Aims. Venous tumour thrombus (VTT) is a rare finding in osteosarcoma. Despite the high rate of VTT in osteosarcoma of the pelvis, there are very few descriptions of VTT associated with extrapelvic primary osteosarcoma. We therefore sought to describe the prevalence and presenting features of VTT in osteosarcoma of both the pelvis and the limbs. Methods. Records from a single institution were retrospectively reviewed for 308 patients with osteosarcoma of the pelvis or limb treated between January 2000 and December 2022. Primary lesions were located in an upper limb (n = 40), lower limb (n = 198), or pelvis (n = 70). Preoperative imaging and operative reports were reviewed to identify patients with thrombi in proximity to their primary lesion. Imaging and histopathology were used to determine presence of tumour within the thrombus. Results. Tumours abutted the blood vessels in 131 patients (43%) and encased the vessels in 30 (10%). Any form of venous thrombus was identified in 31 patients (10%). Overall, 21 of these thrombi were determined to be involved with the tumour based on imaging (n = 9) or histopathology (n = 12). The rate of VTT was 25% for pelvic osteosarcoma and 1.7% for limb osteosarcoma. The most common imaging features associated with histopathologically proven VTT were enhancement with contrast (n = 12; 100%), venous enlargement (n = 10; 83%), vessel encasement (n = 8; 66%), and visible intraluminal osteoid matrix (n = 6; 50%). Disease-specific survival (DSS) for patients with VTT was 95% at 12 months (95% CI 0.87 to 1.00), 50% at three years (95% CI 0.31 to 0.80), and 31% at five years (95% CI 0.14 to 0.71). VTT was associated with worse DSS (hazard ratio 2.3 (95% CI 1.11 to 4.84). Conclusion. VTT is rare with osteosarcoma and occurs more commonly in the pelvis than the limbs. Imaging features suggestive of VTT include enhancement with contrast, venous dilation, and vessel encasement. VTT portends a worse prognosis for patients with osteosarcoma, with a similar survivability to metastatic disease. Cite this article: Bone Joint J 2024;106-B(8):865–870

Aims. Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. Methods. We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome. Results. Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002). Conclusion. The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins. Cite this article: Bone Joint J 2024;106-B(1):99–106

Aims. We have previously reported cryoablation-assisted joint-sparing surgery for osteosarcoma with epiphyseal involvement. However, it is not clear whether this is a comparable alternative to conventional joint arthroplasty in terms of oncological and functional outcomes. Methods. A total of 22 patients who had localized osteosarcoma with epiphyseal involvement around the knee and underwent limb salvage surgery were allocated to joint preservation (JP) group and joint arthroplasty (JA) group. Subjects were followed with radiographs, Musculoskeletal Tumor Society (MSTS) score, and clinical evaluations at one, three, and five years postoperatively. Results. Patients in both groups (ten in JP and 12 in JA) did not differ in local recurrence (p ≥ 0.999) and occurrence of metastases (p ≥ 0.999). Overall survival was similar in both groups (p = 0.858). Patients in the JP group had less range of motion (ROM) of the knee (p < 0.001) and lower MSTS scores (p = 0.010) compared with those of the JA group only at one year postoperatively. There was no difference between groups either at three years for ROM (p = 0.185) and MSTS score (p = 0.678) or at five years for ROM (p = 0.687) and MSTS score (p = 0.536), postoperatively. Patients in the JA group tended to have more complications (p = 0.074). Survival of primary reconstruction in the JP group was better than that of the JA group (p = 0.030). Conclusion. Cryoablation-aided joint-sparing surgery offers native joint preservation with comparable functional recovery and more durable reconstruction without jeopardizing oncological outcomes compared with conventional limb salvage surgery. Cite this article: Bone Joint J 2021;103-B(8):1421–1427

