IMP3, CDK4, MDM2 and ß-catenin expression in Enchondroma and Central Chondrosarcoma: Diagnostic and prognostic utility.

INTRODUCTION: The role of IMP3, CDK4, MDM2 and ß-catenin proteins in Enchondroma and Central Chondrosarcoma is not totally understood. The aim of this study is to evaluate the immunoexpression of these proteins, associating histological grade, clinical data and prognosis to these tumors. METHODS: This is a retrospective-analytical study of 32 Enchondroma and 70 Central Chondrosarcoma. RESULTS: IMP3, CDK4, MDM2 and ß-catenin expression was observed in 22.82 %, 13.82 %, 17.17 % and in 8.8 % of cases, respectively. All Enchondromas positive for these immunomarkers were located in short tubular bones. The positivity for these antibodies is directly proportional to Chondrosarcoma's histological grade increase. No difference was found between Enchondroma and Chondrosarcoma, Grade 1 for IMP3, CDK4 and ß-catenin positivity. Significant metastasis outcome was observed for IMP3, CDK4, MDM2 and death for MDM2 expression. CONCLUSION: IMP3, CDK4, MDM2 and ß-catenin expression in Enchondromas of short bones phenotypically characterizes these tumors. Their expression has not proven to be useful either as diagnostic markers of these neoplasms or in distinguishing between Enchondroma and Chondrosarcoma, Grade 1. The significant immunoexpression of IMP3, CDK4 and MDM2 in metastatic Chondrosarcoma and the lower survival in those with positivity for MDM2 suggest a possible association of these proteins with tumor aggressiveness.

Radiofrequency ablation of bilateral splanchnic nerves in a 15-year-old patient with visceral abdominal pain cancer.

Pain, a prevalent and debilitating symptom in cancer patients, significantly diminishes the quality of life for both individuals and their families. Addressing this critical issue, our study presents the case of a 15-year-old diagnosed with synchronous multifocal multicentric osteosarcoma. We utilized radiofrequency ablation of bilateral splanchnic nerves, a strategy of multimodal pain and palliative care. This approach not only proved to be safe and effective but also markedly improved the patient's quality of life. Our findings shine a light of hope, emphasizing the paramount importance of innovative pain management in pediatric oncology, especially in the final stages of life. This case report highlights the unwavering dedication to excellence in relieving suffering, offering hope for patients grappling with cancer.

Pain is a common and serious problem for cancer patients, osteosarcoma is a type of bone cancer that often affects children. making life hard for them and their families. We used a therapy called radiofrequency ablation on specific nerves to manage the pain. In the case of the patient's abdominal pain, this therapy was safe, worked well, and greatly improved the patient's quality of life. Our findings show the importance of new pain management methods in helping children with cancer, helping them reduce pain, using fewer strong pain medications and helping children in this case in the final stage of life.

Dosimetry at cellular level for the alpha-emitting radionuclides actinium-225, astatine-211 and radium-223 for bone metastasis cells from castration resistant prostate cancer.

Objectives.The aim of this work is to evaluate energy deposition in the nucleus and cytoplasm in targeted alpha therapy of metastatic castration-resistant prostate cancer by modeling two cell lines, PC3 (osteolytic) and LNCaP C4-2 (osteoblastic), for actinium-225, astatine-211, and radium-223 and their progeny, using Monte Carlo simulations with the GATE/Geant4 code.Approach.We developed single cell and cell clusters models to Monte Carlo simulations, performed on the GATE platform version 9.3, with the GEANT4-DNA physics list emstandard_opt3_mixed_dna for At-211, Ac-225 and Ra-223 progenies. We considered three radionuclide distributions as a sources: the nucleus, the cytoplasm and the whole cell.Main results.When the nucleus was considered as a target, theS-values (N←N) calculated for At-211, Ac-225 and Ra-223 progenies were significantly higher, within 60%-90%, thanS-values (N←Cy), demonstrating less influence of cytoplasm only internalization. When the cytoplasm was considering as a target, theS-values (Cy←Cy) calculated for At-211, Ac-225 and Ra-223 progeny were significantly higher, within 30%-90%, than theS-values (Cy←N). When no progeny migration occurs and for target nucleus , the cumulativeS-values (N←N) calculated for At-211, Ac-225 and Ra-223 were significantly higher, within 50%-70%, than theS-values (N←N) computed for At-211, Ac-225, and Ra-223. Comparing the cumulativeS-values, Ac-225 and Ra-223 therapies is more effective, in terms of deposited energy in a target, than that with At-211.Significance.The data presented in this research indicates that Ac-225 therapy may be the optimum choice due to the energy deposited in the nucleus, as long as the recoil effects and redistribution of progeny are understood. In contrast, At-211 is an alternative to avoid progeny migration. However, to completely analyze the efficacy of radionuclide therapy, other parameters must be considered, such as biological half-life, stability of the transport molecule, progeny migration, excretion pathways, and uptake in different organs.

