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Purpose: Dedifferentiated low-grade osteosarcomas, which are considered high grade malignancies, can arise from the dedifferentiation of parosteal and low-grade osteosarcomas. Usually, localized dedifferentiated low-grade osteosarcomas are treated by wide resection, and the efficacy of adjuvant chemotherapy is controversial. We conducted a systematic review of studies that investigated the rates of mortality and significant events, such as recurrence and metastases, in localized dedifferentiated low-grade osteosarcoma patients who received wide resection only and in those who received wide resection and (neo-)adjuvant chemotherapy., Methods: We identified 712 studies through systematic searches of Embase, PubMed, and the Cochrane Central Register of Controlled Trials databases. Of those studies, seven were included in this review and none were randomized controlled trials. In the seven studies, 114 localized dedifferentiated low-grade osteosarcoma patients were examined., Results: Mortality rates of the resection plus chemotherapy (R + C) and the resection only (Ronly) groups were 20.3% and 11.4%, respectively [overall pooled odds ratio, 1.59 (P = 0.662); heterogeneity I 2 , 0%]. The local recurrence or distant metastasis rate in the R + C group was 36.7% and that in the Ronly group was 28.6% [overall pooled odds ratio, 1.37 (P = 0.484); heterogeneity I 2 was 0%]., Conclusions: Results show a limited efficacy of adjuvant chemotherapy for localized dedifferentiated low-grade osteosarcoma. However, because this was a systematic review of retrospective studies that examined a small number of patients, future randomized controlled trials are needed., (© 2024. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Purpose: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial carcinoma. The extension of life expectancy has led to an increased incidence of bone metastases (BM) among patients with cancer. BM result in skeletal-related events, including severe pain, pathological fractures, and nerve palsy. Surgery is typically required for the treatment of BM in patients with an impending fracture; however, it may be avoided in those who respond to ICIs. We systematically reviewed studies analyzing BM responses to treatment with ICIs., Methods: This study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement and registered in the UMIN Clinical Trials Registry (ID: UMIN000053707). Studies reporting response rates based on the Response Evaluation Criteria in Solid Tumors (RECIST) or the MD Anderson Cancer Center (MDA) criteria specific for BM in patients treated with ICIs were included; reports of fewer than five cases and review articles were excluded. Studies involving humans, published in English and Japanese, were searched. The PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Ultimately, nine studies were analyzed. The Risk of Bias Assessment tool for Non-randomized Studies was used to assess the quality of studies., Results: Based on the MDA criteria, complete response (CR) or partial response (PR) was observed in 44-78% and 62% patients treated with ICIs plus denosumab for NSCLC and melanoma, respectively. According to the RECIST, CR or PR was recorded in 5% and 7-28% of patients treated with ICIs for renal cell carcinoma and urothelial carcinoma, respectively., Conclusion: Although response rates to ICIs for BM are poor, patients treated with ICI plus denosumab for bone metastases with impending fractures from NSCLC and melanoma are likely to avoid surgery to prevent fractures., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Curettage is recommended for the treatment of Campanacci stages 1-2 giant cell tumor of bone (GCTB) in the extremities, pelvis, sacrum, and spine, without preoperative denosumab treatment. In the distal femur, bone chips and plate fixation are utilized to reduce damage to the subchondral bone and prevent pathological fracture, respectively. For local recurrence, re-curettage may be utilized when feasible. En bloc resection is an option for very aggressive Campanacci stage 3 GCTB in the extremities, pelvis, sacrum, and spine, combined with 1-3 doses of preoperative denosumab treatment. Denosumab monotherapy once every 3 months is currently the standard strategy for inoperable patients and those with metastatic GCTB. However, in case of tumor growth, a possible malignant transformation should be considered. Zoledronic acid appears to be as effective as denosumab; nevertheless, it is a more cost-effective option. Therefore, zoledronic acid may be an alternative treatment option, particularly in developing countries. Surgery is the mainstay treatment for malignant GCTB.

Background and Objective: The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC., Methods: We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions., Results: Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival., Conclusion: The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method., (© 2023 Wiley Periodicals LLC.)

Biopsy is a pivotal component in the diagnostic process of bone and soft tissue tumors. The objective is to obtain adequate tissue without compromising local tumor dissemination and the patient's survival. This review explores contemporary principles and practices in musculoskeletal biopsies, emphasizing the critical role of diagnostic accuracy while also delving into the evolving landscape of liquid biopsies as a promising alternative in the field. A thorough literature search was done in PubMed and Google Scholar as well as in physical books in libraries to summarize the available biopsy techniques for musculoskeletal tumors, discuss the available methods, risk factors, and complications, and to emphasize the challenges related to biopsies in oncology. Research articles that studied the basic principles and specialized techniques of biopsy techniques in tumor patients were deemed eligible. Their advantages and disadvantages, technical and pathophysiological mechanisms, and possible risks and complications were reviewed, summarized, and discussed. An inadequately executed biopsy may hinder diagnosis and subsequently impact treatment outcomes. All lesions should be approached with a presumption of malignancy until proven otherwise. Liquid biopsies have emerged as a potent non-invasive tool for analyzing tumor phenotype, progression, and drug resistance and guiding treatment decisions in bone sarcomas and metastases. Despite advancements, several barriers remain in biopsies, including challenges related to costs, scalability, reproducibility, and isolation methods. It is paramount that orthopedic oncologists work together with radiologists and pathologists to enhance diagnosis, patient outcomes, and healthcare costs.

Dedifferentiated chondrosarcoma (DDCS) is a high-grade subtype of chondrosarcoma with the bimorphic histological appearance of a conventional chondrosarcoma component with abrupt transition to a high-grade, non-cartilaginous sarcoma. DDCS can be radiographically divided into central and peripheral types. Wide resection is currently the main therapeutic option for localized DDCS. Moreover, the effectiveness of adjuvant chemotherapy remains controversial. Therefore, we performed a systematic review of available evidence to evaluate the effect of adjuvant chemotherapy on localized DDCS. The purpose was to compare the 5-year survival rate among patients treated with surgery plus adjuvant chemotherapy or surgery alone for localized DDCS. The search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Of the 217 studies shortlisted, 11 retrospective non-randomized studies (comprising 556 patients with localized DDCS) were selected. The 5-year survival rates were similar between the two treatment groups (28.2% (51/181) vs. 24.0% (90/375), respectively). The overall pooled odds ratio was 1.25 (95% confidence interval: 0.80-1.94; p = 0.324), and heterogeneity I 2 was 2%. However, when limited to peripheral DDCS, adjuvant chemotherapy was associated with prolonged survival ( p = 0.03). Due to the paucity of included studies and the absence of prospective comparative studies, no conclusions can be drawn regarding the effectiveness or ineffectiveness of adjuvant chemotherapy for localized DDCS.

