Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening. Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival. In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed. Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required

Background. The discussion over the duration, type of therapy and regimen to be used in osteoarticular tuberculosis is losing importance in all orthopaedic gathering. Still little consensus is there over the universality of a treatment regime for osteoarticular tuberculosis. Material and Method. 340 new cases of osteoarticular tuberculosis were included in the study that were medically treated in the department of orthopaedics in a tertiary care center between 2001 and 2011. Out of which 202 cases were of spinal tuberculosis and 138 cases of extraspinal tuberculosis. 88 cases of spinal tuberculosis were treated by conventional method and 114 cases by short course chemotherapy. 60 cases of extraarticular tuberculosis were treated by conventional chemotherapy and 78 cases by short course and intermittent therapy. Results. All cases were evaluated on clinical, radiological and haematological basis. Cases who received conventional therapy received 18–24 months of treatment irrespective to the clinical, radiological and haematological parameters. Whereas those who received short course (2HRZE+4 HR) and intermittent therapy (DOTS) were evaluated for clinical improvement. Maximum follow up was of 12.8 years (conventional) minimum follow of 8 years (intermittent). The trend of fall in ESR, clinical and radiological parameters showed improvement beyond 2 years of initiation of treatment in cases that had stopped treatment at 6 months. But the improvement was slow after six months even in cases who received 24 months of chemotherapy. There were no relapses in all the three groups. Conclusion. This study reinforces that chemotherapy tailored to the response of treatment (6-9months) is the rational therapy. This study gives an insight over the evolution of different regimes as well as gives an understanding of the clinical treatment. Level of Evidence. Level 1. No relevant financial disclosures or conflicts of interest from any of the authors

Osteosarcoma and other types of bone cancers often require bone resection, and backfill with cement. A novel silorane-based cement without PMMA's drawbacks, previously developed for dental applications, has been reformulated for orthopedic use. The aim of this study is to assess each cement's ability to elute doxorubicin, maintain its potency, and maintain suitable weight-bearing strength.

The silorane-based epoxy cement was synthesized using a platinum-based Lamoreaux's catalyst. Four groups of cement were prepared. Two PMMA groups, one without any additives, one with 200 mg of doxorubicin. Two silorane groups: one without any additive, one with doxorubicin, added so that the w% of drug into both cements were equal. Pellets 6 × 12 mm were used for testing (ASTM F451). n=10. Ten pellets from each group were kept dry. All others were placed into tubes containing 2.5 mL of PBS and stored at 37 °C. Elution from doxorubicin-containing groups were collected every day for 7 days, with daily PBS changeout. Antibiotic concentrations were determined via HPLC. Compressive strength and compressive modulus of all groups were determined for unsoaked specimens, and those soaked for 7 and 14 days. MTT assays were done using an MG63 osteosarcoma cell line.

Both cements were able to elute doxorubicin over 7 days in clinically-favorable quantities. For PMMA samples, the incorporation of doxorubicin was shown to significantly affect the compressive strength and modulus of the samples (p<0.01). Incorporation of doxorubicin into silorane had no significant effect on either (p>.05). MTT assays indicated that doxorubicin incorporated into the silorane cement maintained its effectiveness whereas that into PMMA did not. At the dosing used, both cements remained above the 70 MPa.

Both PMMA and silorane-based cements can deliver doxorubicin. Doxorubicin, however, interacts chemically with PMMA, inhibiting polymerization and lowering the chemotherapeutic's effectiveness.

