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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 76 - 76
1 Mar 2021
Malik A Alexander J Khan S Scharschmidt T
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The management of primary malignant bone tumors with metastatic disease at presentation remains a challenge. While surgical resection has been shown to improve overall survival among patients with non-metastatic malignant bone tumors, current evidence regarding the utility of surgery in improving overall survival in metastatic patients remains limited. The 2004–2016 National Cancer Database (NCDB) was queried using International Classification of Diseases 3rd Edition (ICD-O-3) topographical codes to identify patients with primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8 and C40.9) and/or pelvis (C41.4). Patients with malignant bone tumors of the axial skeleton (head/skull, trunk and spinal column) were excluded, as these cases are not routinely encountered and/or managed by orthopaedic oncologists. Histological codes were used to categorize the tumors into the following groups - osteosarcomas, chondrosarcomas, and Ewing sarcomas. Patients who were classified as stage I, II or III, based on American Joint Commission of Cancer (AJCC) guidelines, were excluded. Only patients with metastatic disease at presentation were included in the final study sample. The study sample was divided into two distinct groups – those who underwent surgical resection of the primary tumors vs. those who did not receive any surgery of the primary tumor. Kaplan-Meier survival analysis was used to report unadjusted 5-year overall survival rates between patients who underwent surgical resection of the primary tumor, compared to those who did not. Multi-variate Cox regression analyses were used to assess whether undergoing surgical resection of the primary tumor was associated with improved overall survival, after controlling for differences in baseline demographics, tumor characteristics (grade, location, histological type and tumor size), and treatment patterns (underwent metastatectomy of distal and/or regional sites, positive vs. negative surgical margins, use of radiation therapy and/or chemotherapy). Additional sensitivity analyses, stratified by histologic type for osteosarcomas, chondrosarcomas and Ewing sarcomas, were used to assess prognostic factors for overall survival. A total of 2,288 primary malignant bone tumors (1,121 osteosarcomas, 345 chondrosarcomas, and 822 Ewing sarcomas) with metastatic disease at presentation were included – out of which 1,066 (46.0%) underwent a surgical resection of the primary site. Overall 5-year survival rates, on unadjusted Kaplan-Meier log-rank analysis, were significantly better for individuals who underwent surgical resection vs. those who did not receive any surgery (31.7% vs. 17.3%; p<0.001). After controlling for differences in baseline demographics, tumor characteristics and treatment patterns, undergoing surgical resection of primary site was associated with a reduced overall mortality (HR 0.42 [95% CI 0.36–0.49]; p<0.001). Undergoing metastectomy (HR 0.92 [95% CI 0.81–1.05]; p=0.235) was not associated with a significant improvement in overall survival. On stratified analysis, radiation therapy was associated with improved overall survival for Ewing Sarcoma (HR 0.71 [95% CI 0.57–0.88]; p=0.002), but not for osteosarcoma (HR 1.14 [95% CI 0.91–1.43]; p=0.643) or chondrosarcoma (HR 1.08 [95 % CI 0.78–1.50]; p=0.643). Chemotherapy was associated with improved overall survival for osteosarcoma (HR 0.50 [95% CI 0.39–0.64]; p<0.001) and chondrosarcoma (HR 0.62 [95% CI 0.45–0.85]; p=0.003), but not Ewing sarcoma (HR 0.79 [95% CI 0.46–1.35]; p=0.385). Surgical resection of the primary site significantly improves overall survival for primary malignant bone tumors with metastatic disease at presentation. Physicians should strongly consider surgical resection of the primary tumor, with adjunct systemic and/or radiation therapy (dependent on tumor histology), in patients presenting with metastatic disease at presentation


