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.

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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.

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Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines.

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Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses.

Aims. To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods. Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results. OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion. Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803

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The aim of this study was to identify factors that determine outcomes of treatment for patients with chondroblastic osteosarcomas (COS) of the limbs and pelvis.

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The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology.

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We retrospectively report our experience of managing 30 patients with a primary malignant tumour of the distal tibia; 25 were treated by limb salvage surgery and five by amputation. We compared the clinical outcomes of following the use of different methods of reconstruction.

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Osteosarcoma of the pelvis is a particularly difficult tumour to treat as it often presents late, may be of considerable size and/or associated with metastases when it presents, and is frequently chondroid in origin and resistant to chemotherapy.

The aim of this study was to review our experience of managing this group of patients and to identify features predictive of a poor outcome.

We retrospectively reviewed 30 patients with a diffuse-type giant-cell tumour (Dt-GCT) (previously known as pigmented villonodular synovitis) around the knee in order to assess the influence of the type of surgery on the functional outcome and quality of life (QOL). Between 1980 and 2001, 15 of these tumours had been treated primarily at our tertiary referral centre and 15 had been referred from elsewhere with recurrent lesions.

The mean follow-up was 64 months (24 to 393). Functional outcome and QOL were assessed with range of movement and the Knee injury and Osteoarthritis Outcome Score (KOOS), the Musculoskeletal Tumour Society (MSTS) score, the Toronto Extremity Salvage Score (TESS) and the SF-36 questionnaire. There was recurrence in four of 14 patients treated initially by open synovectomy. Local control was achieved after a second operation in 13 of 14 (93%). Recurrence occurred in 15 of 16 patients treated initially by arthroscopic synovectomy. These patients underwent a mean of 1.8 arthroscopies (one to eight) before open synovectomy. This achieved local control in 8 of 15 (53%) after the first synovectomy and in 12 of 15 (80%) after two. The functional outcome and QOL of patients who had undergone primary arthroscopic synovectomy and its attendant subsequent surgical procedures were compared with those who had had a primary open synovectomy using the following measures: range of movement (114º versus 127º; p = 0.03); KOOS (48 versus 71; p = 0.003); MSTS (19 versus 24; p = 0.02); TESS (75 versus 86; p = 0.03); and SF-36 (62 versus 80; p = 0.01).

Those who had undergone open synovectomy needed fewer subsequent operations. Most patients who had been referred with a recurrence had undergone an initial arthroscopic synovectomy followed by multiple further synovectomies. At the final follow-up of eight years (2 to 32), these patients had impaired function and QOL compared with those who had undergone open synovectomy initially.

We conclude that the natural history of Dt-GCT in patients who are treated by arthroscopic synovectomy has an unfavourable outcome, and that primary open synovectomy should be undertaken to prevent recurrence or residual disease.

Cite this article: Bone Joint J 2014; 96-B:1111–18.

Avascular necrosis (AVN) is a serious complication of high-dose chemotherapy for haematological malignancy in childhood. In order to describe its incidence and main risk factors and to evaluate the current treatment options, we reviewed 105 children with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic or acute myeloid leukaemia, or a non-Hodgkin’s lymphoma. Overall, eight children (7.6%) developed AVN after a mean of 16.8 months (8 to 49). There were four boys and four girls with a mean age of 14.4 years (9.8 to 16.8) and a total of 18 involved sites, 12 of which were in the femoral head. All these children were aged > nine years (p < 0.001). All had received steroid treatment with a mean cumulative dose of prednisone of 5967 mg (4425 to 9599) compared with a mean of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No difference existed between genders and no thrombophilic disorders were identified. Their initial treatment included 11 core decompressions and two bipolar hip replacements. Later, two salvage osteotomies were done and three patients (four hips) eventually needed a total joint replacement. We conclude that AVN mostly affects the weight-bearing epiphyses. Its risk increases with age and higher steroid doses. These high-risk patients may benefit from early screening for AVN.

Cite this article: Bone Joint J 2013;95-B:1708–13.

We aimed to identify the incidence, outcome and prognostic factors associated with spindle cell sarcomas of bone (SCSB). We studied 196 patients with a primary non-metastatic tumour treated with the intent to cure. The results were compared with those of osteosarcoma patients treated at our hospital during the same period. The overall incidence of SCSB was 7.8% of all patients with a primary bone sarcoma. The five- and ten-year survival rates were 67.0% and 60.0%, respectively, which were better than those of patients with osteosarcoma treated over the same period. All histological subtypes had similar outcomes. On univariate analysis, factors that were significantly associated with decreased survival were age > 40 years, size > 8 cm, the presence of a pathological fracture, amputation, involved margins and a poor response to pre-operative chemotherapy. Multivariate analyses showed that age > 65 years, amputation and involved margins were all statistically significant prognostic factors. Involved margins and poor response to pre-operative chemotherapy were associated with an increased risk of local recurrence. SCSB has a better prognosis than osteosarcoma when matched for age. Most prognostic factors for osteosarcoma also seem to apply to SCSB. Patients with SCSB should be treated in the same way as patients of the same age with osteosarcoma.

We retrospectively studied 14 patients with proximal and diaphyseal tumours and disappearing bone (Gorham’s) disease of the humerus treated with wide resection and reconstruction using an allograft-resurfacing composite (ARC). There were ten women and four men, with a mean age of 35 years (8 to 69). At a mean follow-up of 25 months (10 to 89), two patients had a fracture of the allograft. In one of these it was revised with a similar ARC and in the other with an intercalary prosthesis. A further patient had an infection and a fracture of the allograft that was revised with a megaprosthesis. In all patients with an ARC, healing of the ARC-host bone interface was observed. One patient had failure of the locking mechanism of the total elbow replacement. The mean post-operative Musculoskeletal Tumor Society score for the upper extremity was 77% (46.7% to 86.7%), which represents good and excellent results; one patient had a poor result (46.7%).

In the short term ARC effectively relieves pain and restores shoulder function in patients with wide resection of the proximal humerus. Fracture and infection remain significant complications.

We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% vs 3%, p = 0.003; overall lung metastasis rate: 51.4% vs 18.8%, p < 0.001). Patients who had manipulative therapy had higher local recurrence rates in comparison to patients who did not (29% vs 6%, p = 0.011). The prognosis for patients with osteosarcoma who had manipulative therapy was significantly poorer than those who had not. Manipulative therapy was an independent factor for survival.

This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma.

We describe a retrospective review of 38 cases of reconstruction following resection of the metaphysiodiaphysis of the lower limb for malignant bone tumours using free vascularised fibular grafts. The mean follow-up was for 7.6 years (0.4 to 18.4). The mean Musculoskeletal Tumor Society score was 27.2 (20 to 30). The score was significantly higher when the graft was carried out in a one-stage procedure after resection of the tumour rather than in two stages. Bony union was achieved in 89% of the cases. The overall mean time to union was 1.7 years (0.2 to 10.3).

Free vascularised fibular transfer is a major operation with frequent, but preventable, complications which allows salvage of the limb with satisfactory functional results.

We identified eight patients of 2900 with a primary malignant bone tumour who had coexisting neurofibromatosis type 1. This was a much higher incidence than would be expected by chance. The patients had a mean age of 22.4 years (9 to 54): five were male. Two patients subsequently developed a second bone sarcoma, one of which was radiation induced. Four of the primary tumours were osteosarcomas, four were spindle-cell sarcomas and one a Ewing’s sarcoma. All the patients were treated with chemotherapy and surgery: six of the eight appear to be cured.

This study suggests a possible relationship between neurofibromatosis type 1 and the development of a bone sarcoma, the increased risk being estimated at eight times that of the normal population. We recommend that further research into this possible link should be considered.

We undertook a prospective study to evaluate the prognostic significance of the serum levels of vascular endothelial growth factor (VEGF) in predicting the survival of patients with osteosarcoma. The levels were measured by an enzyme-linked immunosorbent assay in 15 patients with osteosarcoma before commencing treatment. The patients were divided into two groups, with a high or a low serum VEGF level, and the incidence of metastases and overall survival rate were compared.

No significant relationship was observed between the serum VEGF levels and gender, age, the size of the tumour or the response to pre-operative chemotherapy. Patients with a serum VEGF > 1000 pg/ml had significantly worse survival than those with a level < 1000 pg/ml (p = 0.002). The serum VEGF level may be useful in predicting the prognosis for survival in patients with osteosarcoma.

We studied the safety of external fixation during post-operative chemotherapy in 28 patients who had undergone distraction osteogenesis (17, group A) or vascularised fibular grafting (11, group B) after resection of a tumour. Four cycles of multi-agent post-operative chemotherapy were administered over a mean period of 14 weeks (6 to 27). The mean duration of external fixation for all patients was 350 days (91 to 828). In total 204 wires and 240 half pins were used.

During the period of post-operative chemotherapy, 14 patients (11 in group A, 3 in group B) developed wire- and pin-track infection. A total of ten wires (4.9%) and 11 half pins (4.6%) became infected. Seven of the ten infected wires were in periarticular locations.

External fixation during post-operative chemotherapy was used safely and successfully for fixation of a vascularised fibular graft and distraction osteogenesis in 27 of 28 patients. Post-operative chemotherapy for malignant bone tumours did not adversely affect the ability to achieve union or cause hypertrophy of the vascularised fibular graft and had a minimal effect on distraction osteogenesis. Only one patient developed osteomyelitis which required further surgery.

We have reviewed the data from our regional Bone Tumour Registry on patients with osteosarcoma diagnosed between 1933 and 2004 in order to investigate the relationship between survival and changes in treatment. There were 184 patients with non-metastatic appendicular osteosarcoma diagnosed at the age of 18 or under. Survival was calculated using Kaplan-Meier curves, and multivariate analysis was performed using the Cox regression proportional hazards model.

The five-year survival improved from 21% between 1933 and 1959, to 62% between 1990 and 1999. During this time, a multi-disciplinary organisation was gradually developed to manage treatment. The most significant variable affecting outcome was the date of diagnosis, with trends in improved survival mirroring the introduction of increasingly effective chemotherapy. Our experience suggests that the guidelines of the National Institute for Clinical Excellence on the minimum throughput of centres for treatment should be enforced flexibly in those that can demonstrate that their historical and contemporary results are comparable to those published nationally and internationally.

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure.

After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site.

The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour.