Primary bone tumours are tumours that start in the bone. In contrast, secondary bone cancer is where the cancer started in another part of the body but has then spread to the bones.
The most common types of primary bone tumour are osteosarcoma and Ewing's sarcoma, both of which are most frequently diagnosed in children and young adults. Other less common types of bone cancer include: Chondrosarcoma (a cancer arising in cartilage cells, usually found in adults between ages 50-75, though the less common mesenchymal-chondrosarcoma is more frequent in younger patients), Malignant Fibrous Histiocytoma of bone (MFH), Chondoma (a rare low grade malignancy occuring mostly between ages 30 -70), and other rare tumours.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
Information is reviewed by a panel of scientific and clinical experts, patients, parents/ carers, Further info. BCRT became a registered the charity in 2006 and raises funds for research into primary bone cancer, and provides information and support for patients and their families. The Website includes information booklets, personal stories and a section for teenagers.
Newcastle upon Tyne Hospitals NHS Foundation Trust One of the 5 specialist centres in England funded for the investigation and surgical treatment of primary bone tumours. Patients come from the North East of England, Cumbria, Yorkshire and beyond.
PubMed Central search for free-access publications about Bone Cancer (primary) MeSH term: Bone Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
A website by orthopedic surgeon Dr. Henry DeGroot, with contributions from numerous clinical colleagues. It includes numerous case studies, including radiology and pathology images, and information covering a comprehensive range of bone tumours.
BioMed Central an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
Membership organisation for medics in the USA and Canada
Newcastle Sarcoma Notes This Prezi attempts to summarise all the aspiring orthopaedic surgeon needs to know about Orthopaedic Oncology. By Craig Gerrand, a Consultant Orthopaedic Surgeon. Licensed for Educational Use only.
A site by Dr. James Wittig, Chief of Orthopedic Oncology at Mount Sinai Medical Center, NY. The site has many case studies including annotated images of presenting radiology, gross pathology, microscopic pathology and surgery.
Pelvic reconstruction after sacral resection is challenging in terms of anatomical complexity, excessive loadbearing, and wide defects. Nevertheless, the technological development of 3D-printed implants enables us to overcome these difficulties. Here, we present a case of sacral osteosarcoma surgically treated with hemisacrectomy and sacral reconstruction using a 3D-printed implant. The implant was printed as a customized titanium prosthesis from a 3D real-sized reconstruction of a patient's CT images. It consisted mostly of a porous mesh and incorporated a dense strut. After 3-months of neoadjuvant chemotherapy, the patient underwent hemisacretomy with preservation of contralateral sacral nerves. The implant was anatomically installed on the defect and fixed with a screw-rod system up to the level of L3. Postoperative pain was significantly low and the patient recovered sufficiently to walk as early as 2 weeks postoperatively. The patient showed left-side foot drop only, without loss of sphincter function. In 1-year follow-up CT, excellent bony fusion was noticed. To our knowledge, this is the first report of a case of hemisacral reconstruction using a custom-made 3D-printed implant. We believe that this technique can be applied to spinal reconstructions after a partial or complete spondylectomy in a wide variety of spinal diseases.
Andritsch E, Beishon M, Bielack S, et al. ECCO Essential Requirements for Quality Cancer Care: Soft Tissue Sarcoma in Adults and Bone Sarcoma. A critical review. Crit Rev Oncol Hematol. 2017; 110:94-105 [PubMed] Related Publications
BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Sarcoma: essential requirements for quality care • Sarcomas - which can be classified into soft tissue and bone sarcomas - are rare, but all rare cancers make up more than 20% of cancers in Europe, and there are substantial inequalities in access to high-quality care. Sarcomas, of which there are many subtypes, comprise a particularly complex and demanding challenge for healthcare systems and providers. This paper presents essential requirements for quality cancer care of soft tissue sarcomas in adults and bone sarcomas. • High-quality care must only be carried out in specialised sarcoma centres (including paediatric cancer centres) which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Access to such units is far from universal in all European countries. • It is essential that, to meet European aspirations for high-quality comprehensive cancer control, healthcare organisations implement the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis and follow-up, to treatment, to improve survival and quality of life for patients. CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality service for soft tissue sarcomas in adults and bone sarcomas. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary teams is guaranteed to all patients with sarcoma.
Liu W, Liu SY, He YB, et al. MiR-451 suppresses proliferation, migration and promotes apoptosis of the human osteosarcoma by targeting macrophage migration inhibitory factor. Biomed Pharmacother. 2017; 87:621-627 [PubMed] Related Publications
Previous studies have shown that MiR-451 plays an important role in human osteosarcoma carcinogenesis, but the underlying mechanism by which MiR-451 affects the osteosarcoma has not been fully understood. This study intends to uncover the mechanism by which MiR-451 functions as a tumor suppressor. The expression of MiR-451 in osteosarcoma tissues and osteosarcoma cell lines was monitored by real-time PCR. The proliferation ability was examined by MTT and cell cycle assay. The migration and apoptosis of cells were monitored by migration assay and flow cytometry, respectively. Moreover, the angiogenesis of HUVEC cells transfected with MiR-451 mimics was examined by tube formation assay. The effect of MiR-451 on MIF was determined by luciferase assays and Western blot assay. The results showed that MiR-451 expression level was significantly reduced in the osteosarcoma compared with normal bone tissues. Overexpression of MiR-451 significantly attenuated the proliferation and migration, and induced the apoptosis of osteosarcoma cells. Furthermore, the angiogenesis of HUVEC cells transfected with MiR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. Finally, we demonstrated that MiR-451 overexpression inhibited the malignant behavior of osteosarcoma by downregulating MIF. These findings suggest that MiR-451 may act as a tumor suppressor in osteosarcoma. MiR-451 inhibited cell proliferation, migration and angiogenesis and promoted apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of MIF. MiR-451/MIF may be a novel therapeutic target in treatment of osteosarcoma.
