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. Methods. Through retrospective review of 140 patients of all ages (mean 53 years; 2 to 88) diagnosed with soft-tissue sarcoma of the extremity with a mean follow-up of 33 months (0 to 291), we sought to determine the overall incidence of isolated abdominopelvic metastases, their temporal relationship to chest involvement, the rate of false positives, and to identify disparate rates of metastases based on sarcoma subtype. Results. A total of four patients (2.9%) exhibited isolated abdominopelvic metastatic disease during the surveillance period. In all cases of concomitant chest and abdominopelvic disease, chest involvement preceded abominopelvic involvement. There was a significant false positive rate requiring invasive workup. Conclusions. In the setting of a relative paucity of evidence concerning a rare disease process and in difference to recently published investigations, we add a clinical cohort not supportive of routine cross sectional imaging of the abdomen and pelvis. Cite this article: Bone Joint Res 2015;4:45–9

Most lumps found in the extremity are benign. Some, however, are not. An approach to tertiary referral is required to accommodate the need for specialist evaluation of all concerning lumps, while maintaining an acceptable time to diagnosis and definitive management. We describe a new approach to tertiary sarcoma service, utilising modern communication technology and the “virtual clinic” approach. Methods. Data from 1053 consecutive patients referred to the MSK oncology service at Glasgow Royal Infirmary between January 2010 and August 2012 was prospectively collected. Results. All suspected musculoskeletal sarcoma cases were discussed referred to our tertiary sarcoma virtual clinic were discussed. Mean time from referral to clinic for the 625 patents referred from January 2011 was 5.1 days. 41% of referrals came from out-with our health trust. 28.3% of patients were discharged from the virtual clinic without need for physical appointment. 45.8% were sent for further investigation prior to first clinic appointment, with the remaining 25.5% given an urgent clinic appointment. Final diagnoses of soft tissue tumours, bone tumours and “tumour like conditions” were present in almost equal parts. 358 patients (34%) of patients went on to have surgery, with 59 malignant soft tissue and 53 malignant bone tumours over this time period. Conclusions. Through an early, virtual clinic approach to tertiary sarcoma care, a third of referrals have been managed quickly without the need for an unnecessary appointment for the patient. For a further 45% of patients the first appointment will be after all necessary investigations have been performed to facilitate rapid decision making. This enables shorter clinic waiting times and rapid transition from first referral to definitive management

The role of perioperative antibiotic prophylaxis in sarcoma surgery is well established. There are no guidelines for their use in this context but there is pressure from microbiologists to comply with agreed prophylaxis for joint arthroplasty despite major differences between patient groups and risks of infection in sarcoma surgery. Two simple surveys were conducted online, the first for bone sarcoma surgery, the second for soft tissue sarcomas. An email was sent to the major centres worldwide conducting such surgery with links to the online surveys to assess current practice regarding antibiotic prophylaxis and surgical drains. The survey was limited to 8 questions, the emphasis being a simple survey, but included questions on indications, choice, duration of therapy as well as use, size and duration of surgical drains. We received 38 responses from 15 countries to the bone sarcoma survey and 33 responses from 12 countries to the soft tissue sarcoma survey. Current antibiotic prophylaxis regimens varied widely among surgeons, emphasising the controversy that exists regarding what constitutes best clinical practice. Opinions regarding use of perioperative antibiotic prophylaxis in sarcoma surgery vary widely among orthopaedic surgeons worldwide, illustrating the controversy as to what constitutes best clinical practice. This survey suggests the need for a randomised clinical trial to aid in the development of guidelines in this area

