Introduction

An aneurysmatic bone cyst (ABC) is a benign cystic lesion of bone composed of blood-filled spaces separated by connective septa.

The most common treatment is curettage with or without bone grafting. Curettage with bone grafting and Ethibloc injection therapy have a comparable recurrence rate. Ethibloc is a radiopaque alcohol solution of corn protein which is percutaneously injected in the ABC.

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.

Aim

Assess the oncological and clinical outcomes associated with intralesional curettage, phenol and bone grafting of the lesions.

Aim

To determine whether delayed diagnosis (lapse from initial symptoms to the beginning of treatment) has influence on the possibilities of crossing the physis by the tumour, and/or on the outcome in pediatric patients with high grade metaphyseal osteosarcoma.

Aim

The saddle prosthesis was originally developed for reconstruction of large acetabular defects in hip revision arthroplasty. Later on the saddle prosthesis was also used for hip reconstruction after resection of peri-acetabular tumours. In case of patient survival a long-term good hip function is required of the saddle prosthesis. The goal of this study is the measurement of long-term clinical results of saddle prosthesis after reconstruction of peri-acetabular tumours.

Synovial sarcoma (SS) is rare but increasingly diagnosed and associated with poor prognosis. Primary surgical resection with wide margins and adjuvant radiation-therapy is considered gold standard in treatment of primary SS. Although (Neo)adjuvant chemo- and radiationtherapy are used in the primary treatment of SS, they are not advocated outside a clinical trial setting. In patients with primary SS and pulmonary metastases, (neo)adjuvant chemotherapy is often added to the treatment protocol but it’s effect on overall survival seems limited.

Between 1985 and 2004 33 patients with primary SS were treated in our clinic. Seventeen patients were diagnosed with pulmonary metastases at presentation (9) or during postoperative follow-up (8). Wide resection or focally marginal resection followed by radiotherapy was used as primary treatment for all patients. All primary metastasized patients were treated with adjuvant multi-agent chemotherapy including Isofosfamide. Average survival in this group was 32 months (5 year OS 50%), compared to 60 months in the late metastasized patient-group (2 and 5 year OS 50 and 11%). Wide resection was not related to improved overall survival when compared to marginal margins and additional radiation therapy. In the early metastasized group combined chemo-radiaton therapy provided no significant improvement in overall survival over adjuvant chemotherapy or radiation therapy alone. However additional chemotherapy in the late metastasized group was slightly associated with increased overall survival (5 year OS 0% vs 66%).

Treatment of early pulmonary metastasized SS remains highly dependent of the individual preference of patient and physician. In contrast to the reported prolonged disease free/overall survival of Enneking stage IIA and IIB SS patients, aggressive surgical and chemo-radiation therapy has not yet been associated with improvement of disease free/overall survival in stage III disease. Patients presenting with late pulmonary metastasis might benefit from adjuvant multi-agent chemotherapy treatment.

A retrospective study focusing on long-term follow up of 28 patients with a malignant bone tumour in the distal femur was conducted. Patients with a mean age of 50 (18–90) were clinically and radiologically followed-up for a mean period of 64 months (7–144). Osteosarcoma was the most common primary bone tumour, occurring in 15 patients. The 5-year survival for all patients was 80,9%. At final follow-up, 19 patients were still alive and had a mean follow up of 74,6 months (7–137).

Clinical evaluation was done with the MSTS questionnaire (mean score: 70,0 (26,7–93,3)) and the use of the TESS (mean score: 82,5 (45–99,2) and SF-36 (mean Physical Component Score (PCS): 46,6 (27,1–56,5), mean Mental Component Score (MCS): 53,7 (range 37,0–62,1) was introduced

There were 12 complications: 5 aseptic loosenings, two deep prosthetic infections, two luxations, one prosthetic fracture and two fissures. Six failures were re-operated. An overall prosthetic survival at 5-years of 77,0 % was found. A total of eight (29%) prostheses were considered to have failed after a mean follow up of 27,4 months (0–97). Risk factors in failure of the prosthetics were: non HA-coated stem and top stem-ratio > 1.2. Not length of the endoprosthesis and base stem-ratio. The top-ratio had a mean value of 1,14 (1,00–1,52) and for the four patients with an aseptic loosening the mean top-ratio was 1,23 (1,12–1,51) which was significantly different (p< 0,05 Mann-Whitney U test).

