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

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

The primary aim of this study was to compare the clinical outcomes of osteoid osteoma (OO) between the group of patients with the presence of nidus on biopsy samples from radiofrequency ablation (RFA) with those without nidus. Secondly, we aimed to examine other factors that may affect the outcomes of OO reflecting our experience as a tertiary orthopaedic oncology centre. We retrospectively reviewed 88 consecutive patients diagnosed with OO treated with RFA between November 2005 and March 2015, consisting of 63 males (72%) and 25 females (28%). Sixty-six patients (75%) had nidus present in their biopsy samples. Patients’ mean age was 17.6 years (4-53). Median duration of follow-up was 12.5 months (6-20.8). Lesions were located in the appendicular skeleton in seventy-nine patients (90%) while nine patients (10%) had an OO in the axial skeleton. Outcomes assessed were based on patients’ pain alleviation (partial, complete, or no pain improvement) and the need for further interventions. Pain improvement in the patient group with nidus in histology sample was significantly better than the group without nidus (OR 7.4, CI 1.35-41.4, p=0.021). The patient group with nidus on biopsy demonstrated less likelihood of having a repeat procedure compared to the group without nidus (OR 0.092, CI 0.016-0.542, p=0.008). Our study showed significantly better outcomes in pain improvement in appendicular lesions compared to the axially located lesions (p = 0.005). Patients with spinal lesions tend to have relatively poor pain relief than those with appendicular or pelvic lesions (p=0.007). Patients with nidus on histology had better pain alleviation compared to patients without nidus. The histological presence of nidus significantly reduces the chance of repeat interventions. The pain alleviation of OO following RFA is better in patients with appendicular lesions than spinal or axially located lesions

Decreasing the chance of local relapse or infection after surgical excision of bone metastases is a main goals in orthopedic oncology. Indeed, bone metastases have high incidence rate (up to 75%) and important cross-relations with infection and bone regeneration. Even in patients with advanced cancer, bone gaps resulting from tumor excision must be filled with bone substitutes. Functionalization of these substitutes with antitumor and antibacterial compounds could constitute a promising approach to overcome infection and tumor at one same time. Here, for the first time, we propose the use of nanostructured zinc-bone apatite coatings having antitumor and antimicrobial efficacy. The coatings are obtained by Ionized Jet Deposition from composite targets of zinc and bovine-derived bone apatite. Antibacterial and antibiofilm efficacy of the coatings is demonstrated in vitro against S. Aureus and E. Coli. Anti-tumor efficacy is investigated against MDA- MB-231 cells and biocompatibility is assessed on L929 and MSCs. A microfluidic based approach is used to select the optimal concentration of zinc to be used to obtain antitumor efficacy and avoid cytotoxicity, exploiting a custom gradient generator microfluidic device, specifically designed for the experiments. Then, coatings capable of releasing the desired amount of active compounds are manufactured. Films morphology, composition and ion-release are studies by FEG- SEM/EDS, XRD and ICP. Efficacy and biocompatibility of the coatings are verified by investigating MDA, MSCs and L929 viability and morphology by Alamar Blue, Live/Dead Assay and FEG-SEM at different timepoints. Statistical analysis is performed by SPSS/PC + Statistics TM 25.0 software, one-way ANOVA and post-hoc Sheffe? test. Data are reported as Mean ± standard Deviation at a significance level of p <0.05. Results and Discussion. Coatings have a nanostructured surface morphology and a composition mimicking the target. They permit sustained zinc release for over 14 days in medium. Thanks to these characteristics, they show high antibacterial ability (inhibition of bacteria viability and adhesion to substrate) against both the gram + and gram – strain. The gradient generator microfluidic device permits a fine selection of the concentration of zinc to be used, with many potential perspectives for the design of biomaterials. For the first time, we show that zinc and zinc-based coatings have a selective efficacy against MDA cells. Upon mixing with bone apatite, the efficacy is maintained and cytotoxicity is avoided. For the first time, new antibacterial metal-based films are proposed for addressing bone metastases and infection at one same time. At the same time, a new approach is proposed for the design of the coatings, based on a microfluidic approach. We demonstrated the efficacy of Zn against the MDA-MB-231 cells, characterized for their ability to form bone metastases in vivo, and the possibility to use nanostructured metallic coatings against bone tumors. At the same time, we show that the gradient-generator approach is promising for the design of antitumor biomaterials. Efficacy of Zn films must be verified in vivo, but the dual-efficacy coatings appear promising for orthopedic applications

Spinal surgery deals with the treatment of different pathological conditions of the spine such as tumors, deformities, degenerative disease, infections and traumas. Research in the field of vertebral surgery can be divided into two main areas: 1) research lines transversal to the different branches; 2) specific research lines for the different branches. The transversal lines of research are represented by strategies for the reduction of complications, by the development of minimally invasive surgical techniques, by the development of surgical navigation systems and by the development of increasingly reliable systems for the control of intra-operative monitoring. Instead, specific lines of research are developed within the different branches. In the field of oncological pathology, the current research concerns the development of in vitro models for the study of metastases and research for the study of targeted treatment methods such as electrochemotherapy and mesenchymal stem cells for the treatment of aneurysmal bone cysts. Research in the field of spinal deformities is focused on the development of increasingly minimally invasive methods and systems which, combined with appropriate pharmacological treatments, help reduce trauma, stress and post-operative pain. Scaffolds based on blood clots are also being developed to promote vertebral fusion, a fundamental requirement for improving the outcome of vertebral arthrodesis performed for the treatment of degenerative disc disease. To improve the management and the medical and surgical treatment of vertebral infections, research has focused on the definition of multidisciplinary strategies aimed at identifying the best possible treatment path. Thus, flow-charts have been created which allow to manage the patient suffering from vertebral infection. In addition, dedicated silver-coated surgical instrumentation and bone substitutes have been developed that simultaneously guarantee mechanical stability and reduce the risk of further local infection. In the field of vertebral traumatology, the most recent research studies have focused on the development of methods for the biostimulation of the bone growth in order to obtain, when possible, healing without surgery. Methods have also been developed that allow the minimally invasive percutaneous treatment of fractures by means of vertebral augmentation with PMMA, or more recently with the use of silicone which from a biomechanical point of view has an elastic modulus more similar to that of bone. It is clear that scientific research has changed clinical practice both in terms of medical and surgical management of patients with spinal pathologies. The results obtained stimulate the basic research to achieve even more. For this reason, new lines of research have been undertaken which, in the oncology field, aim at developing increasingly specific therapies against target receptors. Research efforts are also being multiplied to achieve regeneration of the degenerated intervertebral disc and to develop implants with characteristics increasingly similar to those of bone in order to improve mechanical stability and durability over time. Photodynamic therapies are being developed for the treatment of infections in order to reduce the use of antibiotic therapies. Finally, innovative lines of research are being launched to treat and regenerate damaged nerve structures with the goal, still far from today, of making patients with spinal cord injuries to walk

Adverse events (AEs) are still a major problem in spinal surgery, despite advances in surgical techniques, innovative technologies available and the introduction of checklist and predictive score systems aimed at reducing surgical complications. We previously analysed the results of the introduction of the WHO Safety Surgical Checklist (SSC) in our Institution, comparing the incidence of complications between two periods: from January to December 2010 (without checklist) and from January 2011 and December 2012 (with checklist), in order to assess the checklist effectiveness. The sample size was 917 patients with an average of 30 months of follow-up. Complications were observed in 107 patients (11.6%) among 917 spinal surgery procedures performed, with 159 (17.3%) complications in total. The overall incidence of complications for trauma, infectious pathology, oncology, and degenerative disease was 22.2%, 19.2%, 18.4%, and 15.3%, respectively. We observed a reduction of the overall incidence of complications following the introduction of the WHO Surgical Checklist: in 2010 without checklist, the incidence of complications was 24.2%, while in 2011 and 2012, following the checklist introduction, the incidence of complications was 16.7% and 11.7%, respectively (mean 14.2%) (p<0.0005). Thus, the SSC appeared to be an effective tool to reduce complications in spinal surgery and we proposed to extend the use of checklist system also to the pre-operative and post-operative phases in order to further reduce the incidence of complications. We also believe that a correct capture and classification of complications is fundamental to generate a clinical decision support system aimed at improving patients’ safety in spinal surgery. In the period between January 2017 and January 2018 we prospectively recorded the adverse events and complications of patients undergoing spinal surgery in our department, without using any collection system. Then we retrospectively recorded the intraoperative and postoperative adverse events of surgically treated patients during the same one-year period, using the SAVES v2 system introduced by Rampersaud and collaborators (Rampersaud YR et al. J Neurosurg Spine 2016 Aug; 25 (2): 256-63) to classify them. In the one-year period from January 2017 to January 2018 a total of 336 patients underwent spinal surgery: 223 for degenerative conditions and 113 for spinal tumors. Comorbidities were collected (Charlson Comorbidity Index [CCI]). Overall, a higher number of adverse events (AEs) was recorded using SAVES compared to the prospective recording without the use of any capture system and the increased number was statistically significant for early postoperative AEs (138/336 vs 44/336, p<0.001). 210 adverse events were retrospectively recorded using the SAVES system (30 intraoperative adverse events, 138 early postoperative and 42 late postoperative adverse events). 99 patients (29.5%) on the cohort had at least one complication. Furthermore, the correlation between some risk factors and the onset of complications or the prolonged length of stay was statistically analyzed. The risk factors taken into account were: age, presence of comorbidities (CCI), ASA score, previous surgery at the same level, type of intervention, location of the disease, duration of the surgery. In particular, the duration of the surgery (more than 3 hours) and the presence of previous surgeries resulted to be risk factors for complications in multivariate analyses