The typical presentation of giant cell tumor of bone is a solitary lesion involving the meta-epiphyseal region of the long bones. The presence of more than one distinct giant cell tumor in the same patient is rare. This study reports on 7 patients with multicentric giant cell tumor of bone. Clinical and radiologic features were reviewed to evaluate the behavior of multicentric giant cell tumor of bone. Immunohistochemistry and genetic analysis for the H3F3A gene were performed to confirm the diagnosis. The knee was most frequently involved, and most of the lesions were in an ipsilateral extremity. All of the patients received surgical management with curettage or resection. The overall median follow-up was 194 months (interquartile range, 41-336 months). Five of 7 patients had local recurrence (71%), but considering the number of surgically treated lesions, the risk of local recurrence was 33% (5 local recurrences among 15 treated lesions). No lung metastases occurred. Multicentric giant cell tumor of bone tends to exhibit the same aggressive clinical behavior as solitary giant cell tumor of bone. Patients should be monitored for the occurrence of other lesions, especially in the ipsilateral extremity. [ Orthopedics . 2023;46(6):e376-e380.].

Background: Fluid-fluid levels (FFLs) is found in 10%-16% of giant cell tumor of bone (GCTB), and the presence of FFLs raises the suspicion of GCTB with secondary aneurysmal bone cyst (ABC), which can lead to increased intraoperative bleeding and, blurring the operative field, be associated with a risk of local recurrence. The first objective of this study is to determine whether secondary ABC is associated with a higher risk of local recurrence after curettage in patients with GCTB of the extremities. The second objective of this study is to investigate the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of FFLs detected on magnetic resonance imaging (MRI) to diagnose secondary ABC associated with GCTB., Methods: Two hundred and eighty patients with GCTB of the extremities who underwent curettage at the authors' institutions between 1980 and 2021 were included in this study., Results: Secondary ABC was found in 36 of 280 patients (12.9%) and local recurrence occurred in 66 of 280 patients (23.6%). Multivariate analysis showed no significant correlation between secondary ABC and local recurrence (hazard ratio [HR]: 1.87 (95% confidence interval [CI]: 1.00-3.53]; p = 0.051). Preoperative MRI revealed FFLs in 13 of 82 patients (15.9%). Sensitivity, specificity, positive predictive value, and negative predictive value of FFLs detected on preoperative MRI to diagnose secondary ABC were 36.8%, 90.5%, 53.8%, and 82.6%, respectively., Conclusion: The results of this study showed that secondary ABC does not increase the risk of local recurrence after curettage in patients with GCTB of the extremities. Although rare, FFLs were present in patients with GCTB and half of those with FFLs detected on preoperative MRI had secondary ABC., (© 2023 Wiley Periodicals LLC.)

Background: Osteosarcoma is a highly aggressive malignant bone tumor that affects mainly adolescents and young adults. We analyzed serum biomarkers for their prognostic significance in children with osteosarcoma., Methods: In this retrospective study, we investigated the prognostic factors in 210 children who were treated for appendicular osteosarcoma, including patient age and sex, tumor site and size (≥8 cm or <8 cm), presence of metastasis, chemotherapy-induced tumor necrosis, serum levels of alkaline phosphatase (AP), C-reactive protein, serum hemoglobin, lactate dehydrogenase, erythrocyte sedimentation rate (ESR), leukocyte counts, platelet count, and neutrophil-lymphocyte ratio., Results: A multivariate Cox regression model showed that high level of AP [HR of 1.73; 95% CI, 1.02 to 2.94], poor chemotherapy-induced tumor necrosis [HR of 2.40; 95% CI, 1.41 to 4.08] and presence of metastases at presentation [HR of 3.71; 95% CI, 2.19 to 6.29] were associated with poor prognosis at 5 years ( p < 0.05). Inadequate surgical margins [HR 11.28; 95% CI, 1.37 to 92.79] and high levels of ESR [HR 3.58; 95% CI, 1.29 to 9.98] showed a greater risk of local recurrence at 5 years follow-up ( p < 0.05)., Conclusions: AP and ESR can identify osteosarcoma-diagnosed children with a greater risk of death and local recurrence, respectively.

Orthopedic oncology has begun to use three-dimensional-printing technology, which is expected to improve the accuracy of osteotomies, ensure a safe margin, and facilitate precise surgery. However, several difficulties should be considered. Cadaver and clinical studies have reported more accurate osteotomies for bone-tumor resection using patient-specific cutting guides, especially in challenging areas such as the sacrum and pelvis, compared to manual osteotomies. Patient-specific cutting guides can help surgeons achieve resection with negative margins and reduce blood loss and operating time. Furthermore, this patient-specific cutting guide could be combined with more precise reconstruction using patient-specific implants or massive bone allografts. This review provides an overview of the basic technologies used in the production of patient-specific cutting guides and discusses their current status, advantages, and limitations. Moreover, we summarize cadaveric and clinical studies on the use of these guides in orthopedic oncology., Competing Interests: The authors declare no conflict of interest.

Purpose: Denosumab enables joint-sparing surgery (curettage) and surgical downstaging in patients with giant cell tumour of bone (GCTB), where joint preservation is not possible. However, denosumab treatment causes osteosclerosis of the lesion, making it difficult to curet the lesion, leaving the tumour behind, and increasing the local recurrence rate. We performed a three-centre retrospective study to investigate the postoperative local re-recurrence rate, joint preservation status, and functional outcomes of locally recurrent lesions after preoperative denosumab treatment and curettage in patients with difficult joint preservation., Methods: We included 38 of 142 patients with primary GCTB of the extremities who underwent preoperative denosumab and curettage between 2009 and 2021 with local recurrence. Preoperative denosumab was indicated in patients with minimal residual periarticular and subchondral bones, large extraosseous lesions (Campanacci stage 3), and pathological fractures that made joint preservation difficult., Results: Local re-recurrence occurred in 6 (15.8%) of the 38 patients. In 29 patients who underwent re-curettage, local re-recurrence occurred in six patients (20.7%); however, in nine patients who underwent en bloc resection, no local re-recurrence was observed. The joint preservation rate was 63.2% (24 of 38 patients), with a median Musculoskeletal Tumor Society score of 28 (interquartile range: 26.8-29.0). The median follow-up period after surgery for local recurrence was 63.5 months (interquartile range: 42.5-82.4)., Conclusion: Since the local re-recurrence rate after re-curettage for local recurrence was low, and the joint preservation rate and affected limb function were good, preoperative denosumab administration may be considered in patients who require downstaging to maintain good limb function (joint preservation)., (© 2022. The Author(s) under exclusive licence to SICOT aisbl.)

En bloc resection is typically performed to treat giant cell tumors of bone (GCTB), particularly when curettage can be challenging owing to extensive bone cortex destruction with soft tissue extension. Few reports have addressed the clinical outcomes after reoperation for local recurrence in patients with GCTB who underwent en bloc resection. In this multicenter retrospective study, we investigated local recurrence, distant metastasis, malignant transformation, mortality, and limb function in patients treated for local recurrence following en bloc resection for GCTB. Among 205 patients who underwent en bloc resection for GCTB of the extremities between 1980 and 2021, we included 29 with local recurrence. En bloc resection was performed for large tumors with soft tissue extension, pathological fractures with joint invasion, complex fractures, and dispensable bones, such as the proximal fibula and distal ulna. Local re-recurrence, distant metastasis, malignant transformation, and mortality rates were 41.4% (12/29), 34.5% (10/29), 6.9% (2/29), and 6.9% (2/29), respectively. The median Musculoskeletal Tumor Society score was 26 (interquartile range, 23-28). The median follow-up period after surgery for local recurrence was 70.1 months (interquartile range, 40.5-123.8 months). Local recurrence following en bloc resection for GCTB could indicate an aggressive GCTB, necessitating careful follow-up., Competing Interests: The authors declare no conflict of interest.

Background and Objective: The effects of adjuvant chemotherapy on periosteal osteosarcoma are controversial. Therefore, we conducted a systematic review of studies comparing mortality, local recurrence, distant metastasis and secondary malignancy incidence among patients who underwent surgery and (neo-) adjuvant chemotherapy or surgery alone for periosteal osteosarcoma without distant metastases at diagnosis., Methods: Of the 210 studies identified in the search, 13 were included in this study, involving 291 patients with periosteal osteosarcoma in total., Results: The mortality rates in the surgery and (neo-) adjuvant chemotherapy and surgery alone groups were 11.3% (8/71) and 16.3% (16/98), respectively. The overall pooled odds ratio was 0.89 (P = 0.800). The local recurrence rate in the surgery and (neo-) adjuvant chemotherapy group was 12.1% (8/66), while that in the surgery alone group was 17.6% (13/74). The overall pooled odds ratio was 1.31 (P = 0.601). The distant metastasis rate in the surgery and (neo-) adjuvant chemotherapy group was 15.2% (10/66) and that in the surgery alone group was 10.8% (8/74). The overall pooled odds ratio was 1.51 (P = 0.444). The incidence of secondary malignancy in the surgery and (neo-) adjuvant chemotherapy group was 7.6% (9/118) and that in the surgery alone group was 2.7% (2/74). The overall pooled odds ratio was 2.29 (P = 0.187)., Conclusions: Adjuvant chemotherapy did not appear to improve the prognosis of patients with periosteal osteosarcoma. No association was found between the use of adjuvant chemotherapy and development of secondary malignancies., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities., Methods: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16)., Results: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003)., Conclusions: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation., (© 2022. The Author(s).)

Introduction: Osteosarcoma (OS) is the most common primary osseous malignant tumour, with high propensity to metastasise in lungs. Pulmonary micro-metastases are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been shown to have anti-cancer properties in vitro and in vivo, and inhibit angiogenesis - effects that may prove beneficial for several types of cancer. The aim of the present work was to study how Dox affects OS cell growth in vitro and in vivo and OS-driven pulmonary metastasis in vivo., Methods: In vitro, the effect of Dox was measured in MG-63 and 143B human OS cell viability, apoptosis, invasion and migration. In vivo, highly metastatic 143B cells were orthotopically implanted into the tibia of SCID mice. The tumour growth and pulmonary metastases between Dox treated and untreated, non-amputated and early amputated xenografts were examined., Results: In vitro, Dox decreased viability, inhibited invasion, migration, and induced the apoptosis of OS cells. In vivo, Dox significantly enhanced tumour necrosis at primary OS sites, similarly to its in vitro effect, and downregulated the expression of Ki67, MMP2, MMP9, VEGFA and ezrin. It also decreased circulating VEGFA and MMP9 protein levels, in line with the decreased metastatic burden in Dox-treated mice (non-amputated and early-amputated)., Conclusions: Reprofiling of Dox can prevent the evolvement of pulmonary micro-metastases to clinically detectable macro-metastases and suppress the lethal progress of OS by inhibiting the expression of MMPs, VEGFA and ezrin at primary sites., (Copyright © 2022. Published by Elsevier Ltd.)

Giant cell tumour of bone (GCTB) typically occurs in young adults from 20-40 years old. Although the majority of lesions are located in the epi-metaphyses of the long bones, approximately one third of tumours are located in the axial skeleton, of which only 4% in the sacrum. Sacral tumours tend to be large at the time of presentation, and they present with aggressive features such as marked cortical destruction and an associated soft tissue component. The 2020 World Health Organisation classification of Soft Tissue and Bone Tumours describes GCTB as a neoplasm which is locally aggressive and rarely metastasizing. The tumour contains three different cell types: neoplastic mononuclear stromal cells, macrophages and osteoclast-like giant cells. Two tumour subtypes were defined: conventional GCTB and malignant GCTB. Only 1-4% of GCTB is malignant. In this review article, we will discuss imaging findings at the time of diagnosis to guide the musculoskeletal radiologist in reporting these tumours. In addition, imaging for response evaluation after various treatment options will be addressed, such as surgery, radiotherapy, embolization and denosumab. Specific findings will be presented per imaging modality and illustrated by cases from our tertiary sarcoma referral center. Common postoperative and post-radiotherapy findings in GCTB of the sacrum on MRI will be discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: There is no standard treatment for giant cell tumors of the sacrum. We compared the outcomes and complications in patients with sacral giant cell tumors who underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies versus those who underwent non-surgical treatment (denosumab therapy and/or embolization)., Methods: We retrospectively investigated 15 cases of sacral giant cell tumors treated at two institutions between 2005 and 2020. Nine patients underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies, and six patients received non-surgical treatment. The mean follow-up period was 85 months for the surgical group (range, 25-154 months) and 59 months (range, 17-94 months) for the non-surgical group., Results: The local recurrence rate was 44% in the surgical group, and the tumor progression rate was 0% in the non-surgical group. There were two surgery-related complications (infection and bladder laceration) and three denosumab-related complications (apical granuloma of the tooth, stress fracture of the sacroiliac joint, and osteonecrosis of the jaw). In the surgical group, the mean modified Biagini score (bowel, bladder, and motor function) was 0.9; in the non-surgical group, it was 0.5. None of the 11 female patients became pregnant or delivered a baby after developing a sacral giant cell tumor., Conclusions: The cure rate of intralesional nerve-sparing surgery is over 50%. Non-surgical treatment has a similar risk of complications to intralesional nerve-sparing surgery and has better functional outcomes than intralesional nerve-sparing surgery, but patients must remain on therapy over time. Based on our results, the decision on the choice of treatment for sacral giant cell tumors could be discussed between the surgeon and the patient based on the tumor size and location., (© 2021. The Author(s).)

