Aims. The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. Methods. The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures. Results. In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. Conclusion. This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease. Cite this article: Bone Jt Open 2023;4(6):424–431

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. Methods. 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. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

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. Methods. This was a retrospective study which included all patients who had presented for surgery with metastatic bone disease. The data collected included patient, surgical, and oncological variables. Univariable and multivariable analysis identified which factors were associated with a survival time of less than six months and less than one year. A model to predict survival based on these factors was developed using Cox regression. Results. A total of 164 patients were included with a median survival time of 1.6 years (interquartile range 0.5 to 3.1) after surgery. On multivariable analysis, a higher American Society of Anesthesiologists grade (p < 0.001), a high white cell count (p = 0.002), hyponatraemia (p = 0.001), a preoperative resting heart rate of > 100 bpm (p = 0.052), and the type of primary cancer (p = 0.026) remained significant predictors of reduced survival time. The predictive model developed showed good discrimination and calibration to predict both six- and 12-month survival in patients with metastatic bone disease. Conclusion. In addition to surgical and oncological factors, the level of comorbidity and physiological state of the patient has a significant impact on survival in patients with metastatic bone disease. These factors should be considered when assessing the appropriateness of surgical intervention. This is the first study to examine other patient factors alongside surgical and oncological data to identify a relationship between these and survival. Cite this article: Bone Joint J 2021;103-B(11):1725–1730

Objectives. In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians. Methods. A total of 39 patients with non-fractured femoral metastatic lesions who were irradiated for pain were included from three radiotherapy institutes. During follow-up, nine pathological fractures occurred in seven patients. Quantitative CT-based FE models were generated for all patients. Femoral failure load was calculated and compared between the fractured and non-fractured femurs. Due to inter-scanner differences, patients were analyzed separately for the three institutes. In addition, the FE-based predictions were compared with fracture risk assessments by experienced clinicians. Results. In institute 1, median failure load was significantly lower for patients who sustained a fracture than for patients with no fractures. In institutes 2 and 3, the number of patients with a fracture was too low to make a clear distinction. Fracture locations were well predicted by the FE model when compared with post-fracture radiographs. The FE model was more accurate in identifying patients with a high fracture risk compared with experienced clinicians, with a sensitivity of 89% versus 0% to 33% for clinical assessments. Specificity was 79% for the FE models versus 84% to 95% for clinical assessments. Conclusion. FE models can be a valuable tool to improve clinical fracture risk predictions in metastatic bone disease. Future work in a larger patient population should confirm the higher predictive power of FE models compared with current clinical guidelines. Cite this article: F. Eggermont, L. C. Derikx, N. Verdonschot, I. C. M. van der Geest, M. A. A. de Jong, A. Snyers, Y. M. van der Linden, E. Tanck. Can patient-specific finite element models better predict fractures in metastatic bone disease than experienced clinicians? Towards computational modelling in daily clinical practice. Bone Joint Res 2018;7:430–439. DOI: 10.1302/2046-3758.76.BJR-2017-0325.R2

Advances in cancer therapy have prolonged cancer patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in patients more likely to walk after surgery, longer survival, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data for MBD patients (2009–2016) in order to determine which features are most commonly associated with fracture. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 1146 patients comprising 224 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray. The clinical data includes patient demographics, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. Each of Mirel's criteria has been further subdivided and recorded for each lesion. We have trained a convolutional neural network (CNN) with X-ray images of 1146 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. This model converges on two fully connected deep neural network layers that output the fracture risk. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a test's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Five-fold cross validation testing of our fully trained model revealed accurate classification for 88.2% of patients with metastatic bone disease of the proximal femur. The F1 statistic is 0.87. This represents a 24% error reduction from using Mirel's criteria alone to classify the risk of fracture in this cohort. This is the first reported application of convolutional neural networks, a machine learning algorithm, to an important Orthopaedic problem. Our neural network model was able to achieve impressive accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to validate this algorithm on an external cohort

Aims. Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD. Methods. This will be a prospective, longitudinal study across six UK orthopaedic centres powered to identify the influence of ten patient variables on quality of life at three months after surgery for MBD. Adult patients managed for bone metastases will be screened by their treating consultant and posted out participant materials. If they opt in to participate, they will receive questionnaire packs at regular intervals from three to 24 months post-surgery and their electronic records will be screened until death or five years from recruitment. The primary outcome is quality of life as measured by the European Organisation for Research and the Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ) C30 questionnaire. The protocol has been approved by the Newcastle & North Tyneside 2 Research Ethics Committee (REC ref 19/NE/0303) and the study is funded by the Royal College of Physicians and Surgeons of Glasgow (RCPSG) and the Association for Cancer Surgery (BASO-ACS). Discussion. This will be the first powered study internationally to investigate patient-reported outcomes after orthopaedic treatment for bone metastases. We will assess quality of life, function, and pain relief at three to 24 months post-surgery and identify which patient variables are significantly associated with a good outcome after MBD treatment. Cite this article: Bone Jt Open 2021;2(2):79–85

Advances in cancer therapy have prolonged patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in longer survival, preserved mobility, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The ideal clinical decision support tool will be of the highest sensitivity and specificity, non-invasive, generalizable to all patients, and not a burden on hospital resources or the patient's time. Our research uses novel machine learning techniques to develop a model to fill this considerable gap in the treatment pathway of MBD of the femur. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data of consecutive MBD patients presenting from 2009–2016. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 546 patients comprising 114 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray and clinical data including patient demographics, Mirel's criteria, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. We have trained a convolutional neural network (CNN) with AP X-ray images of 546 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. The model converges on two fully connected deep neural network layers that output the risk of fracture. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections, until overall prediction accuracy is optimized. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across five test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a model's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Our model achieved 88.2% accuracy in predicting fracture risk across five-fold cross validation testing. The F1 statistic is 0.87. This is the first reported application of convolutional neural networks, a machine learning algorithm, to this important Orthopaedic problem. Our neural network model was able to achieve reasonable accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to externally validate this algorithm on an international cohort

Surgical management for acute or impending pathologic fractures in metastatic bone disease (MBD) places patients at high-risk for post-operative venous thromboembolism (VTE). Due to the combination of malignancy, systemic cancer treatment, and surgical treatment, VTE-risk is increased 7-fold in patients with MBD compared to non-cancer patients undergoing the same procedure. The extent and duration of post-operative hypercoagulability in patients with MBD remains unknown and thromboprophylaxis guidelines were developed for non-cancer patients, limiting their applicability to address the elevated VTE-risk in cancer patients. Thrombelastography (TEG) analysis is a point-of-care test that measures clot formation, stabilization, and lysis in whole blood samples. The TEG parameter, maximal amplitude (MA), indicates clot strength and the threshold of ≥65 mm has been used to define hypercoagulability and predict VTE events in non-cancer patients requiring orthopaedic surgery. Therefore, this study aims to quantify the extent and duration of post-operative hypercoagulability in patients with MBD using serial TEG analysis. Consecutive adults (≥18 years) with MBD who required orthopaedic surgery for acute or impending pathologic fractures were enrolled into this single-centre, prospective cohort study. Serial TEG analysis was performed onsite using a TEG®6s haemostasis analyzer (Haemonetics Corporation, Boston, MA) on whole blood samples collected at seven timepoints: pre-operatively; on post-operative day (POD) 1, 3, and 5; and at 2-, 6-, and 12-weeks post-operatively. Hypercoagulability was defined as MA ≥65 mm. Participants received standardized thromboprophylaxis for four weeks and patient-reported compliance with thromboprophylaxis was recorded. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were performed and difference between pre-operative MA values of participants with VTE versus no VTE was evaluated using Student's t-test (p≤0.05). Twenty-one participants (10 female; 47.6%) with a mean age of 70 ± 12 years were enrolled. Nine different primary cancers were identified amongst participants, with breast (23.8%), colorectal (19.0%), and lung cancer (14.3%) most frequently reported. Most participants (57.1%) were hypercoagulable pre-operatively, and nearly half remained hypercoagulable at 6- and 12-weeks post-operatively (47.1 and 46.7%, respectively). VTE occurred in 5 patients (23.8%) and mean MA was 68.1 ± 4.6 mm at the time of diagnosis. Mean pre-operative MA values were significantly higher (p=0.02) in patients who experienced VTE (68.9 ± 3.5 mm) compared to those who did not (62.7 ± 6.5 mm). VTE incidence was highest in the first week post-operatively, during which time four VTE events (80%) occurred. The proportion of patients in a hypercoagulable state increased at three consecutive timepoints, beginning on POD3 (85.0%), increasing on POD5 (87.5%), and peaking at 2-weeks post-operatively (88.9%). Current thromboprophylaxis guidelines do not consider cancer-associated risk factors that contribute to increased VTE incidence and prescription duration may be inadequate to address prolonged post-operative hypercoagulability in patients with MBD. The high rate of VTE events observed and sustained hypercoagulable state indicate that thromboprophylaxis may be prematurely terminated while patients remain at high risk for VTE. Therefore, extending thromboprophylaxis duration beyond 4-weeks post-operatively in patients with MBD warrants further investigation

Due to advances in the assessment and treatment of patients with metastatic bone disease, the survival has improved in recent years. It was the aim of this met-analysis to assess the outcome of patients with metastatic bone disease across Europe. Five major bone tumour treatment centres participated in the met-analyses. Data had been collected prospectively and was retrieved from the databases for the purpose of this study. All patients were referred to the bone tumour centre for assessment and possible surgical treatment. The data of almost 2500 patients were analysed. The average age at diagnosis was 60 years and the male to female ratio was 1:1.07. The overall 5-year survival was 35%, but this was significantly better in metastatic disease of the thyroid and breast as well as multiple myeloma. The number and site of metastases or the presence of a pathological fracture were not prognostic factors in terms of survival. Patients who were female or younger than 50 years of age at time of diagnosis had a better outcome. This registry will be expanded and more information analysed to try and provide useful information about prognostic factors and outcome for patients with meta-static bone disease

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. Methods. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve. Results. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians’ experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs. Cite this article: Bone Joint Res 2024;13(9):497–506

The presence of metastatic bone disease (MBD) often necessitates major orthopaedic surgery. Patients will enter surgical care either through emergent or electively scheduled care pathways. Patients in a pain crisis or with an acute fracture are generally admitted via emergent care pathways whereas patients with identified high-risk bone lesions are often booked for urgent yet scheduled elective procedures. The purpose of this study is to compare the post-operative outcomes of patients who present through emergent or electively scheduled care pathways in patients in a Canadian health care system. We have conducted a retrospective, multicenter cohort study of all patients presenting for surgery for MBD of the femur, humerus, tibia or pelvis in southern Alberta between 2006 and 2021. Patients were identified by a search query of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or actual pathologic fracture in the Calgary, South and Central Alberta Zones. Subsequent chart reviews were performed. Emergent surgeries were defined by patients admitted to hospital via urgent care mechanisms and managed via unscheduled surgical bookings (“on call list”). Elective surgeries were defined by patients seen by an orthopaedic surgeon at least once prior to surgery, and booked for a scheduled urgent, yet elective procedure. Outcomes include overall survival from the time of surgery, hospital length of stay, and 30-day hospital readmission rate. We have identified 402 patients to date for inclusion. 273 patients (67.9%) underwent surgery through emergent pathways and 129 patients (32.1%) were treated through urgent, electively scheduled pathways. Lung, prostate, renal cell, and breast cancer were the most common primary malignancies and there was no significant difference in these primaries amongst the groups (p=0.06). Not surprisingly, emergent patients were more likely to be treated for a pathologic fracture (p<0.001) whereas elective patients were more likely to be treated for an impending fracture (p<0.001). Overall survival was significantly shorter in the emergent group (5.0 months, 95%CI: 4.0-6.1) compared to the elective group (14.9 months 95%CI: 10.4-24.6) [p<0.001]. Hospital length of stay was significantly longer in the emergent group (13 days, 95%CI: 12-16 versus 5 days, 95%CI: 5-7 days). There was a significantly greater rate of 30-day hospital readmission in the emergent group (13.3% versus 7.8%) [p=0.01]. Electively managed MBD has multiple benefits including longer post-operative survival, shorter length of hospital stay, and a lower rate of 30-day hospital readmission. These findings from a Canadian healthcare system demonstrate clinical value in providing elective orthopaedic care when possible for patients with MBD. Furthermore, care delivery interventions capable of decreasing the footprint of emergent surgery through enhanced screening or follow-up of patients with MBD has the potential to significantly improve clinical outcomes in this population. This is an ongoing study that will justify refinements to the current surgical care pathways for MBD in order to identify patients prior to emergent presentation. Future directions will evaluate the costs associated with each care delivery method to provide opportunity for health economic efficiencies

Cite this article: Bone Joint J 2024;106-B(1):6–8.

