Aims

Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses.

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: Bone Joint J 2014; 96-B:677–83

Aims. 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. Methods. 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. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722

Aims. Accurate estimations of the risk of fracture due to metastatic bone disease in the femur is essential in order to avoid both under-treatment and over-treatment of patients with an impending pathological fracture. The purpose of the current retrospective in vivo study was to use CT-based finite element analyses (CTFEA) to identify a clear quantitative differentiating factor between patients who are at imminent risk of fracturing their femur and those who are not, and to identify the exact location of maximal weakness where the fracture is most likely to occur. Methods. Data were collected on 82 patients with femoral metastatic bone disease, 41 of whom did not undergo prophylactic fixation. A total of 15 had a pathological fracture within six months following the CT scan, and 26 were fracture-free during the five months following the scan. The Mirels score and strain fold ratio (SFR) based on CTFEA was computed for all patients. A SFR value of 1.48 was used as the threshold for a pathological fracture. The sensitivity, specificity, positive, and negative predicted values for Mirels score and SFR predictions were computed for nine patients who fractured and 24 who did not, as well as a comparison of areas under the receiver operating characteristic curves (AUC of the ROC curves). Results. The sensitivity of SFR was 100% compared with 88% for the Mirels score, and the specificity of SFR was 67% compared with 38% for the Mirels score. The AUC was 0.905 for SFR compared with 0.578 for the Mirels score (p = 0.008). Conclusion. All the patients who sustained a pathological fracture of the femur had an SFR of > 1.48. CTFEA was far better at predicting the risk of fracture and its location accurately compared with the Mirels score. CTFEA is quick and automated and can be incorporated into the protocol of CT scanners. Cite this article: Bone Joint J 2020;102-B(5):638–645

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.

Aims

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.

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.

Aim. Grade is the most important predictor of the biological behaviour of soft tissue sarcomas. Assigning a pathologic grade is always a difficult task as discordance rate is 30-40% even among experienced sarcoma pathologists. Many of these tumours are heterogeneously large and only small fractions are sampled for biopsy. This emphasizes the need for an objective and accurate assessment of histology. Our aim is to evaluate the role of Choline as a tumour marker in (i) differentiating benign from malignant soft tissue tumour, (ii) to distinguish recurrent/residual tumours using in-vivo MR spectroscopy. Methods. PMRS Study was performed at 1.5Tesla MRI machine of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumour in 15 cases by using point – resolved spectroscopic sequence (PRESS) with echo time TR=2000/TE = 30, 135 & 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered significant. MRS results and histopathologic findings were correlated and P < 0.001, considered being significant. Results. Choline peak was found in 17 out of 17 patients with sarcomas where as three patient with benign and five treated sarcomas patients with no residual disease did not show any choline. In vivo spectroscopy here shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each. In vivo spectroscopy shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each where as preoperative biopsy shows 75%, 100%, 100%, 72.7% and 85% respectively. Conclusion. Choline peak in PMRS study can predict the grade, margin status and tumour activity in recurrent and/or residual tumour. A major study should be done to validate its efficacy for routine use in oncology

Aim. Grade is the most important predictor of the biological behaviour of soft tissue sarcomas. Assigning a pathologic grade is always a difficult task as discordance rate is 30-40% even among experienced sarcoma pathologists. Many of these tumours are heterogeneously large and only small fractions are sampled for biopsy. This emphasizes the need for an objective and accurate assessment of histology. Our aim is to evaluate the role of Choline as a tumour marker in (i) differentiating benign from malignant soft tissue tumour, (ii) to distinguish recurrent/residual tumours using in-vivo MR spectroscopy. Methods. PMRS Study was performed at 1.5Tesla MRI machine of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumour in 15 cases by using point – resolved spectroscopic sequence (PRESS) with echo time TR=2000/TE = 30, 135 & 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered significant. MRS results and histopathologic findings were correlated and P < 0.001, considered being significant. Results. Choline peak was found in 17 out of 17 patients with sarcomas where as three patient with benign and five treated sarcomas patients with no residual disease did not show any choline. In vivo spectroscopy here shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each. In vivo spectroscopy shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each where as preoperative biopsy shows 75%, 100%, 100%, 72.7% and 85% respectively. Conclusion. Choline peak in PMRS study can predict the grade, margin status and tumour activity in recurrent and/or residual tumour. A major study should be done to validate its efficacy for routine use in oncology

Aims

Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses.

SSX was initially identified as a melanoma associated tumour antigen MEL2 and in the SS18/SSX fusion gene of synovial sarcoma. It consists of a family of nine, highly homologous X chromosome genes, being SSX1, SSX2 and SSX4 the most commonly expressed in tumours. In normal tissue, SSX expression is restricted to germ cells, trophoblasts, and mesenchymal stem cells. In malignant cells, SSX expression is over-represented in sarcomas. SSX expression is epigenetically regulated by methylation and histone deacetylation. Aim. To investigate the oncogenic properties of SSX. Validate it as tumour target and identify lead compounds. Methods. RNAi system for conditional silencing of SSX expression, Protein analysis and Mass Spec, PCR arrays, tumour xenographs and drug library screening. Results. SSX expression peaks at the G1/S phase of the cell cycle where it interacts with histone H3, H4 and β-catenin. This interaction promotes the phosphorylation of β-catenin at tyrosine residues and the transactivation of β-catenin genes MMP2 and cyclin D1. The association of SSX and MMP2 expression resulted in an increased invasion capacity of tumour cells. In vivo, silencing of SSX in tumour xenographs significantly affected the tumour growth. These tumours were characterized by large necrotic areas, impaired vascularization and cytoplasmic β-catenin. In contrast, tumour xenographs expressing SSX were highly proliferative, vascularized and exibited nuclear β-catenin. We further screened a chemical library and have identified lead compounds that target SSX. Conclusion. Our results demonstrate that SSX is a tumour target for drug development. We hypothesise that drugs targeting of SSX could affect functions related with the mesenchymal cell phenotype having potential cytostatic effect in sarcomas and/or epithelial tumour cells that undergo a epithelial-to-mesenchymal transition prior to metastasis

Aims

The aims of this retrospective study were to report the feasibility of using 3D-printing technology for patients with a pelvic tumour who underwent reconstruction.

In 1999, we developed a technique for biological reconstruction after excision of a bone tumour, which involved using autografts of the bone containing the tumour treated with liquid nitrogen. We have previously reported the use of this technique in 28 patients at a mean follow up of 27 months (10 to 54).

In this study, we included 72 patients who underwent reconstruction using this technique. A total of 33 patients died and three were lost to follow-up, at a mean of 23 months (2 to 56) post-operatively, leaving 36 patients available for a assessment at a mean of 101 months 16 to 163) post-operatively. The methods of reconstruction included an osteo-articular graft in 16, an intercalary in 13 and, a composite graft with prosthesis in seven.

Post-operative function was excellent in 26 patients (72.2%), good in seven (19.4%), and fair in three (8.3%) according to the functional evaluation system of Enneking. No recurrent tumour occurred within the grafts. The autografts survived in 29 patients (80.6%), and the rates of survival at five and ten years were 86.1% and 80.6 %, respectively. Seven of 16 osteo-articular grafts (44%) failed because of fracture or infection, but all the composite and intercalary grafts survived.

The long-term outcomes of frozen autografting, particularly using composite and intercalary grafts, are satisfactory and thus represent a good method of treatment for patients with a sarcoma of bone or soft tissue.

Cite this article: Bone Joint J 2014;96-B:555–61.

There is currently no consensus about the mean volume of blood lost during spinal tumour surgery and surgery for metastatic spinal disease. We conducted a systematic review of papers published in the English language between 31 January 1992 and 31 January 2012. Only papers that clearly presented blood loss data in spinal surgery for metastatic disease were included. The random effects model was used to obtain the pooled estimate of mean blood loss.

We selected 18 papers, including six case series, ten retrospective reviews and two prospective studies. Altogether, there were 760 patients who had undergone spinal tumour surgery and surgery for metastatic spinal disease. The pooled estimate of peri-operative blood loss was 2180 ml (95% confidence interval 1805 to 2554) with catastrophic blood loss as high as 5000 ml, which is rare. Aside from two studies that reported large amounts of mean blood loss (> 5500 ml), the resulting funnel plot suggested an absence of publication bias. This was confirmed by Egger’s test, which did not show any small-study effects (p = 0.119). However, there was strong evidence of heterogeneity between studies (I² = 90%; p < 0.001).

Spinal surgery for metastatic disease is associated with significant blood loss and the possibility of catastrophic blood loss. There is a need to establish standardised methods of calculating and reporting this blood loss. Analysis should include assessment by area of the spine, primary pathology and nature of surgery so that the amount of blood loss can be predicted. Consideration should be given to autotransfusion in these patients.

Cite this article: Bone Joint J 2013;95-B:683–8.

Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R² = 0.90 and R² = 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.

We have developed a hollow perforated cannulated screw. One or more of these was implanted percutaneously in 11 patients with an osteolytic metastasis in the femoral neck and multiple metastases elsewhere. They were supplemented by one or two additional standard 6.5 mm cannulated screws in nine patients. Polymethylmethacrylate bone cement was injected through the screw into the neck of the femur using small syringes, as in vertebroplasty. The mean amount of cement injected was 23.2 ml (17 to 30). Radiotherapy was started on the fourth post-operative day and chemotherapy, on average, was resumed a day later.

Good structural stability and satisfactory relief from pain were achieved in all the patients. This technique may be useful in the palliation of metastases in the femoral neck.

We used a knee-sparing distal femoral endoprosthesis in young patients with malignant bone tumours of the distal femur in whom it was possible to resect the tumour and to preserve the distal femoral condyles. The proximal shaft of the endoprosthesis had a coated hydroxyapatite collar, while the distal end had hydroxyapatite-coated extracortical plates to secure it to the small residual femoral condylar fragment. We reviewed the preliminary results of this endoprosthesis in eight patients with primary bone tumours of the distal femur. Their mean age at surgery was 17.years (14 to 21). The mean follow-up was 24 months (20 to 31). At final follow-up the mean flexion at the knee was 102° (20° to 120°) and the mean Musculoskeletal Tumour Society score was 80% (57% to 96.7%).

There was excellent osteointegration at the prosthesis-proximal bone interface with formation of new bone around the hydroxyapatite collar. The prosthesis allowed preservation of the knee and achieved a good functional result. Formation of new bone and remodelling at the interface make the implant more secure. Further follow-up is required to determine the long-term structural integrity of the prosthesis.

We report our early experience with the use of a non-invasive distal femoral expandable endoprosthesis in seven skeletally immature patients with osteosarcoma of the distal femur. The patients had a mean age of 12.1 years (9 to 15) at the time of surgery. The prosthesis was lengthened at appropriate intervals in outpatient clinics, without anaesthesia, using the principle of electromagnetic induction. The patients were functionally evaluated using the Musculoskeletal Tumour Society scoring system. The mean follow-up was 20.2 months (14 to 30). The prostheses were lengthened by a mean of 25 mm (4.25 to 55) and maintained a mean knee flexion of 110° (100° to 120°). The mean Musculoskeletal Tumour Society score was 68% (11 to 29). Complications developed in two patients; one developed a flexion deformity of 25° at the knee joint, which was subsequently overcome and one died of disseminated disease. The early results from patients treated with this device have been encouraging. The implant avoids multiple surgical procedures, general anaesthesia and assists in maintaining leg-length equality.

We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of en bloc excision of the tumour, removal of soft tissue, curettage of the tumour, drilling and preparation for internal fixation or prosthetic replacement before incubation for 20 minutes in liquid nitrogen, thawing at room temperature for 15 minutes, thawing in distilled water for ten minutes, and internal fixation with an intramedullary nail, plate or composite use of prosthetic replacement. Bone graft or cement was used to augment bone strength when necessary.

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.