Cheng JH, Chiang LY, Kuo DJ Inadvertently boarding a pirate ship: disease progression in a paediatric patient with relapsed metastatic Ewing sarcoma receiving treatment at a centre for alternative therapy in Mexico. BMJ Case Rep. 2017; 2017 [PubMed] Related Publications
Complementary and alternative medicine (CAM) therapies are commonly incorporated into the care of patients with paediatric cancer. Many modalities are safe and effective during cancer treatment and have proved beneficial for symptom relief and quality of life. However, situations where alternative therapy is provided without allopathic medical care supportive care resources can pose a safety risk to patients. This report describes the case of a 16-year-old Chinese girl with metastatic Ewing sarcoma who sought treatment with alternative treatment in Mexico. When her disease progressed with an ensuing significant loss of function, the centre personnel were unable to respond to her acute deterioration or provide necessary medical care. This resulted in her being stranded in a foreign country paralysed, isolated, and with large unanticipated financial expenditures.
Drazin D, Bhamb N, Al-Khouja LT, et al. Image-guided resection of aggressive sacral tumors. Neurosurg Focus. 2017; 42(1):E15 [PubMed] Related Publications
OBJECTIVE The aim of this study was to identify and discuss operative nuances utilizing image guidance in the surgical management of aggressive sacral tumors. METHODS The authors report on their single-institution, multi-surgeon, retrospective case series involving patients with pathology-proven aggressive sacral tumors treated between 2009 and 2016. They also reviewed the literature to identify articles related to aggressive sacral tumors, their diagnosis, and their surgical treatment and discuss the results together with their own experience. Information, including background, imaging, treatment, and surgical pearls, is organized by tumor type. RESULTS Review of the institutional records identified 6 patients with sacral tumors who underwent surgery between 2009 and 2016. All 6 patients were treated with image-guided surgery using cone-beam CT technology (O-arm). The surgical technique used is described in detail, and 2 illustrative cases are presented. From the literature, the authors compiled information about chordomas, chondrosarcomas, giant cell tumors, and osteosarcomas and organized it by tumor type, providing a detailed discussion of background, imaging, and treatment as well as surgical pearls for each tumor type. CONCLUSIONS Aggressive sacral tumors can be an extremely difficult challenge for both the patient and the treating physician. The selected surgical intervention varies depending on the type of tumor, size, and location. Surgery can have profound risks including neural compression, lumbopelvic instability, and suboptimal oncological resection. Focusing on the operative nuances for each type can help prevent many of these complications. Anecdotal evidence is provided that utilization of image-guided surgery to aid in tumor resection at our institution has helped reduce blood loss and the local recurrence rate while preserving function in both malignant and aggressive benign tumors affecting the sacrum.
Qu Q, Chu X, Wang P MicroRNA-195-5p suppresses osteosarcoma cell proliferation and invasion by suppressing naked cuticle homolog 1. Cell Biol Int. 2017; 41(3):287-295 [PubMed] Related Publications
MiR-195-5p has been shown to play an essential role in human cancer progression. Nevertheless, the biological role of miR-195-5p in osteosarcoma development remains unclear. In this study, real-time PCR was performed to examine the miR-195-5p expression in human osteosarcoma cell lines. CCK-8 assay and Transwell assay were carried out to measure the effect of miR-195-5p on cell proliferation and invasion. Luciferase reporter assay was used to identify the targets of miR-195-5p. The results showed that miR-195-5p was significantly downregulated in osteosarcoma cells. Forced expression of miR-195-5p significantly inhibited cell proliferation, suppressed cell migration and invasion, compared with wild-type and control-transfected osteosarcoma cells. Luciferase reporter assay revealed that miR-195-5p binds to the 3'-untranslated region (UTR) of Naked cuticle homolog 1 (NKD1), indicating that NKD1 was a novel target of miR-195-5p. NKD1 mRNA and protein levels were reduced after overexpression of miR-195-5p. Moreover, silencing of NKD1 significantly inhibited the proliferation and invasion of osteosarcoma cells. Accordingly, our results support a tumor suppressor role of miR-195-5p in osteosarcoma through inhibiting NKD1, and it may be a promising therapeutic target for osteosarcoma.