Purpose: To perform translation, cross-cultural adaptation, and validation of the Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) scoring system in Greek patients with lower extremity sarcoma., Methods: The Greek version of the MSTS for the lower extremity and TESS questionnaires was developed using previously reported methods. Included were 100 patients with musculoskeletal sarcoma who underwent limb salvage surgery. The test-retest reliability [interclass correlation coefficient (ICC) between 2 different time points], internal consistency (Cronbach's alpha), construct validity (Kaiser's criteria, Eigenvalue > 1 rule), and external validity (Short form-36, Spearman's Rho) were assessed., Results: The test-retest reliability (ICC was 0.99 for MSTS-LE and 1 for TESS) and internal consistency were high (Cronbach's alpha was 0.763 for MSTS-LE and 0.924 for TESS) for both questionnaires. Based on the Scree plot, the number of factors retained was 1 for MSTS-LE and 2 for TESS. The TESS showed a strong correlation with SF-36 (Spearman's rho = 0.714, p < 0.001), but the correlation between MSTS for lower extremity and SF-36 was weak (Spearman's Rho = 0.313, p = 0.002)., Conclusions: The Greek version of both the MSTS for lower extremity and TESS questionnaire showed sufficient reliability, internal consistency and good performance using the loading factor analysis when used postoperatively in Greek patients who underwent surgical resection of lower extremity sarcoma. However, only the TESS showed strong correlation with the SF-36, indicating that MSTS for lower extremity was not as powerful for the evaluation of the global health status of these patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Chondrosarcomas of the small bones of the hands and feet are uncommon and account for less than 2% of all chondrosarcomas in the skeleton; a 4.2% rate of malignant degeneration of enchondromas to secondary chondrosarcomas has been reported. We performed this study to assess the outcome of the patients with chondrosarcomas of the small bones. We hypothesized that the presumed better prognosis of chondrosarcomas in these locations could be biased as the majority of these tumors tend to be of lower grades and are removed when still small sized, and that less aggressive surgery has an adverse effect on local control MATERIALS AND METHODS: We retrospectively studied the files of 44 patients with chondrosarcomas of the small bones of the hands and feet. There were 23 female and 21 male patients with a mean age of 50.9 years (range, 6-86 years). The mean follow-up was 13 years (range, 5-40 years). We recorded the patients' details including gender and age at diagnosis, type and duration of symptoms, tumor location and histology, type of surgery and complications, and outcome (local recurrences and metastases)., Results: The most common anatomical location for chondrosarcomas of the hands was the metacarpals and proximal phalanges. The most common presenting symptom was a slowly enlarging palpable mass. Overall, 36 chondrosarcomas were secondary to a pre-existing cartilaginous tumor. Patients with syndromes were affected in younger age compared to the others. The mean age at diagnosis was higher for higher grade chondrosarcomas. Overall, 13 patients (29.5%) experienced a local recurrence; the rate of local recurrence was higher after curettage regardless the histological grade of the tumors. After wide resection of the first local recurrence, five patients experienced local re-recurrence. Five patients (11.4%) experienced lung metastases, two patients at presentation. All these patients had a high grade chondrosarcomas. At the last follow-up, one patient with lung metastases died from disease, and another patient died from unrelated cause., Conclusions: The patients with chondrosarcomas of the small bones of the hands and feet may have a dismal outcome if treated improperly. A careful treatment planning is required to avoid unnecessary amputations. Curettage is associated with a high rate for local recurrence that should be treated with a more aggressive surgical resection to avoid re-recurrences. Although the risk is low, the patients may develop lung metastases, especially those with higher grade chondrosarcomas, therefore, they should be staged and followed closely., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Metastatic bone disease is a common complication of malignant tumours. As cancer treatment improves the overall survival of patients, the number of patients with bone metastases is expected to increase. The treatments for bone metastases include surgery, radiotherapy, and bone-modifying agents, with patients with a short expected prognosis requiring less invasive treatment. Patients with metastatic bone disease show greatly varying primary tumour histology, metastases sites and numbers, and comorbidities. Therefore, randomised clinical trials are indispensable to compare treatments for these patients. This editorial reviews recent findings on the diagnosis and prognosis prediction and discusses the current treatment of patients with metastatic bone disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

We performed a systematic analysis of existing studies to determine whether preoperative denosumab reduces the risk of local recurrence for patients with giant cell tumor of bone treated with en bloc resection and to address the optimal duration of preoperative denosumab with respect to the risk of local recurrence after en bloc resection. Denosumab did not decrease the risk of local recurrence after en bloc resection; the proportion of patients with local recurrence was 3.6% (2 of 56) in the en bloc resection with preoperative denosumab group vs 14.2% (40 of 280) in the en bloc resection alone group, with an overall pooled odds ratio of 0.76 ( P =.67). Meta-regression models revealed no association between the duration of preoperative denosumab and the odds of local recurrence after en bloc resection ( P =.83). Administration of denosumab for 3 months before en bloc resection is appropriate for sufficient bone hardening to reduce tumor cell spillage and does not result in denosumab-related complications. [ Orthopedics . 2021;44(6):326-332.].

The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient's prognosis, quality of life, postoperative function, and risk of postoperative complications. Therefore, bone metastasis treatment requires a multidisciplinary team approach, including radiologists, oncologists, and orthopedic surgeons. Recently, many novel palliative treatment options have emerged for bone metastases, such as stereotactic body radiation therapy, radiopharmaceuticals, vertebroplasty, minimally invasive spine stabilization with percutaneous pedicle screws, acetabuloplasty, embolization, thermal ablation techniques, electrochemotherapy, and high-intensity focused ultrasound. These techniques are beneficial for patients who may not benefit from surgery or radiotherapy.

We reviewed the recent literature related to primary musculoskeletal tumors and metastatic bone tumors. With regard to primary bone tumors, computer navigation systems and three-dimensional-printed prostheses seem to be new treatment options, especially in challenging anatomical locations, such as the sacrum and pelvis. Regarding the treatment of giant cell tumor of bone, recent studies have suggested that denosumab administration is related to a higher local recurrence rate following curettage, but a lower local recurrence rate following en bloc resection. In addition, there was no difference in the local recurrence rate at five years after surgery between short-term and long-term denosumab therapy. With regard to soft tissue tumors, percutaneous cryoablation appears to be a new treatment option for extra-abdominal desmoid tumors, with encouraging results. Regarding soft tissue sarcomas, a negative surgical margin of < 1 mm is sufficient to control local recurrence. Pexidartinib seems to be a promising systemic therapy for the treatment of tenosynovial giant cell tumors for which surgery is not expected to improve the function of the affected limb. Finally, the life expectancy of patients is the most important factor in determining the optimal surgical procedure for patients with impending or pathological fractures of the long bone due to metastatic bone tumors. Elevated C-reactive protein level was found to be an independent poor prognostic factor at 1 year after surgery for long bone metastases., (© 2021. The Author(s).)

The optimal type of reconstruction after intercalary tumor resection is unclear. Megaprosthetic and biologic reconstructions may restore bone stock, but their complexity may result in complications and delays in rehabilitation and initiation of adjuvant treatment. Instead, cement spacer permanent reconstruction can be performed as index surgery. The authors studied the files of 20 patients who had bone tumors of the humerus and femur and underwent wide margin resection and permanent cement spacer intercalary reconstruction. Mean follow-up was 52 months (range, 2-255 months). The authors evaluated the survival and function of the patients and the outcome of the cement spacer reconstructions. Five patients who had metastatic bone disease died of their disease with their cement spacer reconstruction in place without complications. One patient who had bone sarcoma experienced a local recurrence that was treated with hip disarticulation. Three patients who had bone sarcomas were converted to biologic reconstruction because of disease remission and had improved prognosis without complications related to cement spacer reconstruction. Two patients experienced mechanical failure of femoral reconstruction and underwent revision with an intercalary biologic reconstruction. No patient who had a cement spacer humeral reconstruction experienced a complication, and no patient experienced infection of the reconstruction. Mean Musculoskeletal Tumor Society score of the patients with cement spacer humeral and femoral reconstructions was 85% and 82%, respectively. [ Orthopedics . 2021;44(4):e593-e599.].

Fluid-fluid levels result from the separation of two fluids of differing densities within a cavernous space with the boundary between the two layers running in a horizontal plane at 90 degrees to the direction of gravity. Magnetic resonance imaging is the most sensitive imaging modality to identify fluid-fluid levels. Although the most common bone lesions containing fluid-fluid levels are aneurysmal bone cyst and telangiectatic osteosarcoma, fluid-fluid levels can be observed in a wide variety of bone and soft tissue lesions. Therefore, fluid-fluid levels cannot be considered diagnostic of any particular type of tumor and the diagnosis should be made on the basis of other clinical, radiological and pathological findings. This article summarizes the pathophysiology and imaging characteristics of fluid-fluid levels and discusses the differential diagnosis of tumors with this imaging sign., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The outcomes of patients with lung metastases from giant cell tumor of bone (GCTB) vary from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management approach for patients with lung metastases from GCTB, we evaluated the outcomes of patients who were initially managed by observation., Methods: We retrospectively reviewed the data of 22 patients with lung metastases from histologically confirmed GCTB who received observation as a first-line treatment approach. The median follow-up period was 116 months., Results: Disease progression occurred in 12 patients (54.5%). The median interval between the discovery of lung metastases and progression was 8 months. Eight patients underwent metastasectomy following initial observation. The median interval between the discovery of lung metastases and treatment by metastasectomy was 13.5 months. None of the patients experienced spontaneous regression. Of the 22 patients, 36.4% needed a metastasectomy, and 9.1% required denosumab treatment during the course of the follow-up period. Disease progression occurred in 45.5% of the 11 patients with lung nodules ≤ 5 mm, while all five of the patients with lung nodules > 5 mm experienced disease progression. Progression-free survival was significantly worse in the group with lung nodules > 5 mm compared to the group with lung nodules ≤ 5 mm (p = 0.022)., Conclusions: Observation is a safe first-line method of managing patients with lung metastases from GCTB. According to radiological imaging, approximately half of the patients progressed, and approximately half required a metastasectomy or denosumab treatment. However, patients with lung nodules > 5 mm should receive careful observation because of the high rate of disease progression in this group.

There are conflicting reports regarding the outcome and effect of denosumab for distal radius giant cell tumor of bone (GCTB). The authors performed this study to evaluate the behavior of distal radius GCTB in relation to the type of treatment and the administration of denosumab. The files of 72 patients with distal radius GCTB treated from 1984 to 2018 were reviewed. Fourteen patients were administered denosumab. Surgical treatment consisted of curettage (25 patients) or resection (47 patients) and allograft or vascularized fibular head graft reconstruction. Median follow-up was 63.1 months (interquartile range [IQR], 35.5-107.1 months). The authors evaluated local recurrences, metastasis, function, and complications. The local recurrence rate was 30.6% at a median of 14.0 months (IQR, 10-19 months), with no difference between curettage and resection. The local recurrence rate was significantly higher in the patients who received denosumab. The metastasis rate was 9.7% at a median of 41.0 months (IQR, 15-114 months), with no difference regarding denosumab administration. Function was significantly better in patients after curettage. The complication rate was 25%; vascularized fibular graft reconstruction was associated with fewer complications. This study found that denosumab increases the risk of local recurrence after curettage, function is better after curettage, and vascularized fibular graft is the optimal reconstruction after resection of distal radius GCTB. [Orthopedics. 2020;43(5):284-291.]., (Copyright 2020, SLACK Incorporated.)

Approximately one-fourth of osteosarcoma patients have metastases at presentation. The best treatment options for these patients include chemotherapy, surgery, and radiotherapy; however, the optimal scheme has not yet been defined. Standard chemotherapy for osteosarcoma metastatic at presentation is based on high-dose methotrexate, doxorubicin, and cisplatin (the MAP regimen), with the possible addition of ifosfamide. Surgical treatment continues to be fundamental; complete surgical resection of all sites of disease (primary and metastatic) remains essential for survival. In patients whose tumors do not respond to neoadjuvant chemotherapy, early surgical resection of the primary tumor with limb-salvage surgery or amputation and multiple metastasectomies, if feasible, after the completion of adjuvant chemotherapy is a reasonable option, as the reduction of the tumor volume could probably increase the effect of chemotherapy. Advanced radiotherapy techniques, such as carbon ion radiotherapy and stereotactic radiosurgery, and molecular targeted chemo-therapy with drugs such as pazopanib or apatinib have improved the dismal prognosis, especially for patients who are medically inoperable or who refuse surgery. Given that the presence of metastatic disease at diagnosis of a patient with osteosarcoma is a poor prognostic factor, a multidisciplinary approach by surgeons, medical oncologists, and radiotherapists is important. [Orthopedics. 2020;43(5):e345-e358.]., (Copyright 2020, SLACK Incorporated.)