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

Metastatic bone disease resulting in acetabular destruction can provide the orthopaedic surgeon with the difficult challenge of achieving a stable reconstruction of the hip to provide pain relief and restoration of mobility. We review of twenty patients with metastatic disease requiring major acetabular reconstruction presenting to our orthopaedic oncology unit over a five year period was undertaken. This yielded 15 female and 5 male patients with mean age 59 years. The primary lesion was breast (8 cases), renal (3) prostate (2), myeloma (2) and others (5) with a solitary acetabular metastasis in 75% of cases. Eight patients had received radiotherapy to the region pre-operatively. In all cases, diseased bone was macroscopically cleared from the pelvis and reconstruction performed by means of a Harrington procedure with threaded pins passed antegrade from the iliac crest 915 cases) or mesh and screws (5 cases), all reinforced with cement around which a total hip arthroplasty was performed. Mean follow-up was 16 months. Complications were broken pin (1 case), dislocation of femoral prosthesis (1) and deep venous thrombosis (1). Three patients died of their disease at a mean of 12 months from surgery. The remaining 17 patients continue to function at a satisfactory level with no patients having required revision surgery for loosening or deep infection. We believe that surgical reconstruction of the acetabulum is worthwhile and can provide these deserving patients with improvement in quality of life

The aim of the study is to review the results of prophylactic reconstruction of subtrochanteric metastatic bone disease of femur using a Long Gamma Nail. Metastasis in the subtrochanteric region of femur can be challenging to treat not only due to peculiarities in biomechanics and anatomy, but also due to weak and deficient bone stock due to metastasis. Between 1996 and 2002, 28 subtrochanteric metastatic lesions of femur in 25 patients (3 bilateral) were treated with Long Gamma Nail. The outcome measures used in this study were pain relief, postoperative mobilization, and medical and implant related complications rate. There were 16 female and 9 male patients with an average age of 64 years. All patients reported marked pain relief. All but one regained pre-operative mobilization status. There were no intra-operative deaths including 3 bilateral nailings. Significant surgical and implant related complications were seen in 3(12%) patients. Postoperative medical complications were seen in 3 (12%) patients. There were no implant failures and reoperations. At the time of study 14 patients died with an average survival of 9 months and 11 patients were alive with an average survival of 16.5 months. Long Gamma Nail is valuable reconstruction device for the prophylactic treatment of subtrochanteric metastatic bone disease of femur. It is strong, versatile and biomechanically superior to extramedullary devises and compares favourably with other intramedullary devices. In our experience Long Gamma Nail allows immediate unrestricted mobilization with marked pain relief

Introduction. The rising incidence of metastatic bone disease (MBD) in the UK poses a significant management problem. Poorly defined levels of service provision have meant that improvements in patient prognosis have been mediocre at best. For that reason the British Orthopaedic Association (BOA) in conjunction with the British Orthopaedic Oncology Society (BOOS) issued guidelines in 2002 on good practice in the management of MBD. Despite the availability of these standards, there is very little robust data available for audit. The aim of this study was to conduct a regional survey of how these guidelines are being used in the management of MBD. Methods. A questionnaire was designed with 9 multiple choice questions representing the most common MBD scenarios. This was posted to 106 Consultant Orthopaedic Surgeons in 12 NHS Trusts in the South East of England. Results. The overall response rate to the questionnaire was 44%. There was considerable variation in the management of solitary femoral diaphyseal lesions, pathological subtrochanteric and intertrochanteric femoral neck fractures and vertebral metastases. Furthermore only 2 out of the 12 Trusts surveyed had a designated MBD lead as per the BOA/BOOS guidelines. Discussion. Our study reflects the variation in the management of MBD throughout the region, which may in turn be linked to poorer clinical outcomes. The results demonstrate the possibility of (i) inappropriate initial treatment, (ii) subsequent late tertiary referral and (iii) poor understanding of the biomechanical basis of orthopaedic implants, with the potential for inappropriate choice of prostheses and high failure rates. Streamlining cancer care will involve establishing regional MBD units within large centres where multidisciplinary services are available. Consequently all surrounding hospitals will need a designated MBD lead that can function as a conduit to this integrated care for selected patients

Introduction: Sending intramedullary reamings for histology in patients with metastaic bone disease (MBD) is routinely done in many centres. However, whether the results of these reamings help in the diagnosis of MBD remains unclear. Recent studies have shown that on the basis of biopsy of the metastases alone, only 35% of the primary tumours are detected. British Orthopaedic Oncology Society guidelines recommend further investigations and a bone biopsy if the primary disease is unknown. Aim:The aim of this study was to correlate clinical, radiological and histological findings for patients with metastatic bone disease and assess the diagnostic accuracy of the reamings in MBD. Method: Demographic details, clinical evaluation, radiological findings and the histology results of the bone biopsy or reamings were reviewed retrospectively for all patients admitted in the year 2003 with suspected MBD. Results:Records and x-rays were identified of 50 patients admitted in 2003 with suspected primary or MBD of a long bone and pain or pathological fracture. . 56% were male. Average age was 69.2years (range 10–98years). 6 patients had primary bone tumour and were referred to the tumour specialist. Of the remaining patients with suspected MBD all required fixation and in all cases intramedullary reamings were sent for histology. 18 patients had a known primary tumour of which 8 (44%) had no evidence of malignancy on histology. 22 patients had an unknown primary tumour of which 19 (86%) had no evidence of malignancy on histology. Conclusion: Reamings, are a poor method of diagnosis, even in cases where the primary is known the histology is still less than 50 % accurate in confirming malignancy. Therefore, in patients with MBD the diagnostic accuracy of reamings should be re-evaluated due to the high false negative results

The burden of metastatic bone disease (MBD) in our Canadian cancer population continues to increase. MBD has a significant effect on patient morbidity, mortality, and health-related quality of life (HRQOL). There are various technical options used to surgically stabilize MBD lesions, surgical decision-making is variable and largely dependent on anatomic and surgeon-based factors. There is a paucity of research examining how surgical decision-making for MBD can be modified or individualized to improve quality of life (QOL) and functional outcomes, while more accurately aligning with patient-reported goals and expectations. The objective of this study was tosurvey MBD patients, support persons, physicians, and allied health care providers (HCP) with the goal of identifying 1) important contributors to HRQOL, 2) discordance in peri-operative expectations, and 3) perceived measures of success in the surgical management of MBD. This project is a longitudinal patient-engaged research initiative in MBD. A survey was developed based on HRQOL themes in the literature and based on feedback from our patient research partners. Participants were asked to identify 1) important contributors to HRQOL and 2) perceived measures of success relevant to the surgical management of MBD. Participants were asked to rank themes from ‘extremely important’ to ‘not important at all’. Using open-ended questions, participants were asked to identify areas of improvement. Responses from the open-ended questions were analyzed by an experienced qualitative researcher using conventional content analysis. Participant's demographics were calculated using descriptive statistics. Concordance or discordance of perceived measure of success was assessed via a Chi-Square test of independence. All statistical analyses were performed using IBM SPSS® software. Nine patients, seven support persons, 23 orthopaedic surgeons, 11 medical oncologists, 16 radiation oncologists, 16 nurses, and eight physiotherapists completed the survey. Regarding perceived measures of success, increased life expectancy (p Two main themes emerged around the timeliness of surgical care and the coordination of multidisciplinary care from patients and support persons. Patients and support persons expressed a sense of urgency in progressing to surgery/treatment, and frustration at perceived delays in treatment. Within coordination of care, patients and support persons would like clearer communication from the health care team. There is discordance between patient/support person goals compared to physicians/HCP goals in the surgical management of MBD. Surgical decision-making and operative techniques that minimize disease progression and improve survival are important to MBD patients. Timely access to surgery/surgical consultation and improved multidisciplinary communication is important to patients. This data suggests improved peri-operative communication and education is needed for MBD patients. Furthermore, future research evaluating how modern orthopaedic surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients with MBD

Introduction: The rising incidence of metastatic bone disease (MBD) in the UK poses a significant management problem. Poorly defined levels of service provision have meant that improvements in patient prognosis have been mediocre at best. For that reason the British Orthopaedic Association (BOA) in conjunction with the British Orthopaedic Oncology Society (BOOS) issued guidelines in 2002 on good practice in the management of MBD. Despite the availability of these standards, there is very little robust data available for audit. The aim of this study was to conduct a regional survey of how these guidelines are being used in the management of MBD. Methods: A questionnaire was designed with 9 multiple choice questions representing the most common MBD scenarios. This was posted to 106 Consultant Orthopaedic Surgeons in 12 NHS Trusts in the South East of England. Results: The overall response rate to the questionnaire was 44%. There was considerable variation in the management of solitary femoral diaphyseal lesions, pathological subtrochanteric and intertrochanteric femoral neck fractures and vertebral metastases. Furthermore only 2 out of the 12 Trusts surveyed had a designated MBD lead as per the BOA/BOOS guidelines. Discussion: Our study reflects the variation in the management of MBD throughout the region, which may in turn be linked to poorer clinical outcomes. The results demonstrate the possibility of. inappropriate initial treatment,. subsequent late tertiary referral and. poor understanding of the biomechanical basis of orthopaedic implants, with the potential for inappropriate choice of prostheses and high failure rates. Streamlining cancer care will involve establishing regional MBD units within large centres where multidisciplinary services are available. Consequently all surrounding hospitals will need a designated MBD lead that can function as a conduit to this integrated care for selected patients

The management of pathological fractures due to Metastatic Bone Disease (MBD) and Primary Bone Tumours (PBTs) has implications for the Trauma service due to the extra pressures on staff, service delivery and budgets. We undertook an analysis of a cohort of patients presenting with MBD and PBTs. A retrospective chart review of all cases with MBD and PBTs admitted to a 40-bed Trauma Unit between 2005 and 2009 was conducted. The study looked at frequency, primary pathology, and site of pathology/fracture, time from primary diagnosis to referral, subsequent interventions and others. The results identified 34 patients, 21 females (62%) and 13 males (38%) (mean age: 64.6 years) with MBD or PBTs. Metastases secondary to breast cancer (n=13, 38%) and Myeloma (n=5, 15%) were the most common with the majority being found in the femur (n=22, 65%) and the Humerus (n=6, 18%). The mean time from primary tumour diagnosis to fracture referral was 29.6 months with 27 (79%) patients undergoing definitive surgical management within the unit. The conclusions of the study demonstrate that a wide variety of pathology presented to the unit over a 5 year period. Considerable variation was noted in the time from primary tumour diagnosis to presentation with a fracture. This could be due to improvements in treatments of specific cancers or a lack of understanding of what an Orthopaedic surgeon can offer the cancer patient. No definitive increase in pathological fractures was seen. The consensus opinion is that prompt and appropriate management of pathological fractures in cancer patients is cost effective. Management of these injuries, in a Trauma Unit, represents a small, but significant part of the annual work-load. While no significant trend has been seen, with respect to an increased incidence, it is noted that a proportion of these patients were a number of years from their initial diagnosis. With improvements in the survivorship of cancer patients, close scrutiny will be required to determine whether this ultimately translates into an increased fracture burden

Objectives

Guidelines for the management of patients with metastatic bone disease (MBD) have been available to the orthopaedic community for more than a decade, with little improvement in service provision to this increasingly large patient group. Improvements in adjuvant and neo-adjuvant treatments have increased both the number and overall survival of patients living with MBD. As a consequence the incidence of complications of MBD presenting to surgeons has increased and is set to increase further. The British Orthopaedic Oncology Society (BOOS) are to publish more revised detailed guidelines on what represents ‘best practice’ in managing patients with MBD. This article is designed to coincide with and publicise new BOOS guidelines and once again champion the cause of patients with MBD.

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.

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.

To assess the referral system, clinical notes and radiographs of patients presenting with metastatic disease of long bones in a regional oncology unit.

Thirty questionnaires were sent to oncologists asking about reasons for referral to orthopaedics and use of scoring system to assess risk of pathological fracture.

Ninety three percent of oncologists did not use a reliable scoring system to assess risk of pathological fracture. The majority referred in respect to pain on mobilising and the presence of a lytic lesion. Sixty percent felt an improvement in communication between the departments was required.

The notes and radiographs were reviewed of thirty-seven patients presenting with femoral metastatic lesions to the oncology department.

Sixteen patients had a Mirels score of greater than eight. Four patients were referred for an Orthopaedic opinion. All patients underwent prophylactic fixation. Twelve patients with a score of greater than eight were not referred. Seven of theses patients suffered a pathological fracture within three months.

Five patients had a Mirels score of 8. One patient had prophylactic fixation. No fractures occurred.

Sixteen patients had a Mirels score of less than 8. None of these patients were referred for an orthopaedic opinion. None of these patients had a pathological fracture within three months.

In conclusion, we presently do not offer a multidisciplinary approach to metastatic disease affecting the appendicular skeleton.

The majority of patients’ who score eight or above in the Mirels scoring system are at risk of fracture and do require prophylactic surgery.

In keeping with the BOA guidelines, “Metastatic Bone Disease: A Guide to Good Practice”, we would recommend that the introduction of a multidisciplinary approach and the use of a recognised scoring system is essential to improve patient care.

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 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.

Aims

The purpose of the study was to investigate whether closed intramedullary (IM) nailing with percutaneous cement augmentation is better than conventional closed nailing at relieving pain and suppressing tumours in patients with metastases of the femur and humerus.

Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease pathophysiology and novel advanced therapies is one of the major challenges that will predict more effectively and efficiently the clinical response. Preclinical traditional models have been largely used as they can provide standardization and simplicity, moreover, further advancements have been made with 3D cultures, by spheroids and artificial matrices, patient derived xenografts and microfluidics. Despite these models recapitulate numerous aspects of tumour complexity, they do not completely mimic the clinical native microenvironment. Thus, to fulfil this need, in our study we developed a new, advanced and alternative model of human breast cancer bone metastasis as potential biologic assay for cancer research. The study involved breast cancer bone metastasis samples obtained from three female patients undergoing wide spinal decompression and stabilization through a posterior approach. Samples were cultured in a TubeSpin Bioreactor on a rolling apparatus under hypoxic conditions at time 0 and for up to 40 days and evaluated for viability by the Alamar Blue test, gene expression profile, histology and immunohistochemistry. Results showed the maintenance and preservation, at time 0 and after 40 days of culture, of the tissue viability, biological activity, as well as molecular markers, i.e. several key genes involved in the complex interactions between the tumour cells and bone able to drive cancer progression, cancer aggressiveness and metastasis to bone. A good tis sue morphological and microarchitectural preservation with the presence of lacunar osteolysis, fragmented trabeculae locally surrounded by osteoclast cells and malignant cells and an intense infiltration by tumour cells in bone marrow compartment in all examined samples. Histomorphometrical data on the levels of bone resorption and bone apposition parameters remained constant between T0 and T40 for all analysed patients. Additionally, immunohistochemistry showed homogeneous expression and location of CDH1, CDH2, KRT8, KRT18, Ki67, CASP3, ESR1, CD8 and CD68 between T0 and T40, thus further confirming the invasive behaviour of breast cancer cells and indicating the maintaining of the metastatic microenvironment. The novel tissue culture, set-up in this study, has significant advantages in comparison to the pre-existent 3D models: the tumour environment is the same of the clinical scenario, including all cell types as well as the native extracellular matrix; it can be quickly set-up employing only small samples of breast cancer bone metastasis tissue in a simple, ethically correct and cost-effective manner; it bypasses and/or decreases the necessity to use more complex preclinical model, thus reducing the ethical burden following the guiding principles aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes; it can allow the study of the interactions within the breast cancer bone metastasis tissue over a relatively long period of up to 40 days, preserving the tumour morphology and architecture and allowing also the evaluation of different biological factors, parameters and activities. Therefore, the study provides for the first time the feasibility and rationale for the use of a human-derived advanced alternative model for cancer research and testing of drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses

Aims. Proximal femoral endoprosthetic replacements (PFEPRs) are the most common reconstruction option for osseous defects following primary and metastatic tumour resection. This study aimed to compare the rate of implant failure between PFEPRs with monopolar and bipolar hemiarthroplasties and acetabular arthroplasties, and determine the optimum articulation for revision PFEPRs. Methods. This is a retrospective review of 233 patients who underwent PFEPR. The mean age was 54.7 years (SD 18.2), and 99 (42.5%) were male. There were 90 patients with primary bone tumours (38.6%), 122 with metastatic bone disease (52.4%), and 21 with haematological malignancy (9.0%). A total of 128 patients had monopolar (54.9%), 74 had bipolar hemiarthroplasty heads (31.8%), and 31 underwent acetabular arthroplasty (13.3%). Results. At a mean 74.4 months follow-up, the overall revision rate was 15.0%. Primary malignancy (p < 0.001) and age < 50 years (p < 0.001) were risk factors for revision. The risks of death and implant failure were similar in patients with primary disease (p = 0.872), but the risk of death was significantly greater for patients who had metastatic bone disease (p < 0.001). Acetabular-related implant failures comprised 74.3% of revisions; however, no difference between hemiarthroplasty or arthroplasty groups (p = 0.209), or between monopolar or bipolar hemiarthroplasties (p = 0.307), was observed. There was greater radiological wear in patients with longer follow-up and primary bone malignancy. Re-revision rates following a revision PFEPR was 34.3%, with dual-mobility bearings having the lowest rate of instability and re-revision (15.4%). Conclusion. Hemiarthroplasty and arthroplasty PFEPRs carry the same risk of revision in the medium term, and is primarily due to acetabular complications. There is no difference in revision rates or erosion between monopolar and bipolar hemiarthroplasties. The main causes of failure were acetabular wear in the hemiarthroplasty group and instability in the arthroplasty group. These risks should be balanced and patient prognosis considered when contemplating the bearing choice. Dual-mobility, constrained bearings, or large diameter heads (> 32 mm) are recommended in all revision PFEPRs. Cite this article: Bone Joint J 2021;103-B(10):1633–1640

The August 2024 Research Roundup. 360. looks at: Effect of vitamin D deficiency on periprosthetic joint infection and complications after primary total joint replacement; Postoperative angiotensin receptor blocker use associated with decreased rates of manipulation under anaesthesia in patients undergoing total knee arthroplasty; Central sensitization: the missing link between psychological distress and poor outcome following primary total knee arthroplasty; Thromboprophylaxis for the trauma and orthopaedic surgeon; Life expectancy after treatment of metastatic bone disease: an international trend analysis

Aims. Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK. Methods. A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion. Results. A total of 846 patients with pelvic and appendicular MBD were analyzed, after excluding those with only spinal metastatic disease. A designated MBD lead was not present in 39% of centres (33/84). Adequate radiographs were not performed in 19% of patients (160/846), and 29% (247/846) did not have an up-to-date CT of thorax, abdomen, and pelvis to stage their disease. Compliance was low obtaining an oncological opinion (69%; 584/846) and prognosis estimations (38%; 223/846). Surgery was performed in 38% of patients (319/846), with the rates of up-to-date radiological investigations and oncology input with prognosis below the expected standard. Of the 25% (215/846) presenting with a solitary metastasis, a tertiary opinion from a MBD centre and biopsy was sought in 60% (130/215). Conclusion. Current practice in the UK does not comply with national guidelines, especially regarding investigations prior to surgery and for patients with solitary metastases. This study highlights the need for investment and improvement in care. The recent publication of British Orthopaedic Association Standards for Trauma (BOAST) defines auditable standards to drive these improvements for this vulnerable patient group. Cite this article: Bone Joint J 2023;105-B(10):1115–1122

Aims. Despite multiple trials and case series on hip hemiarthroplasty designs, guidance is still lacking on which implant to use. One particularly deficient area is long-term outcomes. We present over 1,000 consecutive cemented Thompson’s hemiarthroplasties over a ten-year period, recording all accessible patient and implant outcomes. Methods. Patient identifiers for a consecutive cohort treated between 1 January 2003 and 31 December 2011 were linked to radiographs, surgical notes, clinic letters, and mortality data from a national dataset. This allowed charting of their postoperative course, complications, readmissions, returns to theatre, revisions, and deaths. We also identified all postoperative attendances at the Emergency and Outpatient Departments, and recorded any subsequent skeletal injuries. Results. In total, 1,312 Thompson’s hemiarthroplasties were analyzed (mean age at surgery 82.8 years); 125 complications were recorded, necessitating 82 returns to theatre. These included 14 patients undergoing aspiration or manipulation under anaesthesia, 68 reoperations (5.2%) for debridement and implant retention (n = 12), haematoma evacuation (n = 2), open reduction for dislocation (n = 1), fixation of periprosthetic fracture (n = 5), and 48 revised stems (3.7%), for infection (n = 13), dislocation (n = 12), aseptic loosening (n = 9), persistent pain (n = 6), periprosthetic fracture (n = 4), acetabular erosion (n = 3), and metastatic bone disease (n = 1). Their status at ten years is summarized as follows: 1,180 (89.9%) dead without revision, 34 (2.6%) dead having had revision, 84 (6.6%) alive with the stem unrevised, and 14 (1.1%) alive having had revision. Cumulative implant survivorship was 90.3% at ten years; patient survivorship was 7.4%. Conclusion. The Thompson’s stem demonstrates very low rates of complications requiring reoperation and revision, up to ten years after the index procedure. Fewer than one in ten patients live for ten years after fracture. This study supports the use of a cemented Thompson’s implant as a cost-effective option for frail hip fracture patients. Cite this article: Bone Jt Open 2022;3(9):710–715

Osteoclasts (OCs) are multinucleated cells that play a pivotal role in skeletal development and bone remodeling. Abnormal activation of OCs contributes to the development of bone-related diseases, such as osteoporosis, bone metastasis and osteoarthritis. Restoring the normal function of OCs is crucial for bone homeostasis. Recently, RNA therapeutics emerged as a new field of research for osteoarticular diseases. The aim of this study is to use non-coding RNAs (ncRNAs) to molecularly engineer OCs and modulate their function. Specifically, we investigated the role of the microRNAs (namely miR-16) and long ncRNAs (namely DLEU1) in OCs differentiation and fusion. DLEU1/DLEU2 region, located at chromosome 13q14, also encodes miR-15 and miR-16. Our results show that levels of these ncRNA transcripts are differently expressed at distinct stages of the OCs differentiation. Specifically, silencing of DLEU1 by small interfering RNAs (siDLEU1) and overexpression of miR-16 by synthetic miRNA mimics (miR-16-mimics) led to a significant reduction in the number of OCs formed per field (OC/field), both at day 5 and 9 of the differentiation stage. Importantly, time-lapse analysis, used to track OCs behavior, revealed a significant decrease in fusion events after transfection with siDLEU1 or miR-16-mimics and an alteration in the fusion mode and partners. Next, we investigated the migration profile of these OCs, and the results show that only miR-16-mimics-OCs, but not siDLEU-OCs, have a lower percentage of immobile cells and an increase in cells with mobile regime, compared with controls. No differences in cell shape were found. Moreover, mass-spectrometry quantitative proteomic analysis revealed independent effects of siDLEU1 and miR-16-mimics at the protein levels. Importantly, DLEU1 and miR-16 act by distinct processes and pathways. Collectively, our findings support the ncRNAs DLEU1 and miR-16 as therapeutic targets to modulate early stages of OCs differentiation and, consequently, to impair OC fusion, advancing ncRNA-therapeutics for bone-related diseases. Acknowledgements: Authors would like to thank to AO CMF / AO Foundation (AOCMFS-21-23A). SRM and MIA are supported by FCT (SFRH/BD/147229/2019 and BiotechHealth Program; CEECINST/00091/2018/CP1500/CT0011, respectively)

The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs. . We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage. . Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease. Cite this article: Bone Joint J 2016;98-B:160–5

Metastatic bone disease (MBD) is a significant contributor to diminished quality of life in cancer patients, often leading to pathologic fractures, hypercalcaemia, intractable bone pain, and reduced functional independence. Standard of care management for MBD patients undergoing orthopaedic surgery is multi-disciplinary, includes regular surgical follow-up, case by case assessment for use of bone protective medications, and post-operative radiation therapy to the operative site. The number of patients in southern Alberta receiving standard of care post-operative management is currently unclear. Our aim is to develop a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD and to assess for deficiencies and opportunities to ensure standard of care for this complex patient population. Patients were identified for database inclusion by a search query of the Alberta Cancer Registry of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or pathologic fracture in the Calgary, South and Central Alberta Zones. Demographic information, primary cancer history, previous local and systemic treatments, anatomical location of MBD event(s), surgical fixation techniques, and post-operative care details were collected. The rate of standard of care post-operative treatment was evaluated. A comparison of outcomes between tertiary urban centres and rural centres was also completed. Survival was calculated from time of first operation to date of death. Univariate and multivariate analyses were performed to identify the impact of post-operative care variables on survival amongst patients surviving longer than one month. We identified 402 patients who have undergone surgical treatment for MBD in southern Alberta from 2006-2018. Median age at time of surgery was 66.3 years and 52.7% of patients were female. Breast, lung, prostate, renal cell and multiple myeloma were the most common primary malignancies (n=328, 81.6%). Median post-operative survival was 6.8 months (95%CI: 5.7-8.3). 203 patients (52.5%) were treated with post-operative radiotherapy and 159 patients (50.8%) had post-operative surgical follow-up. Only 39 patients (11.3%) received bone protective agents in the peri-operative period. On multivariate survival analysis, post-operative surgical follow-up was associated with improved survival (p<0.001). Patients were treated at nine hospitals across southern Alberta with most patients treated in an urban center (65.9%). Post-operative survival was significantly longer amongst patients treated in an urban center (9.0 months, 95%CI: 6.9-12.3 versus 4.3 months, 95%CI: 3.4-5.6, p<0.001). The burden of MBD is significant and increasing. With treatment occurring at multiple provincial sites, there is a need for standardized, primary disease-specific peri- and post-operative protocols to ensure quality and efficacious patient care. To provide evidence informed treatment recommendations, we have developed a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD. Our results demonstrate that many patients were not treated according to post-operative standard of care recommendations. Notably, half of the included patients did not have documented surgical follow-up, post-operative radiation treatment was low and only 11% were actively treated with bone protective agents. This data justifies the need for established surgical MBD care pathways and provides reference data to benchmark prospective QA and QI outcomes in this patient population

The aim of this study was to evaluate whether duration of surgery correlates with the survival and final outcome of the patient with metastatic bone disease. Between 1999 and 2002, 23 consecutive patients with impending or complete pathological fractures of the femur due to metastatic bone disease caused by variety of malignancies or an unknown primary were reviewed. These fractures were treated with intramedullary fixation in the form of long intramedullary hip screw, long Gamma nail or AO nail. These patients were followed up clinically and radiologically until death from the primary disease. The results obtained demonstrate a mean survival time between 9 days to 12 months. Pain relief was achieved in 90% patients. Ambulatory status was improved in 47% patients. The postoperative course was complicated by four technical and five systemic complications. Intramedullary nailing is a safe and effective method in the treatment of metastatic bone disease. It provides good functional result with pain relief and improved mobility. The operating time does not predictably correlate with the survival and final outcome of the patient