Zhang H, Mai Q, Chen J MicroRNA-210 is increased and it is required for dedifferentiation of osteosarcoma cell line. Cell Biol Int. 2017; 41(3):267-275 [PubMed] Related Publications
Osteosarcoma (OS) is the most common malignant bone tumor and is prevalent in adolescents. In clinical studies, miR-210 has been reported to be tightly correlated to the poor prognosis of OS. Nevertheless, its roles in OS have not been fully elucidated. In view of the central role played by OS stem cells (OSCs) in the malignant progression of OS, this study investigated the influence of miR-210 on the formation of OSCs. Our previous findings suggested that the microenvironment of bone, abundant TGF-β1 and hypoxia, could induce OS cells to dedifferentiate into OSCs. In this study, we found that miR-210 participated in the dedifferentiation of OS cells into OSCs, and inhibiting it significantly suppressed the formation of OSCs. Further results suggested that miR-210 promoted the expression of TGF-β1 and its downstream effectors Snail1 and Slug which were highly elevated in the process of OS dedifferentiation. Additionally, the target gene of miR-210 was also investigated. It was found that NFIC was significantly reduced by miR-210 treatment and also during OS dedifferentiation. Therefore, this study suggested that miR-210 promoted OS cells dedifferentiation and uncovered its role in the malignant progress of OS.
Kotake Y, Goto T, Naemura M, et al. Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells. Anticancer Res. 2017; 37(1):81-85 [PubMed] Related Publications
BACKGROUND: A long noncoding RNA, p21-associated ncRNA DNA damage-activated (PANDA), associates with nuclear transcription factor Y subunit alpha (NF-YA) and inhibits its binding to promoters of apoptosis-related genes, thereby repressing apoptosis in normal human fibroblasts. Here, we show that PANDA is involved in regulating proliferation in the U2OS human osteosarcoma cell line. MATERIALS AND METHODS: U2OS cells were transfected with siRNAs against PANDA 72 h later and they were subjected to reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and cell-cycle analysis. RESULTS: PANDA was highly expressed in U2OS cells, and its expression was induced by DNA damage. Silencing PANDA caused arrest at the G1 phase of the cell cycle, leading to inhibition of cell proliferation. Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which caused G1 phase arrest. CONCLUSION: These results suggest that PANDA promotes G1-S transition by repressing p18 transcription, and thus promotes U2OS cell proliferation.
Ning X, Shang XW, Zhuang Y, et al. Correlation between TRAIL and caspase-8 expression and their relationship with cell proliferation and apoptosis in human osteosarcoma. Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Osteosarcoma is a common malignant bone tumor that mainly affects children and adolescents. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily. Caspase-8 appears in the upstream of apoptosis signaling pathway among caspases. We investigated TRAIL and caspase-8 levels in osteosarcoma patients to determine their correlation with cell proliferation and apoptosis. Osteosarcoma and osteochondroma patients receiving surgery in our hospital were selected. TRAIL and caspase-8 expression levels in tissue were determined by immunohistochemistry, and protein levels in cells were evaluated by western blotting. Human osteosarcoma cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The osteosarcoma and osteochondroma cell cycles and apoptosis were investigated by flow cytometry. Correlation analysis was applied to TRAIL and caspase-8 levels during cell apoptosis. Positive TRAIL and caspase-8 expression rates in osteosarcoma tissue were significantly lower than in the controls (P < 0.05). TRAIL (0.114 ± 0.002) and caspase-8 (0.352 ± 0.124) levels in experimental cells were obviously lower than in the controls (P < 0.05). Osteosarcoma cells in the experimental group demonstrated higher proliferation and lower apoptosis at 24, 48, and 72 h (P < 0.05). The experimental cell number increased in the G1 stage and decreased in the S stage (P < 0.05). TRAIL and caspase-8 proteins showed positive correlation with apoptosis in osteosarcoma (P < 0.05). Human osteosarcoma presented reduced TRAIL and caspase-8 levels with enhanced cell proliferation and reduced apoptosis. TRAIL and caspase-8 expression levels were positively correlated with apoptosis in osteosarcoma.
Armakolas N, Armakolas A, Antonopoulos A, et al. The role of the IGF-1 Ec in myoskeletal system and osteosarcoma pathophysiology. Crit Rev Oncol Hematol. 2016; 108:137-145 [PubMed] Related Publications
Growth hormone (GH) regulated mainly liver-produced insulin-like growth factor 1 (IGF-1) is a key molecule in embryonic & post embryonic development that is also involved in cancer biology. Herein we review new insights of the role of igf-1 gene products and of the IGF-1Ec isoform in muscle and bone development/repair and its role in osteosarcoma pathophysiology, underlying the possible role of the Ec peptide as a future therapeutic target.
Leopizzi M, Cocchiola R, Milanetti E, et al. IKKα inibition by a glucosamine derivative enhances Maspin expression in osteosarcoma cell line. Chem Biol Interact. 2017; 262:19-28 [PubMed] Related Publications
Chronic inflammation has been associated to cancer development by the alteration of several inflammatory pathways, such as Nuclear Factor-κB pathway. In particular, IκB kinase α (IKKα), one of two catalytic subunit of IKK complex, has been described to be associated to cancer progression and metastasis in a number of cancers. The molecular mechanism by which IKKα affects cancer progression is not yet completely clarified, anyway an association between IKKα and the expression of Maspin (Mammary Serine Protease Inhibitor or SerpinB5), a tumor suppressor protein, has been described. IKKα shuttles between cytoplasm and nucleus, and when is localized into the nuclei, IKKα regulates the expression of several genes, among them Maspin gene, whose expression is repressed by high amount of nuclear IKKα. Considering that high levels of Maspin have been associated with reduced metastatic progression, it could be hypothesized that the repression of IKKα nuclear translocation could be associated with the repression of metastatic phenotype. The present study is aimed to explore the ability of a glucosamine derivative, 2-(N-Carbobenzyloxy)l-phenylalanylamido-2-deoxy-β-d-glucose (NCPA), synthesized in our laboratory, to stimulate the production of Maspin in an osteosarcoma cell line, 143B. Immunofluorescence and Western blotting experiments showed that NCPA is able to inhibit IKKα nuclear translocation, and to stimulate Maspin production. Moreover, in association with stimulation of Maspin production we found the decrease of β1 Integrin expression, the down-regulation of metalloproteases MMP-9 and MMP-13 production and cell migration inhibition. Taking in account that β1 Integrin and MMP-9 and -13 have been correlated with the invasiveness of osteosarcoma, considering that NCPA affects the invasiveness of 143B cell line, we suggest that this molecule could affect the osteosarcoma metastatic ability.
