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1.
Biosci Rep ; 40(3)2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32096822

RESUMO

Secondary injury after spinal cord injury (SCI) is one reversible pathological change mainly involving excessive inflammatory response and neuro-apoptosis. Since in recent years, microRNAs (miRNAs) have been proposed as novel regulators of inflammation in different disease conditions. However, the role of miRNAs in the inflammatory response and apoptosis of secondary injury after SCI remains to be fully elucidated. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. The expression profiles of miRNA were examined using miRNA microarray, and among the candidate miRNAs, miR-129-5p was found to be the most down-regulated miRNA in spinal tissues. Overexpression of miR-129-5p using agomir-miR-129-5p promoted injury mice functional recovery, suppressed the apoptosis and alleviated inflammatory response in spinal tissues. Using LPS-induced BV-2 cell model, we found miR-129-5p was also proved in protecting inflammatory response and cell apoptosis in vitro. High-mobility group protein B1 (HMGB1), a well-known inflammatory mediator, was found to be directly targeted by miR-129-5p and it was associated with the inhibitory effect of miR-129-5p on the activation of toll-like receptor (TLR)-4 (TLR4)/ nuclear factor-κB (NF-κB) pathway in vitro and in vivo. Further experiments revealed that the anti-apoptosis and anti-inflammatory effects of miR-129-5p were reversed by HMGB1 overexpression in BV-2 cells. Collectively, these data revealed that miR-129-5p alleviated SCI in mice via suppressing the apoptosis and inflammatory response through HMGB1//TLR4/NF-κB pathway. Our data suggest that up-regulation of miR-129-5p may be a novel therapeutic target for SCI.

2.
Bone Joint J ; 102-B(2): 177-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009426

RESUMO

AIMS: To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). METHODS: This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). RESULTS: There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. CONCLUSION: Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177-185.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/cirurgia , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/cirurgia , Sacro/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Criança , Terapia Combinada , Curetagem/métodos , Feminino , Tumor de Células Gigantes do Osso/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
3.
Foot Ankle Surg ; 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31874789

RESUMO

BACKGROUND: Amputation has been regarded as the standard surgical treatment for distal fibula osteosarcoma. With the advances in surgery and adjuvant chemotherapy, it have made limb salvage possible. However, the choice of a specific reconstruction procedure is frequently based on the surgeon's preference and it lacks of guidelines and high quality studies with the objective result on the subject. MATERIALS AND METHODS: Six patients with the distal fibular osteosarcoma which were received biological reconstruction were retrospectively reviewed at our bone tumor center from November 2003 to November 2015. There were 6 male with a mean age of 24.2 years (range, 12-47 years). The minimum follow-up duration was 53.3 months (median, 96.3 months; average, 108.4 months; range, 53.3-204.1 months). No patient was lost at the last follow-up. All data were obtained from the clinical and radiograph records. Furthermore, the literature review was based on the Google Scholar, Medline, EMBASE and Pubmed databases. The search was performed using the terms "distal fibula", "lower limb tumour", "sarcoma", "fibular metastasis" and "limb-salvage surgery" for the literature review from 1979 to 2017. RESULTS: Of the six patients with the final follow-up in the present study, four cases (83.3%, 4/6) achieved excellent prognosis without oncologic complications. A second surgical procedure was performed in two patients, one to treat local recurrence and one to receive metastasectomy due to the pulmonary metastasis. Case 6 received the below knee amputation due to recurrence. All the cases available for functional evaluation at the final follow-up had a mean functional MSTS score of 29.6 (range, 28-30) except case 6 receiving the amputation below the knee. Meanwhile, the VAS evaluation had a mean functional score of 0.2 points (range, 0-1 points). The results of our cohort and literature review illustrated that the patient with the malignant tumor of lateral malleolus could obtain excellent oncological prognosis and ankle function. CONCLUSIONS: We have provided treatment recommendations depending on the tumor volume and associated extent and proposed the primary ankle arthrodesis was performed after en bloc resection of Type II and III lateral malleolus osteosarcoma, based on the proposed classification. Furthermore, the patient with the malignant tumor of lateral malleolus could obtain excellent oncological prognosis.

4.
World J Surg Oncol ; 17(1): 194, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31739788

RESUMO

BACKGROUND: Revised Tokuhashi score (RTS) is no longer accurate to predict the survival of patients with lung cancer metastases to the spine. This study is to identify additional prognostic factors in those patients, develop a modified prognostic score based on RTS, and verify the accuracy of the score in prediction. METHODS: Our study included patients with lung cancer metastases to the spine who underwent surgery for spine metastasis. Potential prognostic factors were analyzed. Points were allocated for prognostic factors obtained from survival analyses. A modified score was developed by including prognostic factors and their points to RTS. Accuracy of the modified score was evaluated by comparing the coincidence between predicted and observed survival. Kaplan-Meier analysis and Cox regression models were used. Predictive values of scores for 6-month survival were measured via receiver operating characteristic (ROC) curves. RESULTS: Targeted therapy and tumor markers were additional independent prognostic factors. In the modified score, 2 and 1 points were allocated to the new evaluation factors. The points for factors based on RTS remained the same, and two prognostic groups were redefined. For group A patients who were predicted to live for less than 6 months, conservative procedures would be recommended. For group B patients who were predicted to live for 6 months or more, palliative surgery would be recommended. When comparing the modified score to RTS, the area under the receiver operating characteristic curve (AUCROC) and accuracy of score were improved. CONCLUSIONS: The modified RTS has improved prognostic accuracy in patients with lung cancer metastases to the spine.

5.
Medicine (Baltimore) ; 98(36): e17029, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490390

RESUMO

There is an increased enthusiasm in treating osteolytic metastatic acetabulum via injecting polymethyl-methacrylate (PMMA) as a bone filler to provide pain relief and potential structural support. The aim of this respective study is to determine the function and quality of life improvement after cement acetabuloplasty.Thirty two patients underwent acetabular cement augmentation between May 2014 and March 2018 were respectively reviewed. Isolated percutaneous acetabuloplasty (PA) was performed in 15 patients (group A) while radiofrequency ablation with PA (RFA-PA) in 12 patients (group B). Together with PA, open reconstructive surgery on ipsilateral femur was performed in another 5 cases (group C). Pre- and posttreatment functional evaluation and quality of life (QoL) assessment were carried out.The average followup duration was 11.5 (range, 3-36) months. None of major complications occurred. 81.2% (26/32) of patients achieved complete pain relief. Reduction of pain intensity and improvement of functional status achieved significantly differences after treatment (P = .00). Significant improvement (P = .00) was observed in scales of global QoL and pain-related restrictions in daily activities. Both isolated PA and RFA-PA procedures were equally effective towards the improvement of function and quality of life (P > .05). Regarding 5 patients in group C, pain intensity decreased when loading the affected limb and they could walk with crutches or cane.Bone cement acetabuloplasty is an adequate and effective mini-invasive procedure to relieve pain, restore function, and enhance the quality of life of patients for as long as possible in metastatic patients with short life expectancy. Ipsilateral surgery appears to be safe and well tolerated.


Assuntos
Acetabuloplastia/métodos , Acetábulo/cirurgia , Neoplasias Ósseas/cirurgia , Carcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cimentos para Ossos , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Carcinoma/radioterapia , Carcinoma/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Ablação por Radiofrequência , Recuperação de Função Fisiológica , Estudos Retrospectivos
6.
BMC Musculoskelet Disord ; 20(1): 367, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399083

RESUMO

BACKGROUND: Reconstruction for large bone defect of distal tibia after wide resection of tumor is difficult, and the best option remains controversial. This study presents a novel "double-strut" fibula ankle arthrodesis for this issue. METHODS: Nine patients with malignant or aggressive tumors of distal tibia underwent novel "double-strut" fibula ankle arthrodesis after wide tumor resection were retrospectively reviewed. We assessed the bone union time, complications and oncology outcome clinically and radiographically. The Musculoskeletal Tumor Society (MSTS) score and the Foot and Ankle Outcome Score (FAOS) were used to evaluate the functional outcome. RESULTS: The average followup period was 53 ± 46 months. There was no deep infection or graft fracture observed in this series. Internal fixation loosening was found in one case. In these patients, eight achieved union at both proximal and distal junctions, while one achieved union only distally. The mean union time of the proximal junctions and distal junctions was 10.5 ± 1.6 months and 8.7 ± 2.3 months, respectively. The mean postoperative MSTS score was 83% ± 8%. The subscales of FAOS indicating the most problem was Sport and Recreation Function with a mean score of 18 ± 11. At the final follow-up, one of them (1/9, 11%) experienced local recurrence in soft tissue and received another resection surgery, and four (4/9, 44%) patients developed lung metastases. CONCLUSIONS: For large bone defect of distal tibia, this novel "double-strut" fibula reconstruction can be a viable alternative, which is capable of achieving durable ankle fusion and functional salvaged limb with low rate of complications.


Assuntos
Artrodese/métodos , Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Fíbula/transplante , Salvamento de Membro/métodos , Osteossarcoma/cirurgia , Adolescente , Adulto , Articulação do Tornozelo/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/efeitos adversos , Estudos Retrospectivos , Tíbia/cirurgia , Resultado do Tratamento , Adulto Jovem
7.
Cancer Manag Res ; 11: 7183-7195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447583

RESUMO

Purpose: We intend to analyze the gain and loss from transcatheter intra-arterial (IA) limb infusion of cisplatin for extremity osteosarcoma in the past six years. Patients and methods: Between December 2009 and August 2014, a total of 99 patients were analyzed for efficiency and followed up for long-term survival. Based on the different administration methods of cisplatin, we divided them into the following two cohorts: IA infusion of cisplatin (n=48) and intravenous (IV) infusion of cisplatin (n=51). Except for cisplatin, all the other drugs were given intravenously. Cisplatin was given intra-arterially with an infusion time of 3 hrs or 6 hrs using a pump, whereas historical controls received IV infusion of cisplatin within 60 mins. Tumor neovascularity (TNV) was analyzed before infusion, and subsequent arteriograms were compared with the baseline to determine percent changes. Definitive surgery with intended wide resection and postoperative pathological evaluation were performed in all these patients. Results: No local or overall survival benefit was found in the patients preoperatively treated with IA infusion of cisplatin compared with IV infusion (P=0.336 and 0.173, respectively). Furthermore, serial arteriography was used to predict a good histologic response with an accuracy of 73.1% and a sensitivity of 100%. There were sporadic cases with the telangiectatic subtype, which did not respond very well to IV chemotherapy, but later, the tumor obviously shrank after IA infusion of cisplatin. Our study also showed that the rates of the complication of skin and muscle necrosis were not so low as reported. Conclusion: We did not observe any survival advantage of chemotherapy using IA infusion in osteosarcoma of the extremities. Arteriography for TNV can be used to predict the tumor histologic response. Malposition of the catheter might severely increase the complication of skin or muscle necrosis.

8.
World Neurosurg ; 129: 531-537.e1, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207371

RESUMO

BACKGROUND: Primary malignancies involving the mobile spine often require total en bloc spondylectomy with complex mechanical reconstruction, which can be augmented with novel application of the 3-dimensional (3D)-printing technique. CASE DESCRIPTION: A 51-year-old man presented with a 12-month history of progressive thigh pain and lower limb motor function loss, 36 months after T12-L4 instrumentation and fusion for giant cell tumor (GCT) of the L2 vertebrae before referral. The patient subsequently underwent successful curative management of recurrent GCT through denosumab treatment, L1-L3 total en bloc spondylectomy (TES), and a novel lumbopelvic reconstruction method with a 3D-printed lumbar vertebrae and screw-rod system. CONCLUSIONS: To our knowledge, this is the first reported case of multilevel lumbar TES for GCT reconstructed using a 3D-printed vertebrae. Although TES-specifically in the lumbosacral spine-remains challenging due to its unique anatomy and increased risk of neurologic insult, it is an effective option for curative management of GCTs.


Assuntos
Tumor de Células Gigantes do Osso/cirurgia , Impressão Tridimensional , Procedimentos Cirúrgicos Reconstrutivos/métodos , Neoplasias da Coluna Vertebral/cirurgia , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia
9.
Pharm Biol ; 57(1): 263-268, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31124385

RESUMO

Context: Researchers in a variety of fields have extensively focused on histone deacetylase 6 (HDAC6) due to its aggravation of inflammatory reaction. However, relevant studies examining whether HDAC6 could exacerbate lipopolysaccharide (LPS)-induced inflammation are still lacking. Objective: We assessed the role of HDAC6 in LPS-induced brain inflammation and used the HDAC6-selective inhibitor Tubastatin A (TBSA) to investigate the potential mechanisms further. Materials and methods: Brain inflammation was induced in Kunming (KM) mice via intraperitoneal (I.P.), injection of Lipopolysaccharide (LPS) (1 mg/kg), the TBSA (0.5 mg/kg) was delivered via intraperitoneal. The phosphorylated p38 (p-p38) Mitogen-activated protein kinases (MAPK) and expression of typical inflammatory mediators, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in both the hippocampus and cortex, were examined by immunoblotting. Nissl staining was used to detect the neuronal damage in the hippocampus and the cortex. Results: About 1 mg/kg LPS via daily intraperitoneal (I.P.) injections for 12 days significantly increased p38 MAPK phosphorylation, TNF-α and IL-6 expression, and neuronal loss. However, 0.5 mg/kg TBSA (three days before LPS treatment) by I.P. injections for 15 days could reverse the above results. Conclusions: This present study provided evidence that TBSA significantly suppressed LPS-induced neuroinflammation and the expression of p-p38. Results derived from our study might help reveal the effective targeting strategies of LPS-induced brain inflammation through inhibiting HDAC6.


Assuntos
Encefalite/prevenção & controle , Inibidores Enzimáticos/farmacologia , Desacetilase 6 de Histona/antagonistas & inibidores , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Lipopolissacarídeos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Modelos Animais de Doenças , Encefalite/enzimologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos , Fosforilação
10.
Medicine (Baltimore) ; 98(22): e15787, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145303

RESUMO

Since the standard reconstructive option after large segmental resection of proximal humeral tumors remained controversial, we designed and applied plate-prosthesis composite (PPC) for this circumstance. The purposes of the study were to: compare the functional outcome, implant survival (IS), surgical risk of PPC with those of conventional proximal humeral prosthesis (PHP); and describe the design and reconstructive procedure of PPC.Twenty patients (11 males, 9 females), who received intraarticular proximal humeral resection without preservation of abductor mechanism, were included in this study, with a mean resection length accounting for 72.5% (range, 61.9-81.8%) of whole humeral length. According to the reconstructive options, we categorized patients into PPC group (9 patients) and PHP group (11 patients). PPC was a semi-custom-made endoprosthesis, with modular proximal part same as PHP and custom-made distal part including dumpy stem and composite lateral anatomic plate for distal humerus. The mechanical prosthetic complication was defined as the imaging evidence regardless of reoperation. The IS was defined as the time from surgery to the occurrence of mechanical prosthetic complication.The mean follow-up time was 40.1 months (range, 14-129). The Musculoskeletal Tumor Society 93 scores of PPC and PHP group showed no significant difference (73.3% vs 70.0%, P = .46). Compared to PHP group, PPC group showed significantly lower mechanical prosthetic complication rates (0 vs 45.4%, P = .03) and better IS (86.0 vs 59.3 ±â€Š21.7 months, P = .028). Moreover, the comparison of surgical time (3.2 vs 3.3 hours, P = .60), blood loss (288.9 vs 376.4 mL, P = .15) and perioperative complication rates (11.1% vs 18.2%, P = .58) between 2 groups showed no differences.For reconstruction after large segmental resection of proximal humeral tumors, PPC achieved better IS while maintained similar functional outcome compared to conventional PHP without influencing the complexity and safety of surgery.


Assuntos
Membros Artificiais , Neoplasias Ósseas/cirurgia , Placas Ósseas , Aloenxertos Compostos , Úmero/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adolescente , Adulto , Idoso , Neoplasias Ósseas/patologia , Criança , Feminino , Humanos , Úmero/patologia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Ombro/cirurgia , Resultado do Tratamento , Adulto Jovem
11.
Injury ; 50(3): 777-783, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30772050

RESUMO

INTRODUCTION: This is a retrospective study that evaluate the outcome of patients with extremity sarcoma between extramedullary plate and intramedullary nailing for the biological reconstruction after tumor resection. METHODS: 58 patients (40 treated with plate fixation and 18 with intramedullary nailing, IM group) with sarcomas of the lower and upper extremity who received biological reconstruction at our bone tumor center from November 2003 to November 2015 were reviewed for the study. There were 29 male and 29 female patients with a mean age of 20.8 years (range, 5-72 years). The mean follow-up duration was 90.8 months (range, 12.2-244.4 months). All data were obtained from the clinical, radiograph records and follow-up information. The analysis of outcome, survival, local recurrence, function and complications of patients in the plate group and IM group was performed. RESULTS: 28 cases in the plate group lived at the last follow-up, of which 26 had no evidence of disease, 2 lived with the pulmonary metastasis, whereas 15 in the IM group lived at the last follow-up, of which all had no evidence of disease and no lived with the pulmonary metastasis. There was no significant difference between the two groups for the prognosis. Meanwhile, there was no significant difference of incidence of nonunion, graft fracture and fixation breakage between the two groups, whereas the time to diaphysis union in the plate group (11.6 ± 2.7 months) was shorter than that in IM group (14.7 ± 4.8 months, P = 0.015). It had the tendency that the time to mechanical complications in the intramedullary nailing group (38.1 ± 39.6 months) was longer than that in the plate group (15.7 ± 13.4 months, P = 0.058,95% CI,-45.6-0.8). Furthermore, the infection occurred in 12 cases and five grafts of them developed the deep infection and the mean time to deep infection was 14.8 ± 20.5 months. Furthermore, the incidence of local recurrence for the patients who had plate fixation was similar to the incidence of patients who had nailing fixation. At the last follow-up, the functional evaluation was performed for 39 patients. There was no significant difference in MSTS and VAS functional score for patients between in the plate group (n = 32) and IM group (n = 7). CONCLUSIONS: The findings of the present study showed that intramedullary nailing does not improve the union rate or decrease the incidence of mechanical complications for patients with extremity sarcoma after biological reconstruction. However, intramedullary nailing may have potential advantages on the service life for the biological reconstruction after extremity sarcoma resection.


Assuntos
Extremidades/cirurgia , Fixação Intramedular de Fraturas/métodos , Consolidação da Fratura/fisiologia , Fraturas Espontâneas/cirurgia , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Pinos Ortopédicos , Placas Ósseas , Criança , Extremidades/diagnóstico por imagem , Extremidades/patologia , Feminino , Seguimentos , Fixação Intramedular de Fraturas/efeitos adversos , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Radiografia , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Resultado do Tratamento , Adulto Jovem
12.
J Bone Oncol ; 14: 100209, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30581724

RESUMO

Background: Primary malignant or aggressive benign bone tumors rarely occur in distal tibia, and limb salvage remains the mainstay of surgical options. However, reconstruction methods for large bone defect after wide tumor resection in this location are debatable. The purpose of this systematical review is to critically evaluate each reconstruction method regarding the postoperative complications and functional outcome. Methods: A systematic review of the 33 studies including 337 cases with tumors affecting distal tibia was performed after searching the PubMed and EMBASE databases. Pooled descriptive statistics with separate analyses for postoperative complications and functional outcome of different reconstruction options were performed. Results: 290 (86.1%) patients received limb salvage procedures. Reconstruction strategies including biological reconstruction, such as autograft, allograft, distraction osteogenesis and non-biological prosthetic replacement. The patients received limb salvage procedures tended to have a higher MSTS score (77.1% vs 70.9%, P = .055) and a higher incidence of local relapse (28/290 vs 0/47, P = .052) than those amputated. Biological reconstruction methods provided better functional outcome (78.4% vs 72.2%, P = .017) compared with non-biological prosthetic reconstruction, although similarity of incidence of major complications (51/253 vs 12/37, P = .091). With respect to the comparison between autograft and allograft reconstruction, the autograft seemed to have less major postoperative complications occurrence (27/165 vs 22/78, P = .032), and consequently better functional outcome (MSTS score, 80.2% vs 74.3%, P = .025) than allograft reconstruction. Conclusions: Limb salvage results in better functional outcome compared with amputation. Biological reconstruction is more advocated than prosthetics replacement, and furthermore, autograft might be suggested to be the optimal reconstructive method with regard to better postoperative functional outcome and less major complications.

13.
Oncologist ; 24(7): e542-e550, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30559126

RESUMO

BACKGROUND: Antiangiogenesis tyrosine kinase inhibitors (TKIs) have been shown to prolong progression-free survival (PFS) in advanced osteosarcoma. Methylsulfonic apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-2. We aim to assess apatinib in patients with advanced high-grade osteosarcoma progressing upon chemotherapy. MATERIALS AND METHODS: This phase II trial was conducted at Peking University People's Hospital. We enrolled participants (≥16 years of age) with progressive relapsed or unresectable osteosarcoma. Participants received 750 mg or 500 mg of apatinib according to body surface area once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and PFS at 4 months. RESULTS: A total of 37 participants were finally included into the analysis. Until final follow-up, the objective response rate (complete response + partial response) was 43.24% (16/37). The 4-month PFS rate was 56.76% (95% confidence interval [CI], 39.43%-70.84%). Median PFS and overall survival were 4.50 (95% CI, 3.47-6.27) and 9.87 (95% CI 7.97-18.93) months, respectively. Toxic effects led to dose reductions or interruptions in a total of 25 of 37 (67.57%) patients. The most common grade 3-4 adverse events were pneumothorax in six (16.22%) patients, wound dehiscence in four (10.81%), proteinuria in three (8.11%), diarrhea in three (8.11%), and palmar-plantar erythrodysesthesia syndrome in three (8.11%). No other serious adverse events were reported during the trial. There were no treatment-related deaths. CONCLUSION: Apatinib is a sensitive drug for advanced osteosarcoma with a high response rate after failure of chemotherapy, with similar duration of response compared to other TKIs. IMPLICATIONS FOR PRACTICE: For advanced osteosarcoma progressing upon chemotherapy, antiangiogenesis tyrosine kinase inhibitors (TKIs) have been proved to be effective in prolonging the progression-free survival in previous multicenter trials and have been included into new National Comprehensive Cancer Network guidelines as second-line therapy. Apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-2, which is domestically made in China. This phase II trial supports the use of apatinib in patients with advanced osteosarcoma progressing after chemotherapy.

14.
Crit Care ; 22(1): 229, 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30244686

RESUMO

BACKGROUND: There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. METHODS: This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. RESULTS: A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2-19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2-3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353-0.599; p < 0.001). AGI 4 was significantly associated with lower hazard of EN administration (HR 0.056; 95% CI 0.008-0.398; p = 0.004). In a linear regression model, greater Sequential Organ Failure Assessment scores (coefficient - 0.002, 95% CI - 0.008 to - 0.001; p = 0.024) and male gender (coefficient - 0.144, 95% CI - 0.203 to - 0.085; p < 0.001) were found to be associated with lower EN proportion. As compared with AGI 1, AGI 2-3 was associated with lower EN proportion (coefficient - 0.206, 95% CI - 0.273 to - 0.139; p < 0.001). CONCLUSIONS: The study showed that EN delivery was suboptimal in Chinese ICUs. More attention should be paid to EN use in the early days after ICU admission.


Assuntos
Nutrição Enteral/normas , Resultado do Tratamento , APACHE , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , China , Estudos Transversais , Nutrição Enteral/métodos , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Modelos de Riscos Proporcionais
15.
Cancer Med ; 7(10): 4903-4913, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30141256

RESUMO

BACKGROUND: Venous tumor thrombus (VTT) in pelvic osteosarcoma has been regarded as a rare oncological condition and few literatures investigated this issue. METHODS: We retrospectively reviewed 115 cases of pelvic osteosarcoma treated in our center from 2006 to 2016. Diagnosis of VTTs was made based on histo-pathological findings. We summarized the radiological manifestations of VTTs on CT, MRI, and PET/CT. We also compared the demographical, oncological, and radiological data between cases with or without VTTs to identify its predisposing factors. RESULTS: Seventeen cases (14.8%) were diagnosed with VTT. Manifestations of VTTs on CT included increased caliber (64.7%), calcification (47.1%), low density on plain scan (100%), filling defect (100%), and streak-like enhancement (35.7%) on contrast enhancement. On MRI, the VTTs could be hypo- or iso-intense on T1WI (100%), hyperintense on T2WI (100%), and filling defect on contrast enhancement (100%). PET/CT showed high metabolic activity of the VTTs. The ranges of the VTTs included unilateral external iliac vein (EIV) (two cases), unilateral internal iliac vein (IIV) (one case), unilateral common iliac vein (CIV) and IIV (five cases), unilateral CIV + EIV (two cases), inferior vena cava (IVC) and unilateral CIV + EIV (one case), IVC and unilateral CIV + IIV (four cases), IVC and bilateral CIVs + IIVs (two cases). Multivariate analysis indicated that chondroblastic subtype and involvement of L5/S1 intervertebral foramen might predispose to VTTs. CONCLUSION: The incidence of VTTs in pelvic osteosarcoma was 14.8%. Comprehensive radiological studies help preoperative diagnosis of VTTs. Predisposing factors included chondroblasic subtype and involvement of L5/S1 intervertebral foramen.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Osteossarcoma/diagnóstico por imagem , Ossos Pélvicos/patologia , Trombose Venosa/diagnóstico por imagem , Adolescente , Adulto , Feminino , Humanos , Incidência , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Trombose Venosa/epidemiologia , Adulto Jovem
16.
J BUON ; 23(2): 453-459, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29745092

RESUMO

PURPOSE: Denosumab, a new monoclonal antibody that inhibits receptor activator for nuclear factor Kß ligand (RANKL), has recently been approved by FDA for the treatment of aggressive giant cell tumor of bone (GCTB). So we initiated this study to evaluate the clinical benifits of denosumab used preoperatively or postoperatively. METHODS: Patients diagnosed with classic sacral GCT without metastasis were included in this study. Patients were assigned into 3 groups according to the use of denosumab: control group 1, post-operative group 2 and neoadjuvant group 3. The latter two groups were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. The primary endpoints were event-free-survival (EFS) and objective response rate (OPR) based on RECIST criteria. A system (MUD system) proposed by our center was applied to score the sacral nerve deficit changes before surgery in group 3. RESULTS: A total 30 patients (13 men and 17 women, mean age 34.7 years, range 15-56) were enrolled from April 2014 to July 2016. Group 1 included 10 patients, group 2 9 and group 3 11. The study ended in March 01, 2017, and followup ranged from 3 to 36 months (mean 18.3). Two patients with PET-CT showed SUV max uptake down to muscle tissue level. In the neoadjuvant group 3 7 patients had partial responses and 4 stable disease (ORR 63.6%; 95% CI 35-92). Most (80%) patients achieved significant improvement in pain and great relief in the bladder and bowel functions. In 4 patients the urocatheter was removed after neoadjuvant denosumab. CONCLUSION: Neoadjuvant therapy with denosumab can significantly relieve the symptoms and neurologic deficits.


Assuntos
Denosumab/administração & dosagem , Tumor de Células Gigantes do Osso/tratamento farmacológico , Terapia Neoadjuvante , Dor/tratamento farmacológico , Adolescente , Adulto , Denosumab/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tumor de Células Gigantes do Osso/genética , Tumor de Células Gigantes do Osso/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Dor/genética , Dor/patologia , Período Pós-Operatório , Ligante RANK/genética , Sacro/efeitos dos fármacos , Sacro/patologia , Resultado do Tratamento , Adulto Jovem
17.
Spine (Phila Pa 1976) ; 43(18): 1268-1274, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29538241

RESUMO

STUDY DESIGN: We retrospectively analyzed factors associated with spinopelvic mechanical failure after total sacrectomy. OBJECTIVE: To find the rate and type of mechanical fixation failure after total sacrectomy and to identify the associated risk factors. SUMMARY OF BACKGROUND DATA: Although rigid fixation has been achieved, mechanical failure is sometimes encountered in reconstruction after total sacrectomy. The incidence and factors associated with spinopelvic fixation mechanical failure after total sacrectomy are still not clear. METHODS: The study comprised 63 patients who underwent spinopelvic reconstruction after total sacrectomy. The potential risk factors for fixation mechanical failure after total sacrectomy were evaluated, which included age, sex, body mass index, type of tumor (benign or malignant), and adjuvant treatment received (e.g., chemotherapy, radiation therapy). The surgery-related factors included the classification of tumor resection (en bloc or piecemeal resection) and the type of iliosacral resection. Adoption of anterior spinal column fixation (ASCF), posterior pelvic ring fixation (PPRF), four-rod technique (FRT) of spinopelvic fixation (SPF), and structural or morselized bone grafting after total sacrectomy in patients were considered reconstruction-related factors. Cox regression models were used to analyze associations between postoperative fixation failure and risk factors for all models. RESULTS: Postoperative fixation mechanical failure occurred in 25% of patients (16/63) who underwent total sacrectomy. Univariate analysis showed that the factors associated with spinopelvic fixation mechanical failure after total sacrectomy were the non-adoption of FRT of SPF and ASCF, the adoption of Type II sacroiliac resection, and female sex, whereas multivariate analysis demonstrated similar results, except for the adoption of Type II sacroilliac resection. CONCLUSION: FRT connection of SPF and ASCF should be adopted in reconstruction after total sacrectomy, especially in female patients. LEVEL OF EVIDENCE: 3.


Assuntos
Ossos Pélvicos/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/tendências , Sacro/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Fenômenos Biomecânicos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/diagnóstico por imagem , Estudos Retrospectivos , Sacro/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Falha de Tratamento , Adulto Jovem
18.
Clin Orthop Relat Res ; 476(3): 490-498, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29529630

RESUMO

BACKGROUND: Although aortic balloon occlusion has been shown to reduce blood loss during sacral tumor resections, it has not been validated in larger sacral tumors involving the lower lumbar spine. If such an approach were shown to be associated with less blood loss, it might aid the tumor surgeon in resecting these difficult tumors. QUESTIONS/PURPOSES: (1) Is the use of aortic balloon occlusion associated with reduced blood loss in sacral tumor resections when the lower lumbar spine is also involved? (2) Does the use of the aortic balloon prolong total operating time? (3) What complications are associated with the use of a balloon? METHODS: We retrospectively studied all 56 patients diagnosed with sacral tumors involving the lower lumbar spine (L4, L5) who were treated surgically between 2004 and 2015 at our institute. During that time, 30 of the patients received aortic balloon occlusion therapy, whereas 26 of the patients did not. We generally used aortic balloon occlusion during procedures for hypervascular lesions (for example, giant cell tumors or metastatic renal cancers), primary malignant lesions, and recurrent lesions. We generally avoided use of aortic balloon occlusion in patients with anatomic defects of the aorta (aortic dissection or aneurysm was strictly contraindicated), renal artery bifurcation caudal to the L2 to L3 disc, age older than 70 years or younger than 12 years, history of Stage 2 hypertension [], history of balloon use in previous surgeries, and presence of unstable plaque on abdominal CT. The demographic data, intraoperative blood loss, transfusion volume, operating time, and postoperative wound drainage between the two groups were collected and analyzed. Balloon-related complications were identified. Followup in terms of balloon-related complications was conducted in all 56 patients for at least 6 months after surgery. RESULTS: Intraoperative blood loss was determined to be less in patients treated with the balloon compared with those treated without the balloon (median volume, 2000 mL, range, 400-6000 mL versus 2650 mL, range, 550-6800 mL, respectively; median difference, 605 mL; 95% confidence interval [CI], 100-1500 mL; p = 0.035). Total operative time was not prolonged in the balloon group (including balloon insertion time) compared with those treated without it (median time, 215 minutes, range, 110-430 minutes versus 225 minutes, range, 115-340 minutes, respectively; median difference, 10 minutes; 95% CI, -40 to 30 minutes; p = 0.902). Balloon-related vascular complications included local hematoma at the puncture site in five patients, femoral artery spasm in three patients, lower limb ischemia in one patient, and femoral artery pseudoaneurysm in one patient. Acute kidney injury was found in two patients in the balloon group. CONCLUSIONS: This study demonstrated that placement of the aortic balloon at a level just caudal to the renal artery bifurcation was associated with lower intraoperative blood loss and transfusion in lumbosacral tumor resections. However, procedure-specific complications were common and there was no benefit to total operative time. We suggest that the surgical procedures still need to be further refined to minimize complications. We also recommend that prospective studies be undertaken to confirm the efficacy of aortic balloon occlusion in surgery for lumbosacral tumors. LEVEL OF EVIDENCE: Level III, therapeutic study.


Assuntos
Aorta , Oclusão com Balão , Perda Sanguínea Cirúrgica/prevenção & controle , Vértebras Lombares/cirurgia , Procedimentos Ortopédicos , Sacro/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Aortografia , Oclusão com Balão/efeitos adversos , Feminino , Humanos , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Procedimentos Ortopédicos/efeitos adversos , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Fatores de Risco , Sacro/patologia , Neoplasias da Coluna Vertebral/patologia , Fatores de Tempo , Resultado do Tratamento
19.
Neurosci Lett ; 672: 46-52, 2018 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-29474875

RESUMO

The retinoic acid-inducible gene I (RIG-I) is a crucial cytoplasmic pathogen recognition receptor involved in neuroinflammation in degenerative diseases. In the present study, in vitro human astrocytes were subjected to a chemical hypoxia model using cobalt chloride pretreatment. Chemical hypoxia induces the up-regulation of RIG-I in astrocytes and results in the expression of inflammatory cytokines IL-1ß, IL-6, and TNF-α in an NF-κB dependent manner. Elevated RIG-I modulates the interaction of interferon-ß promoter stimulator-1 (IPS-1) and TNF receptor-associated factor 6 (TRAF6) following chemical hypoxia. Inhibition of IPS-1 or TRAF6 suppresses RIG-I-induced NF-κB activation and inflammatory cytokines in response to chemical hypoxia. These data suggest that chemical hypoxia leads to RIG-I activation and the expression of inflammatory cytokines through the NF-κB pathway. Blocking IPS-1/TRAF6 pathway relieves RIG-I-induced neuroinflammation in astrocytes subjected to hypoxia.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Astrócitos/metabolismo , Hipóxia Celular/fisiologia , Proteína DEAD-box 58/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Astrócitos/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cobalto/farmacologia , Humanos , Inflamação/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
20.
Int Orthop ; 42(3): 695-703, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29404667

RESUMO

INTRODUCTION: With the development of surgical techniques and improvements in hemi-pelvic prosthesis systems, extra-articular resection can be performed as a limb-salvage procedure in selected patients whose hip joint is invaded by a sarcoma. The aim of this study was to describe the indications for and the technical details, post-operative complications, and oncologic and functional outcomes of this procedure. METHODS: Eighteen patients with Enneking IIB or IB sarcoma who underwent extra-articular resection of the hip joint were enrolled. A modular pelvic endoprosthesis combined with a femoral endoprosthesis was used to reconstruct the bone and joint defect. Pathological diagnoses included osteosarcoma (7 patients), chondrosarcoma (7), undifferentiated high-grade pleomorphic sarcoma (3), and malignant peripheral nerve-sheath tumour (1). RESULTS: Wide, marginal and intralesional surgical margin was achieved in 13, four and one patients, respectively. There was one peri-operative death and the other 17 patients were followed up for 35.0 months (range, 10-75 months). Three patients had early-stage dislocations. One had a traumatic dislocation three years later. Two patients had wound complications. The average MSTS 93 score was 63.5% ± 10.8%. Four patients had local recurrence. The estimated three-year disease-free survival and overall survival for the 18 patients were both 50.0%. CONCLUSION: Although technically demanding, extra-articular resection of hip is a limb-salvage procedure that is worth considering for carefully selected patients.


Assuntos
Neoplasias Ósseas/cirurgia , Articulação do Quadril/cirurgia , Salvamento de Membro/métodos , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Ferimentos e Lesões/cirurgia , Adolescente , Adulto , Idoso , Artroplastia , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Próteses e Implantes , Implantação de Prótese , Procedimentos Cirúrgicos Reconstrutivos , Sarcoma/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Resultado do Tratamento , Ferimentos e Lesões/etiologia , Adulto Jovem
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