Functional outcomes are commonly reported in studies of musculoskeletal oncology patients undergoing limb salvage surgery; however, interpretation requires knowledge of the smallest amount of improvement that is important to patients – the minimally important difference (MID). We established the MIDs for the Musculoskeletal Tumor Society Rating Scale (MSTS) and Toronto Extremity Salvage Score (TESS) in patients with bone tumors undergoing lower limb salvage surgery. This study was a secondary analysis of the recently completed PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) study. This data was used to calculate: (1) the anchor-based MIDs using an overall function scale and a receiver operating curve analysis, and (2) the distribution-based MIDs based on one-half of the standard deviation of the change scores from baseline to 12-month follow-up, for both the MSTS and TESS. There were 591 patients available for analysis. The Pearson correlation coefficients for the association between changes in MSTS and TESS scores and changes in the external anchor scores were 0.71 and 0.57, indicating “high” and “moderate” correlation. Anchor-based MIDs were 12 points and 11 points for the MSTS and TESS, respectively. Distribution-based calculations yielded MIDs of 16-17 points for the MSTS and 14 points for the TESS. The current study proposes MID scores for both the MSTS and TESS outcome measures based on 591 patients with bone tumors undergoing lower extremity endoprosthetic reconstruction. These thresholds will optimize interpretation of the magnitude of treatment effects, which will enable shared decision-making with patients in trading off desirable and undesirable outcomes of alternative management strategies. We recommend anchor-based MIDs as they are grounded in changes in functional status that are meaningful to patients

Abstract. Background. Extracorporeal radiation therapy (ECRT) has been reported as an oncologically safe and effective reconstruction technique for limb salvage in diaphyseal sarcomas with promising functional results. Factors affecting the ECRT graft-host bone incorporation have not been fully investigated. Methods. In our series of 51 patients of primary bone tumors treated with ECRT, we improvised this technique by using a modified V-shaped osteotomy, additional plates and intra-medullary fibula across the diaphyseal osteotomy in an attempt to increase the stability of fixation, augment graft strength and enhance union at the osteotomy sites. We analyzed our patients for various factors that affected union time and union rate at the osteotomy sites. Results. On univariate analysis, age <20 years, metaphyseal osteotomy site, V-shaped diaphyseal osteotomy, extramedullary plate fixation and use of additional plate at diaphyseal ostetomy had a significantly faster time to union while gender, tumor type, resection length, chemotherapy and use of intra-medullary fibula did not influence union time. In multivariate analysis, metaphyseal ostoeotomy, V-shaped diaphyseal osteotomy and use of additional plate at diaphyseal ostetomy were the independent factors with favourable time to union. Although the rate of union was higher with V-shaped diaphyseal osteotomy and use of additional plate and intra-medullary fibula at diaphyseal ostetomy, this difference could not be established statistically. None of the analyzed factors apparently affected the union rate in univariate analysis. Conclusion. Judicious choice of osteosynthesis and augmentation of ECRT graft can enhance incorporation with reduced complications and good functional outcome

Functional outcomes are important for patients with bone tumors undergoing lower extremity endoprosthetic reconstruction; however, there is limited empirical evidence evaluating function longitudinally. The objective of this study was to determine the changes in function over time in patients undergoing endoprosthetic reconstructions of the proximal femur, distal femur and proximal tibia. We conducted a secondary analysis of functional outcome data from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. Patient function was assessed with the Musculoskeletal Tumor Society Score 93 (MSTS) and the Toronto Extremity Salvage Score (TESS), which were administered preoperatively and at 3, 6 and 12 months postoperatively. Both instruments are scored from 0-100, with higher scores indicated greater function. Mean functional scores were evaluated over time and we explored for differences among patients undergoing proximal femur reconstructions (PFR), distal femur reconstructions (DFR) and proximal tibia reconstructions (PTR). The patient-importance of statistically significant differences in function was evaluated utilizing the minimally important difference (MID) of 12 for the MSTS and 11 for the TESS. We explored for differences in change scores between each time interval with paired t-tests. Differences based on endoprosthetic reconstruction undertaken were evaluated by analysis of variance and post-hoc comparisons using the Tukey test. A total of 573 patients were included. The overall mean MSTS and TESS scores were 77.1(SD±21) and 80.2(SD±20) respectively at 1-year post-surgery, demonstrating approximately a 20-point improvement from baseline for both instruments. When evaluating change scores over time by type of reconstruction, PFR patients experienced significant functional improvement during the 3-6 and 6-12 month follow-up intervals, DFR patients demonstrated significant improvements in function at each follow-up interval, and PTR patients reported a significant decrease in function from baseline to 3 months, and subsequent improvements during the 3-6 and 6-12 month intervals. On average, patients undergoing endoprosthetic reconstruction of the lower extremity experience important improvements in function from baseline within the first year. Patterns of functional recovery varied significantly based on type of reconstruction performed. The results of this study will inform both clinicians and patients about the expected rehabilitation course and functional outcomes following endoprosthetic reconstruction of the lower extremity

Introduction. We demonstrate the preliminary results with a novel technique to solve large bone defects using two lengthening nails, working together and aligned in a custom made device. An illustrative case that successfully produced 17 cm bone in 3.5 months, is presented. Materials and Methods. A 28 year old healthy male presented with a slowly growing mass in the left femur. No general symptoms were reported, no weight loss, no previous illness. Histopathology, CT and MRI scans revealed a malignant diaphyseal bone tumor. A three-stage trifocal bone transport was projected and conducted based on a 3D model test. Results. Trifocal bone transport using two lengthening nails in a custom made device, reduced the 17 cm bone defect in 3.5 months. Follow up was 9 months. Conclusions. The presented technique successfully solved the clinical problem and is a showcase for further developments of internal devices for complex and large bone losses and lengthenings

Salmonella osteomyelitis occurs infrequently in children without a sickle cell disease, and its subacute form is rare. Diagnosis is often delayed because its slow onset, intermittent pain and it can be confused with bone tumors. An otherwise healthy 13-year-old boy was admitted from another center in order to discard bone tumor in proximal tibia, with compatible radiologic findings. There was no history of trauma or previous illness. Twenty days ago, he had flu symptoms and myalgia. On the physical examination the child was feverless, showed increased heat over his left knee, considerable effusion and painful restriction of movement. Inflammatory laboratory results revealed erythrocyte sedimentation rate 46mm/h and C-Reactive protein, 11,2 mg/L. Radiographs revealed a lytic lesion localized in the proximal metaphysis and epiphysis. The MRI showed an area of edema around the lytic lesion and surrounding soft tissues. Images supported the diagnosis of subacute osteomyelitis, (Brodie abscess). Empirically, intravenous cefuroxime was started. Forty-eight hours post admission, the patient underwent abscess surgical debridement, washout and cavity curettage. Samples were sent for cytology, culture and sensitivity and acid fast bacilli culture and sensitivity. Collection´s count cell was 173.000/ L white cells. Collection´s culture revealed Salmonella B sensitive to ciprofloxacin. Stool culture did not yield any growth. Intravenous cefuroxime was administered during 10 days. The patient responded well as evidenced by clinical and laboratory improvement He was discharged with his left leg immobilized in a cast during 1 month and treatment was completed with oral ciprofloxacin 500mg /12 h during 2 months. The patient had full range of knee motion after 2 months. Last reviewed, after two years of the income, he was completed recovered, and the radiograph showed bone healing without physeal neither damage nor limb leg discrepancy. The most effective therapy of a confirmed salmonella osteomyelitis is a combination of radical operative intervention and targeted intravenous antibiotics as in our case. Faced with a subacute osteomyelitis, we have to remember that it may mimic bone tumors. We highlight the isolation of Salmonella B in a patient without sickle cell disease

Foreword. Silver coatings, used in many surgical devices, have demonstrated good antimicrobial activity and low toxicity. Oncological musculoskeletal surgery have an high risk of infection, so in the last decades, silver coated mega-prostheses have been introduced and are becoming increasingly widespread. Material and methods. We performed a retrospective analysis of 158 cases of bone tumors, primary or metastatic, treated between 2002–2014 with wide margins resection and reconstruction with tumoral implants. The average age was 59 years (range 11–78 years), all patients were treated by the same surgeon, with antibiotic prophylaxis according to a standard protocol. In 58.5% of patients were implanted silver-coated prostheses, in the remaining part, standard tumor prosthesis. Patients were re-evaluated annually and were recorded complications, with particular attention to infectious diseases. Results. The mean follow-up was 39.5 months. 23.4% of patients died at a median time of 34.9 months after surgery. 18.4% develop complications that required a new surgery, in 12.6% of cases due to infectious problems. Patients treated with silver-coated implants developed early infection in 2.2% of cases against the 10.7% of the patients treated with standard tumor prosthesis. This different among the two groups was statistically significant, while the percentage of late infections, occurred from 6 months after surgery, was similar between groups. Assuming a reduction of antimicrobial silver activity in the time, it was carried out a microscopic analyses [Fig. 1] of silver-coated prostheses explanted 82 months and 27 months after surgery. It confirmed an important degradation of the coating surface with almost complete absence of silver. Silver blood level, taken in a sample of patients, at different time after surgery, always showed values well below the threshold of toxicity, and no patient has never shown any sign of local or general toxicity secondary to silver [Fig. 2]. Discussion. Our study demonstrates that tumor silver-coated implants have a rate of early infection significantly less than traditional implants, while there were no differences in the rate of late infections, as described also in the literature. This likely is related to wear of the silver coating, which occurs on average around 2 years after implantation. Conclusion. We recommend to use silver–coated prosthesis as primary implants for limb salvage surgery, in primary or metastatic bone tumors, considering the absence of signs of toxicity and the lower rate of early infection

Osteosarcoma (OS) is the most prevalent bone tumor in children and young adults. Most tumors arise from the metaphysis of the long bones and easily metastasize to the lungs. Current therapeutic strategies of osteosarcoma are routinely surgical resection and chemotherapy, which are limited to the patients suffering from metastatic recurrence. Therefore, to investigate molecular mechanisms that contribute to osteosarcoma progression is very important and may shed light on targeted therapeutic approach to improve the survival of patients with this disease. Several miRNAs have been found expressed differentially in osteosarcoma (OS), In this study, we found that miR-144 significantly suppresses osteosarcoma cell proliferation, migration andinvasion ability in vitro, and inhibited tumor growth and metastasisin vivo. The function and molecular mechanism of miR-144 in Osteosarcoma was further investigated. Tissue samples from fifty-one osteosarcoma patients were obtained from Shanghai Ninth People's Hospital. The in vitro function of miR-144 in Osteosarcoma was investigated by cell viability assay, wound healing assay, invasion assay, the molecular mechanism was identified by Biotin-coupled miRNA capture, Dual-luciferase reporter assays, etc. the in vivo function of miR-144 in osteosarcoma was confirmed by osteosarcoma animal model and miR-144−/− zebrafish model. Mechanically, we demonstrated that Ras homolog family member A (RhoA) and its pivotal downstream effector Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) were both identified as direct targets of miR-144. Moreover, the negative co-relation between downregulated miR-144 and upregulated ROCK1/RhoA was verified both in the osteosarcoma cell lines and clinical patients' specimens. Functionally, RhoA with or without ROCK1 co-overexpression resulted a rescue phenotype on the miR-144 inhibited cell growth, migration and invasion abilities, while individual overexpression of ROCK1 had no statistical significance compared with control in miR-144 transfected SAOS2 and U2-OS cells. This study demonstrates that miR-144 inhibited tumor growth and metastasis in osteosarcoma via dual-suppressing of RhoA and ROCK1, which could be a new therapeutic approach for the treatment ofosteosarcoma

Objectives. Our objectives were to describe the therapeutic aspects and assess the prognosis of chronic osteomyelitis in children. Materials and methods. We made a retrospective study from January 2007 to December 2016. The study concerned children from 0 to15 years, treated for chronic osteomyelitis and monitored in the pediatric surgery department of the teaching hospital Gabriel Toure, Bamako (Mali). The other types of bone infections, osteitis and bone tumors were not included in the study. In 10 years we received and treated 215 children with chronic osteomyelitis. This represented 3.56% of all the hospitalizations. The mean age was 8.8 (± 6.67) years with extremes of 28 days and 15 years. The patients were first seen by the traditional healer in 165 (76.7%) cases. The sex ratio was 1.26. The major clinical feature was local swelling associated with pain in 110 cases (51.2%). In 135 cases (62.8%) the staphylococcus aureus was found in direct examination or culture. After a year we performed a functional and morphological assessment according to the method of DIMEGLIO. Results. Surgical treatment was performed in all patients. The average delay of stay in hospital was 4.95 ± 4.57 weeks, with extremes of 2 and 12 weeks. The means follow-up was 13 months with extremes of 3 and 20 months. Good results were found in 115 patients, fair in 60 (40 in keloid knee valgus to 11 ° in 10, muscular atrophy 10), bad in 40 (shortening member in 25 non-union in 10 valgus to 18 ° in 5) According Dimeglio score. There was no significant association between the time of consultation, prior treatment received, the surgical technique and the occurrence of complications (p> 0.05). Conclusion. The management of the chronic osteomyelitis is well codified. The functional prognosis is dependent on an early care and sequels can be dramatic in children of school age. Keywords. Chronic osteomyelitis, Treatment, Prognosis, Children

The rate of fracture and subsequent nonunion after radiation therapy for soft-tissue sarcomas and bone tumors has been demonstrated to quite high. There is a paucity of data describing the optimal treatment for these nonunions. Free vascularized fibular grafts (FVFG) have been used successfully in the treatment of large segmental bone defects in the axial and appendicular skeleton, however, their efficacy with respect to treatment of radiated nonunions remains unclear. The purpose of the study was to assess the 1) union rate, 2) clinical outcomes, and 3) complications following FVFG for radiation-induced femoral fracture nonunions. We identified 24 patients who underwent FVFG for the treatment of radiation-induced femoral fracture nonunion between 1991 and 2015. Medical records were reviewed in order to determine oncologic diagnosis, total preoperative radiation dose, type of surgical treatment for the nonunion, clinical outcomes, and postoperative complications. There were 11 males and 13 females, with a mean age of 59 years (range, 29 – 78) and a mean follow-up duration of 61 months (range, 10 – 183 months). Three patients had a history of diabetes mellitus and three were current tobacco users at the time of FVFG. No patient was receiving chemotherapy during recovery from FVFG. Oncologic diagnoses included unspecified soft tissue sarcomas (n = 5), undifferentiated pleomorphic sarcoma (UPS) (n = 3), myxofibrosarcoma (n = 3), liposarcoma (n = 2), Ewing's sarcoma (n = 2), lymphoma (n = 2), hemangiopericytoma, leiomyosarcoma, multiple myeloma, myxoid chondrosarcoma, myxoid liposarcoma, neurofibrosarcoma, and renal cell carcinoma. Mean total radiation dose was 56.3 Gy (range, 39 – 72.5), given at a mean of 10.2 years prior to FVFG. The average FVFG length was 16.4 cm. In addition to FVFG, 13 patients underwent simultaneous autogenous iliac crest bone grafting, nine had other cancellous autografting, one received cancellous allograft, and three were treated with synthetic graft products. The FVFG was fixed as an onlay graft using lag screws in all cases, additional fixation was obtained with an intramedullary nail (n = 19), dynamic compression plate (n = 2), blade plate (n = 2), or lateral locking plate (n = 1). Nineteen (79%) fractures went on to union at a mean of 13.1 months (range, 4.8 – 28.1 months). Musculoskeletal Tumor Society scores improved from eight preoperatively to 22 at latest follow-up (p < 0.0001). Among the five fractures that failed to unite, two were converted to proximal femoral replacements (PFR), two remained stable pseudarthroses, and one was converted to a total hip arthroplasty. A 6th case did unite initially, however, subsequent failure lead to PFR. Seven patients (29%) required a second operative grafting. There were five additional complications including three infections, one wound dehiscence, and one screw fracture. No patient required amputation. Free vascularized fibular grafts are a reliable treatment option for radiation-induced pathologic femoral fracture nonunions, providing a union rate of 79%. Surgeons should remain cognizant, however, of the elevated rate of infectious complications and need for additional operative grafting procedures

Advances in cancer therapy have prolonged patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in longer survival, preserved mobility, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The ideal clinical decision support tool will be of the highest sensitivity and specificity, non-invasive, generalizable to all patients, and not a burden on hospital resources or the patient's time. Our research uses novel machine learning techniques to develop a model to fill this considerable gap in the treatment pathway of MBD of the femur. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data of consecutive MBD patients presenting from 2009–2016. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 546 patients comprising 114 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray and clinical data including patient demographics, Mirel's criteria, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. We have trained a convolutional neural network (CNN) with AP X-ray images of 546 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. The model converges on two fully connected deep neural network layers that output the risk of fracture. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections, until overall prediction accuracy is optimized. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across five test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a model's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Our model achieved 88.2% accuracy in predicting fracture risk across five-fold cross validation testing. The F1 statistic is 0.87. This is the first reported application of convolutional neural networks, a machine learning algorithm, to this important Orthopaedic problem. Our neural network model was able to achieve reasonable accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to externally validate this algorithm on an international cohort

Advances in cancer therapy have prolonged cancer patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in patients more likely to walk after surgery, longer survival, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data for MBD patients (2009–2016) in order to determine which features are most commonly associated with fracture. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 1146 patients comprising 224 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray. The clinical data includes patient demographics, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. Each of Mirel's criteria has been further subdivided and recorded for each lesion. We have trained a convolutional neural network (CNN) with X-ray images of 1146 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. This model converges on two fully connected deep neural network layers that output the fracture risk. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a test's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Five-fold cross validation testing of our fully trained model revealed accurate classification for 88.2% of patients with metastatic bone disease of the proximal femur. The F1 statistic is 0.87. This represents a 24% error reduction from using Mirel's criteria alone to classify the risk of fracture in this cohort. This is the first reported application of convolutional neural networks, a machine learning algorithm, to an important Orthopaedic problem. Our neural network model was able to achieve impressive accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to validate this algorithm on an external cohort

Background. Distal femoral replacements (DFR) are used in children for limb-salvage procedures after bone tumor surgery. These are typically modular devices involving a hinged knee axle that has peripheral metal-on-polyethylene (MoP) and central metal-on-metal (M-M) articulations. While modular connections and M-M surfaces in hip devices have been extensively studied, little is known about long-term wear or corrosion mechanisms of DFRs. Retrieved axles were examined to identify common features and patterns of surface damage, wear and corrosion. Methods. The cobalt chromium alloy axle components from 13 retrieved DFRs were cleaned and examined by eye and with a stereo microscope up to 1000× magnification. Each axle was marked into 6 zones for visual inspection: the proximal and distal views, and the middle (M-M) and 2 peripheral (MoP) zones. The approximate percentage of the following features were recorded per zone: polishing, abrasion or scratching, gouges or detectable wear, impingement wear (i.e. from non- intentional articulation), discoloration and pitting. Results. In each case, the middle M-M zones showed more damage features compared with peripheral MoP zones. Brown discoloration, presumably due to tribofilm deposits, was the predominant M-M area feature, particularly at the junction between the MoP and M-M zones. Higher magnification showed areas of polishing underlying the discoloration, suggesting repetitive removal of the surface metal and re-deposition of tribofilms (Fig 2B). 9 cases demonstrated reflective patches resembling “thumbprint” or “fish scale” markings, which, under higher magnification, showed signs of scratching and grooving in a radial pattern (Figs 2D, 3A). Pits were occasionally present but appeared to be from third-body damage as signs of corrosion were absent. Features that resembled carbides, sometimes with associated “comet” patterns of scratching were apparent under higher magnification in some areas. The MoP zones showed variable scratching, abrasion and wear polishing. The MoP to M-M junctional areas were demarcated by a distinct band corresponding, in some cases, to a narrow wear groove or gouge. 3 axles showed evidence of severe impingement wear on one proximal end. Discussion. This study of retrieved axle components demonstrated varying types of surface wear damage but no clear evidence of corrosion. This is presumably because these parts are in nearly constant motion during gait. Third-body damage may have resulted from the breakdown of surface carbides, leading to scratching, abrasion and wear polishing under high contact stress. Severe impingement wear presumably occurred after catastrophic damage to the polyethylene bushings, allowing eccentric loading and extensive metal wear. The components were revised for a range of clinical reasons including aseptic loosening and the need to expand the prosthesis during growth. With the exception of the few cases with severe impingement, it is unlikely that the wear features seen here contributed to the need for revision. While it was reassuring that corrosion was not a prominent feature of these modular M-M articulations, retrieval analysis of DFR components should be continued to confirm this finding, better document the in vivo wear processes and point to design features that might be improved for future patients. For any figures or tables, please contact the authors directly

Aim. The demand for a synthetic bone substitute that can build bone and at the same time kill bacteria is high. The aim of this study was to compare the elution of gentamicin from a new synthetic bone substitute in vitro with the performance in clinical applications. Method. Gentamicin release was measured from a synthetic bone graft substitute, comparing in vitro and clinical conditions:. 1). elution in Ringers solution. The bone graft substitute contained 175mg gentamicin per 10mL. The material was introduced either as paste or as pre-set beads with a high or low surface areas, >100cm. 2. and 24cm. 2. respectively. The gentamycin release was measured by daily collection of samples. 2). elution in patients treated for trochanteric hip fractures(n=6) or uncemented hip revisions(n=5) 7,3±1,1mL of substitute was implanted and drainage was collected at 6h,12h,24h,30h,36h post-op. Blood serum was collected every hour for the first 6h and thereafter every 6h until 4 days post-op, urine – daily for the first 7 days post-op. 3). elution in patients treated after bone tumor resection(n=8), 12,1±5,5mL of substitute was implanted and both drainage and blood serum were collected daily until 2 days post-op. Gentamicin concentrations were analyzed using antibody technique. Results. In the in vitro study, there was an initial peak in the gentamicin concentration (GC) for all the samples and at a level above 4mg/L, which is the MIC break point, during the whole test period of 28 days. All gentamicin was released during the test period and more than 95 % had been released after 2–4 days independently of the surface area of the material, or if it was pre-set or paste. In the clinical studies similar results were found. Gentamicin was detected in the drainage until 2 days post-op. and the hip patients 40% less GC – compared to the tumor patients. In the blood serum with higher GC in the tumor patients and non-detectable levels after 2 days post-op for the hip patients. The GC was significantly lower than maximum systemic level recommended of 12 mg/L. In the urine, GC was above the MIC of 4mg/L for the first seven days post-op. Conclusions. A reliable in vitro test method has been identified for the future development of additional new and effective antibiotic containing bone substitutes. The new bone regenerating carrier gives very high local antibiotic release for a controlled short time after surgery and high systemic serum concentrations are avoided

Introduction. The number of total hip arthroplasties has been increasing worldwide, and it is expected that revision surgeries will increase significantly in the near future. Although reconstructing normal hip biomechanics with extensive bone loss in the revision surgery remains challenging. The custom−made acetabular component produced by additive manufacturing, which can be fitted to a patient's anatomy and bone defect, is expected to be a predominant reconstruction material. However, there have been few reports on the setting precision and molding precision of this type of material. The purpose of this study was to validate the custom−made acetabular component regarding postoperative three−dimensional positioning and alignment. Methods. Severe bone defects (Paprosky type 3A and 3B) were made in both four fresh cadaveric hip joints using an acetabular reamer mimicking clinical cases of acetabular component loosening or osteolysis in total hip arthroplasty. On the basis of computed tomography (CT) after making the bone defect, two types of custom−made acetabular components (augmented type and tri−flanged type) that adapted to the bone defect substantially were produced by an additive manufacturing machine. A confirmative CT scan was taken after implantation of the component, and then the data were installed in an analysis workstation to compare the postoperative component position and angle to those in the preoperative planning. Results. The mean absolute deviations of the center of the hip joint between preoperative planning and the actual component position in the augmented type were 0.7 ± 0.4 mm for the horizontal position, 0.2 ± 0.1 mm for the vertical position, and 0.5 ± 0.3 mm for the antero−posterior position. The mean absolute deviations of the center of the hip joint in the tri−flanged type in the horizontal, vertical, and antero−posterior positions were 1.0 ± 0.4 mm, 0.4 ± 0.2 mm, 0.3 ± 0.1 mm, respectively. The mean absolute deviations of the component angle were 3.5° ± 0.9° at inclination and 2.0° ± 1.7° at anteversion in the augmented type and 0.6° ± 0.5° at inclination and 0.9° ± 0.3° at anteversion in the tri−flanged type. Conclusion. Since custom−made orthopaedic implants produced by additive manufacturing can support individual anatomy and bone defect, this type of implant is expected to be applied to revision surgery and bone tumor surgery for severe bone defects. The present study demonstrated that preoperative planning of the center of the hip joint was successfully reproduced after the implantation of both types of custom−made acetabular components. In the tri−flanged type, better satisfactory results were provided in the component position and angle by comparing the past CAOS tools such as a surgical navigation system and a patient−specific guide. There is scope for further improvement, but the custom−made acetabular component produced by additive manufacturing may become very useful reconstruction material in hip revision surgeries. Problems to be addressed in the future include the improvement of the reproducibility of the preoperative planning and investigation of long−term clinical results

To document early in-vivo concentrations of gentamicin in plasma and drain fluid after bone defect reconstruction using a gentamicin-eluting bone graft substitute. Introduction. Reconstruction of bone defects after surgical bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent bone defect reconstruction with a gentamicin-eluting bone graft substitute (CERAMENT™|G – BONESUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting bone graft substitute was used, either alone or in combination with cancellous allograft and/or a bone graft substitute not containing gentamicin (CERAMENT™|BVF – BONESUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2. Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting bone graft substitute for bone defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations

Ewing sarcoma (ES) and Osteosarcoma (OS) are the 2 most common malignant primary bone tumors. A patient's response to neoadjuvant chemotherapy has important implications in subsequent patient management and prognosis, as a favourable response to chemotherapy allows orthopedic oncologists to be more aggressive in pursuing limb-sparing surgery. An accurate and non-invasive pre-operative marker of response would be ideal for planning surgical margins and as a prognostic tool. ES and OS have differing biological characterisitcs and respond differently to chemotherapy. We reviewed 18F-FDG PET imaging characteristics of ES and OS patients at baseline and following treatment to determine whether this biological variation is reflected in their imaging phenotype. A retrospective review of ES and OS patients treated with neoadjuvant chemotherapy and surgery was done, correlating PET results with histologic response to chemotherapy. Change in the maximum standardized Uptake Value (SUVmax) between baseline and post-treatment scanning was not significantly associated with histologic response for either ES or OS. Metabolic tumor volume (MTV) and the percentage of injected 18F-FDG dose (%ID) in the primary tumor were found to be different for ES and OS response subgroups. A 50% reduction in MTV (MTV2:1 < 0.5) was found to be significantly associated with histologic response in OS. Using the same criteria for ES incorrectly predicted good responders. Increasing the cut-offs for ES to a 90% reduction in MTV (MTV 2:1 < 0.1) resulted in association with histologic response. Response to neoadjuvant chemotherapy as reflected by changes in PET characteristics should be interpreted differently for ES and OS

Most types of bone tumor surgery require intra-operative imaging or measurement to control margins and prevent unnecessary bone loss. Computer Assisted Surgery (CAS) has been used as a replacement of fluoroscopy or direct measurement tools in four specific types of oncological orthopaedic surgical approaches. There are intralesional treatments, image-based resections, image-based resections with image-based reconstructions and image-based resections with imageless tumor prostheses reconstruction. Since 2006 we have performed 130 oncological surgeries with CAS. Most cases were excochleations, 64, where CAS replaces fluoroscopy as an intra-operative imaging modality. Advantages over fluoroscopy are real time three dimensional feedback, high-res image and no use of ionizing radiation. It is especially useful in larger lesions or lesions located in the femoral head or pelvis. Currently a study is being performed on patient satisfaction, recurrence and complications. Another application where CAS has often been used is in resections and segmental resections (together 45). These can be preplanned before surgery, incorporating the margin required, and checked intra-operatively. Coloration of the tumor, critical structures is useful to avoid these. Sometimes it's possible with careful planning to spare structures that otherwise probably would not confidently have spared. With hemicortical resection (5) it's possible to use CAS to exactly copy the shape of the resected bone to an allograft. A Ct scan of one case shows an average gap between host and graft of 0.9 mm (range 0–5.4) along the 6 cm resection. Finally in 16 cases of imageless use in placement of tumor prostheses it feels greatly helpful in reconstructing the joint line, length and correct rotation. There were 8 failures in these 130 cases with the system or software. Setup time was measured in 47 cases and was on average 6:50 (range 2:26–14:27). Indication and performance of CAS in orthopedic oncology is an under researched aspect of CAS. In our opinion CAS shows great promise in the field of orthopedic oncology and is a valuable tool in the operating room

INTRODUCTION. Allograft reconstruction after resection of primary bone sarcomas has a non-union rate of approximately 20%. Achieving a wide surface area of contact between host and allograft bone is one of the most important factors to help reduce the non-union rate. We developed a novel technique of haptic robot-assisted surgery to reconstruct bone defects left after primary bone sarcoma resection with structural allograft. METHODS. Using a sawbone distal femur joint-sparing hemimetaphyseal resection/reconstruction model, an identical bone defect was created in six sawbone distal femur specimens. A tumor-fellowship trained orthopedic surgeon reconstructed the defect using a simulated sawbone allograft femur. First, a standard, ‘all-manual’ technique was used to cut and prepare the allograft to best fit the defect. Then, using an identical sawbone copy of the allograft, the novel haptic-robot technique was used to prepare the allograft to best fit the defect. All specimens were scanned via CT. Using a separately validated technique, the surface area of contact between host and allograft was measured for both (1) the all-manual reconstruction and (2) the robot-assisted reconstruction. All contact surface areas were normalized by dividing absolute contact area by the available surface area on the exposed cut surface of host bone. RESULTS. The mean area of contact between host and allograft bone was 24% (of the available host surface area) for the all-manual group and 76% for the haptic robot-assisted group (p=0.004). CONCLUSIONS. This is the first report to our knowledge of using haptic robot technology to assist in structural bone allograft reconstruction of defects left after primary bone tumor resection. The findings strongly indicate that this technology has the potential to be of substantial clinical benefit. Further studies are warranted

