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. 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.Aims
Methods
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. 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).Aims
Methods
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. 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).Aims
Methods
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. 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.Aims
Methods
Internal hemipelvectomy without reconstruction of the pelvis is a viable treatment for pelvic sarcoma; however, the time it takes to return to excellent function is quite variable. Some patients require greater time and rehabilitation than others. To determine if psoas muscle recovery is associated with changes in ambulatory function, we retrospectively evaluated psoas muscle size and limb-length discrepancy (LLD) before and after treatment and their correlation with objective functional outcomes. T1-weighted MR images were evaluated at three intervals for 12 pelvic sarcoma patients following interval hemipelvectomy without reconstruction. Correlations between the measured changes and improvements in Timed Up and Go test (TUG) and gait speed outcomes were assessed both independently and using a stepwise multivariate regression model.Aims
Methods
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. 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.Aims
Methods
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. Results. Overall, 25 patients met inclusion criteria. There were eight benign tumours, seven metastatic, seven primary sarcomas, one multiple myeloma, and two patients without a biopsy proven diagnosis. There was no priority level 0, two priority level I, six priority level II, and 17 priority level III cases. The mean duration of delay for priority level I was 114 days (84 to 143), priority level II was 88 days (63 to 133), and priority level III was 77 days (35 to 269). Prolonged pain/disability and delay in diagnosis, affecting 52% and 40%,respectively, represented the two most frequent morbidities. Local tumour progression and increased systemic disease affected 32% and 24% respectively. No patients tested positive for COVID-19. Conclusion. COVID-19 related delays in surgical management led to major morbidity in this studied orthopaedic oncologic patient population. By understanding these morbidities through clearer hindsight, a thoughtful approach can be developed to
Aims Although chondrosarcomas (CSs) display true malignant features, including local recurrence (LR) and metastases, their behaviour in the hands and feet is thought to differ from that in other parts of the axial and appendicular skeleton by having a lower metastatic potential. The purpose of this study was to investigate the disease-specific and surgical factors that affect the local and systemic prognosis of CS of the hands and feet. A multicentre retrospective study was carried out at two tertiary sarcoma centres. A database search identified all patients with a CS treated between January 1995 and January 2018. There were 810 CSs of which 76 (9.4%) were located in the fingers, toes, metacarpals, and metatarsal bones. The median age of the study population was 55 years (36 to 68) with a median follow-up of 52 months (22 to 87) months. Overall, 70% of the tumours were in the hand (n = 54) and 30% in the foot (n = 22). Predictors for LR were margin (p = 0.011), anatomical location (p = 0.017), and method of surgical management (p = 0.003). Anatomical location (p = 0.026), histological grade between 1 and 3 (p = 0.004) or 2 and 3 (p = 0.016), and surgical management (p = 0.001) were significant factors for LR-free survival. Disease-specific survival was affected by histological grade (p < 0.001), but not by LR (p = 0.397).Methods
Results
Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma.Aims
Methods
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. 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.Aims
Methods
Aims. The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. Patients and Methods. A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). Results. Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). Conclusion. We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The
The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment. This prospective cohort study run in two Dutch referral centres assessed patient-reported outcome measures (PROMs; 36-Item Short-Form Health Survey (SF-36), visual analogue scale (VAS) for pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 359 consecutive patients with localized- and diffuse-type TGCT of large joints. Patients with recurrent disease (n = 121) and a wait-and-see policy (n = 32) were excluded. Collected data were analyzed at specified time intervals preoperatively (baseline) and/or postoperatively up to five years.Aims
Patients and Methods
The aims of this study were to evaluate the efficacy of preoperative denosumab in achieving prospectively decided intention of therapy in operable giant cell tumour of bone (GCTB) patients, and to document local recurrence-free survival (LRFS). A total of 44 patients received preoperative denosumab: 22 to facilitate curettage, 16 to facilitate resection, and six with intent of converting resection to curettage. There were 26 male and 18 female patients. The mean age was 27 years (13 to 47).Aims
Patients and Methods
Few studies dealing with chondrosarcoma of the pelvis are currently
available. Different data about the overall survival and prognostic
factors have been published but without a detailed analysis of surgery-related complications.
We aimed to analyse the outcome of a series of pelvic chondrosarcomas
treated at a single institution, with particular attention to the
prognostic factors. Based on a competing risk model, our objective
was to identify risk factors for the development of complications. In a retrospective single-centre study, 58 chondrosarcomas (26
patients alive, 32 patients dead) of the pelvis were reviewed. The
mean follow-up was 13 years (one week to 23.1 years).Aims
Patients and Methods
The aim of the study was to investigate the controversial issue
of whether the pelvic ring should be reconstructed following resection
of the sarcomas of the ilium. From our database, we identified 64 patients who underwent excision
of a tumour involving the ilium between 1976 and 2015. A total of
35 underwent complete resection, of whom 24 were reconstructed with
a non-vascularised fibula graft, and four with extracorporeal irradiation
and reimplantation. A total of 29 patients had a partial resection.
The mean follow-up was 9.2 years (1.1 to 25.6). Functional outcomes
were assessed using the Toronto Extremity Salvation Score (TESS)
at final follow-up. In all, 32 patients (50%) had a chondrosarcoma.Aims
Patients and Methods
We investigated whether the presence of a pathological
fracture increased the risk of local recurrence in patients with
a giant cell tumour (GCT) of bone. We also assessed if curettage
is still an appropriate form of treatment in the presence of a pathological
fracture. We conducted a comprehensive review and meta-analysis
of papers which reported outcomes in patients with a GCT with and
without a pathological fracture at presentation. We computed the
odds ratio (OR) of local recurrence in those with and without a
pathological fracture. We selected 19 eligible papers for final analysis. This included
3215 patients, of whom 580 (18.0%) had a pathological fracture.
The pooled OR for local recurrence between patients with and without
a pathological fracture was 1.05 (95% confidence interval (CI) 0.66
to 1.67, p = 0.854). Amongst the subgroup of patients who were treated with
curettage, the pooled OR for local recurrence was 1.23 (95% CI 0.75
to 2.01, p = 0.417). A There is no difference in local recurrence rates between patients
who have a GCT of bone with and without a pathological fracture
at the time of presentation. The presence of a pathological fracture
should not preclude the decision to perform curettage as carefully
selected patients who undergo curettage can have similar outcomes
in terms of local recurrence to those without such a fracture. Cite this article:
Clinical studies of patients with bone sarcomas have been challenged
by insufficient numbers at individual centres to draw valid conclusions.
Our objective was to assess the feasibility of conducting a definitive
multi-centre randomised controlled trial (RCT) to determine whether
a five-day regimen of post-operative antibiotics, in comparison
to a
24-hour regimen, decreases surgical site infections in patients
undergoing endoprosthetic reconstruction for lower extremity primary
bone tumours. We performed a pilot international multi-centre RCT. We used
central randomisation to conceal treatment allocation and sham antibiotics
to blind participants, surgeons, and data collectors. We determined
feasibility by measuring patient enrolment, completeness of follow-up,
and protocol deviations for the antibiotic regimens. Objective
Methods
Giant cell tumour is the most common aggressive
benign tumour of the musculoskeletal system and has a high rate of
local recurrence. When it occurs in proximity to the hip, reconstruction
of the joint is a challenge. Options for reconstruction after wide
resection include the use of a megaprosthesis or an allograft-prosthesis
composite. We performed a clinical and radiological study to evaluate
the functional results of a proximal femoral allograft-prosthesis
composite in the treatment of proximal femoral giant cell tumour
after wide resection. This was an observational study, between 2006
and 2012, of 18 patients with a mean age of 32 years (28 to 42)
and a mean follow-up of 54 months (18 to 79). We achieved excellent
outcomes using Harris Hip Score in 13 patients and a good outcome
in five. All allografts united. There were no complications such
as infection, failure, fracture or resorption of the graft, or recurrent
tumour. Resection and reconstruction of giant cell tumours with
proximal femoral allograft–prosthesis composite is a better option
than using a prosthesis considering preservation of bone stock and excellent
restoration of function. A good result requires demanding bone banking techniques, effective
measures to prevent infection and stability at the allograft-host
junction. Cite this article:
A total of 157 hindquarter amputations were carried
out in our institution during the last 30 years. We have investigated
the reasons why this procedure is still required and the outcome.
This operation was used as treatment for 13% of all pelvic bone
sarcomas. It was curative in 140 and palliative in 17, usually to
relieve pain. There were 90 primary procedures (57%) with the remaining
67 following the failure of previous operations to control the disease
locally. The indication for amputation in primary disease was for
large tumours for which limb-salvage surgery was no longer feasible.
The peri-operative mortality was 1.3% (n = 2) and major complications
of wound healing or infection arose in 71 (45%) patients. The survival
at five years after hindquarter amputation with the intent to cure
was 45%, and at ten years 38%. Local recurrence occurred in 23 patients
(15%). Phantom pain was a significant problem, and only 20% used
their prosthesis regularly. Functional scores were a mean of 57%.
With careful patient selection the oncological results and functional outcomes
of hindquarter amputation justify its continued use. Cite this article:
Rarely, the extent of a malignant bone tumour
may necessitate resection of the complete humerus to achieve adequate
oncological clearance. We present our experience with reconstruction
in such cases using a total humeral endoprosthesis (THER) in 20
patients (12 male and eight female) with a mean age of 22 years
(6 to 59). We assessed the complications, the oncological and functional
outcomes and implant survival. Surgery was performed between June
2001 and October 2009. The diagnosis included osteosarcoma in nine,
Ewing’s sarcoma in eight and chondrosarcoma in three. One patient
was lost to follow-up. The mean follow-up was 41 months (10 to 120)
for all patients and 56 months (25 to 120) in survivors. There were
five local recurrences (26.3%) and 11 patients were alive at time
of last follow-up, with overall survival for all patients being
52% (95% confidence interval (CI) 23.8 to 74) at five years. The
mean Musculoskeletal Tumor Society score for the survivors was 22
(73%; 16 to 23). The implant survival was 95% (95% CI 69.5 to 99.3)
at five years. The use of a THER in the treatment of malignant tumours of bone
is oncologically safe; it gives consistent and predictable results
with low rates of complication.
