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BACKGROUND: The surgical efficacy and prognostic outcomes of patients with unspecific malignant bone tumors (UMBTs) remain unclear. The study is to address: 1) What are the clinicopathological features and prognostic determinants for patients with UMBTs? 2) Can a nomogram be developed for clinicians to predict the short and long-term outcomes for individuals with UMBTs? 3) Does surgery improve outcomes for UMBT patients who received radiotherapy or chemotherapy after balancing the confounding bias? METHODS: 400 UMBT patients were filtrated from the Surveillance, Epidemiology, and End Results database to assess the clinicopathological features, treatments, and factors affecting prognosis. The optimal cutoff values of continuous variables were identified by the x-tile software. Kaplan-Meier method and multivariate Cox proportional hazard modeling were performed to evaluate the independent prognostic factors. Nomogram was further developed by using R software with rms package. The surgical efficacy was further assessed for patients receiving radiotherapy or chemotherapy after performing propensity score matching. RESULTS: The enrolled cohort included 195 (48.8%) female and 205 (51.2%) male patients. The 2- and 5-year cancer-specific survival (CSS) and overall survival (OS) rate were 58.2 ± 3.0%, 46.8 ± 3.2%, and 46.5 ± 2.6%, 34.4 ± 2.5%, respectively. Nomogram was finally developed for CSS and OS according to the identified independent factors: age, tumor extent, primary tumor surgery, tumor size, and pathology grade. For UMBT patients who received radiotherapy or chemotherapy, surgical intervention was associated with better CSS (pr = 0.003, pc = 0.002) and OS (pr = 0.035, pc = 0.002), respectively. CONCLUSIONS: Nomogram was developed for individual UMBT patient to predict short and long-term CSS and OS rate, and more external patient cohorts are warranted for validation. Surgery improves outcomes for UMBT patients who received either radiotherapy or chemotherapy.
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Neoplasias Ósseas , Nomogramas , Humanos , Masculino , Feminino , Programa de SEER , Estadiamento de Neoplasias , Prognóstico , Neoplasias Ósseas/cirurgiaRESUMO
Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs; however, the complexities in carrier materials and functional integration make it challenging to promote these candidates for clinical translation. In this study, a facile method to prepare carrier-free anticancer nanodrug with inherent bone targeting and osteoclastogenesis inhibition capabilities is reported. Phytic acid, a naturally occurring and nontoxic product, is reacted with cisplatin to form uniform nanoparticles of different sizes. The prepared nanoparticles possess high drug loading and pH-responsive drug release behaviors. Phytic acid in the nanomedicine ensures high bone targeting and osteoclastogenesis inhibition, and the released platinum drugs triggered by tumor extracellular acidity eradicate tumor cells. The nanomedicine around 100 nm shows high anticancer activity and much reduced side effects in a subcutaneous breast cancer model when compared with cisplatin. In addition, it shows high accumulation at osteolytic lesions, and efficiently inhibits tumor growth and tumor-associated osteolysis in a bone metastatic breast cancer model. Here, a facile and efficient strategy to prepare carrier-free nanomedicines with high anticancer drug loading, inherent bone targeting, and osteoclast inhibitory activities for cancer therapy is provided.
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Antineoplásicos , Nanopartículas , Neoplasias , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , PlatinaRESUMO
The tumor-initiating cells (TICs) are a cell population that can initiate tumor occurrence, mediate drug resistance, and give rise to metastasis. FOXD3 is a forkhead box (Fox) transcription factor family that regulates the pluripotency of embryonic stem cell and tumorigenicity. However, it is unclear whether FOXD3 plays any role in TIC and tumor metastasis. The functional analysis of FOXD3 was performed by oncospheres formation and redifferentiation, drug resistance assay, and cell migration. Global genomic RNA-Seq and ChIP-Seq analysis were used to identify the direct target of FOXD3 in lung cancer. We demonstrated that downregulation of FOXD3 in TICs was positively correlated with higher histologic grades and positive lymph node metastasis. FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, we found that FOXD3 represses WDR5, which regulates TIC-related signaling pathway. Moreover, WDR5 were positively correlated with the TIC abundance and tumor progression. Besides, patients with high expression of WDR5 presented a poorer overall survival. FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer. Stem Cells 2019;37:582-592.
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Resistencia a Medicamentos Antineoplásicos/genética , Fatores de Transcrição Forkhead/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Animais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Paclitaxel/farmacologiaRESUMO
PURPOSE: The aim of the study was to report the long-term outcomes and analyze the potential prognostic factors that may contribute to symptomatic patients with aneurysmal bone cyst (ABC) of the spine undergoing surgical treatments. METHODS: A retrospective analysis of consecutive patients with ABCs of the spine was performed. The clinical features were reviewed, and the disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Factors with p values ≤ 0.05 were subjected to multivariate analysis by Cox proportional hazards model to identify the independent prognostic contributors. p values < 0.05 were considered statistically significant. RESULTS: A total of 42 patients with ABCs of the spine were included in the study. All patients received surgical treatments. The mean follow-up period was 41.3 months (median 39.5, range 24-64). Local recurrence was detected in eight patients after surgery in our center, whereas death occurred in three patients. The estimated 5-year DFS and OS rate was 54.1% and 76.8%, respectively. The statistical analyses indicated that both en bloc resection and primary/secondary tumor status were independent prognostic factors for DFS. CONCLUSIONS: Secondary ABC status may be associated with worse prognosis, and en bloc resection remains the treatment of choice for ABCs with neurologic deficits or spinal instability of the spine, which is correlated with better prognosis for local tumor control. These slides can be retrieved under Electronic Supplementary Material.
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Cistos Ósseos Aneurismáticos/mortalidade , Cistos Ósseos Aneurismáticos/cirurgia , Doenças da Coluna Vertebral/mortalidade , Doenças da Coluna Vertebral/cirurgia , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Surgical resection represents the main therapeutic method for sacral chordoma, but plans for resection mode must weigh neurological loss against complete tumor excision, a difficult balance to strike. The purpose of this study was to provide useful information contributing to surgical decision making in sacral chordoma. METHODS: A retrospective review was performed on 47 patients with large sacral chordoma. Prognostic factors affecting recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Quality of life was assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and compared using Student's t test. RESULTS: Resection mode was the independent prognostic factor affecting RFS, while independent prognostic factors affecting OS were resection mode and postoperative recurrence. As for quality of life, the en bloc resection group showed a higher score in emotional well-being, while the piecemeal resection group scored better in function well-being. No significant difference was identified in total the FACT-G score between two groups. CONCLUSIONS: On the one hand, en bloc resection showed huge advantages in disease control for sacral chordoma. On the other hand, despite the unsatisfaction in functional well-being, en bloc resection did not sacrifice quality of life significantly in terms of the total FACT-G score.
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Cordoma/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Sacro/patologiaRESUMO
BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare entity of soft tissue malignancies with uncommon spinal involvements. Surgical management should be the best choice of cure. METHODS: Five patients with spinal ASPS were interviewed retrospectively, where data was collected. The relevant literatures were also systematically examined. Thereafter, patient and surgical data were obtained and pooled for prognostic analysis. RESULTS: A total of five patients with eight surgeries were reviewed retrospectively, and three patients previously reported were also included. All patients were surgically treated, where five of them underwent additional adjuvant therapies such as chemotherapy, radiotherapy, and targeted therapy in order to manage their local and/or systematic diseases. One patient was lost in follow-up. For the remaining seven patients, the mean follow-up period was 19.7 ± 8.8 months, two succumbed to disease while five were alive at the time of the study. CONCLUSIONS: Surgical management is shown to be the most important and the most effective treatment strategy for spinal ASPS, whereas adjuvant therapies made little impact. The prognostic factors for spinal ASPS are primary or metastatic lesions, neurological status, disease progression, systematic conditions, and resection approaches.