Biomechanical interpretations of bone adaptation in biological reconstructions following bone tumors would be crucial for orthopedic oncologists, particularly if based on quantitative observations. This would help to plan for surgical treatments, rehabilitative programs and communication with the patients. In particular, outcomes of the Capanna technique, which combines bone allograft and vascularized fibula autograft, lead to stable and durable reconstructions [1, 2], and different remodeling patterns have been described [3] as a response to mechanical loading. However, there are several events that are not understood and require a biomechanical interpretation, as the evolution patterns can evolve towards conditions that threaten the strength of the reconstruction. We aimed to (i) analyze the biomechanical adaptation of a femoral reconstruction after Ewing sarcoma, in terms of morphological and densitometric evolution of bone from CT data, internal loads acting on the bone during movement, mechanical competence of the reconstruction, and (ii) relate in-progress bone resorption to the mechanical stimulus induced by different motor activities. Eight CT datasets of a patient (8 yrs at surgery using the Capanna technique) during 76-month follow-up were available. The evolution of bone morphology, density and moments of inertia was quantified. At the last control, the patient underwent gait analysis (walking, chair rise/sit, stair ascent/descent, squat). We created a multiscale musculoskeletal and finite element model from CT scans and motion analysis data at the end of follow-up, using state-of-the-art modeling workflows [4, 5], to analyze muscle and joint loads, and to compare the mechanical competence of the reconstructed bone with the contralateral limb, in the current real condition and in a possible revision surgery that removed proximal screws. Although there were no reconstruction complications and osteo-fusion with intense remodeling between allograft and autograft was shown, there was a progressive decrease in allograft cortical thickness and density. There were strategies of muscle coordination that led to differences in joint loads between limbs more marked in more demanding motor activities, and generally larger in the contralateral limb. The operated femur presented a markedly low ratio of physiological strain due to load-sharing with the metal implant, particularly in the lateral aspect. A possible revision surgery removing the three most proximal screws would help restore a physiological strain configuration, while the safety of the reconstruction would not be threatened. We suggest that bone resorption is related to load-sharing and to the internal forces exerted during movement, and the mechanical stimulus should be improved by adopting modifications in the surgical treatment and by promoting physical therapy aimed at specific muscle strengthening

Introduction. Vascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. This study aimed to assess the surgical and oncological outcomes of patients treated in Denmark between 2010 and 2022. Method. We present a retrospective review of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (range: 2-39), and the median follow-up was 82 months (range: 12-138). Patients were analyzed overall and stratified into upper and lower extremity groups based on tumor location. Result. The primary rate of graft union was 63%, and after secondary procedures, the overall rate of graft union was 67%, with a median time to union of 13 months (range: 7-29). The reoperation rate was 74%, while the rate of limb salvage was 93%, with two patients undergoing amputation during follow-up. The 5-year overall survival rate was 81% (95% CI: 61-92). Patients with upper extremity tumors were more likely to attain graft union (92% vs. 47%, p=0.02) and less likely to undergo multiple reoperations (17% vs 60%, p=0.047) compared to patients with lower extremity tumors. Conclusion. Vascularized fibula grafting remains a valuable option in limb salvage surgery with acceptable long-term outcomes. However, especially in lower extremity cases, a low rate of graft union and multiple reoperations are to be expected

Primary malignant bone and soft tissue tumours often occur in the lower extremities of active individuals including children, teenagers and young adults. Survivors routinely face long-term physical disability. Participation in sports is particularly important for active young people but the impact of sarcoma treatment is not widely recognised and clinicians may be unable to provide objective advice about returning to sports. We aimed to identify and summarise the current evidence for involvement in sports following treatment of lower limb primary malignant bone and soft tissue tumours. A comprehensive search strategy was used to identify relevant studies combining the main concepts of interest: (1) Bone/Soft Tissue Tumour, (2) Lower Limb, (3) Surgical Interventions and (4) Sports. Studies were selected according to eligibility criteria with the consensus of three authors. Customised data extraction and quality assessment tools were used. 22 studies were selected, published between 1985 – 2020, and comprising 1005 patients. Fifteen studies with data on return to sports including 705 participants of which 412 (58.4%) returned to some form of sport at a mean follow-up period of 7.6 years. Four studies directly compared limb sparing and amputation; none of these were able to identify a difference in sports participation or ability. Return to sports is important for patients treated for musculoskeletal tumours, however, there is insufficient published research to provide good information and support for patients. Future prospective studies are needed to collect better pre and post-treatment data at multiple time intervals and validated clinical and patient sports participation outcomes such as type of sports participation, level and frequency and a validated sports specific outcome score, such as UCLA assessment. In particular, more comparison between limb sparing and amputation would be welcome