Our results suggest that of the MUTARS endoprosthesis has a good 5-year survival.

The use with a HA coating is preferable. The use of a stem-cortex ratio (> 1.2) at the top of the prosthetic stem can be predictor for aseptic loosening. The addition of the TESS and SF-36 scores give more insight information in how patients undergo their disease: half do not feel disabled.

Sacrococcygeal chordoma is a slow growing, malignant tumour with a clinical poor outcome due to a high local recurrence (LR) rate. Several studies emphasize that margin-free tumour resection is the most important predictor of survival and LR in patients with sacrococcygeal chordoma. However, a high recurrence rate still remains. The purpose of this report is to define the role of postoperative radiotherapy (RT).

15 patients (7 females and 8 males) underwent surgical treatment for sacrococcygeal chordoma between 1981 and 2003. The mean age at surgery was 54 (range 31–70) years. The mean follow up was 8.5 (range 4 – 20) years. Most patients suffered from local swelling and pain; only one patient had a mild urinary continence being the only pre- and postoperative neurological deficit. Mean time of preoperative complaints was 4.5 (range 0.8 – 8) years. In 9 patients an en bloc resection was performed, in 6 patients a subtotal resection was achieved. Most patients with a subtotal resection received RT (5/6 patients) following surgery, patients with en bloc resection only received RT (> 50Gray) after LR (6/9 patients).

After en bloc resection (no initial RT) all patients had local recurrence of the tumour with a mean time to recurrence of 3 (range 0.8 – 13) yrs. Only two patients in the group with subtotal resection had LR after 11 yrs. Six of 9 patients with LR after en bloc surgery received RT after recurrence and had a survival of at least 9 (range 5 – 20) years. There were no major complications. The time to recurrence was significantly longer in the group that received immediate RT after surgery, even after resection with irradical margins. There was no difference in survival between both surgical groups.

Our results suggest that postoperative RT is more important in the prevention of local recurrence than margin-free tumour resection. This supports the strategy to add radiotherapy as a standard adjuvant therapy to tumour resection in patients with sacrococcygeal chordoma.

Giant cell tumour of bone (GCT) is a primary osteolytic neoplasm, histopathologically characterized by osteoclast-like giant cells and clinically characterized by local bone destruction and high recurrence rates. There is a need to identify risk factors for recurrence. In order to reduce the recurrence rate we initiated an international, multicenter, randomised phase II trial with adjuvantzoledronic acid as compared to standard care for high risk GCT patients.

One hundred and sixteen GCT patients, treated at the LUMC from 1971 to 2006, with a minimal follow-up of a year, were retrospectively analysed for the following risk factors for local recurrence: GCT grade III and tumour involvement into soft tissue caused by ingrowth or fracture. Resection was used as treatment in 21 patients (group A), intralesional surgery with cement or adjuvant in 24 (group B) and intralesional surgery with cementation and adjuvant in 71 patients (group C).

GCT recurred in 5% (1/21) in group A. Risk factors were found in 90% of patients without recurrence (18/20). Group B shows a recurrence of 25% (6/24). Risk factors were found in 83% (5/6) of recurring GCTs, compared with 28% in patients without recurrence. In group C, a recurrence rate of 23% (16/71) was found. Risk factors were present in 94% (15/16) of recurrences, compared to 36% (20/55) in patients without recurrence.

Soft tissue involvement and GCT grade 3 and up are risk factors for recurrence in GCT. Recurrence rates are lowest when resection is used. Risk factors may influence the choice of treatment. High risk patients may benefit from resection or systemic treatment with adjuvant therapy.

Chondrosarcomas are notorious for their resistance to conventional chemo- and radiotherapy, indicating there are no curative treatment possibilities for patients with inoperable or metastatic disease. We therefore explored the existence of molecular targets for systemic treatment of chondrosarcoma using kinome profiling.

Peptide array was performed for 4 chondrosarcoma cell lines and 9 primary chondrosarcoma cultures. Acitivity of kinases was verified using immunoblot and active Src- and PDGFR signaling were further explored using imatinib and dasatinib on chondrosarcoma cell lines and primary cultures.

The AKT1/GSK3B pathway was clearly active in chondrosarcoma. In addition, the PDGFR pathway and the Src kinase family were active. PDGFR and Src kinases can be inhibited by imatinib and dasatinib, respectively. While imatinib did not show any effect on chondrosarcoma cell cultures, dasatinib showed a decrease in cell viability at nanomolar concentrations in 3 out of 5 chondrosarcoma cultures. Whereas inhibition of phosphorylated Src (Y419) was found both in responsive and non-responsive cells, caspase-3 related apoptosis was found only in cell line GIST882, suggesting that the mechanism of decreased cell viability in chondrosarcoma by dasatinib is caspase-3 independent.

In conclusion, using kinome profiling we found the Src pathway to be active in chondrosarcoma. Moreover, in the chondrosarcoma cell lines and primary cultures we showed that the inhibitor of the Src pathway, dasatinib, may provide a potential therapeutic benefit for chondrosarcoma patients which are not eligible for surgery.

Giant cell tumors (GCT) of the sacrum have a high recurrence rate, up to 33%. Treatment of Giant Cell Tumors (GCT) of the sacrum has many options. Although curettage is more often performed than partial sacral resection the indications are not well described. Large resection in the sacral area is limited, and adequate local adjuvant therapy potentially damages the nervous system. Therefore the type of surgical treatment of sacral GCT is still under debate.

The purpose of this study was to compare clinical outcome after surgical treatment in GCT of the sacrum using two different surgical techniques: curettage and Extended Cortical Excision (ECE).

Pre-operative embolisation was routinely performed, followed by curettage or PSR followed by reconstruction if indicated. Between 1994–2005 11 patients were treated for GCT of the sacrum. Eight were female, 3 men. The median age was 43.5 (14–66) years. The median follow-up period was 60 (6–156) months. Five patients were eventually treated by ECE. The other patients were operated on using different techniques, mainly curettage and/or adjuvant therapy.

Two patients died disease-related 42 and 6 months after primary treatment, both metastasized. All other patients are alive and currently disease-free. Six patients had a recurrence, after 33 (4–140) months. Three patients had a recurrence twice. Three patients received radiotherapy, 1 as palliative treatment and 2 as (adjuvant) therapy for recurrence. No recurrences were seen after ECE compared to 86% (6/7) after curettage only, and 50% (2/4) after curettage with adjuvant therapy.

Extended cortical excision may improve the recurrence rate in sacral GCT.

Resection of pulmonary metastases has previously been reported to improve outcome in high grade osteosarcoma (OS) patients with pulmonary metastases. In this study factors influencing survival in OS patients with pulmonary metastases were determined.

One hundred ninety seven patients with OS treated at our institution between 1990 and 2008 under the age of 40 were included. Excluded were patients with insufficient follow-up data (n=12) and irresectable primary tumour (n=11). Of the 174 remaining patients, 26 patients had pulmonary metastases at diagnosis and 62 developed pulmonary metastases during follow-up. Twenty-two of 88 patients (25%) also had extra-pulmonary metastases. Almost all patients with primary non-metastatic OS who experienced a relapse within 310 days (first tertile) died of disease, whereas patients with a relapse free interval of more than 310 days (second and third tertiles) have a significantly better overall survival at about 20% (p=0.02).

In total, 56 (63.6%) of 88 patients with pulmonary metastases were treated by metastasectomy. The main reason not to perform metastasectomy was irresect-ability by number and site. Patients with irresectable pulmonary metastases had higher numbers of pulmonary nodules (mean of six vs. three nodules) and more frequent bilateral involvement than patients eligible for surgery (p-values respectively 0.002 and 0.06). Independent risk factors determining survival after metastasectomy in multivariate analysis were male sex (p=0.05), higher numbers of pulmonary nodules (p=0.03) and necrotic metastases (p=0.04). Patients undergoing repeated metastasectomies had a similar chance of survival as patients who underwent metastasectomy once.

