Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168

In our database of 7935 patients referred for investigation of a soft-tissue mass, only 100 were found to have a soft-tissue metastasis (1.3%). Our aim was to define the clinical features of such patients and to identify the site of their primary tumour. The most common presentation was a painful lump, deep to the fascia, ranging between 2 cm and 35 cm (mean 8.3 cm) with 78% of the lumps located deep to the fascia. The mean age of the patients at presentation was 64 years (22 to 84) and there were almost equal numbers of men and women. Of 53 patients with a history of malignancy, 52 had metastases from the same primary (lung in 12, melanoma in ten, kidney in nine, gastrointestinal track in four, breast in five, bladder in four, and others in eight). The other 47 had no history of malignancy and the metastasis was the first presentation. The primary sites in these cases were the lung in 19, gastro-intestinal track in four, kidney in two, melanoma in nine, other in three, and unknown (despite investigations) in ten. There was no correlation between the site of the metastases and the primary tumour. Of the 7935 patients, 516 had a history of malignancy. Of these, only 10% had a soft-tissue metastasis, 29% had a benign diagnosis, 55% a soft-tissue sarcoma and 6% another malignancy. Patients with soft-tissue metastases have similar clinical features to those with soft-tissue sarcomas and should be considered for assessment at appropriate diagnostic centres for patients with suspicious soft-tissue lumps

Aims. Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results. Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion. A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149

Aims. The aim of this study was to present the long-term surgical outcomes, complications, implant survival, and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins. Patients and Methods. A cohort of 50 consecutive patients who underwent the modified Harrington procedure for periacetabular metastasis or haematological malignancy between January 1996 and April 2018 were studied. The median follow-up time for all survivors was 3.2 years (interquartile range 0.9 to 7.6 years). Results. The five-year overall survival rate was 33% for all the patients. However, implant survival rates were 100% and 46% at five and ten years, respectively. Eight patients survived beyond five years. There was no immediate perioperative mortality or complications. A total of 15 late complications occurred in 11 patients (22%). Five patients (10%) required further surgery to treat complications. The most frequent complication was pin breakage without evidence of acetabular loosening (6%). Two patients (4%) underwent revision for aseptic loosening at 6.5 and 8.9 years after surgery. Ambulatory status and pain level were improved in 83% and 89%, respectively. Conclusion. The modified Harrington procedure for acetabular destruction has low complication rates, good functional outcome, and improved pain relief in selected patients. Cite this article: Bone Joint J 2019;101-B:1557–1562

Aims. Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients. Methods. MEDLINE (PubMed), EMBASE (Ovid), Cochrane, and CINAHL databases were searched focusing on VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, or wound complication rates. Results. In all, 17 studies published from 1998 to 2018 met the inclusion criteria for the systematic review. The mean incidence of all VTE events in orthopaedic oncology patients was 10.7% (1.1% to 27.7%). The rate of PE was 2.4% (0.1% to 10.6%) while the rate of lethal PE was 0.6% (0.0% to 4.3%). The overall rate of DVT was 8.8% (1.1% to 22.3%) and the rate of symptomatic DVT was 2.9% (0.0% to 6.2%). From the studies that screened all patients prior to hospital discharge, the rate of asymptomatic DVT was 10.9% (2.0% to 20.2%). The most common risk factors identified for VTE were endoprosthetic replacements, hip and pelvic resections, presence of metastases, surgical procedures taking longer than three hours, and patients having chemotherapy. Mean incidence of VTE with and without chemical prophylaxis was 7.9% (1.1% to 21.8%) and 8.7% (2.0% to 23.4%; p = 0.11), respectively. No difference in the incidence of bleeding or wound complications between prophylaxis groups was reported. Conclusion. Current evidence is limited to guide clinicians. It is our consensus opinion, based upon logic and deduction, that all patients be considered for both mechanical and chemical VTE prophylaxis, particularly in high-risk patients (pelvic or hip resections, prosthetic reconstruction, malignant diagnosis, presence of metastases, or surgical procedures longer than three hours). Additionally, the surgeon must determine, in each patient, if the risk of haemorrhage outweighs the risk of VTE. No individual pharmacological agent has been identified as being superior in the prevention of VTE events. Cite this article: Bone Joint J 2020;102-B(12)1743:–1751

