Previous studies have shown improved outcome following surgery for spinal cord compression due to metastatic disease. Further papers have shown that many patients with metastatic disease are not referred for orthopaedic opinion. The aims of this paper are to study the survival and morbidity of patients with spinal metastatic disease who receive radiotherapy. Do patients develop instability and progressive neurological compromise? Can we predict which patients will benefit from surgery?. Retrospective review of patients receiving radiotherapy for pain relief or cord compression as a result of metastatic disease. Patients were scored with regards to Tomita and Tokuhashi, survival and for deterioration in neurology or spinal instability. 94 patients reviewed. All patients were followed up for a minimum of 1 year or until deceased. Majority of patients had a primary diagnosis of lung, prostate or breast carcinoma. Mean Tomita score of 6, Tokuhashi score 7, and mean survival following radiotherapy of 8 months. 11:94 patients referred for surgical opinion. Poor correlation with Tomita scores (-0.25) & Tokuhashi scores (0.24) to predict survival. Four patients developed progressive neurology on follow-up. One patient developed spinal instability. The remainder of the patients did not deteriorate in neurology and did not develop spinal instability. All patients with normal neurology at time of radiotherapy did not develop spinal cord compression or cauda equina at a later date. This study suggests that the vast majority of patients with spinal metastatic disease do not progress to spinal instability or cord compression, and that prophylactic surgery would not be of benefit. The predictive scoring systems remain unreliable making it difficult to select those patients who would benefit. The referral rate to spinal surgeons remains low as few patients under the care of the oncologists develop spinal complications

Several different algorithms attempt to estimate life expectancy for patients with metastatic spine disease. The Skeletal Oncology Research Group (SORG) has recently developed a nomogram to estimate survival of patients with metastatic spine disease. Whilst the use of the SORG nomogram has been validated in the international context, there has been no study to date that validates the use of the SORG nomogram in New Zealand. This study aimed to validate the use of the SORG nomogram in Aotearoa New Zealand. We collected data on 100 patients who presented to Waikato Hospital with a diagnosis of spinal metastatic disease. The SORG nomogram gave survival probabilities for each patient at each time point. Receiver Operating Characteristic (ROC) Area Under Curve (AUC) analysis was performed to assess the predictive accuracy of the SORG score. A calibration curve was also performed, and Brier scores calculated. A multivariate Cox regression analysis was performed. The SORG score was correlated with 30 day (AUC = 0.72) and 90-day mortality (AUC = 0.71). The correlation between the SORG score and 90-day mortality was weaker (AUC = 0.69). Using this method, the nomogram was correct for 79 (79%) patients at 30-days, 59 patients (59%) at 90-days, and 42 patients (42%) at 365-days. Calibration curves demonstrated poor forecasting of the SORG nomogram at 30 (Brier score = 0.65) and 365 days (Brier score = 0.33). The calibration curve demonstrated borderline forecasting of the SORG nomogram at 90 days (Brier score = 0.28). Several components of the SORG nomogram were not found to be correlated with mortality. In this New Zealand cohort the SORG nomogram demonstrated only acceptable discrimination at best in predicting life 30-, 90- or 356-day mortality in patients with metastatic spinal disease