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Complicações Pós-Operatórias , Sarcoma Alveolar de Partes Moles/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Sarcoma Alveolar de Partes Moles/patologia , Neoplasias de Tecidos Moles/patologia , Neoplasias da Coluna Vertebral/patologia , Adulto JovemRESUMO
BACKGROUND: The surgical treatment of upper cervical spine metastases are controversial up to now. By summarizing and analyzing the clinical data of the upper cervical spine involved metastases treated surgically in our center, we mainly aimed to investigate the surgical decisions and outcomes so as to provide more references for the clinical treatment of this special and complex spine metastasis. METHODS: We evaluated the patients' pre- and post-operative neck pain and neurologic function with paired t test, followed by the statistics of the selection of surgical approaches, ways of reconstruction, and related complications. Moreover, the Kaplan-Meier survival analysis was adopted to analyze the patients' survival according to different growth group (rapid, moderate, and slow). RESULTS: There were 39 patients with atlantoaxial metastases in this study. The most common symptom (94.87%) was occipital-cervical pain, which relieved greatly after surgical interventions (p < 0.01). The metastases mainly resulted from lung cancer and nasopharyngeal cancer with an incidence of 38.46 and 10.26%, respectively. As to different growth group, the rapid-growth tumors accounted for 69.23% in all atlantoaxial metastases. Tumor resection and stabilization were performed mainly via the combined anterior and posterior approach (66.67%). The 1-, 2-, and 3-year overall survival rate at the last follow-up was 58.5, 40, and 28.3%, respectively, with a median survival time of 18 months. The rate of complications associated with the surgical intervention was 12.82% (5/39), which is lower than that of the previous reports and generally controllable. CONCLUSIONS: Relatively radical interventions with surgery for upper cervical spine metastases offered satisfactory outcomes with a low mortality. Together with adjuvant therapy, surgical treatment benefits patients with atlantoaxial metastases by relieving regional pain, restoring or improving the neurologic function, stabilizing the quality of life, and prolonging the survival time of such patients.
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Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Neoplasias/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/patologia , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: For a long time, chordoma has been known as an osseous tumor mainly found at the clivus and sacrococcygeal region. However, spine extra-osseous chordoma (SEC) with a better prognosis than the classic type has been neglected. According to our literature review, only several case reports have been published in English literatures. Here in this article, three cases of SEC, plus a literature review, are presented. CASE PRESENTATION: Three cases of SEC were presented from our center. Surprisingly, neurologic tumors were considered as the first diagnosis. Thereafter, en bloc resection was performed in all the three cases. Especially, the dumbbell-shaped one in the cervical spine was removed by en bloc through the combined anterior and posterior approach for the first time. Follow-up within 12-58 months after surgeries proved no recurrence or metastasis. CONCLUSIONS: Spine extra-osseous chordoma, commonly located in the cervical and epidural region, is extremely rarely met. SEC is characterized with less aggressiveness, the lower rate of recurrence and metastasis, and better prognosis than those of the osseous origin. Though complete excision can be achieved generally, differential diagnosis of spine neurogenic tumors and the following en bloc resection should be made as carefully as possible.
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Vértebras Cervicais/cirurgia , Cordoma/patologia , Cordoma/cirurgia , Neoplasias da Medula Espinal/patologia , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Biópsia por Agulha , Vértebras Cervicais/irrigação sanguínea , Vértebras Cervicais/diagnóstico por imagem , Cordoma/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Feminino , Seguimentos , Gadolínio/administração & dosagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Procedimentos Neurocirúrgicos/instrumentação , Procedimentos Neurocirúrgicos/métodos , Sacro/diagnóstico por imagem , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagemRESUMO
Bone metastasis is a frequent and fatal complication of cancer that lacks effective clinical treatment. Photothermal therapy represents a new strategy for the destruction of multiple cancers. In this study, trifolium-like platinum nanoparticles (TPNs) with small size and excellent photothermal conversion property are prepared via a facile and green method. TPNs show minimal cytotoxicity on normal cell lines and kill cancer cells upon exposure to a near-infrared light. These nanoparticles effectively inhibit tumor growth and prevent osteolysis in a bone metastasis model. This study offers a promising strategy in the treatment of bone metastasis.
