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

An increased long-term survival of patients with malignant tumours also increases the possibility of the development of skeletal metastases and pathological fractures. The management of bone metastases includes the removal of gross disease and the administration of local adjuvants. We have investigated the possibility of adding antiblastic drugs to acrylic cement. Cylinders of acrylic cement were manufactured containing three different antiblastic drugs, methotrexate, cisplatin and doxorubicin. We performed in vitro analysis on MCF-7 human breast cancer cells in order to evaluate the biological effect of the mixtures and surface analysis of the acrylic cement-cisplatin cylinders using energy-dispersive x-ray analysis (EDAX). All drugs were released in an active form from the cement. Each drug had a different effect on cell viability. Doxorubicin had the greatest effect on breast cancer cells. Surface analysis showed that antiblastic drugs were present in the form of granules. These results confirm the potential of antiblastic-loaded cement as a possible adjuvant in the local treatment of bone metastases. Further studies should be undertaken to determine whether the release of antiblastic drugs from cement is elution or if they are only released from the surface

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

We identified 42 patients who presented to our unit over a 27-year period with a secondary radiation-induced sarcoma of bone. We reviewed patient, tumour and treatment factors to identify those that affected outcome. The mean age of the patients at presentation was 45.6 years (10 to 84) and the mean latent interval between radiotherapy and diagnosis of the sarcoma was 17 years (4 to 50). The median dose of radiotherapy given was estimated at 50 Gy (mean 49; 20 to 66). There was no correlation between radiation dose and the time to development of a sarcoma. The pelvis was the most commonly affected site (14 patients (33%)). Breast cancer was the most common primary tumour (eight patients; 19%). Metastases were present at diagnosis of the sarcoma in nine patients (21.4%). Osteosarcoma was the most common diagnosis and occurred in 30 cases (71.4%). Treatment was by surgery and chemotherapy when indicated: 30 patients (71.4%) were treated with the intention to cure. The survival rate was 41% at five years for those treated with the intention to cure but in those treated palliatively the mean survival was only 8.8 months (2 to 22), and all had died by two years. The only factor found to be significant for survival was the ability to completely resect the tumour. Limb sarcomas had a better prognosis (66% survival at five years) than central ones (12% survival at five years) (p = 0.009). Radiation-induced sarcoma is a rare complication of radiotherapy. Both surgical and oncological treatment is likely to be compromised by the treatment received previously by the patient

Aims

We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton.

Aims

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.

Aims

This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival.

Aims

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.

Aims

The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

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.

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We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone.

Aims

The proximal tibia (PT) is the anatomical site most frequently affected by primary bone tumours after the distal femur. Reconstruction of the PT remains challenging because of the poor soft-tissue cover and the need to reconstruct the extensor mechanism. Reconstructive techniques include implantation of massive endoprosthesis (megaprosthesis), osteoarticular allografts (OAs), or allograft-prosthesis composites (APCs).

Aims

Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma.

Aims

The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this.

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.

Aims

The purpose of this study was to identify prognostic indicators of outcome at presentation to the orthopaedic surgeon, in patients with metastatic prostate cancer. Our aim was to use this information in a pragmatic, clinic-based approach so that surgical decision making could be optimized to benefit the patient in their remaining lifetime.

Aims

Surgical intervention in patients with bone metastases from breast cancer is dependent on the estimated survival of the patient. The purpose of this paper was to identify factors that would predict survival so that specific decisions could be made in terms of surgical (or non-surgical) management.

Aims

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.

Aims

The aim of this study was to validate the Mirels score in predicting pathological fractures in metastatic disease of the lower limb.

Aims

Pelvic reconstruction after the resection of a tumour around the acetabulum is a challenging procedure due to the complex anatomy and biomechanics. Several pelvic endoprostheses have been introduced, but the rates of complication remain high. Our aim was to review the use of a stemmed acetabular pedestal cup in the management of these patients.

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.

We report our early experience with a new peri-acetabular reconstruction endoprosthesis used for pelvic reconstruction after tumour resection. The outcome of 21 patients who underwent limb salvage following type II pelvic resection and reconstruction using the peri-acetabular reconstruction prosthesis between 2000 and 2006 was retrospectively reviewed. This prosthesis was designed to use the remaining part of the ilium to support a horizontally placed acetabular component secured with internal fixation and bone cement. Into this device a constrained acetabular liner is positioned which is articulates with a conventional femoral component to which a modular extension and modular head are attached. The mean follow-up was 20.5 months (1 to 77). The most common complications were deep infection, superficial wound infections, and dislocation. The mean musculoskeletal tumor society functional outcome score for the survivors was 20.1(11 to 27).

We recommend the use of the peri-acetabular reconstruction prosthesis for reconstruction of large defects after type II pelvic resection, as this design has a greater inherent stability over other available prostheses.

Aims

The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton.

The humerus is a common site for skeletal metastases in the adult. Surgical stabilisation of such lesions is often necessary to relieve pain and restore function. These procedures are essentially palliative and should therefore provide effective relief from pain for the remainder of the patient’s life without the need for further surgical intervention.

We report a retrospective analysis of 35 patients (37 nails) with symptomatic metastases in the shaft of the humerus which were treated by locked, antegrade nailing. There were 27 true fractures (73.0%) and ten painful deposits (27.0%). Relief from pain was excellent in four (11.4%), good in 29 (82.9%) and fair in two (5.7%) on discharge. Function was improved in all but one patient. One case of palsy of the radial nerve was noted. The mean postoperative survival was 7.1 months (0.2 to 45.5) which emphasises the poor prognosis in this group of patients. There were no failures of fixation and no case in which further surgery was required.