Aims . Osteosarcoma of the pelvis is a particularly difficult tumour to treat as it often presents late, may be of considerable size and/or associated with metastases when it presents, and is frequently chondroid in origin and resistant to chemotherapy. The aim of this study was to review our experience of managing this group of patients and to identify features predictive of a poor outcome. Patients and Methods. Between 1983 and 2014, 121 patients, (74 females and 47 males) were treated at a single hospital: 74 (61.2%) patients had a primary osteosarcoma and 47 (38.8%) had an osteosarcoma which was secondary either to Paget’s disease (22; 18.2%) or to previous pelvic irradiation (25; 20.7%). . The mean age of those with a primary osteosarcoma was 29.3 years (nine to 76) and their mean follow-up 2.9 years (0 to 29). The mean age of those with a secondary sarcoma was 61.9 years (15 to 85) and their mean follow-up was one year (0 to 14). . A total of 22 patients with a primary sarcoma (52.4%) and 20 of those with a secondary sarcoma (47.6%) had metastases at the time of presentation. . Results. The disease-specific survival at five years for all patients was 27.2%. For those without metastases at the time of diagnosis, the five-year survival was 32.7%. Factors associated with a poor outcome were metastases at diagnosis and secondary tumours. In primary osteosarcoma, sacral location, surgical margin and a diameter > 10 cm were associated with a poor outcome. Conclusion. In this, the largest single series of patients with an osteosarcoma of the pelvis treated in a single hospital, those with secondary tumours and those with metastases at presentation had a particularly poor outcome. For those with a primary sarcoma, sacral location, an intralesional margin and a diameter of > 10 cm were poor prognostic indicators. Cite this article: Bone Joint J 2016;98-B:555–63

Objectives. Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. Methods. To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. Results. eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. Conclusion. Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression. Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186–193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2

Aims. The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. Patients and Methods. A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. Results. Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. Conclusion. The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024–1031

Aims. For paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy. Methods. We retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment. Results. The mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30). Conclusion. TER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article: Bone Joint J 2020;102-B(6):772–778

Aims. Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. Methods. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay. Results. The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2. Conclusion. In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: Bone Joint Res 2020;9(11):821–826

Aims. To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods. Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results. OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion. Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803

Opinion remains divided as to whether the development of pathological fracture affects the prognosis of patients with an osteosarcoma of the extremities. We conducted a comprehensive systematic review and meta-analysis of papers which reported the outcomes of osteosarcoma patients with and without a pathological fracture. There were eight eligible papers for final analysis which reported on 1713 patients, of whom 303 (17.7%) had a pathological fracture. The mean age for 1464 patients in six studies was 23.2 years old (2 to 82). The mean follow-up for 1481 patients in seven studies was 90.1 months (6 to 240). The pooled estimates of local recurrence rates in osteosarcoma patients with and without pathological fractures were 14.4% (8.7 to 20.0) versus 11.4% (8.0 to 14.8). The pooled estimate of relative risk was 1.39 (0.89 to 2.20). The pooled estimates of five-year event-free survival rates in osteosarcoma patients with and without a pathological fracture were 49.3% (95% CI 43.6 to 54.9) versus 66.8% (95% CI 60.7 to 72.8). The pooled estimate of relative risk was 1.33 (1.12 to 1.59). There was no significant difference in the rate of local recurrence between patients who were treated by amputation or limb salvage. The development of a pathological fracture is a negative prognostic indicator in osteosarcoma and is associated with a reduced five-year event-free survival and a possibly higher rate of local recurrence. Our findings suggest that there is no absolute indication for amputation, as similar rates of local recurrence can be achieved in patients who are carefully selected for limb salvage. . Cite this article: Bone Joint J 2014; 96-B:1396–1403

Aims. The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction. Methods. From June 2011 to January 2016 a retrospective study was carried out of patients with primary osteosarcoma of lower limbs who underwent combined biological intercalary reconstruction. Patients were categorized into two groups based on the reconstructive technique: frozen tumour-bearing autograft combined with concurrent VFG (Group 1) and the Capanna method (Group 2). Demographics, operating procedures, oncological outcomes, graft union, limb function, and postoperative complications were compared. Results. A total of 23 patients were identified for analysis: eight in Group 1 and 15 in Group 2. There was no difference in the demographics (age, sex, and affected site) and operating procedures (resection length, duration of surgery, and blood loss) between the two groups. No significant difference was found in local recurrence in Group 1 versus Group 2 (p = 0.585). Mean union time for the frozen autograft-host junction was 8.4 months (7.0 to 11.0), significantly earlier than for the allograft-host junction in Group 2 (mean 14.1 months (10.0 to 28.0); p < 0.001). Mean Musculoskeletal Tumor Society scores in groups 1 and 2 were 90.3% (SD 7.4%) and 88.0% (SD 9.0%), respectively, with no significant statistical difference (p = 0.535). In terms of complications, infection (n = 1, 6.7%) and delayed union (n = 2, 13.3%) occurred in Group 2, but no such complications were observed in Group 1. Conclusion. Frozen tumour-bearing autograft in combination with VFG can be used as an alternative to the Capanna reconstruction in properly selected patients with osteosarcoma. Cite this article: Bone Joint J 2020;102-B(5):646–652

