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Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 474 - 474
1 Jul 2010
van de Sande M Dijkstra P Bovee J Taminiau A
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Synovial sarcoma (SS) is rare but increasingly diagnosed and associated with poor prognosis. Primary surgical resection with wide margins and adjuvant radiation-therapy is considered gold standard in treatment of primary SS. Although (Neo)adjuvant chemo- and radiationtherapy are used in the primary treatment of SS, they are not advocated outside a clinical trial setting. In patients with primary SS and pulmonary metastases, (neo)adjuvant chemotherapy is often added to the treatment protocol but it’s effect on overall survival seems limited.

Between 1985 and 2004 33 patients with primary SS were treated in our clinic. Seventeen patients were diagnosed with pulmonary metastases at presentation (9) or during postoperative follow-up (8). Wide resection or focally marginal resection followed by radiotherapy was used as primary treatment for all patients. All primary metastasized patients were treated with adjuvant multi-agent chemotherapy including Isofosfamide. Average survival in this group was 32 months (5 year OS 50%), compared to 60 months in the late metastasized patient-group (2 and 5 year OS 50 and 11%). Wide resection was not related to improved overall survival when compared to marginal margins and additional radiation therapy. In the early metastasized group combined chemo-radiaton therapy provided no significant improvement in overall survival over adjuvant chemotherapy or radiation therapy alone. However additional chemotherapy in the late metastasized group was slightly associated with increased overall survival (5 year OS 0% vs 66%).

Treatment of early pulmonary metastasized SS remains highly dependent of the individual preference of patient and physician. In contrast to the reported prolonged disease free/overall survival of Enneking stage IIA and IIB SS patients, aggressive surgical and chemo-radiation therapy has not yet been associated with improvement of disease free/overall survival in stage III disease. Patients presenting with late pulmonary metastasis might benefit from adjuvant multi-agent chemotherapy treatment.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1011 - 1016
1 Sep 2022
Acem I van de Sande MAJ

Prediction tools are instruments which are commonly used to estimate the prognosis in oncology and facilitate clinical decision-making in a more personalized manner. Their popularity is shown by the increasing numbers of prediction tools, which have been described in the medical literature. Many of these tools have been shown to be useful in the field of soft-tissue sarcoma of the extremities (eSTS). In this annotation, we aim to provide an overview of the available prediction tools for eSTS, provide an approach for clinicians to evaluate the performance and usefulness of the available tools for their own patients, and discuss their possible applications in the management of patients with an eSTS.

Cite this article: Bone Joint J 2022;104-B(9):1011–1016.


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 425 - 429
1 May 2024
Jeys LM Thorkildsen J Kurisunkal V Puri A Ruggieri P Houdek MT Boyle RA Ebeid W Botello E Morris GV Laitinen MK

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting. Cite this article: Bone Joint J 2024;106-B(5):425–429


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_14 | Pages 36 - 36
1 Dec 2022
Falzetti L Fermi M Ghermandi R Girolami M Pipola V Presutti L Gasbarrini A
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Chordoma of the cervical spine is a rare but life-threatening disease with a relentless tendency towards local recurrence. Wide en bloc resection is recommended, but it is frequently not feasible in the cervical spine. Radiation therapy including high-energy particle therapy is commonly used as adjuvant therapy. The goal of this study was to examine treatment and outcome of patients with chordoma of the cervical spine. Patients affected by cervical spine chordoma who underwent surgery at the Rizzoli Institute and University Hospital of Modena, between 2007 and 2021 were identified. The clinical, pathologic, and radiographic data were reviewed in all cases. Patient outcomes including local recurrence and disease-specific survival (DSS) were analyzed using chi-square test and Kaplan-Meier survival analysis. Characteristics of the 29 patients (10 females; 19 males) included: median age at surgery 52.0 years (IQR 35.5 - 62.5 years), 10 (35%) involved upper cervical spine, 16 (55%) with tumors in the mid cervical spine, and 4 in the lower cervical spine (10%). Median tumor volume was 16 cm. 3. (IQR 8.7 - 20.8). Thirteen patients (45%) were previously treated surgically while 9 patients (31%) had previous radiation therapy. All patients underwent surgery: en bloc resection was passible in 4 patients (14 %), seventeen patients (59%) were treated with gross total resection while 8 patients (27%) underwent subtotal resection. Tumor volume was associated with a significantly higher risk of intraoperative complications (p < 0.01). Nineteen patients (65%) received adjuvant high-energy particle therapy. The median follow-up was 26 months (IQR 11 - 44). Twelve patients (41%) had local recurrence of disease. Patients treated with adjuvant high-energy particle therapy had a significant higher local control than patients who received photons or no adjuvant treatment (p = 0.01). Recurrence was the only factor significantly associated with worse DSS (p = 0.03 – OR 1.7), being the survival of the group of patients with recurrent disease 58.3% while the survival of the group of patients with no recurrent disease was 100%. Post-operative high-energy particle therapy improved local control in patients with cervical chordoma after surgical resection. Increased tumor volume was associated with increased risk of intraoperative complications. Recurrence of the disease was the only factor significantly associated with disease mortality


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 99 - 99
1 Dec 2022
St George S Clarkson P
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Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open). Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 76 - 76
1 Dec 2022
Eltit F Ng T Gokaslan Z Fisher C Dea N Charest-Morin R
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Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 64 - 64
1 Dec 2022
St George S Clarkson P
Full Access

Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open). Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_14 | Pages 29 - 29
1 Dec 2022
Pedrini F Salmaso L Mori F Sassu P Innocenti M
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Open limb fractures are typically due to a high energy trauma. Several recent studied have showed treatment's superiority when a multidisciplinary approach is applied. World Health Organization reports that isolate limb traumas have an incidence rate of 11.5/100.000, causing high costs in terms of hospitalization and patient disability. A lack of experience in soft tissue management in orthopaedics and traumatology seems to be the determining factor in the clinical worsening of complex cases. The therapeutic possibilities offered by microsurgery currently permit simultaneous reconstruction of multiple tissues including vessels and nerves, reducing the rate of amputations, recovery time and preventing postoperative complications. Several scoring systems to assess complex limb traumas exist, among them: NISSSA, MESS, AO and Gustilo Anderson. In 2010, a further scoring system was introduced to focus open fractures of all locations: OTA-OFC. Rather than using a single composite score, the OTA-OFC comprises five components grades (skin, arterial, muscle, bone loss and contamination), each rated from mild to severe. The International Consensus Meeting of 2018 on musculoskeletal infections in orthopaedic surgery identified the OTA-OFC score as an efficient catalogue system with interobserver agreement that is comparable or superior to the Gustilo-Anderson classification. OTA-OFC predicts outcomes such as the need for adjuvant treatments or the likelihood of early amputation. An orthoplastic approach reconstruction must pay adequate attention to bone and soft tissue infections management. Concerning bone management: there is little to no difference in terms of infection rates for Gustilo-Anderson types I–II treated by reamed intramedullary nail, circular external fixator, or unreamed intramedullary nail. In Gustilo-Anderson IIIA-B fractures, circular external fixation appears to provide the lowest infection rates when compared to all other fixation methods. Different technique can be used for the reconstruction of bone and soft tissue defects based on each clinical scenario. Open fracture management with fasciocutaneous or muscle flaps shows comparable outcomes in terms of bone healing, soft tissue coverage, acute infection and chronic osteomyelitis prevention. The type of flap should be tailored based on the type of the defect, bone or soft tissue, location, extension and depth of the defect, size of the osseous gap, fracture type, and orthopaedic implantation. Local flaps should be considered in low energy trauma, when skin and soft tissue is not traumatized. In high energy fractures with bone exposure, muscle flaps may offer a more reliable reconstruction with fewer flap failures and lower reoperation rates. On exposed fractures several studies report precise timing for a proper reconstruction. Hence, timing of soft tissue coverage is a critical for length of in-hospital stay and most of the early postoperative complications and outcomes. Early coverage has been associated with higher union rates and lower complications and infection rates compared to those reconstructed after 5-7 days. Furthermore, early reconstruction improves flap survival and reduces surgical complexity, as microsurgical free flap procedures become more challenging with a delay due to an increased pro-thrombotic environment, tissue edema and the increasingly friable vessels. Only those patients presenting to facilities with an actual dedicated orthoplastic trauma service are likely to receive definitive treatment of a severe open fracture with tissue loss within the established parameters of good practice. We conclude that the surgeon's experience appears to be the decisive element in the orthoplastic approach, although reconstructive algorithms may assist in decisional and planification of surgery


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 87 - 87
1 Dec 2021
Mannala G Rupp M Walter N Brunotte M Alagboso F Docheva D Brochhausen C Alt V
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Aim. Here, we are aimed to evaluate bacteriophage (191219) to treat S. aureus implant-associated bone infections by means of testing against S. aureus during its planktonic, biofilm and intracellular growth phases and finally assessing antimicrobial effect on in vivo biofilm formed on metal K-wire in an alternative insect model Galleria mellonella. Method. The bacteriophages (191219) were provided from D&D Pharma GmbH. These bacteriophages were tested against S. aureus EDCC 5055 (MSSA) and S. aureus DSM 21979 (MRSA) strains. To assess the activity of bacteriophages against planktonic growth phase, bacteriophages, and S. aureus EDCC 5055(1×10. 7. CFU/ml) were co-cultured in LB media as multiplicity of infection (MOI) of 10, 1, 0.1, and 0.01 for 24 hours at 37. o. C and finally plated out on the LB agar plates to estimate the bacterial growth. The antimicrobial activity of bacteriophages on biofilms in vitro was measured by analysing the incubating the several fold dilutions of bacteriophages in LB media with biofilms formed on 96-well plate. The eradication of biofilm was analysed with crystal violet as well as CFU analysis methods. Later, the effect of bacteriophages on intracellular growth of S. aureus in side osteoblast was tested by treating the S. aureus infected osteoblasts at 2h, 4h and 24h time points of post treatment. In addition, we have analysed synergistic effect with gentamicin and rifampicin antibiotics to clear intracellular S. aureus. Finally, experiments are performed to prove the effect of bacteriophages to clear in vivo biofilm using alternative insect model G. mellonella as well as to detect the presence of bacteriophages inside the osteoblasts through transmission electron microscopy (TEM) analysis. Results. Our results demonstrate the in vitro efficacy of bacteriophages against planktonic S. aureus. Transmission electron microscopy (TEM) experiments revealed severe infection of bacteria by bacteriophages. Bacteriophages also eradicated in a dose-dependent manner in vitro S. aureus biofilm formation and were active against intracellular S. aureus in an osteoblastic cell line. TEM analysis visualized the effect of the bacteriophages on S. aureus inside the osteoblasts with the destruction of the intracellular bacteria and formation of new bacteriophages. For the Galleria infection model, single administration of phages failed to show improvement in survival rates, but exhibited some synergistic effects with gentamicin or rifampicin, which was not statistically significant. Conclusions. In summary, bacteriophages could be a potential adjuvant treatment strategy for patients with implant-associated biofilm infections. Further preclinical and clinical trials are required to establish adequate treatment protocols


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 89 - 89
1 Jul 2020
Chua K
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Osteosarcoma is the most common primary bone tumour worldwide. This disease presents a formidable challenge to the orthopaedic surgeon, with a mortality rate of 30 per cent, even after surgical clearance. Aberrant Wnt signalling has been implicated in the pathogenesis osteoblastic tumours. The objective of this study is 2 fold- to investigate if osteosarcoma does indeed demonstrate aberrant Wnt signaling, and if so, does osteosarcoma respond to a novel Wnt inhibitor(ETC159). This can potentially lead to the development of a new adjuvant treatment modality for osteosarcoma. A novel Wnt signaling pathway protein antibody (YJ5) was used in immunihistochemistry staining of clinical osteosarcoma samples. A Wnt high osteosarcoma cell line(SJSA-1) was then implanted subcutaneously in a mouse model. These mice were treated with a novel PORCN inhibitor, ETC 159 for a period of 4 weeks in a two-arm randomised control study. The results of treatment were evaulated by clinical outcome parameters as well as immunohstochemistry. 100 per cent of clinical osteosarcoma samples demonstrated increased WLS expression and Wnt protein expression. SJSA-1 showed no significant decrease in tumour volume after 30 days of drug treatment (3070 SD 625 mm3 vs 3480 SD 433 mm3 p= 0.605 and 2060 SD 209 vs 1677 SD 213 mm3 p=0.219 respectively). Significantly, SJSA-1 demonstrated increased tumour necrosis in the treatment arm(30–60 percent increase across all samples p < 0 .005) Treated tumours also demonstrated markedly less angiogenesis compared to the non treatment arm. Osteosarcoma demonstrates aberrant Wnt signaling in a large percentage of cases. The use of a novel PORCN inhibitor ETC 159 for the treatment of Osteosarcoma has a marked effect on tumour necrosis. Our results suggest that ETC159 may cause tumour necrosis by inhibiting angiogenesis within the tumour. Further evaluation and understanding of the mechanism of Wnt singaling in regulating tumour pathogenesis may hold the potential for developing a curative therapeutic drug for this deadly disease


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 146 - 146
1 Jul 2020
Al-Shakfa F Wang Z Truong V
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Spinal metastases are seen in 10–30% of cancer patients. Twenty percent of these metastases occur in the lumbo-sacral spine. Lumbo-sacral spine has different mechanical properties and encloses the cauda equina. Few studies took interest in this spinal segment. The objective of this study is to evaluate prognostic factors of lumbo-sacral spinal metastasis treated in our center. We retrospectively reviewed 376 patients who were operated in our center from 2010 to 2018. Eighty-nine patients presented lumbo-sacral metastases and thus were included. Data collected included age, smoking, tumor histology, American spinal injury association (ASIA) score, modified Tokuhashi score, modified Bauer score, ambulation status and adjuvant treatment. The mean population age was 60.9 years old (35–85). The tumor histology was predominantly lung (19 patients, 21.3%), breast (13 patients, 14.6%), kidney (11 patients, 12.4%) and prostate (9 patients 10.1%). Twenty-two patients (24.7%) were unable to walk preoperatively. Seventy-nine patients (88.8%) underwent a posterior open approach with corpectomy in 65 patients (73%). Eighteen patients regained ambulation post-operatively (81.8%). The mean survival was 24.03 months (CI95% 17,38–30,67, Range 0–90) and the median of survival was 9 months (CI95% 4.38–13.62). Better preoperative ASIA score had a significant favorable effect (p=0.03) on survival. Patients who regained their ability to walk had better survival (25.1 months (CI95% 18.2–32) VS 0.5 months (CI95% 0–1.1). Postoperative radiotherapy had a benefic effect on survival (p=0.019): Survival Increased from 10.5 months (CI95% 2.4–18.7) to 27.6 months (CI95% 19.5–35.8). The modified Tokuhashi and the modified Bauer scores underestimated the survival of the patients with lumbosacral metastases. Lumbosacral spinal metastases has better survival than expected by Tokuhashi and Bauer score. Surgical procedure have an important impact on survival and the ability to walk


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 17 - 17
1 Apr 2012
Norum O Giercksky K Berg K
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Aim. Local recurrence after surgery of soft tissue sarcomas is dependent on surgical margins. Wide margins require large resections which may lead to impaired function or loss of limb. In some cases it may be technical impossible or even ethical unacceptable to achieve ideal surgical margins. Standard adjuvant treatment in such cases is ionising radiation, which may cause severe toxic side effects. PCI is a unique procedure for site-specific delivery of several types of membrane impermeable molecules. The technology is based on the photochemical induced cytosolic release of endocytosed macromolecules from endosomes and lysosomes into the cytosol. PCI has in this study been evaluated as an adjuvant to the surgical resection of sarcoma. Method. Human fibrosarcom (HT1080) was transplanted to athymic mice. The photosensitizer aluminium phthalocyanine disulfonat (AlPcS2a), and bleomycin (BLM) was systemically administrated 48 hours and 30 minutes respectively prior to surgery and light exposure. After resection with intralesional margin the tumour bed was illuminated at 670 nm (15 J/cm2). Results. PCI was found to induce longer delay in tumour growth than photodynamic therapy (PDT). In combination with surgery little was achieved with respect to tumour growth delay by adding the photosensitizer and light (photodynamic therapy, PDT) while PCI induced synergistic effect. Conclusion. The results indicate that PCI targets the viable peripheral zone of the tumour where PDT is apparently less effective. PCI with BLM seems promising as an adjuvant treatment after inadequate resection of sarcomas. The PCI technology is currently explored in a Phase I/II trial in University Hospital (London, UK)


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 111 - 111
1 Nov 2018
Mogensen SL Rasmussen MK Le D Nielsen A Foldager CB
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Osteoarthritis (OA) is an inflammatory degenerative disease that affects every fourth person with irreversible damage to the articular. Mesenchymal stem cells (MSCs) have been shown to affect host cells by paracrine stimulation in regenerative environments. Here we apply hyaluronic acid (HA), an essential part of the extracellular matrix in cartilage, for MSC immobilization. The aim was to investigate long-term MSC survival and paracrine effect on chondrocytes in an inflammatory co-culture environment. We hypothesized that MSCs immobilized in a HA hydrogel could provide a long-term immunomodulatory effect on chondrocytes in vitro. Human MSCs were seeded in a HA hydrogel and co-cultured with non-osteoarthritic human chondrocytes in biphasic wells inhibiting cellular contact. An inflammatory environment was induced by IL1-beta and compared with standard culture medium. Relative gene expressions of collagen types I, II and X, aggrecan, SOX9, MMP-13 and ADAMTS-5) were examined at day 3,7,14 and 28. Significant up-regulation of SOX9 at day 7, 14 and 28 and a significant down-regulation of ADAMTS-5 (day 14 and 28) was observed with co-culture of HA-immobilized MSCs and MSCs compared with controls with or without HA (without MSCs)No changes in expression was observed for aggrecan and collagen type 1. We showed that MSC affect the expression of SOX9 and ADAMTS-5 in a paracrine manner when co-cultured with chondrocytes in an inflammatory environment. MSCs immobilized in HA hydrogels survived and were contained in the hydrogel for up to 28 days. This suggests that HA-immobilized MSCs could potentially be used as adjuvant treatment of OA


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 50 - 50
1 Jan 2003
Grimer RJ Tillman RM Carter SR Spooner D Peake D
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Local recurrence (LR) following treatment of a sarcoma is generally accepted to be a poor prognostic sign and an indicator both of inadequate local control as well as of the failure of adjuvant treatment. Of 2589 patients with non metastatic Ewings, osteo-sarcoma, chondrosarcoma or a soft tissue sarcoma, 316 have developed LR at some stage following initial treatment of their tumour. 120 were already known to have metastases elsewhere when they developed LR or were found to have them at time of restaging but 196 developed LR as the first sign of relapse. The mean time to development of LR was 24 months and 72% had arisen within the first two years. Overall survival following LR was 25% at 5 years and 20% at 10 yrs. In patients with metastases at the time of LR or who were found to have them at the time of restaging the median survival was 6 months with only 12% being alive at 2 years. In those with LR as first sign of relapse median survival was 3 years with 30% long term survivors. Patients with low grade tumours had a better outcome than those with high grade – 50% being cured by further surgery. Of the high grade tumours without metastases at time of diagnosis relapsed Ewing’s had the worst prognosis with median survival of 8 months compared with 22 months for osteosarcoma, 36 months for STS and 36 months for chondrosarcoma, despite which overall survival was 16% for both Ewing’s and osteo-sarcoma patients but was 30% for chondrosarcoma and STS. LR following sarcoma surgery is due to a combination of aggressive disease with inadequate surgery and ineffective adjuvant treatment. In isolated LR aggressive further treatment is justified with an outcome similar to that of metastatic disease


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 492 - 492
1 Sep 2012
Ruggieri P Mavrogenis A Ussia G Angelini A Pala E Guerra G Drago G Mercuri M
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Background. There is doubt regarding resection compared to curettage for pelvic metastases. Previous studies have reported that curettage is associated with decreased survival compared with wide resection, and have justified a radical surgical approach to achieve pain palliation and tumor control. Aim. To evaluate the role of wide en bloc resection compared to curettage/marginal resection for patients with pelvic metastases. The rationale was that wide resection does not improve survival even in patients with solitary pelvic metastases. Method. Between 1985 and 2009, 21 patients (6 women, 15 men; age, 34–76 years) were treated for pelvic metastases. Histology included thyroid carcinoma in 5 patients, bladder carcinoma in 4 patients, renal and endometrium in 2 cases each and colon, ovarium, cerebral and lung carcinoma in 1 case each; the primary tumor was undiagnosed in 4 patients. Three patients had sacral and 1 patient had sacroiliac joint metastasis. According to Enneking's classification of the anatomical site involved, 5 patients had type I, 1 patient had type II, 6 patients had type III, 1 patient had type I and II, and 4 patients had type II and III pelvic metastasis. Metastatic disease was localized in the pelvic ring in 15 patients and multifocal in 6 patients. Eight patients had surgical treatment only; 13 patients had surgical treatment in addition to radiation therapy (2 patients), chemotherapy (1 patient), embolization (3 patients), or combined adjuvant treatments (7 patients). 21 patients with pelvic metastases were treated with wide resection (12 patients) and curettage/marginal resection (9 patients) and adjuvants. Sixteen patients had solitary pelvic metastases. Reconstruction of the hip joint was performed in three patients. Results. At a mean of 27.6 months (range, 2–152 months), the overall survival to death and local recurrence was 15% at 66 months and 47% at 26 months, respectively. Survival to death of patients treated with wide en bloc resection was 18% at 46 months compared to 62% at 12months of patients treated with curettage/marginal resection; no difference in survival to death between wide en bloc resection and curettage/marginal resection was observed (p=0.570). Survival to local recurrence of patients treated with wide en bloc resection was 67% at 24 months compared to 26% at 24 months of patients treated with curettage/marginal resection; this was also not statistically significant (p=0.0683). One patient treated with wide en bloc resection for a solitary pelvic bone metastasis had a postoperative complication. Conclusion. This series showed that neither the combination of surgical and adjuvant treatments nor the type of surgical resection were statistically significant parameters for local recurrence. We found no difference in survival to death or local recurrence 1 with wide en bloc resection compared to curettage or marginal resection, even in patients with solitary pelvic metastases


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_I | Pages - 59
1 Mar 2002
Missenard G Mascard E Court C
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Purpose: Use of massive allografts for reconstruction of major bone stock defects remains a controversial issue. We reviewed our experience to compare results with other methods, particularly free vascularised bone transfer reconstructions. Material and method: Between 1983 and 1995, 36 patients (15 men and 21 women) underwent cancerological resection of a long bone shaft for primary malignant tumour. Mean age was 19 years (8–84). The tumour was a high-grade sarcoma in 26 cases, low grade sarcoma in eight and adamantinoma in two. Mean length of resection was 19 cm (14–34). Cryopreserved allografts were used in 24 cases, gamma irradiated allografts in 12. Various osteosynthesis procedures were used, generally combining an axial assembly with a single or dual epiphyseal construct. Localisations were: femur 24, tibia ten and humerus four. All patients were reviewed at a minimum follow-up of five years (range 5–16 years, mean 8 years). Functional outcome was assessed with the Enneking criteria. Bone healing at junctions was considered to be achieved when there was no clinical expression and radiographic images remained unchanged for two years. Results: All immediate complications were infections (one femur four tibias) and required partial or total ablation of the allograft in four cases and amputation in one (tibia). The predominant late complications were late consolidation (n=13) and stress fracture of the allograft (n=6). Six patients died before bone healing and were not retained for analysis. Among the 28 patients retained for analysis (eight excluded: six deaths, one amputation, one total ablation of the allograft), only ten achieved bone healing after one procedure. The other eighteen required on the average four reoperations to achieve consolidation (3–11 procedures for osteosynthesis and new allograft material). All patients had achieved bone healing at last follow-up. Functional outcome was excellent for femurs, good for tibias, and fair for humeri due to the impact on shoulder function. There was no significant difference in consolidation with cryopreserved and irradiated bone material but two irradiated grafts could not be used correctly because they were to friable. Discussion: These more or less satisfactory results must be examined in light of the context. Cancerologicl resection (periosteum + soft tissue), generally combined with adjuvant treatment (chemotherapy for 24 patients and radiotherapy for three), places the patient in conditions highly unfavourable for bone healing. Use of allografts alone, combined with approximate fixation procedures early in our experience, demonstrated the limitations of the technique (only two primary consolidations among 18 patients). However, when the allograft was combined with axial fixation and immediate allograft or allograft after adjuvant treatment, primary consolidation was achieved in 80% of the cases (eight out of ten). All patients who achieved long-term remission conserved a functional limb with relatively preserved bone stock. Conclusion: Despite controversial results, massive allograft reconstructions can provide a useful alternative to fill major bone stock defects of the femur or humerus. For the tibia the risk of infections may require further discussion before determining the best approach. These results should be compared with those in a homogeneous series of patients treated with a vascularised free bone transfer, but to our knowledge no such series is available in the literature


Aims

To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs.

Methods

The medical records of 75 patients who underwent surgery between 2000 and 2020 were retrospectively reviewed, and 44 patients who were alive and available for follow-up (at a mean of 9.7 years postoperatively) were included in the study. Leg length discrepancy was measured on whole-leg radiographs, and functional assessment was performed with PROMs (Toronto Extremity Salvage Score (TESS) and Comprehensive Outcome Measure for Musculoskeletal Oncology Lower Extremity (COMMON-LE)) with two different aspects. The thresholds for unfavourable PROMs were determined using anchor questions regarding satisfaction, and the risk factors for unfavourable PROMs were investigated.


Bone & Joint Open
Vol. 4, Issue 11 | Pages 846 - 852
8 Nov 2023
Kim RG Maher AW Karunaratne S Stalley PD Boyle RA

Aims

Tenosynovial giant cell tumour (TGCT) is a rare benign tumour of the musculoskeletal system. Surgical management is fraught with challenges due to high recurrence rates. The aim of this study was to describe surgical treatment and evaluate surgical outcomes of TGCT at an Australian tertiary referral centre for musculoskeletal tumours and to identify factors affecting recurrence rates.

Methods

A prospective database of all patients with TGCT surgically managed by two orthopaedic oncology surgeons was reviewed. All cases irrespective of previous treatment were included and patients without follow-up were excluded. Pertinent tumour characteristics and surgical outcomes were collected for analysis.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_1 | Pages 102 - 102
1 Feb 2015
Mont M
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Knee stiffness is a well-recognised postoperative problem that has been reported to occur in 6% to 15% of all patients who undergo total knee arthroplasty (TKA), and there are multiple preoperative, intraoperative, and postoperative risk factors that may predispose patients to postTKA knee stiffness. Preoperative risk factors include poor baseline range of motion (ROM), obesity, and a history of previous knee surgery and/or trauma. Potential intraoperative risk factors for having a stiff knee are malalignment, gap imbalance, and under-resection of patella. Possible postoperative risk factors include heterotopic ossification, pain, poor patient motivation, and poor physical therapy compliance. Three commonly used adjuvant treatments for this condition are custom knee devices, Botox, and ASTYM. These treatment modalities are most effective when used within 6 weeks after surgery. Multiple case series have reported that CKD can improve range of motion while maximising patient-reported functional outcomes. Botox can improve range of motion by paralyzing the muscle where the contracture is located. ASTYM therapy has recently been reported to resolve muscle contractures by effectively stimulating tissue turnover, scar tissue resorption, and regeneration of the normal soft tissue structure. When these adjuvant therapies fail, manipulation under anesthesia has been reported to be efficacious in restoring some of the original ROM. If this fails, there are surgical treatment options such as arthroscopic debridement, surgical release, revision TKA, or peroneal nerve release


The Bone & Joint Journal
Vol. 104-B, Issue 5 | Pages 575 - 580
2 May 2022
Hamad C Chowdhry M Sindeldecker D Bernthal NM Stoodley P McPherson EJ

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.