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Aims: To investigate whether the oncological outcomes of patients with osteosarcomas in the upper distal extremity are similar to other sites and assess if limb-salvage surgery is safe in this location., Methods: The centre database was used to identify all patients with osteosarcomas in the lower humerus and distally between 1985 and 2012. Patient, tumor, treatment and outcome data was collected., Results: Twenty-six patients were included in this study. There were 9 males and 17 females with a mean age of 33 years (9-90). Seventeen osteosarcomas were located in the forearm bones (65%), six in the distal humerus (23%), and three (12%) in the hand. The three most common sub-diagnoses were parosteal 7/21 (33%), fibroblastic 4/21 (19%) and osteoblastic osteosarcomas 3/21 (14%). 2 patients (8%) had Paget's disease and 19 patients (73%) had high-grade tumors. Local excision was carried out in 12 patients (48%), 4 patients underwent endoprosthetic replacement (16%) and 9 underwent amputation (36%). The overall risk of local recurrence was 4% in our series. The five-year overall survival rate was 67%, with low tumor grade and parosteal type of osteosarcoma being positive predictors of survival., Conclusion: This series has shown that patients with high-grade osteosarcomas of the upper distal extremities have a higher amputation risk than other limb sites but have favorable outcomes with limb-salvage surgery, comparable to other anatomical sites. Parosteal osteosarcomas in particular have a good prognosis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A poor response to chemotherapy (≤ 90% necrosis) for osteosarcomas leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over limb salvage surgery (LSS) with narrow margins in patients who respond poorly to chemotherapy. We only analysed patients with an osteosarcoma of the limb, a poor response to chemotherapy and close margins on LSS (marginal/intralesional) or primary amputation: 360 patients (36 LSS (intralesional margins), 197 LSS (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following LSS with intralesional margins, and 39 (20%) following LSS with marginal margins. There was no local recurrence in patients who underwent amputation. The five-year survival for all patients was 41% (95% confidence interval (CI) 35 to 46), but for those treated by LSS with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by LSS with intralesional margins. Patients who had LSS and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 patients but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over LSS with marginal margins in these patients with a poor overall prognosis., (©2015 The British Editorial Society of Bone & Joint Surgery.)

Aims: The aim of this study was to clarify the clinical features and outcomes of diaphyseal osteosarcoma., Methods: Patients with newly-diagnosed high-grade osteosarcoma occurring in the long bone were eligible for this retrospective study. Clinicopathological information was collected from our database and compared with 36 diaphyseal, 405 proximal and 519 distal metaphyseal, and 14 whole bone osteosarcoma patients. Additionally, case-control study matching by age, gender, site, and metastatic status at diagnosis with 1:3 ratio of 36 diaphyseal to 108 metaphyseal osteosarcomas patients was also conducted., Results: Five-year overall survival and metastasis-free survival of the three groups including diaphyseal, metaphyseal, and whole bone osteosarcoma patients showed significant difference (P = .029 and P = .013, respectively), although there is no difference for the survivals between proximal and distal metaphyseal osteosarcoma patients. Case-control study showed that patients with diaphyseal osteosarcomas had a significantly larger tumour (mean 13.5 cm vs 10 cm, P = .026), and demonstrated higher pathologic fracture rate (28% vs 12%, P = .033), superior 5-year metastasis-free survival (74% vs 40%, P = .0068), and slightly better 5-year overall survival (68% vs 46%, P = .074). Prognostic factor analysis showed that a pathologic fracture significantly decreased the survival of the patients with diaphyseal osteosarcoma., Conclusions: The current study showed that diaphyseal osteosarcoma has distinct clinical features from metaphyseal osteosarcoma having an increased risk of pathologic fractures but with favorable survival outcome., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Limb-salvage surgery plays a major role in the management of patients with osteosarcoma. As prognosis improves, reconstructive options have come under greater scrutiny with regard to their durability and functionality. The advent of computer navigation-guided reconstruction is discussed in detail, along with methods by which resections can be performed more conservatively, thus facilitating less radical reconstruction. The known modalities of reconstruction, namely biological, nonbiological and composite, are described with reference to the most recent literature. We also discuss changes that have been introduced in order to reduce known complication risks, such as infection, in patients with osteosarcoma. Areas requiring further consideration are highlighted.

Background: Excision of a bone tumor requires reconstruction if limb salvage is a priority. Reconstruction with an endoprosthetic implant is preferred in our unit, as the patient typically can return rapidly to full weight-bearing and functional activities. Long-term complications, such as deep infection, aseptic loosening, and mechanical failure of the implants, have led to concerns about the efficacy of reconstruction and the ability to revise failed implants while maintaining limb salvage in the longer term. The purpose of this study was to investigate the survival of endoprosthetic reconstructions in the medium to long term in order to determine the factors associated with their failure., Methods: A consecutive series of 776 patients underwent endoprosthetic reconstruction following resection of a bone tumor at a minimum of ten years prior to this investigation. One hundred and nine children with a so-called growing endoprosthesis were excluded as they often require revision to an adult prosthesis near skeletal maturity. Six patients were excluded because of a lack of adequate follow-up data, leaving 661 patients for analysis. Kaplan-Meier survival analysis of the implant was performed, with implant revision for any cause (infection, local recurrence, and mechanical failure), mechanical failure alone, and amputation used as the end points., Results: The mean duration of follow-up was fifteen years for patients who survived the original disease. Two hundred and twenty-seven patients (34%) had revision surgery because of mechanical failure (116 patients), infection (seventy-five patients), and locally recurrent disease (thirty-six patients). Implant survival at ten years was 75% with mechanical failure as the end point and 58% with failure from any cause as the end point. The limb salvage rate was 84% at twenty years., Conclusions: We believe these medium to long-term results with first-generation endoprostheses are encouraging and justify the continued use of endoprostheses for reconstruction following the excision of a bone tumor.

Background: Children rarely require hip replacement, and therefore very little is known about the most effective procedure for children who require hip replacement after proximal femoral resection for a tumor., Methods: We reviewed the outcome of forty hip replacements in children between two and fifteen years old who had a proximal femoral replacement for malignant disease. Twenty-one children survived the illness and were followed for three to twenty-one years. Cemented acetabular components were used initially to restore hip function, but, in more recent procedures, unipolar replacements and uncemented implants were used., Results: Children who were over the age of eleven years at the time of surgery had a rate of failure (defined as revision of the acetabular component) of 25% at ten years compared with a rate of 75% in younger children. Unipolar replacements in children of all ages failed by ten years, either because of pain or subluxation that led to revision. In children over the age of eleven years, both cemented and uncemented acetabular implants performed well., Conclusions: The preferred method for restoration of hip function in children under the age of eleven years following proximal femoral resection for a tumor remains unclear. We recommend that at the initial hip surgery an attempt should be made to cause as little damage as possible to the acetabulum, but most children will inevitably need revision surgery as they get older. We hope that this study will guide others in their decision-making with regard to this relatively rare condition.

Background: Despite neo-adjuvant chemotherapy osteosarcomas having significant mortality, recent studies have shown survival advantages following infections for some tumour types. This study investigates the effect of post-operative infection in patients treated for osteosarcoma using endoprosthetic replacement and neo-adjuvant chemotherapy., Material and Methods: A consecutive series of 547 patients underwent surgery between 1981 and 2001 for osteosarcoma. Patients were excluded from the study if over 60 years old at diagnosis (n = 14) as they would not routinely receive chemotherapy. Studies showed that 70% of deep infections occur within one year from reconstruction. Therefore landmark analysis was performed; all patients infected after 12 months of reconstruction were excluded (15 patients, 2.7%) and those who died within 12 months from diagnosis due to metastases were excluded (105 patients, 19.2%), leaving 412 patients. Any survival advantage of early infection was analysed by Kaplan-Meier survival analysis from this landmark point., Results: Overall population survival was 65% at 10 years after landmarking. There were 41 patients (10%) who developed an infection within one year of implantation. These patients had significantly better survival (p = 0.017). The 10-year survival for patients with osteosarcoma with infection was 84.5% compared to 62.3% in the non-infected group after landmarking. There was no significant difference in the percentage post-chemotherapy specimen necrosis between the two groups (p = 0.36). Infection was an independent prognostic factor on cox regression analysis., Conclusions: There was evidence for increased survival after deep post-operative infection in osteosarcoma patients, in keeping with other research. The authors feel this warrants further investigation.

The influence of pathological fracture on surgical management, local recurrence and survival was established in patients with high grade, localised, extremity osteosarcoma (n=484), chondrosarcoma (n=130) and Ewing's sarcoma (n=156). Limb salvage was possible in 79% of patients with a fracture compared to 84% of patients without a fracture (p=0.17). No difference in local recurrence was found between fracture and control groups. In univariate analysis, survival in the fracture group was lower than in the control group for osteosarcoma (34% versus 58%, p<0.01) and chondrosarcoma (35% versus 63%, p=0.04), but not for Ewing's sarcoma (75% versus 64%, p=0.80). In multivariate analysis, fracture remained a significant predictor of survival for osteosarcoma, but not for chondrosarcoma, where dedifferentiated subtype appeared to be decisive. Pathological fracture independently predicts worse survival in osteosarcoma, but not chondrosarcoma and Ewing's sarcoma. Limb saving surgery seems safe, if adequate resection margins are achieved.

We identified 42 patients who presented to our unit over a 27-year period with a secondary radiation-induced sarcoma of bone. We reviewed patient, tumour and treatment factors to identify those that affected outcome. The mean age of the patients at presentation was 45.6 years (10 to 84) and the mean latent interval between radiotherapy and diagnosis of the sarcoma was 17 years (4 to 50). The median dose of radiotherapy given was estimated at 50 Gy (mean 49; 20 to 66). There was no correlation between radiation dose and the time to development of a sarcoma. The pelvis was the most commonly affected site (14 patients (33%)). Breast cancer was the most common primary tumour (eight patients; 19%). Metastases were present at diagnosis of the sarcoma in nine patients (21.4%). Osteosarcoma was the most common diagnosis and occurred in 30 cases (71.4%). Treatment was by surgery and chemotherapy when indicated: 30 patients (71.4%) were treated with the intention to cure. The survival rate was 41% at five years for those treated with the intention to cure but in those treated palliatively the mean survival was only 8.8 months (2 to 22), and all had died by two years. The only factor found to be significant for survival was the ability to completely resect the tumour. Limb sarcomas had a better prognosis (66% survival at five years) than central ones (12% survival at five years) (p = 0.009). Radiation-induced sarcoma is a rare complication of radiotherapy. Both surgical and oncological treatment is likely to be compromised by the treatment received previously by the patient.

The prognostic value of alkaline phosphatase (AP) measured before and after chemotherapy, but before surgery was established in a retrospective survey of patients. The patients were 18 years or older, with non-metastatic high-grade osteosarcoma. Pre-chemotherapy AP was available in 89 cases, post-chemotherapy AP in 86 patients, and both in 71 cases. AP was classified as Normal (< 100% upper limit), High (100% < or = AP < 200%) or Very High (AP > or = 200%). Osteosarcoma subtype was predominantly conventional. No correlation was found between subtype and chemotherapy response, local recurrence or survival. Pre-chemotherapy AP was raised more in the osteoblastic subtype. Post-chemotherapy AP and normalisation were the same among different subtypes. AP was not correlated with local recurrence. Normal or High pre-chemotherapy AP correlated with better survival at 10 years (64% and 70%) than Very High pre-chemotherapy AP (37%, P = 0.005). Post-chemotherapy AP correlated with survival (68%, 39% and 25% in the Normal, High and Very High group, P = 0.0007) and response to chemotherapy (P = 0.049). A pre-chemotherapy AP above twice Normal correlated with worse survival. If AP decreased after chemotherapy, but was still raised, survival was better, but still worse than if AP normalised. A raised post-chemotherapy AP predicts poor chemotherapy response.

Thirty-four patients with infected massive endoprostheses had two-stage revision procedures to cure the infection and retain a useful functioning limb. An antibiotic impregnated cement spacer constructed with two cement gun liners and a Kuntscher nail provided temporary stability and also allowed a high dose of local antibiotic concentration. In three patients the infection never was controlled, and one of these patients had a successful second revision surgery. Six other patients had reinfection varying from 14 to 92 months after surgery. Risk factors for reinfection were previous radiotherapy and any additional operative intervention. The overall success rate for controlling infection was 91% at 1 year and 74% at 5 years. Six patients required amputation. The mean functional outcome for the retained limbs using the Musculoskeletal Tumor Society scoring system was 77%. Two-stage revisions seem almost as effective at controlling infection in massive endoprostheses as in conventional joint replacements, particularly if additional surgical interventions can be avoided.

Over a 25-year period we have treated 36 patients with osteosarcoma of the pelvis. Of the tumours, 24 (67%) were primary osteosarcomas and 12 (33%) arose either after irradiation or in association with Paget's disease. Six patients had a hindquarter amputation and 12 were treated by a limb-salvage procedure with intrapelvic excision. The five-year survival rate of all the patients with pelvic osteosarcoma was 18%, while for 17 treated by chemotherapy and surgery it was 41%. The prognosis for patients presenting with metastases or with secondary osteosarcoma was appalling and none survived after 29 months. No patient over the age of 50 years when seen initially survived for a year. Youth and a good response to chemotherapy along with complete surgical excision offer the best chance of cure.

We carried out extensible endoprosthetic replacement of the proximal or total humerus in 18 children aged between six and 12 years, after resection of primary bone tumours mainly for osteosarcoma and Ewing's sarcoma. In 11 patients we performed 44 lengthening procedures, with an average of two per child annually and a mean total extension of 29.9 mm per patient. We were able to achieve lengthening of the operated limb with few complications and a mean functional rating of 79.3% according to the Enneking system. Progressive lengthening of these prostheses does not adversely affect the overall function of the arm, and superior subluxation of the head of the prosthesis has not been a problem.

We reviewed the surgical treatment and oncological results of 40 patients with pathological fractures from localised osteosarcoma of the long bones to determine the outcome of limb salvage in their management. All had had adjuvant chemotherapy. There were 26 males and 14 females with a median age at diagnosis of 18 years (2 to 46) and a median follow-up of 55 months (8 to 175). We performed limb salvage in 27 patients and amputation in 13. The margins of resection were radical in five patients, wide in 26, marginal in six, wide but contaminated in two and intralesional in one. Local recurrence developed in 19% of those treated by limb salvage and in none of those who had an amputation. The cumulative five-year survival of all the patients was 57% and in those treated by limb salvage or amputation it was 64% and 47%, respectively (p > 0.05). Limb-sparing surgery with adequate margins of excision can be achieved in many patients with pathological fractures from primary osteosarcoma without compromising survival, but the risk of local recurrence is significant.

The response to pre-operative adjuvant chemotherapy was assessed with computed tomography (CT) in 41 osteosarcomas of the long bones of the lower limb. Measurements were made of cross-sectional tumour areas and volumes on both the pre- and post-chemotherapy CT examinations. Changes in these measurements were compared with the percentage necrosis determined from examination of the tumour histology from the excised specimen in 39 cases. An increase in the relative size of the tumour (expressed as a ratio of the pretreatment volume) showed a statistically significant correlation with a poor tumour response as judged by the degree of tumour necrosis. Further analysis of the results showed that quantitative assessment of tumour response by CT is able to identify cases with poor response to therapy (negative predictive value = 0.9). This is, however, only achieved with a low specificity (0.5-0.6). These findings are in agreement with other studies of tumour volume changes using MR imaging.

BACKGROUND Resection of pulmonary metastases may be followed by long term survival and now that it is an accepted method of treatment for patients with osteogenic sarcoma indicators of favourable prognosis are needed to aid the assessment of suitability for resection. This study compares the survival rates of patients who did and did not undergo resection of their pulmonary metastases and relates them to prognostic indicators. METHODS The study population was the 43 patients with osteosarcoma who developed pulmonary metastases out of the 111 patients with osteosarcoma treated by the Birmingham bone tumour treatment service during 1977-83. All patients who developed metastases confined to the lungs were considered for resection, thoracotomy being advised for all patients (provided that they were fit enough) who had metastases thought to be resectable even if they were multiple. RESULTS Of the 18 patients who did not have a thoracotomy, 15 died of disseminated disease after a mean interval of eight months; one patient died of cardiomyopathy and two are alive after 26 and eight months. Of the 25 patients who underwent thoracotomy in an attempt to resect metastases, three were found to have inoperable disease and died after a mean interval of 5.4 months from thoracotomy. Overall, after thoracotomy (repeated if necessary) there was a 20% survival at five years from the first thoracotomy. When survival was assessed with respect to the disease free interval and the number and bilaterality of the metastases no significant relationships were found. There was, however, a significant relation between survival and the position of metastases, patients with metastases confined to one lobe of the lung having a mean survival of 29.5 months, compared with 13.7 months in patients with disease in more than one lobe. CONCLUSION Thus patients who had a thoracotomy survived longer from the time of diagnosis of pulmonary metastasis than those not undergoing thoracotomy; metastases confined to one lobe predicted a better prognosis.

Since the inception of the authors' facility, 365 patients with osteogenic sarcoma have been treated. While other facilities were surgically treating patients with primary amputation, this facility attempted limb-salvage surgery. The majority of patients being treated with limb-salvage surgery had the resected bone replaced by a metallic endoprosthetic replacement. The emphasis on conservative surgery led to the development of growing endoprosthetic replacements with the first being used in 1975. The cumulative survival of those patients with Stage 2 osteosarcoma treated at this facility between 1977 and 1984 is 48% at five years.