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The Bone & Joint Journal
Vol. 104-B, Issue 10 | Pages 1180 - 1188
1 Oct 2022
Qu H Mou H Wang K Tao H Huang X Yan X Lin N Ye Z

Aims. Dislocation of the hip remains a major complication after periacetabular tumour resection and endoprosthetic reconstruction. The position of the acetabular component is an important modifiable factor for surgeons in determining the risk of postoperative dislocation. We investigated the significance of horizontal, vertical, and sagittal displacement of the hip centre of rotation (COR) on postoperative dislocation using a CT-based 3D model, as well as other potential risk factors for dislocation. Methods. A total of 122 patients who underwent reconstruction following resection of periacetabular tumour between January 2011 and January 2020 were studied. The risk factors for dislocation were investigated with univariate and multivariate logistic regression analysis on patient-specific, resection-specific, and reconstruction-specific variables. Results. The dislocation rate was 13.9% (n = 17). The hip COR was found to be significantly shifted anteriorly and inferiorly in most patients in the dislocation group compared with the non-dislocation group. Three independent risk factors were found to be related to dislocation: resection of gluteus medius (odds ratio (OR) 3.68 (95% confidence interval (CI) 1.24 to 19.70); p = 0.039), vertical shift of COR > 18 mm (OR 24.8 (95% CI 6.23 to 128.00); p = 0.001), and sagittal shift of COR > 20 mm (OR 6.22 (95% CI 1.33 to 32.2); p = 0.026). Conclusion. Among the 17 patients who dislocated, 70.3% (n = 12) were anterior dislocations. Three independent risk factors were identified, suggesting the importance of proper restoration of the COR and the role of the gluteus medius in maintaining hip joint stability. Cite this article: Bone Joint J 2022;104-B(10):1180–1188


Bone & Joint Open
Vol. 4, Issue 6 | Pages 442 - 446
12 Jun 2023
Toda Y Iwata S Kobayashi E Ogura K Osaki S Fukushima S Mawatari M Kawai A

Aims. The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Methods. Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively). Results. There were 24 patients in the VSS group and 54 in the non-VSS group. There were no significant differences between the two groups in terms of clinicopathological background. The total drainage volume in the VSS group was significantly less than that in the non-VSS group (1,176 ml vs 3,114 ml; p = 0.018). Moreover, the drainage and hospitalization durations were significantly shorter in the VSS group compared to the non-VSS group (p = 0.017 and p = 0.024, respectively). Conclusion. Our results suggest that use of VSS can help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Cite this article: Bone Jt Open 2023;4(6):442–446


Aims. To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs. Methods. The medical records of 75 patients who underwent surgery between 2000 and 2020 were retrospectively reviewed, and 44 patients who were alive and available for follow-up (at a mean of 9.7 years postoperatively) were included in the study. Leg length discrepancy was measured on whole-leg radiographs, and functional assessment was performed with PROMs (Toronto Extremity Salvage Score (TESS) and Comprehensive Outcome Measure for Musculoskeletal Oncology Lower Extremity (COMMON-LE)) with two different aspects. The thresholds for unfavourable PROMs were determined using anchor questions regarding satisfaction, and the risk factors for unfavourable PROMs were investigated. Results. The thresholds for favourable TESS and COMMON were 64.8 and 70.4 points, respectively. Multivariate analysis showed that age at surgery (p = 0.004) and postoperative leg length discrepancy (p = 0.043) were significant risk factors for unfavourable TESS results, while age at surgery (p < 0.001) was a significant risk factor for unfavourable COMMON-LE results. Following receiver operating characteristic analysis, the threshold for both TESS and COMMON-LE was 29 years of age at surgery. Additionally, a leg length discrepancy of 8.2 mm was the threshold for unfavourable TESS. Conclusion. Patients aged > 29 years at the time of surgery require appropriate preoperative counselling and adequate postoperative physical and socioemotional support. Reconstruction equivalent to the length of the resected bone can reduce the risk of functional disabilities in daily living. Cite this article: Bone Jt Open 2023;4(12):906–913


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1405 - 1413
1 Aug 2021
Ogura K Fujiwara T Morris CD Boland PJ Healey JH

Aims. Rotating-hinge knee prostheses are commonly used to reconstruct the distal femur after resection of a tumour, despite the projected long-term burden of reoperation due to complications. Few studies have examined the factors that influence their failure and none, to our knowledge, have used competing risk models to do so. The purpose of this study was to determine the risk factors for failure of a rotating-hinge knee distal femoral arthroplasty using the Fine-Gray competing risk model. Methods. We retrospectively reviewed 209 consecutive patients who, between 1991 and 2016, had undergone resection of the distal femur for tumour and reconstruction using a rotating-hinge knee prosthesis. The study endpoint was failure of the prosthesis, defined as removal of the femoral component, the tibial component, or the bone-implant fixation; major revision (exchange of the femoral component, tibial component, or the bone-implant fixation); or amputation. Results. Multivariate Fine-Gray regression analyses revealed different hazards for each Henderson failure mode: percentage of femoral resection (p = 0.001) and extent of quadriceps muscle resection (p = 0.005) for overall prosthetic failure; extent of quadriceps muscle resection (p = 0.002) and fixation of femoral component (p = 0.011) for type 2 failure (aseptic loosening); age (p = 0.009) and percentage of femoral resection (p = 0.019) for type 3 failure (mechanical failure); and type of joint resection (p = 0.037) for type 4 (infection) were independent predictors. A bone stem ratio of > 2.5 reliably predicted aseptic loosening. Conclusion. We identified independent risk factors for overall and cause-specific prosthetic failure after rotating-hinge knee distal femoral arthroplasty using a competing risk Fine-Gray model. A bone stem ratio > 2.5 reliably predicts aseptic loosening. An accurate knowledge of the risks of distal femoral arthroplasty after resection for tumour assists surgical planning and managing patient expectations. Cite this article: Bone Joint J 2021;103-B(8):1405–1413


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 382 - 390
1 Feb 2021
Wang H Tang X Ji T Yan T Yang R Guo W