Summary. Methotrexate chemotherapy (commonly used in treating cancers and rheumatoid arthritis) creates an inflammatory condition in bone, decreasing osteogenesis, enhancing adipogenesis, increasing osteoclastogenesis, leading to bone loss and marrow adiposity; treatment with fish oil or folinic acid counteracts these negative effects and prevents bone loss. Introduction. Chemotherapy with anti-metabolite methotrexate (MTX) is commonly used in treating cancers and rheumatoid arthritis; however it is known to cause bone loss for which currently there are no adjunct preventative treatments. Methods and Materials. Using a rat model, this study investigated the damaging effects in bones caused by daily MTX injections (0.75mg/kg) for 5 consecutive days (mimicking induction phase treatment for childhood leukaemia) and also the potential protective benefits of omega-3 fatty acid-rich fish oil at different doses (0.25, 0.5 or 0.75 mL/100g BW) in comparison to antidote folinic acid (given i.p at 0.75mg/kg 6 hours post MTX, which is clinically used to reduce MTX toxicities in soft tissues). Results. Histological analysis showed that MTX significantly reduced primary spongiosa bone height and metaphyseal trabecular bone volume. MTX also significantly reduced density of osteoblasts at the secondary spongiosa. Ex vivo differentiation assays with bone marrow stromal cell populations of treated rats revealed a significant reduction in osteogenic differentiation but an increase in adipogenesis. Consistently, RT-PCR gene expression study within the stromal cell population revealed a lower expression of osteogenic transcription factors Runx2 and Osx and bone matrix protein osteocalcin but a significantly upregulated adipogenesis-related genes FABP4 and PPARγ, indicating that MTX chemotherapy induces a switch in the differentiation potential towards adipogenesis at the expense of osteogenesis. MTX increased the density of osteoclasts within the metaphyseal bone as revealed by histological analysis and osteoclast precursor cell pool as shown by ex vivo osteoclastogenesis assay with bone marrow samples. Consistently, mRNA expression of proinflammatory and osteoclastogenic cytokines IL-1, IL-6, TNF-α, and the RANKL/OPG ratio were significantly upregulated by MTX. Supplementary treatment with fish oil (0.5mL/100g BW) or folinic acid significantly preserved metaphyseal trabecular bone volume, osteoblast density, and bone marrow stromal cell osteogenic differentiation and suppressed MTX-induced adipogenesis. These supplements also prevented MTX-induced increased osteoclast density, osteoclastogenesis, and expression of proinflammatory and osteoclastogenic cytokines. Conclusion. These results suggest that MTX chemotherapy creates an inflammatory condition in bone resulting in increased osteoclast formation and decreased osteoblast formation thus leading to bone loss, and that supplementary treatment with fish oil at 0.5mL/100g BW or folinic acid counteract these negative effects, helping to conserve bone formation, suppress bone resorption and bone marrow adiposity, and thus prevent bone loss during MTX chemotherapy

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.

Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months.

The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm³ (sd 261) and 545 cells/mm³ (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm³ (sd 343)) still remained lower than that of group I (1071 cells/mm³ (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

Osteosarcoma (OS) is a highly malignant primary tumor frequently occurring in children and adolescents. The mainstay of therapy is neoadjuvant chemotherapy and surgical removal of the lesion yielding a 50–70% of 5-year survival rate. Unfortunately, chemotherapy is currently unable to induce complete tumor necrosis leaving residual tumor cells free to metastasize or recidivate, thus resulting in a 30% mortality. The major limitation in those patients is the development of multidrug resistance (MDR) and the low water solubility of drugs such as Paclitaxel (PTX) that is in fact not included in the majority of chemotherapy protocols for OS treatment. We thus hypothesized to prevent the emergence of MDR and obtain significant tumor reduction, by engineering innovative nanoparticles (NPs) able to vehiculate the PTX and induce a dual synergic action: the cytostatic effect of PTX and the cytotoxicity generated by reactive oxygen species produced from light triggered photoactivation (PDT) of Chlorin e6 photosensitizer. To further improve the efficacy and reduce the side effects of NPs systemic administration, Mesenchymal Stromal Cells (MSC) are used as a “Trojan horse” to deliver the NPs directly to tumor cells, taking advantage of MSC ability to selectively recognize and efficiently engraft in OS tumor stroma. HSA were conjugated with photosensitizer Ce6 and the functionalized protein was used to produce PTX loaded nanoparticles through desolvation technique and drug-induced protein self-assembly (PTX-Ce6@HSA NP). Human MSC lines, isolated from the Bone marrow (BM) of different donors, were then loaded with different dosages of nanoparticles and their ability to internalize and transport the NPs, migrate and induce cytotoxic ROS upon light treatment were tested in in vitro cultures. Preliminary results showed that MSC efficiently internalize PTX-Ce6@HSA NPs and the photosensitizer Ce6 remains active inside the cells for at least 3 days after loading. Electron microscopy performed onto loaded MSC showed that NPs internalization take places via clathrin mediated transport, whereas HPLC analysis demonstrated a release kinetics of PTX mediated by exocytosis. Finally, PTX-Ce6@HSA NPs loaded MSC co-cultured with the OS tumor cell line SaOS-2 showed a significant tumor cell growth reduction. So fare, advances in drug delivery have failed to produce specific tool to improve the overall survival of OS patients. However, given our preliminary in vitro data we believe that the proposed multimodal therapy will minimize the side effects of the systemic chemotherapy and enhance the efficacy through the synergic effect of PTX and PDT. In the future, our strategy could be intended as an innovative co-adjuvant approach for OS treatment to be performed right before surgery to eliminate residual tumors cells after tumor mass removal

