The role of conventional radiography to assess the outcome of oncologic skeletal reconstructions of lower limbs aided by vascularized fibular autograft

IntroductionVascularized fibular autografts (VFA) are used in the oncologic skeletal reconstructions of long bones, alone or combined with massive bone allografts (MBA). Data regarding the role of imaging in assessing these complex skeletal reconstructions are lacking, and have mainly focused on Computed Tomography (CT). Our aim was to evaluate if early conventional radiography (CR) findings are correlated with the outcome of these skeletal reconstructions.Materials and methodsAll consecutive patients who underwent oncologic resection of lower limbs long bones followed by VFA reconstruction were included in this single-center retrospective study. We compared the CR obtained immediately after surgery with the CR at the 6-month control, as well as the CR at 6 months with the CT at 6 months when available. The following scores were assigned to the VFA: 0 (unchanged), 1 (osteopenia-cortical bone thinning), 2 (increase in bone density-cortical thickening). We then investigated whether this score correlated with the implant outcome within 12 months (optimal integration, suboptimal integration, integration requiring further surgery or lack of integration) using Kaplan-Meier and Cox regression analyses, considering the occurrence of integration and the duration time before the surgical removal of the whole bone reconstruction.ResultsForty-five patients were included (32 men [71.1%], mean age 14.6 years), 26 affected by osteosarcoma, 14 by Ewing sarcoma, 3 by adamantinoma and 2 operated for the failure of previous reconstructions for bone sarcoma. VFA changes on 6-month CR were significantly associated with optimal integration of the implants (log-rank P = 0.0137, multivariate Hazard ratio = 7.62, 95% confidence interval = 1.13–51.25). None of the other clinical and surgical features were associated with the implant outcome. The findings on 6-month CR and CT follow-up were not significantly different. CT at 6 months was available in 36 patients (80.0%).ConclusionThe assessment of VFA morphological changes on CR performed at 6 months can predict the outcome of the skeletal implant. This data should be considered for clinical decision-making, selecting patients requiring additional images (CT), and possible subsequent revision surgical procedures.     

LPS对骨肉瘤细胞迁移、侵袭及TLR4/HOTAIR通路的影响

目的探讨脂多糖(LPS)对骨肉瘤细胞迁移和侵袭的影响及其潜在的作用机制。方法将人MG-63骨肉瘤细胞随机分为2组:对照组和LPS组。LPS组细胞用10 g/ml的LPS干预24 h,对照组用生理盐水干预。ELISA检测干预后培养基中促炎因子的水平,Transwell实验检测细胞迁移和侵袭能力,Western Blot检测相关蛋白的表达。结果与对照组相比,LPS组培养基中促炎因子TNF-α、IL-1和IL-6的释放水平均显著增高(P<0.05),LPS组迁移细胞数和侵袭细胞数均显著增高(P<0.05),LPS组中E-cadherin的表达显著降低(P<0.05),而N-cadherin、α-SMA、波形蛋白、TLR4和HOTAIR的表达均显著增高(P<0.05)。结论LPS诱导的肿瘤微环境可促进骨肉瘤细胞的迁移和侵袭,其机制与TLR4/HOTAIR途径介导的EMT过程的发生有密切关系。     

Notch信号通路可通过激活Slug调控骨肉瘤上皮-间质转化

目的 探究Notch信号通路对骨肉瘤上皮-间质转化的影响及其机制。方法 通过慢病毒转染技术转染骨肉瘤细胞，利用si-slug敲除Slug基因，采用免疫荧光染色技术、Western blot、qRT-PCR、相差显微镜、划痕实验和TranswellTM实验检测相应骨肉瘤细胞形态、侵袭、转移及上皮间质转化（EMT）情况。动物实验比较各组小鼠成瘤后体积、重量变化；采用qRT-PCR检测离体肿瘤组织中Slug和N-cadherin的表达。结果 成功得到Notch信号通路激活或抑制的骨肉瘤细胞，Notch信号通路激活组E-cadherin表达无明显变化，N-cadherin表达显著升高，骨肉瘤细胞长/短轴比率上调，Slug、Twist1表达上调，侵袭及转移能力增强。动物实验发现Notch信号通路激活可促进体内成瘤，离体骨肉瘤组织中Slug、N-cadherin阳性率增高。Slug被成功敲除后Notch信号激活组骨肉瘤细胞形态、侵袭及转移能力发生逆转。结论 Notch信号通路对骨肉瘤上皮-间质转化过程具有促进作用，其机制可能与激活Slug有关。     

1999-2018年贵州省黔南州居民骨肉瘤发病特征及变化趋势分析

目的 分析1999-2018年黔南州居民骨肉瘤发病特征及变化趋势，为制定防治措施提供参考依据。方法 提取黔南州肿瘤登记处系统中1999-2018年新发骨肉瘤病例发病信息进行性别、年龄分析，计算发病率、中国标化发病率（中标率）、世界标化发病率（世标率）、年龄别发病率和年均变化百分比（APC）等。并对黔南州不同民族骨肉瘤患者病理类型分布特征进行统计分析。结果 1999-2018年黔南州居民新发骨肉瘤237例（男性147例，女性90例），发病率为3.66/100万（男性4.39/100万，女性2.87/100万），中标率2.49/100万（男性2.76/100万，女性2.17/100万），世标率为2.90/100万（男性3.45/100万，女性2.35/100万）。发病率在9岁以前处于较低水平，9岁以后迅速升高，10～19岁年龄段达到峰值14.97/100万（男性16.03/100万，女性12.85/100万），20岁以后迅速下降，60岁以上年龄段发病率逐渐减低，男、女年龄别发病率变化趋势基本一致。237例骨肉瘤患者病理诊断主要以常规性骨肉瘤最为常见，占83.54%。布依族骨肉瘤患者病理类型分布与苗族、水族、毛南族、汉族及其他民族骨肉瘤患者比较，差异均有统计学意义（x2值分别为16.125、14.709、12.486、9.613、10.078、28.727，P=0.001）。结论 贵州省黔南州居民20年来骨肉瘤发病率有呈上升趋势，男性、10～29岁年龄段和布依族居民是防治的重点人群。     

骨水泥型与非骨水泥型假体置换治疗膝关节周围骨肉瘤的疗效评价

目的回顾性分析骨水泥型与非骨水泥型假体置换治疗膝关节周围骨肉瘤的近期临床疗效。方法 2014年6月至2019年6月,71例累及膝关节周围骨肉瘤患者于我院行保肢治疗,男43例,女28例,平均10.4 (6~49)岁。接受骨水泥型和非骨水泥型假体置换分别54例和17例。采用MSTS功能评分对两种假体置换手术进行评分。结果所有患者随访10~76个月,平均31个月。骨水泥型和非骨水泥型假体置换组MSTS功能评分分别为(23.8±3.3)分、(25.9±1.7)分,两组差异有统计学意义(P <0.05)。骨水泥型假体置换组1例发生假体周围骨折,2例发生假体无菌性松动。非骨水泥组随访期间均未出现感染、假体脱位、假体松动等并发症。本组11例死于肿瘤相关疾病,48例无瘤生存,12例带瘤生存。24例(24/71,33.8%)术后4~29个月内发生肺部转移或其它部位多发转移,8例(8/71,11.3%)出现局部复发。结论随着骨肉瘤患者总生存期的延长和生存率的提高,对于预生存期较长、活动量较大且骨质较好的患者而言,非骨水泥型假体不失为一种有效的治疗选择。     

Dysregulation of microRNA-106a-5p-RUNX1 axis associates with clinical progression and prognosis of osteosarcoma patients