Aims. There is an increased risk of dislocation of the hip after the resection of a periacetabular tumour and endoprosthetic reconstruction of the defect in the hemipelvis. The aim of this study was to determine the rate and timing of dislocation and to identify its risk factors. Methods. To determine the dislocation rate, we conducted a retrospective single-institution study of 441 patients with a periacetabular tumour who had undergone a standard modular hemipelvic endoprosthetic reconstruction between 2003 and 2019. After excluding ineligible patients, 420 patients were enrolled. Patient-specific, resection-specific, and reconstruction-specific variables were studied using univariate and multivariate analyses. Results. The dislocation rate was 9.3% (n = 41). Dislocation was most likely to occur in the first three months after surgery. Four independent risk factors were found, one of which was older age at operation (p = 0.039). The odds ratios (ORs) of those aged ≥ 60 years and 30 to 60 years were 8.50 and 4.64, respectively, compared with those aged < 30 years. The other three risk factors were resection of gluteus maximus (p = 0.010, OR = 5.8), vertical shift of the centre of rotation (COR) of the hip by ≥ 20 mm (p = 0.008, OR = 3.60), and a type I+II+III pelvic resection (p = 0.014, OR = 3.04). Conclusion. Hemipelvic endoprosthetic reconstruction after resection of a periacetabular tumour has a dislocation rate of 9.3% (n = 41). Patients are most likely to dislocate in the first three months after surgery. The risk is increased for older patients (especially those aged > 60 years) and for those with gluteus maximus resection, vertical shift of the COR ≥ 20 mm, and a type I+II+III pelvic resection. Cite this article: Bone Joint J 2021;103-B(2):382–390


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1392 - 1398
3 Oct 2020
Zhao Y Tang X Yan T Ji T Yang R Guo W

Aims. There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?. Methods. A total of 114 patients with a sacral GCT who underwent nerve-sparing surgery at our hospital between July 2005 and August 2017 were reviewed. The rate of local recurrence was determined, and Kaplan-Meier survival analysis carried out to evaluate the mean recurrence-free survival. Possible risks factors including demographics, tumour characteristics, adjuvant therapy, operation, and laboratory indices were analyzed using univariate analysis. Variables with p < 0.100 in the univariate analysis were further considered in a multivariate Cox regression analysis to identify the risk factors. Results. The rate of local recurrence of sacral GCT treated with nerve-sparing surgery was 28.95% (33/114). Multivariate Cox regression analysis showed that large tumour size (> 8.80 cm) (hazard ratio (HR) 3.16; 95% confidence interval (CI) 1.27 to 7.87; p = 0.014), high neutrophil-to-lymphocyte ratio (NLR) (> 2.09) (HR 3.13; 95% CI 1.28 to 7.62; p = 0.012), involvement of a sacroiliac joint (HR 3.09; 95% CI 1.06 to 9.04; p = 0.039), and massive intraoperative blood loss (> 1,550 ml) (HR 2.47; 95% CI 1.14 to 5.36; p = 0.022) were independent risk factors for local recurrence. Conclusion. Patients with a sacral GCT who undergo nerve-sparing surgery have a local recurrence rate of 29%. Large tumour size, high NLR, involvement of a sacroiliac joint, and massive intraoperative blood loss are independent risk factors. Cite this article: Bone Joint J 2020;102-B(10):1392–1398


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 280 - 284
1 Mar 2020
Ogura K Boland PJ Fabbri N Healey JH

Aims. Although internal hemipelvectomy is associated with a high incidence of morbidity, especially wound complications, few studies have examined rates of wound complications in these patients or have identified factors associated with the consequences. The present study aimed to: 1) determine the rate of wound and other complications requiring surgery after internal hemipelvectomy; and 2) identify factors that affect the rate of wound complications and can be used to stratify patients by risk of wound complications. Methods. The medical records of 123 patients undergoing internal hemipelvectomy were retrospectively reviewed, with a focus on both overall complications and wound complications. Logistic regression analyses were performed to examine the association between host, tumour, and surgical factors and rates of postoperative wound complications. Results. The overall rate of postoperative complications requiring surgery was 49.6%. Wound complications were observed in 34.1% of patients, hardware-related complications in 13.2%, graft-related complications in 9.1%, and local recurrence in 5.7%. On multivariate analysis, extrapelvic tumour extension (odds ratio (OR) 23.28; 95% confidence interval (CI), 1.97 to 274.67; p = 0.012), both intra- and extrapelvic tumour extension (OR 46.48; 95% CI, 3.50 to 617.77; p = 0.004), blood transfusion ≥ 20 units (OR 50.28; 95% CI, 1.63 to 1550.32; p = 0.025), vascular sacrifice of the internal iliac artery (OR 64.56; 95% CI, 6.33 to 658.43; p < 0.001), and use of a structural allograft (OR, 6.57; 95% CI, 1.70 to 25.34; p = 0.001) were significantly associated with postoperative wound complications. Conclusion. Internal hemipelvectomy is associated with high rates of morbidity, especially wound complications. Several host, tumour, and surgical variables are associated with wound complications. The ability to stratify patients by risk of wound complications can help refine surgical and wound-healing planning and may lead to better outcomes in patients undergoing internal hemipelvectomy. Cite this article: Bone Joint J 2020;102-B(3):280–284


The Bone & Joint Journal
Vol. 101-B, Issue 8 | Pages 1024 - 1031
1 Aug 2019
Fujiwara T Medellin MR Sambri A Tsuda Y Balko J Sumathi V Gregory J Jeys L Abudu A

Aims. The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. Patients and Methods. A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. Results. Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. Conclusion. The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024–1031


The Bone & Joint Journal
Vol. 100-B, Issue 2 | Pages 247 - 255
1 Feb 2018
Albergo JI Gaston CLL Parry MC Laitinen MK Jeys LM Tillman RM Abudu AT Grimer RJ

Aims. The aim of this study was to analyse a group of patients with non-metastatic Ewing’s sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. Patients and Methods. A retrospective review of all patients with a Ewing’s sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. Results. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (. sd. 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Conclusion. Local recurrence significantly affects the overall survival in patients with a Ewing’s sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247–55


The Bone & Joint Journal
Vol. 95-B, Issue 4 | Pages 558 - 562
1 Apr 2013
Kim SM Park JM Shin SH Seo SW

It is important to be able to identify patients with an increased risk of venous thromboembolism (VTE) in order to minimise the risk of an event. We investigated the incidence and risk factors for post-operative VTE in 168 consecutive patients with a malignancy of the lower limb. The period of study included ten months before and 12 months after the introduction of chemical thromboprophylaxis. All data about the potential risk factors were identified and classified into three groups (patient-, surgery- and tumour-related). The outcome measure was a thromboembolic event within 90 days of surgery. Of the 168 patients, eight (4.8%) had a confirmed symptomatic deep-vein thrombosis and one (0.6%) a fatal pulmonary embolism. Of the 28 variables tested, age > 60 years, higher American Society of Anesthesiologists grade and metastatic tumour were independent risk factors for VTE. The overall rate of symptomatic VTE was not significantly different between patients who received chemical thromboprophylaxis and those who did not. Knowledge of these risk factors may be of value in improving the surgical outcome of patients with a malignancy of the lower limb. Cite this article: Bone Joint J 2013;95-B:558–62


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 10 | Pages 1352 - 1355
1 Oct 2007
Jeys LM Luscombe JS Grimer RJ Abudu A Tillman RM Carter SR