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Neoplasias Ósseas/terapia , Nanopartículas Metálicas/química , Osteólise/fisiopatologia , Fototerapia/métodos , Platina/química , Trifolium/química , Animais , Materiais Biocompatíveis/química , Peso Corporal , Neoplasias Ósseas/secundário , Linhagem Celular , Linhagem Celular Tumoral , Células HeLa , Humanos , Imageamento Tridimensional , Raios Infravermelhos , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Metástase Neoplásica , Neoplasias/patologia , Fotoquímica , Compostos de Platina/química , Povidona/química , Tomografia Computadorizada por Raios X , Microtomografia por Raio-XRESUMO
Integrin-linked kinase-associated phosphatase (ILKAP) is a serine/threonine (S/T) phosphatase that belongs to the protein phosphatase 2C (PP2C) family. Many previous studies have demonstrated that ILKAP plays key roles in the regulation of cell survival and apoptosis. Researchers have thus far considered ILKAP a cytoplasmic protein that negatively regulates integrin signaling by interacting with and phosphorylating integrin-linked kinase 1 (ILK1). In this study, we found that both endogenous and tagged ILKAP mainly localize to the nucleus and that the nuclear transport of ILKAP is nuclear localization signal (NLS) importin-mediated. The ILKAP protein interacts directly with importin α1, α3, and α5. The NLS in ILKAP is located in the N-terminal region between amino acids 71 and 86, and the NLS-deleted ILKAP protein was distributed in the cytoplasm. In addition, we show that Lys-78 and Arg-79 are critical for the binding of ILKAP to importin α. We also found that nuclear ILKAP interacts with ribosomal protein S6 kinase-2 (RSK2) and induces apoptosis by inhibiting RSK2 activity and down-regulating the expression level of the RSK2 downstream substrate cyclin D1. These results indicate that ILKAP is a nuclear protein that regulates cell survival and apoptosis through the regulation of RSK2 signaling.
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Regulação Enzimológica da Expressão Gênica/fisiologia , Sinais de Localização Nuclear/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/biossíntese , Transdução de Sinais/fisiologia , Apoptose/fisiologia , Regulação para Baixo/fisiologia , Células Hep G2 , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Sinais de Localização Nuclear/genética , Proteínas Nucleares/genética , Fosfoproteínas Fosfatases/genética , Estrutura Terciária de Proteína , Proteínas Quinases S6 Ribossômicas 90-kDa/genéticaRESUMO
Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an "Off-On" release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. This study provides a new insight into biomedical applications of dendrimers and dendrimer-encapsulated nanoparticles.
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Antineoplásicos/farmacologia , Dendrímeros/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Glutationa/química , Ouro/química , Nanopartículas Metálicas/química , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Compostos de Sulfidrila/químicaRESUMO
Understanding the specificity and complexity of the tumor microenvironment (TME) of Ewing sarcoma (ES) is essential for identifying the immune characteristics of ES, improving the prediction of immunotherapeutic response, and facilitating therapeutic target discovery. In this study, we not only evaluated the gene sets associated with TME in ES using ESTIMATE and WGCNA algorithms based on the transcriptome data of ES, but also constructed a prognostic model (ES Score) using univariate Cox regression and Lasso regression and assessed its predictive ability on immune cell infiltration. Subsequently, we identified ARAP3 as a key gene affecting the TME of ES. In addition, bioinformatic analyses and in vitro experiments proved that the high expression of ARAP3 regulated ES cell proliferation, migration, as well as apoptosis via the p53 signaling pathway and affected macrophage infiltration and osteoclast differentiation through regulating IL1B and IL11 secretion of tumor cells.
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Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients. However, the highly complex cell origin involved in osteosarcoma (OS) limits the utility of traditional bulk RNA sequencing for OS subclassification. Single-cell RNA sequencing (scRNA-seq) holds great promise for identifying cell heterogeneity. However, this technique has rarely been used in the study of tumor subclassification. By analyzing scRNA-seq data for six conventional OS and nine cancellous bone (CB) samples, we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell (CSC)-like subset, which allowed us to classify OS samples into three groups. The classification model was further examined using the TARGET dataset. Each subgroup of OS had different prognoses and possible drug sensitivities, and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment. In addition, we verified the classification model through IHC staining in 138 OS samples, revealing a worse prognosis for Group B patients. Furthermore, we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS. These findings provide a novel subclassification method based on scRNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.
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Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.
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A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the "vicious" cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.