Sarcoma de Ewing extraesquelético: reporte de caso / Extraskeletal Ewing's Sarcoma: a Case Report

Introducción: El sarcoma de Ewing es un tumor maligno de alto grado con localización principalmente ósea; se han reportado aproximadamente 12% con presentación extra-esquelética. Actualmente, existen alrededor de 20 casos descritos en la literatura con origen mediastinal y 10 casos con origen pulmonar. Caso clínico: Se presenta el caso de una mujer de 25 años con un mes de disnea y dolor torácico, con el hallazgo de derrame pleural masivo y tumoración mediastinal en hemitórax derecho. Se le realiza toracotomía anterior bilateral con esternotomía transversa de Clamshell, con resección parcial que demuestra, por patología, sarcoma monomórfico de alto grado e inmunohistoquímica concluyente de sarcoma de Ewing. Conclusión: Este caso es una entidad rara y conlleva un reto diagnóstico para el clínico; sin embargo, debe sospecharse considerando la presentación clínica y radiológica del paciente, buscando incrementar la tasa de supervivencia mediante el diagnóstico y tratamiento oportuno.

Introduction: Ewing's sarcoma is a high-grade malignant tumor with mainly bony lo-calization; approximately 12% have been reported with extraskeletal presentation. Currently, there are about 20 cases described in the literature with mediastinal origin and 10 pulmonary cases. Case Report: We present the case of a 25-year-old woman with one month of dysp-nea and chest pain, with massive pleural effusion and mediastinal tumor in the right hemithorax who underwent bilateral anterior thoracotomy with Clamshell transverse sternotomy, with partial resection demonstrating, by pathology, high-grade monomorphic sarcoma and conclusive immunohistochemistry of Ewing's sarcoma. Conclusion: This case is a rare entity and involves a diagnostic challenge for the clinician; however, it should be suspected considering the clinical and radiological presentation of the patient, seeking to increase the survival rate through timely diagnosis and treatment.

Bone Radiation-Induced Sarcomas: Outcomes Based on Histology and Surgical Treatment: A Systematic Review of the Literature.

BACKGROUND: Bone radiation-induced sarcomas (B-RIS) are secondary neoplasms with reportedly worse overall survival than de novo bone sarcoma. Treatment strategy for these neoplasms remains uncertain. Our systematic review sought to assess overall survival based on histology and surgical intervention. METHODS: A systemic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO (438415). Studies describing oncologic outcomes of patients with B-RIS in the appendicular and axial skeleton were included. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for quality assessment. Survival analysis by histologic subtype and surgery type was performed in a subset of 234 patients from 11 articles with individualized data. A total of 20 articles with a total of 566 patients were included. The most frequent location was the pelvis (27.7%), and the main histological types were osteosarcoma (69.4%), undifferentiated pleomorphic sarcoma (14.1%), and fibrosarcoma (9.2%). Limb-salvage and amputation were performed in 68.5% and 31.5% of cases, respectively. RESULTS: Local recurrence was 13%, without difference between limb-salvage surgery and amputation (p = 0.51). The metastasis rate was 42.3%. Five-year OS was 43.7% (95% confidence interval [CI], 33.3%-53.5%) for osteosarcoma, 31.5% (95% CI, 11.3%-54.2%) for UPS, and 28.1% (95% CI, 10.6%-48.8%) for fibrosarcoma. Five-year OS was 49.2% (95% CI, 35.3%-61.6%) for limb-salvage and 46.9% (95% CI, 29.1%-62.9%) for amputation. There was no difference in 5-year OS between histologic subtypes (p = 0.18) or treatment type (p = 0.86). CONCLUSION: B-RIS demonstrated poor OS at 5 years after initial management regardless of histology. Limb-salvage surgery was not associated with lower 5-year OS compared with amputation. Future studies should compare both groups while controlling for confounders. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Rib myelolipoma: a case report.