Purpose. Extraskeletal chondrosarcoma is a rare tumor with an indolent course and high propensity for local recurrence and metastasis. This tumor most commonly presents in the proximal extremities of middle-aged males, and is commonly asymptomatic. Although slow growing, these tumors have a significant risk of eventual relapse and metastases, especially to the lung. There are no clinical trials that investigated the best treatment options for this tumor given its very low incidence. The aim of this study is to present the surgical and clinical results of extraskeletal chondrosarcoma, which is a rare tumor. Methods. In our clinic, the information of 13 patients who were diagnosed with extra-skeletal chondrosarcoma between 2006 and 2018 were retrospectively reviewed. Demographic information, tumor size, surgical treatments, chemotherapy and radiotherapy status, follow-up times, recurrence and metastases of the patients were recorded. Results. This study included 13 patients with an average age of 53.6 ± 15 (range, 28 to 73) years diagnosed with extraskelatal chondrosarcoma. In 8 of the patients, the tumor was located in the lower limbs and it was observed that the thigh was located mostly (46.2%). The mean follow-up period of the patients was 52.8 ± 19.9 (range, 24 to 96) months. All patients underwent extensive resection and only one patient had a positive surgical margin. In the follow-up, 5 (38.5%) of the patients developed recurrence, while 6 patients had lung metastasis (46.2%) and 53.8% (7 patients) of the patients exitus. The mean tumor size was 10.4 ± 3.2 (range, 5 to 17) cm. The median survival time of the patients in the study was 61 (50.5–71.4) months. The 5-year survival rate is 51.8%. There was no significant difference between survival times according to age, gender, side, limb location, postoperative RT, recurrence and presence of lung metastasis (log rank tests p > 0.05). The cut off value for exitus obtained by ROC analysis of tumor size was determined as 11 cm (fig 1). Accordingly, the survival time of patients with 11 cm and above tumor size was observed to be statistically significantly shorter. Conclusion. Consequently, ECM is a rare soft tissue sarcoma with high local recurrence and metastasis capacity. Therefore, close follow-up is recommended. The first option should be extensive resection. Studies with large patient series on the prognostic factors of the future ECM are needed. For any figures or tables, please contact the authors directly

Summary Statement. RANK is expressed in 18% of human osteosarcomas and is likely to provide additional prognostic information for clinical purposes in osteosarcoma patients at the time of diagnosis. Introduction. The receptor activator of nuclear factor kappa (RANK), a member of the tumor necrosis factor family, is activated by its ligand and regulates the differentiation of osteoclasts and dendritic cells. Local growth of osteosarcoma involves destruction of the host bone by osteoclasts and proteolytic mechanisms. Although prognosis of osteosarcoma has been improved by chemotherapy during the last decades, the problem of non responders and the lack of prognostic markers remains. It is the aim of this study to investigate the prognostic and predictive value of RANK expression in human osteosarcoma. Patients & Methods. The expression of RANK was examined immunohistochemically in biopsies of 43 patients (mean age 25.7 years) with high grade osteosarcoma and the results were correlated with histologic response to chemotherapy, disease free and overall survival. Tumors with more than 40% positive osteosarcoma cells were scored positive. Results. In 8 of 43 (18%) osteosarcoma specimens RANK expression could be dedected, the rest were negative. RANK expression showed a statistically significant correlation with overall survival of patients. 7/8 patients with RANK expressing tumours died, whereas only one in the negative group (88% in RANK positive tumours versus 37%; p<0.05). No significant difference was found when comparing RANK expression status with response to chemotherapy; 50% had a poor and 50% had a good response in RANK positive and 30,3% had a good and 69,7% had a bad response in RANK negative osteosarcomas. The appearance of metastases did not correlate with RANK expression status (37,5% metastases in RANK positive tumours versus 28,6% in negative). Discussion/Conclusion. In conclusion our findings suggest that RANK is likely to provide additional prognostic information for clinical purposes in osteosarcoma patients at the time of diagnosis

Summary. There is little consensus regarding the regime for treatment of tuberculosis of spine, although WHO has laid down guidelines couple of years back classifying spinal tuberculosis in Category 1. This study proves the efficacy of WHO regime in spinal tuberculosis by clinico-radiological evaluation. Introduction. The medical fraternity is divided over the duration of chemotherapy in cases spinal tuberculosis. WHO clearly recommend spinal tuberculosis under Category I, but not accepted by most clinicians. Patient and Methods. In this prospective study during the period between August 2005 and July 2012, a total of 76 cases were diagnosed and evaluated clinico-radiologically to test the efficacy of WHO protocol (2HRZE+4HR) in our hospital with a mean follow up of 50 months (30 – 80 months). Results. Spinal tuberculosis was seen in 56% of all osteoarticular tuberculosis. Maximum population was between 11–50 years, females were involved more than males (66%), and regional distribution was different in males (Lumbar) and females (Thoracic). Skip and multifocal lesions were seen in 13% (6 cases), more common in immune compromised cases. Pain was the most common symptom (95%) followed by constitutional symptoms. Radiographic changes were nonspecific, appear late and suggestive of tuberculosis in 53%case, MRI is very useful in diagnosing in 95% cases especially when X ray is contributory. ESR is useful tool for follow up of patients, elevated in 94%cases. Results were evaluated on clinical, hematological and radiological basis. Of the total 64cases (after dropouts, lost in follow up, mortality), 50 patients (78%) received treatment for 6 months and14 cases for more than 6months (P value<0.001). No MDR cases were present. In 50 patients fall in ESR at the end of 2 months was found to be statistically significant (P value<0.05) and hence were given a treatment for 6 months, the fall at the end of 6 months was highly significant (P value<0.001). In rest of the 14 cases the duration of treatment was given for more than 6 months as the trend of fall of ESR was not significant. MRI changes were assessed in the form of osteitis, osteitis with discitis, abscess formation and granulation tissue on initiation of treatment, completion of treatment and 6 months after completion of treatment. Conclusion and Discussion. The experience shows that spinal tuberculosis is common in a tertiary health care centre in India with diagnosis possible by combination of clinical evaluation and radiological evaluation. Statistical significance was found in clinical symptoms, ESR trends and MRI evaluation in cases receiving 6 months of chemotherapy. With this study, WHO short course chemotherapy was found to be effective in spinal tuberculosis, with no relapse over a period of 6 years

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

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

Osteosarcoma (OS) is an aggressive bone malignancy with a high relapse rate despite combined treatment with surgery and multiagent chemotherapy. As for other cancers, OS-associated microenvironment may contribute to tumor initiation, growth, and metastasis. We consider mesenchymal stromal cells (MSC) as a relevant cellular component of OS microenvironment, and have previously found that the interaction between MSC and tumor cells is bidirectional: tumor cells can modulate their peripheral environment that in turn becomes more favourable to tumor growth through metabolic reprogramming (1). Stem-like cells were derived from HOS osteosarcoma cell line by using the spherogenic system (2). CSC isolated from HOS (HOS-CSC) were co-coltured with MSC isolated from bone marrow. Cell lysates and supernatants were collected for the analysis of RNA expression and of secreted cytokines, by Q-RT-PCR and specific ELISA assays, respectively. Here, we determined the effects of MSC on OS stemness and migration, two major features associated with recurrence and chemoresistance. Recruitment of MSC to the tumor environment leads to enhanced proliferation of OS stem cells, which increase the expression levels of TGFβ1. The latter, in turn, could be responsible for the activation of NF-kB genes and IL-6 secretion by MSC. Pro-tumorigenic effects of MSC, via IL-6, including induction of HOS-CSC migration and sphere growth, can be counteracted by IL-6 neutralizing antibody. The presence of MSC is also responsible for increased expression of adhesion molecules involved in intra- or extra-vasation. Stromal cells in combination with OS spheres exploit a vicious cycle where the presence of CSC stimulates mesenchymal cytokine secretion, which in turn increases stemness, proliferation, migration, and metastatic potential of CSC. Furthermore, for the first time we identified a novel OS stem cell marker, the Met proto-oncogene, that is frequently overexpressed and is pathogenetically relevant in OS (2 and 3). Altogether, our data corroborates the concept that a comprehensive knowledge of the interplay between tumor and stroma that also includes the stem-like fraction of tumor cells is needed to develop novel and effective anti-cancer therapies

Summary Statement. In this study we suggested a possible role of prion proteins genes in osteosarcoma. Therefore, the inhibition of prion proteins expression must be tested because it could represent a new approach to the molecular treatment of osteosarcoma. Introduction. Although osteosarcoma is the most common bone malignancy, the molecular and cellular mechanisms influencing its pathogenesis have remained elusive. Prion proteins (PRNP and PRND), known mostly for its involvement in neurodegenerative spongiform encephalopathies, have been recently demonstrated to be involved in resistance to apoptosis, tumorigenesis, proliferation and metastasis. Patients & Methods. The main aim of research was to study whether prion proteins were over-expressed in human osteosarcoma, and if prion proteins could have a role also in osteosarcomas. We evaluated differential gene expression between 22 cases of osteosarcoma and 40 cases of normal bone specimens through cDNA microarray analysis spanning a substantial fraction of the human genome. Results. PRNP and PRND are significantly over-expressed in osteosarcoma. PRNP and PRND appear involved with some important genes related to tumorigenesis and apoptosis. PRNP is linked to PTK2, RBBP9 and TGFB1 while PRND is linked to TNFSF10, BCL2A1, NFKB2 and TP53RK. Discussion/Conclusion. Increased expression on Affymetrix arrays of prion proteins seems to be associated with the development of osteosarcoma. Prions seem to induce a negative regulation of apoptosis, thus promoting osteosarcoma development and progression. Osteosarcoma is a very aggressive tumor and even after modern chemotherapy and excision of tumors efforts are needed to improve clinical outcome. Since Prion proteins seem to be related to osteosarcoma development, their inhibition could represent a new approach to the molecular treatment of osteosarcoma

Summary. Neurological deficits resulting from spinal cord compression occur infrequently. When presented with neurological compromise, the most common management was radiotherapy, with surgery only being offered to patients who developed neurological deficit or pathological fracture resulting in unresolved severe pain post radiotherapy. Introduction. Nasopharyngeal carcinoma has been reported to have a higher incidence of distant metastases to the spine. This study was conducted to evaluate the incidence, presentation and management of neurological involvement related to spinal metastasis from nasopharyngeal carcinoma. Patients and Methods. 814 patients with the diagnosis of NPC who presented to the National University Hospital (NUH), Singapore, over a 5-year period (2007–2011) were recruited for this study. Case records from clinics, wards, operating theatres at NUH and nationwide electronic records of polyclinics and Emergency Medical Department (EMD) were obtained and reviewed. The data collected included demographics, medical history, radiologic and histopathology reports. Results. Of 814 patients with NPC, 99 had spinal metastasis. 26 were treated with radiotherapy, 25 with chemotherapy, 5 with both chemo and radiotherapy and 6 with surgery. Out of 6 patients requiring spinal surgical procedure, 3 had neurological deficits in the form of focal sensory or motor deficits and 4 had symptoms of pathologic fracture. One patient had both neurological deficit and pathological fracture. All these 6 patients were treated with a spinal surgical procedure of stabilization and/or decompression. Discussion/Conclusion. Spinal metastasis is common in patients with NPC and back pain is the usual presentation. Neurological deficits resulting from nerve root or spinal cord compression occur infrequently. When presented with neurological compromise, the most common management was radiotherapy, with surgery only being offered to patients who developed neurological deficit or pathological fracture resulting in unresolved severe pain post radiotherapy

Bony tumours of the foot account for approximately 3% of all osseous tumours. However, literature regarding os calcis tumours comprises individual case reports, short case series or literature reviews, with the last large case series in 1973. We retrospectively reviewed the medical notes and imaging for all patients with calcaneal tumours recorded in the Scottish Bone Tumour Registry since the 1940's. Demographics, presentation, investigation, histology, management and outcome were reviewed. 38 calcaneal tumours were identified. Male to female ratio 2:1, mean age at presentation 30 with heel pain and swelling, average length of symptoms 9 months. 4 cases present with pathological fracture. 24 tumours benign including 6 unicameral bone cysts, 3 chondroblastoma, 3 PVNS with calcaneal erosion, and a wide variety of individual lesions. 13 malignant tumours comprising 6 osteosarcoma, 5 chondrosarcoma and 2 Ewings sarcoma. 1 metastatic carcinoma. Tumours of the calcaneus frequently are delayed in diagnosis due to their rarity and lack of clinician familiarity. They are more common in men and have a 1 in 3 risk of malignancy, covering a wide variety of lesions. Outcome is dependent on early diagnosis, timely surgery and most importantly neo-adjuvant chemotherapy. Diagnosis is often made on plain radiograph but MRI is the gold standard. We present the largest case series of calcaneal tumours, from our experience with the Scottish Bone Tumour Registry. Despite their rarity clinicians should maintain a high index of suspicion as accurate and timely diagnosis is important to management and outcome

Bone tumours may recur locally even after wide surgical excision and systemic chemotherapy. Local control of growth may be accomplished by the addition of cytostatic drugs such as methotrexate (MTX) to bone cement used to fill the defect after surgery and to stabilise the reconstructive prosthesis. We have studied the elution kinetics of MTX and its solvent N-methyl-pyrrolidone (NMP) from bone cement and their biological activities in five cell lines of osteosarcoma and in osteoblasts, and compared them with the effects of the parent compounds alone and in combination. Our findings show that MTX is released continuously over months at concentrations highly cytotoxic to osteosarcoma cells and suggest that the impregnated bone cement would be effective in the long term. Proliferating osteoblasts, however, were much less sensitive towards MTX. The dose-response relationship for NMP and experiments with MTX/NMP-mixtures show that the eluted concentrations of solvent are not toxic and do not influence the effects of MTX. We suggest that bone cement containing MTX dissolved in NMP releases the drug in a suitable and effective way and may be of value in the treatment of bone tumours

Objectives

The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method.

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.

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage.

Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test.

Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02).

We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue.

We examined osteochondral autografts, obtained at a mean of 19.5 months (3 to 48) following extracorporeal irradiation and re-implantation to replace bone defects after removal of tumours. The specimens were obtained from six patients (mean age 13.3 years (10 to 18)) and consisted of articular cartilage (five), subchondral bone (five), external callus (one) and tendon (one). The tumour cells in the grafts were eradicated by a single radiation dose of 60 Gy. In three cartilage specimens, viable chondrocytes were detected. The survival of chondrocytes was confirmed with S-100 protein staining. Three specimens from the subchondral region and a tendon displayed features of regeneration. Callus was seen at the junction between host and irradiated bone.