Among the advanced technology developed and tested for orthopaedic surgery, the Rizzoli (IOR) has a long experience on custom-made design and implant of devices for joint and bone replacements. This follows the recent advancements in additive manufacturing, which now allows to obtain products also in metal alloy by deposition of material layer-by-layer according to a digital model. The process starts from medical image, goes through anatomical modelling, prosthesis design, prototyping, and final production in 3D printers and in case post-production. These devices have demonstrated already to be accurate enough to address properly the specific needs and conditions of the patient and of his/her physician. These guarantee also minimum removal of the tissues, partial replacements, no size related issues, minimal invasiveness, limited instrumentation. The thorough preparation of the treatment results also in a considerable shortening of the surgical and of recovery time. The necessary additional efforts and costs of custom-made implants seem to be well balanced by these advantages and savings, which shall include the lower failures and revision surgery rates. This also allows thoughtful optimization of the component-to-bone interfaces, by advanced lattice structures, with topologies mimicking the trabecular bone, possibly to promote osteointegration and to prevent infection. IOR's experience comprises all sub-disciplines and anatomical areas, here mentioned in historical order. Originally, several systems of Patient-Specific instrumentation have been exploited in total knee and total ankle replacements. A few massive osteoarticular reconstructions in the shank and foot for severe bone fractures were performed, starting from mirroring the contralateral area. Something very similar was performed also for pelvic surgery in the Oncology department, where massive skeletal reconstructions for bone tumours are necessary. To this aim, in addition to the standard anatomical modelling, prosthesis design, technical/technological refinements, and manufacturing, surgical guides for the correct execution of the osteotomies are also designed and 3D printed. Another original experience is about en-block replacement of vertebral bodies for severe bone loss, in particular for tumours. In this project, technological and biological aspects have also been addressed, to enhance osteointegration and to diminish the risk of infection. In our series there is also a case of successful custom reconstruction of the anterior chest wall. Initial experiences are in progress also for shoulder and elbow surgery, in particular for pre-op planning and surgical guide design in complex re-alignment osteotomies for severe bone deformities. Also in complex flat-foot deformities, in preparation of surgical corrections, 3D digital reconstruction and 3D printing in cheap ABS filaments have been valuable, for indication, planning of surgery and patient communication; with special materials mimicking bone strength, these 3D physical models are precious also for training and preparation of the surgery. In Paediatric surgery severe multi planar & multifocal deformities in children are addressed with personalized pre-op planning and custom cutting-guides for the necessary osteotomies, most of which require custom allografts. A number of complex hip revision surgeries have been performed, where 3D reconstruction for possible final solutions with exact implants on the remaining bone were developed. Elective surgery has been addressed as well, in particular the customization of an original total ankle replacement designed at IOR. Also a novel system with a high-tibial-osteotomy, including a custom cutting jig and the fixation plate was tested. An initial experience for the design and test of custom ankle & foot orthotics is also in progress, starting with 3D surface scanning of the shank and foot including the plantar aspect. Clearly, for achieving these results, multi-disciplinary teams have been formed, including physicians, radiologists, bioengineers and technologists, working together for the same goal