BACKGROUND: Myelolipoma is an uncommon benign tumor composed of mature adipose tissue and hematopoietic elements. These tumors generally affect the adrenal glands, with anomalous presentations being rare and with few cases described in the literature. Most myelolipomas are asymptomatic and discovered incidentally, either through imaging tests or at autopsies. However, depending on the location and size of the lesion, myelolipomas can cause symptoms of mass effect. This article aims to report a very rare presentation of a symptomatic primary myelolipoma affecting the ribs. CASE PRESENTATION: A 21-year-old white female patient presented with a complaint of burning chest pain over 3 months, with gradual worsening in intensity, accompanied by a progressively growing bulge in the right thoracic wall. The patient underwent thoracotomy of the fifth and sixth ribs with complete excision of the lesion with a safety margin. Thoracic wall reconstruction was performed using a polypropylene mesh. The patient had a good postoperative course and was discharged on postoperative day 3. Histopathological examination revealed a histological image consistent with myelolipoma. CONCLUSIONS: This report underscores the importance of considering a myelolipoma diagnosis for tumor masses in the ribs.

Metallocompounds as anticancer agents against osteosarcoma.

Metallocompounds are a class of anticancer compounds largely used in the treatment of several types of solid tumors, including bone cancer. Osteosarcoma (OS) is a primary malignant bone tumor that frequently affects children, adolescents and young adults. It is a very invasive type of tumor, so ∼40% of patients develop distant metastases, showing elevated mortality rates. In this review, we present an outline of the chemistry and antitumor properties of metal-based compounds in preclinical (in vitro and in vivo) and clinical OS models, focusing on the relationship between structure-activity, molecular targets and the study of the mechanism of action involved in metallocompound anticancer activity.

[Delayed diagnosis of osteosarcoma in adults: a prognostic factor to be considered]. / Retraso en el diagnóstico de osteosarcoma en adultos: un factor pronóstico que debemos considerar.

INTRODUCTION: different variables have been associated with a worse prognosis of patients with osteosarcoma (OS), highlighting tumor size, location in the axial skeleton and the presence of metastases. The objective of this study is to analyze the prognostic impact of diagnostic delay in osteosarcoma in adults in the Mexican population in a center specialized in sarcomas. MATERIAL AND METHODS: retrospective cohort study from January 1, 2005, to December 31, 2016, 96 patients over 21 years of age with a diagnosis of osteosarcoma were analyzed. RESULTS: the median time to diagnosis from the onset of symptoms was six months (range: 2-36). This variable was dichotomized by applying the operator-dependent curve (ROC) analysis and we determined a cut-off value greater than five months, with an area under the curve (AUC) = 0.93 [95% CI 0.86-0.97], sensitivity 93.2% and specificity 94.6%. CONCLUSION: time until diagnosis is a critical factor in the survival of adult patients with osteosarcoma, highlighting its influence on disease progression and the appearance of metastasis. The correlation between diagnostic delay and an unfavorable prognosis reinforces the need for rapid and efficient evaluation in suspected cases of osteosarcoma.

INTRODUCCIÓN: diferentes variables se han asociado con un peor pronóstico de los pacientes con osteosarcoma, destacando el tamaño tumoral, la localización en esqueleto axial y la presencia de metástasis. El objetivo de este estudio fue analizar el impacto pronóstico del retraso diagnóstico en osteosarcoma en adultos en población mexicana en un centro especializado en sarcomas. MATERIAL Y MÉTODOS: estudio de tipo cohorte retrospectiva del 1 de Enero del 2005 al 31 de Diciembre de 2016, se analizaron 96 pacientes mayores de 21 años con diagnóstico de osteosarcoma. RESULTADOS: la mediana de tiempo al diagnóstico desde el inicio de síntomas fue de seis meses (rango: 2-36). Esta variable se dicotomizó aplicando el análisis de curva dependiente de operador (ROC) y determinamos un valor de corte mayor a cinco meses con un área bajo la curva (AUC) = 0.93 [IC95% 0.86-0.97], sensibilidad 93.2% y especificidad 94.6%. CONCLUSIÓN: el tiempo hasta el diagnóstico es un factor crítico en la supervivencia de los pacientes adultos con osteosarcoma, destacando su influencia en la progresión de la enfermedad y la aparición de metástasis. La correlación entre el retraso diagnóstico y un pronóstico desfavorable refuerza la necesidad de una evaluación rápida y eficiente en casos sospechosos de osteosarcoma.

[Percutaneous radiofrequency ablation of osteoid osteoma: results from 9 years of experience in a third-level center.] / Ablación percutánea por radiofrecuencia de osteoma osteoide: resultados en 9 años de experiencia en un centro de tercer nivel.

