Objectives

The clinical utility of routine cross sectional imaging of the abdomen and pelvis in the screening and surveillance of patients with primary soft-tissue sarcoma of the extremities for metastatic disease is controversial, based on its questionable yield paired with concerns regarding the risks of radiation exposure, cost, and morbidity resulting from false positive findings.

Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response. Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care

Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)). Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO. 4. and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO. 4. to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA. Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality. Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with spinal metastases

Abstract. Objectives. To analyse the costs and benefits of sending femoral head specimens for histopathological analysis and whether our practice had changed since the original study five years ago. Methods. The cohort definition was patients who had both undergone hip hemiarthroplasties (HHAs) and had femoral head specimens sent for histopathological analysis at our tertiary care institution from 2013 to 2016. Retrospective review of clinical and electronic notes was performed on these patients for history of malignancy, histopathological diagnosis of femoral head, indication for histopathological examination and radiological studies. The total number of HHAs performed at the centre and the costs involved in analysing each femoral head specimen were identified. Results. A total of 805 HHAs were performed at the centre. We identified 56 femoral head specimens from 56 patients (6.96%) that were sent for histopathological analysis after HHA. 29 patients (51.79%) had a known history of malignancy. Three femoral head specimens (10.34%) were histologically positive for malignancy. Two patients had hip radiographs demonstrating metastasis to the femoral head. The third patient had a PET-CT scan two weeks prior to fracture that did not show signs of metastatic disease. 27 patients (48.21%) had no history of malignancy. None of their femoral head specimens were found to be histologically positive for malignancy. 10 patients had no appropriate indication for histopathological analysis. The cost savings for 27 patients with no previous history of malignancy ranged from €2,295 to €9,504. The cost savings for 10 patients with no appropriate indication ranged from €850 to €3,520. Conclusions. Histopathological analysis of femoral head specimens after HHA has little benefit for patients without a history of malignancy. The practice at our institution had not changed significantly in the past five years. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Metastatic osteosarcoma is seen in 10-20% of patients at initial presentation with the lung the most common site of metastasis. Historically, prognosis has been poor. We studied trends in survival in our small developed nation and aimed to identify correlations between the survival rate and three factors: newer chemotherapy, advances in radiological imaging and a more aggressive approach adopted by cardiothoracic surgeons for lung metastases. Our national bone tumour registry was used to identify patients at the age of 18 or under, who presented with metastatic disease at initial diagnosis between 1933 and 2006. There were 30 patients identified. Kaplan-Meier analysis was used to determine survival rates and univariate analysis was performed using the Cox regression proportional hazards model. Median survival has improved over the last 50 years; highlighted by the ‘Kotz’ eras demonstrating incremental improvement with more effective chemotherapy agents (p=0.004), and a current 5-year survival of 16%. Aggressive primary and metastatic surgery also show improving trends in survival. Three patients have survived beyond 5 years. The introduction of computerised tomography scanning has led to an increase in the prevalence of metastases at initial diagnosis. Metastatic osteosarcoma remains with a very poor prognostic factor, however, aggressive management has been shown to prolong survival

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

Summary. Metastatic spinal disease is a common entity of much debate in terms of ideal surgical treatment. The introduction of MIS can be a game-changer in the treatment of MSD due to less peri-operative morbidity and allowing earlier radiotherapy and/or chemotherapy. Introduction. Less invasive techniques have always been welcome for management of patients with ‘Metastatic Spinal Disorders’. This is because these patients can be poor candidates for extensive / major invasive surgery even though radiologically, there may be an indication for one. The aim of the treatment with Minimal Invasive Fixation (MIS) systems is mainly for ‘pain relief’ than to radically decrease tumour burden or to achieve near total spinal cord decompression, which could be major presentations in these patients. These procedures address the ‘spinal instability’ very well and they can address pain associated with compression fractures resulting from metastatic disease from a solid organ as well as multiple myeloma with minimal complications. These procedures can be combined with radiology and chemotherapy without much concern for wound problems in the way of infection or dehiscence. They also have a great advantage of timing of adjunct therapy closer to the index procedure. The disadvantage, however, are they do not allow thorough decompression of the spinal cord. There could also be problem in addressing patients who have severe vertebral height loss or loss of integrity of the anterior column where anterior column reconstruction may be required. There is a risk of inadequate fixation or implant loosening or failure. We aim to examine the results of MIS surgery in our department and support the rationale for its use. Patients and Methods. We prospectively collected data of patients who underwent MIS posterior instrumentation for MSD. Between June 2011 and December 2012, 10 patients presented with acute motor deficit, instability and/or threatening radiological features. Effectiveness of MIS was assessed in terms of operative parameters and clinical outcomes. Results. No patient suffered intra-operative complications. The median surgical time was 198 minutes (range: 149 – 403), median blood loss was 100 ml (range: 60 – 400). All patients maintained full neurological function and reported effective pain reduction. All patients were discharged with a median hospital stay was 13 days (range: 4 – 45) post-surgery. 9 patients started oncological treatment as planned. The median time in 7 patients who had radiotherapy post-surgery was 23 days (range: 20 – 40). Chemotherapy was initiated in 4 patients at a median of 9 days post-surgery (range: 6 – 23). No patient as yet has required open procedure due to progression of the disease. Discussion/Conclusion. We have shown that satisfactory outcomes are achievable with MIS in a selected group of patients with MSD. While our results are limited by small study size, we have been able to improve patient quality of living through minimally invasive intervention. By reducing surgical morbidity and enabling early implementation of oncological treatment, MIS has the potential to re-evaluate multi-disciplinary decision making for early surgery in MSD

We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45°C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia.

The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung.

We used a canine intercalary bone defect model to determine the effects of recombinant human osteogenic protein 1 (rhOP-1) on allograft incorporation. The allograft was treated with an implant made up of rhOP-1 and type I collagen or with type I collagen alone.

Radiographic analysis showed an increased volume of periosteal callus in both test groups compared with the control group at weeks 4, 6, 8 and 10. Mechanical testing after 12 weeks revealed increased maximal torque and stiffness in the rhOP-1 treated groups compared with the control group.

These results indicate a benefit from the use of an rhOP-1 implant in the healing of bone allografts. The effect was independent of the position of the implant. There may be a beneficial clinical application for this treatment.

The aim of this biomechanical study was to investigate the role of the dorsal vertebral cortex in transpedicular screw fixation. Moss transpedicular screws were introduced into both pedicles of each vertebra in 25 human cadaver vertebrae. The dorsal vertebral cortex and subcortical bone corresponding to the entrance site of the screw were removed on one side and preserved on the other. Biomechanical testing showed that the mean peak pull-out strength for the inserted screws, following removal of the dorsal cortex, was 956.16 N. If the dorsal cortex was preserved, the mean peak pullout strength was 1295.64 N. The mean increase was 339.48 N (26.13%; p = 0.033). The bone mineral density correlated positively with peak pull-out strength.

Preservation of the dorsal vertebral cortex at the site of insertion of the screw offers a significant increase in peak pull-out strength. This may result from engagement by the final screw threads in the denser bone of the dorsal cortex and the underlying subcortical area. Every effort should be made to preserve the dorsal vertebral cortex during insertion of transpedicular screws.