MicroRNA-106a-5p (miR-106a-5p) functions as a tumor suppressor in osteosarcoma cells. Here, we aimed to identify novel target genes of miR-106a-5p in osteosarcoma, as well as to investigate their prognostic value and the biological functions. At first, the mammalian runt-related factor 1 (RUNX1) was identified as one of the target genes of miR-106a-5p in osteosarcoma cells by luciferase reporter gene assay, real-time quantitative RT-PCR and Western blot analysis. Then, the expression levels of miR-106a-5p and RUNX1 in osteosarcoma tissues were detected, and their associations with clinicopathological features and patients' prognosis were statistically analyzed. Compared with adjacent non-cancerous tissues, miR-106a-5p and RUNX1 mRNA/protein expression in osteosarcoma tissues were significantly decreased and increased, respectively (all P < 0.01). Low miR-106a-5p, high RUNX1 and miR-106a-5p-low/RUNX1-high expression in osteosarcoma tissues were all significantly associated with advanced Enneking stage, positive metastasis and shorter overall survival (all P < 0.05). Moreover, miR-106a-5p and RUNX1 expression, alone or in combination, were identified as independent prognostic factors for osteosarcoma patients' overall survival. Functionally, the enforced expression of miR-106a-5p significantly suppressed proliferation and invasion of osteosarcoma cells, while the overexpression of RUNX1 effectively reversed its suppressive roles. In conclusion, our findings show the dysregulation of miR-106a-5p-RUNX1 axis in human osteosarcoma tissues and suggest its crucial roles in cancer progression and patients' prognosis. More interestingly, miR-106a-5p may function as a tumor suppressor in osteosarcoma cells via regulating its target gene RUNX1.     

重组沙门氏菌VNP20009-M对骨肉瘤的治疗作用

目的 研究携带甲硫氨酸酶基因的减毒沙门氏菌VNP20009-M对骨肉瘤的治疗作用及其机制。方法 将重组沙门氏菌VNP20009-M与骨肉瘤细胞MNNG-HOS共培养；骨肉瘤细胞MNNGHOS、U2OS及SaoS-2均高表达甲硫氨酸酶基因后探索细胞增殖、迁移及凋亡能力的变化；构建MNNG-HOS裸鼠皮下荷瘤模型，评价不同剂量的VNP20009-M在动物模型中的治疗效果。结果 通过质粒PCR验证甲硫氨酸酶基因只存在于目的菌株VNP20009-M中，且具有较高的甲硫氨酸酶活性，重组沙门氏菌构建成功。VNP20009-M显著诱导骨肉瘤细胞MNNG-HOS的凋亡。相比对照组，甲硫氨酸酶基因过表达的骨肉瘤细胞增殖、迁移能力被显著抑制。VNP20009-M治疗后小鼠皮下肿瘤生长被显著抑制。结论 VNP20009-M可诱导骨肉瘤细胞凋亡并抑制癌细胞增殖和迁移，可以作为一种新型高效的药物为临床提供新的治疗方式。     

新辅助化疗治疗头颈部骨肉瘤单中心临床效果回顾

目的 评价新辅助化疗在头颈部骨肉瘤治疗中的效果。方法 回顾2007—2015年于上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科接受治疗的头颈部骨肉瘤患者的基本信息、围术期治疗信息、影像学信息、病理学信息以及随访记录,采用SPSS 17.0软件包对数据进行统计学分析。结果 最终纳入患者157例,男68例,女89例,5年总生存率（OS）为50.96%。≤30岁51例,31~60岁85例,≥61岁21例。91例肿瘤位于下颌骨,66例位于上颌骨及颅底。高级别骨肉瘤141例,低级别骨肉瘤8例,分化程度未知8例。54例肿瘤最大直径>4 cm,103例肿瘤直径≤4 cm。术区切缘阳性7例。单纯手术治疗65例,手术联合化疗15例,手术联合放、化疗23例,手术及放疗54例。单因素分析显示,肿瘤远处转移的相关因素为上颌骨及颅底肿瘤（P=0.022）、高级别骨肉瘤（P=0.011）以及阳性切缘（P=0.031）;下颌骨骨肉瘤（P=0.032）、阴性切缘（P=0.006）与患者OS相关;阴性切缘（P=0.007）与患者无瘤生存率（DFS）相关。多因素分析显示,肿瘤部位（P=0.034）、切缘（P=0.006）、化疗（P=0.025）、病理学亚型（P=0.012）与患者总体生存率相关;阳性切缘（P=0.002）、未接受放疗（P=0.005）与肿瘤局部复发相关。结论 术区安全切缘是头颈部骨肉瘤良好预后的关键,放疗在一定程度上可以抑制肿瘤复发,化疗（新辅助化疗、辅助化疗）可提高患者术后总体生存状况。