Telemedicine is the delivery of healthcare from a remote location using integrated computer/communication technology. This systematic review aims to explore evidence for telemedicine in orthopaedics to determine its advantages, validity, effectiveness and utilisation particularly during our current pandemic where patient contact is limited. Databases of PubMed, Scopus and CINHAL were systematically searched and articles were included if they involved any form of telephone or video consultation in an orthopaedic population. Findings were synthesised into four themes: patient/clinician satisfaction, accuracy and validity of examination, safety and patient outcomes and cost effectiveness. Quality assessment was undertaken using Cochrane and Joanna Briggs Institute appraisal tools. Twenty studies were included consisting of nine RCTs across numerous orthopaedic subspecialties including fracture care, elective orthopaedics and oncology. Studies revealed high patient satisfaction with telemedicine for convenience, less waiting and travelling time. Telemedicine was cost effective particularly if patients had to travel long distances, required hospital transport or time off work. No clinically significant differences were found in patient examination nor measurement of patient reported outcome measures. Telemedicine was reported to be a safe method of consultation. However, studies were of variable methodological quality with selection bias. In conclusion, evidence suggests that telemedicine in orthopaedics can be safe, cost effective, valid in clinical assessment with high patient/clinician satisfaction. Further work with high quality RCTs is required to elucidate long term outcomes. This systematic review presents up-to-date evidence on the use of telemedicine and provides data for organisations considering its use in the current COVID-19 pandemic and beyond

Introduction. To face the problem of surgical complications, which is generally relevant in surgical fields, an intraoperative checklist (Safety Surgical Checklist, SSC) was elaborated and released by the World Health Organization in 2008, and its use has been described in 2009. In our Institution, the WHO SSC was introduced in 2011. In spinal surgery, many preventive measures were investigated to reduce complications, but there is no report on the effectiveness of the WHO checklist in reducing complications. Aim. The aim of this study was to compare the incidence of complications between the two periods, from January to December 2010 (without checklist) and from January 2011 to December 2012 (with checklist), in order to assess the checklist effectiveness. Materials and Methods. A retrospective and single center study was carried out on patients who underwent spinal surgery during the three-year period from January 2010 to December 2012. Patients were classified according to the spine pathology and the different presentation of the complication. We registered the complications arising in patients treated from 2010 to 2012 during a 3 years follow up period for each patient, assessing the possible differences before and after the checklist's introduction. Results. The sample size was 917 patients, the mean age was 52.88 years. The majority of procedures were performed for oncological diseases (54.4%) and degenerative diseases (39.8%). 159 complications in total were detected (17.3%). The overall incidence of complications for trauma, infectious pathology, oncology, and degenerative disease was 22.2%, 19.2%, 18.4%, and 15.3%, respectively. No correlation was observed between the type of pathology and the complication incidence. We observed a reduction of the overall incidence of complications following the introduction of the SSC: in 2010 without checklist, the incidence of complications was 24.2%, while in 2011 and 2012, following the checklist introduction, the incidence of complications was 16.7% and 11.7%, respectively (mean 14.2%). Conclusion. Despite the limitations of the study, in particular the impossibility to carry out a randomized study, SSC seems to be an effective tool to reduce complications in spinal surgery. We propose to extend the use of checklist system also to the pre-operative and post-operative phases in order to further reduce the incidence of complications

Objectives. We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods. We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results. The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. Conclusion. We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143

Our goal is to repurpose drugs to block the growth of lung metastases, the lethal process in osteosarcoma. We therefore screened the NCI-panel of 114 FDA-approved oncology drugs to identify agents that potently reduce growth of osteosarcoma spheroids (sarcospheres). We first developed a system to routinely generate large numbers of highly-uniform spherical sarcospheres (1/well) with a 400um diameter, to most closely simulate micrometatases. Our primary drug screen (Z’-factor=0.70+0.10) utilized sarcospheres from three highly-metastatic human osteosarcoma cell lines (LM7, 143B, and MG63.3) in the presence and absence of MAP chemotherapeutics. Dose-response experiments with 13 of the most effective drugs confirmed initial results and allowed comparison with each drug's toxicity on normal human osteoblasts and normal small airway epithelial cells. Romidepsin, a HDAC inhibitor (HDACi), had the most favorable toxicity/efficacy ratios (TD. 50. /IC. 50. =57–580, depending on cell line). The only other HDACi in the panel of FDA-approved drugs (vorinostat) also ranked highly in the screen. Since newer HDACi's may have improved toxicity/efficacy ratios, we compared romidepsin and vorinostat with the three other HDACi's that are FDA-approved (belinostat, panobinostat, and valproic acid) plus one that is in clinical trials (entinostat). Romidepsin (C. max. /IC. 50. =36–360) and belinostat (C. max. /IC. 50. =14–20) reduced sarcosphere growth at clinically-achievable levels, in the presence or absence of MAP. Importantly, both romidepsin and belinostat were synergistic with MAP (BLISS scores=5–15). Propidium iodide staining showed that both romidepsin and MAP substantially induced cell death throughout the sarcospheres. Our results strongly support future studies to determine effects of romidepsin and belinostat on growth of lung metastases in vivo