Verdegaal SH, van Rijswijk CS, Brouwers HF, et al. MRI appearances of atypical cartilaginous tumour/grade I chondrosarcoma after treatment by curettage, phenolisation and allografting: recommendations for follow-up. Bone Joint J. 2016; 98-B(12):1674-1681 [PubMed] Related Publications
AIMS: The purpose of this retrospective study was to differentiate between the MRI features of normal post-operative change and those of residual or recurrent disease after intralesional treatment of an atypical cartilage tumour (ACT)/grade I chondrosarcoma. PATIENTS AND METHODS: We reviewed the case notes, radiology and histology of 75 patients, who had been treated for an ACT/grade I chondrosarcoma by curettage, phenolisation and bone allografting between 1994 and 2005. The first post-operative Gd-enhanced MRI scan was carried out within one year of surgery. Patients had a minimum of two scans and a mean follow-up of 72 months (13 to 169). Further surgery was undertaken in cases of suspected recurrence. RESULTS: In 14 patients (18.6%) a second procedure was undertaken after a mean period of 59 months (8 to 114). Radio frequency ablation (RFA) was used in lesions of < 10 mm and curettage, phenolisation and bone grafting for those ≥ 10 mm. Only six of these (8% of total) had a histologically-proven recurrence. No increase in tumour grade was seen at time of recurrence. CONCLUSION: Based on this study, we have been able to classify the post-operative MRI appearances into four groups. These groups differ in follow-up, and have a different risk of recurrence of the lesion. Follow-up and treatment vary for the patients in each group. We present a flow diagram for the appropriate and safe follow-up for this specific group of patients. Cite this article: Bone Joint J 2016;98-B:1674-81.
Sun L, Yang C, Xu J, et al. Long Noncoding RNA EWSAT1 Promotes Osteosarcoma Cell Growth and Metastasis Through Suppression of MEG3 Expression. DNA Cell Biol. 2016; 35(12):812-818 [PubMed] Related Publications
Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. Long noncoding RNAs (lncRNAs) are a class of transcriptional products of the genome without protein-coding potential. Recently, lncRNA Ewing sarcoma-associated transcript 1 (EWSAT1) was functionally identified in Ewing sarcoma, a highly aggressive primary pediatric bone tumor. However, whether EWSAT1 plays a role in OS remains unclear. In the present study, gain- and loss-of-function assays demonstrated that EWSAT1 enhanced OS cell proliferation, migration, and invasion. Further mechanistic studies found that EWSAT1 positively regulated lncRNA MEG3 expression in the transcriptional level. Finally, we observed that EWSAT1 facilitates OS cell growth and metastasis through regulation of MEG3, suggesting that EWSAT1-MEG3 axis might be a promising target for OS treatment.
Kamal AF, Widyawarman H, Husodo K, et al. Clinical Outcome and Survival of Osteosarcoma Patients in Cipto Mangunkusumo Hospital: Limb Salvage Surgery versus Amputation. Acta Med Indones. 2016; 48(3):175-183 [PubMed] Related Publications
AIM: to analyze the outcome and survival rate of osteosarcoma patients in our hospital as well as the factors affecting prognosis and functional outcome. METHODS: this is a retrospective cohort study of osteosarcoma patients in Cipto Mangunkusumo Hospital underwent limb salvage surgery (LSS), amputation, LSS + amputation, and refused surgery from year 1995 to 2014. The surgical decision was based on patient's age, staging, location, neurovascular involvement, Huvos type, functional demand, patient preference, and general condition. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) score with the maximum score of 30. RESULTS: subjects consisted of 80 male and 52 female aged 4 to 61 year-old. They underwent limb salvage surgery (LSS) (n=37), amputation (n=42), LSS + amputation (n=2), and refused surgery (n=51). Overall 5-year cumulative survival rate was 14.6%. The 5-year survival rate for each group; LSS, amputation, combined LSS and amputation, and refused surgery was 34.8%; 15.9%; 0%; and 0%, respectively. Patients with tumor size <8 cm tend to underwent LSS compared to amputations (60.7% vs 39.3%, p=0.046). Local recurrence-free survival for LSS and amputation was 96.2% and 86.5% respectively (p=0.586). MSTS score was higher in LSS than amputation group (25.0 vs 18.5, p=0.011). CONCLUSION: LSS had higher survival rate than amputation in osteosarcoma patients who were treated in Cipto Mangunkusumo Hospital. MSTS functional score in the LSS group was higher than amputation group.
He F, Zhang W, Shen Y, et al. Effects of resection margins on local recurrence of osteosarcoma in extremity and pelvis: Systematic review and meta-analysis. Int J Surg. 2016; 36(Pt A):283-292 [PubMed] Related Publications
PURPOSE: There are conflicting findings about the effect of resection margins on local recurrence in osteosarcoma after surgery. In this meta-analysis, we examined the association between local recurrence and resection margins for osteosarcoma in extremity and pelvis. METHODS: EMBASE, PubMed and Cochrane CENTRAL were searched from January 1980 to July 2016. The quality of included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale. The odds ratio and 95% confidence interval of local recurrence were estimated, respectively, for inadequate vs adequate margins and marginal vs wide margins using a random-effect model. Chi-square test was performed to comparing the local recurrence rate between extremity and pelvic osteosarcomas with an identical surgical margin. RESULTS: Thirteen articles involving 1559 patients (175 with and 1384 without local recurrence) were included in this study. The meta-analysis showed that the osteosarcoma resected with inadequate and marginal margins, whether in extremity or in pelvis, were associated with a significantly higher local recurrence rate than the osteosarcoma resected with adequate and wide margins, respectively. Chi-square test showed that, when pelvic and extremity osteosarcomas were removed with an identical resection margin, the local recurrence was significantly more frequent in pelvis osteosarcoma than in extremity osteosarcoma. CONCLUSION: This study provides level IIa evidence to support that the surgery with adequate or wide resection margin has positive effect on reducing the risk of local recurrence in osteosarcoma. In addition, the factors independent of resection margin are more likely to increase the risk of local recurrence in pelvic osteosarcoma. LEVEL OF EVIDENCE: Level IIa, Therapeutic study.
Heaton TE, Hammond WJ, Farber BA, et al. A 20-year retrospective analysis of CT-based pre-operative identification of pulmonary metastases in patients with osteosarcoma: A single-center review. J Pediatr Surg. 2017; 52(1):115-119 [PubMed] Related Publications
PURPOSE: Cooperative studies support complete metastasectomy in osteosarcoma (OS). Pre-operative CT is used to identify and quantify metastases and can facilitate minimally invasive techniques. Here we assess the accuracy of pre-operative CT compared to findings at thoracotomy and its change over time. METHODS: We reviewed OS thoracotomies performed at our institution from 1996 to 2015. The number of metastases identified on pre-operative chest CT was compared to the number of metastases seen on pathology (both metastases with viable cells and non-viable, osteoid-only metastases). RESULTS: Eighty-eight patients underwent 161 thoracotomies with a median of 14days (range, 1-85) between CT and surgery, a median of 2 CT-identified lesions (range, 0-15), and a median of 4 resected lesions (range, 1-25). In 56 (34.8%) cases, more metastases were found surgically than were seen on CT, and among these, 34 (21.1%) had a greater number of viable metastases. There was poor overall correlation between CT and pathology findings (Kendall Tau-b=0.506), regardless of CT slice thickness, decade of thoracotomy, or total number of CT-identified lesions. CONCLUSIONS: CT accuracy in pre-operatively quantifying OS pulmonary metastases has not improved in recent decades. Consequently, we recommend an open technique with direct lung palpation for complete identification and resection of OS pulmonary metastases. LEVEL OF EVIDENCE: Level IV, retrospective study with no comparison group.
To explore a novel combination of chemotherapy, gene therapy, and thermotherapy for osteosarcoma, a targeted heat-sensitive co-delivery system based on bacterial magnetosomes (BMs) was developed. The optimal culture conditions of magnetotactic bacteria (MTB) AMB-1 and characterization of BMs were achieved. A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under transcriptional control of a thermosensitive promoter (human HSP70 promoter) was constructed for gene therapy. Doxorubicin (DOX) and pHSP70-Plk1-shRNA were included in the targeted thermosensitive co-delivery system, and in vitro DOX release activity, targeted gene silencing efficiency and in vitro antitumor efficacy were investigated. The results showed that the optimal culture conditions of MTB AMB-1 are an oxygen concentration of 4.0%, a pH value of 7.0, 20 μmol/L of ferrous sulfate, 800 mg/L of sodium nitrate, and 200 mg/L of succinic acid. The temperature of BMs reached 43°C within 3 minutes and could be maintained for 30 minutes by adjusting the magnitude of the alternating magnetic field (AMF). The diameters of BMs, BM-DOX, BM-recombinant eukaryotic plasmid pHSP70-Plk1-shRNA (shPlk1), and BM-DOX-shPlk1 were 43.7±4.6, 79.2±5.4, 88.9±7.8, and 133.5±11.4 nm, respectively. The zeta potentials of BMs, BM-DOX, BM-shPlk1, and BM-DOX-shPlk1 were -29.4±6.9, -9.5±5.6, -16.7±4.8, and -10.3±3.1 mV, respectively. Besides, the system exhibited good release behavior. DOX release rate from BM-DOX-shPlk1 was 54% after incubation with phosphate-buffered saline at 43°C and 37% after incubation with 50% fetal bovine serum, which was significantly higher than that at 37°C (P<0.05). In addition, the expressions of Plk1 mRNA and protein were significantly suppressed in cells treated with BM-DOX-shPlk1 following hyperthermia treatment under the influence of an AMF compared to other groups (P<0.05). Furthermore, evaluation of the effect of in vitro antitumor revealed that BM-DOX-shPlk1 following hyperthermia treatment under the influence of an AMF was significantly more effective than others in tumor inhibition. In conclusion, the new heat-sensitive co-delivery system represents a promising approach for the treatment of cancer.
Cernat E, Docquier PL, Paul L, et al. Patient Specific Instruments for Complex Tumor Resection-Reconstruction Surgery within the Pelvis: A Series of 4 Cases. Chirurgia (Bucur). 2016 Sept-Oct; 111(5):439-444 [PubMed] Related Publications
The pelvis bone resection-reconstruction surgery is one of the most challenging fields in orthopedics. Being applied for tumors, as for other complex reconstruction cases, this type of surgery needs careful planning and is time consuming, in order to obtain proper accuracy. Unfortunately not all the time the expected accuracy is met, with consequences for the patients. PSI proved to provide good cutting accuracy during simulated tumor surgery within the pelvis. This article present a series of 4 patients operated in our department between June 2014 and Mars 2015 for tumors resectionreconstructions. The patients were imaged using a CT and an MRI scan and the images were reconstructed in 3D. According to the bone bank stock, the most similar allograft was chosen and the stored CT scan was reconstructed in 3D. Patient specific instruments (PSI) were designed and manufactured using rapid-prototyping technology for the resection of the native tissues as for the resection of the careful selected hemipelvic allografts. Allografts fitting to the pelvis of the patients was excellent and allowed stable osteosynthesis.
Starc MT, Rosenblum MK, Meyers PA, Hatzoglou V Rare presentation of Ewing sarcoma metastasis to the sella and suprasellar cistern. Clin Imaging. 2017 Jan - Feb; 41:73-77 [PubMed] Article available free on PMC after 01/01/2018 Related Publications
We present an exceedingly rare case of a Ewing sarcoma metastasis manifesting as a sellar mass mimicking a pituitary adenoma. The differential diagnosis of the young adult with a sellar mass is presented and correlated with a review of available literature, demonstrating this case's unique potential for clinical teaching. More specifically, this case illustrates that in a patient with a clinical history of Ewing sarcoma, a metastasis may involve the sella and suprasellar cistern without apparent osseous involvement.
Park SK, Lee IS, Cho KH, et al. Osteosarcoma of pelvic bones: imaging features. Clin Imaging. 2017 Jan - Feb; 41:59-64 [PubMed] Related Publications
The metaphyseal locations of tubular bones with osteoid mineralization in young patients are important diagnostic radiologic features of osteosarcoma. The pelvic bones are an unusual location of osteosarcoma. Although osteosarcoma occurring in pelvic bones is not common, the osteoid matrix may be a critical finding for differentiating osteosarcoma from other common pelvic bone tumors. Therefore, the possibility of osteosarcoma in pelvic bones may be considered in the presence of osteoid matrix even in the old age group.
De Amorim Bernstein K, Liebsch N, Chen YL, et al. Clinical outcomes for patients after surgery and radiation therapy for mesenchymal chondrosarcomas. J Surg Oncol. 2016; 114(8):982-986 [PubMed] Related Publications
He T, Surdez D, Rantala JK, et al. High-throughput RNAi screen in Ewing sarcoma cells identifies leucine rich repeats and WD repeat domain containing 1 (LRWD1) as a regulator of EWS-FLI1 driven cell viability. Gene. 2017; 596:137-146 [PubMed] Related Publications
A translocation leading to the formation of an oncogenic EWS-ETS fusion protein defines Ewing sarcoma. The most frequent gene fusion, present in 85 percent of Ewing sarcomas, is EWS-FLI1. Here, a high-throughput RNA interference screen was performed to identify genes whose function is critical for EWS-FLI1 driven cell viability. In total, 6781 genes were targeted by siRNA molecules and the screen was performed both in presence and absence of doxycycline-inducible expression of the EWS-FLI1 shRNA in A673/TR/shEF Ewing sarcoma cells. The Leucine rich repeats and WD repeat Domain containing 1 (LRWD1) targeting siRNA pool was the strongest hit reducing cell viability only in EWS-FLI1 expressing Ewing sarcoma cells. LRWD1 had been previously described as a testis specific gene with only limited information on its function. Analysis of LRWD1 mRNA levels in patient samples indicated that high expression associated with poor overall survival in Ewing sarcoma. Gene ontology analysis of LRWD1 co-expressed genes in Ewing tumors revealed association with DNA replication and analysis of differentially expressed genes in LRWD1 depleted Ewing sarcoma cells indicated a role in connective tissue development and cellular morphogenesis. Moreover, EWS-FLI1 repressed genes with repressive H3K27me3 chromatin marks were highly enriched among LRWD1 target genes in A673/TR/shEF Ewing sarcoma cells, suggesting that LRWD1 contributes to EWS-FLI1 driven transcriptional regulation. Taken together, we have identified LRWD1 as a novel regulator of EWS-FLI1 driven cell viability in A673/TR/shEF Ewing sarcoma cells, shown association between high LRWD1 mRNA expression and aggressive disease and identified processes by which LRWD1 may promote oncogenesis in Ewing sarcoma.