Introduction: Osteoid osteoma is a benign bone tumor that accounts for roughly 2-3% of primary bone tumors and up to 10-12% of benigns bone neoplasms. It is most commonly seen in young adults, and shows male predominance. Over the last years, minimally invasive thermal ablation techniques such as radiofrequency ablation have gained popularity over classical surgery. In this study we evaluate results and complications of CT guided osteoid osteoma radiofrequency ablation. Materials and methods: In this retrospective cohort study all patients that were diagnosed with osteoid osteoma and treated using radiofrequency ablation between January 2014 and December 2022 were included. Pain was assessed using Visual Analog Scale (VAS) pre and post procedure. Technical success was established as positioning of the radiofrequency electrode in the nidus. Primary clinical success was defined as absence of pain after one radiofrequency session. All patients that required a second radiofrequency ablation were included in the overall clinical success group. Results: During the studied period, 61 osteoid osteoma radiofrequency ablations were performed. Fiftyseven of them were included in this study, 32 were men and 25 female. Pre procedure median pain was 9 according to VAS score. Only 23 patients were treated as outpatient, the rest stayed in hospital for 24 hours. Median follow up time was 21,7 months (SD 8,3). Biopsy was performed in 52 patients. Technical success was accomplished in 57 patients (100%). Primary clinical success was 80,7% (46 patients). Those who continued with pain or had recurrence after a symptoms free period (11 patients), were treated with a second radiofrequency ablation, achieving an overall success rate of 94,7%. Only one patient suffered a minor complication (1,7%). Conclusion: CT guided osteoid osteoma radiofrequency ablation is a safe, effective and low complication rate procedure, that can be performed on an outpatient basis. We believe it should be considered as a first line treatment option for osteoid osteoma.

Introducción: El osteoma osteoide es un tumor óseo benigno, que representa el 2-3% de las neoplasias óseas primarias y hasta el 10-12% de los tumores óseos benignos. Tiene mayor incidencia en adultos jóvenes, con predominancia masculina. En los últimos años las técnicas de termoablación mínimamente invasivas han sido utilizadas para el tratamiento del osteoma osteoide, como alternativa a la cirugía clásica. En este estudio evaluaremos los resultados y complicaciones de ablación por radiofrecuencia de osteoma osteoide. Materiales y métodos: Se analizó una cohorte de pacientes en forma retrospectiva con diagnóstico de osteoma osteoide tratados con radiofrecuencia en el Hospital Italiano de Buenos Aires desde Enero del año 2014 hasta Diciembre del año 2022. Todos los pacientes fueron evaluados con la Escala Visual Analógica del dolor (EVA) pre y post procedimiento. El éxito técnico del procedimiento fue considerado como el correcto posicionamiento del electrodo de radiofrecuencia en el nido de la lesión, y el éxito clínico primario como ausencia de dolor post procedimiento. Mientras que los pacientes que requirieron de una segunda sesión de radiofrecuencia para controlar los síntomas serán incluidos como éxito clínico secundario. Resultados: Durante el período mencionado se realizaron 61 ablaciones percutáneas de osteoma osteoide. Se incluyeron en el análisis 57 pacientes, 32 fueron hombres y 25 mujeres. La media de dolor medido por EVA pre procedimiento fue 9. Del total de los pacientes, 23 fueron tratados de manera ambulatoria, el resto permanecieron internados durante 24hs. El tiempo medio de seguimiento fue de 21,7 meses (DS8,3). Se realizó biopsia de la lesión durante el procedimiento en 52 pacientes. Se logró el éxito técnico en 57 pacientes (100%), de ellos el éxito clínico primario se logró en 46 pacientes (80,7%). Los 11 pacientes que continuaron con dolor o presentaron recurrencia de los síntomas luego de un período asintomáticos fueron tratados con una segunda sesión de radiofrecuencia, logrando un éxito clínico secundario 94,7%. Un solo paciente presentó complicaciones post procedimiento (1,7%), correspondiente a hematoma en la planta del pie. Conclusión: Podemos concluir que la ablación percutánea por radiofrecuencia de OO guiada por tomografía en manos de expertos, es un procedimiento seguro, de alta efectividad y baja tasa de complicaciones que puede realizarse de manera ambulatoria. Por lo que consideramos que debe ser tenida en cuenta como primera elección para el tratamiento de esta patología.

Parosteal osteosarcoma with low grade chondrosarcoma and liposarcoma components. A rare histologic variant. Case report and literature review.