Aims. Chondrosarcoma is the second most common primary sarcoma of bone: conventional chondrosarcoma accounts for 85% of all cases. Conventional chondrosarcoma may be central or peripheral. Most studies group central and peripheral chondrosarcomas together, although there is growing evidence that their clinical behaviour and prognosis differ. The aims of this study were to analyze any differences in characteristics between central and peripheral chondrosarcomas and to investigate the incidence and role of different syndromes. Methods. Data from two international tertiary referral sarcoma centres between January 1995 and December 2018 were retrospectively reviewed. The study population consisted of 714 patients with surgically treated conventional chondrosarcoma of the pelvis and limbs. Results. In patients with Ollier’s disease and Mafucci’s syndrome, 12/20 (60%) and 2/5 (60%) of malignancies, respectively, were in the limbs, most frequently in the proximal humerus, proximal tibia, and in the hands and feet. In patients with hereditary multiple exostosis (HME), 20/29 (69.0%) of chondrosarcomas were in the pelvis and scapula, specifically in the ilium in 13/29 (44.8%) and the scapula in 3/29 (10.3%). In central chondrosarcoma, survival of patients with Ollier’s disease and non-syndromic patients was the same (p = 0.805). In peripheral chondrosarcoma, survival among HME patients was similar (p = 0.676) in patients with tumours of the pelvis and limbs. Conclusion. Both central and peripheral chondrosarcoma have specific characteristics. HME is frequently seen in patients with a peripheral chondrosarcoma, in whom tumours are commonly located in the ilium and scapula. The incidence of Ollier’s disease is uncommon in patients with a central chondrosarcoma. Disease-specific survival is equal in different subtypes after adjustment for histological grade. The local recurrence-free survival is the same for different locations and subtypes after adjustment for surgical margin. Cite this article: Bone Joint J 2021;103-B(5):984–990

Aims. Reconstruction of the acetabulum after resection of a periacetabular malignancy is technically challenging and many different techniques have been used with varying success. Our aim was to prepare a systematic review of the literature dealing with these techniques in order to clarify the management, the rate of complications and the outcomes. Patients and Methods. A search of PubMed and MEDLINE was conducted for English language articles published between January 1990 and February 2017 with combinations of key search terms to identify studies dealing with periacetabular resection with reconstruction in patients with a malignancy. Studies in English that reported radiographic or clinical outcomes were included. Data collected from each study included: the number and type of reconstructions, the pathological diagnosis of the lesions, the mean age and follow-up, gender distribution, implant survivorship, complications, functional outcome, and mortality. The results from individual studies were combined for the general analysis, and then grouped according to the type of reconstruction. . Results. A total of 57 studies met the inclusion criteria and included 1700 patients. Most lesions were metastatic (41%), followed by chondrosarcoma (29%), osteosarcoma (10%), Ewing’s sarcoma (7%), and multiple myeloma (2%). The techniques of reconstruction were divided into seven types for analysis: those involving a Harrington reconstruction, a saddle prosthesis, an allograft and allograft prosthesis composite, a pasteurised autograft, a porous tantalum implant, a custom-made prosthesis and a modular hemipelvic reconstruction. The rate of complications was 50%, with infection (14%) and instability (8%) being the most common. Mortality data were available for 1427 patients (84%); 50% had died of disease progression, 23% were alive with disease, and 27% had no evidence of disease at a mean follow-up of 3.4 years (0 to 34). . Conclusion. Both the rate of complications and mortality are high following resection of oncological periacetabular lesions and reconstruction. Many types of reconstruction have been used with unique challenges and complications for each technique. Newer prostheses, including custom-made prostheses and porous tantalum implants and augments, have shown promising early functional and radiographic outcomes. . Cite this article: Bone Joint J 2018;100-B(1 Supple A):22–30

