Objective To review the research progress of the treatment of osteosarcoma, and to thoroughly understand its current state of research and prospect so as to lay a sol id foundation for the cl inical treatment. Methods The cl inical and experimental research l iteratures about treatment of osteosarcoma were extensively reviewed and analyzed. Results The present treatment of osteosarcoma is still need to comprehensive therapy which combine chemotherapy and surgical treatment. There are some progresses in gene therapy and molecular targeting therapy which can improve survival rate. Furthermore, well-designed studies and cl inical trials are needed to evaluate the potential therapeutic impact before they are used in cl inical. Conclusion Advancement in chemotherapeutic regimens has improved survival and l imb-sparing surgery in the treatment of osteosarcoma, but the progress of gene therapy and molecular targeting therapy gives new hope for osteosarcoma patients.
Objective To investigate the feasibility of the preservation of the epiphysis and joint function of the distal femur in children with osteosarcoma with epiphyseal distraction by external fixator. Methods Between July 2007 and May 2011, 6 children with osteoblastic osteosarcoma of the distal femur underwent epiphyseal distraction by external fixator, combined with tumor resection and repair with massive allograft bone transplantation to preserve the epiphysis and joint function of the distal femur. There were 4 boys and 2 girls, aged from 9 to 14 years (mean, 10.5 years). According to Enneking clinical staging, 4 cases were in stage II A and 2 cases in stage II B. According to San-Julian et al. typing for metaphyseal tumor invasion, 3 cases were in type I and 3 cases in type II. The size of tumor ranged from 6 cm × 4 cm to 12 cm × 9 cm. All patients received 2 cycles of COSS 86 chemotherapy before operation and 4 cycles after operation. Results Poor healing of incision was observed in 1 case because of rejection of allograft bone and good healing was obtained after the symptomatic treatment, healing of incision by first intention was achieved in the other children. All 6 cases were followed up 11 to 56 months (mean, 37.5 months). One case died of lung metastasis at 2 years after operation. X-ray films showed no complication of internal fixator loosening and broken or bone nonunion. According to the functional evaluation criteria of International Society of Limb Salvage (ISOLS) at last follow-up, the results were excellent in 3 cases, good in 2 cases, and fair in 1 case; the excellent and good rate was 83.3%. The length of operated limb was (62.97 ± 7.51) cm, showing significant difference when compared with that of normal limb [(64.03 ± 7.47) cm] (t=0.246 6, P=0.813 4). Conclusion On the premise of adaptable indication, effective chemotherapy, and thoroughly tumor resection, the epiphyseal distraction by external fixator can obtain satisfactory results in limb-length and limb function in children with osteoblastic osteosarcoma of the distal femur.
ObjectiveTo investigate the causes of the complications and prevention strategy by analyzing occurrence of prosthesis-related complications after extensible semi-joint prosthesis replacement for lower limbs osteosarcoma in children. MethodsEleven children with lower limbs osteosarcoma underwent resection of tumor and replacement of the extensible semi-joint prosthesis between May 2006 and October 2012. There were 6 boys and 5 girls, with an average age of 9.3 years (range, 7-12 years). The lesions located at the distal femur in 6 cases, at the proximal femur in 2 cases, and at the proximal tibia in 3 cases. The disease duration was 2-8 months (mean, 3.6 months). According to the Enneking stage, 3 cases were rated as stage ⅡA and 8 cases as stage ⅡB. The pulmonary CT and ECT results showed no pulmonary metastasis or multi spots before operation. All patients received preoperative chemotherapy treatment for 4 times. ResultsPrimary healing of incision was obtained in 10 cases. Infection occurred in 1 case at 1 week after operation, and was cured after symptomatic treatment. Nine patients received postoperative chemotherapy for 12 times, 2 patients for 2 times and 4 times respectively. One case died of multiple metastasis; in 3 cases of pulmonary metastasis, 2 cases died and 1 case survived after resection of metastatic lesion. Eight survival cases received a follow-up of 25-89 months (mean, 42.5 months). Loosening and dislocation of the proximal femoral prosthesis occurred in 1 case, loosening and subsidence of the distal femoral prosthesis in 1 case, subluxation in 1 case, and retraction in 1 case. The incidence of prosthesis-related complications was 50%. Lengthening operation was performed on 3 cases for 1 time, and on 1 case for 2 times. And 4 cases did not undergo lengthening operation. According to Enneking function evaluation standard after malignant tumor limb-salvage surgery, the results were excellent in 1 case, good in 3, fair in 3, and poor in 1 at last follow-up with an excellent and good rate of 50%. ConclusionThe prosthesis-related complications include loosening and subsidence, dislocation, knee instability, and retraction after extensible semi-joint prosthesis replacement for lower limbs osteosarcoma. The prosthesis-related complications can be reduced by the improvement of prosthesis design and manufacture, and the use of intraoperative bone cement, artificial mesh, and postoperative restrictive brace.
Objective To investigate the clinical application and early results of combined epiphyseal preservation and autograft bone transfer for limb salvage in children with osteosarcoma. Methods Between March 2010 and March 2011, 3 children with osteosarcoma were treated with epiphyseal preservation and autograft bone transfer. There were 1 boy and 2 girls with the age of 10-14 years. The disease duration was 2 weeks to 3 months. The tumors were rated as type II according to San-Julian radiological classification and as type IIB according to Enneking surgical classification. The locations were the distal femur in 1 case and the proximal tibia in 2 cases. The surgical technique included preoperative neoadjuvant chemotherapy, excision of part of the epiphysis, preservation of subarticular epiphysis, external fixation with Ilizarov apparatus and transport osteogenesis treatment. Safe excision border was confirmed by histological examination. Postoperative observation included the wound healing, local recurrence or distant metastasis, length, speed, alignment, and regeneration of transplanted bone, the length and function of the affected limb. Results The postoperative histological examination proved the safe surgical margin in all 3 patients. The incision healing by first intention was obtained at distal femur in 1 case and by second intention at proximal tibia in 2 cases at 4 weeks after changes of dressing. Three patients were followed up 12, 18, and 24 months, respectively. There was no local recurrence or distant metastasis during follow-up. Two cases had pin-tract infection at 10 months after external fixation and were cured after changes of dressing and antibiotics administration. The length of transplanted osteogenisis was 18.0, 9.5, and 16.0 cm, respectively. The speed of lengthening was 2.57, 2.07, and 1.20 cm/month, respectively. One patient had alignment deviation during lengthening, which was adjusted under anaesthesia. Bony healing was achieved at 8 months after lengthening end in 2 cases and external fixation was removed; 1 patient had poor bone growth and was given retraction for promoting bone growth. At last follow-up, the length of the affected limbs was 1.0-1.5 cm shorter than that of normal limbs, but no abnormalities was observed at donor sites. The affected knee flexion reached 90° and 120° in 2 patients and poor knee function was observed in 1 patient for external fixation. Conclusion The combined epiphyseal preservation and transport osteogenesis technique can be used for bone defect repair by lengthening the residual bone. It is a promising limb salvage treatment for children with osteosarcoma.
Objective To analyze the effectiveness and application value of epiphysis preserving by the method of physeal distraction for treatment of femur osteosarcoma in children’s limb saving surgery. Methods Between January 2007 and January 2011, 6 patients with femur osteosarcoma underwent epiphysis preserving operation by physeal distraction. There were 4 males and 2 females with a mean age of 11.4 years (range, 9-14 years). The mean disease duration was 4.8 months (range, 1-9 months). The pathology confirmed osteosarcoma in all patients by core needle or open biopsy, including 1 case of osteogenic sarcoma, 1 case of chondroblastic osteogenic sarcoma, 1 case of osteoblastic osteogenic sarcoma, and 3 cases of no classified osteosarcoma. The clinical stage was IIA in 1 case and IIB in 5 cases according to the Enneking staging system. All patients received 2 cycles of neoadjuvant chemotherapy before operation. Then physeal distraction was performed for 4-7 days (mean, 5.7 days) based on Cantilde;adell technique. After 1-2 days of physeal distraction, massive allograft bones and interlocking intramedullary nails were used to reconstruct bone defect after tumor resection. All patients received another 4-6 cycles of chemotherapy and were followed up. Bone healing, limb discrepancy, and complications were recorded. Functional outcomes were assessed by the system of the Musculoskeletal Tumor Society (MSTS) and the range of motion (ROM) of both knee joints. Results Superficial infection occurred in 1 case and was cured after dressing change, and primary healing was obtained in the other patients. All 6 patients were followed up 2.5 years on average (range, 1-5 years). Symptoms of pain and swelling disappeared. No complication of allograft rejection, loosening or breaking of fixation occurred. No relapse or metastasis happened during follow-up. Bone healing was observed at the metaphysis junction in 5 cases at 6-9 months after operation and in 1 case at 14 months. Delayed union happened at the diaphysis junction in all patients. Different amount of callus formation was seen at the surface of diaphysis junction, but the fracture line remained clear at 12-48 months after operation. At last follow-up, limb discrepancy was 1-3 cm in 4 patients and 3-5 cm in 2 patients; 3 patients had compensatory scoliosis, and 2 patients had claudication. The MSTS score was 27.20 ± 1.92, showing significant difference (t= — 4.12, P=0.00) when compared with preoperative score (19.60 ± 2.74). The ROM of affected knee was (127.00 ± 17.89)°, showing no significant differences when compared with preoperative ROM (109.00 ± 12.45)° (t= — 1.84, P=0.10) and with ROM of normal knee (126.00 ± 9.62)° (t= — 0.11, P=0.92). Conclusion Limb saving surgery by physeal distraction can be used in young patients with open epiphyseal plate, which has the advantages of simple operation, good effectiveness, and less complications.
Objective To assess the efficacy of high-dose chemotherapy versus moderate-dose chemotherapy in the treatment of osteosarcoma. Methods We searched MEDLINE, EMbase, OVID database, CBMdisc, Cochrane CENTRAL Register of Controlled Trials in The Cochrane Library, and handsearched Journal of Chinese Oncology, Journal of Chinese Clinical Oncology and Tumor. The search time was updated to Feburary 2006.The quality of the included studies was evaluated by two reviewers and meta-analyses were performed on the results of homogenous studies. Results Four studies involving 937 participants with primary, high-grade and non-metastatic extremity osteosarcoma were included. All the included studies were judged to be inadequate at reporting randomization and blinding, only one reported allocation concealment. All included studies reported the number of withdrawals and the reasons for these. The meta-analyses showed that there were no significant differences in 5-year event free survival (EFS) (RR 1.10, 95% CI 0.96 to1.25), 5-year overall survival (OS) (RR 1.08, 95% CI 0.97 to1.20), local recurrence rate (RR 0.92, 95% CI 0.54 to 1.57), proportion of good histological response (RR 0.93, 95% CI 0.81 to 1.07), proportion of limb salvage [RR 0.97, 95% CI 0.92 to 1.02) between the high-dose group and the moderate-dose group. The 5-year EFS of the good histological response group was significantly higher than in the poor histological response group [OR 2.45, 95% CI 1.76 to 3.39,Plt;0.00001 ). Conclusions No advantage is shown for high-dose chemotherapy over moderate-dose chemotherapy in 5-year EFS, 5-year OS, local recurrence rate, proportion of good histological response and proportion of limb salvage. Histological response to preoperative chemotherapy is an independent prognosis factor for osteosarcoma. Due to the potential risk of selection bias, performance bias and publication bias, the evidence is not b enough to judge whether high-dose chemotherapy is better than moderate-dose chemotherapy in the treatment of osteosarcoma. Our conclusion suggests that large-scale randomized trials should be performed.
Objective To evaluate the relationship of systemic immune inflammatory index (SII) with the clinical features and prognosis of osteosarcoma patients. Methods The clinical data of patients with osteosarcoma surgically treated in Fuzhou Second Hospital between January 2012 and December 2017 were retrospectively collected. The preoperative SII value was calculated, which was defined as platelet × neutrophil/lymphocyte count. The best critical value of SII was determined by receiver operating characteristic (ROC) curve analysis, and the relationship between SII and clinical features of patients was analyzed by χ2 test. Kaplan-Meier method and Cox proportional hazard model were used to study the effect of SII on overall survival (OS). The nomogram prediction model was established according to the independent risk factors of patients’ prognosis. Results A total of 108 patients with osteosarcoma were included in this study. Preoperative high SII was significantly correlated with tumor diameter, Enneking stage, local recurrence and metastasis (P<0.05). The median follow-up time was 62 months. The 1-, 3-, 5-year survival rates of the low SII group were significantly higher than those of the high SII group (100.0%, 96.4%, 85.1% vs. 95.4%, 73.7%, 30.7%), and the survival of the two groups were statistically different (P<0.05). Univariate Cox regression analyses showed that tumor diameter, Enneking stage, local recurrence, metastasis and SII were associated with OS (P<0.05). Multiple Cox regression analysis showed that Enneking stage (P=0.031), local recurrence (P=0.035) and SII (P=0.001) were independent risk factors of OS. The nomogram constructed according to the independent risk factors screened by the Cox regression model had good discrimination and consistency (C-index=0.774), and the calibration curve showed that the nomogram had a high consistency with the actual results. In addition, the ROC curve indicated that the nomogram had a good prediction efficiency (area under the curve=0.880). Conclusions The preoperative SII level is expected to become an important prognostic parameter for patients with osteosarcoma. The higher the SII level is, the worse the prognosis of patients will be. The nomogram prediction model built on preoperative SII level, Enneking stage and local recurrence has a good prediction efficiency, and can be used to guide the diagnosis and treatment of clinical osteosarcoma.
Objective To investigate the effect of limb salvage on treating osteosarcoma with pathological fracture. Methods From October 2002 to January 2003, 2 cases of osteosarcoma with pathological fracture were treated by limb salvage. Intraarterial chemotherapy was given by subcutaneous implantable delivery system with caffeine. Replacement with prosthesis was performed after 5 times of chemotherapy. Results Two patients were followed up for twenty-four months and 21 months respectively. No infection, aseptic loosening, local recurrence or metastasis occurred, and function recovery of joints was satisfactory. Conclusion Limb salvage can be considered in condition that primary osteosarcoma with pathological fracture can be treated by effective and comprehensive chemotherapy.
Objective To explore the effect of pyropheophorbide-a methyl ester-mediated photodynamic therapy (MPPa-PDT) on the apoptosis in human osteosarcoma cell line MG63 and the underlying mechanism. Methods Human osteosarcoma MG63 cells in logarithmic growth phase were divided into 4 groups: blank control group (control group), the MPPa treatment group (MPPa group), the light irradiation group (LED group), and MPPa-PDT treatment group (MPPa-PDT group). MPPa-PDT group and MPPa group were incubated with MPPa (0.75 μmol/ L) for 20 hours in dark condition; control group and LED group were incubated with equal volume of fresh medium for 20 hours in the same condition. After washing with PBS and replacement with fresh culture medium, LED group and MPPa-PDT group cells were exposed to light (4.8 J/cm2) for 120 seconds. After light exposure, all groups were cultured in dark condition again. Then cellular morphology changes were observed by an inverted phase contrast microscopy, endoplasmic reticulum morphology changes were observed by transmission electron microscopy, cellular apoptosis was detected by Hoechst33258 nuclear staining, cell apoptotic rate and the levels of Ca in cells were analyzed by flow cytometry, the expression of p-PERK, C/EBP homologous protein (CHOP), cleaved-Caspase-12 were assayed by Western blot. Results In MPPa-PDT group, the retracted and round cells were observed; Hoechst33258 nuclear staining showed nuclear condensation, fragmentation, and other typical apoptotic morphological changes; the cell apoptotic rate (48.76%±3.54%) was significantly higher than that of control group (5.04%±0.41%), MPPa group (5.33%±0.38%), and LED group (6.48%±0.46%) (P < 0.05); the levels of Ca2+ in cells (485.29±58.77) was also significantly higher than that of control group (97.24±4.77), MPPa group (97.95±6.30), and LED group (101.17±5.26) (P < 0.05); swelling endoplasmic reticulum was observed under transmission electron microscope; the expressions of p-PERK, CHOP, and cleaved-Caspase-12 gradually increased at 1, 3, and 6 hours after treatment respectively, which were significantly higher than those of the other groups (P < 0.05). There was no typical apoptotic morphological changes and endoplasmic reticulum morphological changes in control group, MPPa group, and LED group, and there was no significant difference in the above indexes among 3 groups (P > 0.05). Conclusion MPPa-PDT can significantly induce apoptosis in MG63 cells. The endoplasmic reticulum stress pathway is involved in the MPPa-PDT induced apoptosis.
ObjectiveTo explore the effectiveness and safety of high-intensity focused ultrasound (HIFU) for bone tumors, so as to provide a reference for clinical decision. MethodsPubMed, EMbase, The Cochrane Library, CNKI and VIP databases were systematically searched for clinical effectiveness and safety studies of HIFU for bone tumors up to August 2014. Study selection, data extraction and quality assessment were applied independently by two reviewers, and then RevMan 5.1 software was used for conducting meta-analysis. If the data cannot be synthesized, the research outcome was described with a qualitative analysis. ResultsA total of 10 case series including 257 patients (157 males, 100 females) were included. The current evidence indicated that overall survival rates for all primary bone malignancy at 1-, 2-, 3- and 5-year were 89.8%, 72.3%, 60.5% and 50.5%, respectively. For the patients with clinical stage Ⅱb, the rates were 93.3%, 82.4%, 75% and 63.7%, respectively. For those with clinical stage Ⅲ, the rates were 79.2%, 42.2%, 21.1% and 15.8%, respectively. The local recurrence rate of HIFU for bone tumors was 7% to 9%, and recurrences at 1-, 2-, 3- and 5-year were 0%, 6.2%, 11.8% and 11.8%, respectively. The amputation rate was 2% to 7%. The adverse reaction rate was 27.2% (70/257), and among them the main was mild skin burn (21/257, 8.2%), followed by I degree burns (16/257, 6.2%), nerve damage (10/257, 3.9%) and fracture (6/257, 2.3%). ConclusionHIFU provide an alternative choice for patients with bone malignancy, with a certain effectiveness and safety. However, high-quality, large-scale randomized controlled trials or cohort studies which may focus on vary kinds of tumors, clinical stage and site of lesions are urgently needed, so that clinicians can use sufficient evidence for their clinical decision-making.