The management of primary malignant bone tumors with metastatic disease at presentation remains a challenge. While surgical resection has been shown to improve overall survival among patients with non-metastatic malignant bone tumors, current evidence regarding the utility of surgery in improving overall survival in metastatic patients remains limited. The 2004–2016 National Cancer Database (NCDB) was queried using International Classification of Diseases 3rd Edition (ICD-O-3) topographical codes to identify patients with primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8 and C40.9) and/or pelvis (C41.4). Patients with malignant bone tumors of the axial skeleton (head/skull, trunk and spinal column) were excluded, as these cases are not routinely encountered and/or managed by orthopaedic oncologists. Histological codes were used to categorize the tumors into the following groups - osteosarcomas, chondrosarcomas, and Ewing sarcomas. Patients who were classified as stage I, II or III, based on American Joint Commission of Cancer (AJCC) guidelines, were excluded. Only patients with metastatic disease at presentation were included in the final study sample. The study sample was divided into two distinct groups – those who underwent surgical resection of the primary tumors vs. those who did not receive any surgery of the primary tumor. Kaplan-Meier survival analysis was used to report unadjusted 5-year overall survival rates between patients who underwent surgical resection of the primary tumor, compared to those who did not. Multi-variate Cox regression analyses were used to assess whether undergoing surgical resection of the primary tumor was associated with improved overall survival, after controlling for differences in baseline demographics, tumor characteristics (grade, location, histological type and tumor size), and treatment patterns (underwent metastatectomy of distal and/or regional sites, positive vs. negative surgical margins, use of radiation therapy and/or chemotherapy). Additional sensitivity analyses, stratified by histologic type for osteosarcomas, chondrosarcomas and Ewing sarcomas, were used to assess prognostic factors for overall survival. A total of 2,288 primary malignant bone tumors (1,121 osteosarcomas, 345 chondrosarcomas, and 822 Ewing sarcomas) with metastatic disease at presentation were included – out of which 1,066 (46.0%) underwent a surgical resection of the primary site. Overall 5-year survival rates, on unadjusted Kaplan-Meier log-rank analysis, were significantly better for individuals who underwent surgical resection vs. those who did not receive any surgery (31.7% vs. 17.3%; p<0.001). After controlling for differences in baseline demographics, tumor characteristics and treatment patterns, undergoing surgical resection of primary site was associated with a reduced overall mortality (HR 0.42 [95% CI 0.36–0.49]; p<0.001). Undergoing metastectomy (HR 0.92 [95% CI 0.81–1.05]; p=0.235) was not associated with a significant improvement in overall survival. On stratified analysis, radiation therapy was associated with improved overall survival for Ewing Sarcoma (HR 0.71 [95% CI 0.57–0.88]; p=0.002), but not for osteosarcoma (HR 1.14 [95% CI 0.91–1.43]; p=0.643) or chondrosarcoma (HR 1.08 [95 % CI 0.78–1.50]; p=0.643). Chemotherapy was associated with improved overall survival for osteosarcoma (HR 0.50 [95% CI 0.39–0.64]; p<0.001) and chondrosarcoma (HR 0.62 [95% CI 0.45–0.85]; p=0.003), but not Ewing sarcoma (HR 0.79 [95% CI 0.46–1.35]; p=0.385). Surgical resection of the primary site significantly improves overall survival for primary malignant bone tumors with metastatic disease at presentation. Physicians should strongly consider surgical resection of the primary tumor, with adjunct systemic and/or radiation therapy (dependent on tumor histology), in patients presenting with metastatic disease at presentation

Sarcopenia has been observed to be a predictor of mortality in international studies of patients with metastatic disease of the spine. This study aimed to validate sarcopenia as a prognostic tool in a New Zealand setting. A secondary aim of this study was to assess the intra-observer reliability of measurements of psoas and vertebral body cross sectional areas on computed tomography imaging. A cohort of patients who had presented to Waikato Hospital with secondary neoplasia in the spinal column from 2014 to 2018 was selected. Cross sectional psoas and vertebral body areas were measured at the mid-pedicle L3 level, followed by calculation of the psoas to vertebral body cross sectional area ratio. Psoas to vertebral body cross sectional area ratio was compared with survivorship. The strength of the correlation between sarcopenia and survivorship was compared with the correlation between serum albumin and survivorship, as well as the correlation between the Metastatic Spine Risk Index (MSRI) and survivorship. A total of 110 patients who received operative (34) and non-operative (76) were included. The results demonstrate that psoas to vertebral body cross sectional area ratio is not statistically significantly correlated with survivorship (p=0.53). Serum albumin is significantly correlated with survivorship (p<0.0001), as was the MSRI. There is good intra-observer and inter-observer reliability for measurements of psoas to vertebral body cross sectional area. This study failed to demonstrate the utility for the psoas to vertebral body cross sectional area ratio that other studies have demonstrated in estimating survivorship. Serum albumin levels remain a useful prognostic indicator in patients with secondary tumours in the vertebral column

Traditional staging systems for high grade osteosarcoma (Enneking, MSTS) are based largely on gross surgical margins and were developed before the widespread use of neoadjuvant chemotherapy. It is now well known that both microscopic margins and chemotherapy are predictors of local recurrence. However, neither of these variables are used in the traditional surgical staging and the precise safe margin distance is debated. Recently, a novel staging system utilizing a 2mm margin cutoff and incorporating precent necrosis was proposed and demonstrated improved prognostic value for local recurrence free survival (LRFS) when compared to the MSTS staging system. This staging system has not been validated beyond the original patient cohort. We propose to analyze this staging system in a cohort of patients with high-grade osteosarcoma, as well as evaluate the ability of additional variables to predict the risk of local recurrence and overall survival. A retrospective review of a prospectively collected database of all sarcoma patients between 1985 and 2020 at a tertiary sarcoma care center was performed. All patients with high-grade osteosarcoma receiving neo-adjuvant chemotherapy and with no evidence of metastatic disease on presentation were isolated and analyzed. A minimum of two year follow up was used for surviving patients. A total of 225 patients were identified meeting these criteria. Univariate analysis was performed to evaluate variable that were associated with LRFS. Multivariate analysis is used to further analyze factors associated with LRFS on univariate analysis. There were 20 patients (8.9%) who had locally recurrent disease. Five-year LRFS was significantly different for patients with surgical margins 2mm or less (77.6% v. 93.3%; p=0.006) and those with a central tumor location (67.9 v. 94.4; <0.001). A four-tiered staging system using 2mm surgical margins and a percent necrosis of 90% of greater was also a significant predictor of 5-year LRFS (p=0.019) in this cohort. Notably, percent necrosis in isolation was not a predictor of LRFS in this cohort (p=0.875). Tumor size, gender, and type of surgery (amputation v. limb salvage) were also analyzed and not associated with LRFS. The MSTS surgical margin staging system did not significantly stratify groups (0.066). A 2mm surgical margin cutoff was predictive of 5-year LRFS in this cohort of patients with localized high-grade osteosarcoma and a combination of a 2mm margin and percent necrosis outperformed the prognostic value of the traditional MSTS staging system. Utilization of this system may improve the ability of surgeons to stage thier patients. Additional variables may increase the value of this system and further validation is required