Background: Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established., Questions/purposes: (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage?, Methods: We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis., Results: The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group., Conclusions: The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage.

Despite the evolution in imaging, especially the introduction of advanced imaging technologies, radiographs still are the key for the initial assessment of a bone tumor. Important aspects to be considered in radiographs are the location, shape and size or volume, margins, periosteal reaction, and internal mineralization of the tumor's matrix; careful evaluation of these may provide for accurate diagnosis in >80% of cases. Computed tomography and magnetic resonance imaging are often diagnostic for lesions with typical findings such as the nidus of osteoid osteoma and bone destruction such as in Ewing sarcoma and lymphoma that may be difficult to detect with radiographs; they may also be used for surgical planning. Magnetic resonance imaging accurately determines the intraosseous extent and articular and vascular involvement by the tumor. This article summarizes the diagnostic accuracy of imaging analyses in bone tumors and emphasizes the specific radiographic findings for optimal radiographic diagnosis of the patients with these tumors.

We reviewed the files of 203 patients with extremities GCTB treated with curettage as first surgery from 1990 to 2013. Median follow-up was 84.2 months. We evaluated whether the years of practice and training in orthopaedic oncology are associated with local recurrences, function and complications after curettage as first surgery for giant cell tumour of bone (GCTB). Local recurrences were not significantly different between orthopaedic oncology trained and non-trained orthopaedic surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. Function was not significantly different between orthopaedic oncology trained and non-trained surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. The only important univariate and multivariate predictor for local recurrence was PMMA adjuvant. Complications were not significantly different between orthopaedic oncology trained and non-trained orthopaedic surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. Curettage may be effectively performed as first surgery for GCTB by early-career (< 10 years of practice) non-trained orthopaedic oncology orthopaedic surgeons. PMMA adjuvant is recommended after appropriate curettage.

The spinal column represents the third most common site for metastases after the lungs and the liver, and the most common site for metastatic bone disease. With life-extending advances in the systemic treatment of cancer patients, the surgical procedures performed for spinal metastases will increase, and their related complications will increase unavoidably. Furthermore, considering the high complication rates reported in the spinal literature regarding spine surgery overall, it becomes clear that a better understanding of complications that the cancer patients with spinal metastases may experience is necessary. This article aims to summarize and critically examine the current evidence for complications after spine surgery for metastatic spinal disease, in both the perioperative and postoperative period. This paper would be useful for the treating physicians of these patients in their clinical practice.

Metastases are the most common malignancy in bone. In patients with bone metastases, especially if a limited expected survival, the indications for surgical treatment are limited, immediate pain relief and improvement in the functional status are important, and complications of treatments are unwanted. Novel medical treatments can offer an effective palliative option in these patients. Advances in interventional radiology and surgery have led to the development of less invasive techniques with the aim to achieve the same clinical results with less surgical morbidity. These include embolization, electrochemotherapy, magnetic resonance imaging-guided high-intensity focused ultrasound, and thermal ablation. Less invasive techniques combine the advantages of less invasive procedures including decreased blood loss, earlier functional recovery and initiation of adjuvant medical therapies and seem to be both effective in pain relief and local tumor control.

Background: There are conflicting reports for the outcome of the patients with giant cell tumor of bone (GCTB) and pathological fracture at presentation treated with curettage or resection. This study compared local recurrence, complications, and function after curettage versus resection for these patients., Materials and Methods: We retrospectively studied the files of 46 patients with histologically confirmed GCTB of the extremities admitted and treated from 1982 to 2015. The median follow-up was 79.5 months (57.0-125.5 months). We evaluated local recurrence and type of surgery-related complications with imaging and function with the Musculoskeletal Tumor Society (MSTS) score., Results: Overall local recurrence was 6.5%. There were one patient with curettage and two patients with resection; local recurrence rate was similar between the two procedures but the time to local recurrence was shorter after curettage. MSTS score was significantly better after curettage. Complications occurred in two patients after curettage and in five patients after resection; because of the low number of patients with complications, a statistical comparison was not possible; however, by direct comparison of the numbers, complications were more common after resection compared with curettage., Conclusion: Curettage is recommended for GCTB and pathological fracture at presentation because of similar local recurrence but better function compared with resection. The treating physicians should be aware and inform their patients for a shorter time to local recurrence after curettage and for more complications after resection., (© 2019 Wiley Periodicals, Inc.)

Purpose: There are conflicting reports on the effect of denosumab on lung metastases in patients with giant cell tumor (GCT) of bone. To address these reports, we performed this study to determine if denosumab prevents lung metastasis and to evaluate univariate and multivariate predictors for lung metastases in these patients., Materials and Methods: We retrospectively studied 381 GCT patients with surgery alone and 30 GCT patients with surgery and denosumab administration. The median follow-up was 85.2 months (IQR, 54.2-124.4 months). We evaluated lung metastases and local recurrences, univariate and multivariate predictors for lung metastases, response, and adverse events of denosumab administration., Results: The occurrence of lung metastases was similar (surgery alone 4.7%, 18 patients; denosumab administration 3.3%, 1 patient); however, the occurrence of local recurrences was significantly higher in the patients with denosumab administration. Denosumab administration was not an important predictor for lung metastases; Campanacci stage and type of surgery were the only univariate predictors for lung metastases, and type of surgery and local recurrence were the only multivariate predictors for lung metastases. Histology showed viable tumour in all tumor specimens of the patients with denosumab administration., Conclusion: Denosumab does not decrease the risk of lung metastases in patients with bone GCT; the only important predictors for lung metastases in these patients are type of surgery and local recurrence. However, because the number of patients with lung metastases was small for a multivariate analysis, the possibility of denosumab's effect could not be completely eliminated.