Aims. The aim of this study was to identify factors that determine outcomes of treatment for patients with chondroblastic osteosarcomas (COS) of the limbs and pelvis. Patients and Methods. The authors carried out a retrospective review of prospectively collected data from 256 patients diagnosed between 1979 and 2015. Of the 256 patients diagnosed with COS of the pelvis and the limbs, 147 patients (57%) were male and 109 patients (43%) were female. The mean age at presentation was 20 years (0 to 90). Results. In all, 82% of the patients had a poor response to chemotherapy, which was associated with the presence of a predominantly chondroblastic component (more than 50% of tumour volume). The incidence of local recurrence was 15%. Synchronous or metachronous metastasis was diagnosed in 60% of patients. Overall survival was 51% and 42% after five and ten years, respectively. Limb localization and wide surgical margins were associated with a lower risk of local recurrence after multivariable analysis, while the response to chemotherapy was not. Local recurrence, advanced patient age, pelvic tumours, and large volume negatively influenced survival. Resection of pulmonary metastases was associated with a survival benefit in the limited number of patients in whom this was undertaken. Conclusion. COS demonstrates a poor response to chemotherapy and a high incidence of metastases. Wide resection is associated with improved local control and overall survival, while excision of pulmonary metastases is associated with improved survival in selected patients. Cite this article: Bone Joint J 2019;101-B:739–744

Aims. The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. Patients and Methods. We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. Results. The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. Conclusion. Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745–752

Aims. The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa. Methods. We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis. Results. This study comprised 77 patients at a three-year minimum follow-up. The predictors of poor OS were: the median age of ≤ 19 years (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.92 to 0.99; p = 0.021); median duration of symptoms ≥ five months (HR 0.91; 95% CI 0.83 to 0.99; p < 0.037); metastasis at diagnosis (i.e. Enneking stage III) (HR 3.33; 95% CI 1.81 to 6.00; p < 0.001); increased alkaline phosphatase (HR 3.28; 95% CI 1.33 to 8.11; p < 0.010); palliative treatment (HR 7.27; 95% CI 2.69 to 19.70); p < 0.001); and amputation (HR 3.71; 95% CI 1.12 to 12.25; p < 0.032). In contrast, definitive surgery (HR 0.11; 95% CI 0.03 to 0.38; p < 0.001) and curative treatment (HR 0.18; 95% CI 0.10 to 0.33; p < 0.001) were a protective factor. The Kaplan-Meier median survival time was 24 months, with OS of 57.1% at the three years. The projected five-year event-free survival was 10.3% and OS of 29.8% (HR 0.76; 95% CI 0.52 to 1.12; p = 0.128). Conclusion. In this series of high-grade conventional osteosarcoma of the appendicular skeleton from South Africa, 58.4% (n = 45) had detectable metastases at presentation; hence, an impoverished OS of five years was 29.8%. Large-scale future research is needed to validate our results. Cite this article: Bone Jt Open 2024;5(3):210–217

Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168

The October 2023 Oncology Roundup. 360. looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma

The December 2022 Oncology Roundup. 360. looks at: Is high-dose radiation therapy associated with early revision with a cemented endoprosthesis?; Neoadjuvant chemotherapy and endoprosthetic reconstruction for lower extremity sarcomas: does timing impact complication rates?; Late amputation after treatment for lower extremity sarcoma; Osteosarcoma prediagnosed as another tumour: a report from the Cooperative Osteosarcoma Study Group; The influence of site on the incidence and diagnosis of solitary central cartilage tumours of the femur: a 21st century perspective

We conducted an epidemiological study of osteosarcoma in Sweden from 1971 to 1984 to investigate whether the typical features of the disease had changed. Of 294 osteosarcoma patients reviewed, 249 had primary skeletal tumours, and for these the mean annual incidence was 2.1 per million, without any clear trend over time. The mean male/female ratio for the period was 1.6 again with no consistent pattern over time; nor was there any significant change in the distribution of tumours according to location. The only feature which showed a significant change over the 14-year period was the mean age of the patients, being at its lowest (19 years) in 1972 and at its highest (40 years) in 1981. Excluding the 22 patients with craniofacial tumours, the remaining 227 also showed a significant increase in mean age. Analysis of the annual age distribution disclosed an increasing fraction of patients older than those in the classical age peak between 10 and 29 years. A large number of trials have shown improved survival in osteosarcoma over the last 15 years, which has been attributed mainly to adjuvant chemotherapy. The change we have observed in age distribution should also be taken into account in the evaluation of the results of treatment; it may be that older patients have a better prognosis