Summary. Starting from human musculoskeletal sarcomas, we isolated a subset of cells that display cancer stem cell properties. The control of culture conditions is crucial to enhance the isolation of this cell population. Introduction. Cancer stem cells (CSCs) have emerged as the real responsible for the development, chemoresistance, and metastatic spread of different human cancers, including musculoskeletal sarcomas. However, unlike most leukemias and solid tumors, so far, data on musculoskeletal sarcomas refer to CSCs obtained from established cell lines, and only a few authors have reported on the isolation of CSCs from tissue samples [1-7]. Reasonably due to some peculiar features of mesenchymal tumors, including the lack of unique surface markers that identify tumor progenitors, there are still partial clues on the existence of a CSC population in these cancers. Here, we report the identification of putative CSCs in musculoskeletal sarcomas using the most general accepted isolation method, the sphere culture system. Accordingly to recent reports, we also analyzed the effects of reduced oxygen availability on the behavior of sarcoma CSCs. Patients & Methods. Between 2009 and 2012, we collected fresh tissue samples from 49 patients (25 males and 24 females, age 6–85 yr) with musculoskeletal sarcomas. Cells obtained from samples were cultured in anchorage-independent serum-starved conditions, in the presence of adequate growth factors, until the formation of floating spheres, here called ‘sarcospheres’. To obtain parental tumor cell cultures, single cells obtained from biopsies were in parallel seeded in anchorage-dependent conditions, in the presence of fetal bovine serum until the formation of cell monolayers. The obtained sarcospheres were characterised in terms of gene expression and in vivo tumorigenic potential. We then exposed sarcospheres obtained from a rhabdomyosarcoma model (RD cells) to a hypoxic environment (1% O. 2. ), and analyzed their growth and gene expression to that of sarcospheres grown at standard 21% O. 2. . Results. Using a sphere-forming assay, we established sphere cultures in 5 out of 49 cases (10.2 %). All sarcosphere cultures expressed consistent mRNA levels for OCT3/4, Nanog, and SOX2. CSCs from a chondrosarcoma and from a rhabdomyosarcoma also showed the ability to recapitulate the original tumor morphology in a mouse model. Finally, we observed that hypoxia induced a significant increase of the number and size of CSCs from RD. Discussion/Conclusion. Starting from human sarcoma biopsies and established cell lines, we were able to characterise the CSC subset of musculoskeletal sarcomas, that were isolated through the sphere system assay. These cells had stem-like properties, and showed in vivo tumorigenic ability. We also observed that exposure of CSCs to low oxygen conditions increased the number and size of spheres and the expression of stem cell-related markers, suggesting that the culture in hypoxic conditions could improve the yield of the isolation method here used, and that the oxygen availability is a crucial element in the physiological maintenance of CSCs of musculoskeletal sarcomas

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

Introduction. Hand tumors are usually rare and there is not much literature about series of cases. We have studied a series of 110 cases. Hand tumors do consists of both benign and malignant cases. Methods. We studied series of 110 cases at Karnataka Institute of Medical Sciences, Hubli and Mysore Medical College & Research Institute, Mysore. We retrospectively reviewed the records of 110 patients who underwent double ray amputations at our center over few years: few had amputations of the fourth and fifth rays and others amputation of the second and third rays. Mean age at surgery was 34 years (range, 10–45 years), and minimum follow up was 64 months (mean, 98 months; range, 64–136 months). Some patients had high-grade soft tissue sarcomas of the hand, synovial sarcomas, malignant peripheral nerve sheath tumors, and undifferentiated sarcoma. No patients had detectable metastases at surgery. Results. All patients were completely disease-free at latest follow up. One patient was alive with lung metastases detected 32 months after surgery. No patients developed local tumor recurrence. Functional assessment showed a mean Musculoskeletal Tumor Society score of 24 (range, 19–28) and mean grip strength 24% of the contra lateral side (range, 17%–35%). Conclusions. The majority of osseous tumors of the hand are benign. The surgeon who evaluates and treats osseous tumors of the hand has to be familiar with limb anatomy, tumor biology, various presentations of the tumors and the range of treatment possibilities and their limitations. Lesions in the hand more often present earlier in their course than those at other sites, just because they are more likely to superficial and easily noticed. Ganglion cyst is the most frequently encountered comprising 50–70% of benign tumors of hand. Enchondroma was the next common benign bone tumour followed by osteoid osteoma, osteoblastoma, aneurismal bone cyst, giant cell tumor, epidermoid cyst, and osteochondroma. Although malignant neoplasms in the hand that arise from tissues other than the skin are very rare, the hand may be the site of distant breast, lung, kidney, esophagus, or colon adenocarcinoma metastases, most of which have a predilection for the distal phalanges. Malignant tumours of the hand are rare, although there remain many instances in which marginal excisions are performed for unsuspected malignant hand lesions. Suboptimal biopsy incisions and inadvertent contamination during these excisions may result in larger resections or amputations being necessary to ensure complete removal of the tumour with negative margins

Introduction. Needle guided biopsy of a suspected musculoskeletal malignancy has become increasingly popular as an effective modality for diagnosis. Biopsy performed in a safe manner should be performed in a centre which is also capable of performing the definitive management of such conditions. Our aim was to determine accuracy and success rates of the image guided biopsies performed by our service. Methods. A retrospective review of the Bone and Soft Tissue Sarcoma service database was performed to identify all patients who underwent diagnostic biopsy and to identify the results of such investigations. A biopsy was deemed successful if a sample of the target lesion was sampled at the time of biopsy. The successful biopsies were then classified as diagnostic or non-diagnostic if the diagnosis could be reached from the sampled tissue. Results. 465 of the 1181 new referrals to the Bone and Soft Tissue Sarcoma service in a 4 year period underwent biopsy. 75% (350) were image guided biopsies – 60% (281) ultrasound and 15% (69) CT guided. The rate of successful ultrasound guided biopsy was 94.7% and the rate of a successful diagnostic biopsy was 93.6%. CT guided biopsies were successful in 95.7% and were both successful and diagnostic in 79.7%. Discussion. The rate of a successful diagnostic ultrasound biopsy within our institution reflects the reported rate within the literature. The rate of a successful diagnostic CT guided biopsy is lower however is also consistent with that reported within the literature. Lipomatous and cartilaginous lesions are associated with a more difficult histological diagnosis on biopsy alone which is consistent with our findings. For this reason our institution has stopped performing routine image guided biopsies on these lesions

The surgical management of musculoskeletal tumours is a challenging problem, particularly in pelvic and diaphyseal tumour resection where accurate determination of bony transection points is extremely important to optimise oncologic, functional and reconstructive options. The use of computer assisted navigation in these cases could improve surgical precision and achieve pre-planned oncological margins with improved accuracy. We resected musculoskeletal tumours in ten patients using commercially available computer navigation software (Orthomap 3D, Stryker UK Ltd). Of the five pelvic tumours, two underwent biological reconstruction with extra corporeal irradiation, two endoprosthetic replacement (EPR) and one did not require bony reconstruction. Three tibial diaphyseal tumours had biological reconstruction. One patient with proximal femoral sarcoma underwent extra-articular resection and EPR. One soft tissue sarcoma of the adductor compartment involving the femur was resected with EPR. Histological examination of the resected specimens revealed tumour free margins in all cases. Post-operative radiographs and CT show resection and reconstruction as planned in all cases. Several learning points were identified related to juvenile bony anatomy and intra-operative registration. The use of computer navigation in musculoskeletal oncology allows integration of local anatomy and tumour extent to identify resection margins accurately. Furthermore, it can aid in reconstruction following tumour resection. Our experience thus far has been encouraging. Further clinical trials are required to evaluate its long-term impact on functional & oncological outcomes

Summary Statement. A novel transcutaneous CO. 2. therapy significantly enhanced the antitumor effectiveness of X-ray irradiation in human MFH xenografts The results strongly suggest that transcutaneous CO. 2. therapy could be a novel therapeutic tool for overcoming radioresistance in human malignancies. Introduction. Hypoxia contributes to tumor radioresistance. In the presence of oxygen, reactive oxygen species (ROS) play crucial roles in cellular apoptosis to irradiation. We previously showed that a novel transcutaneous application of CO. 2. can improve hypoxia and that it induces apoptosis and decreases the expression of HIF-1α in sarcoma. Therefore, we hypothesised that a transcutaneous application of CO. 2. may increase radiosensitivity in sarcoma by improvement of hypoxic condition and increasing ROS production in tumors. The purpose of this study is to examine the effect of transcutaneous application of CO. 2. on radiosensitivity in human malignant fibrous histiocytoma (MFH) cells. Methods. Cells. We used a human MFH cell line, Nara-H in this study. X-ray irradiation. X-ray irradiation was performed at a dose rate of 0.64 to 0.66 Gy/min. Colony formation assay. In vitro cell viability after X-ray irradiation was assessed by colony formation assay. In vivo studies. Nara-H cells were subcutaneously implanted to 24 nude mice which were randomly divided into 4 groups; CO. 2. group, X-ray group, Combination group and Control group. CO. 2. therapy was performed as we previously reported (1, 2). In combination group, mice were treated twice a week by X-ray at 3.2 Gy shortly after CO. 2. therapy for 2 weeks. The changes in body weight and tumor volume were monitored for 14 days in all 4 groups. The implanted tumors were excised at the end of experiment. We also excised tumors on the first day of each treatment in all 4 groups, and examined apoptosis and ROS expression by FACS analysis. The animal experiments were approved by the Animal Committee in our institute. Immunoblot analysis. The protein expression of HIF-1α, ROS-related proteins (p38 and JNK/SAPK), and apoptosis-related proteins (caspase-3 and PARP) were assessed by immunoblot analysis. FACS analysis. DNA fragmentation and ROS production in tumors were assessed by FACS analysis. Statistical analysis. ANOVA with post hoc test to compare for continuous values. All tests were considered significant at p<0.05. Results. Approximately 50% of Nara-H cells survived after a total of 3.2 Gy X-ray irradiation. Tumor volume in combination group was significantly reduced at the end of experiment (47% of that in X-ray group and 28% of that in control group). In Combination group, apoptosis with ROS production markedly increased when compared with those in Control, CO. 2. or X-ray group at 24 hours after treatment. Immunoblot analysis showed that, in combination group, the expression of phospho-p38, phospho-JNK/SPAK, and cleavage of both caspase-3 and PARP were increased compared with other groups, conversely, the expression of HIF-1α was decreased. Discussion/Conclusion. In this study, we demonstrated that the combination therapy showed more significant effects on apoptosis and ROS production through improving hypoxia in MFH cells in vivo. Our findings strongly suggest that the combination therapy of CO. 2. and X-ray could be a novel therapeutic strategy for the treatment of human MFH, and that transcutaneous application of CO. 2. may be one of the best radiosensitisers

Extracorporeal irradiation and re-implantation of a bone segment is a technique employed in bone sarcoma surgery for limb salvage in the setting of reasonable bone stock. There is neither consensus nor rationale given for the dosage of irradiation used in previous studies, with values of up to 300Gy applied. We investigated the influence of extracorporeal irradiation on the elastic and viscoelastic properties of bone. Bone specimens were extracted from mature cattle and subdivided into thirteen groups; twelve groups exposed to increasing levels of irradiation and a control group. The specimens, once irradiated, underwent mechanical testing in saline at 37°C. Mechanical properties were calculated by experimental means which included Young's Modulus, Storage Modulus and Loss Modulus. These were all obtained for comparison of the irradiated specimens to the control group. There were non-significant negligible changes in all of the mechanical properties of bone that were assessed with increasing dosage of irradiation. Therefore, we conclude that the overall mechanical effect of high levels of extracorporeal irradiation (300Gy) is minute, and can be administered to reduce the risk of malignancy recurrence

Primary bone tumours of the clavicle are rare. Currently the existing literature is limited to a single case series and case reports or cases. Information regarding the patient's demographics and tumour types is therefore limited. The aim of this study was to investigate the and also suggest a management protocol for suspected primary bone tumours of the clavicle. We retrospectively reviewed the Scottish Bone Tumour Register from January 1971 to January 2012 and included all primary bone tumours of the clavicle. We identified only sixteen primary bone tumours over forty one year's highlighting the rarity of these tumours. There were ten benign and six malignant tumours with a mean age of 32 years (Range 4 to 66). The average presentation to orthopaedics after onset of symptoms was two months with five patients presenting following a pathological fracture. Malignant tumour types identified were consistent with previous literature with two cases of Ewing's sarcoma and osteosarcoma and a single case of osteosarcoma post radiotherapy and a single case of chondrosarcoma. Benign tumours were treated effectively with intralesional procedures. Malignant tumours were treated with wide local excision and subtotal or total clavicle excision. We suggest an investigatory and treatment protocol for patients with a suspected primary bone tumour of the clavicle. This is the largest series of primary bone tumours of the clavicle in the literature

Summary Statement. Survivin is a member of the inhibitor of apoptosis family, which may contribute to the progression of human MFH via inhibiting the mitochondrial apoptosis, and may be considered as a potent therapeutic target for the treatment of human MFH. Introduction. Survivin is a member of the inhibitor of apoptosis (IAP) family, which usually expresses in the embryonic lung and fetal organs in the developmental stages, but is undetectable in normal adult tissues other than thymus, placenta, CD34. +. stem cells, and basal colonic epitherial cells. However, several studies reported that survivin is highly expressed in various human malignancies, including sarcomas, and increased expression of survivin is an unfavorable prognostic marker correlating with decreased overall survival in cancer patients. We have previously reported that survivin was strongly expressed in human malignant fibrous histiocyoma (MFH), however, the roles of survivin in human MFH have not been studied. The aim of this study was to evaluate the effect of survivin inhibition on apoptotic activity in human MFH cells. Methods. Nara-H, a human MFH cell line which expresses the high levels of survivin, was used in this study. Cells were cultured in DMEM supplemented with 10% FBS and 1% penicillin/streptomycin at 37°C in a humidified atmosphere containing 5% CO. 2. To evaluate the effect of survivin inhibition on MFH cell apoptosis, cells were transfected with either a survivin specific siRNA (survivin-siRNA) or a non-specific control siRNA (control-siRNA) by lipofection method. After siRNA transfection, the efficiency of siRNA knockdown of survivin was assessed by quantitative real time PCR. Expressions of apoptosis-related proteins, such as caspase-3, caspase-9 and PARP, were assessed by immunoblot analysis, and the apoptotic activity was evaluated by flow cytometric analysis. Results. Transfection of survivin-siRNA strongly suppressed the expression of survivin compared with control-siRNA. Immunoblot analyses revealed that expressions of cleaved forms of caspase-3, caspase-9 and PARP were increased in survivin-siRNA transfected cells, while the expressions were barely detected in control cells. In flow cytometric analysis, the number of apoptotic cells was significantly increased in survivin-siRNA transfected cells compared with that in control cells. Discussion/Conclusion. Previous studies revealed that survivin regulates the mitochondrial apoptotic pathway, and that overexpression of survivin is associated with tumor growth, progression, and resistance to conventional targeted anticancer agents in various human malignancies. In the current study, we demonstrated that siRNA knockdown of survivin induced the cleavage of caspase-3, caspase-9 and PARP, and increased the apoptotic activity in human MFH cells. The findings in this study strongly suggest that survivin may contribute to the progression of human MFH via inhibiting the mitochondrial apoptosis in human MFH, and may be considered as a potent therapeutic target for the treatment of human MFH

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

Local treatment with phenol is often used after intralesional excision of chondroblastomas and giant-cell tumours which involve bone near joints, and has been shown to reduce the rate of recurrence. The ideal concentration of phenol is uncertain, but may be important because of the high rate of absorption and toxicity. We have studied the effectiveness of different concentrations on standard sarcoma cell lines. Our results suggest that a 5% solution of phenol is effective against dispersed single cells, and that higher concentrations give no significant advantage, but create problems due to lack of homogeneous mixing, temperature and safety

We performed positron emission tomography (PET) with . 18. fluorine-fluoro-2-deoxy-D-glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in order to evaluate its role in operative planning. The standardised uptake value (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions, the cases were divided into high (≥ 1.9) and low (< 1.9) SUV groups. The sensitivity of PET for correctly diagnosing malignancy was 100% with a specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for metastatic lesions was twice that for primary sarcomas (p < 0.0015). Our results suggest that the SUV may be useful in differentiating malignant tumours from benign lesions. However, some of the latter, such as schwannomas, had high SUVs so that biopsy or wide resection was selected as the first operation. Thus, some other quantitative analysis may be required for preoperative planning in cases of high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain reaction revealed that the RNA message of a key enzyme in glucose metabolism, phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only high FDG-uptake lesions, suggesting that a high expression of the PHI message may be associated with accumulation of FDG in musculoskeletal tumours

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H₂O₂) and 50% zinc chloride (ZnCI₂) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions.

Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H₂O₂ and 50% ZnCI₂. The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures.

These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone.