The purpose of this study was to compare the outcome, complications and survival of the three most commonly used surgical reconstructions of the proximal humerus in adult patients after trans-articular tumour resection. Between1985 and 2005 thirty-eight consecutive proximal humeral reconstructions using either, allograft-prosthesis composite (n=10), osteoarticular allograft (n=13) or a modular tumour prosthesis (n=14), were performed in our clinic. Their mean follow-up was ten years (nine months to 25 years). Of these, twenty-seven were disease free at latest follow-up (Mean follow-up 16.8 years) and ten had died of disease (4.2 years). Complications and implant survival with revision surgery as end-point are presented for the total group of patients, functional scores for surviving patients only. The endoprosthetic group presented the smallest complication rate of 21%, compared to 40% in the allograftprosthesis- composite and 62% in the osteoarticular allograft group. Only one revision was performed in the endoprosthetic group, in a case of shoulder instability. Infection after revision (n=3), pseudoarthrosis (n=2), fracture of the allograft (n=3), and shoulder instability (n=4) were major complications of allograft use in general. Kaplan-Meier-analysis showed a significantly better implant survival for the endoprosthetic group (log-rank p=0.002). At final follow-up the MusculoSkeletal Tumour Society scores averaged at; 72% for the allograft-prosthetic-composite (n=7, mean follow-up 19 years), 76% for the osteoarticular allograft (n=3, 16 years), and 77% for the endoprosthetic reconstruction (n=10, 6 years) groups.Method
Results
In proximal humerus reconstructions, osteoarticular massive allograft (OA) allows a biologic reattachment of tendineous structures of the host providing stability and functional recovery. Allograft-prosthesis composites (APC) are more technically demanding, but functional advantages with new prosthetic design are expected with lower fracture and failure rate with time. We compared the outcome of patients treated with OA reconstruction (group A) and patients treated with an APC (group B) after humerus resection for bone tumours. Thirty six patients treated between 1996 and 2009 were included in the study (18 group A; 18 group B). The diagnosis was a malignant bone tumour in 28 cases, an aggressive benign bone tumour in 6 and a bone metastasis in 2. Three total humerus resections were performed (two in group A and one in group B). Three different type of prosthesis were used (conventional, reverse and resurfacing). In group A, at an average follow-up of 66 months (2-116), 16 patients were continuously disease free. Ten patients (56%) had no complication; in 6 cases (33%) we observed a fracture of the graft and in 3 cases (17%) a pseudoarthrosis. In group B, at an average follow up of 44 months (3-164), 16 patients were continuously disease free. Thirteen patients (72%) had no complication, in 2 cases (11%) stem loosening, in 2 cases (11%) dislocation, in 1 case pseudoarthrosis and in 1 case resorption and detachment of allograft's great tuberosity was observed. Functional outcome was evaluated using MSTS scoring system: a mean score of 24 (13-30) in group A and 23 (15-27) in group B was observed. In our experience, proximal humerus APC showed functional results comparable to OA allograft with lower complication rate. In conclusion, in biologic reconstruction of the proximal humerus, APC seems to provide a more reliable solution than OA allograft at long term
To determine the overall survival of patients with Pelvic Ewing's Sarcoma treated in our unit and to identify prognostic factors in pelvic primaries that could be used to select patients who would most likely benefit from high intensity treatment. Between 1977 and 2009, 80 male and 66 female patients aged 2 to 60 (mean, 18) years with Pelvic Ewing's Sarcomas were retrospectively reviewed from the Royal Orthopaedic Hospital Oncology Service Registry. Treatments included surgery, radiotherapy, chemotherapy, or any of them in combination. Event-free (from presentation to recurrence) and overall (from presentation to death/latest follow-up) survival rates were calculated using the Kaplan- Meier method. Influence of various factors (age at diagnosis, gender, tumour site, metastasis at presentation, surgery (and surgical margins), radiotherapy, and type of treatment on survival was assessed using SPSS 14.0 statistical software.Aim
Method
The use of megaprostheses for knee reconstruction after distal femur resection in young bone sarcoma patients has become popular since early ′80. The authors reviewed their experience with different distal femur megaprostheses in children. Clinico-radiographic evolution in a consecutive series of 113 children, that had implanted below age 15 (range 6-14) a distal femur megaprosthesis in the period 1984-2007, was analized. A modular implant was used in 97 cases with uncemented femoral stem (three different models along the period). The implant presented fixed-hinge joint in 78 cases while rotating-hinge knee was utilized in 19 cases. In 39 cases the fixed-hinge joint had a tibial component with a polished stem to allow the residual growth of proximal tibia; in two cases a mechanically extendable prosthesis was used. A custom-made noninvasive extendable prosthesis with cemented femoral stem and smooth uncemented tibial stem was used in 15 cases since 2002. Radiological and functional results were analysed and a statistical comparison of implant outcome according different stems was obtained.Aim
Method
Improving the quality of clinical and radiologic differential diagnosis of intramedullary tumours of long bones. A database includes clinical and radiologic (X-ray, CT and MRI methods) signs of 106 patients with osteosarcoma (n = 44), chondrosarcoma (n = 31) and giant cell tumour (n = 31). Multivariate analysis of clinical and radiologic characteristics and developing informative set of criteria (decision rule) for the differential diagnosis of osteosarcoma, chondrosarcoma and giant cell tumour were provided with program «ASTA».Aim
Methods
Preoperative serum CRP has been identified as an independent predictor in various malignancies. For osteosarcoma, however, the value of serological markers is unreliable. Aim of this study was to evaluate the prognostic power of preoperative CRP in patients with osteosarcoma. Out of our prospective database, 87 patients with osteosarcoma (43 female, 44 male with an average age of 20.4 years) have been identified with complete documentation of peri-operative CRP-levels, a minimum two year follow-up and after exclusion of concomitant infection, smoking-history or cardio-vascular disease. Pre-operative CRP before tumour resection was correlated with clinical and pathological factors, overall survival and infection rates in an uni- and multi-variate statistical model with and without landmark analysis.Aim
Method
Patients treated with limb salvage surgery for bone sarcomas of the extremities (upper and lower) may have physical disability as a result of treatment. Goal of this study was to evaluate the quality of life after treatment (chemotherapy and conservative surgery) at long term. 208 patients resected for a bone sarcoma and with prosthetic reconstruction (45 in the upper and 163 in the lower limb) were evaluated. Assessment of results was done using the Karnofsky Scale (K.S.). Patients were followed in the clinic and functional results assessed according to the Musculoskeletal Tumour Society (MSTS) system. Moreover the Toronto Extremity Salvage Score questionnaire (TESS) was mailed to 144 patients.Aim
Method
The aim of this study was to investigate the results of a series of cases from a single institution with respect to local disease control and patient survival to determine prognostic factors. Electronic patient records were reviewed on all patients with STS between February 1963 and January 2007. 2445 patients had over 30 types of STS. 1639 (67%) had not received any treatment prior to presentation, however, 770 patients (32%) had undergone a previous attempted excision. Survival analyses were done using Kaplan Meier and Cox regression analyses, however, for prognostic factor analysis, only patients presenting without prior treatment were included.Introduction
Methods
The rising incidence of atraumatic fractures in patients either with Ewing's sarcoma or osteosarcoma years after chemotherapy revealed a growing population of childhood cancer survivors with a decreased bone mineral density (BMD) possibly due to a long-term effect of the chemotherapy. Therefore we started to screen our patients below 50y of age who were treated for bone malignancies between 1994 and 2009. The first series of measurements included 15 patients – eight Ewing's sarcoma, three female and five male, with a mean age of 18y (±13SD), and seven osteosarcoma, two female and five male, with a mean age of 19y(±9SD). We screened the patients for deficits in their bone status using DEXA (dual-energy-x-ray-absorptiometry) to gain the T-and Z-Scores of the proximal femur and the lumbal spine. Additionally we took blood samples for endocrinological analysis and utilised a questionnaire to scan the patient's liefestyle. The mean time between diagnosis and investigation was 95months (±79SD) in Ewing's sarcoma and 105months (±54 SD) in osteosarcoma. The results of the age and gender matched lumbal measurement (Z-Score) of the Ewing's sarcoma patients showed a reduction of the BMD in six cases (6/8), including three times osteopenia (3/8) and two times osteoporosis (2/8). The osteosarcoma patients presented a BMD-decline in four cases (4/7) with two times osteopenia (2/7) and one osteoporosis (1/7). In the proximal femur six Ewing's sarcoma (6/8) and six osteosarcoma patients (6/7) showed a BMD-decrease including three osteopenic (3/8) and one osteoporotic (1/8) Ewing's sarcoma and four osteopenic osteosarcoma (4/7). We found two cases of pathologic fractures (2/15), one Ewing's sarcoma 29 months after diagnosis with a fracture of the distal femur and the proximal Tibia (1/8) and one osteosarcoma with a fractured distal femur after 72 months (1/7). As presented in our case series osteoporosis after chemotherapy is an underestimated long-term effect of the chemotherapeutic treatment. In our series BMD-reduction seems to be independent of tumour-type and chemotherapeutic agent like MTX.
Early diagnosis is assumed to improve patient survival, but whether symptom interval (SI i.e. the period between the onset of the first symptoms signs of the disease and its definitive diagnosis) has significant impact on outcome or not remain unclear. In a series of 575 patients < 21 years of age with soft tissue sarcomas (STS) we investigated the association patterns between SI patient/tumour characteristics or disease outcome. The analysis was based on multivariate models (linear for association's patient/tumour characteristics and Cox's for survival). The SI ranged between one week and 60 months (median 2 months) and tended to be longer the older the patient (i.e. the interval was longer in adolescents than in children) and the larger tumour's size and for tumours located at the extremities and for “non rhabmomio sarcoma” STS (as opposed to rhabmomio sarcomas). A longer SI unfavourably influenced survival (p=0.002): for SI of 1, 12 and 24 months, the 5-year survival for rhabmomio sarcoma was 65%, 46% and 19% respectively. A different pattern of association between SI and survival emerged for different types of STS histology.Methods
Results
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. Retrospective review of a prospective database that was started in 1986 identifying the actual diagnosis. 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 onwardsMethod
Results
Multiple (hereditary) osteochondroma (MO) is a rare autosomal dominant disease. Previous reports show that the risk of a malignant degeneration varies between 5-25%, but these are often combined with data on other cartilaginous diseases. The aim of this study was to establish clinical and radiological parameters that could identify a group of MO patients who are at risk for peripheral chondrosarcoma. A database of 64 MO patients surgically treated between 1980-2009 was established. For 24 patients full radiological (including MRI), surgical and pathological records were complete. This group contained 14 osteochondroma patients and 10 chondrosarcoma patients. Non-parametric tests and Kaplan-Meier survival analysis were used to establish a cartilage-cap thickness cut off point and a volume cut off point.Aim
Methods
Angiosarcoma is a rare complication of breast cancer treatment. In order to define predictors, clinical presentation, and outcome, we characterized a population-based 50-year cohort of angiosarcomas after breast cancer. Clinical data were collected from all females with previous breast cancer who developed angiosarcomas/lymphangiosarcomas on the thoracic wall/upper extremity between 1958 and 2008 in the Southern Swedish health care region.Background
Methods
CT guided percutaneous radiofrequency thermocoagulation is the treatment of choice for osteoid osteomas. Good results with a low complication rate have been shown for spinal lesions. When lesions are within close proximity to neurological structures or if patients have radicular symptoms surgery rather than radiofrequency ablation has been advocated. We present our experience of radiofrequency ablation of spinal osteoid osteomas which are less than 5mm from neurological structures, including those causing radicular symptoms. Data was collected prospectively on all patients with a spinal osteoid osteoma within 5mm of nerve roots or the spinal cord as measured on CT scanning. There were nine patients, five female and four male with a mean age of 15 years. Four tumours were located in the thoracic spine, three in the lumbar spine and two in the cervical spine. The mean distance to the nearest neurological structure was 3mm. Radicular symptoms were present in two patients. The mean number of probe positions used was two. Lesions were heated to 90 degrees for 5 minutes for each probe position. There were two cases of recurrence, both treated successfully with one further procedure each. There were no cases of neurological injury. The two patients with radicular symptoms had full resolution of their symptoms. At a mean follow up of 2 years following treatment all patients are asymptomatic. Radiofrequency ablation can be safely performed to treat osteoid osteomas located within 5mm of neurological structures and has a low rate of recurrence.
To study the efficacy of Zoledronic acid in the treatment of benign osteolytic tumours or tumour like conditions of bone as a therapeutic or as an adjuvant agent 31 patients- 19 female, 12 male, age from 8 yrs to 42 yrs, were treated with intravenous zoledronic acid. In 17 patients (fibrous dysplasia-10, nonossifying fibroma- 4, UBC- 3) zoledronic acid alone was used as a therapeutic agent. In 14 patients (ABC- 3, GCT- 11), it was used as an adjuvant agent after curettage. Four patients presented with pathological fracture. In all patients, 4 mg. zoledronic acid was given at 2 monthly intervals. In 12 adult patients, in addition oral bisphosphonates - alendronate was given weekly for at least 6 months.Aim
Method
Prognostic stratification of patients with non-metastatic osteosarcoma may improve the clinical management and the design of clinical trials. Data from 773 patients [median age 15 years (3-40)] treated at our Institute from 1983 to 2000 with high-dose methotrexate, cisplatin, doxorubicin and ifosfamide (neoadjuvant chemotherapy) were analyzed. After multivariate analysis including age, site, tumour volume (cut-off 200 mL), serum LDH and Alkaline Phosphatase (SAP), histology (osteoblastic and chondroblastic vs others), high LDH and SAP, osteoblastic and chondroblastic histotypes resulted independent prognostic factors of DFS. Patients were grouped according to a score from 0 (absence) to 3 (one to 3 adverse factors). The scoring system was implemented by the addition of PgP expression and grade of chemotherapy-induced necrosis. A score of 0, 1, 2, 3 was given to 14%, 38%, 32% and 16% of patients respectively.10-year DFS was 80% (95%CI 72-89) for score of 0, 58% (95%CI 52-64) for 1, 53% (95%CI 46-59) for 2 and 40% (95%CI 32-50) for 3 (p= 0.001). PgP expression (168 patients) identified patients with 100% probability of DFS (score of 0 and negative PgP) and patients with 18% (95%CI 52-64) DFS (score of 3 and positive PgP). Good (GR) and poor responder (PR) patients had the same probability of DFS in case of score of 0 [GR82% (95% CI 72-91), PR79% (95% CI 65-93)] and score of 3 [GR43% (95% CI 32-55) PR36% (95% CI 21-51)]. Different probability of DFS in case of score of 1 [GR64% (95% CI 57-72) PR47% (95% CI 36-59)] and score of 2 [GR63% (95% CI 55-71) PR36% (95% CI 21-51)]. It is possible to stratify outcomes of patients with non metastatic osteosarcoma of the extremity by means of a simple score based on easily available clinical parameters. This scoring system is worth to be validated on larger series.