Aims. The aim of this study was to validate the Mirels score in predicting pathological fractures in metastatic disease of the lower limb. Patients and Methods. A total of 62 patients with confirmed metastatic disease met the inclusion criteria. Of the 62 patients, 32 were female and 30 were male. The mean age of patients was 65 years (35 to 89). The primary malignancy originated from the breast in 27 (44%) patients, prostate in 15 (24%) patients, kidney in seven (11%), and lung in four (6%) of patients. One patient (2%) had metastatic carcinoma from the lacrimal gland, two patients (3%) had multiple myeloma, one patient (2%) had lymphoma of bone, and five patients (8%) had metastatic carcinoma of unknown primary. Plain radiographs at the time of initial presentation were scored using Mirels system by the four authors. The radiographic components of the score (anatomical site, size, and radiographic appearance) were scored two weeks apart. Inter- and intraobserver reliability were calculated with Fleiss’ kappa test. Bland-Altman plots were created to compare the variances of the individual components of the score and the total Mirels score. Results. Kappa values for the interobserver variability of the components of the Mirels score were k = 0.554 (95% CI 0.483 to 0.626) for site, k = 0.342 (95% CI 0.285 to 0.400) for size, k = 0.443 (95% CI 0.387 to 0.499) for radiographic appearance, and k = 0.294 (95% CI 0.258 to 0.331)for the total score. Kappa values for the intra-observer reliability were k = 0.608 (95% CI 0.506 to 0.710) for site, k = 0.579 (95% CI 0.487 to 0.670) for size, k = 0.614 (95% CI 0.522 to 0.703) for radiographic appearance, and k = 0.323 (95% CI 0.266 to 0.379) for total score. Conclusion. Our study showed fair to moderate agreement between authors when using the Mirels score, and moderate to substantial agreement when authors rescored radiographs. The Mirels score is subjective and lacks reproducibility in predicting the risk of pathological fracture. Cite this article: Bone Joint J 2018;100-B:1100–5

Tumours of the sacrum are difficult to manage. The sacrum provides the structural connection between the torso and lower half of the body and is subject to both axial and rotational forces. Thus, tumours or their treatment can compromise the stability of the spinopelvic junction. Additionally, nerves responsible for lower limb motor groups as well as bowel, bladder, and sexual function traverse or abut the sacrum. Preservation or sacrifice of these nerves in the treatment of sacral tumours has profound implications on the function and quality of life of the patient. This annotation will discuss current treatment protocols for sacral tumours.

Cite this article: Bone Joint J 2022;104-B(12):1284–1291.

The December 2023 Oncology Roundup³⁶⁰ looks at: A single osteotomy technique for frozen autograft; Complications, function, and survival of tumour-devitalized autografts used in patients with limb-sparing surgery; Is liquid nitrogen recycled bone and vascular fibula the biological reconstruction of choice?; Solitary pulmonary metastases at first recurrence of osteosarcoma; Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?; Open versus core needle biopsy in lower-limb sarcoma – current practice patterns and patient outcomes; Natural history of intraosseous low-grade chondroid lesions of the proximal humerus; Local treatment modalities and event-free survival in patients with localized Ewing’s sarcoma; Awaiting biopsy results in solitary pathological proximal femoral fractures.

Aims

To identify factors influencing clinicians’ decisions to undertake a nonoperative hip fracture management approach among older people, and to determine whether there is global heterogeneity regarding these factors between clinicians from high-income countries (HIC) and low- and middle-income countries (LMIC).

The October 2023 Research Roundup³⁶⁰ looks at: Gut microbiota in high-risk individuals for rheumatoid arthritis associated with disturbed metabolome and initiates arthritis by triggering mucosal immunity imbalance; International Consensus on Anaemia Management in Surgical Patients (ICCAMS); Sleep disturbance trends in the short-term postoperative period for patients undergoing total joint replacement; Achilles tendon tissue turnover before and immediately after an acute rupture; Quadriceps or hip exercises for patellofemoral pain? A randomized controlled equivalence trial; Total-body MRI for screening in patients with multiple osteochondromas.

The October 2023 Oncology Roundup³⁶⁰ looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma.

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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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Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

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Prior to the availability of vaccines, mortality for hip fracture patients with concomitant COVID-19 infection was three times higher than pre-pandemic rates. The primary aim of this study was to determine the 30-day mortality rate of hip fracture patients in the post-vaccine era.

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The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI).

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The sacroiliac joint (SIJ) is the only mechanical connection between the axial skeleton and lower limbs. Following iliosacral resection, there is debate on whether reconstruction of the joint is necessary. There is a paucity of data comparing the outcomes of patients undergoing reconstruction and those who are not formally reconstructed.

Aims

The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients.

The August 2024 Research Roundup³⁶⁰ looks at: Effect of vitamin D deficiency on periprosthetic joint infection and complications after primary total joint replacement; Postoperative angiotensin receptor blocker use associated with decreased rates of manipulation under anaesthesia in patients undergoing total knee arthroplasty; Central sensitization: the missing link between psychological distress and poor outcome following primary total knee arthroplasty; Thromboprophylaxis for the trauma and orthopaedic surgeon; Life expectancy after treatment of metastatic bone disease: an international trend analysis.