Between 1966 and 2001, 1254 patients underwent excision of a bone tumour with endoprosthetic replacement. All patients who had radiotherapy were identified. Their clinical details were retrieved from their records. A total of 63 patients (5%) had received adjunctive radiotherapy, 29 pre-operatively and 34 post-operatively. The mean post-operative Musculoskeletal Tumor Society scores of irradiated patients were significantly lower (log-rank test, p = 0.009). The infection rate in the group who had not been irradiated was 9.8% (117 of 1191), compared with 20.7% (6 of 29) in those who had pre-operative radiotherapy and 35.3% (12 of 34) in those who radiotherapy post-operatively. The infection-free survival rate at ten years was 85.5% for patients without radiotherapy, 74.1% for those who had pre-operative radiotherapy and 44.8% for those who had post-operative radiotherapy (log-rank test, p < 0.001). The ten-year limb salvage rate was 89% for those who did not have radiotherapy and 76% for those who did (log-rank test, p = 0.02). Radiotherapy increased the risk of revision (log-rank test, p = 0.015). A total of ten amputations were necessary to control infection, of which nine were successful. Radiotherapy may be necessary for the treatment of a bone sarcoma but increases the risk of deep infection for which amputation may be the only solution


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 4 | Pages 566 - 573
1 May 2004
Van der Linden YM Dijkstra PDS Kroon HM Lok JJ Noordijk EM Leer JWH Marijnen CAM

A number of risk factors based upon mostly retrospective surgical data, have been formulated in order to identify impending pathological fractures of the femur from low-risk metastases. We have followed up patients taking part in a randomised trial of radiotherapy, prospectively, in order to determine if these factors were effective in predicting fractures. In 102 patients with 110 femoral lesions, 14 fractures occurred during follow-up. The risk factors studied were increasing pain, the size of the lesion, radiographic appearance, localisation, transverse/axial/circumferential involvement of the cortex and the scoring system of Mirels. Only axial cortical involvement > 30 mm (p = 0.01), and circumferential cortical involvement > 50% (p = 0.03) were predictive of fracture. Mirels’ scoring system was insufficiently specific to predict a fracture (p = 0.36). Our results indicate that most conventional risk factors overestimate the actual occurrence of pathological fractures of the femur. The risk factor of axial cortical involvement provides a simple, objective tool in order to decide which treatment is appropriate


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 1 | Pages 93 - 99
1 Jan 2002
Fiorenza F Abudu A Grimer RJ Carter SR Tillman RM Ayoub K Mangham DC Davies AM

We studied 153 patients with non-metastatic chondrosarcoma of bone to determine the risk factors for survival and local tumour control. The minimum follow-up was for five years; 52 patients had axial and 101 appendicular tumours. Surgical treatment was by amputation in 27 and limb-preserving surgery in 126. The cumulative rate of survival of all patients, at 10 and 15 years, was 70% and 63%, respectively; 40 patients developed a local recurrence between 3 and 87 months after surgery and 49 developed metastases. Local recurrence was associated with poor survival in patients with concomitant metastases but not in those without. On multivariate analysis independent risk factors for rates of survival include extracompartmental spread, development of local recurrence and high histological grade. Independent risk factors for local recurrence include inadequate surgical margins and tumour size greater than 10 cm. Location within the body, the type of surgery and the duration of symptoms are of no prognostic significance. Surgical excision with an oncologically wide margin provides the best prospect both for cure and local control in these patients


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 8 | Pages 1135 - 1142
1 Aug 2012
Derikx LC van Aken JB Janssen D Snyers A van der Linden YM Verdonschot N Tanck E

Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R. 2. = 0.90 and R. 2. = 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 7 | Pages 1041 - 1046
1 Sep 2004
Porter DE Lonie L Fraser M Dobson-Stone C Porter JR Monaco AP Simpson AHRW

We performed a prospective genotype-phenotype study using molecular screening and clinical assessment to compare the severity of disease and the risk of sarcoma in 172 individuals (78 families) with hereditary multiple exostoses. We calculated the severity of disease including stature, number of exostoses, number of surgical procedures that were necessary, deformity and functional parameters and used molecular techniques to identify the genetic mutations in affected individuals. Each arm of the genotype-phenotype study was blind to the outcome of the other. Mutations EXT1 and EXT2 were almost equally common, and were identified in 83% of individuals. Non-parametric statistical tests were used. There was a wide variation in the severity of disease. Children under ten years of age had fewer exostoses, consistent with the known age-related penetrance of this condition. The severity of the disease did not differ significantly with gender and was very variable within any given family. The sites of mutation affected the severity of disease with patients with EXT1 mutations having a significantly worse condition than those with EXT2 mutations in three of five parameters of severity (stature, deformity and functional parameters). A single sarcoma developed in an EXT2 mutation carrier, compared with seven in EXT1 mutation carriers. There was no evidence that sarcomas arose more commonly in families in whom the disease was more severe. The sarcoma risk in EXT1 carriers is similar to the risk of breast cancer in an older population subjected to breast-screening, suggesting that a role for regular screening in patients with hereditary multiple exostoses is justifiable


The Bone & Joint Journal
Vol. 95-B, Issue 10 | Pages 1417 - 1424
1 Oct 2013
Jeys L Matharu GS Nandra RS Grimer RJ

We hypothesised that the use of computer navigation-assisted surgery for pelvic and sacral tumours would reduce the risk of an intralesional margin. We reviewed 31 patients (18 men and 13 women) with a mean age of 52.9 years (13.5 to 77.2) in whom computer navigation-assisted surgery had been carried out for a bone tumour of the pelvis or sacrum. There were 23 primary malignant bone tumours, four metastatic tumours and four locally advanced primary tumours of the rectum. The registration error when using computer navigation was <  1 mm in each case. There were no complications related to the navigation, which allowed the preservation of sacral nerve roots (n = 13), resection of otherwise inoperable disease (n = 4) and the avoidance of hindquarter amputation (n = 3). The intralesional resection rate for primary tumours of the pelvis and sacrum was 8.7% (n = 2): clear bone resection margins were achieved in all cases. At a mean follow-up of 13.1 months (3 to 34) three patients (13%) had developed a local recurrence. The mean time alive from diagnosis was 16.8 months (4 to 48). . Computer navigation-assisted surgery is safe and has reduced our intralesional resection rate for primary tumours of the pelvis and sacrum. We recommend this technique as being worthy of further consideration for this group of patients. Cite this article: Bone Joint J 2013;95-B:1417–24


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 8 | Pages 1149 - 1155
1 Nov 2001
Gerrand CH Wunder JS Kandel RA O’Sullivan B Catton CN Bell RS Griffin AM Davis AM

