We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured. Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value

Abstract. Background. Schwannomas are slow-growing, benign tumours normally originating from the Schwann cells of the nerve sheath. Intraosseous schwannoma accounts for 0.175% of primary bone tumours and extremely rare especially outside the axial skeleton. Monoclonal gammopathy has been associated with soft tissue schwannomas but never with the intraosseous variety. Presenting problem. A 55-year-old woman with a background of monoclonal gammopathy of undetermined significance (MGUS) presented with a 2-year history of right thigh pain. CT scan showed a well defined, lytic lesion with a thin peripheral rim of sclerosis in the midshaft of the femur. MRI displayed a hyperintense, well marginated and homogenous lesion. Definitive diagnosis was made based on the classical histopathological appearance of schwannoma. Clinical management. We managed our patient with local curettage and prophylactic cephalomedullary nailing on the basis of a high mirel score. Discussion. Intraosseous schwannomas are poorly understood but most commonly reported in middle-aged women. Radiologically, their differential diagnosis includes malignant bone tumours, solitary bone cysts, aneurysmal bone cysts and giant cell tumours. As a result, they are usually diagnosed incidentally on histology. Although malignant transformation is possible in soft tissue schwannomas, all intraosseous schwannomas reported to date have been benign. This case demonstrates the importance of suspecting intraosseous schwannoma as a differential diagnosis for lytic bone lesions to avoid the overtreatment of patients. We also highlight monoclonal gammopathy of undetermined significance as a potential risk factor for a poorly understood disease and make recommendations about the appropriate management of these lesions. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

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 aim of this project is to test the parameters of Patient Specific Instruments (PSIs) and measuring accuracy of surgical cuts using sawblades with different depths of PSI cutting guide slot. Clear operative oncological margins are the main target in malignant bone tumour resections. Novel techniques like patient specific instruments (PSIs) are becoming more popular in orthopaedic oncology surgeries and arthroplasty in general with studies suggesting improved accuracy and reduced operating time using PSIs compared to conventional techniques and computer assisted surgery. Improved accuracy would allow preservation of more natural bone of patients with smaller tumour margin. Novel low-cost technology improving accuracy of surgical cuts, would facilitate highly delicate surgeries such as Joint Preserving Surgery (JPS) that improves quality of life for patients by preserving the tibial plateau and muscle attachments around the knee whilst removing bone tumours with adequate tumour margins. There are no universal guidelines on PSI designs and there are no studies showing how specific design of PSIs would affect accuracy of the surgical cuts. We hypothesised if an increased depth of the cutting slot guide for sawblades on the PSI would improve accuracy of cuts. A pilot drybone experiment was set up, testing 3 different designs of a PSI with changing cutting slot depth, simulating removal of a tumour on the proximal tibia. A handheld 3D scanner (Artec Spider, Luxembourg) was used to scan tibia drybones and Computer Aided Design (CAD) software was used to simulate osteosarcoma position and plan intentioned cuts. PSI were designed accordingly to allow sufficient tumour. The only change for the 3 designs is the cutting slot depth (10mm, 15mm & 20mm). 7 orthopaedic surgeons were recruited to participate and perform JPS on the drybones using each design 2 times. Each fragment was then scanned with the 3D scanner and were then matched onto the reference tibia with customized software to calculate how each cut (inferior-superior-vertical) deviated from plan in millimetres and degrees. In order to tackle PSI placement error, a dedicated 3D-printed mould was used. Comparing actual cuts to planned cuts, changing the height of the cutting slot guide on the designed PSI did not deviate accuracy enough to interfere with a tumour resection margin set to maximum 10mm. We have obtained very accurate cuts with the mean deviations(error) for the 3 different designs were: [10mm slot: 0.76 ± 0.52mm, 2.37 ± 1.26°], [15 mm slot: 0.43 ± 0.40 mm, 1.89 ± 1.04°] and [20 mm: 0.74 ± 0.65 mm, 2.40 ± 1.78°] respectively, with no significant difference between mean error for each design overall, but the inferior cuts deviation in mm did show to be more precise with 15 mm cutting slot (p<0.05). Simulating a cut to resect an osteosarcoma, none of the proposed designs introduced error that would interfere with the tumour margin set. Though 15mm showed increased precision on only one parameter, we concluded that 10mm cutting slot would be sufficient for the accuracy needed for this specific surgical intervention. Future work would include comparing PSI slot depth with position of knee implants after arthroplasty, and how optimisation of other design parameters of PSIs can continue to improve accuracy of orthopaedic surgery and allow increase of bone and joint preservation

Summary. Reciprocal metabolic reprogramming of MSCs and osteosarcoma cells influences tumor-stroma cross talk. Drugs targeting Warburg metabolism may define innovative therapeutic approaches in osteosarcoma. Introduction. Osteosarcoma (OS) is a malignant primary bone tumour of mesenchymal origin, in which cells with stem-like characteristics (CSCs) have been described. Recent studies have demonstrated a mutual interaction between stroma and tumor cells in exploiting a role in the pathogenesis and progression of cancer, and also in the enhancing stemness phenotype. Here we take in consideration the complex juxtacrine and paracrine intercellular cross talk played by mesenchymal stromal cells (MSCs) with adherent osteosarcoma cells and OS cells with stem-like characteristics (CSCs). Methods. MSCs were isolated from human adipose tissue and expanded. To evaluate the interaction between the stroma and the cancer cell compartment, we used two different osteosarcoma cancer cell lines (Saos-2 and HOS) and co-cultured them with MSCs. The different cell populations were sorted to study the reciprocal interaction including metabolic reprogramming. CSCs were obtained from SAOS-2 and HOS cell lines using the sphere formation assay and characterised for their self-renewal, mesenchymal stem cell properties and expression of pluripotency markers. CSCs sensitivity to paracrine factors produced by human MSCs was analysed in a model of co-culture system. Mitochondrial activity in the co-culture systems was also evaluated. Results. Our results revealed that upon intercellular contact, MSCs undergo Warburg metabolism and mitochondrial oxidative stress. In particular, the cell contact activated the stromal component, triggering autophagy and increased expression of monocarboxylate transporter-4 (MCT4) responsible for the extrusion of lactate. Conversely, osteosarcoma cancer cells, upon contact with MSCs, increased their aerobic metabolism and their development. In addition, using a co-culture method without cell contact, we observed that MSCs grown in serum-starvation conditions promoted proliferation of the CSCs obtained from OS cells, probably by secreting one or several soluble factors. By Real Time PCR we evaluated the gene expression of stemness markers like Oct4, Nanog and SOX2, which appeared to have increased in CSCs. Conclusions. The final goal is to have a better understanding of the role of the stroma on tumor cell metabolism. Apparently, our data show that MSCs may exploit a role in the modulation of tumor metabolic activity and stemness/differentiation in osteosarcoma. Importantly, these findings suggest an adaptation of cancer cells to bioenergetic changes “engaging” stromal cells as their survival strategy. Understanding the interactions in the tumor microenvironment should present new opportunities for the design of cancer therapeutics

Objectives

We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model.

Objectives

Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results.