This well-defined cohort of patients with extensive follow-up data enabled us to identify important risk factors determining survival in OS patients with pulmonary metastases. Risk factors determining poor survival after pulmonary metastasectomy were male sex, higher numbers of pulmonary nodules and resection of vital metastases. Furthermore, we demonstrate that even after repeated metastasectomies, curation can be achieved.

Enchondromatosis is a non-hereditary disease, characterised by the presence of multiple enchondromas. While Ollier Disease is typified by multiple enchondromas, in Maffucci Syndrome they are combined with haemangioma.

Due to the rarity of these diseases, systematic studies on clinical behaviour providing information how to treat patients are lacking.

This study intends to answer the following questions: What are predictive factors for developing chondrosarcoma? When is extensive surgery necessary? How often patients die due to dedifferentiation or metastasis?

Twelve institutes in eight countries participated in this descriptive retrospective EMSOS-study. 118 Patients with Ollier Disease and 15 patients with Maffucci Syndrome were included. Unilateral localization of disease was found in 60% of Ollier patients and 40% of patients with Maffucci Syndrome.

One of the predictive factors for developing chondrosarcoma is the location of the enchondromas; the risk increases especially when enchondromas are located in the scapula (33%), humerus (18%), pelvis (26%) or femur (15%). For the phalanges, this risk is 14% in the hand and 16% in the feet. The decision whether or not to perform extensive surgery is difficult, especially in patients who suffer multiple chondrosarcomas.

Malignant transformation was found in fourty-four patients with Ollier Disease (37%) and eight patients with Maffucci Syndrome (53%). Multiple synchronous or metachronous chondrosarcomas were found in 15 patients.

Nine patients died (range 21–54 yrs). Seven of them died disease related due to pulmonary metastasis (2 humerus, 2 pelvis, 3 femur). Two patients died from glioma of the brain.

In conclusion, one important predictive factor for developing chondrosarcoma is the location of the enchondromas; interestingly, only patients with chondrosarcoma outside the small bones died of their disease. In this series, no dedifferentiation of chondrosarcoma was seen. A first design flow-chart how to approach chondrosarcoma in patients with Ollier Disease and Maffucci Syndrome is in preparation.

Ollier disease is a rare skeletal disorder. It is characterized by the occurrence of multiple enchondromas with a marked unilateral predominance mainly affecting medulla of the metaphyses and diaphyses of the short and long tubular bones of the limbs, especially the hands and feet. The risk of malignant transformation is suggested to be up to 35%. We hypothesise that Ollier disease is a mosaic condition as it is polyostotic and because of its unilateral predominance. Here we aimed to identify molecular defects in Ollier disease related enchondromas and chondrosarcomas using high resolution single nucleotide polymorphism (SNP) array approach. Affymetrix SNP 6.0 was performed on 67 samples which include 10 blood samples and 3 matched blood-saliva samples as a control; 13 enchondromas and 26 chondrosarcomas of different grades from 30 Ollier patients and normal DNA from 12 Ollier patients for paired comparison.

All samples were divided into three groups: normals, enchondromas and chondrosarcomas. The number of numerical genomic changes in the chromosomes were not different for the enchondromas (p=0.36) while large genomic aberrations were seen in chondrosarcomas as compared to normals (p=0.01). Copy number variation (CNV) analysis showed 95K amplification at 4q13 in 5 out of 13 enchondromas and a 2K deletion at 14q11 in 6 out of 13 enchondromas. Paired loss of heterozygosity (LOH) analysis failed to show LOH in 5 enchondromas at higher resolution. Paired LOH was observed at 3q, 5p, 6p, 6q, 7q, 9p, 12p, 13p and 13q in 7 high grade chondrosarcomas associated with loss of chromosomes.

The results of this study indicate involvement of chromosomes 4 and 14 for the development of enchondromas. We were unable to detect LOH in enchondromas at 1Mb resolution containing approximately 500 SNP probes. High grade chondrosarcomas showed LOH at different chromosomes. In future, we will study LOH and CNV changes at gene level and select candidate genes.