Radiation induced sarcoma of bone is a rare but challenging disease process associated with a poor prognosis. To date, series are limited by small patient numbers; data to inform prognosis and the optimal management for these patients is needed. We hypothesized that patients with radiation-induced pelvic bone sarcomas would have worse surgical, oncologic, and functional outcomes than patients diagnosed with primary pelvic bone sarcomas. This was a multi-institution, comparative cohort analysis. A retrospective chart review was performed of all patients diagnosed with a radiation-induced pelvic and sacral bone sarcoma between January 1st, 1985 and January 1st, 2020 (defined as a histologically confirmed bone sarcoma of the pelvis in a previously irradiated field with a minimum 3-year interval between radiation and sarcoma diagnosis). We also identified a comparison group including all patients diagnosed with a primary pelvic osteosarcoma/spindle cell sarcoma of bone (i.e. eligible for osteosarcoma-type chemotherapy) during the same time interval. The primary outcome measure was disease-free and overall survival. We identified 85 patients with primary osteosarcoma of the pelvis (POP) and 39 patients with confirmed radiation induced sarcoma of the bony pelvis (RISB) undergoing surgical resection. Patients with RISB were older than patients with POP (50.5 years vs. 36.5 years, p67.7% of patients with POP underwent limb salvage as compared to 77% of patients with RISB; the type of surgery was not different between groups (p=.0.24). There was no difference in the rate of margin positive surgery for RISB vs. POP (21.1% vs. 14.1%, p=0.16). For patients undergoing surgical resection, the rate of surgical complications was high, with more RISB patients experiencing complications (79.5%) than POP patients (64.7%); this approached statistical significance (p=0.09). 15.4% of patients with RISB died perioperative period (within 90 days of surgery) as compared to 3.5% of patients with POP (p= 0.02). For patients undergoing surgical resection, 5-year OS was significantly worse for patients with RISB vs. POP (27.3% vs. 47.7%, p=0.02). When considering only patients without metastatic disease at presentation, a significant difference in 5-year survival remains for patients with RISB vs. POP (28.6% vs. 50%, p=0.03) was a trend towards poorer 5-year DFS for patients with RISB vs. POP (30% vs. 47.5%), though this did not achieve statistical significance (p=0.09). POP and RISB represent challenging disease processes and the oncologic outcomes are similarly poor between the two; however, the disease course for patients with RISB appears to be worse overall. While surgery can result in a favorable outcome for a small subset of patients, surgical treatment is fraught with complications

One out of nine Canadian males would suffer prostate cancer (PC) during his lifetime. Life expectancy of males with PC has increased with modern therapy and 90% live >10 years. However, 20% of PC-affected males would develop incurable metastatic diseases. Bone metastases (BM) are present in ~80% of metastatic PC patients, and are the most severe complication of PC, generating severe pain, fractures, spinal cord compression, and death. Interestingly, PC-BMs are mostly osteoblastic. However, the structure of this newly formed bone and how it relates to pain and fracture are unknown. Due to androgen antagonist treatment, different PC phenotypes develop with differential dependency on androgen receptor (AR) signaling: androgen-dependent (AR+), double negative (AR-) and neuroendocrine. How these phenotypes are related to changes in bone structure has not been studied. Here we show a state-of-the-art structural characterization of PCBM and how PC phenotypes are associated to abnormal bone formation in PCBM. Cadaveric samples (n=14) obtained from metastases of PC in thoracic or lumbar vertebrae (mean age 74yo) were used to analyze bone structure. We used micro-computed tomography (mCT) to analyze the three-dimensional structure of the bone samples. After imaging, the samples were sectioned and one 3mm thick section was embedded in epoxy-resin, ground and polished. Scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS) and quantitative backscattering electron (qBSE) imaging were used to determine mineral morphology and composition. Another section was used for histological analysis of the PC-affected bone. Collagen structure, fibril orientation and extracellular matrix composition were characterized using histochemistry. Additionally, we obtained biopsies of 3 PCBM patients undergoing emergency decompression surgery following vertebral fracture and used them for immunohistological characterization. By using mCT, we observed three dysmorphic bone patterns: osteolytic pattern with thinned trabecula of otherwise well-organized structures, osteoblastic pattern defined as accumulation of disorganized matrix deposited on pre-existing trabecula, and osteoblastic pattern with minimum residual trabecula and bone space dominated by accumulation of disorganized mineralized matrix. Comparing mCT data with patho/clinical parameters revealed a trend for higher bone density in males with larger PSA increase. Through histological sections, we observed that PC-affected bone, lacks collagen alignment structure, have a higher number of lacunae and increased amount of proteoglycans as decorin. Immunohistochemistry of biopsies revealed that PC-cells inside bone organize into two manners: i) glandular-like structures where cells maintain their polarization in the expression of prostate markers, ii) diffuse infiltrate that spreads along bone surfaces, with loss of cell polarity. These cells take direct contact with osteoblasts in the surface of trabecula. We define that PCBM are mostly composed by AR+ with some double negative cells. We did not observe neuroendocrine phenotype cells. PCBMs generate predominantly osteoblastic lesions that are characterized by high lacunar density, lack of collagen organization and elevated proteoglycan content. These structural changes are associated with the infiltration of PC cells that are mostly androgen-dependent but have lost their polarization and contact directly with osteoblasts, perhaps altering their function. These changes could be associated with lower mechanical properties that led to fracture and weakness of the PCBM affected bone

The orthopaedic surgeon may need to act as an important adjunct to the oncologist in management of the cancer patient with metastatic hip disease. Management of the cancer patient with routine hip pathology may be relatively straightforward but the surgeon should note that the cancer patient may be on treatment protocols which affect wound healing, the immune system and the risk of DVT. The principles of managing metastatic disease include recognising the presence of lesions in bone about the hip, the occasional need for biopsy, the use of radiation in sensitive tumors and finally surgical stabilisation or replacement when needed. In some cases percutaneous cementation of metastatic disease or radiofrequency ablation may be appropriate. Factors which may complicate management of patients who have completed treatment of peri-pelvic cancer, may include radiation therapy which can lead to osteonecrosis of the acetabulum. Greater than 500 Cgy of radiation has been associated with high rates of acetabular fixation failure regardless of fixation type in several series. Decision making in these patients can be aided by consultation with previous radiation therapy providers to estimate the dose sustained by the local tissues under consideration. Increased rates of infection and wound healing have also been noted secondary to long term lymphatic obliteration caused by radiation. These concerns also affect the surgeon who must manage patients with acute metastatic disease who may also be undergoing chemotherapy as well as radiation

Background. Decisions about local treatment are important in osteosarcoma treatment. The purpose of this study was to review decisions about local treatment in one centre. Methods. This was a retrospective review of the records of all patients with high-grade extremity osteosarcoma presenting to our centre between 1997 and 2008. Particular attention was paid to local control decisions. Results. 54 patients were included, 37 were male. Median age was 18 (4.1 to 71.3 years). The anatomical location was distal femur in 33, tibia in 8, humerus in 7, ankle/foot in 3, fibula in 2 and clavicle in 1. 8 (14.8%) patients had metastases at presentation. 13 (24.1%) patients underwent primary amputation, predominantly in the early years of the series. The remaining 41 patients had limb-sparing surgery, 5 of whom had microscopically positive margins. 21 of 54 (38.8%) had >90% necrosis in the resected tumour. 3 patients had poor necrosis and positive margins. These were a 70 yo intolerant of chemotherapy, who refused amputation, developed LR and metastatic disease; a 15 yo with metastatic disease, who had a secondary amputation and metastatectomy and survived and a 43 yo who developed metastases and LR on chemotherapy. 4 further patients had local recurrence after LSS. All had poor necrosis after chemotherapy but adequate margins. All developed metastatic disease and 3 have died. Overall survival was 60%. 5-year survival without metastatic disease at presentation was 65%. Conclusion. Our series is similar to other centres. Challenges include older patients, poor response to chemotherapy and metastases

Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality

Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality

The orthopaedist may need to act as an important adjunct to the oncologist in management of the cancer patient with hip disease. Management of the cancer patient with routine hip pathology may be relatively straightforward but the surgeon should note that the cancer patient may be on treatment protocols which affect wound healing, the immune system and the risk of DVT. The principles of managing metastatic disease include recognising the presence of lesions in bone about the hip, the occasional need for biopsy, the use of radiation in sensitive tumors and finally surgical stabilization or replacement when needed. In some cases percutaneous cementation of metastatic disease or radiofrequency ablation may be appropriate. Factors which can complicate management of patients who have completed treatment of peri-pelvic cancer, may include radiation therapy which can lead to osteonecrosis of the acetabulum. Greater than 500Cgy of radiation has been associated with high rates of acetabular fixation failure regardless of fixation type in several series. Decision making in these patients can be aided by consultation with previous radiation therapy providers to estimate the dose sustained by the local tissues under consideration. Increased rates of infection and wound healing have also been noted secondary to long term lymphatic obliteration caused by radiation. These concerns also affect the surgeon who must manage patients with acute metastatic disease where radiation and immune-compromise secondary to chemotherapy are often present

Aim. Squamous cell carcinoma (SCC) is a rare but often devastating complication of chronic osteomyelitis. Optimum diagnosis and management are not well established. This paper aimed to develop a definitive, evidence-based approach to its diagnosis and management. Method. A systematic review of relevant published studies available in English from 1999-present was conducted. Strict inclusion criteria ensured that the diagnoses of osteomyelitis and SCC were explicit and valid. Additional cases from our institution were included using the same eligibility criteria. Data regarding patient demographics, osteomyelitis diagnosis, SCC diagnosis and its management and patient outcomes were collected. Statistical significance was assessed by Fisher's exact test. Results. Nineteen publications involving 98 patients plus eight patients managed locally were included. Eighty percent of patients were male, diagnosed with SCC at an average age of 59 years old (24–82 years), 31 years after their osteomyelitis diagnosis (3–67 years). Multiple bones were affected: tibia or fibula (59%), femur (17%), pelvis and sacrum (8%), bones of the foot and ankle (8%) and upper limbs (6%). Malignant transformation was associated predominantly with sinus (82%), ulceration (61%) and discharge (41%). SCC was diagnosed by biopsy (77%) or incidentally (23%) following definitive management for osteomyelitis. Twenty-two percent of patients had a staging CT scan. Seventy-six percent of patients underwent amputation, 16% underwent limb-sparing wide local excision and the remaining patients were palliated. Incidental diagnosis of SCC was associated with poorer outcomes in terms of death or disease recurrence (one year, p=0.052, five years p=0.021, Fisher's exact test) as was metastatic disease at SCC diagnosis (one year, p=0.006, five years, p=0.032, Fisher's exact test) and pelvic or sacral disease (one year p<0.001, five years p=0.002, Fisher's exact test). All patients who were not actively treated died within one year of SCC diagnosis. Data was suggestive that more patients who underwent amputation (versus wide local excision) were disease free at one and five years, but this was not statistically significant (one year, p=0.058, five years, p= 0.152, Fisher's exact test). Conclusions. SCC should be suspected in all cases of chronic osteomyelitis with skin changes, particularly where changes exceed 3 years duration and involve the pelvis. Multiple biopsies for histology should be taken in all suspected cases, as well as routinely during surgical excision of osteomyelitis when chronic skin changes are present. Once SCC is identified, staging CT scan should be performed to guide management. Amputation, where possible, should be considered

The orthopaedic surgeon is often consulted to manage pathologic fractures due to metastatic disease, even though he or she may not be an orthopaedic oncologist. A good understanding of the principles of management of metastatic disease is therefore important. The skeleton remains a common site for metastasis, and certain cancers have a predilection for bone, namely, tumors of the breast, prostate, lung, thyroid, and kidney. Myeloma and lymphoma also often involve bone. The proximal femur and pelvis are most commonly affected, so we will focus on those anatomic sites. The patient may present with pain and impending fracture, or with actual fracture. Careful preoperative medical optimization is recommended. If the lesion is solitary, or the primary is unknown, the diagnosis must be made by a full workup and biopsy before definitive treatment is planned. For patients with known metastasis (the most common situation), the options for treatment of pathologic lesions of the proximal femur generally center on internal fixation versus prosthetic replacement. Patients with breast or prostate metastasis can live for several years after pathologic fracture, so constructs must be relatively durable. If fixation is chosen, it must be stable enough to allow full weight bearing, since the overwhelming majority of pathologic fractures will never heal. In general, long constructs are chosen to protect the entire length of the bone. Nails should protect the femoral neck as well, so cephalomedullary devices are typically chosen. Megaprostheses can be useful in situations where bony destruction precludes stable internal fixation. Postoperative radiation is recommended after wound healing. Acetabular involvement typically requires reinforcement rings or cement augmentation with the Harrington technique. Careful multi-disciplinary medical management is recommended to minimise complications

STS are rare malignant tumours of mesenchymal origin giving a wide array of histological types and behaviour. Common sites of involvement include the extremities which are of most relevance to orthopaedic surgeons. Like almost all other malignancies, STS become more common with increasing age with median age of 65 years. All patients aged 65 and over with STS of the extremities referred to the NZ Tumour Registry at Middlemore Hospital between 1967 and 2010 were included in the study. Data collected include baseline demographics (age, sex), diagnosis, site, time of referral, definitive treatment, adjuvant therapy, surgical margins (if applicable), local recurrence, survival, and cause of death. Each patient was staged according to AJCC (1997, 5th edition) and Enneking's staging systems. Primary outcomes were measured in terms of 5-year survival alongside with cause of death. A total of 116 patients. 21 upper extremities, 95 lower extremities. Average age of 74 with a 1.2:1 female to male ratio. Stage 1 disease was uncommon, accounting for only 5 cases (4%). 3 patients died within 5 years (1 due to metastatic disease and 2 from non-sarcoma related disease). 2 patients were still alive in 2010 with 1 of them surviving >5yrs. Stage 2 disease was found in 41 patients (35%). Common histologies included malignant fibrous histiocytoma (MFH), liposarcomas, or leiomyosarcomas (LMS). 44% (n=18) had greater than 5-year survival. 20% (n=8) died within 5 years succumbing to metastatic disease. 11 were under 5-yr follow up. Stage 3 disease was found in 48 patients (41%). MFH was by far the most common diagnosis accounting for 63% of patients. 5-year survival 25% (n=12). 5-year mortality 56% (n=27) mainly from advanced disease and metastases. Rest (n=9) are still within 5-yr follow up. Distant metastases at presentation were seen in about 10% of all patients (12 cases) with the most common site of involvement being the lung. 9/13 died of metastatic disease within 5 yrs while others are still within the 5 yr follow up period. STS are most commonly observed in the elderly and prognosis depends on several factors. Management should ideally be carried in a specialised centre with early referral and combined multidisciplinary approach to optimise patient outcome

Considerable efforts have been invested into identifying risk factors for periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). Preoperative identification of risk factors for developing PJI is imperative for medical optimization and targeted prophylaxis. The purpose of this study was to create a preoperative risk calculator for PJI by assessing a patient's individual risks for developing PJI with resistant organisms and S.aureus. A retrospective review of 27117 patients (43253 TJAs) from 1999 to 2014, including 1035 PJIs, was performed. A total of 41 risk factors including demographics, comorbidities (using the Elixhauser and Charlson Index), and the number of previous TJAs, were evaluated. Multivariate analysis was performed; coefficients of the models were scaled to produce useful integer scoring. Predictive model strength was assessed employing area under the curve (AUC) analysis. Among the 41 assessed variables, the following were significant risk factors in descending order of significance: prior surgeries (p<0.0001), drug abuse (p=0.0003), revision surgery (p<0.0001), human immunodeficiency virus (p=0.0004), coagulopathy (p<0.0001), renal disease (p<0.0001), congestive heart-failure (p<0.0001), psychoses (p=0.0024), rheumatological disease (p<0.0001), knee involvement (p<0.0001), diabetes (p<0.0001), anemia (p<0.0001), males (p<0.0001), liver disease (p=0.0093), smoking (p=0.0268), and high BMI (p<0.0001). Furthermore, presence of heart-valve disease (p=0.0409), metastatic disease (p=0.0006), and pulmonary disease (p=0.0042) increased the resistant organism PJIs. Patients with metastatic disease were also more likely to be infected with S. aureus (p=0.0002). AUCs were 0.83 for any PJI, 0.86 for resistant PJI, and 0.84 for S.aureus PJI models. This large-scale single-institutional study has determined various risk factors for PJI. Some factors are modifiable and need to be addressed before elective arthroplasty. It is imperative that surgeons are aware of these risk factors and implement all possible preventative measures, including targeted prophylaxis, in patients with high-risk of PJI. Continued efforts are needed to find novel and effective solutions to minimize the burden PJI

Preoperative antibiotic prophylaxis remains one of the most important strategies for preventing periprosthetic joint infection (PJI). Current guidelines recommend giving universal antibiotic prophylaxis to all total joint arthroplasty (TJA) patients regardless of their medical conditions or immune status. The aims of this study were to determine if comorbidities influence the organism profile of PJIs and to investigate if the efficacy of the two most frequently used perioperative antibiotics (cefazolin or vancomycin) are affected by patient comorbidities. Using an institutional database, the influence of comorbidities on the organism profile of 1022 PJIs was evaluated. To investigate the influence of perioperative antibiotic monotherapy (cefazolin or vancomycin therapy) on PJI, 8575 primary TJAs were identified and analyzed based on their comorbidities. Patients with multiple perioperative antibiotics, prior septic arthritis, unavailable perioperative antibiotic information, or who underwent aseptic revision were excluded. PJI was determined from ICD-9 codes. While no comorbidities were associated with an increased rate of gram-positive or gram-negative infections, metastatic disease (odds ratio [OR] 7.54, p=0.006), rheumatologic disease (OR 1.63, p=0.046), and chronic pulmonary disease (OR 1.46, p=0.030) demonstrated an increased risk of Staphylococcus aureus PJI. In addition, metastatic disease (OR 5.71, 95% confidence interval [CI] 1.12–26.93, p=0.018), congestive heart failure (OR 2.2, 95% CI 1.16–4.00, p=0.010), chronic pulmonary disease (OR 1.76; 95% CI 1.09–2.78, p=0.015), and diabetes (OR 1.66; 95% CI 1.08–2.52, p=0.019) were associated with PJI from antibiotic resistant organisms. However, there was no difference in the rate of PJI between cefazolin and vancomycin monotherapy when stratified for the aforementioned comorbidities. The present study reveals that comorbidities do not significantly alter the organism profile of high-risk comorbidities and that comorbidities associated with immune deficits do not influence the rate of PJI between two different antibiotics. The results of this study thus support current guidelines, which provide a universal recommendation rather than a protocol that is tailored to a patient's preexisting comorbidities

INTRODUCTION. Bone tumour resection and subsequent reconstruction remains challenging for the surgeon. Obtaining adequate margins is mandatory to decrease the risk of local recurrence. Improving surgical margins quality without excessive resection, reducing surgical time and increasing the quality of the reconstruction are the main goals of today's research in bone tumour surgical management. With the outstanding improvements in imaging and computerised planning, it is now a standard. However, surgical accuracy is essential in orthopaedic oncologic surgery (Grimmer 2005). Patient specific instruments (PSI) may greatly improve the surgeon's ability to achieve the targeted resection. Thanks to its physical support, PSI can physically guide the blade yielding to a better control over the cutting process (Wong, 2014). Surgical time might significantly be reduced as well when compared to conventional method or navigated procedure. Finally, reconstruction may gain in rapidity and quality especially when allograft is the preferred solution as PSI can be designed as well for allograft cutting (Bellanova, 2013). Since 2011, PSI have systematically been used in our institution for bone tumour resection and when applicable allograft reconstruction. This paper reports the mid- to long-term medical outcomes on a large series. MATERIALS AND METHODS. Between 2011 and 2016, we systematically used PSI to remove bone tumours in 30 patients. The pre-operative planning involved the tumour delineation drawn on MRI by the surgeon. The MRI and obtained tumour volume were transferred to the CT-scan by image fusion (co- registration). Cutting planes were positioned around the tumour including a safe margin. The PSI were designed to ensure a sufficient stability but kept thin enough to limit the bone exposure. The PSI was manufactured by 3D-printing in a biocompatible and sterilisable material. PSI has been intraoperatively to cut the bone with predetermined margins. Medical files were reviewed for large data collection: type, size and site of the tumour, pre-and post-operative metastatic status, bone and soft tissues resection margins, local recurrence, use of an allograft and a PSI for graft adjustment or not for the reconstruction, the fusion of the allograft when applicable, the follow-up time and early/late complications. RESULTS. Over a period of 5 years, 30 patients were operated on with PSI (10 osteosarcomas, 4 chondrosarcomas, 10 Ewing sarcomas and 6 other types of bone tumours). Mean follow-up was 27±20 months. 18 cases out of 30 have more than 2 years follow-up and 13 out of 30 have more than 3 years of follow-up. Mean operating time was 6h02±3h44. Mean size of the tumours was 8,4±4,7cm and location was the upper limb in 5 cases, inferior limb in 15 cases and the pelvis in 10 occurrences. Metastatic disease developed postoperatively in 5 patients. Surgical margins in the bone were R0 in all cases but one case where a R1 surgery was planned to preserve a nerve root. We did not observe any local recurrence in the bone. Within soft tissues, margins were classified as R0 in 28 patients and R1 in 2 patients. In 26 cases, an allograft was used to reconstruct the bone defect. In 23 of those patients, the allograft was selected by CT scan and cut using a PSI. In the 3 allografts cut free-handily, only one demonstrated a fusion. Of the 23 cut with a guide, 12 fused completely, 2 demonstrated a partial fusion and 9 were not fused at the last follow-up. At the last follow-up, 2 patients were dead of disease, 5 were alive with metastatic disease and 23 were alive without disease. DISCUSSION. Oncology is probably the field where PSI can bring the largest advantage when compared to the conventional procedure. Several papers have reported the use of PSI for bone tumour resection. All of them have shown very promising results on in-vitro experiments (Cartiaux 2014), cadaver experiment (Wong 2012) or small clinical series (Bellanova 2013, Gouin, 2014). None of these papers report a large patient series associated with a clinically relevant follow-up. This series is the first mid- to long-term follow-up series involving PSI tumour surgery. These results are showing strong evidences of clinical improvements. It comes into contradiction with PSI for total knee arthroplasty where controversial results on the patient's outcome has been reported (Thienpont 2014). R0 margin has been systematically obtained for all bone cuttings, and local recurrence has been strongly decreased (3%) when compared to the usual recurrence rates published in the literature (from 15% to 35% according to the location). Allograft fusion seems improved as well thanks to the shape-matching of the selected allograft and a close contact between host and allograft at bony junctions. With a longer follow-up, these evidences should be stronger to definitely make PSI the best option for bone tumour resection

The management of skeletal metastases can be challenging for the orthopaedic surgeon. They represent a significant source of pain and disability for cancer patients, adding to the morbidity of their condition. Treatment is directed at the alleviation of symptoms and the restoration of function. Metastatic involvement of the proximal humerus can be especially debilitating, having the potential to cause severe pain which leads to loss of function, and may also be complicated by pathological fracture and hence attenuate upper limb function. We present a report of four cases where the use of reverse geometry proximal shoulder prostheses has provided excellent symptomatic relief and a pain free functional range of movement in metastatic proximal humerus disease. To demonstrate a novel, effective surgical strategy for the management of proximal humeral metastatic disease in elderly patients with concomitant poor rotator cuff function, a review of the medical records and radiographic imaging who underwent reverse geometry shoulder replacement for metastatic disease of the proximal humerus was performed. Two cases were secondary to breast cancer, the other two of unknown primary. All four patients were referred with severe shoulder pain significantly limiting range of movement, in one case pathological fracture was demonstrated. In all cases significant symptomatic relief was achieved in the post operative phase, signified by a marked reduction in analgesic requirements. Two patients were completely pain-free at follow up, whilst the remaining two used only minimal oral analgesia. Upper limb function was preserved in all cases, with demonstration of a satisfactory range of motion adequate for activities of daily living in all patients. No surgical complications were noted. The use of reverse geometry shoulder prostheses in proximal humeral metastases (either with or without an associated proximal humeral fracture) demonstrates a reliable and effective method of pain relief with excellent restoration of upper limb function. The unique implant geometry allows the patient to achieve a functional range of motion without reliance on the rotator cuff musculature, which is often defunct in elderly patient groups

Purpose. Evaluate the demographics, stages and outcomes in Myxoid (ML) and Round Cell liposarcoma (RCL). Establish the incidence of local recurrence and metastases. Outline the use and benefits of radiotherapy and chemotherapy. Provide guidelines for future management of these rare tumors. Method. Multicentric retrospective study of 421 cases of MRCLS primarily managed by multidisciplinary sarcoma teams in Canada. Data were collected in each centers through a standardized database and statistically analysed. Results. There were 247 males (59%) Age ranged from 14 to 88 years old (avg: 46 yrs) and the average follow-up was 5.9 yrs (range: 1 mo–21.3 yrs). Tumor volume averaged 745 cc (range: 1.5–14580 cc). The proximal lower limb, including the thigh, the buttock and the inguinal region, was the location in 314 cases (75%). Tumors were deep in 81%. On histology 305 patients were classified as pure myxoid liposarcoma, 87 had mixed myxoid/round cell histology (≥ 5% round cell content)and 19 were pure round cells only. AJCC staging were Ia: 44, Ib: 114, IIa: 115, IIb: 57, IIc: 2, III: 56, IV: 9, unknown: 24. Radiotherapy was given to 310 pts and chemotherapy to 26 pts as part of initial management. 419 underwent surgery (407 limb salvage and 12 amputations) Margins were R0 in 309, R1 in 94 and R2 in 15 patients. Overall 10 yrs local control rate was 92% and no differences were recorded between ML and RCL. Radiotherapy was significant in preventing local relapse (p= 0.03) but did not impact survival. Metastatic disease was recorded in 82 patients (19%). Chemotherapy did not prevent metastatic occurrence and survival was statistically worse for the chemotherapy group (p= 0.01). Location of first metastasis was often multiple (29), followed by lung or soft tissue (14 each), retroperitoneum (12) and bone (10). Thirty-four patients had bone involvement with spine involved in 27. The 5 and 10 yrs metastatic free survival were respectively 84 and 73% for ML and 73 and 49% for RCL (p= 0.003). Latest disease status were: 323 alive with no evidence of disease, 27 alive with disease, 8 alive with unknown status, 52 deadfrom tumor and 11 dead from other causes. Conclusion. Myxoid and Round cell Liposarcoma present different prognoses. Metastatic disease at the time of diagnosis is an unusual event. Local control is good but radiotherapy decreased the incidence of local relapse. The effectiveness of chemotherapy remains to be established for round cell liposarcoma. New staging stategies need to be identified to account for the unusual metastatic pattern of these sarcoma