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

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Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments.

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The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

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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.

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Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension.

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Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS.

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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.

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Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment.

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Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture.

We performed a prospective genotype-phenotype study using molecular screening and clinical assessment to compare the severity of disease and the risk of sarcoma in 172 individuals (78 families) with hereditary multiple exostoses. We calculated the severity of disease including stature, number of exostoses, number of surgical procedures that were necessary, deformity and functional parameters and used molecular techniques to identify the genetic mutations in affected individuals. Each arm of the genotype-phenotype study was blind to the outcome of the other. Mutations EXT1 and EXT2 were almost equally common, and were identified in 83% of individuals. Non-parametric statistical tests were used. There was a wide variation in the severity of disease. Children under ten years of age had fewer exostoses, consistent with the known age-related penetrance of this condition. The severity of the disease did not differ significantly with gender and was very variable within any given family. The sites of mutation affected the severity of disease with patients with EXT1 mutations having a significantly worse condition than those with EXT2 mutations in three of five parameters of severity (stature, deformity and functional parameters). A single sarcoma developed in an EXT2 mutation carrier, compared with seven in EXT1 mutation carriers. There was no evidence that sarcomas arose more commonly in families in whom the disease was more severe. The sarcoma risk in EXT1 carriers is similar to the risk of breast cancer in an older population subjected to breast-screening, suggesting that a role for regular screening in patients with hereditary multiple exostoses is justifiable

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Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

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Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway.

Objectives. The most concerning infection of allografts and operative procedures is methicillin resistant Staphylococcus aureus (MRSA) and no current iontophoresed antibiotics effectively combat this microbe. It was initially hypothesised that iontophoresis of vancomycin through bone would not be effective due to its large molecular size and lack of charge. The aim of this study was to determine whether this was a viable procedure and to find the optimum conditions for its use. . Methods. An iontophoresis cell was set up with varying concentrations of Vancomycin within the medulla of a section of sheep tibia, sealed from an external saline solution. The cell was run for varying times, Vancomycin concentrations and voltages, to gain information on optimisation of conditions for impregnating the graft. Each graft was then sectioned and dust ground from the exposed surface. The dust was serially washed to extract the Vancomycin and concentrations measured and plotted for all variables tested. Results. Vancomycin was successfully delivered and impregnated to the graft using the iontophoresis technique. The first order fit to the whole data set gave a significant result (p = 0.0233), with a significant concentration (p = 0.02774) component. The time component was the next most significant (p = 0.0597), but did not exceed the 95% confidence level. Conclusions. Iontophoresis is an effective method for delivering Vancomycin to allograft bone. The concentrations of the vancomycin solution affected the bone concentration, but results were highly variable. Further study should be done on the effectiveness of delivering different antibiotics using this method. Cite this article: Bone Joint Res 2014;3:101–7

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To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs).

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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.

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The aim of this study is to evaluate the clinical results of operative intervention for femoral metastases which were selected based on expected survival and to discuss appropriate surgical strategies.

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The aims of this study were to evaluate the long-term outcome of surgery for bone or soft-tissue metastases from renal cell carcinoma (RCC) and to determine factors that affect prognosis.

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This study aims to assess first, whether mutations in the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes are associated with overall survival (OS) in patients who present with symptomatic bone metastases from non-small cell lung cancer (NSCLC) and secondly, whether mutation status should be incorporated into prognostic models that are used when deciding on the appropriate palliative treatment for symptomatic bone metastases.

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The aim of this study was to identify any progression between benign osteofibrous dysplasia (OFD), OFD-like adamantinoma and malignant adamantinoma, and to investigate the rates of local recurrence, metastases and survival, in order to develop treatment algorithms for each.

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT.

Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered.

The aim of this study was to define the incidence of venous thromboembolism (VTE) and risk factors for the development of deep-vein thrombosis (DVT) after the resection of a musculoskeletal tumour. A total of 94 patients who underwent resection of a musculoskeletal tumour between January 2003 and December 2005 were prospectively studied. There were 42 men and 52 women with a mean age of 54.4 years (18 to 86). All patients wore intermittent pneumatic compression devices and graduated compression stockings. Ultrasound examination of the lower limbs was conducted to screen for DVT between the fifth and ninth post-operative days.