We considered whether a positive margin occurring after resection of a soft-tissue sarcoma of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection. Of 566 patients in a prospective database, 87 with positive margins after limb-sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 492 - 500
1 May 2024
Miwa S Yamamoto N Hayashi K Takeuchi A Igarashi K Tada K Taniguchi Y Morinaga S Asano Y Tsuchiya H

Aims. Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment. Methods. A total of 547 patients with STS who underwent tumour resection between 2005 and 2021 were divided into a development cohort and a validation cohort. In the development cohort of 402 patients, the least absolute shrinkage and selection operator (LASSO) regression model was used to screen possible risk factors of SSI. To select risk factors and construct the prediction nomogram, multivariate logistic regression was used. The predictive power of the nomogram was evaluated by receiver operating curve (ROC) analysis in the validation cohort of 145 patients. Results. LASSO regression analysis selected possible risk factors for SSI, including age, diabetes, operating time, skin graft or flap, resected tumour size, smoking, and radiation therapy. Multivariate analysis revealed that age, diabetes, smoking during the previous year, operating time, and radiation therapy were independent risk factors for SSI. A nomogram was developed based on the results of multivariate logistic regression analysis. In the development cohort, the incidence of SSI was 4.5% in the low-risk group (risk score < 6.89) and 26.6% in the high-risk group (risk score ≥ 6.89; p < 0.001). In the validation cohort, the incidence of SSI was 2.0% in the low-risk group and 15.9% in the high-risk group (p = 0.004). Conclusion. Our nomogram will enable surgeons to assess the risk of SSI in patients with STS. In patients with high risk of SSI, frequent monitoring and aggressive interventions should be considered to prevent this. Cite this article: Bone Joint J 2024;106-B(5):492–500


Bone & Joint Open
Vol. 5, Issue 10 | Pages 868 - 878
14 Oct 2024
Sekita T Asano N Kobayashi H Yonemoto T Kobayashi E Ishii T Kawai A Nakayama R

Aims. Surgical limb sparing for knee-bearing paediatric bone sarcoma is considered to have a clinically significant influence on postoperative function due to complications and leg-length discrepancies. However, researchers have not fully evaluated the long-term postoperative functional outcomes. Therefore, in this study, we aimed to elucidate the risk factors and long-term functional prognosis associated with paediatric limb-sparing surgery. Methods. We reviewed 40 patients aged under 14 years who underwent limb-sparing surgery for knee bone sarcoma (15 cases in the proximal tibia and 25 in the distal femur) between January 2000 and December 2013, and were followed up for a minimum of five years. A total of 35 patients underwent reconstruction using artificial materials, and five underwent biological reconstruction. We evaluated the patients’ postoperative complications, survival rate of reconstruction material, and limb, limb function, and leg-length discrepancy at the final follow-up, as well as the risk factors for each. Results. Complications were observed in 55% (22/40) of patients. The limb survival and reconstruction material rates at five and ten years were 95% and 91%, and 88% and 66%, respectively. Infection was the only risk factor in both survivals (p < 0.001, p = 0.019). In the 35 patients with limb preservation, the median International Society of Limb Salvage (ISOLS) score at the final follow-up was 80 (47% to 97%). Younger age (p = 0.027) and complications (p = 0.005) were poor prognostic factors. A negative correlation was found between age and leg-length discrepancy (R = −0.426; p = 0.011). The ISOLS scores were significantly lower in patients with a leg-length discrepancy of more than 5 cm (p = 0.005). Conclusion. Young age and complications were linked to an unfavourable functional prognosis. Leg-length correction was insufficient, especially in very young children, resulting in decreased function of the affected limb. Limb-sparing surgery for these children remains a considerable challenge. Cite this article: Bone Jt Open 2024;5(10):868–878


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 559 - 567
1 May 2023
Aoude A Nikomarov D Perera JR Ibe IK Griffin AM Tsoi KM Ferguson PC Wunder JS

Aims. Giant cell tumour of bone (GCTB) is a locally aggressive lesion that is difficult to treat as salvaging the joint can be associated with a high rate of local recurrence (LR). We evaluated the risk factors for tumour relapse after treatment of a GCTB of the limbs. Methods. A total of 354 consecutive patients with a GCTB underwent joint salvage by curettage and reconstruction with bone graft and/or cement or en bloc resection. Patient, tumour, and treatment factors were analyzed for their impact on LR. Patients treated with denosumab were excluded. Results. There were 53 LRs (15%) at a mean 30.5 months (5 to 116). LR was higher after curettage (18.4%) than after resection (4.6%; p = 0.008). Neither pathological fracture (p = 0.240), Campanacci grade (p = 0.734), soft-tissue extension (p = 0.297), or tumour size (p = 0.872) affected the risk of recurrence. Joint salvage was possible in 74% of patients overall (262/354), and 98% after curettage alone (262/267). Of 49 patients with LR after curettage, 44 (90%) underwent repeated curettage and joint salvage. For patients treated by curettage, only age less than 30 years (p = 0.042) and location in the distal radius (p = 0.043) predicted higher LR. The rate of LR did not differ whether cement or bone graft was used (p = 0.753), but may have been reduced by the use of hydrogen peroxide (p = 0.069). Complications occurred in 15.3% of cases (54/354) and did not differ by treatment. Conclusion. Most patients with a GCTB can undergo successful joint salvage by aggressive curettage, even in the presence of a soft-tissue mass, pathological fracture, or a large lesion, with an 18.4% risk of local recurrence. However, 90% of local relapses after curettage can be treated by repeat joint salvage. Maximizing joint salvage is important to optimize long-term function since most patients with a GCTB are young adults. Younger patients and those with distal radius tumours treated with joint-sparing procedures have a higher rate of local relapse and may require more aggressive treatment and closer follow-up. Cite this article: Bone Joint J 2023;105-B(5):559–567


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

Aims. Tenosynovial giant cell tumour (TGCT) is a rare benign tumour of the musculoskeletal system. Surgical management is fraught with challenges due to high recurrence rates. The aim of this study was to describe surgical treatment and evaluate surgical outcomes of TGCT at an Australian tertiary referral centre for musculoskeletal tumours and to identify factors affecting recurrence rates. Methods. A prospective database of all patients with TGCT surgically managed by two orthopaedic oncology surgeons was reviewed. All cases irrespective of previous treatment were included and patients without follow-up were excluded. Pertinent tumour characteristics and surgical outcomes were collected for analysis. Results. There were 111 total cases included in the study; 71 (64%) were female, the mean age was 36 years (SD 13.6), and the knee (n = 64; 57.7%) was the most commonly affected joint. In all, 60 patients (54.1%) had diffuse-type (D-TGCT) disease, and 94 patients (84.7%) presented therapy-naïve as "primary cases" (PC). The overall recurrence rate was 46.8% for TGCT. There was a statistically significant difference in recurrence rates between D-TGCT and localized disease (75.0% vs 13.7%, relative risk (RR) 3.40, 95% confidence interval (CI) 2.17 to 5.34; p < 0.001), and for those who were referred in the ”revision cases” (RC) group compared to the PC group (82.4% vs 48.9%, RR 1.68, 95% CI 1.24 to 2.28; p = 0.011). Age, sex, tumour volume, and mean duration of symptoms were not associated with recurrence (p > 0.05). Conclusion. Recurrence rates remain high even at a tertiary referral hospital. Highest rates are seen in D-TGCT and “revision cases”. Due to the risks of recurrence, the complexity of surgery, and the need for adjuvant therapy, this paper further supports the management of TGCT in a tertiary referral multi-disciplinary orthopaedic oncology service. Cite this article: Bone Jt Open 2023;4(11):846–852


The Bone & Joint Journal
Vol. 104-B, Issue 4 | Pages 504 - 509
1 Apr 2022
Kennedy JW Farhan-Alanie OM Young D Kelly MP Young PS

Aims. The aim of this study was to assess the clinical and radiological outcomes of an antiprotrusio acetabular cage (APC) when used in the surgical treatment of periacetabular bone metastases. Methods. This retrospective cohort study using a prospectively collected database involved 56 patients who underwent acetabular reconstruction for periacetabular bone metastases or haematological malignancy using a single APC between January 2009 and 2020. The mean follow-up was 20 months (1 to 143). The primary outcome measure was implant survival. Postoperative radiographs were analyzed for loosening and failure. Patient and implant survival were assessed using a competing risk analysis. Secondary parameters included primary malignancy, oncological treatment, surgical factors, length of stay in hospital, and postoperative complications. Results. A total of 33 patients (59%) died during the study period at a mean of 15 months postoperatively (1 to 63). No patient had radiological evidence of loosening or failure. Acetabular component survival was 100%. Three patients (5.4%) had further surgery; one (1.8%) underwent revision of the femoral component for dislocation, one required debridement with implant retention for periprosthetic joint infection, and one required closed reduction for dislocation. Using death as a competing risk, at 100 months, the probability of revision was 0.036 and the risk of death was 0.84. Conclusion. With appropriate patient selection, the antiprotrusio cage offers good implant survival, with a reasonable perioperative complication rate in this high-risk group of patients when managing metastatic disease or haematological malignancy around the acetabulum. Cite this article: Bone Joint J 2022;104-B(4):504–509


Bone & Joint Open
Vol. 5, Issue 4 | Pages 350 - 360
23 Apr 2024
Wang S Chen Z Wang K Li H Qu H Mou H Lin N Ye Z

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360


Aims. For rare cases when a tumour infiltrates into the hip joint, extra-articular resection is required to obtain a safe margin. Endoprosthetic reconstruction following tumour resection can effectively ensure local control and improve postoperative function. However, maximizing bone preservation without compromising surgical margin remains a challenge for surgeons due to the complexity of the procedure. The purpose of the current study was to report clinical outcomes of patients who underwent extra-articular resection of the hip joint using a custom-made osteotomy guide and 3D-printed endoprosthesis. Methods. We reviewed 15 patients over a five-year period (January 2017 to December 2022) who had undergone extra-articular resection of the hip joint due to malignant tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis. Each of the 15 patients had a single lesion, with six originating from the acetabulum side and nine from the proximal femur. All patients had their posterior column preserved according to the surgical plan. Results. Postoperative pathological assessment revealed a negative surgical margin was achieved in all patients. At final follow-up, 13.3% (2/15) died and no recurrence occurred. The overall survival was 81.7% at five years. None of the patients showed any signs of aseptic loosening, and no wound healing issues were observed. In total, 20% (3/15) developed complications, with two cases of early hip dislocation and one case of deep infection. The cumulative incidence of mechanical and non-mechanical failure in this series was 13.7% and 9.3%, respectively, at five years. In this cohort, the mean time to full weightbearing was 5.89 (SD 0.92) weeks and the mean Musculoskeletal Tumor Society score was 24.1 (SD 4.4). Conclusion. For patients with a hip joint tumour who met the inclusion criteria and were deemed suitable for posterior column preservation, a custom-made osteotomy guide combined with 3D-printed endoprosthesis is worth performing when treating patients who require extra-articular resection of the hip joint, as it can achieve adequate margin for local control, maximize bone preservation to maintain pelvic ring integrity, reduce the risk of complications by simplifying the surgical procedure, and allow for more precise reconstruction for better function. Cite this article: Bone Jt Open 2024;5(11):1027–1036


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1633 - 1640
1 Oct 2021
Lex JR Evans S Parry MC Jeys L Stevenson JD

Aims. 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. Methods. This is a retrospective review of 233 patients who underwent PFEPR. The mean age was 54.7 years (SD 18.2), and 99 (42.5%) were male. There were 90 patients with primary bone tumours (38.6%), 122 with metastatic bone disease (52.4%), and 21 with haematological malignancy (9.0%). A total of 128 patients had monopolar (54.9%), 74 had bipolar hemiarthroplasty heads (31.8%), and 31 underwent acetabular arthroplasty (13.3%). Results. At a mean 74.4 months follow-up, the overall revision rate was 15.0%. Primary malignancy (p < 0.001) and age < 50 years (p < 0.001) were risk factors for revision. The risks of death and implant failure were similar in patients with primary disease (p = 0.872), but the risk of death was significantly greater for patients who had metastatic bone disease (p < 0.001). Acetabular-related implant failures comprised 74.3% of revisions; however, no difference between hemiarthroplasty or arthroplasty groups (p = 0.209), or between monopolar or bipolar hemiarthroplasties (p = 0.307), was observed. There was greater radiological wear in patients with longer follow-up and primary bone malignancy. Re-revision rates following a revision PFEPR was 34.3%, with dual-mobility bearings having the lowest rate of instability and re-revision (15.4%). Conclusion. Hemiarthroplasty and arthroplasty PFEPRs carry the same risk of revision in the medium term, and is primarily due to acetabular complications. There is no difference in revision rates or erosion between monopolar and bipolar hemiarthroplasties. The main causes of failure were acetabular wear in the hemiarthroplasty group and instability in the arthroplasty group. These risks should be balanced and patient prognosis considered when contemplating the bearing choice. Dual-mobility, constrained bearings, or large diameter heads (> 32 mm) are recommended in all revision PFEPRs. Cite this article: Bone Joint J 2021;103-B(10):1633–1640


The Bone & Joint Journal
Vol. 105-B, Issue 11 | Pages 1216 - 1225
1 Nov 2023
Fujiwara T Kunisada T Nakata E Mitsuhashi T Ozaki T Kawai A

Aims. Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods. The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results. The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion. Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents. Cite this article: Bone Joint J 2023;105-B(11):1216–1225


The Bone & Joint Journal
Vol. 104-B, Issue 2 | Pages 290 - 296
1 Feb 2022
Gosheger G Ahrens H Dreher P Schneider KN Deventer N Budny T Heitkötter B Schulze M Theil C

Aims. Iliosacral sarcoma resections have been shown to have high rates of local recurrence (LR) and poor overall survival. There is also no universal classification for the resection of pelvic sarcomas invading the sacrum. This study proposes a novel classification system and analyzes the survival and risk of recurrence, when using this system. Methods. This is a retrospective analysis of 151 patients (with median follow-up in survivors of 44 months (interquartile range 12 to 77)) who underwent hemipelvectomy with iliosacral resection at a single centre between 2007 and 2019. The proposed classification differentiates the extent of iliosacral resection and defines types S1 to S6 (S1 resection medial and parallel to the sacroiliac joint, S2 resection through the ipsilateral sacral lateral mass to the neuroforamina, S3 resection through the ipsilateral neuroforamina, S4 resection through ipsilateral the spinal canal, and S5 and S6 contralateral sacral resections). Descriptive statistics and the chi-squared test were used for categorical variables, and the Kaplan-Meier survival analysis were performed. Results. Resections were S1 in 25/151 patients (17%), S2 in 70/151 (46%), S3 in 33/151 (22%), S4 in 77/151 (11%), S5 in 4/151 (3%), and S6 in 2/151 (1%). An internal hemipelvectomy was performed in 113/151 patients (75%), and 38/151 patients (25%) had an external hemipelvectomy. The predominant types of sarcoma were high-grade osteosarcoma in 48/151 patients (32%), chondrosarcoma in 41/151 (27%), Ewing sarcoma in 33/151 (22%), pleomorphic sarcoma in 17/151 (11%), and others in 2/151 (8%). LR was found in 24/151 patients (15%) with S3, S5, with S6 resections showing the highest rate of LR (p = 0.038). Overall, 19/151 patients (16%) had evidence of metastastic disease at the time of surgery and these patients showed poorer survival when compared to patients with no metastasis. Conclusion. The proposed classification can help to report and compare different surgical and reconstructive approaches in these difficult cases who are still have a considerable risk of LR. Cite this article: Bone Joint J 2022;104-B(2):290–296


Bone & Joint Research
Vol. 11, Issue 5 | Pages 278 - 291
12 May 2022
Hu X Fujiwara T Houdek MT Chen L Huang W Sun Z Sun Y Yan W

Aims. Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. Methods. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). Results. Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). Conclusion. In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278–291


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1743 - 1751
1 Dec 2020
Lex JR Evans S Cool P Gregory J Ashford RU Rankin KS Cosker T Kumar A Gerrand C Stevenson J

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


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 553 - 561
1 Mar 2021
Smolle MA Leithner A Kapper M Demmer G Trost C Bergovec M Windhager R Hobusch GM

Aims. The aims of the study were to analyze differences in surgical and oncological outcomes, as well as quality of life (QoL) and function in patients with ankle sarcomas undergoing three forms of surgical treatment, minor or major limb salvage surgery (LSS), or amputation. Methods. A total of 69 patients with ankle sarcomas, treated between 1981 and 2017 at two tumour centres, were retrospectively reviewed (mean age at surgery: 46.3 years (SD 22.0); 31 females (45%)). Among these 69 patients 25 were analyzed prospectively (mean age at latest follow-up: 61.2 years (SD 20.7); 11 females (44%)), and assessed for mobility using the Prosthetic Limb Users Survey of Mobility (PLUS-M; for amputees only), the Toronto Extremity Salvage Score (TESS), and the University of California, Los Angeles (UCLA) Activity Score. Individual QoL was evaluated in these 25 patients using the five-level EuroQol five-dimension (EQ-5D-5L) and Fragebogen zur Lebenszufriedenheit/Questions on Life Satisfaction (FLZ). Results. Of the total number of patients in the study, 22 (32%) underwent minor LSS and 22 (32%) underwent major LSS; 25 underwent primary amputation (36%). Complications developed in 26 (38%) patients, and were more common in those with major or minor LSS in comparison to amputation (59% vs 36% vs 20%; p = 0.022). A time-dependent trend towards higher complication risk following any LSS was present (relative risk: 0.204; 95% confidence interval (CI) 0.026 to 1.614; p = 0.095). In the prospective cohort, mean TESS was higher following minor LSS in comparison to amputation (91.0 vs 67.3; p = 0.006), while there was no statistically significant difference between major LSS and amputation (81.6 vs 67.3; p = 0.099). There was no difference in mean UCLA (p = 0.334) between the three groups (p = 0.334). None of the items in FLZ or EQ-5D-5L were different between the three groups (all p > 0.05), except for FLZ item “self-relation”, being lower in amputees. Conclusion. Complications are common following LSS for ankle sarcomas. QoL is comparable between patients with LSS or amputation, despite better mobility scores for patients following minor LSS. We conclude that these results allow a decision for amputation to be made more easily in patients particularly where the principles of oncological surgery would otherwise be at risk. Cite this article: Bone Joint J 2021;103-B(3):553–561


The Bone & Joint Journal
Vol. 102-B, Issue 2 | Pages 170 - 176
1 Feb 2020
Bernthal NM Burke ZDC Hegde V Upfill-Brown A Chen CJ Hwang R Eckardt JJ

Aims. We aimed to examine the long-term mechanical survivorship, describe the modes of all-cause failure, and identify risk factors for mechanical failure of all-polyethylene tibial components in endoprosthetic reconstruction. Methods. This is a retrospective database review of consecutive endoprosthetic reconstructions performed for oncological indications between 1980 and 2019. Patients with all-polyethylene tibial components were isolated and analyzed for revision for mechanical failure. Outcomes included survival of the all-polyethylene tibial component, revision surgery categorized according to the Henderson Failure Mode Classification, and complications and functional outcome, as assessed by the Musculoskeletal Tumor Society (MSTS) score at the final follow-up. Results. A total of 278 patients were identified with 289 all-polyethylene tibial components. Mechanical survival was 98.4%, 91.1%, and 85.2% at five, ten and 15 years, respectively. A total of 15 mechanical failures were identified at the final follow-up. Of the 13 all-polyethylene tibial components used for revision of a previous tibial component, five (38.5%) failed mechanically. Younger patients (< 18 years vs > 18 years; p = 0.005) and those used as revision components (p < 0.001) had significantly increased rates of failure. Multivariate logistic regression modelling showed revision status to be a positive risk factor for failure (odds ratio (OR) 19.498, 95% confidence interval (CI) 4.598 to 82.676) and increasing age was a negative risk factor for failure (OR 0.927, 95% CI 0.872 to 0.987). Age-stratified risk analysis showed that age > 24 years was no longer a statistically significant risk factor for failure. The final mean MSTS score for all patients was 89% (8.5% to 100.0%). Conclusion. The long-term mechanical survivorship of all-polyethylene tibial components when used for tumour endoprostheses was excellent. Tumour surgeons should consider using these components for their durability and the secondary benefits of reduced cost and ease of removal and revision. However, caution should be taken when using all-polyethylene tibial components in the revision setting as a significantly higher rate of mechanical failure was seen in this group of patients. Cite this article: Bone Joint J. 2020;102-B(2):170–176


