Enneking Stage Research Articles

The epidemiological and clinical features of primary giant cell tumor around the knee: A report from the multicenter retrospective study in china

ObjectivesWe aimed to determine the demographic characteristics of giant cell tumor around the knee in China. MethodsBetween March 2000 and June 2014, patients with primary giant cell tumor around the knee were recruited from 6 institutions located in different regions of China, and were reviewed retrospectively the clinical features according to gender and age. Results334 qualified patients were included in this study. The sex ratio was 1.14:1 (178/156), with mean ages of 36.9 years in men and 33.1 years in women, constituting a significant difference (P=0.007). The prevalence of pathological fracture was 32.9% overall (28.7% in men and 37.8% in women). The prevalence of simple fracture was significantly higher in women (26.3%) than in men (15.2%), P=0.042. Tumor location and staging did not differ significantly according to sex (P>0.05). However, comparing with >40 years old, those patients aged ≤40 were more likely to have a right knee tumor (56.7% vs. 44.7%, P=0.042), less likely to have Enneking stage 3 disease (18.6% vs. 35.0%, P=0.005), and less likely to have both soft-tissue extension and a mass (18.6% vs. 34.0%, P=0.009). ConclusionsGiant cell tumor around the knee was more common in men than in women, although female patients were younger on average. Further, cases among patients ≤40 years old were observed to be milder than cases among older patients. The results suggest that efficient treatment and preservation of function should both be valued for young patients with giant cell tumor around the knee.

Expression of Leptin and Sirtuin-1 is associated with poor prognosis in patients with osteosarcoma

Sirtuin-1 (SIRT1) is a downstream target of Leptin, and its inhibition promotes p53-mediated apoptosis. This study aimed to evaluate the expression and prognostic significance of Leptin and SIRT1 in osteosarcoma. Leptin and SIRT1 levels in osteosarcoma samples from 89 patients were evaluated by immunohistochemical staining. The correlations between Leptin and SIRT1 expression with clinical parameters were analyzed by Spearman's test and Pearson's chi-squared test. Prognostic factors were identified by Univariate and multivariate Cox regression analysis. We found that Leptin and SIRT1 expression was low in 23.6% and 20.2%; moderate in 25.8% and 24.7%; and high in 50.5% and 55.1% of patients with osteosarcoma, respectively. Both Leptin and SIRT1 expression were significantly associated with the Enneking stage, distant metastasis and neo-adjuvant chemotherapy. Leptin expression and SIRT1 expression were significantly correlated and they were significantly associated with shorter overall survival. Among osteosarcoma patients who received neo-adjuvant chemotherapy, both Leptin and SIRT1 expression were significantly associated with overall survival of osteosarcoma patients in univariate analysis, but only SIRT1 expression was significantly associated with overall survival of osteosarcoma patients in multivariate analysis. In conclusion, Leptin and SIRT1 expressions are significantly associated with shorter overall survival of osteosarcoma patients, and SIRT1 expression is a significant independent prognostic indicator in patients with osteosarcoma.

Gelsolin promotes cell growth and invasion through the upregulation of p-AKT and p-P38 pathway in osteosarcoma

The gelsolin (GSN) has been involved in the regulation of tumor formation and development, but the biological role of GSN in the pathogenesis of osteosarcoma (OS) has not been well characterized. In this study, we show that high expression of GSN was observed in OS tissues and correlated with tumor size, advanced Enneking stage, and poor patient prognosis. Knockdown of GSN significantly inhibited cell proliferation and invasiveness in the OS cell lines. Furthermore, stable overexpression of GSN in OS cells resulted in a significant increase in cell growth and motility with the downregulation of p-AKT and p-P38 pathway. Finally, overexpression of GSN promoted growth of OS tumors in SCID mice. Taken together, these results provided the first evidence that GSN might contribute to OS cancer development and could be an attractive therapeutic target for patients with OS.

Association between interleukin 8 −251 A/T and +781 C/T polymorphisms and osteosarcoma risk in Chinese population: a case–control study

Interleukin-8 (IL-8) is an angiogenic chemokine that plays a potent role in both development and progression of many human malignancies. However, there are no data about the role of IL-8 polymorphism in development of osteosarcoma. A hospital-based case-control study was conducted among 190 patients with osteosarcoma and 190 healthy controls to investigate the possible association between the IL-8 -251 A/T and +781 C/T polymorphisms, respectively, and the risk of osteosarcoma. Significant differences of genotype distribution were observed between osteosarcoma cases and controls at the IL-8 -251T/A genotypes. Compared with the IL-8 -251T/A homozygote TT, the heterozygous TA genotype was associated with significantly increased risk for osteosarcoma (odds ratio (OR) = 2.16, 95% confidence interval (CI) = (1.38-4.52), P = 0.021); the AA genotype was associated with increased risk for osteosarcoma (OR = 1.94, 95% CI = 1.31-3.83, P = 0.018). TA and AA combined variants were associated with increased risk for osteosarcoma compared with the TT genotype (OR = 1.72, 95% CI = 1.45-4.41, P = 0.023). Moreover, the genotype AA of IL-8 -251T/A carried a higher risk of osteosarcoma metastasis and later Enneking stages, compared with the TT genotype. However, the genotype and allele frequencies of IL-8 +781 C/T polymorphisms in osteosarcoma patients were not significantly different from controls. Our results showed that the IL-8 -251 A/T genotype was associated with increased risk for development and metastasis of osteosarcoma in Chinese Han population.

Expression of metabotropic glutamate receptor 4 in osteosarcoma.

Metabotropic glutamate receptor 4 (mGluR4) has been associated with the pathogenesis of osteosarcoma. The aim of this study was to investigate mGluR4 expression and its clinical significance in osteosarcoma patients. mGluR4 expression was investigated using immunohistochemistry (IHC) in 58 osteosarcomas and 32 giant-cell tumors of bone. The correlations between mGluR4 expression and clinicopathological characteristics were analyzed with the Chi-squared test and survival curves were generated using the Kaplan-Meier method. The IHC results demonstrated that 20.69% (12/58) of the osteosarcomas and 43.75% (14/32) of the giant-cell tumors were mGluR4-positive. The statistical analysis revealed that mGluR4 expression was correlated with gender, age, Enneking stage and tumor volume in osteosarcomas (P<0.05). In the multivariate stepwise Cox regression analysis, Enneking stage was found to be statistically significantly associated with survival (P<0.05) and the survival analysis demonstrated that the survival probability was significantly higher in patients with higher mGluR4 expression compared with those with lower expression (P<0.05). Therefore, mGluR4 expression may be used to estimate the prognosis of osteosarcoma patients.

Development and validation of a pretreatment prognostic index to predict death and lung metastases in extremity osteosarcoma.

To develop a prognostic index to predict the 5-year overall survival (OS) and 5-year lung metastasis-free survival (LMFS) of patients with extremity osteosarcoma at the time of diagnosis. We retrospectively evaluated 454 patients with extremity osteosarcoma at our center from 2005 to 2013. The cohort was randomly divided into training and validation sets. The association of potential risk factors with OS and LMFS was assessed by Cox proportional hazards analysis in the training set, and a prognostic index was created according to scores that were proportional to a regression coefficient for each factor. This prognostic index was assessed in the validation set. For the 5-year OS, 5 independent prognostic factors were identified: tumor size, Enneking stage, pretreatment platelet, alkaline phosphatase(ALP), and neutrophils. The multivariate Cox model identified tumor size, pretreatment platelets, ALP, and neutrophils as associated with the 5-year LMFS. A prognostic index for death and lung metastases was calculated. Three risk groups were defined for each survival point: low, intermediate, and high risk for the 5-year OS; low, intermediate, and high risk for the 5-year LMFS. The C statistic for the 5-year OS was 0.723 in the training set and 0.710 in the validation set. The C statistic for the 5-year LMFS was 0.661 and 0.693 respectively. This prognostic index is based on routine tests and characteristics of extremity osteosarcoma patients and is a useful predictor of OS and lung metastases. This index could be applied to clinical practice and trials for individualized risk-adapted therapies.

Overexpression of Trps1 contributes to tumor angiogenesis and poor prognosis of human osteosarcoma.

BackgroundTrichorhinophalangeal syndrome 1 (Trps1) gene is a member of GATA transcription factor family and has an important function in tumorigenesis and progression. However, there are rare studies on its roles in carcinogenesis and prognostic significance in human osteosarcoma.MethodsThe expression of Trps1 was detected by immunohistochemistry, and MVD was evaluated to determine the amounts of microvessels by counting CD31-positive endothelial cells.ResultsOf the 74 cases that underwent study, Trps1-positive cases were 24. And it was associated with MVD significantly (P = 0.008). The data also exhibited more cases of remote metastasis (P = 0.013) and higher Enneking stage (P = 0.017) in Trps1-positive group compared to Trps1-negative group. Univariate analysis revealed that distant metastasis, MVD and Trps1 expression were associated with a lower 3-year overall survival rate and disease-free survival rate (P = 0.003, and P = 0.012 respectively). Furthermore, Trps1 and distant metastasis retained their significant prognostic effects on patients survival rate by multivariate analysis (P < 0.05).ConclusionsTrps1 plays a crucial role in osteosarcoma angiogenesis, metastasis and clinical surgical stage. Trps1 can be a novel promising prognostic marker and therapeutic target, and antiangiogenic therapy which targets Trps1 molecule in patients with osteosarcoma may lead to improved prognosis and longer-term survival.

3419 Knee reconstruction with endoprosthesis after extraarticular and intraarticur resection of osteosarcoma

Objective: Extra-articular resection is necessary to obtain a wide margin for primary osteosarcomas invading the knee joint, and the limb is often reconstructed using a prosthesis. Here, outcomes of extra-articular and intra-articular procedures were compared. Methods: Between 1999 and 2012, 14 patients with osteosarcoma underwent extra-articular excision (n ¼ 6; ages 23 –6 5 years; mean follow-up 82.8 months) or intra-articular excision (n ¼ 8; ages 8–58 years; mean follow-up 96.4 months). In the extra-articular group, there was one Enneking Stage IIA case and five Enneking Stage IIB cases. No local recurrences were noted in either group. Results: Patient outcomes were as follows (extra-articular cases vs. intra-articular cases): continuous disease-free (2 vs. 7), alive with disease (2 vs. 0) and death from disease (1 vs. 1). Average Musculoskeletal Tumor Society functional scores were 69.4% (range 63.3 –8 3.3%) and 88.3% (range 70.0 –9 6.7%) in the extra-articular and intra-articular groups, respectively, constituting a significant difference (P , 0.05). The 5-year oncological overall survival exceeded 80% in both groups. Amputation was necessary for one patient in the extra-articular group. The 5-year event-free prosthesis survival rates in the extra-articular and intra-articular groups were 33.3 and 75.0%, respectively (P , 0.05). Conclusion: The extra-articular excision group developed more complications than the intraarticular excision group, as a result of extensive bone and muscle excision. The limb survival rates were similar in both groups. Our results suggest that extra-articular resection was a necessary and clinically acceptable procedure.

Biological roles of microRNA-140 in tumor growth, migration, and metastasis of osteosarcoma in vivo and in vitro.

The objective of this study was to explore the biological roles of microRNA-140 (miR-140) in tumor growth, migration, and metastasis of osteosarcoma (OS) in vivo and in vitro. Between 2007 and 2014, 47 cases of OS samples and normal bone tissue samples adjacent to OS were selected from our hospital. Tissue biopsies from OS patients were used to measure miR-140 levels to obtain a correlation between clinicopathological features and miR-140 expression. In vitro, MG63 human osteosarcoma cells were divided into four groups: blank group, miR-140 mimic group, miR-140 inhibitor group, and negative control (NC; empty plasmid) group. qRT-PCR was used to detect miR-140 expression, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell proliferation, flow cytometry was used to detect cell cycle distribution, and scratch migration assay was used to detect cell migration. In vivo, the relative expression of miR-140 level in OS tissue was lower than that in the adjacent normal bone tissue. miR-140 expression is inversely correlated with tumor size, Enneking stage, and tumor metastasis. In vitro, compared with blank group and NC group, relative miR-140 expression was increased, cell proliferation was inhibited, cell population in G0/G1 phase was increased, cell population in G2/M phase and S phases and proliferation index (PI), and cell migration distance were decreased in the miR-140 mimic group, but the relative expression and all the cell indexes were found opposite trend in the miR-140 inhibitor group. In conclusion, in vivo and vitro findings provided evidence that miR-140 could inhibit the growth, migration, and metastasis of OS cells.

Aberrant CXCR4 and β-catenin expression in osteosarcoma correlates with patient survival.

To determine the clinical significance of C-X-C chemokine receptor type 4 (CXCR4) and β-catenin in osteosarcoma, their protein expression levels were assessed in 96 osteosarcoma and 20 osteochondroma cases using immunohistochemistry. Additionally, CXCR4 and β-catenin mRNA expression levels were measured in 16 fresh osteosarcoma and 16 adjacent healthy tissue samples using fluorescent reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In the osteosarcoma samples, the positive CXCR4 protein expression rate was significantly higher than the rate in the osteochondroma samples (68.75 vs. 20.00%; P<0.01). Furthermore, β-catenin protein expression was detected in 61.46% of osteosarcoma cases and 25.00% of osteochondroma cases. Similarly, the RT-qPCR data identified increased CXCR4 and β-catenin mRNA expression levels in the osteosarcoma compared with adjacent control tissues. It was determined that CXCR4 (P<0.01) and β-catenin (P<0.05) expression were significantly associated with the clinical Enneking stage, metastasis and survival of osteosarcoma. Furthermore, multivariate analysis identified CXCR4 and β-catenin protein expression levels, as well as clinical stage and metastasis, as significant risk factors for survival in patients with osteosarcoma (P<0.05). In conclusion, the present study determined that CXCR4 and β-catenin are abnormally expressed in osteosarcoma tissues, and, therefore, may be important during osteosarcoma progression.

Giant cell tumors of the spine: has denosumab changed the treatment paradigm?

OBJECT Giant cell tumors (GCTs) of the spine are rare and complex to treat. They have a propensity for local recurrence and the potential to metastasize. Treatment is currently surgical and presents unique challenges due to the proximity of neural structures and the need for reconstruction. Denosumab has been shown in clinical trials to be an effective treatment for GCT, but has not yet been studied specifically in GCT of the spine or as a surgical adjunct. To the authors' knowledge this is the first such reported series. METHODS A multicenter, prospective series of 5 patients with GCT of the spine treated with denosumab were included. Patient demographic data, oncological history, neurological status, tumor staging, treatment details and adverse events, surgical procedure, complications, radiological and histological responses, and patient outcome were analyzed. RESULTS All patients were women, with a mean age of 38 years, and presented with pain; 2 patients had additional neurological signs and symptoms. The mean duration of symptoms was 62 weeks. No patient had a prior tumor or metastatic disease at presentation. All patients had Enneking Stage III tumors and were treated with monthly cycles of 120 mg of denosumab, with initial additional loading doses on Days 8 and 15. Patients were given daily supplements of calcium (500 mg) and vitamin D (400 IU). There were no denosumab-related adverse events. All patients had a radiological response to denosumab. One patient failed to have a histological response to denosumab, with > 90% of tumor cells found to be viable on histological investigation. CONCLUSIONS This study reports the early experience of using denosumab in the treatment of spinal GCT. The results demonstrate a clinically beneficial radiological response and an impressive histological response in most but not all patients. Further experience with denosumab and longer patient follow-up is required. Denosumab has the potential to change the treatment paradigm for spinal GCT.

Establishment and assessment of a nomogram for predicting the individual prognosis of osteosarcoma

Objective To develop an accurate prognostic nomogram for osteosarcoma and to validate it in order to provide scientific basis for risk evaluation, though analyzing the clinicopathologic, radiologic and follow-up data of osteosarcoma patients. Methods All of 235 osteosarcoma patients who diagnosed in the department of Musculoskeletal Oncology in the first affiliated hospital of Sun Yat-Sen University during 1998 to 2008 and met the inclusion criteria, were included in a primary cohort, and 55 patients diagnosed in 2009 were included in a validation cohort. In univariate survival analysis of the primary cohort, Kaplan-Meier method was used to plot Survival curves, and the log-rank test to compare differences. In the multivariate analysis, the Cox proportional hazard model had been used to identify the independent prognostic factors. Then a nomogram created by R software was validated by Bootstrap resampling as internal validation and by the validation cohort as external validation. Concordance index (C-index) was applied to the predictive evaluation of the nomogram and calibration curves were drawn to test the nomogram-prediction and actual observation of the five-year overall survival rate. Results The five-year over-all survival rates of the primary cohort and validation cohort were 46.1%±6.7% and 61.8%±12.9%, respectively. In multivariate analysis, pathologic fracture, pre-ALP, tumor maximum diameter, Enneking stage and postoperative chemotherapy had been identified as independent prognostic factors. Good concordance of survival probability between nomogram-prediction and actual observation was shown by the calibration curves. The C-index of the nomogram for predicting survival, 0.74(95% CI, 0.70-0.78), was statistically higher than that of the Enneking system (C-index: 0.54). Of the validation cohort, C-index of the nomogram, Enneking and American Joint Committee on Cancer (AJCC) stage system was 0.71, 0.54 and 0.56, respectively, indicating the nomogram had a higher accuracy in prognostic prediction than the others. Conclusion The nomogram as proposed is an effective tool for predicting the overall survival of osteosarcoma patients. Compared with Enneking and AJCC stage system, the nomogram was more accurate and visible. Key words: Osteosarcoma; Nomograms; Prognosis

Surgical Management of Osteoblastoma of the Spine: Case Series and Review of the Literature.

To describe the demographics, clinical and radiologic presentation, surgical considerations, and clinical outcomes associated with spinal osteoblastoma. A spinal tumor database of 522 patients treated surgically at a single institution between January 2002 and June 2012 was analyzed and five patients with spinal osteoblastoma were identified and included in this study. Basic demographic and epidemiological data were recorded. Tumor characteristics, surgical parameters, and clinical follow-up data were noted. The mean follow-up was 21.9 months. There were four males and one female, and the mean age at diagnosis was 28.4 years. There was a mean reported symptom length of 26.4 months prior to diagnosis. There were three cervical lesions, one lumbar lesion, and one sacrococcygeal lesion. One patient was Enneking stage III and four patients were Enneking stage II. Based on spinal instability neoplastic score criteria, two patients were stable and three patients were potentially unstable. Four patients had intralesional gross total resections and one patient had an en bloc marginal resection. All patients remained neurologically stable or improved postoperatively. A single patient had recurrence of a previously resected osteoid osteoma with progression to osteoblastoma. Aggressive surgical resection of spinal osteoblastoma is suggested to minimize the risk of tumor recurrence, although this may still occur even with en bloc resection. Patients rarely present with preoperative spinal instability, but surgical fusion is often required due to removal of structural elements of the spine during resection. Of note, osteoid osteoma may progress to osteoblastoma in the spine despite prior resection.

Neglected orthopedic oncology--Causes, epidemiology and challenges for management in developing countries.

Management of malignant bone and soft tissue tumors remains an overwhelming confront to orthopedic surgeons. The challenge is discriminating in developing countries due to inadequate diagnostic and therapeutic amenities and unawareness. A lot has been discussed about the neglected orthopedic trauma, but the published literature on the causes and management of neglected bone and soft tissue tumors is sparse. Hence, current study was undertaken to highlight the causes of neglect and therapeutic challenges for managing these neglected tumors in developing countries. To determine the causes of neglect of malignant bone and soft tissue tumors, their epidemiology (including their relative frequencies, age, gender discrimination, anatomical sites of occurrence and histological characteristics) and difficult aspect of management due to neglect or delayed presentation. This was an appraisal of the neglected malignant bone and soft tissue tumors presented to J. N. Medical College and Hospital from June 2008 to May 2013. Criteria for labeling the tumor as neglected malignant bone and soft tissue tumor was delayed presentation (>3 months), locally advanced disease, ulceration, sepsis, fungating mass or metastasis at the time of presentation. All the cases were reviewed and analyzed for age, gender, histological types, educational status and socioeconomic status of the family, any prior treatment by traditional bone setters or registered medical practitioner, cause of delay for seeking medical advice. We have also analyzed the treatment given at our institute and the outcome of the tumor. Eighteen patients fulfilled the criteria for neglected malignant bone and soft tissue tumors, hence were included in study. Eight cases were of osteosarcoma, five cases were of Ewing's sarcoma, three cases were of chondrosarcoma and 1 case each was of pleomorphic liposarcoma and primary lymphoma of bone. According to Enneking staging system 11 cases were of stage III (distant metastasis) and 7 were stage II-B. Seven were females, and 11 were males. Age range was 5-68 years. 15 patients (83.3%) belonged to low socioeconomic status with 17 patients (94.4%) belonged to uneducated background. Cause of delay in seeking medical advice was neglect by the patient and family due to financial constraints, cultural and religious believes, lack of access to health care facilities, consultation with traditional bone setters and even misdiagnosis by qualified orthopedic surgeons. The tumors included were all unresectable and of huge sizes, hence were managed with amputation/dis-articulation, chemotherapy or radiation. The current study tries to highlight the causes and quantity of neglect of malignant bone and soft tissue tumors prevalent in our country, which poses a therapeutic challenge for management and consequent mutilating surgeries with poor outcome resulting in loss of extremity and existence.

The clinical pathological significance of FRAT1 and ROR2 expression in cartilage tumors.

Chondrosarcoma is a malignant bone tumor with poor prognosis. Surgical treatment is the first choice for chondrosarcomas. Chondrosarcoma is not sensitive to chemotherapy and radiotherapy. Identification of biological markers is important for the early diagnosis and targeted treatment of chondrosarcoma. This study investigated the protein expression and clinicopathological significance of ROR2 and FRAT1 in 59 chondrosarcomas and 33 osteochondromas. ROR2 and FRAT1 protein expression in tissues was measured by immunohistochemistry. The percentage of positive ROR2 and FRAT1 expression was significantly higher in patients with chondrosarcoma than in patients with osteochondroma (P < 0.01). The percentage of positive ROR2 and FRAT1 expression was significantly lower in patients with histological grade I, AJCC stage I/II stage, Enneking stage I, non-metastatic and invasive chondrosarcoma than patients with histological grade III, AJCC stage III/IV, Enneking stage II + III, metastatic and invasive chondrosarcoma (P < 0.05 or P < 0.01). ROR2 expression was positively correlated with FRAT1 expression in chondrosarcoma. Kaplan-Meier survival analysis demonstrated that histological grade, AJCC stage, Enneking stage, metastasis, invasion, and ROR2 and FRAT1 expression significantly correlated with a short mean survival time of patients with chondrosarcoma (P < 0.05 or P < 0.01). Cox multivariate analysis showed that positive ROR2 and FRAT1 expression was an independent prognostic factor that negatively correlated with postoperative survival and positively correlated with mortality. Positive ROR2 and FRAT1 expression is associated with the progression and poor prognosis of chondrosarcoma.

Effectiveness of mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review protocol

Effectiveness of mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review protocol

Postoperative nomogram to predict the probability of metastasis in Enneking stage IIB extremity osteosarcoma.

BackgroundMetastasis is the most crucial prognostic factor in osteosarcoma. The goal of this study was to develop a new nomogram to predict the probability of metastasis in Enneking stage IIB extremity osteosarcoma after neoadjuvant chemotherapy and limb salvage surgery.MethodsWe examined medical records of 91 patients who had undergone surgery between March 1994 and March 2007. A nomogram was developed using multivariate logistic regression. The nomogram was validated internally by bootstrapping-method (200 repetitions) and externally in independent validation set (n = 34). A Youden-derived cutoff value was assigned to the nomogram to predict dichotomous outcomes for metastasis.ResultsThe nomogram was built from four predictors of tumor site, serum alkaline phosphatase, intracapsular extension, and Huvos grade, and an additional clause that the cutoff value should be added to the total points in the cases of incomplete surgical resection. P-value of Hosmer and Lemshow Goodness-of-fit test of this model was 0.649. Area under receiver operating curve values of 0.83 (95% confidence interval [CI], 0.75 to 0.92) in the training set and 0.80 (95% CI, 0.63 to 0.96) in the validation set were obtained. The accuracy of dichotomous outcomes was 79.1% (95% CI, 0.69 to 0.86) and 82.4% (95% CI, 0.63 to 0.92) in the training and validation sets.ConclusionsWe have developed a new high-performance nomogram to predict the probability of metastasis in Enneking stage IIB extremity osteosarcoma after limb salvage surgery.

Alcohol-Inactivated Autograft Replantation with Joint Preservation in the Management of Osteosarcoma of the Distal Femur: A Preliminary Study

SummaryAim: To evaluate clinical outcomes in patients who underwent alcohol-inactivated autograft replantation with joint preservation for the treatment of osteosarcoma of the distal femur. Patients and Methods: 10 patients (7 men, 3 women; mean age: 20.1 years) were treated. 9 patients had Enneking stage IIb tumors and 1 patient had stage III. The mean follow-up time was 34 months. All patients obtained first-stage healing. Results: 1 patient died of local recurrence and multiple metastases 13 months after surgery; 3 patients died of multiple metastases 9, 12, and 24 months after surgery, respectively. 3 patients required second surgery because of fracture of the inactivated autograft, 1 patient died 6 months later, 1 patient experienced bony healing 4 months later with no further complications, and 1 patient required subsequent open reduction and bone implantation with internal fixation (bony healing was evident 6 months later; however, joint instability and limited knee flexion were apparent). At final follow-up, the mean International Society of Limb Salvage (ISOLS) graft score was 31 (87%), whereas the mean Musculoskeletal Tumour Society (MSTS) function score was 23 (77%). Conclusions: These preliminary findings indicate that alcohol-inactivated autograft replantation with joint preservation may be effective in treating osteosarcoma of the distal femur in some patients. Larger-scale studies are needed to fully evaluate the efficacy/safety of this approach.

HMGB1 promotes cellular proliferation and invasion, suppresses cellular apoptosis in osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence indicated that the deregulation of DNA-binding protein high-mobility group box 1 (HMGB1) was associated with the development of cancer. This study aimed to explore the expression of HMGB1 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the role of HMGB1 in the development of osteosarcoma. The results from RT-PCR and Western blot showed that the expression rate of HMGB1 messenger RNA (mRNA) and the expression of HMGB1 in the osteosarcoma tissues were significantly higher than those in normal bone tissue (p < 0.05), the expression rate of HMGB1 mRNA and the expression of HMGB1 in the carcinoma tissues with positive lung metastasis were significantly higher than those without lung metastasis (p < 0.05), and with increasing Enneking stage, the expression rate of HMGB1 mRNA and the expression of HMGB1 also increased (p < 0.05). In order to explore the role of HMGB1 in osteosarcoma, the expression of HMGB1 in the human osteosarcoma MG-63 cell line was downregulated by the technique of RNA interference. Western blot results showed that the protein expression of HMGB1 was significantly decreased in the MG-63 cells from HMGB1-siRNA transfection group (p < 0.05), which suggested that HMGB1 was successfully downregulated in the MG-63 cells. Then the changes in proliferation, apoptosis, and invasion of MG-63 cells were examined by MTT test, PI staining, annexin V staining, and transwell chamber assay. Results showed that the abilities of proliferation and invasion were suppressed in HMGB1 knockdown MG-63 cells, and the abilities of apoptosis were enhanced in HMGB1 knockdown MG-63 cells. The expression of cyclin D1, MMP-9 was downregulated in HMGB1 knockdown MG-63 cells, and the expression of caspase-3 was upregulated in HMGB1 knockdown MG-63 cells. Taken together, the overexpression of HMGB1 in osteosarcoma might be related to the tumorigenesis, invasion, and metastasis of osteosarcoma, which might be a potential target for the treatment of osteosarcoma.

Aneurysmal bone cysts of the spine: treatment options and considerations.

Aneurysmal bone cysts (ABCs) are benign bone lesions with annual incidences ranging from 1.4 to 3.2 cases per million people. Approximately, 10-30% of ABCs are found in the spine. Such lesions are traditionally treated with curettage or other intralesional techniques. Because ABCs can be locally aggressive, intralesional resection can be incomplete and result in recurrence. This has led to increased use of novel techniques, including selective arterial embolization (SAE). This study aims to: (1) compare outcomes based on extent of surgical resection, and (2) compare the efficacy of SAE versus surgical resection. Clinical data pertaining to 71 cases of spinal ABCs were ambispectively collected from nine institutions in Europe, North America, and Australia. Twenty-two spinal ABCs were treated with surgery, 32 received preoperative embolization and surgery, and 17 were treated with SAE. Most tumors were classified as Enneking stage 2 (n = 29, 41%) and stage 3 (n = 29, 41%). Local recurrence and survival were investigated and a significant difference was not observed between treatment groups. However, all three local recurrences occurred following surgical resection. Surgical resection was further categorized based on Enneking appropriateness. Recurrences only occurred following intralesional Enneking inappropriate (EI) resections (P = 0.10), a classification that characterized 47% of all surgical resections. Furthermore, 56% of intralesional resections were EI, compared to only 10% of en bloc resections (P = 0.01). Although SAE treatment did not result in any local recurrences, 35% involved more than five embolization procedures. Spinal ABCs can be effectively treated with intralesional resection, en bloc resection, or SAE. Preoperative embolization should be considered before intralesional resection to limit intraoperative bleeding. Treatment plans must be guided by lesion characteristics and clinical presentation.