INTRODUCTION: conventional parosteal osteosarcoma is an uncommon malignant bone tumor, comprising 4% of all osteosarcomas. Although rare, parosteal osteosarcoma is the most common type of osteosarcoma of the bone surface. We present the clinical, histological and imaging characteristics of a rare histologic variant of a parosteal osteosarcoma, review the literature and emphasize the importance of radio-pathological correlation as well as the interpretation of a representative biopsy in order to obtain the correct diagnosis. CASE REPORT: a 36-year old woman began her condition one year prior to admission to the hospital with increased volume in the left knee and pain. Image studies showed a juxtacortical heterogeneous tumor localized on the posterior surface of the distal femoral metaphysis. An incisional biopsy was performed, with the diagnosis of a Parosteal Osteosarcoma and a wide surgical resection was undertaken. According to the findings of the surgical specimen, the diagnosis of a Parosteal Osteosarcoma with low grade chondrosarcoma and liposarcoma components was made. The knowledge of this rare parosteal osteosarcoma variant can lead the orthopedic oncologists to avoid overlooking the adipose component and provide adequate surgical margins. CONCLUSION: we present the clinical, histological and imaging characteristics of a Parosteal Osteosarcoma with low grade liposarcoma and chondrosarcoma components.

INTRODUCCIÓN: el osteosarcoma parosteal convencional es un tumor óseo maligno poco común, que comprende el 4% de todos los osteosarcomas. Aunque es poco común, el osteosarcoma parosteal es el tipo más común de osteosarcoma de la superficie ósea. Presentamos las características clínicas, histológicas y de imagen de una variante histológica rara de un osteosarcoma parosteal, revisamos la literatura y enfatizamos la importancia de la correlación radio-patológica, así como la interpretación de una biopsia representativa para obtener el diagnóstico correcto. REPORTE DE CASO: mujer de 36 años inició su cuadro un año antes de su ingreso al hospital con aumento de volumen en rodilla izquierda y dolor. Los estudios de imagen mostraron una tumoración heterogénea yuxtacortical localizada en la superficie posterior de la metáfisis femoral distal. Se realizó biopsia incisional, con diagnóstico de osteosarcoma parosteal y se realizó resección quirúrgica amplia. De acuerdo con los hallazgos de la pieza quirúrgica se realizó el diagnóstico de osteosarcoma parosteal con componentes de condrosarcoma y liposarcoma de bajo grado. El conocimiento de esta rara variante de osteosarcoma parosteal puede llevar a los ortopedistas oncólogos a considerar otros componentes y proporcionar márgenes quirúrgicos adecuados. CONCLUSIÓN: presentamos las características clínicas, histológicas y de imagen de un osteosarcoma parosteal con componentes de liposarcoma y condrosarcoma de bajo grado.

Osteocondroma en una localización atípica. Reporte de Caso / Osteochondroma in an atypical location. Case report

INTRODUCCIÓN. Los osteocondromas son considerados como el tumor benigno más común entre los de origen óseo, se denomina también exostosis, y se lo define por la Organización Mundial de la Salud como una proyección ósea cubierta de una capa cartilaginosa en la superficie externa. Representa el 20-50% de todos los tumores benignos óseos. Se diagnostica en su mayoría en pacientes pediátricos. RESULTADOS. Presentamos el caso de una paciente de 8 años con osteocondroma único en escápula de aparición espontánea, sin otras lesiones en el cuerpo. DISCUSIÓN. Los lugares comunes de aparición de osteocondromas son los huesos largos con placa de crecimiento o metáfisis, localizaciones raras como la escapula comprenden menos del 1%. El tratamiento es expectante y al momento de producirse síntomas, está indicado la excision quirúrgica. CONCLUSIÓN. La enfermedad tiene un curso benigno sin complicaciones cuando se trata de un tumor esporádico, en los síndormes de exostosis, las recurrencias y riesgo de malignidad hacen necesario un seguimiento más cercano.

INTRODUCTION. Osteochondromas are considered the most common benign tumor among those of bone origin, it is also called exostosis, and is considered by the World Health Organization as a bone projection covered with a cartilaginous layer on the external surface), it represents 20­50% of all benign tumors and is mostly diagnosed in pediatric patients. RESULTS. We present the case of an 8-year-old female with a single osteochondroma in the scapula of spontaneous appearance, without other lesions in the body. DISCUSSION: The common places of appearance are long bones with a growth plate or metaphysis, rare locations such as the scapula comprise less than 1%. The treatment is expectant, and when symptoms occur, surgical excision is indicated. CONCLUSION: The disease has a benign course without complications when it is a sporadic tumor, in exostosis syndromes the recurrences and risk of malignancy make closer follow-up necessary.