Schmolders J, Koob S, Schepers P, et al. Lower limb reconstruction in tumor patients using modular silver-coated megaprostheses with regard to perimegaprosthetic joint infection: a case series, including 100 patients and review of the literature. Arch Orthop Trauma Surg. 2017; 137(2):149-153 [PubMed] Related Publications
PURPOSE AND OBJECTIVE: Bone resection regarding adequate surgical margins is the treatment of choice for malignant bone tumors. In the case of metastasis-related complications, so-called skeletal-related events, it is highly important to achieve pain relief and a stable joint situation to re-mobilize the patients immediately following surgery. To bridge the often large osseous defect zones after tumor resection, both cemented and uncemented modular endoprosthetic systems are widely used. Patients undergoing tumor-related endoprosthetic orthopedic surgery are facing high risk for developing a periprosthetic joint infection (PJI). The immunocompromised condition due to anti-neoplastic treatment and long operation time with large exposure of tissue contributes to a high risk of infection. METHODS: The authors present a case series of 100 patients (31% primary bone tumor and 69% metastasis-related surgery) undergoing tumor-related lower limb salvage surgery with special regard to periprosthetic joint infection and the management of this "difficult to treat" situation. Furthermore, a review of the current literature regarding infection following bone tumor resection and endoprosthetic reconstruction is performed and discussed. RESULTS: The median follow-up was 24 months (range 12-108 months). Ten patients (10%) suffered from a periprosthetic joint infection. We recorded six acute infections (type I) <4 weeks after surgery, one infection >4 weeks after surgery (type II), and three late infections (type III). According to the definition of Laffer et al., three of our patients (30%) are probably free of infection, one patient died of PJI-associated sepsis, and five patients were free of infection, but without restoration of the affected joint. CONCLUSION: In conclusion, our own results show that perimegaprosthetic joint infection among silver-coated implants, in patients undergoing tumor-related surgery of the lower limb, is lower compared to non-silver-coated implants. Due to heterogeneity of patients and potential treatment options, the treatment regime should be tailored for the patients' individual situation.
Lugowska I, Mierzejewska E, Lenarcik M, et al. The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults. Tumour Biol. 2016; 37(9):12071-12078 [PubMed] Related Publications
Ezrin is a protein that functions as a cross-linker between actin cytoskeleton and plasma membrane. Its clinical role in osteosarcoma is unclear. The aim of this study was to investigate, in osteosarcoma, the prognostic value of ezrin expression at biopsy and changes in expression levels after preoperative chemotherapy. Thirty-eight newly diagnosed osteosarcoma patients aged 6-23 years were included. At diagnosis, 20 patients had localized disease, the others had distant metastases. Median follow-up was 75 months (range 13-135). Ezrin expression was assessed immunohistochemically in biopsy tissue and primary tumour specimens resected after chemotherapy. The influence on survival of changes in ezrin expression after chemotherapy was analysed. Ezrin expression was significantly higher after preoperative chemotherapy and changes compared to biopsy tissue were significantly lower in patients with early progression than in patients with relapse or no further evidence of disease (p = 0.006 and p = 0.002, respectively). Similarly, ezrin expression was higher after preoperative chemotherapy and exhibited less change in expression in deceased patients compared to patients surviving more than 5 years (both p = 0.001). Ezrin expression at biopsy was significantly associated with both histopathological aggressiveness (p < 0.001) and tumour size (p = 0.037). The results of this study provide evidence that changes in overexpression of ezrin due to preoperative chemotherapy could be a useful predictive and prognostic marker in patients with osteosarcoma.
Niu J, Sun Y, Guo Q, et al. miR-1 Inhibits Cell Growth, Migration, and Invasion by Targeting VEGFA in Osteosarcoma Cells. Dis Markers. 2016; 2016:7068986 [PubMed] Article available free on PMC after 01/01/2018 Related Publications
microRNAs (miRNAs) are small noncoding RNAs and have been shown to play a crucial role in the osteosarcoma (OS) tumorigenesis and progression. VEGFA is a key regulator of angiogenesis and plays an important role in regulation of tumor metastasis. The objective of this study was to determine whether VEGFA was involved in miR-1-mediated suppression of proliferation, migration, and invasion of OS cells. The expression levels of miR-1 were significantly lower in OS tumor tissues than those in adjacent normal tissues and in SAOS-2 and U2OS cell lines compared to a normal osteoblast (NHOst) cell line. VEGFA was upregulated in OS tumor tissues and SAOS-2 and U2OS cell lines. The results of CCK-8 assay and transwell assay showed that miR-1 acted as a tumor suppressor by inhibiting cell proliferation, migration, and invasion in U2OS cells. Dual luciferase reporter assay demonstrated that VEGFA was a direct and functional target gene of miR-1. miR-1 directly inhibits the protein expression of VEGFA via its 3'-UTR. Knockdown of VEGFA by siRNA inhibited proliferation, migration, and invasion of U2OS cells. Our study suggested the potential inhibitory function of miR-1 in OS cell proliferation, migration, and invasion via inhibiting VEGFA.
Hattinger CM, Tavanti E, Fanelli M, et al. Pharmacogenomics of genes involved in antifolate drug response and toxicity in osteosarcoma. Expert Opin Drug Metab Toxicol. 2017; 13(3):245-257 [PubMed] Related Publications
INTRODUCTION: Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities. Here, we summarize the pharmacogenomic information reported so far for genes involved in antifolate metabolism and transport and in MTX-related toxicity in HGOS patients. Expert opinion: Identification and validation of genetic biomarkers that significantly impact clinical antifolate treatment response and related toxicity may provide the basis for a future treatment modulation based on the pharmacogenetic and pharmacogenomic features of HGOS patients.