FT-IR spectroscopy was used to investigate the effect of oxidative stress and to approach the mechanism on cancer bone demineralization, aortic valve mineralization and heterotopic ossification on disease development. The FT-IR spectra obtained from paediatric, adult bone and ex vivo irradiated adult healthy bone with a dose of 20Gy were compared with those of healthy bone. The increase of band intensity changes of vasCH 2, vsCH 2 in the region 3000-2850cm -1 depended on aging, the disease progression and the dose of irradiation. The bands at 3080cm -1 and 1744cm -1 , which originate from olefinic terminal bond (v=CH) and ester carbonyl group (vROCO), respectively, indicate the influence of oxidative stress on lipid degradation and peroxidation, respectively. The new bands at about 1690cm -1 and 1516cm -1 denote the presence of β-sheet conformation of the proteins due to the diseases, confirming the increasing amount of lipophilic environment and fibril formation. Comparison of the FT-IR spectra of calcified aortic valve and hip heterotopic ossification with that of normal bones showed that in the bone-like formation the peroxide anion free radicals play an important role in the disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The survival of patients with tumors around the shoulder treated with extra-articular resection, the rates of reconstructions-related complications, and the function of the shoulder cannot be estimated because of limited available data from mainly small published related series and case reports., Methods: We studied 54 patients with tumors around the shoulder treated with extra-articular shoulder resections and proximal humeral megaprosthetic reconstructions from 1985 to 2012. Mean tumor volume was 549 cm 3 , and the mean length of the proximal humeral resection was 110 mm. Mean follow-up was 7.8 years (range, 3-21 years). We evaluated the outcomes (survival, metastases, recurrences, and function) and the survival and complications of the reconstruction., Results: Survival of patients with malignant tumors was 47%, 38%, and 35%, at 5, 10, and 20 years, respectively. Rates for metastasis and local recurrence were 60% and 18.5%, respectively. Survival was significantly higher for patients without metastases at diagnosis, tumor volume <549 cm 3 , and type IV resections. Survival of reconstructions was 56% at 10 years and 48% 20 years. Overall, 19 patients (35.2%) experienced 30 complications (55.5%), the most common being soft tissue failures that required subsequent surgery without, however, implant removal. The mean Musculoskeletal Tumour Society score was 25 points, without any significant difference between the types of extra-articular resections., Conclusion: Tumor stage and volume as well as type of resection are important predictors of survival of patients with malignant tumors around the shoulder. Survival of the reconstructions is satisfactory; nevertheless, the complication rate is high. The Musculoskeletal Tumour Society score is similar with respect to the type of resection., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Recent clinical studies have suggested that denosumab is associated with beneficial tumour response, surgical down-staging, and reduced surgical morbidity in patients with giant cell tumour of bone. However, these studies reported results of patients still on denosumab treatment, or patients after denosumab treatment but with a short follow-up. Other studies reported that the new osseous tumour matrix and thickened cortical bone that develop with denosumab treatment does not allow the surgeon to delineate the true extent of the tumour, and probably increases the risk for local recurrence. A study showed that cell proliferation is only diminished by denosumab; the cells continue to proliferate in vitro, albeit at a slower rate. More importantly, nine cases of malignant transformation of GCT during denosumab therapy without previous radiation exposure have been reported; inhibition of RANKL may increase the risk of new malignancies due to immunosuppression. With these concerns in mind, this article is an attempt to put essential information in one place, creating a comprehensive review that the curious reader would find interesting and informative.

Skeletal-related events in patients with metastatic bone disease include intractable severe pain, pathologic fracture, spinal cord and nerve compression, hypercalcemia and bone marrow aplasia. In patients with breast cancer, the skeleton is the most frequent site for metastases. Treatment options for metastatic bone disease in these patients include bisphosphonates, chemotherapeutic agents, opioids, hormonal therapy, minimally invasive/interventional and surgical techniques. Interventional oncology techniques for breast cancer patients with bone metastases include diagnostic (biopsy) and therapeutic (palliative and curative) approaches. In the latter, percutaneous ablation, augmentation and stabilization are included. The purpose of this article is to describe the basic concepts of biopsy, ablation, embolization and peripheral skeleton augmentation techniques in patients with metastatic bone disease from breast carcinoma. The necessity for a tailored approach applying different techniques for different cases and locations will be addressed.

Purpose: Chondroblastoma (CB) is a rare benign tumor that occurs most commonly in the second decade of life. No studies on CB in adulthood have been reported. Our purposes were to report a single-institution experience on CB in adults and to discuss the clinical and imaging findings, type of treatment, oncologic and functional outcomes., Patients and Methods: All patients diagnosed and treated for CB from 1981 to 2014 were reviewed. The main inclusion criterion was patients above their 30 years of age at diagnosis. Clinical presentation, imaging, surgical treatment, complications and functional outcome were evaluated. Local recurrences were recorded., Results: There were 15 males (65%) and 8 females (35%) with a mean age of 40 years (range 30-59 years). Tumor involved the small bones (talus, calcaneus, acromion, cuneiform, metatarsals) in 15 patients (65%) and the long bones in eight patients (35%). Treatment consisted of curettage only (6 cases), curettage plus phenol (13 cases), curettage plus radiotherapy (one patient with vertebral tumor), resection (two patients with CB of the acromion) and chopart amputation (one patient with a metatarsal tumor). At a mean follow-up of 8.4 years (range 3-30 years), twenty patients (87%) remained continuously disease-free, whereas three had local recurrences. None of the patients received chemotherapy., Conclusion: This study confirms that the occurrence and outcome of adult patients with CB are similar with those affecting younger patients. The main difference consists of the involved bones; flat bones and short tubular bones of the foot, especially the talus and calcaneus, are most commonly involved as opposed to long tubular bones., Level of Evidence: Therapeutic study, level IV-1 (case series).

An intercalary reconstruction is defined as replacement of the diaphyseal portion of a long bone after segmental skeletal resection (diaphysectomy). Intercalary reconstructions typically result in superior function compared to other limb-sparing procedures as the patient's native joints above and below the reconstruction are left undisturbed. The most popular reconstructive options after segmental resection of a bone sarcoma include allografts, vascularized fibula graft, combined allograft and vascularized fibula, segmental endoprostheses, extracorporeal devitalized autograft, and segmental transport using the principles of distraction osteogenesis. This article aims to review the indications, techniques, limitations, pros and cons, and complications of the aforementioned methods of intercalary bone tumor resections and reconstructions in the context of the ever-growing, brave new field of limb-salvage surgery.

Surgical management of primary musculoskeletal tumors of the shoulder girdle is cognitively and technically demanding. Over the last decades, advances in the medical treatments, imaging and surgical techniques have fostered limb salvage surgery and reduced the need for amputation. Despite well-accepted general principles, an individualized approach is often necessary to accommodate tumor extension, anatomical challenges and patient characteristics. A combination of techniques is often required to achieve optimal oncologic and durable functional outcome. Goal of this article is to review approach and management of patients with locally advanced sarcomas of the shoulder girdle requiring major tumor surgery, to illustrate principles of surgical strategy, outcome and complications, and to provide useful guidelines for the treating physicians.