The December 2023 Oncology Roundup. 360. looks at: A single osteotomy technique for frozen autograft; Complications, function, and survival of tumour-devitalized autografts used in patients with limb-sparing surgery; Is liquid nitrogen recycled bone and vascular fibula the biological reconstruction of choice?; Solitary pulmonary metastases at first recurrence of osteosarcoma; Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?; Open versus core needle biopsy in lower-limb sarcoma – current practice patterns and patient outcomes; Natural history of intraosseous low-grade chondroid lesions of the proximal humerus; Local treatment modalities and event-free survival in patients with localized Ewing’s sarcoma; Awaiting biopsy results in solitary pathological proximal femoral fractures

The incidence of metastatic osteosarcoma is increasing because of improved results following multi-agent chemotherapy and resection of the primary tumour. Metastases occur most commonly in the lungs, whereas bowel metastases are rare. We describe a 25-year-old female who presented with melaena six years after successful resection of an osteosarcoma of her right femur, and one year after resection of a solitary pulmonary metastasis. Imaging revealed a lesion arising within both the duodenum and the pancreas for which a Whipple’s pancreatoduodenectomy was carried out, achieving complete resection. Histological examination confirmed the diagnosis of metastatic osteosarcoma. We believe this is only the second such case reported. At 11 months post-operatively she had no detectable disease. Although rare, osteosarcoma can metastasise to the intestine. The surgeon must be aware of this complication, and that bowel metastases are potentially resectable

There are eight reported cases in the literature of osteosarcomas secreting β-hCG. Our primary aim was to investigate the rate of β-hCG expression in osteosarcoma and attempt to understand the characteristics of osteosarcomas that secrete β-hCG. We reviewed 37 histopathology slides (14 biopsies and 23 surgical specimens) from 32 patients with osteosarcoma. The slides were retrospectively stained for β-hCG expression. Patient and tumour characteristics, including age, gender, tumour location, subtype, proportion of necrosis, presence of metastases and recurrence were recorded. A total of five of the 32 tumours were found to be positive for β-hCG expression (one strongly and four weakly). This incidence of this expression was found in tumours with poor histological response to neoadjuvant chemotherapy. The use of β-hCG expression as a diagnostic, prognostic or follow-up marker is questionable and needs further investigation with a larger sample size

Aims. The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours. Methods. We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital. Results. In all, 17 patients with locally aggressive bone tumours (Enneking stage IIB) located in the femoral shaft underwent JSLSS and reconstruction with 3D-printed modular prostheses between January 2020 and June 2022. The median surgical time was 153 minutes (interquartile range (IQR) 117 to 248), and the median estimated blood loss was 200ml (IQR 125 to 400). Osteosarcoma was the most common pathological type (n = 12; 70.6%). The mean osteotomy length was 197.53 mm (SD 12.34), and the median follow-up was 25 months (IQR 19 to 38). Two patients experienced local recurrence and three developed distant metastases. Postoperative complications included wound infection in one patient and screw loosening in another, both of which were treated successfully with revision surgery. The median Musculoskeletal Tumor Society score at the final follow-up was 28 (IQR 27 to 28). Conclusion. The 3D-printed modular prosthesis is a reliable and feasible reconstruction option for patients with malignant femoral diaphyseal tumours. It helps to improve the limb salvage rate, restore limb function, and achieve better short-term effectiveness. Cite this article: Bone Jt Open 2024;5(4):317–323

The aim of this study was to evaluate the prognostic and therapeutic factors which influence the oncological outcome of parosteal osteosarcoma. A total of 80 patients with a primary parosteal osteosarcoma were included in this retrospective study. There were 51 females and 29 males with a mean age of 29.9 years (11 to 78). The mean follow-up was 11.2 years (1 to 40). Overall survival was 91.8% at five years and 87.8% at ten years. Local recurrence occurred in 14 (17.5%) patients and was associated with intralesional surgery and a large volume of tumour. On histological examination, 80% of the local recurrences were dedifferentiated high-grade tumours. A total of 12 (14.8%) patients developed pulmonary metastases, of whom half had either a dedifferentiated tumour or a local recurrence. Female gender and young age were good prognostic factors. Local recurrence was a poor prognostic factor for survival. Medullary involvement or the use of chemotherapy had no impact on survival. The main goal in treating a parosteal osteosarcoma must be to achieve a wide surgical margin, as inadequate margins are associated with local recurrence. Local recurrence has a significant negative effect on survival, as 80% of the local recurrences are high-grade dedifferentiated tumours, and half of these patients develop metastases. The role of chemotherapy in the treatment of parosteal osteosarcoma is not as obvious as it is in the treatment of conventional osteosarcoma. The mainstay of treatment is wide local excision. Cite this article: Bone Joint J 2015;97-B:1698–1703

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour

Although an osteosarcoma appears to be a solitary lesion clinically, as in this instance, only routine radiographic skeletal survey in such cases will detect multiple osseous involvement. Ross (1964) reported that in ninety-eight cases of osteosarcoma arising in apparently normal bone, fifteen showed metastases to other bones, a much higher incidence than previously recorded. It is also possible that multicentric osteosarcomata, although undoubtedly rare, may be discovered more often if a radiological survey is done. In many large series of osteosarcomata no mention of a skeletal survey has been made, and, while this is routine in some centres, it is not yet general practice

We have reviewed the data from our regional Bone Tumour Registry on patients with osteosarcoma diagnosed between 1933 and 2004 in order to investigate the relationship between survival and changes in treatment. There were 184 patients with non-metastatic appendicular osteosarcoma diagnosed at the age of 18 or under. Survival was calculated using Kaplan-Meier curves, and multivariate analysis was performed using the Cox regression proportional hazards model. The five-year survival improved from 21% between 1933 and 1959, to 62% between 1990 and 1999. During this time, a multi-disciplinary organisation was gradually developed to manage treatment. The most significant variable affecting outcome was the date of diagnosis, with trends in improved survival mirroring the introduction of increasingly effective chemotherapy. Our experience suggests that the guidelines of the National Institute for Clinical Excellence on the minimum throughput of centres for treatment should be enforced flexibly in those that can demonstrate that their historical and contemporary results are comparable to those published nationally and internationally

Over a 25-year period we have treated 36 patients with osteosarcoma of the pelvis. Of the tumours, 24 (67%) were primary osteosarcomas and 12 (33%) arose either after irradiation or in association with Paget’s disease. Six patients had a hindquarter amputation and 12 were treated by a limb-salvage procedure with intrapelvic excision. The five-year survival rate of all the patients with pelvic osteosarcoma was 18%, while for 17 treated by chemotherapy and surgery it was 41%. The prognosis for patients presenting with metastases or with secondary osteosarcoma was appalling and none survived after 29 months. No patient over the age of 50 years when seen initially survived for a year. Youth and a good response to chemotherapy along with complete surgical excision offer the best chance of cure

We undertook a prospective study to evaluate the prognostic significance of the serum levels of vascular endothelial growth factor (VEGF) in predicting the survival of patients with osteosarcoma. The levels were measured by an enzyme-linked immunosorbent assay in 15 patients with osteosarcoma before commencing treatment. The patients were divided into two groups, with a high or a low serum VEGF level, and the incidence of metastases and overall survival rate were compared. No significant relationship was observed between the serum VEGF levels and gender, age, the size of the tumour or the response to pre-operative chemotherapy. Patients with a serum VEGF > 1000 pg/ml had significantly worse survival than those with a level < 1000 pg/ml (p = 0.002). The serum VEGF level may be useful in predicting the prognosis for survival in patients with osteosarcoma

We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% vs 3%, p = 0.003; overall lung metastasis rate: 51.4% vs 18.8%, p < 0.001). Patients who had manipulative therapy had higher local recurrence rates in comparison to patients who did not (29% vs 6%, p = 0.011). The prognosis for patients with osteosarcoma who had manipulative therapy was significantly poorer than those who had not. Manipulative therapy was an independent factor for survival. This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma

We describe a case of osteosarcoma of the scaphoid bone, which to our knowledge is only the second reported case of osteosarcoma in the carpus. A 38-year-old man complained of intense pain in the right wrist and had curettage and a bone graft for a lesion in the scaphoid. Histological examination showed this to be an osteosarcoma. Below-elbow amputation was performed and adjuvant chemotherapy given. There has been no evidence of recurrence or metastases at 33 months after amputation

This review of 27 cases serves to emphasis that periosteal chondrosarcoma and periosteal osteosarcoma are two distinct entities. Clinically, periosteal chondrosarcoma is less painful than periosteal osteosarcoma and runs a slower course. Radiographically, periosteal chondrosarcoma tends to affect the metaphysis and contains granular or "popcorn" opacities; while periosteal osteosarcoma more often affects the mid-diaphysis and shows lytic lesions with some spicules of reactive bone perpendicular to the underlying cortex. Histologically, periosteal chondrosarcoma shows lobular well-differentiated cartilage with Grade I or II (rarely Grade III) malignancy; periosteal osteosarcoma has a chondroid matrix with some osteoid component and Grade II or III malignancy. The prognosis in periosteal chondrosarcoma is good; conservative surgery is usually effective and metastases are very uncommon. In periosteal osteosarcoma the prognosis is less satisfactory but is better than that of other osteosarcomata; wide surgical excision is, however, needed and the incidence of metastases is about 15 per cent

Aims. Children treated for osteosarcoma around the knee often have a substantial leg-length discrepancy at skeletal maturity. The aim of this study was to investigate the results of staged skeletal reconstruction after a leg lengthening procedure using an external fixator in these patients. Patients and Methods. We reviewed 11 patients who underwent staged reconstruction with either an arthroplasty (n = 6) or an arthrodesis (n = 5). A control group of 11 patients who had undergone wide excision and concurrent reconstruction with an arthroplasty were matched for gender, location, and size of tumour. We investigated the change in leg-length discrepancy, function as assessed by the Musculoskeletal Tumor Society Scale (MSTS) score and complications. Results. A mean 5.2 cm (1.7 to 8.9) of lengthening was achieved. The mean MSTS scores significantly improved after staged reconstruction (p = 0.003) but were still worse than those of the control group (p = 0.049). However, the MSTS scores of the arthroplasty subgroup were comparable with those of the controls, although the extensor lag was greater and the range of movement was less. The patient group experienced more complications, but all of these resolved. Conclusion. Approximately 5 cm of lengthening and significant functional improvement can be achieved by staged reconstruction and lengthening, without major complications. Although it has limitations, this method of treatment seems to be a satisfactory surgical option for growing children with a significant leg-length discrepancy after excision of an osteosarcoma around the knee. Cite this article: Bone Joint J 2017;99-B:401–8

1. Nine patients treated for osteogenic sarcoma by elective radical irradiation are reviewed. Five of the nine patients have survived for from three to fourteen years, but one patient has metastases. 2. These results are compared with those from primary amputation. 3. The importance of histological grading in prognosis is emphasised. 4. It is concluded that radical irradiation should be considered in place of primary amputation for osteogenic sarcoma in the upper limb

We have studied 560 patients with osteosarcoma of a limb, who had been treated by neoadjuvant chemotherapy, in order to analyse the incidence of local and systemic recurrence according to the type of surgery undertaken. Of these, 465 patients had a limb-salvage procedure and 95 amputation or rotationplasty. At a median follow-up of 10.5 years there had been 225 recurrences. The five-year disease-free survival and overall survival rates were 60.7% and 68.5%, respectively, with no significant difference between patients undergoing amputation and those undergoing resection. The incidence of local recurrence was the same for patients treated by either amputation or limb salvage and correlated significantly with the margins of surgical excision and the histological response to chemotherapy. The outcome for patients with a local recurrence was significantly worse than for those who had recurrent disease with metastases only. We conclude that limb-salvage procedures are relatively safe in osteosarcoma treated by neoadjuvant chemotherapy. They should, however, only be performed in institutions where the margins of surgical excision and the histological response to chemotherapy can be accurately assessed. If the margins are inadequate and the histological response to chemotherapy is poor an immediate amputation should be considered

A retrospective study of patients with osteosarcoma was undertaken to determine whether there was a relationship between biopsy and survival. Fifty-seven patients treated at the Karolinska Hospital, Stockholm, between 1938 and 1959 were included in this study, all of whom were less than thirty years old, had a metaphysial osteosarcoma in a long bone but had no pulmonary metastases at the time of diagnosis; all were treated by amputation. No clinical variants of osteosarcoma were included. Twenty-four of the fifty-seven patients had an amputation without a prior biopsy; the others had biopsies before amputation. These two groups were fairly closely matched in age, sex, site and size of tumour, and in the level of amputation; some patients in each group received radiation before operation. Evaluation of these two groups of patients revealed that the performance of a biopsy, with or without a delay of not more than thirty days between the biopsy and the definitive operation, had no adverse effect on survival

1. The case histories of four siblings affected by osteogenic sarcoma are described. 2. The lesions appeared over a period of twelve years. The ages of the patients at the onset of symptoms were fifteen, twenty, eleven and twenty-two years. 3. The diagnosis of osteogenic sarcoma was in each case established by radiological and histological methods. 4. Two patients survived for eight and sixteen years after treatment and both are still alive and well

