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The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 980 - 983
1 Jul 2011
Malhas AM Grimer RJ Abudu A Carter SR Tillman RM Jeys L

We investigated the eventual diagnosis in patients referred to a tertiary centre with a possible diagnosis of a primary bone malignancy.

We reviewed our database from between 1986 and 2010, during which time 5922 patients referred with a suspicious bone lesion had a confirmed diagnosis. This included bone sarcoma in 2205 patients (37%), benign bone tumour in 1309 (22%), orthopaedic conditions in 992 (17%), metastatic disease in 533 (9%), infection in 289 (5%) and haematological disease in 303 (5%). There was a similar frequency of all diagnoses at different ages except for metastatic disease. Only 0.6% of patients (17 of 2913) under the age of 35 years had metastatic disease compared with 17.1% (516 of 3009) of those over 35 years (p < 0.0001). Of the 17 patients under 35 years with metastatic disease, only four presented with an isolated lesion, had no past history of cancer and were systematically well.

Patients under the age of 35 years should have suitable focal imaging (plain radiography, CT or MRI) and simple systemic studies (blood tests and chest radiography). Reduction of the time to biopsy can be achieved by avoiding an unnecessary investigation for a primary tumour to rule out metastatic disease.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 568 - 574
1 May 2023
Kobayashi H Ito N Nakai Y Katoh H Okajima K Zhang L Tsuda Y Tanaka S

Aims

The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition.

Methods

The study included 33 patients with TIO who were treated between January 2000 and June 2022. The causative tumour was detected in all patients. We investigated the symptoms and evaluated the radiological patterns of insufficiency fractures of the rib, spine, and limbs.


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.


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.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 808 - 814
1 Jul 2023
Gundavda MK Lazarides AL Burke ZDC Focaccia M Griffin AM Tsoi KM Ferguson PC Wunder JS

Aims

The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade. The most important clinical distinction is between grade 1 chondrosarcomas, which are amenable to curettage, and resection-grade chondrosarcomas (grade 2 and 3) which require en bloc resection. The aim of this study was to evaluate the use of a Radiological Aggressiveness Score (RAS) to predict the grade of primary chondrosarcomas in long bones and thus to guide management.

Methods

A total of 113 patients with a primary chondrosarcoma of a long bone presenting between January 2001 and December 2021 were identified on retrospective review of a single oncology centre’s prospectively collected database. The nine-parameter RAS included variables from radiographs and MRI scans. The best cut-off of parameters to predict the final grade of chondrosarcoma after resection was determined using a receiver operating characteristic curve (ROC), and this was correlated with the biopsy grade.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 551 - 558
1 May 2023
Wang H Ji T Qu H Yan T Li D Yang R Tang X Guo W

Aims

The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours.

Methods

ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied.


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1115 - 1122
1 Oct 2023
Archer JE Chauhan GS Dewan V Osman K Thomson C Nandra RS Ashford RU Cool P Stevenson J

Aims

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

Methods

A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

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.


The Bone & Joint Journal
Vol. 98-B, Issue 12 | Pages 1674 - 1681
1 Dec 2016
Verdegaal SHM van Rijswijk CS Brouwers HFC Dijkstra PDS van de Sande MAJ Hogendoorn PCW Taminiau AHM

Aims. The purpose of this retrospective study was to differentiate between the MRI features of normal post-operative change and those of residual or recurrent disease after intralesional treatment of an atypical cartilage tumour (ACT)/grade I chondrosarcoma. Patients and Methods. We reviewed the case notes, radiology and histology of 75 patients, who had been treated for an ACT/grade I chondrosarcoma by curettage, phenolisation and bone allografting between 1994 and 2005. The first post-operative Gd-enhanced MRI scan was carried out within one year of surgery. Patients had a minimum of two scans and a mean follow-up of 72 months (13 to 169). Further surgery was undertaken in cases of suspected recurrence. Results. In 14 patients (18.6%) a second procedure was undertaken after a mean period of 59 months (8 to 114). Radio frequency ablation (RFA) was used in lesions of < 10 mm and curettage, phenolisation and bone grafting for those ≥ 10 mm. Only six of these (8% of total) had a histologically-proven recurrence. No increase in tumour grade was seen at time of recurrence. Conclusion. Based on this study, we have been able to classify the post-operative MRI appearances into four groups. These groups differ in follow-up, and have a different risk of recurrence of the lesion. Follow-up and treatment vary for the patients in each group. We present a flow diagram for the appropriate and safe follow-up for this specific group of patients. Cite this article: Bone Joint J 2016;98-B:1674–81


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 33 - 33
1 Jul 2012
Cosker T Whitwell D James A Reynolds E Porter C Gibbons M
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Introduction. A GP may only encounter one sarcoma in their professional career. Early diagnosis and treatment will improve the outcomes of this rare and malignant disease. Guidelines designed to lead to earlier diagnosis of the most common cancers were introduced by NICE in 2000 and were updated in 2005. These advise and assist in the early referral of potential bone and soft tissue sarcoma. Prior to 2000 only ~10% of GP referrals were proven to be malignant. Methods. In a referral region of ∼3m, we reviewed the referral patterns of suspected sarcoma by General Practitioners since 2005 in an effort to determine whether the published NICE guidelines had influenced an improvement in the diagnosis and management of malignant disease. Results. 33.3% of all referrals made by General Practitioners using the Thames Valley Cancer Network referral proforma were malignant. Discussion. NICE sarcoma guidelines for GPs have been effective in improving the diagnosis of malignant disease with suspected sarcoma albeit as a triage for malignancy rather than specifically for sarcoma


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 35 - 35
1 Jul 2012
Pennant S Gibbons C Whitwell D Ostlere S Morley J
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Introduction. Tissue diagnosis is essential to direct the definitive management of a suspected soft tissue or bone sarcoma tissue. Knowledge of both the diagnostic yield and accuracy of core needle biopsies is therefore important to give the investigating team information on the likelihood of their initial investigations achieving a diagnosis. Methods. This is a retrospective study of patients referred to a specialist orthopaedic centre for investigation of a suspected soft tissue or bone sarcoma. Details of all core needle biopsies performed in a 13-month period were obtained from the hospital database. We defined a diagnostic biopsy as either a specific tissue diagnosis or a biopsy that decided the definitive management of the patient, specifically if malignancy was excluded and no further intervention was required, to calculate the diagnostic yield. Diagnostic accuracy was established by comparing histological diagnosis at biopsy to that at final excision. Results. The overall diagnostic yield of the biopsies performed was 85% (125 of 148 biopsies) and the diagnostic accuracy was 93% (77 of 83). The diagnostic yield of soft tissue lesions was 93% (79 of 85) and accuracy 98%. For bone lesions the diagnostic yield was 73% (46 of 73) and accuracy was 85%. Discussion. Knowing the diagnostic yield and accuracy of biopsies performed allows the investigating team to give patients and colleagues a figure detailing the likely success of a soft tissue or bone biopsy in being diagnostic. In addition this data provides the investigating team with information on specific biopsy types that are less likely to be diagnostic, such as bone lesions requiring CT guidance. These may benefit from another biopsy method to avoid delay in diagnosis and facilitate timely management


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1435 - 1441
1 Oct 2010
Bischel OE Böhm PM

Endoprosthetic reconstruction following resection of 31 tumours of the proximal femur in 30 patients was performed using a Wagner SL femoral revision stem. The mean follow-up was 25.6 months (0.6 to 130.0). Of the 28 patients with a metastasis, 27 died within a mean follow-up period of 18.1 months (0.6 to 56.3) after the operation, and the remaining patient was excluded from the study 44.4 months post-operatively when the stem was removed. The two patients with primary bone tumours were still alive at the latest follow-up of 81.0 and 130.0 months, respectively. One stem only was removed for suspected low-grade infection 44.4 months post-operatively. The worst-case survival rate with removal of the stem for any cause and/or loss to follow-up was 80.0% (95% confidence interval 44.9 to 100) at 130.0 months. The mean Karnofsky index increased from 44.2% (20% to 70%) pre-operatively to 59.7% (0% to 100%) post-operatively, and the mean Merle d’Aubigné score improved from 4.5 (0 to 15) to 12.0 (0 to 18). The mean post-operative Musculoskeletal Tumour Society score was 62.4% (3.3% to 100%). The Wagner SL femoral revision stem offers an alternative to special tumour prostheses for the treatment of primary and secondary tumours of the proximal femur. The mid-term results are very promising, but long-term experience is necessary


Bone & Joint Research
Vol. 10, Issue 9 | Pages 602 - 610
24 Sep 2021
Tsoi KM Gokgoz N Darville-O'Quinn P Prochazka P Malekoltojari A Griffin AM Ferguson PC Wunder JS Andrulis IL

Aims

Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

Methods

Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1541 - 1549
1 Sep 2021
Fujiwara T Evans S Stevenson J Tsuda Y Gregory J Grimer RJ Abudu S

Aims

While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK.

Methods

The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management.


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 569 - 577
1 Mar 2021
Fujiwara T Grimer RJ Evans S Medellin Rincon MR Tsuda Y Le Nail L Abudu S

Aims

Urgent referral to a specialist centre for patients with a soft-tissue sarcoma (STS) has been recommended by the National Institute for Health and Care Excellence (NICE) in the UK since 2006. However, the impact of this recommendation on the prognosis for these patients remains unclear. We aimed to determine the impact of the NICE guidelines on the disease-specific survival (DSS) of patients with an STS.

Methods

A total of 2,427 patients with an STS referred to a supraregional centre in the ten-year periods before (n = 1,386) and after (n = 1,041) the issue of the NICE guidelines were evaluated.


Bone & Joint Open
Vol. 2, Issue 4 | Pages 236 - 242
1 Apr 2021
Fitzgerald MJ Goodman HJ Kenan S Kenan S

Aims

The aim of this study was to assess orthopaedic oncologic patient morbidity resulting from COVID-19 related institutional delays and surgical shutdowns during the first wave of the pandemic in New York, USA.

Methods

A single-centre retrospective observational study was conducted of all orthopaedic oncologic patients undergoing surgical evaluation from March to June 2020. Patients were prioritized as level 0-IV, 0 being elective and IV being emergent. Only priority levels 0 to III were included. Delay duration was measured in days and resulting morbidities were categorized into seven groups: prolonged pain/disability; unplanned preoperative radiation and/or chemotherapy; local tumour progression; increased systemic disease; missed opportunity for surgery due to progression of disease/lost to follow up; delay in diagnosis; and no morbidity.


The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 411 - 418
1 Mar 2013
Nakamura T Grimer RJ Gaston CL Watanuki M Sudo A Jeys L

The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing’s sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival. Cite this article: Bone Joint J 2013;95-B:411–18


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 6 - 6
1 Apr 2012
Malhas A Grimer RJ Carter S Tillman R Abudu A Jeys L
Full Access

Since1986 we have monitored the actual diagnosis of all cases referred to our Unit with the diagnosis of ‘possible primary malignant bone tumour’. We have excluded all patients referred with a known diagnosis of either a benign condition or known to have bone metastases. In most cases the suspected diagnosis was based on X-rays alone, sometimes supported by further imaging. Method. Retrospective review of a prospective database that was started in 1986 identifying the actual diagnosis. Results. There were 5922 patients with a confirmed diagnosis over the 23 year time period of this study. 2205 (37%) were found to have a primary malignant bone sarcoma and 1309 (22%) had a benign bone tumour. 992 patients had a general orthopaedic condition (e.g. geode or a vascular necrosis) whilst 303 (5%) had a haematological malignancy and 289 (4.9%) infection. 533 patients (9%) had metastases. There was a similar pattern of frequency of all diagnoses except for metastatic disease and haematologic malignancy at different ages. The incidence of metastases increased from the age of 35 onwards. Discussion. Analysis of this data has led to an algorithm for investigating ‘worrying’ bones that should lead to earlier diagnosis whilst avoiding unnecessary investigations


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 32 - 32
1 Jul 2012
Cosker T White HB James A Athanisou N Whitwell D Gibbons M
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Introduction. Primary soft tissue sarcomas of the extremities are uncommon. Many such lesions will present to specialists in other clinics such as specialist Hand or Foot and Ankle clinics. Many are of a small size at presentation and may appear to be alternate, more common pathology. Methods. We collected data from all those patients with acral soft tissues sarcomas and referred to the Oxford Sarcoma Service, Nuffield Orthopaedic Centre, Oxford over a thirteen year period from 1997 – 2010. Data were collected regarding the primary suspected diagnosis, the final diagnosis, the referral route and whether patients had undergone previous inadvertent excision. Results. 38 patients were treated (24 foot, 14 hand tumours). The commonest histological subtype was synovial sarcoma in the foot group, and leiomyosarcoma in the hand group. 25 of the 38 patients had a lesion of less than 5cm at presentation. For those patients in whom a wide excision was performed 50% underwent complex plastic surgical reconstruction. Discussion. This study shows that 30% of patients with acral tumours required further surgery due to previous inadequate/inadvertent excision. 5cm as a benchmark for specialist referral should not be applied to lesions in the hand or feet and we recommend the use of the “marble rule” i.e. any lesion the size of a marble should be referred urgently and no patient should undergo surgery without imaging


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 26 - 26
1 Apr 2012
Verdegaal S Brouwers H Hogendoorn P Taminiau A
Full Access

Aim. Assess the oncological and clinical outcomes associated with intralesional curettage, phenol and bone grafting of the lesions. Method. A retrospective study was performed using data from the Leiden University Medical Center. Ninety patients with low grade central chondrosarcoma of long bones and small tubular bones were treated using phenol and ethanol as adjuvant therapy after intralesional curettage. Standard clinical follow-up contained regular visits to the orthopaedic department, physical examination and radiological follow-up with plain X-rays and dynamic Gadolineum-enhanced MRI scans. Results. Between 1994 and 2005 thirty-three males and fifty-seven females with a mean age of 47 years (range 5.6-73.1) were treated in our clinic. Mean follow-up 6.5 years (range 0.2-14.1). Location of chondrosarcoma. Femur (43%), humerus (32%), tibia (10%), fibula (6%), metacarpalia (4%), radius (2%), ulna (1%), phalanx (1%). Average tumour volume of all lesions, including metacarpals and phalanges, was 22 cm3 (range 1-104). With a mean follow up of 6.5 years, 86% of the patients are free of tumour on plain X-ray and dynamic Gd-MRI. Two femoral fractures occurred within 6 weeks after surgery, treated by ORIF. 14% of the patients had re-intervention(s) due to suspected recurrence or residual tumour on dynamic Gd-MRI (7 recurettage, 6 RFA). Histology: Grade I Chondrosarcoma (7), no recurrence (2), non conclusive (4). Overall, there were no cases of metastases. Conclusion. This study presents a large number of patients included, all with same diagnosis and uniform treatment for lowgrade central chondrosarcoma. Periodically clinical and radiological follow-up by dynamic Gd-MRI only showed 8% histological proven recurrences, no upgrading of tumour or occurrence of metastases were seen. Compared to other studies, the complication rates and impairment for the patients are low. Intralesional treatment of low-grade central chondrosarcoma, followed by phenol and ethanol is an effective and safe method with low morbidity for these patients