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 65 - 65
1 Mar 2021
Perera J Ibe I Aoude A Griffin A Ferguson P Wunder J Tsoi K
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Myxoid or Myxoid Round Cell liposarcoma (MLS) is a mesenchymal malignancy with adipocyte differentiation accounting for 15–20% of liposarcomas and 5% of all adult soft tissue sarcomas (STS). Like other STS, treatment of MLS is generally by wide surgical resection in conjunction with radiotherapy and this approach is associated with low rates of local recurrence [1]. However, most MLS are located between muscles so wide local excision(WLE) can be quite morbid with adverse functional results. MLS are known to be extremely sensitive to radiotherapy which has led to development of treatment protocols utilizing neoadjuvant radiation. Given the radiosensitivity of MLS, we hypothesize that resection with marginal margins (1mm) does not result in higher rates of local recurrence or disease-free survival if performed following pre-operative radiotherapy. We identified all patients with localized MLS who underwent preoperative radiation and surgical resection between January 2000 and January 2018 from a prospectively collected sarcoma database. We calculated the ellipsoid tumour volume(ETV=h x w x d x ()) at diagnosis and after radiation, and documented the necrosis percentage of the tumour and margin status following resection based on histological analysis [2]. Marginal resection was identified by the operative report describing no or only very minimal resection of muscle surrounding the tumour, and a negative surgical margin 0.1cm/1mm as defined histologically. In comparison, WLE was defined if the operative note described an attempt to remove the tumour with a cuff of surrounding muscle, and the final histology reported a negative margin 0.1cm/1mm which included skeletal muscle. The third group for analysis included patients with positive resection margins. There were 91 patients with MLS of mean age 48 years (range 18–88) with 69% male and 31% female. The mean pre-radiotherapy ETV was 507cm. 3. (16.1cm. 3. to 6961cm. 3. ) and decreased to 361cm. 3. (8.7cm. 3. to 5695cm. 3. ) following radiation, with an average percentage reduction in ETV of −45%(+129%to-99%). Mean patient follow-up was 7.3 years (0.2–18) with no differences between margin groups(p=0.284). Only 10(11%) patients had positive margins, of which 43(47%) underwent marginal resection and 38(42%) WLE. Overall the mean necrosis as measured histologically following preoperative radiation was 69% (range 0–100%) with no differences between the 3 resection groups(p-0.151). Similarly, there was no significant difference in reduction in mean ETV between the three resection groups(p=0.311), there was no significant difference between the three treatment groups in 5-year LR-free survival (p=0.469), metastasis-free survival (p=0.841) or overall survival (p=0.873). Most patients with MLS experienced significant reduction in tumour size and necrosis following preoperative radiation. We found no differences in the risk of local recurrence or survival based on the type of surgical approach for patients with MLS. Based on these results, we conclude that MLS can be safely removed by marginal resection following preoperative radiotherapy with high rates of local tumour control. Even following a positive margin resection, local recurrence remains uncommon after preoperative radiation. A marginal surgical approach for patients with MLS reduces the need for major muscle resection and is associated with improved functional outcomes with less complications


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 44 - 44
1 Nov 2016
Nooh A Turcotte R Goulding K
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Wound complications are common in patients with soft tissue sarcomas (STS) treated with surgical excision. Limited data is available on predictive factors for wound complications beyond the relationship to neo-adjuvant or adjuvant radiotherapy. Likewise, the association between blood transfusion, patient comorbidities and post-operative outcomes is not well described. In the present study we identified the predictive factors for blood transfusion and wound complications in patients undergoing surgical resection of soft tissue sarcoma from a national cohort. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent surgical resection of a STS from 2005 to 2013. Primary malignant soft tissue neoplasms were identified using the following ICD-9 codes: 171.2, 171.3 and 171.6. Patients treated with both wide excision and amputation were identified using the current procedural terminology (CPT) codes. Prolonged operative time was defined as greater than 90th percentile of time required per procedure. A multivariable logistic regression model was used to identify associations between patient factors and post-operative wound complications (superficial and deep surgical site infections (SSI), and wound dehiscence). A similar regression model sought to identify prognostic factors for blood transfusion and associations with post-operative outcomes. A total of 788 patients met our inclusion criteria. Of theses, 64.2% had tumours in the lower limb, 23.1% patients had tumours in the upper limb, and 12.7% patients had pelvic tumours. Six hundred and forty patients (81.2%) underwent surgical excision; 148 (18.8%) patients had an amputation. Multivariable logistic regression modeling identified American Society of Anaesthesiologist (ASA) class 3 and 4 (OR=2.3, P=0.03; OR=8.3, P=0.001, respectively), amputation (OR=14.0, P<0.001) and prolonged operative time (OR=4.6, P<0.001) as significant predictors of blood transfusion. Radiotherapy (OR=2.6, P=0.01) and amputation (OR=2.6, P=0.01) were identified as predictors of superficial SSI, whereas ASA class 4 (OR=6.2, P=0.03), prolonged operative time (OR=3.9, P=0.012) and return to the operating room (OR=10.5, P<0.001) were associated with deep SSI. Male gender (OR=1.8, P=0.03), diabetes (OR=2.3, P=0.03), ASA class 3 (OR=2.4, P=0.003), amputation (OR=3.8, P<0.001) and steroids (OR=4.5, P=0.03) were identified as predictors for wound dehiscence and open SSI. A national cohort demonstrates that male gender, diabetes, chronic steroid use, higher ASA score and radiotherapy are associated with an increased incidence of wound complications. One in twenty-three patients undergoing resection of an STS will require a blood transfusion, and this risk is correlated with amputation, prolonged operative time and increased ASA score. Strategies to decrease the risk of blood transfusion and wound complication should be considered for these patient groups


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_3 | Pages 90 - 90
1 Feb 2017
Dai Y Angibaud L Jung A Hamad C Bertrand F Stulberg B Huddleston J
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INTRODUCTION

Studies have reported that only 70–80% of the total knee arthroplasty (TKA) cases using conventional instruments can achieve satisfactory alignment (within ±3° of the mechanical axis). Computer-assisted orthopaedic surgery (CAOS) has been shown to offer increased accuracy and precision to the bony resections compared to conventional techniques [1]. As the early adopters champion the technology, reservation may exist among new CAOS users regarding the ability of achieving the same results. The purpose of this study was to investigate if there are immediate benefits in the accuracy and precision of achieving surgical goals for the novice surgeons, as compared to the experienced surgeons, by using a contemporary CAOS system.

Materials and Methods

Two groups of surgeons were randomly selected from TKAs between October 2012 and January 2016 using a CAOS system (ExactechGPS, Blue-Ortho, Grenoble, FR), including:

Novice group (7 surgeons): no navigation experience prior to the adoption of the system and have performed ≤20 CAOS TKAs. To investigate the intra-group variation, this group was further divided into surgeons with extensive experience in conventional TKA (novice-senior), and surgeons who were less experienced (novice-junior).

Experiences group (6 surgeons): used the CAOS system for more than 150 TKAs.

All the surgeries from the novice group (86 cases) and the most recent 20 cases from each surgeon in the experienced group (120 cases) were studied. Deviations in the resection parameters between the following were investigated for both tibia and femur: 1) planned resection, resection goals defined prior to the bone cuts; 2) checked resection, digitization of the realized bone cuts. The deviations were compared within the novice group (novice-senior vs novice-junior), as well as between the novice and experience groups. Knees with optimal resection (deviation<2°/mm, without clinically alter the joint mechanics [2]) and acceptable resection (deviation<3°/mm, as commonly adopted) were identified. Significance was defined as p<0.05.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 94 - 94
1 Dec 2022
Lazarides A Novak R Burke Z Gundavda M Ghert M Rose P Houdek M Wunder JS Ferguson P Griffin A Tsoi K
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Radiation induced sarcoma of bone is a rare but challenging disease process associated with a poor prognosis. To date, series are limited by small patient numbers; data to inform prognosis and the optimal management for these patients is needed. We hypothesized that patients with radiation-induced pelvic bone sarcomas would have worse surgical, oncologic, and functional outcomes than patients diagnosed with primary pelvic bone sarcomas. This was a multi-institution, comparative cohort analysis. A retrospective chart review was performed of all patients diagnosed with a radiation-induced pelvic and sacral bone sarcoma between January 1st, 1985 and January 1st, 2020 (defined as a histologically confirmed bone sarcoma of the pelvis in a previously irradiated field with a minimum 3-year interval between radiation and sarcoma diagnosis). We also identified a comparison group including all patients diagnosed with a primary pelvic osteosarcoma/spindle cell sarcoma of bone (i.e. eligible for osteosarcoma-type chemotherapy) during the same time interval. The primary outcome measure was disease-free and overall survival. We identified 85 patients with primary osteosarcoma of the pelvis (POP) and 39 patients with confirmed radiation induced sarcoma of the bony pelvis (RISB) undergoing surgical resection. Patients with RISB were older than patients with POP (50.5 years vs. 36.5 years, p67.7% of patients with POP underwent limb salvage as compared to 77% of patients with RISB; the type of surgery was not different between groups (p=.0.24). There was no difference in the rate of margin positive surgery for RISB vs. POP (21.1% vs. 14.1%, p=0.16). For patients undergoing surgical resection, the rate of surgical complications was high, with more RISB patients experiencing complications (79.5%) than POP patients (64.7%); this approached statistical significance (p=0.09). 15.4% of patients with RISB died perioperative period (within 90 days of surgery) as compared to 3.5% of patients with POP (p= 0.02). For patients undergoing surgical resection, 5-year OS was significantly worse for patients with RISB vs. POP (27.3% vs. 47.7%, p=0.02). When considering only patients without metastatic disease at presentation, a significant difference in 5-year survival remains for patients with RISB vs. POP (28.6% vs. 50%, p=0.03) was a trend towards poorer 5-year DFS for patients with RISB vs. POP (30% vs. 47.5%), though this did not achieve statistical significance (p=0.09). POP and RISB represent challenging disease processes and the oncologic outcomes are similarly poor between the two; however, the disease course for patients with RISB appears to be worse overall. While surgery can result in a favorable outcome for a small subset of patients, surgical treatment is fraught with complications


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 103 - 103
1 Dec 2022
Lazarides A Burke Z Gundavda M Griffin A Tsoi K Wunder JS Ferguson P
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Wide resection, with or without adjuvant therapy, is the mainstay of treatment for soft tissue sarcoma of the extremities. The surgical treatment of soft tissue sarcoma can portend a prolonged course of recovery from a functional perspective. However, data to inform the expected course of recovery following sarcoma surgery is lacking. The purpose of this study was to identify time to maximal functional improvement following sarcoma resection and to identify factors that delay the expected course of recovery. A retrospective chart review was performed of all patients undergoing surgical treatment of a soft tissue sarcoma of the extremities between January 1st, 1985 and November 15, 2020 with a minimum of 1 follow up. The primary outcome measure was time to maximal functional improvement, defined as failure to demonstrate improvement on two consecutive follow up appointments, as defined by the functional outcome measures of Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) Score or by achieving 90% of maximum outcome score. We identified 1188 patients who underwent surgical resection of a soft tissue sarcoma of the extremities. Patients typically achieved a return to their baseline level of function by 1 year and achieved “maximal” functional recovery by 2 year's time postoperatively. Patient and tumor factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included older age (p=0.007), female sex (p-0.004), larger tumor size (p < 0 .001), deep tumor location (p < 0 .001), pelvic location (p < 0 .001), higher tumor grade (p < 0 .001). Treatment factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included use of radiation therapy (p < 0 .001), perioperative complications (p < 0 .001), positive margin status (p < 0 .001) and return of disease, locally or systemically (p < 0 .001). Most patients will recover their baseline function by 1 year and achieve “maximal” recovery by 2 years’ time following surgical resection for soft tissue sarcoma of the extremities. Several patient, tumor and treatment factors should be used to counsel patients as to a delayed course of recovery