DVT was detected in 21 patients (22%). Of these, two were symptomatic (2%). One patient (1%) had a fatal pulmonary embolism. Patients aged ≥ 70 years had an increased risk of DVT (p = 0.004).

The overall incidence of DVT (both symptomatic and asymptomatic) after resection of a musculoskeletal tumour with mechanical prophylaxis was high. It seems that both mechanical and anticoagulant prophylaxis is needed to prevent VTE in patients who have undergone the resection of a musculoskeletal tumour.

Cite this article: Bone Joint J 2013;95-B:1280–4.

It is important to be able to identify patients with an increased risk of venous thromboembolism (VTE) in order to minimise the risk of an event. We investigated the incidence and risk factors for post-operative VTE in 168 consecutive patients with a malignancy of the lower limb. The period of study included ten months before and 12 months after the introduction of chemical thromboprophylaxis. All data about the potential risk factors were identified and classified into three groups (patient-, surgery- and tumour-related). The outcome measure was a thromboembolic event within 90 days of surgery.

Of the 168 patients, eight (4.8%) had a confirmed symptomatic deep-vein thrombosis and one (0.6%) a fatal pulmonary embolism. Of the 28 variables tested, age > 60 years, higher American Society of Anesthesiologists grade and metastatic tumour were independent risk factors for VTE. The overall rate of symptomatic VTE was not significantly different between patients who received chemical thromboprophylaxis and those who did not. Knowledge of these risk factors may be of value in improving the surgical outcome of patients with a malignancy of the lower limb.

Cite this article: Bone Joint J 2013;95-B:558–62.

Endoprosthetic replacement of the distal tibia and ankle joint for a primary bone tumour is a rarely attempted and technically challenging procedure. We report the outcome of six patients treated between 1981 and 2007. There were four males and two females, with a mean age of 43.5 years (15 to 75), and a mean follow-up of 9.6 years (1 to 27). No patient developed a local recurrence or metastasis. Two of the six went on to have a below-knee amputation for persistent infection after a mean 16 months (1 to 31). The four patients who retained their endoprosthesis had a mean musculoskeletal tumour society score of 70% and a mean Toronto extremity salvage score of 71%. All were pain free and able to perform most activities of daily living in comfort.

A custom-made endoprosthetic replacement of the distal tibia and ankle joint is a viable treatment option for carefully selected patients with a primary bone tumour. Patients should, however, be informed of the risk of infection and the potential need for amputation if this cannot be controlled.

We have investigated whether improvements in design have altered the outcome for patients undergoing endoprosthetic replacement of the proximal tibia following resection of a tumour. Survival of the implant and ‘servicing’ procedures have been documented using a prospective database.

A total of 194 patients underwent a proximal tibial replacement, with 95 having a fixed-hinge design and 99 a rotating-hinge with a hydroxyapatite collar; their median age was 21.5 years (10 to 74). At a mean follow-up of 14.7 years (5 to 29), 115 patients remain alive. The risk of revision for any reason in the fixed-hinge group was 32% at five years, 61% at ten years and 75% at 15 and 20 years, and in the rotating-hinge group 12% at five years, 25% at ten years and 30% at 15 years. Aseptic loosening was the most common reason for revision in the fixed-hinge knees, fracture of the implant in the early design of rotating hinges and infection in the current version. The risk of revision for aseptic loosening in the fixed-hinge knees was 46% at ten years. This was reduced to 3% in the rotating-hinge knee with a hydroxyapatite collar. The cemented, rotating hinge design currently offers the best chance of long-term survival of the prosthesis.

Despite local treatment with systemic chemotherapy in Ewing’s sarcoma family tumours (ESFT), patients with detectable metastases at presentation have a markedly worse prognosis than those with apparently localised disease. We investigated the clinical, pathological and laboratory differences in 888 patients with ESFT, 702 with localised disease and 186 with overt metastases at presentation, seen at our institution between 1983 and 2006.

Multivariate analyses showed that location in the pelvis, a high level of serum lactic dehydrogenase, the presence of fever and a short interval between the onset of symptoms and diagnosis were indicative of metastatic disease. The rate of overt metastases at presentation was 10% without these four risk factors, 22.7% with one, 31.4% with two, and 50% for those with three or four factors. We concluded that in ESFT the site, the serum level of lactic dehydrogenase, fever, and the interval between the onset of symptoms and diagnosis are indicators of tumours having a particularly aggressive metastatic behaviour.