Tumors of the hand comprise a vast array of lesions involving skin, soft tissue and bone. The majority of tumors in the hand are benign. Malignant tumors, although rare, do occur and frequently have unique characteristics in this specific anatomic location. Careful staging, histological diagnosis and treatment are essential to optimize clinical outcome. However, straightforward most of the time, hand tumor management does have pitfalls; caution is advised, as a missed or delayed diagnosis or an improperly executed biopsy may have devastating consequences. This article reviews the clinical spectrum of the most common benign and malignant bone and soft tissue tumors of the hand and discusses the clinicopathological findings, imaging features and current concepts in treatment for these tumors.

Purpose: To provide treatment guidelines for patients with long bone metastatic disease based on a systematic review of the literature and to propose an algorithm to guide orthopedic surgeons in decision-making for these patients., Materials and Methods: We performed a computerized literature search in MEDLINE, EMBASE and Scopus for studies on patients with long bone metastases. We used the key words "long bones", "metastasis" and "treatment" for published studies that evaluated any treatment for long bone metastases. The articles found were then studied to determine the accuracy of surgical treatments for long bone metastases in every anatomic location, regardless of cancer type, stage and grade of the oncologic disease. Guidelines inferred from this literature review were collected, and an algorithm was proposed., Results: There was no clear evidence to support excision of a long bone metastatic lesion at the same surgical setting with internal fixation or prosthetic reconstruction. However, en bloc resection of an isolated bone metastasis may have a beneficial effect on survival. The life expectancy of the patients should be considered for any surgical treatment. Internal fixation preferably with reconstruction nails is indicated for meta-diaphyseal lesions; their rate of mechanical failure and complications ranges from 2 to 22 %. Prosthetic reconstruction is indicated for extensive lytic lesions or pathologic fractures in a meta-epiphyseal locations; their rate of mechanical failure and complications ranges from 3.7 to 35 %. Most of the internal fixation-related complications occur more than 1 year after treatment, in contrast to prosthetic reconstruction-related complications that may occur earlier., Conclusions: Intramedullary nail fixation or prosthetic reconstruction should be chosen on the basis of the location of the lesion, the extent of bone destruction and the stability of the construct to outlast the expected life of the patient. Implant-related complication is similar but may occur earlier with prosthetic reconstructions.

Purpose: Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-β (TGF-β) superfamily of proteins; they were initially named after their ability to induce ectopic bone formation. Published studies have proved BMPs' role in a variety of biological processes such as embryogenesis and patterning of body axes, and maintaining adult tissue homeostasis. Other studies have focused on BMPs properties, functions and possible involvement in skeletal diseases, including cancer., Methods: A literature search mainly paying attention to the role of BMPs in musculoskeletal tumors was performed in electronic databases., Results: This article discusses BMPs synthesis and signaling, and summarizes their prominent roles in the skeletal system for the differentiation of osteoblasts, osteocytes and chondrocytes., Conclusions: The review emphasizes on the role of BMP signaling in the initiation and progression of musculoskeletal cancer.

Purposes: Telangiectatic osteosarcoma (TOS) is a rare subtype of osteosarcoma. We analyzed (1) oncologic outcome in a large homogeneous series and (2) the role of prognostic factors on prognosis, local recurrence and metastasis., Methods: Eighty-seven patients (47 males, 54 %) were retrospectively analyzed. All except 4 had extracompartmental disease, and ten patients had lung metastasis at diagnosis. Pathologic fracture was present in 27 cases (31 %). Seventy-eight patients were treated with neoadjuvant chemotherapy; nine had surgery as first treatment. Limb-salvage surgery was performed in 71 cases, amputation in 14, and rotationplasty in one. One patient died before surgery. Possible prognostic factors were statistically evaluated., Results: Overall survival was 60.7 % at 10 years of follow-up. Fifty-one patients were disease-free (58.6 %), 2 were alive with disease (2.3 %), 31 died with disease (35.6 %), and 3 died of other causes (3.4 %). Ten local recurrences were observed (11 %). Twenty-five patients (29 %) developed lung (22) or bone (3) metastases. No statistical difference was found considering age, metastases at diagnosis, gender, pathologic fracture, tumor volume, compartmental status, number of neoadjuvant chemotherapy agents and treatment. Induced necrosis was significant at both univariate and multivariate analysis (p < 0.0001)., Conclusions: TOS does not have a poor prognosis as previously reported in literature, with a survival of about 60 % at 10 years. Most of patients can be cured with neoadjuvant chemotherapy plus surgery (limb sparing surgery is possible and safe). Tumor response to chemotherapy as induced necrosis was the only significant prognostic factors on survival, even if small tumor volume at diagnosis correlates with better prognosis at univariate analysis., Level of Evidence: IV.

Background: Metastatic disease is the most common malignancy of the bone. Prostate, breast, lung, kidney, and thyroid cancer account for 80% of skeletal metastases. Bone metastases are associated with significant skeletal morbidity including severe bone pain, pathologic fractures, spinal cord or nerve roots compression, and malignant hypercalcemia. These events compromise greatly the quality of life of the patients. The treatment of cancer patients with bone metastases is mostly aimed at palliation., Objective: This article aims to present these palliative treatments for the patients with bone metastases, summarize the clinical applications, and review the techniques and results., Methods: It gives an extensive overview of the possibilities of palliation in patients with metastatic cancer to the bone., Results and Discussion: Currently, modern treatments are available for the palliative management of patients with metastatic bone disease. These include modern radiation therapy, chemotherapy, embolization, electrochemotherapy, radiofrequency ablation, and high-intensity focused ultrasound. As such it is of interest for all physicians with no experience with these developments to make palliative procedures safer and more reliable.

Angiosarcoma of bone is a rare high-grade malignant vascular tumor accounting for <1% of malignant bone tumors. Tumor location in the distal radius is very rare. Complete surgical resection with limb salvage surgery or amputation is essential for the outcome of the patient. However, the literature is vague regarding the best surgical approach for resection of the distal radius and the optimal reconstruction option after a bone tumor resection. Several reconstruction techniques have been described, varying from arthrodesis to arthroplasties. In this article, we present a report of a patient with angiosarcoma of the distal radius treated with complete resection and reconstruction with a distal radius osteoarticular allograft. We discuss the advantages and the limitations of this surgical technique for the distal radius.