Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

We investigated the eventual diagnosis in patients referred to a tertiary centre with a possible diagnosis of a primary bone malignancy. We reviewed our database from between 1986 and 2010, during which time 5922 patients referred with a suspicious bone lesion had a confirmed diagnosis. This included bone sarcoma in 2205 patients (37%), benign bone tumour in 1309 (22%), orthopaedic conditions in 992 (17%), metastatic disease in 533 (9%), infection in 289 (5%) and haematological disease in 303 (5%). There was a similar frequency of all diagnoses at different ages except for metastatic disease. Only 0.6% of patients (17 of 2913) under the age of 35 years had metastatic disease compared with 17.1% (516 of 3009) of those over 35 years (p < 0.0001). Of the 17 patients under 35 years with metastatic disease, only four presented with an isolated lesion, had no past history of cancer and were systematically well. Patients under the age of 35 years should have suitable focal imaging (plain radiography, CT or MRI) and simple systemic studies (blood tests and chest radiography). Reduction of the time to biopsy can be achieved by avoiding an unnecessary investigation for a primary tumour to rule out metastatic disease

We evaluated the diagnostic accuracy of fine-needle aspiration biopsy in a prospective study of 300 patients with previously undiagnosed bone lesions. Patients with suspected local recurrence of a primary bone tumour or a metastatic lesion of a previously diagnosed malignancy were excluded. Fine-needle aspiration biopsy was performed under radiological control as an outpatient procedure. The series was grouped into three major categories: 1) benign bone lesions including infections; 2) primary malignant bone tumours; and 3) metastases including lymphomas and myelomas. We compared the cytological diagnosis with the final diagnosis as assessed by histological examination and/or the clinical and radiological features. Material considered conclusive for cytological diagnosis was obtained from 251 of the 300 patients. Of the 49 failures, there were 24 aspirates with insufficient cellular yield and 25 in which a diagnosis could not be made although the cytological material was adequate in quantity. Most of the inconclusive aspirates (36/49) were obtained from benign bone lesions. The diagnosis was correct in 239 (95%) of the 251 cases providing adequate cytological material. There were eight (3%) falsely benign diagnoses, one (0.3%) falsely malignant, and three cases in which we were unable to differentiate between sarcoma and a metastasis. Chondrosarcoma (2/12) gave the greatest diagnostic difficulty and Ewing’s sarcoma the least (0/9). There were no decisive errors of treatment. All falsely benign or malignant diagnoses were questioned, and led to open biopsy since they did not correlate with the clinical and radiological features. Our study suggests that fine-needle aspiration biopsy is a valid option for the diagnosis of bone tumours. It is a simple outpatient procedure which gives sufficient cytological material for the correct diagnosis in 80% of cases. As with histological analysis of material from open biopsy, the cytological assessment must agree with the clinical and radiological findings

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour

Simple bone cysts are relatively common in children. When they present to a musculoskeletal oncology unit, they are usually treated by a variety of methods that range from observations following fracture to surgically curettage. The outcome is usually good. Very little is written in the literature regarding adults with a cystic bone lesion. We present 10 consecutive skeletally mature patients who presented with a benign cystic bone lesion. The mean age at diagnosis was 38 years (20–60 years). Three patients has a cyst in the foot, three in the hip, two in the knee, one in the pelvis and the remainder in the shoulder. Full work up, including biopsy, was performed in all cases. All hip lesions required internal fixation for actual or impending fractures. The average follow up was 1.5 years. The surgical outcome was good in all cases. The histological features are similar in all cases. Cementum, as found in Unicameral Bone Cysts, is not seen. This may present a new entity that is not described in the literature

Aims

We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton.

Introduction. Tissue diagnosis is essential to direct the definitive management of a suspected soft tissue or bone sarcoma tissue. Knowledge of both the diagnostic yield and accuracy of core needle biopsies is therefore important to give the investigating team information on the likelihood of their initial investigations achieving a diagnosis. Methods. This is a retrospective study of patients referred to a specialist orthopaedic centre for investigation of a suspected soft tissue or bone sarcoma. Details of all core needle biopsies performed in a 13-month period were obtained from the hospital database. We defined a diagnostic biopsy as either a specific tissue diagnosis or a biopsy that decided the definitive management of the patient, specifically if malignancy was excluded and no further intervention was required, to calculate the diagnostic yield. Diagnostic accuracy was established by comparing histological diagnosis at biopsy to that at final excision. Results. The overall diagnostic yield of the biopsies performed was 85% (125 of 148 biopsies) and the diagnostic accuracy was 93% (77 of 83). The diagnostic yield of soft tissue lesions was 93% (79 of 85) and accuracy 98%. For bone lesions the diagnostic yield was 73% (46 of 73) and accuracy was 85%. Discussion. Knowing the diagnostic yield and accuracy of biopsies performed allows the investigating team to give patients and colleagues a figure detailing the likely success of a soft tissue or bone biopsy in being diagnostic. In addition this data provides the investigating team with information on specific biopsy types that are less likely to be diagnostic, such as bone lesions requiring CT guidance. These may benefit from another biopsy method to avoid delay in diagnosis and facilitate timely management

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Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK.

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The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours.

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The aim of the present study was to analyze the oncological and neurological outcome of patients undergoing interdisciplinary treatment for primary malignant bone and soft-tissue tumours of the spine within the last seven decades, and changes over time.

Introduction. Chondroblastomas are rare bone tumours accounting for approximately 1% of all benign bone lesions. They occur in children and adolescents and are more frequent in males. The conventional treatment for chondroblastomas is surgery, however, this can be difficult and disabling due to the apo- or epiphyseal location. Surgery is curative in most cases, but recurrence rates of 10%–35% have been reported in the literature. Radiofrequency ablation is well established in the treatment of osteoid osteomas and painful bone metastases. We report our experience with the use of radiofrequency ablation in the treatment of chondroblastomas. Methods. Seven patients were identified from our Tumour database with biopsy proven chondroblastomas who were treated with Percutaneous CT Guided Radiofrequency Thermo coagulation. Results. The tumour was successfully treated in all patients with no recurrences. In two cases, complications occurred; infraction of a sub-articular chondroblastoma in one case and cartilage and bone damage in the unaffected compartment of a knee joint in the other. Discussion. Radiofrequency thermocoagulation of chondroblastomas offers a minimally invasive alternative to open surgery. The risk of complications would appear lower than with open surgery. Multi-tined expandable electrode systems allow the treatment of large chondroblastomas

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Giant cell tumours (GCTs) of the proximal femur are rare, and there is no consensus about the best method of filling the defect left by curettage. In this study, we compared the outcome of using a fibular strut allograft and bone cement to reconstruct the bone defect after extended curettage of a GCT of the proximal femur.

Background. Bone lesions in Ewing's sarcoma (ES/PNET) have been traditionally diagnosed with bone Scan. PET-scan is emerging as a promising investigative modality for detection of metastatic lesions. In this prospective study, we compare the utility of both to detect the metastatic sites. Methods. One hundred and seventy five histologically proven cases of ESPNET from 2004-2009 were prospectively staged with bone scan and PET-scan with Breath- hold CT scan- thorax. The diagnostic value of PET-scan to pick up metastatic lesions was compared with bone scan. Results. The site of primary disease was axial in 62(35.4 %) patients, appendicular in 94(53.7 %) patients, and extraskeletal in 19 (10.8 %) patients. 24(13.7 %) patients were metastatic at presentation, while 151(86.2 %) patients had localized disease. In all patients with localized disease, bone scan did not detect any lesion other than that detected on PET-scan. In metastatic patients, PET-scan detected 12 patients with lymph node involvement which were not detected by bone scan, 10 patients were found to have lung metastasis by PET scan with breath-hold CT thorax, bony metastases were seen in two patients where the number and site of lesions were same in both PET and bone scan. In 19 patients with extraskeletal PNET, PET scan detected primary lesion in all while the bone scan was non-avid in any of these. Conclusion. PET- Scan was able to detect all the bony lesions picked up by bone scan at baseline in newly diagnosed patients of PNET/ES. Furthermore, PET-scan was able to detect extra-skeletal sites of metastases. We conclude that PET scan may obviate the need of bone scan in the diagnostic work up of patients with Ewing's sarcoma

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Proximal femoral endoprosthetic replacements (PFEPRs) are the most common reconstruction option for osseous defects following primary and metastatic tumour resection. This study aimed to compare the rate of implant failure between PFEPRs with monopolar and bipolar hemiarthroplasties and acetabular arthroplasties, and determine the optimum articulation for revision PFEPRs.

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Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD.

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Aneurysmal bone cysts (ABCs) are locally aggressive lesions typically found in the long bones of children and adolescents. A variety of management strategies have been reported to be effective in the treatment of these lesions. The purpose of this review was to assess the effectiveness of current strategies for the management of primary ABCs of the long bones.

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Accurate estimations of the risk of fracture due to metastatic bone disease in the femur is essential in order to avoid both under-treatment and over-treatment of patients with an impending pathological fracture. The purpose of the current retrospective in vivo study was to use CT-based finite element analyses (CTFEA) to identify a clear quantitative differentiating factor between patients who are at imminent risk of fracturing their femur and those who are not, and to identify the exact location of maximal weakness where the fracture is most likely to occur.

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The purpose of this study was to identify prognostic indicators of outcome at presentation to the orthopaedic surgeon, in patients with metastatic prostate cancer. Our aim was to use this information in a pragmatic, clinic-based approach so that surgical decision making could be optimized to benefit the patient in their remaining lifetime.

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The aims of this study were to evaluate the long-term outcome of surgery for bone or soft-tissue metastases from renal cell carcinoma (RCC) and to determine factors that affect prognosis.

Skeletal metastases from hepatocellular carcinoma are highly destructive vascular lesions which severely reduce the quality of life. Pre-existing liver cirrhosis presents unique challenges during the surgical management of such lesions. We carried out a retrospective study of 42 patients who had been managed surgically for skeletal metastases from hepatocellular carcinoma affecting the appendicular skeleton between January 2000 and December 2006. There were 38 men and four women with a mean age of 60.2 years (46 to 77). Surgery for a pathological fracture was undertaken in 30 patients and because of a high risk of fracture in 12. An intralesional surgical margin was achieved in 36 and a wide margin in six. Factors influencing survival were determined by univariate and multivariate analyses.

The survival rates at one, two and three years after surgery were 42.2%, 25.8% and 19.8%, respectively. The median survival time was ten months (95% confidence interval 6.29 to 13.71). The number of skeletal metastases and the Child-Pugh grade were identified as independent prognostic factors by Cox regression analysis. The method of management of the hepatocellular carcinoma, its status in the liver, the surgical margin for skeletal metastases, the presence of a pathological fracture and adjuvant radiotherapy were not found to be significantly related to the survival of the patient, which was affected by hepatic function, as represented by the Child-Pugh grade.