Balogh P, Bánusz R, Csóka M, et al. Primary alveolar rhabdomyosarcoma of the bone: two cases and review of the literature. Diagn Pathol. 2016; 11(1):99 [PubMed] Article available free on PMC after 01/01/2018 Related Publications
BACKGROUND: Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin and comprises the largest category of soft-tissue sarcomas both in children and adolescents. From a pediatric oncology point of view, RMS has traditionally been classified into alveolar (ARMS) and embryonal (ERMS) subtypes. The anatomical localization of the tumor may vary, but commonly involve the head/neck regions, male and female urogenital tract or the trunk and extremities. CASE PRESENTATION: Here, we report two challenging cases involving 17- and 9-years-olds males where diffuse and multiplex bone lesions suggested either a hematological disease or a primary bone tumor (mesenchymal chondrosarcoma). Biopsies, proved a massive infiltration of the bone marrow cavity with rhabdomyosarcoma. In both cases, the ARMS subtype was confirmed using FOXO1 break-apart probes (FISH). Radiological examination could not identify primary soft tissue component in any localization at the time of diagnosis in either cases. CONCLUSIONS: Primary alveolar rhabdomyosarcoma of the bone as a subtype of ARMS, seems to be a distinct clinico-pathological entity with challenging diagnostic difficulties and different, yet better, biological behavior in comparison to soft tissue ARMS. However, it is difficult to be characterized or predict its prognosis and long-term survival as only sporadic cases (four) were reported so far.
Kansagra AP, Wan JJ, Devulapalli KK, et al. Malignant Transformation of an Aneurysmal Bone Cyst to Fibroblastic Osteosarcoma. Am J Orthop (Belle Mead NJ). 2016 Sep/Oct; 45(6):E367-E372 [PubMed] Related Publications
Aneurysmal bone cysts are uncommon primary bone tumors typically regarded as histologically and clinically benign. Malignant transformation of these lesions occurs almost exclusively in the context of prior radiation exposure. However, 4 cases of an osteosarcoma developing without prior radiation exposure have been reported. In this article, we report a fifth case of degeneration of an aneurysmal bone cyst to a fibroblastic osteosarcoma. In addition to reviewing the earlier cases, we describe the radiologic, pathologic, and immunohistochemical basis of this diagnosis.
Keller S, Inai R, Sato S, et al. Thallium-201 Uptake of Giant Cell Tumor: One Step Toward the Differential Diagnosis to Atypically Presenting Osteosarcoma. AJR Am J Roentgenol. 2017; 208(1):171-179 [PubMed] Related Publications
OBJECTIVE: The radiologic differential diagnosis of giant cell tumors (GCTs) is challenging because there is a risk of misdiagnosis of GCTs as malignant lesions such as atypically presenting osteosarcomas (OSs). This study aims to assess the feasibility of (201)Tl scintigraphy for the differential diagnosis of GCT and atypical OS. MATERIALS AND METHODS: Thallium-201 scintigraphy scans obtained between January 2006 and October 2015 of patients with histologically proven GCT (23 patients [male-to-female ratio, 15:8]; median age, 33.0 years; age range, 20-61 years) and patients with atypically presenting OS (20 patients [male-to-female ratio, 11:9]; median age, 30.0 years; age range, 12-69 years) were retrospectively reviewed. Morphologic classification of osseous lesions was performed on radiographs and CT scans. The (201)Tl scintigraphy-based tumor-to-background contrast (TBC) and washout rate (WR) were calculated on early phase and delayed phase scans. The laboratory parameters lactate dehydrogenase (LDH), C-reactive protein (CRP), and alkaline phosphatase were obtained. Statistical significance was estimated using the Mann-Whitney U test. Cutoff values were calculated for early phase TBC and delayed phase TBC. RESULTS: Twenty-two of 23 GCTs were detected on the initial radiographs, whereas only six of 20 atypical OSs were detected on the initial radiographs. The early phase TBC was increased in GCT (median, 2.59; range, 0.51-12.26) compared with atypical OS (median, 1.68; range, 0.90-6.45) (p = 0.07). The delayed phase TBC was increased in GCT (median, 1.65; range, 0.22-5.26) compared with atypical OS (median, 0.96; range, 0.39-3.76) (p = 0.02). The median WR was not significantly decreased in GCT. The cutoff value for the early phase TBC was 3.90, and the cutoff value for the delayed phase TBC was 1.64; these cutoff values for early and delayed phase TBC yielded a sensitivity of 80.0% and a specificity of 47.8% and 52.2% respectively. Serum LDH (mean: atypical OS vs GCT, 215.5 vs 170.5 U/L, respectively; p = 0.01), alkaline phosphatase (median: 355.0 vs 252.0 U/L; p = 0.03), and CRP (median: 0.21 vs 0.09 mg/dL; p = 0.04) values were significantly increased in atypical OS compared with GCT. CONCLUSION: The intense (201)Tl uptake of GCT in combination with laboratory OS biomarkers facilitate the differential diagnosis of GCT and atypically presenting OS.