IMMEDIATE FREE FLAP MANDIBULAR RECONSTRUCTION IN OSTEOSARCOMA OF THE MANDIBLE IN CHILDHOOD

Mandibular osteogenic sarcoma (OS) is a very rare entity in childhood. Adequate surgical rejection with a wide margin of normal tissue is the mainstay of treatment of this site, while the role of adjuvant chemotherapy remains uncertain. A case is presented of a 15 1/2-year-old male with a huge OS of the mandible. The boy underwent surgical resection of the mandible with immediate fibula free flap reconstruction and is alive and free of disease 6 1/2 years following unitial diagnosis. This case suggests that immediate bone reconstitution with vascularized grafts have good functional and morphological results for osteosarcoma of the lower jaw.     

骨肉瘤miR-96的表达与细胞增殖和凋亡

背景与目的:微小RNA(microRNA,miRNA)是一类内源性的非编码小分子RNA,其主要通过与靶mRNA作用抑制转录后的翻译。miR-96是在多类肿瘤细胞中高表达的小RNA分子。本研究旨在检测miR-96在骨肉瘤组织中的表达,并研究其在骨肉瘤细胞的增殖、细胞周期及凋亡中的意义。方法:运用TagMan MGB探针法检测40例骨肉瘤组织及对应的骨组织中miR-96的表达;应用反义技术降低骨肉瘤细胞(U2-OS和MG-63)中miR-96的表达;采用MTT比色法检测细胞增殖的改变;应用流式细胞技术检测骨肉瘤细胞细胞周期和凋亡情况。结果:在40例骨肉瘤组织中,62.5%(25/40)的骨肉瘤组织miR-96表达明显高于对应骨组织(P<0.05);反义miR-96转染骨肉瘤细胞U2-OS和MG-63后,miR-96的表达明显降低,U2-OS和MG-63骨肉瘤细胞生长受到明显抑制,其生长主要停滞在G0/G1期,而S期和G2/M期细胞的比例下降。另外,降低miR-96的表达,U2-OS和MG-63骨肉瘤细胞早期凋亡明显增加。结论:miR-96在骨肉瘤组织中表达明显上调,降低其表达能明显抑制U2-OS和MG-63骨肉瘤细胞的生长,并诱导细胞早期凋亡增加,miR-96可能成为骨肉瘤基因表达调控的新靶点。     

化疗联合重组人血管内皮抑素治疗ⅡB期骨肉瘤的前瞻性同期对照非随机临床研究

目的 探讨化疗联合重组人血管内皮抑素（恩度）治疗ⅡB期骨肉瘤的远期疗效及安全性。方法 收集2008年1月至2012年4月北京积水潭医院骨肿瘤科住院治疗的ⅡB期骨肉瘤患者,分为恩度联合化疗组和单纯化疗对照组。化疗方案如下：甲氨蝶呤 10g／m2静滴,d1;异环磷酰胺 3g／m2静滴,d1～d5;顺铂 120mg／m2 静滴,d1;阿霉素30mg／m2静滴,d1～d3。联合组在化疗的基础上加用恩度（15mg静滴,d1～d14,21天为1周期,共4个周期）。结果 388例患者入组,剔除和研究终止有58例,共纳入评价330例,其中联合组58例,对照组272例。随访6～59个月,中位随访时间为20.2个月。对照组1、2、3年无远处转移生存率分别为79％、70％和65％,联合组分别为93％、86％和77％（P=0.045）。对照组1、2、3年无进展生存率分别为76％、66％和60％,联合组分别为90％、83％和74％（P=0.025）。对照组1、2、3年生存率分别为94％、84％和79％,联合组分别为98％、94％和85％（P=0220）。两组的不良反应以1～2级为主,3～4级不良反应主要为白细胞减少,贫血、恶心呕吐和肝功能损害,两组不良反应差异无统计学意义。结论 恩度联合化疗治疗骨肉瘤能显著提高无远处转移生存率和无疾病进展生存率,不良反应可耐受,值得临床深入研究。     

Adverse impact of regional lymph node involvement in osteosarcoma

BackgroundMetastatic dissemination in osteosarcoma occurs haematogenously, though regional lymph node involvement is rarely reported. We investigated incidence, patient characteristics and survival for patients with osteosarcoma and regional lymph node involvement at diagnosis.MethodsWe identified 2748 cases of high-grade osteosarcoma with available information regarding regional lymph node involvement in the Surveillance Epidemiology and End Results database from 1973 to 2009. Demographics were compared using chi-squared tests or t-tests. Overall survival was estimated using Kaplan–Meier method and compared with log-rank tests. Multivariate analysis of overall survival was performed using Cox proportional hazards methods.ResultsThere were 74 patients (2.7%) with regional lymph node involvement at diagnosis of whom 19 (0.7%) were pathologically confirmed. Patients with regional node involvement were more likely to have extraskeletal tumours, distant metastases, tumours arising outside the lower extremity (p < 0.0001 for all comparisons) and larger tumours (p = 0.033). Five-year overall survival in those with and without regional node involvement was 10.9% (95% confidence interval (CI) 4.6–20.4) and 54.3% (95% CI 52.2–56.4; p < 0.0001). In multivariate analysis, regional node involvement remained predictive of inferior survival after controlling for differences in metastatic status, age, tumour site and extraskeletal origin (hazard ratio 2.05, 95% CI 1.57–2.67; p < 0.0001). Similar survival results were found when the analysis was restricted to patients with pathologically confirmed positive or negative regional lymph nodes.ConclusionThis analysis confirms that regional node involvement is a significant adverse prognostic factor that is independent of metastatic status, extraskeletal origin, age and tumour site.     

IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma

Osteosarcoma (OS) is the most common primary malignancy of bone. We investigated the roles of insulin-like growth factor binding protein 5 (IGFBP5) domains in modulating OS tumorigenicity and metastasis. The N-terminal (to a lesser extent the C-terminal) domain inhibited cell proliferation and induced apoptosis while the C-terminal domain inhibited cell migration and invasion. The Linker domain had no independent effects. In vivo, the N-terminal domain decreased tumor growth without affecting pulmonary metastases while the C-terminal domain inhibited tumor growth and metastases. In summary, the N- and C-terminal domains modulated OS tumorigenic phenotypes while the C-terminal domain inhibited OS metastatic phenotypes.     

下颌骨骨肉瘤影像学分析

目的:分析下颌骨骨肉瘤影像学表现,评价不同影像检查方法的优劣。方法:7例下颌骨肿块患者中均经X线和MRI检查,6例行CT并经手术病理证实为下颌骨骨肉瘤。所有病例的影像学特点和诊断价值均被分析比较。结果:X线检查有7例病变显示不清;6例呈棉絮状和不规则高密度,1例呈低密度,内有间隔;3例见骨膜反应呈“日光放射状”和“花边状”。CT平扫显示2例呈高密度,4例呈混合密度伴有骨皮质破坏、中断;5例见“日光放射状”骨膜反应;CT增强显示所有病例均有不均匀强化表现,4例伴有软组织肿块形成。平扫MRI显示5例病变T1WI上呈等、低信号,T2WI上呈高信号;2例在T1WI和T2WI上均呈等、低信号;增强MRI显示2例病灶轻度强化;2例呈边缘强化,其内强化不均。结论:CT和MRI均可清晰显示下颌骨骨肉瘤的形态和内部结构,MRI显示髓内病变范围方面优于CT。     

Impairment and disability following limb salvage procedures for bone sarcoma

Bone sarcomas are the fourth most common cancer in individuals under 25 years. Limb salvage procedures are popular for the treatment of osteosarcomas as they have functional and physiological benefits over traditional amputative procedures. The objective of this study was to apply disease specific measures to a group of intra-articular knee osteosarcoma patients and to evaluate structural and treatment variables predictive of the functional outcome scores. Twenty patients (10 ♀, 10 ♂) treated with tumour resection and endoprosthetic knee arthroplasty took part in the study. The Musculoskeletal Tumour Society (MSTS) rating scale and the Toronto Extremity Salvage Score (TESS) were used to assess impairment and disability respectively. Impairment was recorded as 83% and disability was recorded as 86% suggesting moderate to high function following limb salvage surgery. Task difficulty was shown to increase for activities requiring large knee flexion angles, presumably due to increased patellofemoral forces. Bivariate correlations revealed that loss of quadriceps musculature, knee extension strength and knee flexion range of motion were parameters moderately associated with the assessment instruments. ANOVA revealed no significant differences in impairment (P = 0.962) or disability (P = 0.411) between the differing types of prostheses. In conclusion clinicians and therapists should emphasise restoration of post-surgical range of motion and strength in order to enhance functional recovery.     

肢体骨肉瘤引流区淋巴结转移

目的 了解肢体骨肉瘤患者的引流区淋巴结转移情况，分析其出现的原因及应采取的对策。方法 通过复习病历、手术记录和病理，回顾我院自１９８０年２月～１９９７年１０月肢体骨肉瘤患者的引流我淋巴结转移病程、化疗情况及当时所采取的措施。结果 ７２例患者中有７例出现引流区淋巴结转移，占９．７％，保肢手术引流区淋巴结转移５例，占９．４％（４／５３）。７例患者均未接受正规方案化疗，可能是导致淋巴结转移的重要原因。６     

蛋白指纹图谱技术在骨肉瘤临床诊断中的初步应用

目的 比较骨肉瘤患者和正常对照者血清蛋白表达谱的差异,筛选骨肉瘤相关血清蛋白标志物,并建立基于决策树的预测模型,为筛选和建立骨肉瘤临床诊断的血清学指标提供依据.方法 27例骨肉瘤患者血清(男17例,女10例)及47名相匹配者正常对照血清标本随机分为两组:60份(23例骨肉瘤,37名正常对照)为建模组,14份(4例骨肉瘤,10名正常对照)为盲法筛选组.利用表面增强激光解吸离子化-飞行时间-质谱(surface enhanced laser desorption/ionization time of fight mass spectrometry,SELDI-TOF-MS)技术进行蛋白质谱分析.采用蛋白质飞行质谱仪对结合在CM10芯片上的血清蛋白进行读取分析.通过Biomarker Wizard软件比较两组人群血清蛋白质谱的差异,经生物信息学分析得到决策树模型并进行盲法验证.结果 在质荷比(M/Z)1488.15～19842u范围内,共检测到96个有效蛋白峰,其中9个峰差异有统计学意义.利用三倍交叉证实方法对建模组的蛋白质谱数据进行1000次随机抽样,得到1000个决策树.根据交叉证实的正确率选出最佳的20个决策树模型作为最终预测模型.用其对14个盲法筛选样本进行归类预测的正确率为85.71%.结论 应用SELDI-TOF-MS技术可筛选出骨肉瘤相关血清蛋白标志;建立的决策树模型可以对骨肉瘤作出较为准确的预测判断.