Background. Metastatic bone patients who require surgery needs to be evaluated in order to maximise quality of life and avoiding functional impairment, minimising the risks connected to the surgical procedures. The best surgical procedure needs to be tailored on survival estimation. There are no current available tool or method to evaluate survival estimation with accuracy in patients with bone metastasis. We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on . www.PATHFx.org. , we attempted to externally validate it using independent, international data. Methods. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2008 and 2012, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). Results. The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. Conclusions. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied

Background. Metastatic bone patients who require surgery needs to be evaluated in order to maximise quality of life and avoiding functional impairment, minimising the risks connected to the surgical procedures. The best surgical procedure needs to be tailored on survival estimation. There are no current available tool or method to evaluate survival estimation with accuracy in patients with bone metastasis. We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on . www.PATHFx.org. , we attempted to externally validate it using independent, international data. Methods. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2008 and 2012, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). Results. The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. Conclusions. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied. Level of Evidence. IV. None of the authors have financial disclosures or conflicts of interest to declare. The study presented did not need the approval by ethics committee

The purpose of our study was to identify possible risk factors of patients with GCT of the long bones after curettage and packing the bone cavity with bone cement or bone allografts. We retrospectively reviewed the records of 249 patients with GCT of the limbs treated at Musculoskeletal Oncology Department of our institution between 1990 and 2013, confirmed histologically and recorded in the Bone Tumor Registry. We reviewed 219 cases located in the lower limb and 30 of the upper limb. This series includes 135 females and 114 males, with mean age 32 years (ranging 5 to 80 yrs). According to Campanacci's grading system, 190 cases were stage 2, 48 cases stage 3, and 11 cases stage 1. Treatment was curettage (intralesional surgery). Local adjuvants, such as phenol and cement, were used in 185 cases; whereas in the remaining 64 cases the residual cavity was filled with allografts or autografts only. Oncological outcome shows 203 patients alive and continuously disease-free (CDF), 41 patients NED1 after treatment of local recurrence (LR), 2 patients NED1 after treatment of lung metastases, 2 AWD with lung metastases. One patient died of unrelated causes (DOD). LR rate was 15.3% (38 pts). Lung metastases rate was 1.6% (4 pts). In patients treated by curettage and cement (185 cases) LR was 12% (22 pts). Conversely, in patients treated curettage and bone allografts it was higher (16/64 cases), with an incidence of 25% of cases (p=0.004). Oncological complications seemed to be related with site, more frequently occurring in the proximal femur (p=0.037). LR occurred only in stage 2 or 3 tumors without statistical significance (p>0.05). The mean interval between the first surgical treatment and LR was 22 months (range: 3–89 mos). However, in the multivariate analysis no significant statistical effect on local recurrence rate could be identified for gender, patient's age, Campanacci's grading, or cement vs allografts. The only independent risk factor related to the local recurrence was the site, with a statistical significance higher risk for patients with GCT of the proximal femur (p= 0.008). Our observation on the correlation of tumor location and risk of local recurrence is new. Therefore, special attention must be given to GCTs in the proximal femur. In fact, primary benign bone tumors in the proximal femur are difficult to treat due to the risk of secondary osteonecrosis of the femoral head or pathologic fracture. Numerous methods of reconstructions have been reported. Among these, total hip arthroplasty (THA) or bipolar hip arthroplasty (BHA) should be avoided when possible as more cases are observed in young patients. Therefore, we do not suggest different approach for the proximal femur. GCT in the proximal femur is much more difficult to treat than in other sites, but if curettage is feasible, the best way is to save the joint with a higher risk of local recurrence, knowing that the sacrifice of the hip articulation in case of recurrence is always possible with THA or BHA