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1414 - 1420
1 Aug 2021
Wellings EP Houdek MT Owen AR Bakri K Yaszemski MJ Sim FH Moran SL Rose PS

Aims. Orthopaedic and reconstructive surgeons are faced with large defects after the resection of malignant tumours of the sacrum. Spinopelvic reconstruction is advocated for resections above the level of the S1 neural foramina or involving the sacroiliac joint. Fixation may be augmented with either free vascularized fibular flaps (FVFs) or allograft fibular struts (AFSs) in a cathedral style. However, there are no studies comparing these reconstructive techniques. Methods. We reviewed 44 patients (23 female, 21 male) with a mean age of 40 years (SD 17), who underwent en bloc sacrectomy for a malignant tumour of the sacrum with a reconstruction using a total (n = 20), subtotal (n = 2), or hemicathedral (n = 25) technique. The reconstructions were supplemented with a FVF in 25 patients (57%) and an AFS in 19 patients (43%). The mean length of the strut graft was 13 cm (SD 4). The mean follow-up was seven years (SD 5). Results. There was no difference in the mean age, sex, length of graft, size of the tumour, or the proportion of patients with a history of treatment with radiotherapy in the two groups. Reconstruction using an AFS was associated with nonunion (odds ratio 7.464 (95% confidence interval (CI) 1.77 to 31.36); p = 0.007) and a significantly longer mean time to union (12 months (SD 3) vs eight (SD 3); p = 0.001) compared with a reconstruction using a FVF. Revision for a pseudoarthrosis was more likely to occur in the AFS group compared with the FVF group (hazard ratio 3.84 (95% CI 0.74 to 19.80); p = 0.109); however, this was not significant. Following the procedure, 32 patients (78%) were mobile with a mean Musculoskeletal Tumor Society Score 93 of 52% (SD 24%). There was a significantly higher mean score in patients reconstructed with a FVF compared with an AFS (62% vs 42%; p = 0.003). Conclusion. Supplementation of spinopelvic reconstruction with a FVF was associated with a shorter time to union and a trend towards a reduced risk of hardware failure secondary to nonunion compared with reconstruction using an AFS. Spinopelvic fixation supplemented with a FVF is our preferred technique for reconstruction following resection of a sacral tumour. Cite this article: Bone Joint J 2021;103-B(8):1414–1420


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 702 - 710
1 Jun 2023
Yeramosu T Ahmad W Bashir A Wait J Bassett J Domson G

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.

Methods

Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 497 - 506
16 Sep 2024
Hsieh H Yen H Hsieh W Lin C Pan Y Jaw F Janssen SJ Lin W Hu M Groot O

Aims

Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments.

Methods

This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve.


The Bone & Joint Journal
Vol. 102-B, Issue 5 | Pages 638 - 645
1 May 2020
Sternheim A Traub F Trabelsi N Dadia S Gortzak Y Snir N Gorfine M Yosibash Z

Aims. 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. Methods. Data were collected on 82 patients with femoral metastatic bone disease, 41 of whom did not undergo prophylactic fixation. A total of 15 had a pathological fracture within six months following the CT scan, and 26 were fracture-free during the five months following the scan. The Mirels score and strain fold ratio (SFR) based on CTFEA was computed for all patients. A SFR value of 1.48 was used as the threshold for a pathological fracture. The sensitivity, specificity, positive, and negative predicted values for Mirels score and SFR predictions were computed for nine patients who fractured and 24 who did not, as well as a comparison of areas under the receiver operating characteristic curves (AUC of the ROC curves). Results. The sensitivity of SFR was 100% compared with 88% for the Mirels score, and the specificity of SFR was 67% compared with 38% for the Mirels score. The AUC was 0.905 for SFR compared with 0.578 for the Mirels score (p = 0.008). Conclusion. All the patients who sustained a pathological fracture of the femur had an SFR of > 1.48. CTFEA was far better at predicting the risk of fracture and its location accurately compared with the Mirels score. CTFEA is quick and automated and can be incorporated into the protocol of CT scanners. Cite this article: Bone Joint J 2020;102-B(5):638–645


Bone & Joint Open
Vol. 4, Issue 6 | Pages 424 - 431
5 Jun 2023
Christ AB Piple AS Gettleman BS Duong A Chen M Wang JC Heckmann ND Menendez L

Aims

The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype.

Methods

The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures.


The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 195 - 202
1 Feb 2024
Jamshidi K Kargar Shooroki K Ammar W Mirzaei A

Aims

The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child’s distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach.

Methods

A total of 30 children with a chondroblastoma of the distal femur who had been treated by intraregional curettage and bone grafting were retrospectively reviewed. An intercondylar approach was used in 16 patients (group A) and an epiphyseal approach in 14 (group B). Limb function was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system and Sailhan’s functional criteria.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 317 - 323
18 Apr 2024
Zhu X Hu J Lin J Song G Xu H Lu J Tang Q Wang J

Aims

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.

Methods

We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital.


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 93 - 98
1 Jan 2024
Broida SE Tsoi KM Rose PS Ferguson PC Griffin AM Wunder JS Houdek MT

Aims

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.

Methods

A total of 60 patients (25 females, 35 males; mean age 39 years (SD 18)) undergoing iliosacral resection were reviewed. Most resections were performed for primary malignant tumours (n = 54; 90%). The mean follow-up for surviving patients was nine years (2 to 19).


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1000 - 1007
1 Sep 2024
Gong T Lu M Sheng H Li Z Zhou Y Luo Y Min L Tu C

Aims

Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes.

Methods

This study involved patients who underwent implantation of an uncemented distal femoral endoprosthesis with a short and curved stem between 2014 and 2019. Functional outcomes were assessed using the 1993 version of the Musculoskeletal Tumour Society (MSTS-93) score. Additionally, we quantified five types of complications and assessed osseointegration radiologically. The survivorship of the endoprosthesis was evaluated according to two endpoints. A total of 134 patients with a median age of 26 years (IQR 16 to 41) were included in our study. The median follow-up time was 61 months (IQR 56 to 76), and the median functional MSTS-93 was 83% (IQR 73 to 91) postoperatively.


The Bone & Joint Journal
Vol. 105-B, Issue 12 | Pages 1314 - 1320
1 Dec 2023
Broida SE Sullivan MH Barlow JD Morrey M Scorianz M Wagner ER Sanchez-Sotelo J Rose PS Houdek MT

Aims

The scapula is a rare site for a primary bone tumour. Only a small number of series have studied patient outcomes after treatment. Previous studies have shown a high rate of recurrence, with functional outcomes determined by the preservation of the glenohumeral joint and deltoid. The purpose of the current study was to report the outcome of patients who had undergone tumour resection that included the scapula.

Methods

We reviewed 61 patients (37 male, 24 female; mean age 42 years (SD 19)) who had undergone resection of the scapula. The most common resection was type 2 (n = 34) according to the Tikhoff-Linberg classification, or type S1A (n = 35) on the Enneking classification.


Bone & Joint Open
Vol. 4, Issue 11 | Pages 817 - 824
1 Nov 2023
Filis P Varvarousis D Ntritsos G Dimopoulos D Filis N Giannakeas N Korompilias A Ploumis A

Aims

The standard of surgical treatment for lower limb neoplasms had been characterized by highly interventional techniques, leading to severe kinetic impairment of the patients and incidences of phantom pain. Rotationplasty had arisen as a potent limb salvage treatment option for young cancer patients with lower limb bone tumours, but its impact on the gait through comparative studies still remains unclear several years after the introduction of the procedure. The aim of this study is to assess the effect of rotationplasty on gait parameters measured by gait analysis compared to healthy individuals.

Methods

The MEDLINE, Scopus, and Cochrane databases were systematically searched without time restriction until 10 January 2022 for eligible studies. Gait parameters measured by gait analysis were the outcomes of interest.


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 696 - 701
1 Jun 2023
Kurisunkal V Morris G Kaneuchi Y Bleibleh S James S Botchu R Jeys L Parry MC

Aims

Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee.

Methods

We identified 63 cases of high-grade sarcomas in or around the distal femur that underwent an EA resection from a prospectively maintained database (January 1996 to April 2020). Suspicion of IA disease was noted in 52 cases, six had IA pathological fracture, two had an effusion, two had prior surgical intervention (curettage/IA intervention), and one had an osseous metastasis in the proximal tibia. To ascertain validity, two musculoskeletal radiologists (R1, R2) reviewed the preoperative imaging (MRI) of 63 consecutive cases on two occasions six weeks apart. The radiological criteria for IA disease comprised evidence of tumour extension within the suprapatellar pouch, intercondylar notch, extension along medial/lateral retinaculum, and presence of IA fracture. The radiological predictions were then confirmed with the final histopathology of the resected specimens.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 83 - 90
19 Feb 2024
Amri R Chelly A Ayedi M Rebaii MA Aifa S Masmoudi S Keskes H

Aims

The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

Methods

A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).


Bone & Joint Open
Vol. 5, Issue 3 | Pages 210 - 217
13 Mar 2024
Mthethwa PG Marais LC Aldous CM

Aims

The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa.

Methods

We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis.


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 99 - 106
1 Jan 2024
Khal AA Aiba H Righi A Gambarotti M Atherley O'Meally AO Manfrini M Donati DM Errani C

Aims

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

Methods

We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome.


The Bone & Joint Journal
Vol. 105-B, Issue 11 | Pages 1206 - 1215
1 Nov 2023
Ladegaard TH Sørensen MS Petersen MM

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.

Methods

We conducted a retrospective study on a population-based cohort of all adult patients treated surgically for bony metastases of the appendicular skeleton between January 2014 and December 2019. We excluded patients in whom the status of bone metastases and resection margin was unknown. Patients were followed until the end of the study or to their death. We had no loss to follow-up. We used Kaplan-Meier analysis (with log-rank test) to evaluate patient survival. We identified 506 operations in 459 patients. A total of 120 operations (in 116 patients) were for solitary metastases and 386 (in 345 patients) for multiple metastases. Of the 120 operations, 70 (in 69 patients) had no/an unknown status of visceral metastases (solitary group) and 50 (in 49 patients) had visceral metastases. In the solitary group, 45 operations (in 44 patients) were R0 (resections for cure or complete remission) and 25 (in 25 patients) were R1/R2 (resections leaving microscopic or macroscopic tumour, respectively). The most common types of cancer in the solitary group were kidney (n = 27), lung (n = 25), and breast (n = 20).


Bone & Joint Open
Vol. 5, Issue 10 | Pages 944 - 952
25 Oct 2024
Deveza L El Amine MA Becker AS Nolan J Hwang S Hameed M Vaynrub M

Aims

Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension.

Methods

We performed a retrospective case-control study of patients who underwent extra-articular excision for sarcoma of the knee, hip, or shoulder from 1 June 2000 to 1 November 2020. Radiologists blinded to the pathology results evaluated preoperative MRI for three direct signs of joint invasion (capsular disruption, cortical breach, cartilage invasion) and indirect signs (e.g. joint effusion, synovial thickening). The discriminatory ability of MRI to detect intra-articular tumour extension was determined by receiver operating characteristic analysis.


Aims

This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection.

Methods

We retrospectively reviewed 29 bone tumour resections that used 3DP-PSRGs based on 3D CT and 3D MRI. We evaluated the resection amount errors and resection margin errors relative to the preoperative plans. Guide-fitting errors and guide distortion were evaluated intraoperatively and one month postoperatively, respectively. We categorized each of these error types into three grades (grade 1, < 1 mm; grade 2, 1 to 3 mm; and grade 3, > 3 mm) to evaluate the overall accuracy.


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 865 - 870
1 Aug 2024
Broida SE Sullivan MH Rose PS Wenger DE Houdek MT

Aims

Venous tumour thrombus (VTT) is a rare finding in osteosarcoma. Despite the high rate of VTT in osteosarcoma of the pelvis, there are very few descriptions of VTT associated with extrapelvic primary osteosarcoma. We therefore sought to describe the prevalence and presenting features of VTT in osteosarcoma of both the pelvis and the limbs.

Methods

Records from a single institution were retrospectively reviewed for 308 patients with osteosarcoma of the pelvis or limb treated between January 2000 and December 2022. Primary lesions were located in an upper limb (n = 40), lower limb (n = 198), or pelvis (n = 70). Preoperative imaging and operative reports were reviewed to identify patients with thrombi in proximity to their primary lesion. Imaging and histopathology were used to determine presence of tumour within the thrombus.