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 12 - 12
1 Dec 2021
Rupp M Henssler L Brochhausen C Zustin J Geis S Pfeifer C Alt V Kerschbaum M
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Aim. Adequate debridement of necrotic bone is of paramount importance for eradication of infection in chronic osteomyelitis. Currently, no tools are available to detect the exact amount of necrotic bone in order to optimize surgical resection. The aim of the present study was to evaluate the feasibility of an intraoperative illumination method (VELscope. ®. ) and the correlation between intraoperative and pathohistological findings in surgically treated chronic fracture related infection patients. Method. Ten consecutive patients with chronic fracture related infections of the lower extremity were included into this prospectively performed case series. All patients had to be treated surgically for fracture related infections requiring bony debridement. An intraoperative illumination method (VELscope®) was used to intraoperatively differentiate between viable and necrotic bone. Tissue samples from the identified viable and necrotic bone areas were histopathologically examined and compared to intraoperative findings. Results. In all included patients, the intraoperative illumination was deemed helpful to differentiate between necrotic and viable bone tissues during bony debridement. The histopathological examination of the samples showed good correlation of the intraoperative illumination findings with histopathological signs of necrosis for areas deemed dead and histopathological signs of intact bone for areas deemed vital during illumination. Conclusions. The fluorescence-assisted, intraoperative detection of necrotic and viable bone using the VELscope. ®. is an easy-to-use procedure that can help surgeons to optimize intraoperative bone resection in chronic fracture related infections by unmasking viable from necrotic bone tissue. This may help to improve resection techniques and eventually treatment outcome in patients in the future


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 71 - 71
1 Mar 2021
Ibe I Perera J Aoude A Griffin A Wunder J Ferguson P Tsoi K
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Ewing Sarcoma is the second most common primary bone sarcoma in young patients, however, there remains geographical variation in the treatment of these tumours. All patients receive neoadjuvant chemotherapy and, in most cases, the soft tissue mass diminishes significantly in volume. Controversy surrounds whether to then treat the pre- or post-chemotherapy tumour volume. Many centres advocate either (1) resection of the pre-chemotherapy volume or (2) treatment of the pre-chemotherapy volume with radiation followed by resection of the post-chemotherapy volume. These approaches increase both the short and long-term morbidity for this young patient population. In this study, we retrospectively reviewed our experience resecting only the post-chemotherapy volume without the use of (neo)adjuvant radiotherapy. A retrospective analysis of all patients with Ewing Sarcoma treated at a tertiary orthopaedic oncology centre was conducted. All patients were treated as per the consensus opinion of the multidisciplinary tumour board. Demographic and oncological variables were collected from our institutional database. Presentation and re-staging MRI scans were reviewed to evaluate pre- and post-chemotherapy tumour volumes. Operative and pathology reports were utilized to determine the extent of the surgical resection. Outcome variables included local recurrence free-, metastasis free- and overall survival. Sixty-five patients were identified in our institutional database of which 56 did not receive (neo)adjuvant radiotherapy. Median age at diagnosis was 24 years (range 13–64), 60% of patients were male and 67.6% of tumours were located in the appendicular skeleton. All 56 patients not treated with radiotherapy had resection of the post-chemotherapy tumour volume. There were 3 local recurrences in this group with a mean follow-up of 70.8 months (range 2 to 328). The median overall survival was 47 months and the mean of 70.8months. The rate of local recurrence is comparable to reports in the literature in which patients had their entire pre-chemotherapy tumour volume treated by radiation and/or surgery. Similarly, two-year overall survival for our patient cohort is not significantly different from previous studies in which more aggressive local control measures were employed. Resecting the post-chemotherapy tumour volume in Ewing Sarcoma without the use of (neo)adjuvant radiotherapy does not appear to increase the risk of local recurrence or negatively impact overall survival. This approach should be studied further as it reduces the risk of short and long-term complications for this patient population.”


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 67 - 67
1 Mar 2021
Perera J Atinga A Ibe I Aoude A White L Howarth D Griffin A Tsoi K Ferguson P Wunder J
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Myxofibrosarcoma (MFS) is the second most common subtype of soft tissue sarcoma (STS) and is associated with a high rate of local recurrence after resection. These tumours frequently present with peri-lesional edema, termed “tumour tails” on staging MRI scans [1]. Tumour tails(TT) may contain satellite neoplastic cells or can represent benign reactive edema. There are no clear radiological features to distinguish malignant from reactive peri-lesional edema which limits accurate surgical planning, resulting in either high rates of inadvertently positive resection margins and local recurrences or overly-aggressive resections which negatively impact function and increase morbidity [2]. The objective of this pilot study was to prospectively study a cohort of MFS patients with TTs in an attempt to identify radiological features that predict which type of edema is malignant and requires resection together with the main tumour mass. Patients diagnosed with MFS on biopsy at an orthopaedic oncology referral centre between January 1-December 31 2018 who also had TTs on staging MRI scans were prospectively recruited for the study. Tumours were treated with wide surgical excision, including the TTs, and (neo)adjuvant radiotherapy as per institutional protocol. Staging MRI scans were reviewed in a blinded fashion by two musculoskeletal radiologists to distinguish malignant from reactive TTs. The main tumour mass underwent standard histological evaluation while the regions encompassing the TTs were photographed and sectioned into grids. Each tissue section was examined histologically for the presence of satellite neoplastic cells based on morphological criteria. Radiological and histological findings were compared. Six patients met the inclusion criteria and underwent analysis. All tumours were located in the extremities and were deep to fascia. Mean age at presentation was 67 years (range 51 – 85), with a male:female ratio of 4:2. All patients received radiotherapy (50 Gy), either pre- (n=4) or post-operatively (n=2) based on multidisciplinary tumor board discussion or enrolment in a prospective clinical trial. Radiologically, TTs were labelled as malignant in four patients (66.7%) and as benign TTs in two others. The tails were recognised to be malignant due to the differing signal characteristics to reactive edema on mixed MRI sequences. The radiological evaluation correlated exactly with histological analysis, as satellite neoplastic cells were identified microscopically in the same four cases in which the TTs were designated to be malignant by MRI (specificity&sensitivity=100%). Surgical resection margins were microscopically positive in 50% of cases in the TTs themselves, and 75% of cases in which TTs were designated as malignant on staging MRI. “The malignant nature of peri-lesional edema in MFS, also known as the TT, was accurately predicted in this small pilot study based on specific radiological features which correlated exactly with histologic identification of isolated tumor cells. These findings validate development of a larger prospective study to recruit additional patients with tumor tails beyond just MFS, in order to more robustly study the correlation between the MRI appearance and histological distribution of satellite sarcoma cells in peri-lesional edema in STS. We are already recruiting to this expanded radiological-histological investigation including evaluation of additional novel MRI sequences


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 41 - 41
1 Aug 2020
Zhang X Liu J Li J Chen X Qiao Z Xu J Xiao F Cui P
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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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 38 - 38
1 Aug 2020
Mattei J Alshaygy I Basile G Griffin A Wunder JS Ferguson P
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Sarcomas generally metastasize to the lung, while extra-pulmonary metastases are rare. However, they may occur more frequently in certain histological sub-types. Bone metastases from bone and soft tissue sarcomas account for a significant number of extra-pulmonary disease. Resection of lung metastases is widely accepted as therapeutic option to improve the survival of oligometastatic patients but there is currently no literature supporting curative surgical management of sarcoma bone metastases. Most are treated on a case-by-case basis, following multidisciplinary tumour boards recommendations. One study reported some success in controlling bone metastases using radiofrequency ablation. Our goal was to assess the impact of curative resection of bone metastases from soft tissue and bone sarcomas on oncologic outcomes. Extensive review of literature was done to evaluate epidemiological and outcomes of bone metastases in sarcoma. We examined our prospective database for all cases of bone metastases from sarcoma treated with surgical resection between 1990 and 2016. Epidemiology, pathology, metastatic status upon diagnosis, type of secondary relapses and their treatments were recorded. Overall survival and disease-free survival were calculated and compared to literature. Thirty-five patients were included (18 men, 17 women) with a mean age of 46 years. Fifteen were soft tissue (STS) and 20 were bone (BS) sarcomas. Most STS were fibrosarcomas, leiomyosarcomas or UPS while chondrosarcomas and osteosarcomas were the most frequent BS. Nine (60%) STS were grade 3, 4 (27%) grade 2 and one grade 1 (3%). Eight (23%) were metastatic upon diagnosis (6 lungs, 3 bone). Treatment of the primary tumour included wide excision with reconstruction and (neo)-adjuvant therapies as required. Margins were negative in 32 cases and micro-positive in 3 cases. Amputation occurred in 6 (17%) cases. Primary lung metastases were treated by thoracotomy and primary bone metastases by wide excision. First relapse occurred in bone in 19 cases (54%), lungs and bone in 7 cases, 5 in lungs and 4 in soft-tissues. Lung metastases were treated by thoracotomy and chemotherapy in 3 cases, chemotherapy alone in the remaining cases. Bone metastases were treated by wide resection-reconstruction in 24 cases, extensive curettage in 4. Soft tissue relapses were re-excised in 4 patients. Two amputations were required. All margins were negative except for the 4 treated by curettage. Fourteen second relapses occurred in bone, 7 were radically-excised and 2 curetted. At last follow-up, 6 patients were alive (overall survival of 17%), with a mean survival of 57 months, a median overall survival of 42.5 months and a median disease-free survival (DFS) of 17 months. Overall survival was 17%, compared to an 11% 10-year survival previously reported in metastatic sarcomas. Median disease-free survival was better in this study, compared to 10 months in literature, so as median OS (42.5 months vs 15). Three patients were alive with no evidence of disease. DFS, OS and median survival seemed to be improved by bone metastases wide excision and even if several recurrences occur, curative surgery with adjuvant therapies should be considered


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 40 - 40
1 Mar 2012
Srikanth K Revell M Abudu A Tillman R Grimer R
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Solitary plasmacytomas in the appendicular skeleton are rare monoclonal expansions of plasmacytoid cells. They are two main hazards; local destruction of bone with resultant loss of function and possible fracture, and progression to Myeloma. Between February 1988 and July 2005 seven patients (4 male, 3 female) were treated for solitary plasmacytoma with surgical resection and endoprosthetic reconstruction. The median age was 46.7 (35-75). The site was: distal humerus (2), proximal humerus (2) proximal femur (2) proximal tibia (1). Three patients had sustained a pathological fracture. Five patients had received pre-operative radiotherapy and three received post-operative radiotherapy. Mean follow-up is 8.6 years. Two cases became infected at 2 and 5 years post-operatively and have had revisions of their endoprosthesis. Both remain functional at 18 and 15 years. No patient has suffered a local recurrence. Two patients have progressed to multiple Myeloma but no patients have died. Literature review shows that the progression of solitary bone plasmacytoma to Myeloma is around 53% despite radiotherapy, in an average period of 2-4 years. With resection and endoprosthetic reconstruction, the progression in this series has been 28% despite an average follow up of 8.6 years. Although the numbers are small, due to the rarity of the condition, surgical resection and endoprosthetic reconstruction reduces disease progression than radiotherapy alone. This produces far superior results compared to the intramedullary nailing of the long bones for this condition. Endoprosthetic reconstruction after resection should be given consideration in cases of solitary plasmacytoma of the appendicular skeleton when there is extensive bone destruction present. The optimal timing of local radiotherapy to be combined with surgery is still to be established


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 58 - 58
1 Feb 2012
Nawabi D Sinisi M Birch R
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A schwannoma is a benign nerve sheath tumour originating from schwann cells. It is the most commonly occurring peripheral nerve sheath tumour. The common sites of occurrence are the head and neck followed by the upper and lower limbs. Diagnosis is straightforward and is made clinically. Schwannomas of the tibial nerve pose a problem. The literature describes them as causes of chronic, intractable lower limb pain because their diagnosis is often delayed for several years. The main reason postulated is that a lump is not always palpable in the early phases and hence chronic cramping pain in the calf or foot is attributed to lumbosacral radiculopathy or local neuropathy. We report the largest case series of twenty-five patients diagnosed with a tibial nerve schwannoma. Only three cases were diagnosed within a year of initial presentation. The mean time to diagnosis was eighty-six months. The most common site of pain was the sole of the foot (eighteen cases). A Tinel's sign was elicited in nineteen cases. MRI confirmed the diagnosis in all the twenty cases where it was performed. Surgical resection was performed in all cases yielding excellent results. Only one patient required further neurolysis for persisting pain. In patients with a long history of neuropathic lower limb pain, where lumbar and pelvic lesions have been excluded, a high index of suspicion should be maintained for a peripheral nerve tumour. Delay in diagnosis is commonly due to lack of familiarity with peripheral nerve pathology and the absence of a palpable lump. The delay can result in numerous unnecessary medical and surgical interventions in this group of distressed patients. The Tinel's sign is the key to identifying a tumour of neural origin in the absence of a palpable lump. Surgical resection of the tumour remains safe and effective in providing symptomatic relief