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

Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign lesion of bone originally described by Nora et al in 1983. To date there are no UK-based case series in the literature. Here we present the Scottish Bone Tumour Registry (SBTR) experience of this rare lesion. A retrospective analysis of SBTR records was performed. Histological specimens were re-examined by a consultant musculoskeletal oncology pathologist. Radiographs were re-reported by a consultant musculoskeletal radiologist. From 1983-2009, 13 cases were identified; 6 male, 7 female. Age ranged from 13-65. All patients presented with localised swelling. Pain was present in 5 and trauma in 2. 9 lesions affected the hand, 3 the foot, and 1 the tibial tuberosity. 12 lesions were excised and 1 curetted. There were 7 recurrences of which 6 were excised. 1 patients' recurrence was not treated. 1 lesion recurred a second time. This was excised. There were no metastases. Radiographs typically showed densely mineralised lesions contiguous with an uninvolved cortex. Cortical breakthrough was present in 1 case and scalloping in another. Histology characteristically showed hypercellular cartilage with pleomorphism and calcification/ossification without atypia; bone undergoing maturation; and a spindle-cell stroma. SBTR records indicate that BPOP is a rare lesion with no sex predilection that affects patients over a wide age range. Minor antecedent trauma was present in only 2 cases. In agreement with Nora et al. we feel that trauma is unlikely to represent an aetiological factor. Recurrence was over 50% in this series. Although this is similar to that found in other reports, it may indicate that more extensive resection is required for this aggressive lesion. Finally, although radiological/histological findings are often bizarre there have been no reported metastases and so it is important that BPOP is not mistaken for, or treated as, a malignant process such as chondrosarcoma

Summary. This is the first ever study to report the successful elimination of malignant cells from salvaged blood obtained during metastatic spine tumour surgery using a leucocyte depletion filter. Introduction. Catastrophic bleeding is a significant problem in metastatic spine tumour surgery (MSTS). However, intaoperative cell salvage (IOCS) has traditionally been contraindicated in tumour surgery because of the theoretical concern of promoting tumour dissemination by re-infusing tumour cells into the circulation. Although IOCS has been extensively investigated in patients undergoing surgery for gynaecological, lung, urological, gastrointestinal, and hepatobiliary cancers, to date, there is no prior report of the use of IOCS in MSTS. We conducted a prospective observational study to evaluate whether LDF can eliminate tumour cells from blood salvaged during MSTS. Patients & Methods. After Institutional Review Board (IRB) approval, 21 consecutive patients with metastatic spinal tumours from a known epithelial primary (defined as originating from breast, prostate, thyroid, renal, colorectal, lung, nasopharyngeal) who were scheduled for MSTS were recruited with informed consent. During surgery, a IOCS device (Dideco, Sorin Group, Italy) was used to collect shed blood from the operative field. Salvaged blood was then passed through a leucocyte depletion filter (RS1VAE, Pall Corporation, UK). 15-ml specimens of blood were taken from each of three consecutive stages: (i) operative field prior to cell saver processing (Stage A); (ii) transfusion bag post-cell saver processing (Stage B); (iii) filtered blood after passage through LDF (Stage C). Cell blocks were prepared by the pathology department using a standardised laboratory protocol. From each cell block, 1 haematoxylin and eosin (H&E) slide, and 3 slides each labelled with one of the following monoclonal mouse cytokeratin antibodies AE1/3, MNF 116 and CAM 5.2 were prepared. The cytokeratin antibodies are highly sensitive and specific markers to identify tumour cells of epithelial origin. These slides were read by one of two consultant pathologists who were provided full access to information on operative notes, but were blinded to the actual stages from which the slides were derived. Results. One case was excluded when the final diagnosis was revised to infection instead of metastatic spine tumour. Of the remaining cases, 7/21 tested positive for tumour cells in Stage A, 2 positive in Stage B. No specimen tested positive for tumour cells in Stage C. In 5 cases, posterior instrumentation without tumour manipulation was performed. Discussion/Conclusion. In this first-ever study of cell saver use in spine tumour surgery, we prove that leucocyte-depletion filters (LDF) can effectively eliminate tumour cells from blood salvaged during MSTS. It is now possible to conduct a clinical trial to evaluate IOCS-LDF use in MSTS. Our results are consistent with published results of similar studies performed on IOCS and LDF use outside the field of orthopaedic surgery. Spinal metastases originate from a myriad of primary cancers across various organ systems. If LDF can remove tumour cells from blood salvaged during surgery for spinal metastasis of different histological origin, then the finding can likely be extrapolated to several other fields of surgery where IOCS and LDF have not yet been attempted such as: neurosurgery, otolaryngology and general musculoskeletal oncology. Our results form a proof-of-concept for a paradigm shift in thinking regarding autotransfusion during spine tumour surgery

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine.

Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2.