clinical and radiological follow-up, he has no complications, and the lesion remains stable.

Up-regulated expression of CD147 gene in malignant bone tumor and the possible induction mechanism during osteoclast formation

It is increasingly evident that the microenvironment of bone can influence cancer phenotype in many ways that favor growth in bone. CD147, a transmembrane protein of the immunoglobulin (Ig) superfamily, was identified independently in different species and has many designations across different species. However, expression levels of CD147 mRNA in bone cancer have not been described. In this study, we have used real-time fluorescence quantification (RT-PCR) to demonstrate CD147 expression in malignant bone cancer and benign bone tumor tissues. The results suggested that the expression of CD147 gene was significantly up-regulated in malignant bone cancer. Moreover, we found that over-expressed RANKL progressively enhanced osteoclast formation up to 48 h, which suggested that RANKL could promote the formation of osteoclast, indicating that both CD147 and RANKL play important roles in the formation of osteoclasts. Furthermore, the expressions of four osteoclast specific expression genes, including TRACP, MMP-2, MMP-9 and c-Src, were analyzed using RT-PCR. The results indicated that four osteoclast-specific expression genes were detectable in all osteoclast with different treatments. However, the highest expression level of these four osteoclast-specific expression genes appears in the CD147+ RANKL group and the lowest expression level of these four osteoclast-specific expression genes appears with si-RANKL treatment. Characterization of the role of CD147 in the development of tumors should lead to a better understanding of the changes occurring at the molecular level during the development and progression of primary human bone cancer.

Denosumab, tratamiento alternativo en tumor óseo de células gigantes / Denosumab, an alternative treatment for giant cell tumor of bone

Introducción: el tumor óseo de células gigantes (TOCG) es un tumor benigno pero localmente agresivo. Se presenta en población joven y a nivel epifiso-metafisario. Está compuesto por una población celular estromal y otra multinucleada similar a los osteoclastos, donde se destaca la interacción RANK-RANKL (receptor del activador del factor nuclear kappa-B y su ligando, respectivamente). El anticuerpo monoclonal humano denosumab actúa inhibiendo específicamente RANKL, lo que evita la formación y activación de células multinucleadas. En la bibliografía se evidencia que denosumab tiene resultados alentadores como tratamiento adyuvante de algunos TOCG, generando planes terapéuticos con una menor morbimortalidad que los planteados previamente a la administración del anticuerpo. Material y método: se describe la primera experiencia terapéutica en Uruguay con dos pacientes menores de 40 años que consultaron por gonalgia de larga data, realizándose diagnóstico de TOCG estadio III de Campanacci, donde se realiza tratamiento con denosumab de forma protocolar valorando respuesta clínica, imagenológica, efectos adversos y modificación en plan terapéutico inicial. Resultados: se evidenció una respuesta clínica e imagenológica en los pacientes valorados. No se reportaron efectos adversos, logrando preservar la articulación afectada. Conclusiones: los resultados obtenidos son alentadores respecto al uso terapéutico de denosumab en los pacientes seleccionados. Esto permite considerar a denosumab dentro de las opciones terapéuticas de determinados pacientes con diagnóstico de TOCG.

Introduction: giant cell tumor of bone (GCTB) is a benign tumor, although it is locally aggressive. It arises mainly in young people at the epi-metaphyseal level. It consists of stromal cells and osteoclasts-like populations, where the RANK-RANKL (receptor activator of nuclear factor kappa-B and its ligand, respectively) stands out. Denosumab, the human monoclonal antibody, acts by specifically inhibiting RANKL, what prevents the formation and activation of multinucleate cells. The existing bibliography indicates denosumab has obtained encouraging results as adjuvant treatment for some GCTB, enabling therapeutic plans that have lower morbi-mortality rates than those applied prior to administration of the antibody. Method: the study describes the therapeutic experience of two patients younger than 40 years old, who consulted in Uruguay for long standing gonalgia. Campanacci Stage III GCTB was diagnosed, and denosumab treatment was initiated. Clinical response was assessed, as well as imaging response, adverse side effects and the modification of initial treatment. Results: clinical and imaging response was seen in the assessed patients. No adverse side effects were reported, and the affected joint was preserved. Conclusions: the results obtained are encouraging with regard to the therapeutic use of denosumab in the selected patients. This allows for denosumab to be regarded within the therapeutic options for certain patients with a diagnosis of GCTB.

Introdução: O tumor de células gigantes ósseo (TOCG) é um tumor benigno, porém agressivo. Apresenta-se em jovens localizando-se na metáfise e epífise dos ossos; compõe-se de uma população celular estromal e outra multinucleada similar aos osteoclastos, donde se destaca a interação RANK-RANKL (receptor do ativador do fator nuclear kappa-B e seu ligando, respectivamente). O anticorpo monoclonal humano denosumab age inibindo especificamente o RANKL, evitando a formação e a activação de células multinucleadas. A bibliografia mostra que o denosumab tem resultados animadores como tratamento adjuvante de alguns TOCG, com planos terapêuticos com menor morbimortalidade que os utilizados antes da administração do anticorpo. Material e método: descreve-se a primeira experiencia terapêutica no Uruguai com dois pacientes com menos de 40 anos que consultaram por gonalgia de longa data, realizando-se diagnóstico de TOCG estádio III de Campanacci; realizou-se tratamento com denosumab de acordo com o protocolo e avaliando a resposta clínica, a imagenología, os efeitos adversos e a modificação no esquema terapêutico inicial. Resultados: evidenciou-se uma resposta clínica e na imagenología nos pacientes avaliados. Não se informaram efeitos adversos, sendo possivel preservar a articulação afetada. Conclusões: os resultados obtidos são animadores com relação ao uso terapêutico do denosumab nos pacientes selecionados. Isto permite considerar o denosumab como opção terapêutica para determinados pacientes com diagnóstico de TOCG.

Osteosarcoma multicéntrico sincrónico con múltiples tumores primarios o enfermedad metastásica: Reporte de un caso y revisión de la literatura / Synchronous multicentric osteosarcoma: with multiple primary tumors or metastatic disease. Report of one case and literature review

El osteosarcoma multicéntrico sincrónico, es un tumor cuya presentación ocurre en dos o más sitios sin la aparición de metástasis pulmonares. Tiene una incidencia de 1 al 3% de todos los osteosarcomas y sólo se han documentado menos de 100 casos en la literatura. En nuestro caso, presentamos a un paciente de seis años seis meses de edad con una tumoración dolorosa en muslo izquierdo, diagnosticado mediante toma de biopsia incisional, la cual reportó osteosarcoma convencional de alto grado en fémur distal izquierdo, con una lesión en la extremidad contralateral en fémur distal y tibia proximal, sin respuesta favorable a la quimioterapia. Se detectaron metástasis pulmonares y cerebrales, por lo que se decidió en forma multidisciplinaria brindar manejo paliativo de la enfermedad. Aun años después de su descripción continúa el debate sobre si esta condición realmente corresponde a una variante primaria o bien a una manifestación de la enfermedad metastásica.

Synchronous multicentric osteosarcoma, is a tumor with presentation in two or more sites without the appearance of lung metastasis. The incidence is 1 to 3% of all osteosarcomas and only less than 100 cases have been documented in the literature. In our case, we are presenting a six and a half year old patient with a painful tumor in the left thigh diagnosed with an incisional biopsy that reported a high grade conventional osteosarcoma in the left distal femur, a lesion in the contralateral limb in distal femur and proximal tibia, with no favorable response to chemotherapy. Lung and brain metastases were detected; therefore, we decided to give multidisciplinary palliative care for the disease. Years after its description there is still debate whether this condition really corresponds to a primary variable or to a manifestation of the metastatic disease.

A meta-analysis of limb-salvage versus amputation in the treatment of patients with Enneking II pathologic fracture osteosarcoma.

Introduction: The aim of this meta-analysis was to further explore whether the relapse, 5-year survival and metastasis the same or not between limb-salvage and amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma. Materials and Methods: An electronic search of the Medline, EMBASE and CNKI was done on October 2014. The clinical studies about amputation or limb-salvage surgery in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma were searched and reviewed. The effect size of relapse, 5-year survival and metastasis between the amputation and limb-salvage surgery were pooled by stata11.0 software (Stata Corporation, College Station, TX, USA, http://www.stata.com;) using random or fixed effect model. The funnel plot and Egger's line regression test were used for evaluation of publication bias. Results: A total of 89 studies were identified and seven articles with 200 cases in the limb-salvage surgery group and 84 subjects in the amputation group were finally included in the meta-analysis. The pooled data indicated that no statistical different of risk for developing relapse between limb-salvage and amputation was found relative risk (RR) =1.40, 95% confidence interval (CI): 0.71-2.79, (P = 0.33). The 5-year survival rate of patients underwent limb-salvage surgery was smaller than patients received amputation RR = 1.86, 95%CI: 1.19-2.89, (P = 0.01); the metastasis rate of patients underwent limb-salvage surgery was significant decreased compared with patients received amputation RR = 0.56, 95% CI: 0.34-0.94, (P = 0.03). No publication bias was existed in this meta-analysis. Conclusion: Limb-salvage surgery does not increased the risk of relapse compared with amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma.

Non surgical treatment of sacral osteosarcoma

Osteosarcoma may rarely originate from the axial bones such as pelvis or vertebrae. In some pelvic and most vertebral primary tumors, resection often is not possible completely. In general, these tumors cannot be resected with negative margins so they need additional radiotherapy and chemotherapy, but results are unfavourable because of poor local control and high incidence of distant metastases. This is a case report of sacral osteosarcoma which was treated successfully with chemotherapy and radiation therapy. The patient is a 14-year-old boy with a large osteosarcoma tumor in the first sacral vertebral body, with extra skeletal extension. The patient took radiotherapy [6000 centigray] plus chemotherapy regimen consisting of doxorubicin and cisplatin. In the last follow up 48 months later, the patient was completely asymptomatic with normal performance and there was not any evidence of local progression or distant metastasis

Osseous involvement in pediatric hodgkin’s lymphoma.

Presented here is a report of 3 children, out of 66 total pediatric Hodgkin’s lymphoma (HL) patients (4.5%) with bone involvement over a 3 and a half year period. Two patients presented with osseous lesions at the time of relapse and one had concurrent evidence of non-osseous disease. The clinical presentation, radiographic findings, histology, treatment and outcome of these patients are discussed. Boys and girls are nearly equally affected, local bone pain is the commonest symptom and B-symptoms are common. Vertebrae and pelvis are most frequently involved, commonly with an osteolytic picture. Nodular sclerosis is the predominant histological subtype. Most children received combined modality treatment and the overall response and survival are good.

Ephrin A4 expression in osteosarcoma, impact on prognosis, and patient outcome.

Background : Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family. It was originally identified in a T-lymphoma cell line and seen to be expressed in human adult tissue as well as several tumor types. In our previous study, we showed the unique pattern of ephrin A4 immunohistochemical staining, which differed according to the type of examined bone specimens (normal bone, primary, and metastatic osteosarcoma lesions). The aim of the present study is to evaluate the prognostic impact of ephrin A4 expression in a group of primary osteosarcoma patients. Materials and Methods : Ephrin A4 immunohistochemical expression was carried out on 47 primary osteosarcoma cases. Results : Ephrin A4 was expressed in 82.9% of osteosarcoma cases with cytoplasmic localization in 58.9% of positive cases. The cytoplasmic pattern was significantly associated with aggressive histopathological types of osteosarcoma (P = 0.02), advanced stage (P = 0.04), the presence of metastasis (P = 0.03), inferior response to neoadjuvent chemotherapy (P = 0.04), and tended to be associated with a shorter event-free survival (P = 0.09). Conclusions : The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.