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 26 - 26
1 Dec 2018
Sigmund IK Ferguson J Govaert G Stubbs D McNally M
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Aim. Infected segmental defects are one of the most feared complications of open tibial fractures. This may be due to prolonged treatment time, permanent functional deficits and high reinfection and non-union rates. Distraction osteogenesis techniques such as Ilizarov acute shortening with bifocal relengthening (ASR) and bone transport (BT) are effective surgical treatment options in the tibia. The aim of this study was to compare ASL with bone transport in a consecutive series of complex tibial infected non-unions and osteomyelitis, for the reconstruction of segmental defects created at surgical resection of the infection. Method. In this single centre series, all patients with a segmental defect (>2cm) of the tibia after excision of infected non-union or osteomyelitis were eligible for inclusion. Based on clinical features, bone reconstruction was achieved with either ASR or BT using an Ilizarov fixator. We recorded the external fixation time (months), the external fixation index (EFI), comorbidities, Cierny-Mader or Weber-Cech classification, follow-up duration, time to union, number of operations and complications. Results. Overall, 43 patients with an infected tibial segmental defect were included. An ASR was performed in 19 patients with a median age of 40 years (range: 19 – 66 years). In this group, the median bone defect size was three cm (range: 2 – 5 cm); and the median frame time eight months (range: 5 – 16 months). BT was performed in 24 patients with a median age of 44 years (range: 21 – 70 years). The median bone defect size was six cm (range: 3 – 10 cm), and the median frame time ten months (range: 7 – 17 months). The EFI in the ASR group and the BT group measured 2.2 months/cm (range: 1.3 – 5.4 months/cm) and 1.9 months/cm (range: 0.8 – 2.8 months/cm), respectively. The comparison between the EFI of the ASL group and the BT group showed no statistically significant difference (p=0.147). Five patients of the ASR group (7 surgeries) and 19 patients of the BT group (23 surgeries) needed further unplanned surgery (p=0.001). Docking site surgery was significantly more frequent in BT; 66.7%, versus ASL; 5.3% (p=0.0001). Conclusion. Acute shortening/relengthening and bone transport are both safe and effective distraction osteogenesis techniques for the treatment of infected tibial non-unions. They share similar frame times per centimetre of defect. However, ASR demonstrated a statistically significant lower rate of unplanned surgeries


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_20 | Pages 10 - 10
1 Dec 2017
Dai Y Hamad C Jung A Angibaud L
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Computer-assisted orthopaedic surgery (CAOS) has been demonstrated to increase accuracy to component alignment of total knee arthroplasty compared to conventional techniques. The purpose of this study was to assess if learning affects resection alignment using a specific CAOS system. Nine surgeons, each with >80 TKA experience using a contemporary CAOS system were selected. Prior to the study, six surgeons had already experienced with CAOS TKA (experienced), while the rest three were new to the technology (novice). The following surgical parameters were investigated: 1) planned resection, resection parameters defined by the surgeon prior to the bone cuts; 2) checked resection, digitalisation of the realised resection surfaces. Deviations in the alignment between planned and checked resections were compared between the first 20 cases (in learning curve) and the last 20 cases (well past learning curve) within each surgeon. Any significance detected (p < 0.05) with >1° difference in means indicated clinically meaningful impact on alignment by the learning phase. Both pooled and surgeon-specific analysis exhibited no clinically meaningful significant difference between the first 20 and the last 20 cases from both experienced and novice surgeon groups. The resections in both the first 20 and the last 20 cases demonstrated acceptable rates of over 95% in alignment (<3° deviation) for both experienced and novice surgeons. This study demonstrated that independent of the surgeon's prior CAOS experiences, the CAOS system investigated can provide an accurate and precise solution to assist in achieving surgical resection goals with no clinically meaningful compromise in alignment accuracy and outliers during the learning phase


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_19 | Pages 55 - 55
1 Dec 2014
Thiart M Davis J
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Introduction:. 25% of patients with an unknown primary tumour present to the orthopaedic surgeon with skeletal metastases. The onus is on the orthopaedic surgeon to establish the diagnosis, not only to decrease the patient's anxiety but also because the median survival increases from 6–9 months to 23 months when the primary is identified and allows for specific cancer treatment. The diagnostic work up of an unknown primary includes a multitude of special investigations. Since PET/CT has high sensitivity and specificity for detecting the primary tumours, we asked the question: Can you diagnose the unknown primary in patients with skeletal metastases with a PET/CT?. Method:. We included all PET/CT scans done in our institution between 2010 and 2013 for patients with malignancies known to metastasize to bone (melanoma, breast, lung, head and neck, GIT, other) and all scans done in patients with unknown primaries. After reviewing 686 PET/CT scans, 492 showed metastatic disease, with 78 of these having either spinal or skeletal metastases. Results:. Of these 78 patients, 68 primaries could be detected on the PET/CT scan. Thus the PET/CT detected the primary in 87% of cases. This number could possibly be higher as some were melanoma and breast cancer patients who had already undergone surgical resection. The most common primary detected was lung, followed by a group of other and unknown primaries which included cervical, kidney and thyroid carcinoma. Conclusion:. PET/CT scan is a good modality to use when looking for a primary malignancy in patients who present to the orthopaedic surgeon with bone metastases. We postulate that this might be a possible first line investigation when looking for the primary


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_7 | Pages 97 - 97
1 May 2016
Dai Y Angibaud L Harris B Gulbransen S Begin D
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Introduction. Evaluations of Computer-assisted orthopaedic surgery (CAOS) systems generally overlooked the intrinsic accuracy of the systems themselves, and have been largely focused on the final implant position and alignment in the reconstructed knee [1]. Although accuracy at the system-level has been assessed [2], the study method was system-specific, required a custom test bench, and the results were clinically irrelevant. As such, clinical interpolation/comparison of the results across CAOS systems or multiple studies is challenging. This study quantified and compared the system-level accuracy in the intraoperative measurements of resection alignment between two CAOS systems. Materials and Methods. Computer-assisted TKAs were performed on 10 neutral leg assemblies (MITA knee insert and trainer leg, Medial Models, Bristol, UK) using System I (5 legs, ExactechGPS®, Blue-Ortho, Grenoble, FR) and System II (5 legs, globally established manufacturer). The surgeries referenced a set of pre-defined anatomical landmarks on the inserts (small dimples). Post bone cut, the alignment parameters were collected by the CAOS systems (CAOS measured alignment). The pre- and post- operative leg surfaces were scanned, digitized, and registered (Comet L3D, Steinbichler, Plymouth, MI, USA; Geomagic, Lakewood, CO, USA; and Unigraphics NX version 7.5, Siemens PLM Software, Plano, TX, USA). The alignment parameters were measured virtually, referencing the same pre-defined anatomical landmarks (baseline). The signed and unsigned measurement errors between the baseline and CAOS measured alignment were compared between the two CAOS systems (significance defined as p<0.05), representing the magnitude of measurement errors and bias of the measurement error generated by the CAOS systems, respectively. Results. The measurement errors are presented [Table 1]. For unsigned measurement error, System II was higher in the tibial varus/valgus alignment and posterior slope (p≤0.01), and lower in the femoral varus/valgus alignment (p=0.03), compared to System I [Fig. 1]. System II exhibited higher error bias towards tibial varus alignment (up to 2.59°), more posterior slope (up to 1.41°), and more femoral hyper extension (up to 1.6°) than System I (p<0.01) [Fig. 1]. The mean signed and unsigned errors were generally less than 1°, except for System II in the measurement of tibial varus/valgus alignment (signed and unsigned mean errors=1.93°). Discussion. This study reported system-dependent bias and variability associated with intraoperative measurements of alignment parameters during TKA. The results showed that System I generally had lower variability and less bias than System II. Although the majority of the significant differences found were clinically irrelevant (<1° in means), System II was notably shown to produce on average ∼2° measurement errors in tibial varus/valgus alignment biased towards varus. Intra-operative measurement of surgical resection parameters during imageless computer-assisted TKA surgery is a critical step, in which a surgeon directly relies on the real-time data to prepare the bony resections and check the final realized cuts. Clinical-level accuracy in alignment outcomes has been shown to be system-dependent [2], this study further suggested there are differences in system-level accuracy between CAOS systems


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 110 - 110
1 Sep 2012
Al-Hadithy N Gikas P Perera J Aston W Pollock R Skinner J Lotzof K Cannon S Briggs T
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The surgical treatment of bone tumours can result in large perioperative blood loss due to their large sizes and hypervascularity. Preoperative embolisation has been successfully used to downgrade vascularity, thus reducing perioperative blood loss and its associated complications. Prior to embolization era, blood loss as high as 18,500mL have been reported peri-opratively. Twenty-six patients with a variety of bone tumours (average size 10.5×7.5×5.5cm), who underwent pre-operative embolisation between 2005 and 2009, were retrospectively studied. The group comprised of 17 females and 9 males. Their mean age was 38 years old. All patients underwent surgical resection within 48 hours of embolization. Mean blood loss was 796mL and required on average 1.1units of blood. We experienced no complications. Pre-operative arterial embolisation of large, richly vascular bone tumours in anatomically difficult positions, is a safe and effective method of downstaging vascularity and reducing blood loss


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 115 - 115
1 Jan 2013
Gerrand C Lipede C Rahman K King I Ragbir M
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Introduction and aims. Solitary fibrous tumours (SFT) are rare soft tissue sarcomas. Challenges in management include the variation in anatomical location and uncertain malignant potential. We retrospectively reviewed our experience with the aim of formulating guidelines on appropriate treatment. Methods. An electronic database identified patients with SFT presenting between 2003–2011. Clinical records were reviewed. Results. 23 patients were identified. Mean age was 50.6 years (12–77 years). The anatomic location was lower limb in 8, upper limb 4, intrathoracic 3, retroperitoneal 3, buttock and perianal regions 2, pelvis 1, thoracic spine 1 and brain 1. 10 cases were histologically benign, 5 had malignant potential and 8 were malignant. In 12 cases there was a complete surgical resection. In 6 cases there was a positive margin or piecemeal excision. There were 4 local recurrences and 5 patients with metastases. Completeness of record keeping varied with times and surgical speciality. Conclusions. SFT occur infrequently, are difficult to diagnose, have an unpredictable course and present to a variety of surgical specialists. In order to improve outcomes, we recommend surgical and histological margins are accurately recorded and audited whatever surgical specialty leads the surgery, ideally within a sarcoma MDT. Complete resection at first attempt by specialists with an understanding of the need for complete resection is the goal


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_16 | Pages 11 - 11
1 Oct 2014
Paul L Cartiaux O Odri G Gouin F
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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