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. 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.Aims
Methods
Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated.Aims
Methods
Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment. A total of 547 patients with STS who underwent tumour resection between 2005 and 2021 were divided into a development cohort and a validation cohort. In the development cohort of 402 patients, the least absolute shrinkage and selection operator (LASSO) regression model was used to screen possible risk factors of SSI. To select risk factors and construct the prediction nomogram, multivariate logistic regression was used. The predictive power of the nomogram was evaluated by receiver operating curve (ROC) analysis in the validation cohort of 145 patients.Aims
Methods
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. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses.Aims
Methods
We conducted a case-control study to examine
the merit of silver-coated tumour prostheses. We reviewed 85 patients
with Agluna-treated (silver-coated) tumour implants treated between
2006 and 2011 and matched them with 85 control patients treated
between 2001 and 2011 with identical, but uncoated, tumour prostheses. . In all, 106 men and 64 women with a mean age of 42.2 years (18.4
to 90.4) were included in the study. There were 50 primary reconstructions
(29.4%); 79 one-stage revisions (46.5%) and 41 two-stage revisions
for infection (24.1%). The overall post-operative infection rate of the silver-coated
group was 11.8% compared with 22.4% for the control group (p = 0.033,
chi-square test). A total of seven of the ten infected prostheses
in the silver-coated group were treated successfully with debridement,
antibiotics, and implant retention compared with only six of the
19 patients (31.6%) in the control group (p = 0.048, chi-square
test). Three patients in the silver-coated group (3.5%) and 13 controls
(15.3%) had chronic periprosthetic infection (p = 0.009, chi-square
test). The overall success rates in controlling infection by two-stage
revision in the silver-coated group was 85% (17/20) compared with
57.1% (12/21) in the control group (p = 0.05, chi-square test).
The Agluna-treated endoprostheses were associated with a lower rate
of early periprosthetic infection. These silver-treated implants
were particularly useful in two-stage revisions for infection and
in those patients with incidental positive
Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI.Aims
Methods
Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma.Aims
Methods
Iliac wing (Type I) and iliosacral (Type I/IV) pelvic resections for a primary bone tumour create a large segmental defect in the pelvic ring. The management of this defect is controversial as the surgeon may choose to reconstruct it or not. When no reconstruction is undertaken, the residual ilium collapses back onto the remaining sacrum forming an iliosacral pseudarthrosis. The aim of this study was to evaluate the long-term oncological outcome, complications, and functional outcome after pelvic resection without reconstruction. Between 1989 and 2015, 32 patients underwent a Type I or Type I/IV pelvic resection without reconstruction for a primary bone tumour. There were 21 men and 11 women with a mean age of 35 years (15 to 85). The most common diagnosis was chondrosarcoma (50%, n = 16). Local recurrence-free, metastasis-free, and overall survival were assessed using the Kaplan-Meier method. Patient function was evaluated using the Musculoskeletal Tumour Society (MSTS) and Toronto Extremity Salvage Score (TESS).Aims
Methods
The use of a noninvasive growing endoprosthesis in the management
of primary bone tumours in children is well established. However,
the efficacy of such a prosthesis in those requiring a revision
procedure has yet to be established. The aim of this series was
to present our results using extendable prostheses for the revision
of previous endoprostheses. All patients who had a noninvasive growing endoprosthesis inserted
at the time of a revision procedure were identified from our database.
A total of 21 patients (seven female patients, 14 male) with a mean
age of 20.4 years (10 to 41) at the time of revision were included.
The indications for revision were mechanical failure, trauma or infection
with a residual leg-length discrepancy. The mean follow-up was 70
months (17 to 128). The mean shortening prior to revision was 44 mm
(10 to 100). Lengthening was performed in all but one patient with
a mean lengthening of 51 mm (5 to 140).Aims
Patients and Methods
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. 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.Objectives
Methods
As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration. All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation.Objectives
Methods
The diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial. The Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus.Objectives
Materials and Methods
Clinical studies of patients with bone sarcomas have been challenged
by insufficient numbers at individual centres to draw valid conclusions.
Our objective was to assess the feasibility of conducting a definitive
multi-centre randomised controlled trial (RCT) to determine whether
a five-day regimen of post-operative antibiotics, in comparison
to a
24-hour regimen, decreases surgical site infections in patients
undergoing endoprosthetic reconstruction for lower extremity primary
bone tumours. We performed a pilot international multi-centre RCT. We used
central randomisation to conceal treatment allocation and sham antibiotics
to blind participants, surgeons, and data collectors. We determined
feasibility by measuring patient enrolment, completeness of follow-up,
and protocol deviations for the antibiotic regimens. Objective
Methods
We analysed the outcome of patients with primary
non-metastatic diaphyseal sarcomas who had Extracorporeal irradiation is an oncologically safe and inexpensive
technique for limb salvage in diaphyseal sarcomas and has good functional
results.
Between 1966 and 2001, 1254 patients underwent excision of a bone tumour with endoprosthetic replacement. All patients who had radiotherapy were identified. Their clinical details were retrieved from their records. A total of 63 patients (5%) had received adjunctive radiotherapy, 29 pre-operatively and 34 post-operatively. The mean post-operative Musculoskeletal Tumor Society scores of irradiated patients were significantly lower (log-rank test, p = 0.009). The infection rate in the group who had not been irradiated was 9.8% (117 of 1191), compared with 20.7% (6 of 29) in those who had pre-operative radiotherapy and 35.3% (12 of 34) in those who radiotherapy post-operatively. The infection-free survival rate at ten years was 85.5% for patients without radiotherapy, 74.1% for those who had pre-operative radiotherapy and 44.8% for those who had post-operative radiotherapy (log-rank test, p <
0.001). The ten-year limb salvage rate was 89% for those who did not have radiotherapy and 76% for those who did (log-rank test, p = 0.02). Radiotherapy increased the risk of revision (log-rank test, p = 0.015). A total of ten amputations were necessary to control infection, of which nine were successful. Radiotherapy may be necessary for the treatment of a bone sarcoma but increases the risk of deep infection for which amputation may be the only solution.
We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of The limb function was rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at a mean of 19.8 months after the operation, while 21 remained free from disease with a mean follow-up of 28.1 months (10 to 54). One patient is alive with disease. Bony union was seen at a mean of 6.7 months after the operation in 26 patients. Complications were encountered in seven patients, including three deep infections, two fractures, and two local recurrences. All were managed successfully. Our results suggest that this is a simple and effective method of biological reconstruction.
