Reconstruction strategy in limb salvage surgery for primary malignant tumor of femoral shaft / 中华骨科杂志

Objective:To explore the methods, complications and follow-up results of limb salvage for primary malignant tumors of the femoral shaft.Methods:From October 2006 to October 2019, 41 cases of primary malignant tumors of femoral shaft were analyzed retrospectively, 37 cases were followed up, including 22 males and 15 females, aged 8-46 years with an average age of 20.56±4.72 years old. All the lesions were located in the femoral shaft, and The Enneking stage was IIB. Tumor lesion ranged in the femur from 10 cm to 24 cm, and there was no pathological fracture. Pre-operative puncture biopsy was performed in all cases.22 cases were confirmed as osteosarcoma, 8 as chondrosarcoma, 5 as Ewing sarcoma, 2 as malignant fibrous histiocytoma. Neoadjuvant chemotherapy has been used to treat both osteosarcoma and Ewing sarcoma. Among the 37 patients, 8 cases of patients received total femoral prosthesis replacement, 14 cases of intramedullary nail fixation with allogenic bone graft, 8 cases of allograft-prosthetic composite (APC), and 7 cases of 3D printed prosthesis. The limb function was graded according to MSTS 93 system.Results:37 out of 41 patients were followed up, and the average follow-up time was 23.15±16.74 months (6-62 months). There were 9 patients with pulmonary metastases (26.47%), among which 6 patients passed away due to multiple metastases. 28 patients survived without tumor at last follow-up. The MSTS score was18-28 (average of 22.55±2.57). The average score of 3D printing prosthesis group was 27±1.74, allogeneic bone transplantation group was 22.85±2.59, total femoral prosthesis replacement group was 20.25±2.25, and the APC prosthesis group was 20.5±2.07. There was statistical difference between 3D printing group and other groups. The overall excellent and good rate of lower limb function was 79.41%, in which the 3D group was 100%, allogeneic bone group was 78.5%, APC prosthesis group was 87.5%, total femoral prosthesis replacement group was 62.5%. There was no statistical difference in the excellent and good rate of limb function among the groups. There weren't any cases of hip joint dislocation after total femoral prosthesis replacement. Delayed union of bone healing was seen in 3 cases of allogeneic bone transplantation and 2 cases APC patients. One patient suffered from the postoperative hemorrhage-related diseases-sciatic nerve compression, and the nerve recovered after emergency debridement. One patient suffered from poor wound healing. The overall complication rate was 24.32% (9/37).Conclusion:The patients with primary malignant tumors of the femoral shaft can effectively recover the lower extremity function by choosing the appropriate surgical scheme, in order to achieve the purpose of limb preservation and improve the quality of life of the patients. 3D printing prosthesis provides a new choice in the treatment of femoral shaft tumors.

Effects of Hydralazine and 5-Aza-CdR on cell proliferation of human osteosarcoma cell line MG-63 and expression of gene WW domain-containing oxidoreductase / 中华骨科杂志

Objective To investigate the growth inhibition of human osteosareoma cell line(MG-63) intervened by Hydralazine and 5'-aza-2'-deoxycytidine (5-Aza-CdR),and the effect on the mRNA expression of gene WW domain-containing oxidoreductase (WWOX).Methods Certain volume of 5 × 104/ml of human osteosarcoma cell line MG-63 in logarithmic growth phase were added into 96-well plate.There were Hydralazine group (drug concentration,0.1,1.0,10 μmol/L),5-Aza-CdR group (drug concentration,5,10,20 μmol/L),Hydralazine combined with 5-Aza-CdR group (drug concentration,0.1 μmo/L + 5 μmol/L,1.0 μmol/L + 10 μmol/L,10 μmol/L + 20 μmol/L) and control group (culture medium).Methyl thiazol tetrazolium(MTT) colorimetric methods were used to test the growth inhibition of MG-63 cells intervened by different concentrations of Hydralazine and 5'-aza -2'-deoxycytidine (5-Aza-CdR).Flow cytometry AnnexinV-FITC/PI methods were used to assay the effects of Hydralazine and 5-Aza-CdR inducing apoptosis in osteosarcoma cells in vitro.Real-time polymerase chain reaction (Real-Time PCR)methods were used to detect amplification of WWOX mRNA induced by Hydralazine combined with 5-Aza-CdR or alone.Western-blotting methods were used to examine the expression of WWOX in MG-63 cells.Results Hydralazine and 5-Aza-CdR effectively inhibited the growth of MG-63 cells in a concentration and time-dependent manner.Combined effect was more obvious.Further more the expression levels of WWOX mRNA and protein were increased significantly in combined groups as compared with other groups.Conclusion Hydralazine and 5-Aza-CdR could effectively inhibit the proliferation of MG-63 cells and induce apoptosis which is concurrent with the promotion of the expression of WWOX.The mechanism may be that Hydralazine/5-Aza-CdR effectively cause the demethylated of WWOX gene CpG-rich promoter regions,leading to the high expression of WWOX and inhibit the growth of MG-63 cells.The use of hydralazine in the treatment of osteosarcoma is worthy of further investigation.

Preliminary study of sternal tumor resection and reconstruction with titanium mesh / 中华骨科杂志

Objective To explore the clinical efficacy and complications of the surgical treatment of sternal tumor resection and titanium mesh reconstruction.Methods From 2008 January to 2012 June,there were 8 cases of sternal tumor patients in our hospital,including 5 male and 3 female,with an average age of 50.4 (37-66) years old.The histological morphology included 2 cases of chondrosarcoma,1 case of osteosarcoma,2 cases of malignant fibrous histiocytoma,eosinophilic granuloma in 1 case,and 2 cases of sternal metastasis of breast cancer.Tumor invasion sites included the sternal manubrium in 3 cases,the body in 2 cases,and both in 3 cases.All patients had undergone preoperative puncture or incision biopsy.8 cases of sternal tumor patients were treated with sternal tumor resection and reconstruction of the thorax using titanium mesh.The clinical effect and complications were retrospectively analyzed.Results All patients were followed up for 9 months to 4 years.The operations went well in all cases,with no intraoperative crisis or operative death.Deep wound hematoma occurred in 1 patient 1 week postoperatively,who healed 2 weeks after drainage and debridement.There was no abnormal breathing,subcutaneous emphysema,pneumothorax,infection or other complications in other cases.1 case of malignant fibrous histiocytoma died of lung metastasis at 9 months follow-up,and 1 died of liver metastasis at 14 months,while other patients got no tumor recurrence,with good thoracic shape,free breathing,no titanium mesh loosening,dyspnea,chest tightness,pain,or abnormal respiratory discomfort during follow-up period.The chest radiograph showed no chest deformity,no loosening or fracture of the fixation device.Conclusion Sternal tumor resection and reconstruction with titanium mesh has the advantages of good shaping effect,fewer complications,and simple operation,showing that titanium mesh is an ideal material for the reconstruction of sternum.

Inhibition of arsenic trioxide for the capability of migration and invasion in Ewing' s sarcoma cell in vitro / 肿瘤研究与临床

ObjectiveTo investigate the effect of arsenic trioxide (As2O3) on the metastasis capability of Ewing's sarcoma ceils. MethodsMTT assays were performed to choose appropriate concentrations of As2O3 (＜ 2 μmol/L) for the experiments.Migration and invasion assays were performed to assess the effect of As2O3 on the metastasis of Ewing's sarcoma cells. Changes in matrix metalloproteinase(MMP)-9 expressions were detected by gel zymography assay and the phosphoinositide 3-kinase/AKT(PI3K-AKT)pathway was investigated using Western blot. ResultsThe amount of Ewing's sarcoma cells across basal membrane of Transwell in migration and invasion assay decreased gradually with the increase in As2O3 concentration. The average quantities of A-673 across the membrane after treatment by gradual concentrations accounted for 54.3 ％,49.0 ％ and 17.0 ％ of that of untreated group respectively in migration assay (F=112.78,P ＜ 0.01), while 52.7 ％, 32.3 ％ and 10.3 ％ in invasion assay(F =183.76, P ＜ 0.01). Similarly, the percentage of RD-ES was 46.0 ％,39.0 ％ and 8.0 ％ in migration assay (F =408.25,P ＜ 0.01) and 58.7 ％,22.3 ％ and 9.0 ％ in invasion assay (F =373.25, P ＜ 0.01)respectively. The difference had statistics significance.The expression of MMP-9 was suppressed by As2O3 treatment according to gel zymography assay.Western blot assay showed that PI3K-AKT pathway was inhibited and nuclear factor kappa B(NF-κB)was inactivated.ConclusionLow-concentration As2O3 may inhibit metastasis capability of Ewing's sarcoma cells.

Expression and biological significance of Runx2 in dedifferentiated chondrosarcoma cell line / 肿瘤研究与临床

Objective To detect the different expression of Runx2 in dedifferentiated chondrosarcoma and conventional chondrosarcoma, and to investigate the role of Runx2 in the occurrence and development of dedifferentiated chondrosarcoma. Methods Dedifferentiated chondrosarcoma cell line NDCS-1 and normal chondrosarcoma cell line SW1353 were cultured, then mRNA and total cellular protein were extracted.RT-PCR Western blotting, and immunocytochemistry were used to detect the expression of Runx2.Immunohistochemistry was used to test Runx2's expression in the dedifferentiated chondrosarcoma specim ens that confirmed by pathology. Results Runx2 was high expression in dedifferentiated chondrosarcoma cell line and high-grade component of dedifferentiated chondrosarcoma tissues. Conclusion The high expression of Runx2 in dedifferentiated chondrosarcoma is involved in the occurrence and development of dedifferentiated chondrosarcoma.

The effect of arsenic trioxide on metastasis and invasion of human osteosarcoma cell / 肿瘤研究与临床

Objective To study the effect and mechanism of arsenic trioxide on the motility, metastasis and invasion of osteosarcoma in vitro. Methods Wound healing assay, migration assay, invasion assay and Western-blot were performed to study the effect of arsenic trioxide on metastasis of osteosarcoma. Results Through screening MNNG cell was selected to perform the following research. After treatment of As_2O_3, the ability of MNNC cell flattening and spreading along the edges of the wound was inhibited, and the number of MNNG cells with migration and invasion in As_2O_3 - treated group was significantly less than in control group. Arsenic trioxide treatment also resulted in down-regulation of MMP-9. Conclusion This study is the first to report the effectiveness of arsenic trioxide as an inhibitor of osteosarcoma migration and invasion and the mechanism may be down-regulation of MMP-9.