Introduction: Breast cancer is the most frequently diagnosed cancer in western countries and bone metastases of breast cancer cause significant morbidity. Tumor growth and progression requires the formation of new blood vessels, a process called angiogenesis. Angiogenesis is a complex multifactorial process involving a variety of proangiogenic and proteolytic enzyme activators and inhibitors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF), which is overexpressed in several tumor tissues. The single nucleotide polymorphism 1498 C/T of VEGF was associated with increased plasma levels of VEGF. In this case controlled study, we analyzed the role of this polymorphism in bone metastasis of breast cancer. Material and Methods: We genotyped 839 female breast cancer patients. The study was performed according to the Austrian Gene Technology Act and has been approved by the Ethical Committee of the Medical University Graz. According to breast cancer staging, patients were divided in three groups, representing patients without metastases (n = 708), those with metastases other than bone (n = 69), and those with bone metastasis (n = 62). Results: Frequency of the 1498 CC genotype of VEGF was significantly lower among patients with bone metastases (6.5%) than among those with other metastases (23.2%; p=0.005) or no metastases (23.4%; p=0.002). Odds ratio of the CC genotype for bone metastases was 0.22 (95% CI 0.08 – 0.61; p = 0.004). Conclusion: We conclude that the homozygous 1498 C genotype of VEGF may be protective against development of bone metastasis in breast cancer patients

Prophylactic treatment is advised for metastatic bone disease patients with a high risk of fracture. Clinicians face the task of identifying these patients with high fracture risk and determining the optimal surgical treatment method. Subject-specific finite element (FE) models can aid in this decision process by predicting the mechanical effect of surgical treatment. In this study, we specifically evaluated the potential of FE models to simulate femoroplasty, as uncertainty remains whether this prophylactic procedure provides sufficient mechanical strengthening to the weight-bearing femur. In eight pairs of human cadaveric femurs artificial metastatic lesions were created. In each pair, an identical defect was milled in the left and right femur. Four pairs received a spherical lesion in the neck and the other four an ellipsoidal lesion in the intertrochanteric region, each at the medial, superior/lateral, anterior and posterior side, respectively. One femur of each pair was augmented with polymethylmethacrylate (5–10 ml), while the contralateral femur was left untreated. CT scans were made at three different time points: from the unaffected intact femurs, the defect femurs with lesion and the augmented femurs. Bone strength was measured by mechanical testing until failure in eight defect and eight augmented femurs. Nonlinear CT-based FE models were developed and validated against the experimentally measured bone strength. Subsequently, the validated FE model was applied to the available CT scans for the three different cases: intact (16 scans), defect (16) and augmented (8). The FE predicted strength was compared for the three different cases. The FE models predicted the experimental bone strength with a strong correspondence, both for the defect (R. 2. = 0.97, RMSE= 0.75 kN) and the augmented femurs (R. 2. = 0.90, RMSE = 0.98 kN). Although all lesions had a “moderate” to “high” risk for fracture according to the Mirels’ scoring system (score 7 or 8), three defect femurs did not fracture through the lesion (intertrochanteric anterior, lateral and posterior), indicating that these lesions did not act as a critical weak spot. In accordance with the experimental findings, the FE models indicated almost no reduction in strength between the intact and defect state for these femurs (0.02 ± 0.1%). For the remaining “critical” lesions, bone strength was reduced with 15.7% (± 14.9%) on average. The largest reduction was observed for lesions on the medial side (up to 43.1%). For the femurs with critical lesions, augmentation increased bone strength with 29.5% (± 29.7%) as compared to the defect cases, reaching strength values that were 2.5% (± 3.7%) higher than the intact bone strength. Our findings demonstrate that FE models can accurately predict the experimental bone strength before and after augmentation, thereby enabling to quantify the mechanical benefit of femoroplasty. This way FE models could aid in identifying suitable patients for whom femoroplasty provides sufficient increase in strength. For all lesions evaluated in this study, femoroplasty effectively restored the initial bone strength. Yet, additional studies on larger datasets with a wide variation of lesion types are required to confirm these results

National guidelines recommend that trauma centres have a designated consultant for managing metastatic bone disease (MBD). No such system exists in Scotland. We compared MBD cases in a trauma hospital to a national bone tumour centre to characterise differences in management and outcome. Consecutive patients with metastatic proximal femoral lesions referred to a trauma unit and a national sarcoma centre were compared over a seven-year period (minimum follow-up one year). From Jan 2010-Dec 2016, 195 patients were referred to the trauma unit and 68 to the tumour centre. The trauma unit tended to see older patients (mean 72 vs. 65 years, p<0001) with cancers of poorer prognosis (e.g. 31% 61/195 vs. 13% 9/68 lung primary, p<0.001). Both units had similar operative rates but patients referred to the tumour centre were more likely to have endoprosthetic reconstruction (EPR 44% tumour vs. 3% trauma centre, p<0.001). Patients with an EPR survived longer than those with other types of fixation (81% 17/21 vs. 31% 35/112 one-year survival, p<0.001). Patients undergoing EPR were more likely to have an isolated metastasis (62% 13/21 vs. 17% 4/24, p<0.001). One patient from each centre had a revision for failed metalwork. There was a difference in caseload referred to both units, with the tumour centre seeing younger patients with a better prognosis. Patients suitable for endoprostheses were more likely to have isolated metastatic disease and a longer survival after surgery. An MBD pathway is required to ensure such patients are identified and referred for specialist management where appropriate

Vertebral fracture due to a metabolic bone disease or a neoplastic disease is a common and debilitating condition. It most often is associated with either osteoporosis or metastatic bone disease. Some of the patients suffering from such fractures continue to complain of back pain and deformity despite optimal medical therapy, including radiotherapy and biphosphonates. Vertebroplasty, i.e. transcutaneous injection of bone cement into the vertebral body can serve as an internal fixation device and allows restoration of mechanical strength and partial restoration of the vertebral height. During the year 2000, 17 vertebrae in 12 patients were injected. These were either lumbar or thoracic vertebrae. All patients reported decrease in pain and improved ambulation capacity. Two minor complications were encountered including headache lasting for 72 hours prior to spontaneously resolving. This possibly indicates a transarachnoidal approach, the other complication has been cement leak below the posterior longitudinal ligament. The patient reported pain amelioration. No emergency surgical interventions were necessary to date. Treatment of metastatic bone disease should be staged, with only a few vertebrae injected in each session, to prevent pulmonary embolization. Vertebroplasty appears to allow excellent palliative treatment in patients suffering from unresectable primary tumors of the vertebrae, or more commonly, metastatic bone tumors as well as osteoporotic fractures

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This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection.

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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.

Introduction: Current guidelines from the British Orthopaedic Oncology Society indicate that the role of the orthopaedic surgeon in the management of the meta-static bone disease (MBD) of the long bones falls into two principal categories; prophylactic fixation of meta-static deposits at risk of fracture and stabilisation following pathological fractures. Bone biopsy and MRI scan is advocated if the primary tumour is not identified. Aim: The aim of this study is to audit at the current practice in the South Trent region. Method: A postal questionnaire with three case scenarios was sent to all orthopaedic consultants and SpR’s in the South Trent region. They were asked how they would manage a patient with a fracture and; a single bone metastasis and a known primary tumour, a single bone metastasis and an unknown primary tumour, and multiple metastases of unknown origin. Results: 80 % of the questionnaires were completed and returned. In the presence of a known primary tumour and a single metastasis, 75 % would send intra-medullary reamings for histology at the time of fixation. In the presence of a single metastasis and an unknown primary tumour, 38 % would perform a biopsy prior to fracture fixation. In the event of multiple metastases with an unknown primary, 15 % would perform a biopsy. Conclusion: There is a lack of consensus among the orthopaedic surgeons sampled about the management of the MBD. Intramedullary reamings sent during fixation have a high rate of false negative results but are still preferred by many surgeons to aid diagnosis in MBD. Thorough clinical and radiological assessments are probably more useful in the diagnosis of the primary tumour

Purpose. Versican is a member of the large aggregating chondroitin sulfate proteoglycan family. Structurally, it is made up of an N-terminal G1 domain, a glycosamingoglycan attachment region, and a C-terminus containing a selectin-like (G3) domain. Versican is highly expressed in the interstitial tissues at the invasive margins of breast carcinoma and predictive of relapse and overall survival. The purpose of the study to investigate the role of of versican G3 domain in breast cancer bone metastasis. Method. Mouse mammary tumor cell lines 66c14, 4T07 and 4T1, and human breast cancer cell lines MT-1, MDA-MB-468 and MDA-MB-231 were stably transfected with versican G3. Effects of expression of versican G3 on cell proliferation, migration, invasion, cell cycle progression, and EGFR signaling were observed. The effects of G3 on cell viability in the conditional media of serum free, apoptotic agent C2-ceramide, and chemotherapeutic agents, including Docetaxel, Doxorubicin, Epirubicin were investigated. Colony formation assay and mammosphere formation assay were performed. A syngeneic orthotopic animal model was used to do the in vivo study. Results. In vitro, G3 enhanced breast cancer cell proliferation and migration by up-regulating EGFR signaling, and enhanced cell motility through chemotactic mechanisms to bone stromal cells, which was prevented by inhibitor AG 1478. Experiments in a syngeneic orthotopic animal model demonstrated that G3 promoted tumor growth and bone metastasis in vivo. Versican G3 domain enhanced tumor cell resistance to apoptosis in serum free medium, Doxorubicin, or Epirubicin by up-regulating pERK and GSK-3β (S9P), and promoted cell apoptosis induced by C2-ceramide or Docetaxel by enhanced expression of pSAPK/JNK and decreased GSK-3β (S9P). Versican expresses highly in the breast cancer mammosphere progenitor cells. Expression of versican G3 enhanced breast cancer self-renewal in vitro and in vivo. Conclusion. The activity of G3 on mouse mammary tumor cell growth, migration and its effect on spontaneous metastasis to bone in an orthotopic model was modulated by up-regulating the EGFR-mediated signaling. The dual roles of G3 in modulating breast cancer cell resistance to chemotherapeutic agents indicate a potential mechanism for breast cancer cell sensitivity or resistance to chemotherapy and EGFR therapy. GSK-3β (S9P) works as a key check point for the balance of apoptosis and anti-apoptosis. Over-expression of versican G3 domain enhanced breast cancer self-renewal, and resistant to chemo-drug treatments. Strategies designed to target versican mediated breast cancer self-renewal or GSK-3β (S9P) may lead to an effective therapy benefiting advanced breast cancer patients

Purpose: To determine the surgical and functional outcome of an anatomically based approach to hip reconstruction for metastatic bone disease. Methods: Records of 123 consecutive patients who underwent hip arthroplasty for metastatic bone disease were reviewed. Sixty one patients (63 hips) had pelvic involvement that required periacetabular reconstruction. Sixty two patients (64 hips) had proximal femoral involvement but no acetabular disease. Operative technique was guided by the extent of column and dome disease in addition to the extent of involvement of the femur. Demographic variables, functional data (ECOG scores) and survival data were analyzed. Results: : The cohort included 94 females and 29 males, mean age 62 years (range, 39–85). Breast, lung and kidney were the most common primary sites. The average time from initial primary diagnosis to surgery was 42 months. The average time from initial primary diagnosis to surgery was significantly longer for those with breast cancer compared to those with other primary sites (65 vs. 21 months, P< 0.001). Average blood loss was 788 ml (range, 200–3800 ml) and average operative time was 2.3 hours (range, 2–6 hours). There were three perioperative deaths. Functional scores improved from an average of 2.7 preoperatively to 1.4 postoperatively (P< 0.05). Two patients required closed reduction, two required open trochanteric repair and one required ace-tabular revision. Median survival time was 15 months (range, 0–172 months). Patients with breast cancer enjoyed longer survival compared to patients with other primaries (21 vs. 9 months, P=0.02). Conclusions: Despite the moderate risk of operative complications, an anatomically based approach to reconstruction of metastatic hip disease is effective in improving functional outcome and quality of life in many patients

Purpose: We report a series of 58 patients with metastatic bone disease treated with resection and endoprosthetic reconstruction over a 5 year period at our institution. Introduction: The recent advances in adjuvant and neo-adjuvant therapy in cancer treatment has resulted in improved prognosis of patients with bone metastases. Most patients who have an actual or impending pathological fracture should have operative stabilisation or reconstruction. According to BOA guidelines patients should undergo a single procedure which allows early full weight bearing and lasts the expected lifespan of the patient. The use of modern modular endoprostheses allows these criteria to be met. Methods and Results: We retrospectively identified all patients diagnosed with metastatic disease to bone between 1999 to 2003. 171 patients were diagnosed with bone metastases. Metastatic breast and renal cancer accounted for 47% of the lesions. 58 patients with bone metastasis to the appendicular skeleton had an endo-prosthetic reconstruction. There were 28 males and 30 females. 11 patients had lesions in the upper extremity and 47 patients had lesions in the lower extremity. Mean age at presentation was 62 years (24 to 88 years). 19 patients are still alive, 34 patients had died and 5 were lost to follow-up. Patients died of disease at a mean of 22 months (2 to 51 months) from surgery. Mean follow-up was 55 months (24 to 78 months). There were 5 wound infections, 1 aseptic loosening, 3 dislocations, 1 subluxation and 1 prosthesis rotated requiring open repositioning. Patients were followed up and evaluated using the Musculoskeletal Society Tumour Score (MSTS) and the Toronto Extremity Salvage Score. The mean MSTS score was 73% (57 to 90%) and TESS was 71% (84 to 95%). Conclusions: We conclude that endoprosthetic replacement for the treatment of bone metastases in selected cases achieves the aims of restoring function, allowing early weight bearing and alleviating pain. The complication rate is low

The purpose of this study was to analyse the long-term results of prosthetic joint replacement in patients suffering from metastatic bone disease. The treatment was performed in order to prevent or treat pathological fractures, to control the pain and improve the functionality of the lower limb. 120 patients suffering from metastatic disease of the lower extremities were treated with prosthetic replacement between 1992 and 2004. The patients, 80 females and 40 males, having an age at the time of surgery ranging from 32 to 83 years, were treated by the same equipe in the San Raffaele Hospital in Milan. The primary tumor included breast carcinoma (66), lung carcinoma (19), kidney tumor (17), prostatic tumor (7), plasmocytoma (5), non identified tumor (5), melanoma (1). The metastasis was located in the proximal femur in 112 cases, in the distal femur in 3, in proximal tibia in 5. In 8 out of 120 patients, the metastatic lesion was the first sign of carcinoma, 25 patients had a pathological fracture and the bone metastases were detected from 6 mounth to 13 years after the diagnosis of the primary tumor. Knee: in our casuistry 8 patients with a metastasis in proximal tibia or distal femur were operated with modular prostheses: in 1 case of this group (single lesion of kidney tumor), we have implanted an allograft-prosthesis-composite. Proximal femur: for the treatment of this site, we have included also those patients having a life expectancy inferior to 1 month. In 30 cases the lesion was located in the epiphysis and neck and we have implanted 5 endoprosthesis, 5 total hip prostheses and 20 bipolar prostheses. In 82 patients with a metastasis located in the metaphysis we used a modular prosthesis with a femoral resection up to 16 cm. 69 patients are alive with a follow-up ranging from 6months to 12 years. 5 patients died in early post surgical period. 13 patients developed local recurrence. These latest have suffered from a pathological fracture, which had occurred before the first surgical treatment. Pain relief was achieved in all patients after surgery with acceptable functionality of the operated limb. We considered the risk of pathological fractures more important than life expectancy. Moreover, we believe that the surgery to these patients should be definitive. In fact, the use of prostheses allow for a wide resection of the lesion. This condition represents also an advantage in those cases where radio- or chemiotherapy can not be performed. Moreover, the prostheses permit an immediate weight bearing, a good functional recovery and also, in patients with critical general condition, a more easy assistance. In conclusion, for patients with metastatic bone disease, we consider a correct approach the radical excision of the lesion and the implant of a prosthesis

Introduction and Objectives: Half of primary tumors tend to disseminate to bones, and metastasis to bone is the third most common localisation for disseminated disease, after the lungs and liver. It is also the most common form of neoplasia in the skeleton. Treatment of bone metastasis is essentially palliative, and in select cases improves patient survival. We present results from the last 15 years in our centre. Materials and Methods: Between the years 1988–2003, our surgical oncology unit has treated 451 patients with bone metastasis. Of these, 49% were male, and 51% were female. Average age was 64 years (19–98). The most common causes were metastatic breast cancer (34%), unknown tumours (17%), multiple myeloma (9%), prostate cancer (9%), lung cancer (7%), bladder cancer (6%), and others (18%). Tumours localised to the following locations: femur (31%), spine (27%), multiple locations (13%), pelvis (11.5%), humerus (9%), and other locations (8.5%). In 69% of cases the first symptom was pain, in 28% pathologic fracture, and in the remaining 3% medullary compression. Of the 125 pathologic fractures, 71% were on the femur, 18% on the humerus, and the remaining 11% in other locations. Results: In 60% of cases (271 patients) conservative treatment was used, and in the remaining 40% (180 patients) surgical treatment was used. Of the 180 surgeries, 50.5% were for pathologic fractures, and 49.5% were prophylactic surgeries. Of the 125 pathologic fractures, 91 (73%) received surgical treatment, and the other 34 (27%) were treated conservatively. Intramedullary nailing was the most commonly used form of osteosynthesis (47%). Total resolution of pain was achieved in 86.5% of cases, and partial resolution in 13.5%. Mean time in bed from prophylactic surgery was 3 days. Mean time for recovery of function was 7 days for the arms and 11 days for the legs. Discussion and Conclusions: The fundamental goal is to offer short-term individualized treatment to control pain and avoid bedrest and hospitalization of these patients. Prophylactic surgery does not increase life expectancy of these patients. However, it does alleviate pain, avoids bedrest, and improves functionality. It should be kept in mind that the least aggressive surgical technique possible should be used

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).

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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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The aim of this study was to investigate the feasibility of application of a 3D-printed megaprosthesis with hemiarthroplasty design for defects of the distal humerus or proximal ulna following tumour resection.

Background. Metastatic bone patients who require surgery needs to be evaluated in order to maximise quality of life and avoiding functional impairment, minimising the risks connected to the surgical procedures. The best surgical procedure needs to be tailored on survival estimation. There are no current available tool or method to evaluate survival estimation with accuracy in patients with bone metastasis. We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on . www.PATHFx.org. , we attempted to externally validate it using independent, international data. Methods. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2008 and 2012, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). Results. The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. Conclusions. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied

Background. Metastatic bone patients who require surgery needs to be evaluated in order to maximise quality of life and avoiding functional impairment, minimising the risks connected to the surgical procedures. The best surgical procedure needs to be tailored on survival estimation. There are no current available tool or method to evaluate survival estimation with accuracy in patients with bone metastasis. We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on . www.PATHFx.org. , we attempted to externally validate it using independent, international data. Methods. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2008 and 2012, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). Results. The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. Conclusions. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied. Level of Evidence. IV. None of the authors have financial disclosures or conflicts of interest to declare. The study presented did not need the approval by ethics committee

The February 2024 Oncology Roundup³⁶⁰ looks at: Does primary tumour resection improve survival for patients with sarcomas of the pelvis with metastasis at diagnosis?; Proximal femur replacements for an oncologic indication offer a durable endoprosthetic reconstruction option: a 40-year experience; The importance of awaiting biopsy results in solitary pathological proximal femoral fractures: do we need to biopsy solitary pathological fractures?; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 extremity soft-tissue sarcoma patients; What to choose in bone tumour resections? Patient-specific instrumentation versus surgical navigation; Optimal timing of re-excision in synovial sarcoma patients: immediate intervention versus waiting for local recurrence; Survival differences of patients with resected extraskeletal osteosarcoma receiving two different (neo) adjuvant chemotherapy regimens; Solitary versus multiple bone metastases in the appendicular skeleton: should the surgical treatment be different?.

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The aim of this study was to determine the prevalence and impact of tourniquet use in patients undergoing limb salvage surgery with endoprosthetic reconstruction for a tumour around the knee.

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The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition.

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Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee.

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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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Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas.

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The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.

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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.

Photodynamic therapy (PDT) uses the strong cytotoxicity of singlet oxygen and hyperthermia produced by irradiating excitation light on a photosensitizer. The phototoxic effects of indocyanine green (ICG) and near-infrared light (NIR) have been studied in different types of cancer cells. Plasma proteins bind strongly to ICG, followed by rapid clearance by the liver, resulting in no tumor-selective accumulation after systemic administration. Kimura et al. have proposed using a novel nanoparticle labeled with ICG (ICG-lactosome) that has tumor selective accumulation owing to enhanced permeability and retention (EPR) effect. In this study, we investigated the efficacy of PDT using ICG-lactosome and NIR for a bone metastatic mouse model of breast cancer. Cells from the human breast cancer cell line, MDA-MB-231 were injected into the right tibia of 26 anesthetized BALB/C nu/nu mice at a concentration. The mice were then randomly divided into three groups: the PDT group (n = 9), the laser (laser irradiation only) group (n = 9), and the control group (n = 8). PDT was performed thrice (7, 21, 35 days after cell inoculation) following ICG-lactosome administration via the tail vein 24 hours before irradiation. The mice were percutaneously irradiated with an 810-nm medical diode laser for 10 min. In the laser group, mice were irradiated following saline administration 24 hours before irradiation. Radiographic analysis was performed for 49 days after cell inoculation. The area of osteolytic lesion was quantified. The right hind legs of 3 mice were amputated 24 hours after the third treatment. Histological analysis was performed using hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining of sagittal sections. The data was analyzed using Tukey-Kramer post-hoc test. P-value of <0.05 was considered significant. X-ray on day 49 of the three groups are considered. The area of osteolytic lesion in the PDT group (7.9 ± 1.2 mm. 2. : mean ± SD) was significantly smaller than that of the control (11.4 ± 1.4 mm. 2. ) and laser (11.9 ± 1.2 mm. 2. ) groups. In histological findings, we observed many TUNEL-positive cells in the metastatic tissue 24 hours after PDT. In the control and laser groups, TUNEL-positive cells were occasionally observed. We have previously reported the effect of ICG-lactosome-enhanced PDT on the cytotoxicity of human breast cancer cells in vitroand on the delay of paralysis in a rat spinal metastasis model. In this study, we demonstrated the inhibitory effect of ICG-lactosome-enhanced PDT on bone destruction caused by human breast cancer cells in vivo. This PDT induced apoptosis and necrosis in the tumor cells. Intralesional resection is often performed for spinal metastases in an emergency. The residual tumor may regrow and cause neurological deficits. We believe that ICG-lactosome-enhanced PDT can decrease the rate of local recurrence through reduction of the residual tumor. PDT with ICG-lactosome and NIR had an inhibitory effect on the growth of bone metastasis of a human breast cancer

Periarticular metastasis may be treated with endoprosthetic reconstruction. The extensive surgery required may not, however, be appropriate for all patients. Our aim was to establish if the outcome of locking plate fixation in selected patients with periarticular metastases. Prospective data collection was performed. Twenty one patients underwent surgery for periarticular metastatic tumours. The median duration of follow-up for surviving patients was one year. There have been no cases of implant failure and no requirement for revision surgery. Pain relief was excellent or good in the majority of patients. Patients who had sustained a fracture prior to fixation had restoration of their WHO performance status. All patients had a dramatic improvement in their MSTS scores. The median pre-operative score was 15% (0%-37%) improving to a median score of 80% (75% -96%) post operatively. Locking plates provide reliable fixation and excellent functional restoration in selected patients suffering from periarticular metastatic bone disease

To document early in-vivo concentrations of gentamicin in plasma and drain fluid after bone defect reconstruction using a gentamicin-eluting bone graft substitute. Introduction. Reconstruction of bone defects after surgical bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent bone defect reconstruction with a gentamicin-eluting bone graft substitute (CERAMENT™|G – BONESUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting bone graft substitute was used, either alone or in combination with cancellous allograft and/or a bone graft substitute not containing gentamicin (CERAMENT™|BVF – BONESUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2. Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting bone graft substitute for bone defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations

Demographics changes and the increasing incidence of metastatic bone disease are driving the significant issues of vertebral body (VB) fractures as an important consideration in the quality of life of the elderly. Whilst osteoporotic vertebral fractures have been widely studies both clinically and biomechanically, those fractures arising from metastatic infiltration in the spine are relatively poorly understood. Biomechanical in-vitro assessment of these structurally weaker specimens is an important methodology for gaining an understanding of the mechanics of such fractures in which a key aspect is the development of methodologies for predicting the failure load. Here we report on a method to predict the vertebral strength by combining computed tomography assessment with an engineering beam theory as an alternative to more complex finite element analyses and its verification within a laboratory scenario. Ninety-two human vertebral bodies with 3 different pathologies: osteoporosis, multiple myeloma (MM) and specimens containing cancer metastases were loaded using a define protocol and the failure loads recorded. Analysis of the resulting data demonstrated that the mean difference between predicted and experimental failure loads was 0.25kN, 0.41kN and 0.79 kN, with adjunct correlation coefficients of 0.93, 0.64 and 0.79 for osteoporotic, metastatic and MM VBs, respectively. Issues in predicting vertebral fracture arise from extra-vertebral bony formations which add to vertebral strength in osteoporotic VB but are structurally incompetent in metastatic disease. The methodology is currently used in providing better experimental design/benchmarking within in-vitro investigations together with further exploration of its utility in the clinical arena

Metastatic bone disease is increasing in association with ever improving medical management of osteophylic malignant conditions. The precise timing of surgical intervention for secondary lesions in long bones can be difficult to determine. This paper aims to validate a classic scoring system. All radiographs were examined twice by 3 orthopaedic oncologists and scored according to the Mirels’ scoring system. The Kappa statistic was used for the purpose of statistical analysis. The results show agreement between observers (κ=0.35–0.61) for overall scores at the 2 time intervals. Inter-observer agreement was also seen with subset analysis of size (κ=0.27–0.60), site (κ=0.77–1.0) and nature of the lesion (κ=0.55–0.81). Similarly, low levels of intra-observer variability were noted for each of the 3 surgeons (κ=0.34, 0.39, 0.78 respectively). These results validate the Mirels’ scoring system across a wide spectrum of malignant pathology. We continue to advocate its use in the management of patients with long bone metastases

Purpose: estimate efficiency minimally invasive methods of treatment at patients with tumor lesion of bones. Materials and methods: 145 patients, middle age e 42 years. it has been executed 249 percutaneous vertebroplasty, 15 osteoplasty and 46 radiofrequency thermal ablation Most often minimally invasive methods were carried out to patients with bone metastasis lesion of a breast cancer – 65 (44,8%) and kidneys – 14 (10%) patients. Results: reduction in a painful syndrome on a visual analog scale after operation is noted at 126 (87%) by patients. Positive dynamics Watkins scale at 119 (82%). Improvement of quality of a life on scale Karnofski at 94 (65%) the patient. Complications after vertebroplasty and osteoplasty in the form of methylmethacrylate leak into the surrounding tissues at 19 (18,5%) patients. At one patient after radiofrequency thermal ablation has developed burn skin. There were three pathological bone fractures after radiofrequency thermal ablation. Conclusions: vertebroplasty, osteoplasty and radiofrequency thermal ablation – minimally invasive methods of treatment the patients with tumoral lesion of the bones, allowing in short tim stop a painful syndrome, create adequate stability in a bone segment and improve quality of a life of oncological patients

Introduction. We aimed to determine the extent of osseous integration of the hydroxyapatite collars of tumour endoprostheses implanted in our unit. Methods. We identified 57 patients who had massive endoprostheses implanted over the last six years and reviewed clinical records and x-rays. There were 20 proximal femoral, 23 distal femoral, 6 proximal tibial, 8 proximal humeral and 1 distal humeral replacements. Patients fell into three groups: 1.Primary bone tumours, 2. Metastatic bone tumours and 3. Non-tumour indications. Results. There were 32 patients in Group 1. Mean age 32(10-71) years. Mean follow up was 22 (12-60) months. Osseous integration of the collars was noted in 19 patients (60%). Eight patients had no bony ongrowth on the collars. Nine patients underwent revision, seven for aseptic loosening and one for infection. There were 23 patients in Group 2. Mean age 72(45-83) years. The primary tumour was lung in four and renal in three. One patient had bilateral surgery. Mean follow up was 6(4-9) months. One prosthesis required revision for aseptic loosening in spite of showing good growth over the collar. True osseous integration of the collar occurred only in one patient. There were two patients in Group 3: one with a distal femoral fracture non union who demonstrated good integration of the collar. The other had a revision for infected total hip replacement with no osseous integration. Discussion. Hydroxyapatite coated collars may help integration of massive endoprostheses, but ongrowth is not always seen. Integration is best after resection of primary bone tumours. Their role in metastatic tumour surgery is questionable

Vertebroplasty has been developed during the last decade in France as a method to relieve pain in patients suffering from a metastatic disease of the spine, that are poor surgical candidates. The indications include: mechanical pain, compression fractures, lytic bone metastasis. Contra-indications include neurological compromise, breaching of the posterior wall, complete pedicle destruction or a large anterior soft-tissue mass. Relative contra-indications include a single resectable metastasis and a radiation sensitive tumor. The method has been refined during the last few years by the introduction of specialized delivery systems and tailor-made bone cements. The state of the art of this emerging technique will be discusses as well as some exciting future developments such as cements that can actively destroy tumors by physical or chemical modifications

Cementoplasty, like vertebroplasty, is a technique whereby Polymetylmethacrylate is placed into a bone lesion either percutaneouly or by surgery under image intensifier guidance. Although there have been few studies with regard to cementoplasty percutaneously, there is no series in the literature to support the open surgical technique as a palliative procedure. In our series we describe four patients (1male and 3 females, age range 63-83) with metastatic bone cancer who have benefited from an open surgical procedure. The four patients presented to our hospital between January 2004 and December 2006. They all had gradually worsening hip pain at the time of presentation and pelvic radiographs revealed osteolytic lesions in the acetabulum. A 5 centimetre longitudinal incision proximal to the greater trochanter was made and the malignant lesion identified using the image intensifier. The malignant tissue was curetted and sent for microscopy, culture, sensitivity and histopathology and the remaining void filled with bone cement (via a gun or by hand) under x-ray control. Radiographs were taken in all patients post-operatively and were referred for adjuvant radiotherapy. All patients had immediate relief of pain and were able to mobilise within 48 hours. Two patients died within 6 weeks post-operatively due to complications from their primary malignancy (lung). One patient died at three months due to unknown primary. One patient remained pain free and fully ambulatory at one and a half years post surgery (breast primary). This procedure can be recommended for patients with metastatic bone disease as it provides adequate pain control and improves the quality of life in this group of patients. These patients need a multi-disciplinary approach to their care, but as orthopaedic surgeons, we can make a significant impact to such patients and their families

Introduction. Aseptic loosening is the most common mode of failure of massive endoprostheses. Introduction of Hydroxyapatite coated collars have reduced the incidence of aseptic loosening. However bone growth is not always seen on these collars. Objectives. The aims of our study were to determine the extent of osseous integration of Hydroxyapatite coated collars, attempt a grading system for bone growth and to determine the effect of diagnosis, surgical technique and adjuvant therapy on bone growth. Methods. We reviewed the records and radiographs of 58 patients who had a massive endoprosthesis implanted by two surgeons in our unit over the last five years. Revision surgeries were recorded separately. Bone growth was graded 1–4 based on appearance in antero-posterior and lateral radiographs. Results. Three groups were identified. Group 1-Resections for primary bone tumours (33 patients), Group 2-resections for metastatic bone disease (22 patients) and Group 3- Resections for non tumour indications (3 patients). Overall, 60% of patients had grade 1, 12% had grade 2, 19% had grade 3 and 9% had grade 4 osteointegration. Grade 3 or 4 Collar osteointegration was found in 37% of patients in Group 1, 9% in group 2 and 67% in group 3. 5% of patients with grade 1 integration, 100% patients with grade 2 integration and none of the patients with grade 3 or 4 integration underwent revision for aseptic loosening. Appearance or widening of a gap between the resected bone end and the collar indicated loosening and impending revision. Proximal humeral replacements had the lowest rate of osteointegration (12%). Adjuvant therapy did not affect osteointegration. Conclusion. Osteointegration of collars is seen more often after resection of primary bone tumours. The role of collars in metastatic tumour surgery is questionable. Our radiographic grading system of bone growth predicted aseptic loosening

All patients referred to our unit with previously untreated metastatic renal cancer were included in this review. We investigated likely prognostic factors including age, sex, site, synchronous or metachronous metastasis, stage of the disease and the type of treatment received. From 1976 until 2004, a total of 198 patients were treated by our unit for renal metastases. 15 patients were excluded because they were referred after failure of previous treatment or only had advice. 96 patients were already known to have renal metastasis with their diagnosis having been made between 0.2 and 17 years from the diagnosis of primary cancer (mean 4 years). 33 patients presented to us with a pathological fracture and were found to have renal cancer. A total of 54 patients had multiple metastases and 129 had a solitary metastasis. The cumulative survival from the time of diagnosis of the bone metastasis is 70 percent at 1 year, 40% at 3 years and 18% at 5 years. In patients with a solitary metastasis, the overall survival was 74% at 1 year and 45% at 3 years, whereas in patients with multiple metastases it was 55% at 1 year and 22% at 3 years. (p=0.02) In patients with a solitary metastasis treated by excision of the metastasis, the survival at 1 year was 86% as compared to 38% for those that were treated with just a local procedure. Cox multivariate analysis shows that survival was better in those with solitary metachronus metastasis who underwent a radical procedure. Conclusion. We recommend a radical procedure for patients who present with a solitary renal metastasis, particularly those with a disease-free interval of more than one year

Aims. Bone is a common site of metastatic disease. Skeletal complications include disabling pain and pathological fractures. Palliative surgery for incurable metastatic bone lesions aims to preserve quality of life and function by providing pain relief and stable mobility with fixation or replacement. Current literature has few treatment studies. We present a 5 year longitudinal cohort study of surgery for metastatic bone disease at our large teaching hospital reviewing our complication and mortality rates. Methods. Patients that underwent palliative surgery for metastatic bone lesions were identified from operative records. Demographics, clinical details and outcomes were recorded. Kaplan-Meier analysis was used to calculate survivorship. Results. 43 patients were treated for 44 bone metastases (34 IM Nails, 9 prosthetic replacements, 1 plate). The median age at primary diagnosis was 66 (33–92). Lung cancer was the most common primary. 56% presented with complete fractures and 44% with impending fractures (median Mirel score of 10). Pertrochanteric bone lesions were the most common (74%). Two out of 43 patients died within one day of surgery. 30 day mortality was 12% and 45% at 1 year. In those surviving the 30 day perioperative period, we report a complication rate of 14%. One patient had a dislocated prosthesis. Two patients had delayed or non union and two patients had failure of metalwork. No patient required re operation. Conclusion. Our series observed a 5% fixation failure rate and significant perioperative mortality. Whilst surgery may offer benefit in the non moribund patient with pathological fracture the decision to offer prophylactic surgery is more difficult in light of the high perioperative mortality seen in our study. Indeed, the patients in our study who died within 24 hours of surgery had prophylactic fixations. We conclude that surgical intervention must be carefully considered with realistic expectations of outcomes

Introduction: The ‘Two Week Wait’ (2ww) process has been in force since the year 2000, with the subsequent implementation of 32-day diagnosis and 62-day treatment ‘rules’, as part of reforms to NHS cancer services. The aims of this study were to compile a definitive diagnostic profile of 2ww referrals, establish whether a histological diagnosis was required and consider the current 2ww impact on services in our centre. Methods: Two hundred and nine patients were referred to the North of England Bone and Soft Tissue Tumour service and prospectively recorded on a computerised multidisciplinary tumour database from 2006–8. The data was reviewed and verified using pathology, radiology reports and patient records. Results: Malignancy was diagnosed in 41(20%) patients (n=209). This comprised 21 soft tissue sarcomas (10%), 11 primary bone tumours (5%), and 9 metastatic bone tumours (4%). 63 (30%) benign bone or soft tissue neoplasia and 80 (38%) non-neoplastic conditions were diagnosed. No mass lesion was identifiable in 25 patients (12%). A diagnostic or therapeutic biopsy was undertaken in 108 (52%) patients. Discussion: Fifteen percent of 2ww referrals to our centre have a primary bone or soft tissue malignancy. The 2ww caseload has increased significantly in recent years and non-malignant conditions (80%) must still be diagnosed within the 31 day rule. We utilise a ‘one-stop clinic’ approach, with access to ultrasound guided biopsy, and a weekly multidisciplinary meeting to facilitate timely investigation and treatment of all patients regardless of referral route

In proximal humerus reconstructions, osteoarticular massive allograft (OA) allows a biologic reattachment of tendineous structures of the host providing stability and functional recovery. Allograft-prosthesis composites (APC) are more technically demanding, but functional advantages with new prosthetic design are expected with lower fracture and failure rate with time. We compared the outcome of patients treated with OA reconstruction (group A) and patients treated with an APC (group B) after humerus resection for bone tumours. Thirty six patients treated between 1996 and 2009 were included in the study (18 group A; 18 group B). The diagnosis was a malignant bone tumour in 28 cases, an aggressive benign bone tumour in 6 and a bone metastasis in 2. Three total humerus resections were performed (two in group A and one in group B). Three different type of prosthesis were used (conventional, reverse and resurfacing). In group A, at an average follow-up of 66 months (2-116), 16 patients were continuously disease free. Ten patients (56%) had no complication; in 6 cases (33%) we observed a fracture of the graft and in 3 cases (17%) a pseudoarthrosis. In group B, at an average follow up of 44 months (3-164), 16 patients were continuously disease free. Thirteen patients (72%) had no complication, in 2 cases (11%) stem loosening, in 2 cases (11%) dislocation, in 1 case pseudoarthrosis and in 1 case resorption and detachment of allograft's great tuberosity was observed. Functional outcome was evaluated using MSTS scoring system: a mean score of 24 (13-30) in group A and 23 (15-27) in group B was observed. In our experience, proximal humerus APC showed functional results comparable to OA allograft with lower complication rate. In conclusion, in biologic reconstruction of the proximal humerus, APC seems to provide a more reliable solution than OA allograft at long term

Introduction: The ‘Two Week Wait’ (2ww) process has been in force since the year 2000, with the subsequent implementation of 32-day diagnosis and 62-day treatment ‘rules’ in 2005. The aims of this study were to compile a definitive diagnostic profile of 2ww referrals, establish whether a histological biopsy was required for diagnosis and consider the current 2ww impact on services in our centre. Materials and Methods: Two hundred and nine patients were referred under 2ww to the North of England Bone and Soft Tissue Tumour service and prospectively recorded on a computerised multidisciplinary tumour database from 2006–8. The data was reviewed and verified using pathology, radiology reports and patient records. Results: Malignancy was diagnosed in 41(20%) patients. This comprised 21 soft tissue sarcomas (10%), 11 primary bone tumours (5%), and 9 metastatic bone tumours (4%). 63 (30%) benign bone or soft tissue neoplasia and 80 (38%) non-neoplastic conditions were diagnosed. No mass lesion was identifiable in 25 patients (12%). A diagnostic or therapeutic biopsy was required in 108 (52%) patients. Discussion and Conclusion: 15% of 2ww referrals to our centre have a primary bone or soft tissue sarcoma but over half of all 2ww patients require biopsy for diagnosis creating additional strains on resources under the 32- and 62-day rule. Emphasis is placed on obtaining a rapid diagnosis, to ease pressure on time to treatment, utilising a ‘one-stop clinic’ approach for biopsies of accessible tumours where applicable. The availability of timely radiological resources, facilitated by an MDT involving a designated coordinator (‘patient-tracker’), is key to ensure treatment is not delayed for any cancer patient regardless of referral route. Our centre is 100% compliant for waiting times for sarcoma according to the Department of Health 2008 data

Cancer-induced bone diseases are often associated with increased bone resorption and pathological fractures. In recent years, osteoprotective agents such as bisphosphonates have been studied extensively and have been shown to inhibit cancer-related bone resorption in experimental and clinical studies. The third-generation bisphosphonate, ibandronate (BM 21.0955), is a potent compound for controlling tumour osteolysis and hypercalcaemia in rats bearing Walker 256 carcinosarcoma. We have studied the effect of ibandronate given as an interventional treatment on bone strength and bone loss after the onset of tumour growth in bone. Our results suggest that it is capable of preserving bone quality in rats bearing Walker 256 carcinosarcoma cells. Since other bisphosphonates have produced comparable results in man after their success in the Walker 256 animal models our findings suggest that ibandronate may be a powerful treatment for maintaining skeletal integrity in patients with metastatic bone disease