Antegrade intramedullary nailing is an effective means of stabilising the humerus for the palliative treatment of metastases. It relieves pain and restores function to the upper limb with low attendant morbidity.

Endoprosthetic reconstruction following resection of 31 tumours of the proximal femur in 30 patients was performed using a Wagner SL femoral revision stem. The mean follow-up was 25.6 months (0.6 to 130.0). Of the 28 patients with a metastasis, 27 died within a mean follow-up period of 18.1 months (0.6 to 56.3) after the operation, and the remaining patient was excluded from the study 44.4 months post-operatively when the stem was removed. The two patients with primary bone tumours were still alive at the latest follow-up of 81.0 and 130.0 months, respectively. One stem only was removed for suspected low-grade infection 44.4 months post-operatively. The worst-case survival rate with removal of the stem for any cause and/or loss to follow-up was 80.0% (95% confidence interval 44.9 to 100) at 130.0 months. The mean Karnofsky index increased from 44.2% (20% to 70%) pre-operatively to 59.7% (0% to 100%) post-operatively, and the mean Merle d’Aubigné score improved from 4.5 (0 to 15) to 12.0 (0 to 18). The mean post-operative Musculoskeletal Tumour Society score was 62.4% (3.3% to 100%).

The Wagner SL femoral revision stem offers an alternative to special tumour prostheses for the treatment of primary and secondary tumours of the proximal femur. The mid-term results are very promising, but long-term experience is necessary.

We reviewed the outcome of patients who had been treated operatively for symptomatic peri-acetabular metastases and present an algorithm to guide treatment.

The records of 81 patients who had been treated operatively for symptomatic peri-acetabular metastases between 1987 and 2010 were identified. There were 27 men and 54 women with a mean age of 61 years (15 to 87). The diagnosis, size of lesion, degree of pelvic continuity, type of reconstruction, World Health Organization performance status, survival time, pain, mobility and complications including implant failure were recorded in each case.

The overall patient survivorship at five years was 5%. The longest lived patient survived 16 years from the date of diagnosis. The mean survival was 23 months (< 1 to 16 years) and the median was 15 months. At follow-up 14 patients remained alive. Two cementoplasties failed because of local disease progression. Three Harrington rods broke: one patient needed a subsequent Girdlestone procedure. One ‘ice-cream cone’ prosthesis dislocated and was subsequently revised without further problems. We recommend the ‘ice-cream cone’ for pelvic discontinuity and Harrington rod reconstruction for severe bone loss. Smaller defects can be safely managed using standard revision hip techniques.

Cite this article: Bone Joint J 2014;96-B:132–6.

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.

We set out to determine the impact of surgery on quality of life and function in patients who had undergone surgery for symptomatic peri-acetabular metastases. From a prospective database we retrospectively reviewed 46 consecutive patients who had been treated operatively between June 2003 and June 2009. The mean age of the patients was 56.4 years (20 to 73) and the mean post-operative follow-up was 19.2 months (4 to 70). Functional evaluation and quality-of-life assessments were performed. At the most recent follow-up, 26 patients (56.5%) were alive. Their median survival time was 25.0 months. Ten major postoperative complications had occurred in eight patients (17.4%). The mean post-operative Musculoskeletal Tumor Society score (MSTS 93) was 56.3% (6.7% to 90.0%). Improvement in the Eastern Cooperative Oncology Group (ECOG) performance status was seen in 32 patients (69.6%). On the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire (QLQ-C30) measure of global health status there was a statistically significant improvement from the patients’ pre-operative status (42.8 (sd 13.7)) to that found at the latest follow-up (58.0 (sd 12.5)) (p = 0.001). The only statistically significant change in the nine symptom domains of the QLQ-C30 was a reduction in the mean level of pain (from 59.1 to 29.5 (out of 100)) (p < 0.001).

Surgery for patients with peri-acetabular metastases reduces pain and improves their quality of life, and has a low rate of surgical complications.

We report positive and negative factors associated with the most commonly-used methods of reconstruction after pathological fracture of the proximal femur. The study was based on 142 patients treated surgically for 146 metastatic lesions between 1996 and 2003. The local rate of failure was 10.3% (15 of 146). Of 37 operations involving osteosynthetic devices, six failed (16.2%) compared with nine (8.3%) in 109 operations involving endoprostheses. Of nine cases of prosthetic failure, four were due to periprosthetic fractures and three to recurrent dislocation. In the osteosynthesis group, three (13.6%) of 22 reconstruction nails failed. The two-year risk of re-operation after any type of osteosynthesis was 0.35 compared with 0.18 after any type of endoprosthetic reconstruction (p = 0.07). Endoprosthetic reconstructions are preferable to the use of reconstruction nails and other osteosynthetic devices for the treatment of metastatic lesions in the proximal third of the femur.

Between 1992 and 1999, we treated 350 patients with skeletal metastases. A multivariable analysis of the patients was conducted using the Cox proportional hazards model. We identified five significant prognostic factors for survival, namely, the site of the primary lesion, the performance status (Eastern Cooperative Oncology Group status 3 or 4), the presence of visceral or cerebral metastases, any previous chemotherapy, and multiple skeletal metastases. The score for each significant factor was derived from the corresponding estimated regression coefficients (natural logarithm of the hazard ratio). The prognostic score was calculated by adding all the scores for individual factors.

The rate of survival was 31% at six months and 11% at one year for the patients with a prognostic score of 6 or more. By contrast, patients with a prognostic score of 2 or less had a rate of survival of 98% at six months and 89% at one year. This scoring system can be used to determine the optimal treatment for patients with pathological fractures or epidural compression.