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Antineoplásicos , Neoplasias Ósseas , Nanopartículas , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Terapia Combinada , Humanos , Lipossomos , PolímerosRESUMO
STUDY DESIGN: Retrospective analysis. OBJECTIVE: The study was designed to: (1) figure out risk factors of metastasis; (2) explore prognostic factors and develop a nomogram for pelvis and spine Ewing sarcoma (PSES). SUMMARY OF BACKGROUND DATA: Tools to predict survival of PSES are still insufficient. Nomogram has been widely developed in clinical oncology. Moreover, risk factors of PSES metastasis are still unclear. METHODS: The data were collected and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff values of continuous variables were identified by X-tile software. The prognostic factors of survival were performed by Kaplan-Meier method and multivariate Cox proportional hazards modeling. Nomograms were further constructed for estimating 3- and 5-year cancer-specific survival (CSS) and overall survival (OS) by using R with rms package. Meanwhile, Pearson χ2 test or Fisher exact test, and logistic regression analysis were used to analyze the risk factors for the metastasis of PSES. RESULTS: A total of 371 patients were included in this study. The 3- and 5-year CSS and OS rate were 65.8â±â2.6%, 55.2â±â2.9% and 64.3â±â2.6%, 54.1â±â2.8%, respectively. The year of diagnosis, tumor size, and lymph node invasion were associated with metastasis of patients with PSES. A nomogram was developed based on identified factors including: age, tumor extent, tumor size, and primary site surgery. The concordance index (C-index) of CSS and OS were 0.680 and 0.679, respectively. The calibration plot showed the similar trend of 3-year, 5-year CSS, and OS of PSES patients between nomogram-based prediction and actual observation, respectively. CONCLUSION: PSES patients with earlier diagnostic year (before 2010), larger tumor size (>59âmm), and lymph node invasion, are more likely to have metastasis. We developed a nomogram based on age, tumor extent, tumor size, and surgical treatments for determining the prognosis for patients with PSES, while more external patient cohorts are warranted for validation.Level of Evidence: 3.
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Sarcoma de Ewing , Humanos , Pelve , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/epidemiologia , Sarcoma de Ewing/terapiaRESUMO
OBJECTIVES: Meningioma is a slow-growing neoplasm derived from meningothelial cells. Extradural metastasis of WHO grade II/III meningiomas is relatively rare, and spinal metastatic meningiomas (SMM) have only been described in individual case reports. The aim of the present study is to discuss the clinical features and treatments of SMM patients. METHODS: Fourteen SMM patients who received surgery in our center between 2010 and 2020 were reviewed retrospectively. Possible prognostic factors affecting local progression-free survival (LPFS) and overall survival (OS) were analyzed by log-rank analysis. RESULTS: Our series comprised nine men and five women, with a median age of 49 years. The interval from the primary treatment to SMM varied from 1 to 11 years. Lesions were mainly located in the lumbar-sacral region (7/14, 50.0%), followed by the thoracic spine (5/14, 35.7%) and cervical (2/14, 14.3%) spine. The median follow-up period was 42.7 months, during which six patients (42.9%) passed away. Local tumor progression was detected in four patients (28.6%). Log-rank analysis indicated that circumferential surgery was associated with good LPFS, whereas WHO grade III and visceral metastasis were factors adversely affecting OS. CONCLUSIONS: SMM is a challenging clinical entity, usually occurring in the fourth to fifth decades of life. Circumferential surgery is associated with good LPFS. WHO grade III and visceral metastasis are factors adversely affecting OS of patients with SMM. Long-term follow-up is recommended for patients who have received surgical treatment for primary meningiomas (Simpson Grade III/IV), especially for WHO III lesions.
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Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Criança , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Adulto JovemRESUMO
BACKGROUND: Surgery remains the mainstay of treatment for breast cancer spinal metastasis (BCSM) to relieve symptoms and improve the quality of life of BCSM patients. Therefore, it is important to effectively predict the prognosis of patients to determine whether they can undergo surgical operation. However, the prevalent methods for prognosis evaluation lack specificity and sensitivity for indicated malignancies like breast cancer because they are built on a relatively small number of heterogeneous types of primary tumors. The aim of the present study was to explore a novel predictive model based on the clinical, pathological and blood parameters obtained from BCSM patients before they received surgical intervention. METHODS: Altogether, 144 patients were included in this study. Univariate and multivariate analyses were performed to investigate the significance of preoperative parameters and identify independent factors for prognostic prediction of BCSM. A nomogram for survival prediction was then established and validated. Time-dependent ROC (TDROC) curves were graphed to evaluate the accuracy of the novel model vs other scoring systems including Tomita Score, revised Tokuhashi Score, modified Bauer Score and New England Spinal Metastasis Score. P values <0.05 were considered statistically significant. RESULTS: Independent factors, including preoperative postmenopausal (P=0.034), visceral metastasIs (P=0.021), preoperative Frankel Score (P=0.001), estrogen receptor status (P=0.014), platelet-to-lymphocyte ratio (P=0.012), lymphocyte-monocyte ratio (P<0.001) and albumin-globulin ratio (P=0.017), were selected into the nomogram model with the C-index of 0.834 (95% CI, 0.789-0.890). TDROC curves showed that the Changzheng Hospital (CZ) Score system had the best performance and exhibited the largest IAUC value in comparison with the other scoring systems. CONCLUSION: We constructed a nomogram model known as CZ Score based on the significant factors to predict the prognosis for BCSM patients. The result showed that CZ Score had a better value for prognostic evaluation and surgical decision-making as compared with the other scoring systems.