Seven patients who had malignant proximal femoral tumours were selected for resection and limb salvage with a modular megaprosthesis. Histopathological diagnosis confirmed one solitary bone metastasis from renal cell carcinoma, one dedifferentiated chondrosarcoma, two primary non-Hodgkin lymphomas non-responsive to adjuvant chemo- and radiotherapy and three low-grade chondrosarcomas. The mean age at the time of surgery was 53.5 years. Post-operative survival averaged 54.5 months. The mean functional status score was satisfactory. There was no local tumour recurrence or dislocation of the prosthesis. There were one superficial wound infection and one post-surgical haematoma. Care must be taken in selecting patients to for resection of the proximal femur and implantation of modular megaprostheses. We reserve such treatment only for tumours that, because of the histopathological diagnosis and spread, chemotherapy or radiotherapy alone is not enough. Modular megaprosthesis is currently the method of choice in the treatment of malignant proximal femoral tumours. With this implant joint function can be restored after wide resection, too, offering a valid alternative to the bony massive allografts that are characterised by a high rate of complications and failure

Summary Statement. CXCR4 gene and protein expression is regulated in a dose and time-dependent manner by metallic wear debris but not polyethylene wear debris in vitro and in vivo. Introduction. Progressive osteolysis leading to aseptic loosening among metal-on-metal (MoM) total hip arthroplasties (THA's), and adverse reactions to metallic debris (ARMD) are increasing causes for concern among existing patients who have been implanted with MoM hip replacements. Close surveillance of these patients is necessary and difficulties lie in early detection as well as differentiating low-grade infection from ARMD in the early stages. Several inflammatory markers have been investigated in this context, but to date, none is specific with regards to the offending material. In earlier studies, it has been shown that osteoblastic phenotypes and differentiation are regulated by different types of wear particles. Methods. In vitro experiments were performed using MG63 and SaOs-2 osteoblast-like cells co-cultured with increasing concentrations of metallic (Co-35Ni-20Cr-10Mo and Co-28Cr-6Mo) and polyethylene (UHMWPE-GUR1020) particles simulating periprosthetic wear debris. Real-time Polymerase Chain Reaction (RT-PCR) and Western Blotting were used to quantify gene and protein expression of CXCR4. The expression of TNF-a and the effects of AMD3100 on both CXCR4 and TNF-a expression among these cells was also investigated. Immunohistochemical techniques were used to investigate the in-vivo expression of CXCR4 in retrieval tissues obtained from 2 cohorts of failed metal-on-metal and ceramic-on-polyethylene THA's. Results. In-vitro RT-PCR and experiments demonstrated a dose-dependent increase in CXCR4 mRNA (7.5 fold for MG63 and 4.0 fold for SaOs-2 cells) among cells co-cultured with metal alloy particles. Western blotting also showed a time-dependent increase in protein expression of CXCR4. No regulatory effects on CXCR4 gene expression were seen among cells co-cultured with UHMWPE particles. The attempted blockade of CXCR4 by it's known competitive receptor agonist AMD3100 (bicyclam) led to a significant inhibition of metal particle induced TNF-a mRNA expression. In-vivo immunohistochemical data from the 2 cohorts of patients with failed THA's showed CXCR4 positivity among 83% of patients with metal-on-metal hip replacements but none among ceramic-on-polyethylene hip replacements. Discussion/Conclusion. CXCR4, the chemokine receptor for the chemokine SDF-1 (stromal cell derived factor-1), has been shown to play a pivotal role in bone metastasis, inflammatory and autoimmune conditions but has not been investigated in the context of periprosthetic osteolysis in failed joint replacements. Our in-vivo and in-vitro findings collectively suggest that the CXCR4 chemokine is specifically upregulated in a dose and time-dependent manner in the presence of metallic (cobalt-chrome) wear debris but not by polyethylene wear debris. The CXCR4 chemokine receptor may be a selective and specific biomarker for progressive osteolysis seen in failed MoM hip replacements and this phenomenon could potentially have a translational effect on the practice of orthopaedic surgery. Further research is needed to evaluate the interactions of CXCR4 with osteoclast activation and signalling pathways

Purpose of the study: Available epidemiological data on hand and wrist tumours are scarce and sometimes discordant. In our unit, these tumours are managed conjointly by hand surgeons and tumour specialists. We conducted an epidemiological study of 624 tumours treated from 1980 to 2008. Material and methods: The recruitment used three methods: diagnostic coding in the database, analysis of discharge letters, study of tumour registries. All hand and wrist tumours treated surgically in our unit were included retrospectively. Exclusion criteria were: patients aged less than 15 years and/or managed in the paediatric surgery unit; poorly identified cases; recurrences. Results: The study population included 624 tumours (375 female and 249 male). Mean age was 48 years (range 16–94). Eight tumours were malignant: 4 skin, 3 soft tissue, 1 bone metastasis of a primary renal tumour. Soft tissue tumour concerned 525 patients (84.1% of the study population). Respectively, 71 tumours concerned bone and 28 skin. There were 221 synovial cysts. The bone tumours exhibited a harmonious distribution for age and gender with a peak from 35 to 50 years and a sex ratio of 1/1. There were 43 chondromas found at all ages, mainly in long bones. Discussion: Our series is the third largest reported. A review of the literature identified the eight largest studies available. For 6452 tumours, 81.7% concerned soft tissues, 13% skin, 4.7% bone tissue. These lesions occurred at all ages with female predominance (60%). Malignant tumours were found in 4.4% of the cases. Exclusion of the paediatric cases and the retrospective nature of the data collection were the main biases of this work. Conclusion: Data on 624 hand and wrist tumours were in agreement with published work. Tumours involved mainly soft tissues. Synovial cysts predominated. Chondromas accounted for 70% of the bone tumours. Malignant tumours were rare (2.9%). For suspect cases, we recommend referral to a specialised centre for the management of malignant tumours of the hand. A pluridisciplinary analysis is indicated to adapt the diagnostic and therapeutic strategy

Introduction: Antegrade intramedullary locked nailing is a reliable method for the treatment of humeral shaft fractures. There is a still debate on the functional effect due to a possible damage during surgical approach of the rotator cuff, but in the Literature few paper deal with the analysis of tendons in these patients. Ultrasonography is still considered a reliable method in evaluating rotator cuff tendons. The aim of this study is to evaluate if antegrade intramedullary nailing may induce a possible damage on rotator cuff. Methods: Between May 2002 to December 2005 42 patient suffering of humeral shaft fractures were surgically treated with Unreamed Humeral Nail. Of them 21 (13 males and 8 female) were followed (average follow-up 22,9 months). All the fractures were traumatic except 1 due to bone metastasis of carcinoma. Follow up was clinical with Constant Score, radiographic in 3 projection (neutral, internal and external), and ultrasonographic, evaluating tendon of m. Sovraspinosus. Results: Healing of fractures was obtained after 2 month from surgery in all cases; Constant Score’s average was 77,0. Three cases of impingement syndrome due to excessive length of nail were observed, healed after the nail removal. Ultrasonography showed that in 13 cases rotator cuff was normal. In 5 cases we have found a signicative hyperecogen area, related to the scarf. We have never had a damage of tendon in all its tickness. Conclusion: Our study confirms that antegrade intra-medullary nail is a reliable method for the treatment humeral shaft fractures, not adversely influenced shoulder tendons. Damage of rotator cuff observed in few cases is not related to surgical technique, but depends on surgical pitfall with an excessively long nail and then impingement syndrome

Aims: The purpose of this study is to evaluate the experience of the Prague tumour centre with total hip replacements after tumour resections. Methods: 180 THR were implanted between 1971 and 2001 in the Prague tumour centre after resections of primary and secondary bone tumours. 158 had special long and 22 standard stems. The patients were followed in a minimum one-year interval both clinically and radiologically until their death or for at least þve years. Clinical and radiological data are evaluated. Results: Among the 158 long stem femoral components there were 63 primary bone tumours (10 Ewing sarcoma, 10 myeloma 9 chondrosarcoma, 7 osteosarcoma, 7 malignant þbrous histiocytoma, 4 malignant lymphoma, 4 giant cell tumours and 15 other benign tumours). Most of the 95 metastatic cases originated in the breast, kidney and lungs. The range of motion was surprisingly good when muscles were reattached around the stem. Luxations occurred until the antiluxating cup was developed. Even if these patients showed a higher risk of infection, reoperation was not a severe problem. Conclusions: THR with a long stem is a good salvage method after primary tumour resection around the hip. It is a method of choice in meta-static patients with or without pathologic fractures especially in solitary bone metastasis. Luxation can be a problem when not using an antiluxa-ting cup as well as replacement in children with unþnished skeletal development. Reattachment of the Ç muscle ring È improves the outcome

Purpose: In osteosarcoma, tumour progression leads to osteolysis via direct proteolytic mechanisms and/or osteoclast activation. Nitrogen biphosphonates (N-BP) like zolebronate inhibit osteoclast function and apoptosis of osteoclasts and other tumour cells. In animal models, N-BP decrease bony progression of myeloma, bone metastasis, and breast and prostatic tumours. In vitro studies have demonstrated a synergetic action with classical anti-cancer drugs on apoptosis for myeloma and breast cancer cell lines. The purpose of the present study was to investigate the effect of zoebronic acid on osteosarcoma growth, alone or in combination with ifosfamide. Material and methods: A rat model accepting osteosarcoma transplant was used for the study. Four series of seven rats were treated with zoledronate (100 mg/kg on day 7, 14, 21 and 28 after implantation) in combination or not with ifosfamide (30 mg/kg on day 1”, 14 and 15). Thirty-five days after implantation, the rats were sacrificed to evaluate tumour volume, presence of metastasis, radiography, and pathological examination of the tumour. Zoledronate was also studied in vitro on an OSRGA osteosarcoma cell line isolated from the same tumour. Results: Zoledronate demonstrated efficacy by reducing the osteolysis induced by the sarcoma, but also on local tumour progression (75%) in comparison with untreated animals. In vitro, zoledronate inhibited cell proliferation by 60%. The ifosfsamide-zoledrnoate combination produced greater reduction in tumour progression than ifosfamide alone. Conclusion: This work demonstrates for the first time that zoledronate has an effect on osteosarcoma tumour progression, either by a direct effect or by an antiosteoclastic effect and that the effet increases the efficacy of classical antitumour drugs such as ifosfamide

Proximal femoral fractures, whether it is due to meta-static destruction or periprosthetic fractures with loose femoral component with secondary osteolysis of the proximal femur in the elderly patient is a major task. We find the Cannulock hip system quite useful in tackling this issue. It offers various options for the management of this complex pathology. We present the results of 11 Cannulock Hip Arthroplasty performed in 10 patients (Age Range 55–92). 6 out of 11 patients was noted to have metastatic destruction of proximal femur including the head and neck down to lesser trochanter. Ca of Bronchus and Breast with multiple bony metastsis were responsible for these cases. 4/11 had loose femoral component with type 2 periprosthetic fractures. 1 out of 11 had failed DCS fixation for Reverse oblique fracture. The procedures were done in a district general Hospital in the UK between August 2001–Jan 2006. The patients were mostly ASA 4. The Cannulock Hip system offered the simplicity of a Hemiarthroplasty with an advantage of Intramedullary nailing option. This has the option of fitting standard Bipolar Head or 22 mm metallic head in case of Peri Prosthetic fracture where the acetabular component is intact. Long stem with HA coating and standard options for cemented stem insertion. The long stem with a bow enables easy insertion with distal locking facility. In our study all the patients were excellent with both clinical and readilogical out come, however sadly 1 patient died with in 3 months of surgery. 5/6 patients with metastatic bone tumour were discharged at the mean of 8 weeks with no clinical concerns. 4 patients with femoral stem revisions and 1 patient with failed DCS were discharged at a mean of 4 months. We find the Cannulock hip arthroplasty system quite versatile in the management of these complex injuries

Aims

Type 2 diabetes mellitus (T2DM) impairs bone strength and is a significant risk factor for hip fracture, yet currently there is no reliable tool to assess this risk. Most risk stratification methods rely on bone mineral density, which is not impaired by diabetes, rendering current tests ineffective. CT-based finite element analysis (CTFEA) calculates the mechanical response of bone to load and uses the yield strain, which is reduced in T2DM patients, to measure bone strength. The purpose of this feasibility study was to examine whether CTFEA could be used to assess the hip fracture risk for T2DM patients.

The treatment of bone metastases is usually palliative and aims to achieve adequate control of pain, to prevent and resolve compression of the cord in lesions of the spine and to anticipate or stabilise pathological fractures in the appendicular skeleton. In selected cases the complete resection of an isolated bone metastasis may improve the survival of the patient. During recent decades, the life expectancy of patients affected with metastatic carcinoma has improved considerably because of advances in chemotherapy, immunotherapy, hormonal treatment and radiotherapy. This improvement requires greater reliability in the reconstructive procedure in order to avoid mechanical failure during prolonged survival of the patient. The author experience with modular megaprosthesis by Link (megasystem C) allowed us to present a rapid, effective and functional solution. From June 2001 to December 2007 225 patients have been operated with a megaprosthesis C for tumoral resection. The new megaprosthesis C by Link represents a wide-ranging system that can afford a large variety of reconstructions in the inferior limb, from very short replacement of 5 cm in proximal femur, to a total femur and proximal tibia replacement. Modularity is represented by 1 cm increase in length. The different options of cemented and not cemented stem may be used with intraoperative decision. In cemented stem a rough collar seals the osteotomy and prevents polyethylene debris from entering the femoral canal by inducing a scar tissue around the stem entrance (so-called purse-string effect). Moreover in patients with solitary lesions and very good prognosis an allograft-prosthesis composite can be performed with improved clinical results on walking and function. Of the 225 patients that underwent tumoral resection and reconstruction with a modular megaprosthesis approximately 43% (97 cases) were operated for metastatic disease. Among these cases 55 cases were proximal femoral recontructions, 39 cases were distal femoral reconstructions and 3 cases were proximal tibial reconstructions. All cases were performed with cemented stems. We experienced a 7% of postoperative infections, 2% of dislocations of proximal femoral prosthesis and 3% of mechanical failures. While infections and dislocation rates were in the average for this surgery, mechanical failures seemed relatively high. However in patients with relatively long resections and muscle deficiency the mechanical stress exerted on the prosthesis can explain this kind of mechanical failure

Introduction: Metastatic bone disease of the humerus may be associated with disabling pain and loss of function. Surgery must provide good local tumor control, immediate mechanical stability, and a short rehabilitation period. Between 1980 and 2000, the authors operated 59 patients with metastatic disease of the humerus. The current study summarizes the principles of the surgical technique and functional and oncological outcomes. Materials and Methods: There were 33 females and 26 males. Indications for surgery included pathological fracture (40), impending fracture (11), and intractable pain (6). Anatomic locations of humeral metastases included: around the proximal humeral metaphysic and head (Type I) – 18, humeral diaphysis (Type II) – 39, and humeral condyles (Type III) – 2. Types I and III metastases were treated with resection and endoprosthetic reconstruction. Type II metastases were treated with intralesional tumor removal and cemented nailing. Postoperatively, 31 patients were treated with radiation therapy, 35 with chemotherapy, and 14 with immunotherapy. Follow-up of the study patients included physical examination, radiological evaluation and functional evaluation according to the American Musculoskeletal Tumor Society system. Results: Patients who had cemented nailing had better overall function, emotional acceptance, hand positioning, and lifting ability than patients who underwent endoprosthetic reconstruction. Pain alleviation and dexterity were comparable in both groups. All patients had a stable extremity and overall function of 56 patients (95%) was > 68% of normal upper extremity function. Only two patients (3%) had a local tumor recurrence. Conclusions: An aggressive surgical approach in patients who have humeral metastases and meet the criteria for surgical intervention is beneficial; it provides durable reconstruction and is associated with good function and local tumor control in most patients

Introduction: Mirels scoring system is a recognised method of assessing the risk of fracture in metastatic bone disease (MBD) based on radiological and clinical risk factors. Although reproducible, there are overlaps in the outcome of the scores. Aim: The aim of this study is look at the association between the tumour volume and ratio, and the incidence of pathological fracture. Method: Mirels score was calculated retrospectively from the patient notes. X-rays were scanned and analysed using the IMAGICA program. All tumours were measured twice on two views to the closest 0.1mm. The average of the two readings were used for the final calculations. Tumour volume was measured using 3 axis readings on the anteroposterior (AP) and lateral views of the tumour. The AP and lateral width of the tumour and the long bone shaft was measured to obtain the AP and Lateral Tumour Ratio (APTR and LTR respectively). Results: 58 patients were admitted in 2003 with suspected primary or MBD of a long bone. 50 patients were included. 28(56%) were male. Average age was 69.2years (range 10–98years). 6(12%) patients had a lytic lesion with no fracture and 18(36%) with pathological fracture. We were unable to measure Mirels score due to poor documentation. Patients with lytic lesion and no fracture had lower APTR and LTR, 0.88 and 0.85 respectively compare with the patients with lytic fractures (APTR 0.98 and LTR 0.91). This trend was not seen in tumours with sclerotic and mixed features. The average tumour volume was higher in the patients with lytic lesion and associated fracture than those with no fracture, 27.3 and 20.7cm³. 17(85%) of the lytic lesions, with volume larger than 10 cm³ had pathological fracture. Conclusion: The fracture rate is higher in presence of larger tumour with higher AP and lateral tumour ratio. A single measurement of the tumour volume may be more appropriate in the assessment of a lytic lesion for pathological fracture

Purpose of the study: Nearly all published series of Ewing sarcoma present the present of bone metastasis as a factor of very poor prognosis. Reviewing our experience, we noted that the prognosis is not as bad as expected in these patients if surgical resection of all known foci can be achieved. Case reports: Case n° 1 was a 16-year-old girl who presented a Ewing sarcoma involving the left iliopubic ramus. No other foci could be identified on the plain x-rays, scintigraphy and bone computed tomography. Preopeartive magnetic resonance imaging revealed a metastatic focus in the neck of the homolateral femur. The two foci were resected after preoperative chemotherapy: resection of the left hemi-pelvis and resection of the upper potion of the femur with replacement with a pelvic prosthesis and and massive prosthesis for the proximal femur. Eight years later, the patient has remained in complete primary remission, consulting for orthopedic gait problems related to prosthetic loosening. Case n° 2 was a 13-year-old boy who presented an Ewing sarcoma of the upper tibial metaphysic. Preoperative magnetic resonance imaging revealed three other metastatic localizations in the homolateral femur. Bifocal resection of the tibia and the femur was performed with implantation of an active growth prosthesis. Chemotherapy was continued. Seven years later, the patient remains in primary complete remission. Lengthening the prosthesis has enabled equivalent growth for the two limbs. The patient has a normal life style excepting contact sports which are prohibited. Case n° 3 was a 17-year-old boy who presented a voluminous Ewing sarcoma of the right pelvis. Search for extension revealed a unique metastasis in the fourth lumbar vertebra. The patient was given preoperative chemotherapy before resection of the pelvic tumor then two months later resection of the vertebral metastasis. The patient died 4.5 years later from a traffic accident. He had remained in complete remission. Discussion and conclusion: These three cases of complete long-term primary remission of patients with primary bone metastases show that like other bone sarcomas, eradication of all recognized bone metastases is essential for the prognosis of Ewing sarcoma

Aims

The aticularis genu (AG) is the least substantial and deepest muscle of the anterior compartment of the thigh and of uncertain significance. The aim of the study was to describe the anatomy of AG in cadaveric specimens, to characterize the relevance of AG in pathological distal femur specimens, and to correlate the anatomy and pathology with preoperative magnetic resonance imaging (MRI) of AG.

Solitary fibrous tumour (SFT) is a relatively uncommon mesenchymal neoplasm that most frequently arises in the pleura, but is also known to affect extrathoracic sites. About 15 % of SFT’s behave in an aggressive way, giving rise to local recurrence and/or distant metastasis. However, the behaviour of SFT remains unpredictable and due to the rarity of this tumour, it is difficult to define prognostic factors. The purpose of this study was to describe our experience with SFT, trying to define the pathologic features of this rare entity and better understand its clinical behaviour. We performed a clinicopathologic review of all cases treated for a SFT at the Istituto Ortopedico Rizzoli in Bologna, between 1996 and 2008. We included 24 patients, nine males and fifteen females, ranging in age from 22 to 82 years (median 43.5 years). The anatomical sites involved were: the thigh (12 cases), shoulder region (four cases), gluteus (three cases), foot (two cases), extrapleural thoracic wall (two cases), and the lower leg (one case). The tumour was > 5 cm in 15 cases, ranging in diameter from 2.5 cm to 18 cm (median 7.5 cm). Pain and swelling were the most frequently reported symptoms at presentation, with a mean duration of symptoms of 10 months. All patients were treated by excisional surgery (wide margins in 11, marginal margins in 13). Three patients had undergone pre-operative radiotherapy (44Gy) and one of these had also adjuvant radiotherapy after marginal excision of the tumour. Six tumours showed at least one atypical histologic feature (moderate to marked cytological atypia, extensive tumor necrosis, ≥ four mitoses per ten high-power fields, or infiltrative margins). On immunohistochemistry, 21 cases were positive for CD-34, 10 for CD-99, 17 for vimentin, three for CD-31, four for actin and one for S-100. Subsequent follow-up (average 33 months, range 5 to 112 months) revealed tumour relapse in only one case: a bone metastasis after 36 months of follow-up. The initial lesion was considered a large, deep, malignant SFT of the thigh, treated with wide surgical excision. In the current review, including 24 extrathoracic solitary fibrous tumours, all lesions but one had a benign course. Nevertheless, this entity has a potential to recur or metastasize, and therefore careful long-term follow-up is necessary for all patients, even after wide excisional surgery. Although specific prognostic factors are yet to be defined, a high degree of suspicion for malignant behaviour is warranted for those cases in which atypical histologic features are present, particularly in the context of a deep tumor > 5cm in diameter

Introduction: For longer lasting and bone conserving cementless stem fixation, stable and physiological proximal load transfer from the stem to the canal should be one of the most essential factors. According to this understanding, we have been developing a custom stem system with lateral flare and an off-the-shelf (OTS) lateral flare stem system was added to the series. On the other hand, dysplastic hips are often understood that they have larger neck shaft angle as well as larger anteversion. In other words they are in the status called “coxa valga.” From this point of view we had been mainly using custom stems for the dysplastic cases before. After off-the-shelf lateral flare stem system; which is designed to have very high proximal fit and fill to normal femora; was added, we have been using 3D preoperative planning system to determine custom or OTS. Then in most of the cases, OTS stem were suitably selected. Our pilot study of virtual insertion of OTS lateral flare stem into 38 dysplastic femora has shown very tight fit in all 38 cases. The reason was analyzed that the excessive anteversion is twist of proximal part over the distal part and the proximal part has almost normal geometry. In the present study, 59 femora were examined by the 3D preoperative planning system how the excessive anteversion effect to the coxa valga status. Materials and Methods: Fifty-nine femoral geometry data were examined by the 3D preoperative planning system. Thirty-three hip arithritis, 3 RA, 2 metastatic bone tumours, 5 AVN, 1 knee arthritis, 12 injuries, and 3 normal candidates were included. Among them one arthritic Caucasian and one AVN South American were included. The direction of the femoral landmarks; centre of femoral head (CFH), lesser trochanter (LTR), and asperas in 3 levels (just below LTR, upper 1/3, mid femur; A1-3); were assessed as the angle from knee posterior condylar (PC) line. Neck shaft angle of each case was assessed from the view perpendicular to PC line and neck shaft angle form the view perpendicular to CFH and femoral shaft (i.e. actual neck shaft angle). Results: Average anteversion was 34.4 +/−9.9 degree. CFH and LTR correlated well (i.e. they rotate together). A1, A2, A3 correlated well (i.e. they rotate together). LTR and A1 correlate just a little, LTR and A2 were independent each other. So the twist existed around A1. Neck shaft angle was 138.7+/−6.6 in PC line view and in actual view 130.3+/−4.4. No excessive neck shaft angle was observed in actual view. Even the case that has the largest actual neck shaft angle (140.4), the virtual insertion showed good fit and fill with the lateral flare stem. Conclusion: In many high anteversion cases, coxa valga is a product of the observation from non perpendicular direction to CFH-shaft plane. Selection or designation of the stem for high anteversion cases should be carefully determined by 3D observation

Aims

Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients.

Objective: To present the clinical features, radiological findings and differential diagnosis of this rare benign condition. Design: Melorheostosis (Leri’s Disease) is a rare mesenchymal dysplasia commonly exhibiting hyperostosis on the internal and external aspect of tubular bones in a sclerodermal distribution. It usually occurs in the limbs, frequently crosses joints and there is often ossification in local soft tissues. Presenting features may include pain, restricted joint movement and skin thickening. It very rarely affects the spine and its cause is unknown. Subject: A 40-year-old female presented with insidious onset of mild mid thoracic back pain. There was no history of trauma and she had no past medical or family history. She underwent a six-month course of physiotherapy but this failed to help her symptoms. She developed a small lump over the area of pain and her GP arranged an X-Ray. This showed an irregular area of high attenuation over the right side of the tenth thoracic vertebra. A CT demonstrated a “dripping candle wax” appearance of densely calcified cortical bone undulating over the right side of the body and posterior elements of T10. The ossification crossed the synovial zygoapophyseal joint but not the intervertebral disc and a diagnosis of melorheostosis was suggested. MRI supported the CT findings and confirmed the presence of a soft tissue lesion over the dorsal process of T10. A bone scan verified the solitary nature of the lesion and showed widening of the right side of the body of T10 with increased focal uptake. All blood and urine investigations were normal. Results: The patient underwent an open biopsy to obtain sufficient tissue for histological diagnosis and confirm that the lesion was benign in nature. It was felt that the dense ossification of the lesion would make percutaneous biopsy difficult. The most important differentials to exclude were an osteosclerotic bone metastasis and osteosarcoma. Other differential diagnoses were a parosteal osteoma, a burnt out osteoblastoma and a giant bone island. The soft tissue histology showed a necrotic fibrocartilagenous mass. The bone samples required prolonged decalcification prior to cutting and were composed of compact cortical bone similar to the appearances seen in ivory osteoma and also consistent with melorheostosis. This pathological pattern and the radiological finding of cortical compact bone crossing a synovial joint confirms the diagnosis of melorheostosis. Conclusions: Spinal melorheostosis is a rare condition. The diagnosis should be considered in the differential of atypical osteosclerotic lesions of vertebrae. Adequate histological sampling is essential in order to exclude malignancy

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To evaluate the perioperative complications associated with total en bloc spondylectomy (TES) in patients with spinal tumours, based on the extent and level of tumour resection.

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Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells.

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LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.

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The aim of this study was to present the long-term surgical outcomes, complications, implant survival, and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins.