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
The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied.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
The aim of this study was to report the results of three forms of reconstruction for patients with a ditsl tibial bone tumour: an intercalary resection and reconstruction, an osteoarticular reconstruction, and arthrodesis of the ankle. A total of 73 patients with a median age of 19 years (interquartile range (IQR) 14 to 36) were included in this retrospective, multicentre study.Aims
Methods
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. 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.Aims
Methods
The aim of this study was to analyze the complications and outcomes of treatment in a series of previously untreated patients with a primary aneurysmal bone cyst (ABC) who had been treated by percutaneous sclerosant therapy using polidocanol. Between January 2010 and December 2016, 56 patients were treated primarily with serial intralesional sclerosant injections. Their mean age was 20 years (1 to 54). The sites involved were clavicle (n = 3), humeri (n = 11), radius (n = 1), ulna (n = 3), hand (n = 2), pelvis (n = 12), femur (n = 7), tibia (n = 13), fibula (n = 3), and foot (n = 1). After histopathological confirmation of the diagnosis, 3% polidocanol (hydroxypolyaethoxydodecan) was injected into the lesion under image intensifier guidance. Patients were evaluated clinically and radiologically every six to eight weeks. In the absence of clinical and/or radiological response, a repeat sclerosant injection was given after eight to 12 weeks and repeated at similar intervals if necessary.Aims
Methods
We analyzed the long-term outcomes of patients observed over ten years after resection en bloc and reconstruction with extracorporeal irradiated autografts This retrospective study included 27 patients who underwent resection en bloc and reimplantation of an extracorporeal irradiated autograft. The mean patient age and follow-up period were 31.7 years (9 to 59) and 16.6 years (10.3 to 24.3), respectively. The most common diagnosis was osteosarcoma (n = 10), followed by chondrosarcoma (n = 6). The femur (n = 13) was the most frequently involved site, followed by the tibia (n = 7). There were inlay grafts in five patients, intercalary grafts in 15 patients, and osteoarticular grafts in seven patients. Functional outcome was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system.Aims
Patients and Methods
Aims
Patients and Methods
Adjuvant treatment after intralesional curettage for atypical
cartilaginous tumours (ACTs) of long bones is widely accepted for
extending surgical margins. However, evaluating the isolated effect
of adjuvant treatment is difficult, and it is unclear whether not
using such adjuvants provides poor oncological outcomes. Hence,
we analyzed whether intralesional curettage without cryosurgery
or chemical adjuvants provides poor oncological outcomes in patients
with an ACT. A total of 24 patients (nine men, 15 women) (mean age 45 years;
18 to 62) were treated for ACTs of long bones and followed up for
a median of 66 months (interquartile range 50 to 84). All patients
were treated with extensive manual curettage and limited burring.
Bone cement and grafts were used to fill bone defects in 16 and eight
patients, respectively. No chemical adjuvants or cryosurgery were
used.Aims
Patients and Methods
To assess complications and failure mechanisms of osteoarticular
allograft reconstructions for primary bone tumours. We retrospectively evaluated 38 patients (28 men, 74%) who were
treated at our institution with osteoarticular allograft reconstruction
between 1989 and 2010. Median age was 19 years (interquartile range
14 to 32). Median follow-up was 19.5 years (95% confidence interval
(CI) 13.0 to 26.1) when 26 patients (68%) were alive. In addition, we
systematically searched the literature for clinical studies on osteoarticular
allografts, finding 31 studies suitable for analysis. Results of
papers that reported on one site exclusively were pooled for comparison.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
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
Extracorporeal irradiation of an excised tumour-bearing
segment of bone followed by its re-implantation is a technique used
in bone sarcoma surgery for limb salvage when the bone is of reasonable
quality. There is no agreement among previous studies about the
dose of irradiation to be given: up to 300 Gy have been used. We investigated the influence of extracorporeal irradiation on
the elastic and viscoelastic properties of bone. Bone was harvested
from mature cattle and subdivided into 13 groups: 12 were exposed
to increasing levels of irradiation: one was not and was used as
a control. The specimens, once irradiated, underwent mechanical
testing in
We determined the efficacy of a devitalised autograft
(n = 13) and allograft (n = 16) cortical strut bone graft combined
with long-stem endoprosthetic reconstruction in the treatment of
massive tumours of the lower limb. A total of 29 patients (18 men:11
women, mean age 20.1 years (12 to 45) with a ratio of length of
resection to that of the whole prosthesis of >
50% were treated
between May 2003 and May 2012. The mean follow-up was 47 months
(15 to 132). The stem of the prosthesis was introduced through bone
graft struts filled with cement, then cemented into the residual
bone. Bone healing was achieved in 23 patients (86%). The mean Musculoskeletal
Tumour Society functional score was 85% (57 to 97). The five-year
survival rate of the endoprostheses was 81% (95% confidence intervals
67.3 to 92.3). The mean length of devitalised autografts and allografts
was 8.6 cm (5 to 15), which increased the ratio of the the length
of the stem of the prosthesis to that of the whole length of the
prosthesis from a theoretical 35% to an actual 55%. Cortical strut bone grafting and long-stem endoprosthetic reconstruction
is an option for treating massive segmental defects following resection
of a tumour in the lower limb. Patients can regain good function
with a low incidence of aseptic loosening. The strut graft and the
residual bone together serve as a satisfactory bony environment
for a revision prosthesis, if required, once union is achieved. Cite this article:
Atypical cartilaginous tumours are usually treated
by curettage. The purpose of this study was to show that radiofrequency
ablation was an effective alternative treatment. We enrolled 20 patients (two male, 18 female, mean age 56 years
(36 to 72) in a proof-of-principle study. After inclusion, biopsy
and radiofrequency ablation were performed, followed three months
later by curettage and adjuvant phenolisation. The primary endpoint
was the proportional necrosis in the retrieved material. Secondary endpoints
were correlation with the findings on gadolinium enhanced MRI, functional
outcome and complications. Our results show that 95% to 100% necrosis was obtained in 14
of the 20 patients. MRI had a 91% sensitivity and 67% specificity
for detecting residual tumour after curettage. The mean functional
outcome (MSTS) score six weeks after radiofrequency ablation was
27.1 (23 to 30) compared with 18.1 (12 to 25) after curettage (p
<
0.001). No complications occurred after ablation, while two
patients developed a pathological fracture after curettage. We have shown that radiofrequency ablation is capable of completely
eradicating cartilaginous tumour cells in selective cases. MRI has
a 91% sensitivity for detecting any residual tumour. Radiofrequency
ablation can be performed on an outpatient basis allowing a rapid
return to normal activities. If it can be made more effective, it
has the potential to provide better local control, while improving
functional outcome. Cite this article:
The aim of this study was to evaluate the functional
and oncological outcome of extracorporeally irradiated autografts
used to reconstruct the pelvis after a P1/2 internal hemipelvectomy. The study included 18 patients with a primary malignant bone
tumour of the pelvis. There were 13 males and five females with
a mean age of 24.8 years (8 to 62). Of these, seven had an osteogenic
sarcoma, six a Ewing’s sarcoma, and five a chondrosarcoma. At a
mean follow-up of 51.6 months (4 to 185), nine patients had died
with metastatic disease while nine were free from disease. Local
recurrence occurred in three patients all of whom eventually died of
their disease. Deep infection occurred in three patients and required
removal of their graft in two while the third underwent a hindquarter
amputation for extensive flap necrosis. The mean Musculoskeletal Tumor Society functional score of the
16 patients who could be followed-up for at least 12 months was
77% (50 to 90). Those 15 patients who completed the Toronto Extremity
Salvage Score questionnaire had a mean score of 71% (53 to 85). Extracorporeal irradiation and re-implantation of bone is a valid
method of reconstruction after an internal hemipelvectomy. It has
an acceptable morbidity and a functional outcome that compares favourably
with other available reconstructive techniques. Cite this article:
Giant cell tumour is the most common aggressive
benign tumour of the musculoskeletal system and has a high rate of
local recurrence. When it occurs in proximity to the hip, reconstruction
of the joint is a challenge. Options for reconstruction after wide
resection include the use of a megaprosthesis or an allograft-prosthesis
composite. We performed a clinical and radiological study to evaluate
the functional results of a proximal femoral allograft-prosthesis
composite in the treatment of proximal femoral giant cell tumour
after wide resection. This was an observational study, between 2006
and 2012, of 18 patients with a mean age of 32 years (28 to 42)
and a mean follow-up of 54 months (18 to 79). We achieved excellent
outcomes using Harris Hip Score in 13 patients and a good outcome
in five. All allografts united. There were no complications such
as infection, failure, fracture or resorption of the graft, or recurrent
tumour. Resection and reconstruction of giant cell tumours with
proximal femoral allograft–prosthesis composite is a better option
than using a prosthesis considering preservation of bone stock and excellent
restoration of function. A good result requires demanding bone banking techniques, effective
measures to prevent infection and stability at the allograft-host
junction. Cite this article:
Osteoid osteoma is treated primarily by radiofrequency
(RF) ablation. However, there is little information about the distribution
of heat in bone during the procedure and its safety. We constructed
a model of osteoid osteoma to assess the distribution of heat in
bone and to define the margins of safety for ablation. Cavities
were drilled in cadaver bovine bones and filled with a liver homogenate
to simulate the tumour matrix. Temperature-sensing probes were placed
in the bone in a radial fashion away from the cavities. RF ablation
was performed 107 times in tumours <
10 mm in diameter (72 of
which were in cortical bone, 35 in cancellous bone), and 41 times
in cortical bone with models >
10 mm in diameter. Significantly
higher temperatures were found in cancellous bone than in cortical
bone (p <
0.05). For lesions up to 10 mm in diameter, in both
bone types, the temperature varied directly with the size of the
tumour (p <
0.05), and inversely with the distance from it. Tumours
of >
10 mm in diameter showed a trend similar to those of smaller
lesions. No temperature rise was seen beyond 12 mm from the edge
of a cortical tumour of any size. Formulae were developed to predict
the expected temperature in the bone during ablation. Cite this article:
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
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.