In osteosarcoma, local control of the tumour is absolutely critical otherwise the chances of long term survival are <10% and may effectively approach zero. Radiotherapy is used in case of non-resectable tumours. Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation (XRT) by altering numerous molecular pathways. Therefore, we investigated the effect of the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on radiation response in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines. Clonogenic survival, cell cycle analysis, apoptosis and gammaH2AX phosphorylation as a marker of DNA double strand breaks (DSBs) were examined in two OS (KHOS-24OS, SAOS2) and two RMS (A-204, RD) cell lines treated with SAHA alone and SAHA plus XRT, respectively. Protein expression was investigated via immunoblot analysis, cell cycle analysis, measurement of apoptosis and gammaH2AX expression were performed using flow cytometry.Aim
Methods
Neoadjuvant chemotherapy for osteosarcoma improves outcomes for the majority, but if the chemotherapy does not work then the dilemma often arises as to whether to do limb salvage with a marginal (or worse) margin of excision or to do an amputation. If limb salvage is carried out with a close margin, does post operative radiotherapy make any difference? This study aims to address these questions. All patients with limb osteosarcoma, no metastases, a poor response to chemotherapy and either a marginal excision or primary amputation were identified from a prospective database. This group were investigated in terms of overall survival and local control. There were 182 patients in this category of whom 60 had an amputation, 105 limb salvage with marginal margins and 17 with an intralesional margin. Local recurrence (LR) arose in 41% of those with an intralesional margin, 22% of those with a marginal margin and 13% of those with an amputation. Radiotherapy was used in 21 of the 122 patients and the risk of LR was the same as in those who did not have radiotherapy. Neither age nor sex of the patient, size or site of the tumour affected the risk of LR. The overall survival for this group was 42% at 10 years. The survival was best in those with marginal margins (38%) than those with an amputation (28%) and worst for those with an intralesional margin (20%). Survival was worst in those who did develop LR, but no worse than in those having amputationMethod
Results
For many surgeons amputation is the usual treatment in sarcoma of the foot. The aim of our study was to report the functional and oncologic results of treatment in 54 sarcomas of the foot to assess if conservative treatment was acceptable We retrospectively reviewed the records of 54 patients with sarcomas of the foot, aged 6 to 50 (mean 17), 30 females and 26 males. At time of referral, 18 had a local recurrence of a previous inadequate treatment. There were 27 soft tissue sarcomas (STS: 10 synovial sarcomas, 6 rhadomyosarcomas, 1 liposarcomas and 10 others) and 27 bone tumours (16 Ewing's, 8 chondrosarcomas, 3 osteosarcomas). Toes tumours were excluded, 18 tumours involved the metatarsal, 12 the plantar soft tissues, 11 the calcaneum, 3 the talus, 2 the midtarsal bones. Surgery consisted in 19 resection without reconstruction, 21 resections with bone reconstruction, 9 partial amputations of the foot, and 6 trans tibial amputations. In 34 cases surgical margins were adequate (R0), in 13 patients resection was inadequate (9 R1 and 4 R2). In 7 cases the margins were not assessed. After a 5.5 years average follow-up (3m to 17y), 31 patients had no evidence of disease, 8 were in second remission, 4 had an evolutive disease and 11 were deceased. The mean MSTS score was 26/30 (31 cases). In conclusion, a conservative treatment is feasible in metatarsal bones with skin coverage by flap if necessary. In STS adequate margins are difficult to achieve with a high rate of local recurrence. In calcaneus and talus, a conservative treatment is possible in tumours limited to bone after good response to chemotherapy. In other cases conservative treatment is debatable because amputation gives excellent functional results.
The outcome for patients with Ewing's sarcoma recurrence is poor. Local recurrences occur in 8%-25%of these patients. The aim of the study was to analyze the patients who had a local recurrence to identify factors predicting the local recurrence and if it could be prevented A retrospective analysis of 650 patients who had a diagnosis of Ewing's sarcoma treated between 1975 and 2009 at a single institution was performed and 64 patients (10%) who had a local recurrence were identified and analysed. Fifteen patients had metastases at diagnosis.20 patients had chemotherapy and radiotherapy only while 44 had chemotherapy and surgery +/− post op radiotherapy. Thirteen patients who were suitable for post –operative radiotherapy could not receive the treatment due to various reasons like biological reconstruction. The estimated 5 years survival for the patients was 15%. The risk of local recurrence is higher if the tumour is located in the axial skeleton, treatment with chemotherapy and radiotherapy alone [location and size of the tumour precluding surgery]. The risk of local recurrence is higher if the tumour was in the fibula or radius. One out of three patients who have good response to chemotherapy still went on to develop a LR. The use of biological reconstruction and younger age group often resulted in deferral of post-operative radiotherapy. Location and type of treatment can predict LR. Surgery with clear margins and post-operative radiotherapy given when indicated may reduce the incidence of LR.Methods
Results