Resecting bone tumours within the pelvis is highly challenging and requires good cutting accuracy to achieve sufficient margins. Computer-assisted technologies such as intraoperative navigation have been developed for pelvic bone tumour resection. Patient-specific instruments have been transposed to tumour surgery. The present study reports a series of 11 clinical cases of PSI-assisted bone tumour surgery within the pelvis, and assesses how accurately a preoperative resection strategy can be replicated intraoperatively with the PSI. The patient series consisted in 11 patients eligible for curative surgical resection of primary bone tumor of the pelvis. Eight patients had a bone sarcoma of iliac bone involving the acetabulum, two patients had a sacral tumor, and one patient had a chondrosarcoma of proximal femur with intra-articular hip extension. Resection planning was preoperatively defined including a safe margin defined by the surgeon from 3 up to 15 mm. PSI were designed using a computer-aided design software according to the desired resection strategy and produced by additive manufacturing technology. Intraoperatively, PSI were positioned freehand by the surgeon and fixed on the bone surface using K-wires. The standard surgical approach has been used for each patient. Dissection was in accordance with the routine technique. There was no additional bone exposure to position the PSI. Histopathological analysis of the resected tumor specimens was performed to evaluate the achieved resection margins. Postoperative CT were acquired and matched to the preoperative CT to assess the local control of the tumor. Two parameters were measured: achieved resection margin (minimum distance to the tumor) and location accuracy (maximum distance between achieved and planned cuttings; ISO1101 standard). PSI were quick and easy to use with a positioning onto the bone surface in less than 5 minutes for all cases. The positioning of the PSI was considered unambiguous for all patients. Histopathological analysis classified all achieved resection margins as R0 (tumor-free), except for two patients : R2 because of a morcelised tumour and R1 in soft tissues. The errors in safe margin averaged −0.8 mm (95% CI: −1.8 mm to 0.1 mm). The location accuracy of the achieved cut planes with respect to the desired cut planes averaged 2.5 mm (95% CI: 1.8 to 3.2 mm). Results in terms of safe margin or the location accuracy demonstrated how PSI enabled the surgeon to intraoperatively replicate the resection strategies with a very good cutting accuracy. These findings are consistent with the levels of bone-cutting accuracy published in the literature. PSI technology described in this study achieved clear bone margins for all patients. Longer follow-up period is required but it appears that PSI has the potential to provide clinically acceptable margins

INTRODUCTION. Over the last twenty years, image-guided interventions have been greatly expanded by the advances in medical imaging and computing power. A key step for any image-guided intervention is to find the image-to-patient transformation matrix, which is the transformation matrix between the preoperative 3D model of patient anatomy and the real position of the patient in the operating room. In this work, we propose a robust registration algorithm to match ultrasound (US) images with preoperative Magnetic Resonance (MR) images of the Humerus. MATERIALS AND METHODS. The fusion of preoperative MR images with intra-operative US images is performed through an NDI Spectra® Polaris system and a L12-5L60N TELEMED® ultrasound transducer. The use of an ultrasound probe requires a calibration procedure in order to determine the transformation between an US image pixel and its position according to a global reference system. After the calibration step, the patient anatomy is scanned with US probe. US images are segmented in real time in order to extract the desired bone contour. The use of an optical measurement system together with trackers and the previously-computed calibration matrix makes it possible to assign a world coordinate position to any pixel of the 2D US image. As a result, the set of US pixels extracted from the images results in a cloud of 3D points which will be registered with the 3D Humerus model reconstructed from MR images. The proposed registration method is composed of two steps. The first step consists of US 3D points cloud alignment with the 3D bone model. Then, the second step performs the widely-known Iterative Closest Point (ICP) algorithm. In order to perform this, we define the coordinate system of both the 3D Humerus model and the US points cloud. The frame directions correspond to the directions of the principal axes of inertia calculated from the matrices of inertia of both the preoperative 3D model and the US data obtained intra-operatively. Then, we compute the rotation matrix to estimate the transformation between the two coordinate systems previously calculated. Finally the translation is determined by evaluating the distance between the mass centres of the two 3D surfaces. RESULTS. In order to evaluate the performance of this registration method in terms of precision and accuracy, we performed the US/MRI fusion on 8 patients. The evaluation criterion used for the validation step was the fiducial registration error (FRE) estimation based on 8 anatomic fiducials detected on the Humerus of the patient. The mean, standard deviation, minimum and maximum values of the 8 Fiducial Registration Errors were 4.34, 2.20, 2.81 and 9.48 mm, respectively. DISCUSSIONS. In this work, we propose a robust registration method of MR and US data. Thanks to the optical system, this fusion will allow us for example to guide and assist surgeons in the positioning of the radiofrequency probe for bone tumor ablation. In addition to the fact that it is completely automatic, the proposed image-to-patient registration method is minimally invasive