A study is presented of the aetiology and results of treatment in a group of 125 proven osteosarcomas present in children under fifteen years of age. These cases have been collected from the records of one English and six European treatment centres. There is a slight male preponderance, but the striking aetiological feature is the very high proportion of tumours of the long bones of the limbs (96 per cent). The two and a half and five year disease-free survival rates were respectively 15 and 12 per cent, with a further 9 per cent still living, but under observation for less than two and a half years. Evidence of metastasis after two and a half years is very unusual, but no child with a tumour of an axial or girdle bone lived this length of time. Although the differences in the results of the different methods of treatment employed are not statistically valid, the largest number of long survivors had been treated by early amputation, which method also provided the lowest rate of local tumour recurrences. Reasons are discussed which indicate that prompt ablation is the treatment of choice, perhaps with certain advantages in the light of recent advances in adjuvant treatment. The past situation in connection with childhood osteosarcoma certainly provides strong support for immediate carefully designed clinical trials of the new adjuvant methods cited

In 11 patients juxta-articular osteosarcoma around the knee was treated by intraepiphyseal excision of the tumour and reconstruction of the bone defect by distraction osteogenesis. Preoperative and postoperative chemotherapy was given to eight patients with high-grade tumours. The articular cartilage of the epiphysis and a maximum of healthy soft tissues were preserved. Distraction osteogenesis was then carried out. The mean gain in length was 9.7 cm. Full function of the limb was preserved in all except one patient, with a mean follow-up of 53.8 months. Treatment of juxta-articular osteosarcomas around the knee with joint preservation and biological reconstruction using distraction osteogenesis can give excellent functional results

The method of producing osteogenic sarcoma in rabbits by the injection of beryllium in the form of "zinc beryllium silicate" is presented. In five of ten animals which had such injections, osteogenic sarcomas developed several months later. There was new bone formation in the medullary cavities of the long bones before malignant changes were apparent. It is of particular interest to note that there was atrophy of the spleen in those animals in which bone tumours developed, whereas the spleen seemed to be quite normal in the rabbits which did not develop bone tumours. The tumours usually developed in the metaphysial regions. More than one tumour often developed in the same animal

From the European Osteosarcoma Intergroup study 202 patients were assessed with respect to their surgical treatment. Although treated in three different centres the survival of the three groups was identical (57% at five years). Two of the centres had rates of limb salvage of 85% and 83%, respectively, while the third had a rate of 49%. The corresponding risks of local recurrence were 13.3%, 6.8% and 2.5%, with all local recurrences arising in limbs with attempted limb salvage. Local recurrence was closely related to the adequacy of the margins of excision and to the chemotherapeutic response. Patients who had undergone limb-salvage surgery and who developed local recurrence still survival at five years). Of patients who relapsed, 31% of those with local recurrence alone were cured by further treatment, as compared with only 10% of those with metastases. Limb-salvage surgery with effective chemotherapy remains the optimum treatment for osteosarcoma

A poor response to chemotherapy (≤ 90% necrosis) for osteosarcomas leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over limb salvage surgery (LSS) with narrow margins in patients who respond poorly to chemotherapy. We only analysed patients with an osteosarcoma of the limb, a poor response to chemotherapy and close margins on LSS (marginal/intralesional) or primary amputation: 360 patients (36 LSS (intralesional margins), 197 LSS (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following LSS with intralesional margins, and 39 (20%) following LSS with marginal margins. There was no local recurrence in patients who underwent amputation. The five-year survival for all patients was 41% (95% confidence interval (CI) 35 to 46), but for those treated by LSS with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by LSS with intralesional margins. Patients who had LSS and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 patients but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over LSS with marginal margins in these patients with a poor overall prognosis. Cite this article: Bone Joint J 2015;97-B:115–20

We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45°C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia. The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung

Cite this article: Bone Joint Res 2023;12(5):311–312.

Four cases of extra-osseous osteosarcoma were found among 242 cases recorded as osteosarcoma in the Swedish Cancer Registry during the years 1958 to 1968. The tumours occurred in middle-aged and elderly patients. Three of the tumours were situated in the proximal part of the thigh and one in the scapular region. Histopathologically, all tumours were subclassified as osteoblastic osteosarcomas. The patients were treated by primary local excision which in one case was followed by a radical en bloc excision of the entire tumour bed. All cases subjected to simple excision died of metastatic disease five to twenty-four months after diagnosis. The patient treated by en bloc excision is alive and apparently free from disease fourteen years after diagnosis

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured. Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value