Alteration in the Expression of Circular Rnas and its association with the Development and Progression of Osteosarcoma, an Integrative Review with High Sensitivity Research.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor, mainly affecting children, young adults, and the elderly. It is an aggressive cancer with a poor prognosis, exhibiting low survival rates even with standard treatment. Recently, circular RNA molecules capable of influencing gene expression through various functions, with their main role being acting as microRNA sponges and reducing their intracellular expression, have been identified. Recent studies have linked circular RNAs to osteosarcoma development and progression. Therefore, the present study aimed to investigate the alteration in circular RNA expression during osteosarcoma development and progression. METHODS: An integrative literature review was conducted from September 10th to November 12th, 2021, using the following databases: PubMed/MEDLINE, SCOPUS, Web of Science, OVID, and EMBASE. 129 full articles were included in the review. The obtained data were organized using a standardized data collection instrument, which included the following information: altered expression profile of circular RNAs, associated cancer hallmarks, clinical-pathological relationships of circular RNAs, and perspectives on the studied circular RNAs. RESULTS: A total of 94 distinct circular RNAs were identified, predominantly showing an increased expression pattern. Approximately 91% of the studies that aimed to identify the mechanisms of action of circular RNAs highlighted the function of circular RNAs as microRNA sponges. The most associated cancer hallmarks with the identified circular RNAs were proliferative signaling induction, invasion and metastasis, and resistance to cell death. The altered expression of these circular RNAs generally correlated with a worse prognosis for patients, as evidenced by clinical features such as shorter survival, advanced Enneking and/or TNM stage, higher incidence of metastasis, larger tumor size, and increased chemoresistance. CONSLUSION: These findings indicate the significance of circular RNA molecules in osteosarcoma carcinogenesis, suggesting their potential as new prognostic and/or diagnostic biomarkers, as well as alternative therapeutic targets in the fight against osteosarcoma.

[Prognostic factors associated with failure of modular knee arthroplasty in oncologic patients]. / Factores pronósticos asociados al fracaso de la artroplastía modular de rodilla en pacientes oncológicos.

INTRODUCTION: reconstruction of large bone defects using modular knee arthroplasty (MKA) presents a significant challenge in terms of functionality. The objective of the present work was to identify the different prognostic factors associated with failure of MKA in cancer patients. MATERIAL AND METHODS: a retrospective cohort study was conducted, including patients with a diagnosis of musculoskeletal tumor in the distal femur or proximal tibia, who underwent MKA between January 1, 2010, and December 31, 2021. RESULTS: 49 patients were included, of which 25 (51.02%) were women and 24 (48.98%) men, with a mean age of 29.57 years. Of these, 14 (28.57%) patients experienced some type of MKA failure. The most frequent complication that led to failure was periprosthetic infection, observed in seven (14.29%) patients. Variables associated with MKA failure included biopsies performed outside our hospital (HR 3.2, 95% CI 1.4-6.4, p = 0.02), the length of the long axis of the tumor (HR 2.1, 95% CI 1.2-4.6, p = 0.01) and a prolonged surgical time (HR 3.37, 95% CI 1.1-8.6, p = 0.04). CONCLUSION: the most significant prognostic factors associated with MKA failure in our cohort were tumor size, prolonged surgical time, and performance of the diagnostic biopsy in a center not specialized in the management of this type of patient. These findings highlight the importance of considering these variables to improve outcomes in patients undergoing MKA.

INTRODUCCIÓN: la reconstrucción de grandes defectos óseos mediante artroplastía modular de rodilla (AMR) representa un desafío significativo en términos de funcionalidad. El objetivo del presente trabajo fue identificar los diferentes factores pronósticos asociados al fracaso de la AMR en pacientes oncológicos. MATERIAL Y MÉTODOS: se realizó un estudio de cohorte retrospectiva, incluyendo pacientes con diagnóstico de tumor musculoesquelético en el fémur distal o la tibia proximal, que fueron sometidos a AMR entre el 1 de Enero de 2010 y el 31 de Diciembre de 2021. RESULTADOS: se incluyeron 49 pacientes, de los cuales 25 (51.02%) eran mujeres y 24 (48.98%) hombres, con una edad media de 29.57 años. De éstos, 14 (28.57%) pacientes experimentaron algún tipo de fracaso de la AMR. La complicación más frecuente que condicionó el fracaso fue la infección periprotésica, observada en siete (14.29%) pacientes. Las variables asociadas con el fracaso de las AMR incluyeron biopsias realizadas fuera de nuestro hospital (HR 3.2, IC95% 1.4-6.4, p = 0.02), longitud del eje mayor del tumor (HR 2.1, IC95% 1.2-4.6, p = 0.01) y tiempo quirúrgico prolongado (HR 3.37, IC95% 1.1-8.6, p = 0.04). CONCLUSIÓN: los factores pronósticos asociados al fracaso de las AMR en nuestra cohorte fueron el tamaño del tumor, un tiempo quirúrgico prolongado y la realización de la biopsia diagnóstica en un centro no especializado en el manejo de este tipo de pacientes. Estos hallazgos resaltan la importancia de considerar estas variables en pacientes sometidos a AMR.