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OBJECTIVES: Spinal secondary aneurysmal bone cyst (SABC) is extremely rare with few published reports available at present. Our aim is to explore the clinicopathologic features, surgical modalities and outcomes of spinal SABC. PATIENTS AND METHODS: A retrospective study of 33 patients with spinal SABC who were surgically treated in our center between 2010 and 2018 was performed. Clinical data, treatment options, complications and outcomes were analyzed. RESULTS: Of the 33 patients, 12 were male and 21 were female, with a mean age of 32 years. Eleven lesions were located at the lumbar spine. The underlying lesions included giant cell tumor (GCT) (nâ¯=â¯20), osteoblastoma (nâ¯=â¯7), hemangiaoma (nâ¯=â¯3), fibrous dysplasia (nâ¯=â¯2) and osteosarcoma (nâ¯=â¯1). Preoperative selective arterial embolization was applied in 24 patients. All the patients were treated surgically through either subtotal resection (nâ¯=â¯1), piecemeal total resection (nâ¯=â¯21), or total en bloc resection (nâ¯=â¯11). Four patients experienced recurrence and one patient died during the follow-up period. CONCLUSION: Spinal SABC is popular in the third and fourth decade of life with female predominance. GCT is the most common underlying lesion. Preoperative arterial embolization is recommended, while surgery is the mainstay of treatment for spinal SABC. En bloc resection is recommended for spinal SABCs especially when underlying tumor is aggressive or malignant.
Assuntos
Cistos Ósseos Aneurismáticos/cirurgia , Procedimentos Neurocirúrgicos/métodos , Doenças da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Cistos Ósseos Aneurismáticos/etiologia , Embolização Terapêutica , Feminino , Displasia Fibrosa Óssea/complicações , Displasia Fibrosa Óssea/cirurgia , Tumor de Células Gigantes do Osso/complicações , Tumor de Células Gigantes do Osso/cirurgia , Hemangioma/complicações , Hemangioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoblastoma/complicações , Osteoblastoma/cirurgia , Osteossarcoma/complicações , Osteossarcoma/cirurgia , Cuidados Pré-Operatórios , Falha de Prótese , Doenças da Coluna Vertebral/etiologia , Fusão Vertebral , Neoplasias da Coluna Vertebral/complicações , Infecção da Ferida Cirúrgica , Adulto JovemRESUMO
Breast cancer is a molecularly heterogeneous disease that can be subdivided into different subtypes. Compared with the other subtypes, luminal breast cancer (LBC) is considered more susceptible to bone metastasis. However, the intrinsic mechanisms remain elusive. Bioinformatics analysis of the preset study showed that N-acetyltransferase 1 (NAT1) was specifically expressed in LBC and closely correlated with bone metastasis. In addition, NAT1 could promote LBC cell migration and clonal formation, induce osteoclast differentiation and raise the Rankl/Opg ratio in osteoblasts. Our in vivo experiment demonstrated that NAT1 promoted LBC bone metastasis and bone destruction, which could be reversed by NAT1 inhibitor treatment. The result of cytokine array showed that NAT1 could significantly over activate the NF-κB signaling pathway and up-regulate the expression of IL-1B, which further worked as downstream factors in these processes. All these results demonstrated NAT1 was up-regulated in LBC and promoted the formation of bone metastatic niche and osteolytic bone metastasis through the NAT1/NF-κB/IL-1B axis. This finding may provide a new pathway to help understand the mechanisms of LBC bone metastasis and suggest a novel therapeutic and diagnostic target for its treatment.