Of tumours arising in otherwise normal bones, fibrosarcoma is about one-third as common as osteosarcoma and may have a very slightly better prognosis. A comparison of the aetiology and behaviour of forty-nine fibrosarcomata and 152 osteosarcomata indicates several similar features. Fibrosarcoma lacks the characteristic peak incidence in adolescence of osteosarcoma, but the age and sex distributions of both tumour types in patients of middle life--twenty-five to sixty-five years--are remarkably similar, even in their frequency. With fibrosarcoma, perhaps, lung metastases are fewer and appear later, thus contributing to the slightly better survival, but there is some increase in the proportion of extra-pulmonary secondaries. As with osteosarcoma, patients with fibrosarcoma show some increase in the length of post-metastatic survival when metastases are of later appearance. For the whole series the five-year crude survival rate was 21 per cent, better results being recorded for patients with histologically well differentiated tumours (30 per cent) and for long bone tumours when the patient was metastasis-free initially and the tumour was treated by prompt ablation (40 per cent). These are probably the best results one may expect for osseous fibrosarcoma without recourse to adjuvant antimetastatic therapy. Complete control of the primary tumour is likewise mandatory, and can be assured only by complete surgical removal when this is technically feasible

Concomitant tumour resistance (CTR) is a unique phenomenon in which animals harbouring large primary tumours are resistant to the growth of smaller metastatic tumours by systemic angiogenic suppression. To examine this clinically, in ten patients with osteosarcoma, we investigated the effects of removal of the primary tumour on the development of pulmonary metastases, the systemic angiogenesis-inducing ability and the serum levels of several angiogenesis modulators. We found that removal of the primary tumour significantly elevated systemic angiogenesis-inducing ability in five patients who had post-operative recurrence of the tumour. Post-operative elevation of the angiogenesis-induced ability was suppressed by the addition of an angiogenic inhibitor, endostatin. Also, primary removal of the tumour decreased the serum levels of vascular endothelial growth factor and endostatin. These findings suggest, for the first time, the presence of CTR in patients with osteosarcoma for whom postoperative antiangiogenic therapy may be used to prevent the post-operative progression of micrometastases

At re-examination of all osteosarcomata recorded in the Swedish Cancer Registry during the years 1958 to 1968, 11 cases of parosteal osteosarcoma were found. No case of so-called periosteal osteosarcoma was identified. The tumours constituted 1.6 per cent of all proved primary malignant bone tumours. The ages of the 11 patients (six women and five men) ranged from 17 to 62 years (average 33 years). The clinical and histopathological findings of this study and of those collected from a review of the literature suggest the occurrence of two different types of parosteal osteosarcoma: the predominant type is originally benign but has a definite malignant potential, causing metastases after long symptom-free intervals; the other type is highly malignant from the beginning. Primary amputation is recommended for the latter category of tumours, and compartmental, radical en bloc resection followed by regular review is recommended for the former

The aim of this study was to assess a specific protocol for the treatment of patients with a parosteal osteosarcoma of the distal femur with limb salvage involving hemicortical resection and reconstruction using recycled pasteurised autograft and internal fixation. Between January 2000 and January 2010, 13 patients with a mean age of 26.5 years (17 to 39) underwent this procedure. All the tumours were staged according to Enneking’s criteria: there were eight stage IA tumours and five stage IB tumours. The mean follow-up was 101.6 months (58 to 142), and mean post-operative Musculoskeletal Tumour Society functional score was 88.6% (80% to 100%) at the final follow-up. All the patients had achieved bony union; the mean time to union was 11.2 months (6 to 18). Local recurrence occurred in one patient 27 months post-operatively. No patient had a pulmonary metastasis. A hemicortical procedure for the treatment of a parosteal osteosarcoma is safe and effective. Precise pre-operative planning using MRI is essential in order to define the margins of resection. Although it is a technically demanding procedure, gratifying results make it worthwhile for selected patients. Cite this article: Bone Joint J 2013;95-B:1275–9

Two hundred and forty-eight high-grade central osteosarcomata were treated by amputation or disarticulation; in 5.2 per cent the tumour recurred at the amputation site. The following causes may be responsible for local recurrence: the level of the amputation is too close to the tumour; there is an unrecognised intramedullary extension of the tumour; during a previous block resection tumour cells may have been seeded in the soft tissues; the primary tumour was too extensive even for radical surgery; "skip" metastases may have been present; iatrogenic tumour implantation may have occurred while a biopsy was being performed during the course of an amputation. Treatment of the primary osteosarcoma should take all these possibilities into account. In our experience adjuvant chemotherapy has not significantly changed the frequency of local recurrences which should be treated by radical operation or, if this is not possible, by irradiation; chemotherapy may be used as an adjuvant. The prognosis of local recurrences is bad