Promising Dual Anticancer and Antimetastatic Action by a Cu(II) Complex Derived from Acylhydrazone on Human Osteosarcoma Models.

Osteosarcoma cancers are becoming more common in children and young adults, and existing treatments have low efficacy and a very high mortality rate, making it pressing to search for new chemotherapies with high efficacy and high selectivity index. Copper complexes have shown promise in the treatment of osteosarcoma. Here, we report the synthesis, characterization, and anticancer activity of [Cu(N-N-Fur)(NO3)(H2O)] complex where N-N-Fur is (E)-N'-(2-hydroxy-3-methoxybenzylidene)furan-2-carbohydrazide. The [Cu(N-N-Fur)(NO3)(H2O)] complex was characterized via X-ray diffraction and electron spin resonance (ESR), displaying a copper center in a nearly squared pyramid environment with the nitrate ligand acting as a fifth ligand in the coordination sphere. We observed that [Cu(N-N-Fur)(NO3)(H2O)] binds to DNA in an intercalative manner. Anticancer activity on the MG-63 cell line was evaluated in osteosarcoma monolayer (IC50 2D: 1.1 ± 0.1 µM) and spheroids (IC50 3D: 16.3 ± 3.1 µM). Selectivity assays using nontumoral fibroblast (L929 cell line) showed that [Cu(N-N-Fur)(NO3)(H2O)] has selectivity index value of 2.3 compared to cis-diamminedichloroplatinum(II) (CDDP) (SI = 0.3). Additionally, flow cytometry studies demonstrated that [Cu(N-N-Fur)(NO3)(H2O)] inhibits cell proliferation and conveys cells to apoptosis. Cell viability studies of MG-63 spheroids (IC50 = 16.3 ± 3.1 µM) showed that its IC50 value is 4 times lower than for CDDP (IC50 = 65 ± 6 µM). Besides, we found that cell death events mainly occurred in the center region of the spheroids, indicating efficient transport to the microtumor. Lastly, the complex showed dose-dependent reductions in spheroid cell migration from 7.5 to 20 µM, indicating both anticancer and antimetastatic effects.

Osteosarcoma cells exhibit functional interactions with stromal cells, fostering a lung microenvironment conducive to the establishment of metastatic tumor cells.

BACKGROUND: Osteosarcoma (OS) stands out as the most common bone tumor, with approximately 20% of the patients receiving a diagnosis of metastatic OS at their initial assessment. A significant challenge lies in the frequent existence of undetected metastases during the initial diagnosis. Mesenchymal stem cells (MSCs) possess unique abilities that facilitate tumor growth, and their interaction with OS cells is crucial for metastatic spread. METHODS AND RESULTS: We demonstrated that, in vitro, MSCs exhibited a heightened migration response toward the secretome of non-metastatic OS cells. When challenged to a secretome derived from lungs preloaded with OS cells, MSCs exhibited greater migration toward lungs colonized with metastatic OS cells. Moreover, in vivo, MSCs displayed preferential migratory and homing behavior toward lungs colonized by metastatic OS cells. Metastatic OS cells, in turn, demonstrated an increased migratory response to the MSCs' secretome. This behavior was associated with heightened cathepsin D (CTSD) expression and the release of active metalloproteinase 2 (MMP2) by metastatic OS cells. CONCLUSIONS: Our assessment focused on two complementary tumor capabilities crucial to metastatic spread, emphasizing the significance of inherent cell features. The findings underscore the pivotal role of signaling integration within the niche, with a complex interplay of migratory responses among established OS cells in the lungs, prometastatic OS cells in the primary tumor, and circulating MSCs. Pulmonary metastases continue to be a significant factor contributing to OS mortality. Understanding these mechanisms and identifying differentially expressed genes is essential for pinpointing markers and targets to manage metastatic spread and improve outcomes for patients with OS.

Effects of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in patients with osteosarcoma and their influencing factors.

OBJECTIVE: The objective of this study was to investigate the impact of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in osteosarcoma patients and analyze the factors influencing this effect. METHODS: A retrospective study was conducted on 165 osteosarcoma patients admitted to our hospital from January 2020 to December 2022. Based on the chemotherapy regimen, the patients were divided into two groups: the control group (n = 62) treated with Cisplatin and cyclophosphamide, and the observation group (n = 103) treated with Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline). The general records of both groups were analyzed, and left ventricular ejection fraction (LVEF) was evaluated through echocardiography before and after chemotherapy. Blood cTnT and CK-MB levels were measured using immunoluminescence. The incidence of adverse reactions during chemotherapy was also analyzed. Univariate analysis was performed to identify patients with cardiotoxic events, and multiple logistic regression analysis was done to study the effects of Doxorubicin, Epirubicin, Liposomal Doxorubicin, and their dosages on cardiotoxicity in patients. RESULTS: The general records between the two groups showed no significant differences (P > 0.05). However, at the fourth cycle of chemotherapy, the observation group exhibited a lower LVEF (P < 0.05), and a higher percentage of LVEF decrease compared to the control group (P < 0.05). Moreover, the observation group had higher levels of blood cTnT and CK-MB (P < 0.05). The incidence of cardiotoxicity in the observation group was also higher (P < 0.05), but no significant differences were seen in other adverse reaction rates (P > 0.05). The occurrence of cardiotoxicity was found to be related to the choice and dosage of chemotherapy drugs (P < 0.05), but not significantly correlated with age, sex, and mediastinal irradiation in patients (P > 0.05). Furthermore, the use of Doxorubicin, Epirubicin, and Liposomal Doxorubicin in chemotherapy, as well as an increase in their dosages, was found to elevate the risk of cardiotoxicity in osteosarcoma patients (P < 0.05). However, age, sex, and mediastinal radiation were not significantly associated with cardiotoxicity in osteosarcoma patients (P > 0.05). CONCLUSION: We demonstrated that Doxorubicin, Epirubicin, Liposomal Doxorubicin (Anthracycline), and other drugs adversely affected cardiac function in osteosarcoma patients, increasing the risk of cardiac toxicity. Therefore, close monitoring of cardiac function during chemotherapy is crucial, and timely adjustments to the chemotherapy regimen are necessary. In addition, rational control of drug selection and dosage is essential to minimize the occurrence of cardiac toxicity.

Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells.

The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

Meta-Analysis of Stereotactic Body Radiation ThERapy in Nonspine BONE Metastases (MASTER-BONES).

PURPOSE: The efficacy and safety of stereotactic body radiation therapy (SBRT) for patients with nonspine bone metastases remains in question. A systematic review and meta-analysis were performed to evaluate SBRT treatment outcomes in nonspine bone metastases. METHODS AND MATERIALS: Eligible studies were retrieved from MEDLINE, Embase, Scielo, the Cochrane Library, and annual meeting proceedings through July 6, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline recommendations. Quantitative synthesis was performed using a random-effects model. Meta-regression was performed to determine correlation between clinical and treatment factors with the local failure (LF) and fracture rate. P values ≤.05 were deemed statistically significant. RESULTS: Seven retrospective studies, with a total of 807 patients (1048 lesions) treated with SBRT were included, with median follow-up ranging from 7.6 to 26.5 months. The most common SBRT sites were pelvis (39.2%), ribs (25.8%), femur (16.7%), and humerus/shoulder region (8.7%). At 1 year, the LF and fracture rate were 7% (95% CI, 5.5%-8.5%; I2 = 0; n = 75/1048) and 5.3% (95% CI, 3%-7.5%; I2 = 0; n = 65/1010). The 2-year cumulative LF incidence was 12.1% (95% CI, 10%-15.5%). The overall survival and progression-free survival at 1 year were 82% (95% CI, 75%-88%; I2 = 82%; n = 746/867) and 33.5% (95% CI, 26%-41%; I2 = 0%; n = 51/152), with a median of 20.2 months (95% CI, 10.9-49.1 months) and 8.3 months (95% CI, 6.3-10.3 months) for overall survival and progression-free survival, respectively. Meta-regression analysis revealed a significant relationship between planning target volume and fracture rate (P < .05). Ribs (2.5%) followed by the femur (1.9%; 95% CI, 0%-6.1%) were the most common fracture sites. The occurrence of pain flare, fatigue, and dermatitis were 7%, 5.4%, and 0.65%, respectively. CONCLUSIONS: Stereotactic body radiation proves both safety and efficacy for non-spine bone metastases, and although serious complications (grade 3) are rare, one case of grade 5 complication was reported. Careful consideration of target volume is crucial due to its link with a higher fracture risk.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.