A rotationplasty is a unique surgical procedure used to reconstruct after resection of a tumor of the leg or a congenital defect. This procedure avoids phantom pain, limb length discrepancy and infections or implant related complications. The outcome is unusual for cosmesis but very functional.

Background: Borggreve first described a rotationplasty in Germany in 1930 for a 12 year old patient whose knee was destroyed by tuberculosis. In 1950 Van Nes modified the procedure. Kotz and Saltzer described in 1982 the use of a modified version of a rotationplasty to treat malignant tumors of the distal femur.

Case studies of two such patients will be presented.

A 27 year old man had a non-metastic osteosarcoma of his distal femur at the age of five. He underwent chemotherapy and a rotationplasty. Six years after his operation a correction osteotomy was done. He is doing very well physically and mentally. He graduated business studies, went yearly on Alpine skiing on two legs, likes jogging and perceives no limitations in his life (MSTS, TESS, SF-36).

Although is said that rotationplasty had a poor cosmesis and poor psychosocial acceptance, this is not our experience.

In both Enchondromatosis (EC) and Multiple Osteochondromas (MO), multiple benign cartilaginous tumours occur, which have a severely increased risk of malignant progression. Preventing new tumor formation and malignant progression would benefit the prognosis of these patients. A protective effect of selective Cox-2 inhibitor celecoxib, has been suggested against development and growth of colorectal cancer in familial syndromes. At last year’s EMSOS meeting we reported on expression of Cox-2 in 37% (central) – 46% (peripheral) of conventional chondrosarcomas. mRNA levels of EC related tumours were slightly higher than the solitary tumours. Celecoxib treatment of the chondrosarcoma cell lines resulted in a 3 fold decrease of PGE2 levels already at 5 μM. A significant decrease in proliferation was found at 10 μM in OUMS27 and at 25 μM in SW1353 and CH2879 compared to DMSO controls.

For the present study we assessed the (prophylactic) effect of celecoxib on chondrosarcoma growth in vivo using a xenograft model of immunoincompetent nude mice which were injected with cell line CH2879 subcutaneously. Tumour volume was measured during 8 weeks. Celecoxib serum levels were determined by HPLC. Expression of proliferation marker Ki-67 and Cox-2 was assessed by IHC.

Our in vivo results also showed a beneficial effect of high dose prophylactic celecoxib treatment. Tumour volumes were negatively correlated with celecoxib serum levels (r2=0.152). However, at the end of pubertal growth of the mice, a catch-up tumour growth was observed, resulting in the absence of differences in tumour volume between control and treatment groups. Accordingly, proliferation marker Ki67 was higher expressed in the treated groups at sacrifice.

This suggests that there is no role for celecoxib in the treatment of adult chondrosarcoma patients. Celecoxib treatment of younger patients, especially to prevent formation of new tumours in EC and OC patients, might be beneficial, however more research is necessary.

Limb-sparing surgery has become the preferred surgical treatment of malignant bone tumours of the knee. In patients with intra-articular extension of their tumour, extra-articular limb sparing surgery can prevent the knee from amputation. In a retrospective study between January 1985 and December 2007, we performed 34 extra-articular tumour resections of the knee-joint for a bone- or soft tissue tumour in the distal femur or proximal tibia with (suspect) intra-articular tumour extension into the knee on MRI. Contra-indications were extension of the tumour into the extensor mechanism and/or tumour involvement of the neurovascular bundle. Osteosarcoma (23/34) was the most common primary malignancy. Mean age was 36 years (17–70) and the mean follow up was 9 years (1–19).

Patient survival rates at 5 years and 10 years are 78% and 58% respectively, mean patient survival was 47 months (8–211). In 12 (35%) patients, the primary implanted prosthesis failed during follow up. Prosthetic survival rates including minor revision surgery were 63% at 5 years and 36% at 10 years. Six (18%) patients had local recurrence of their malignancy, 5 of them in the popliteal fossa. Local recurrence was significantly correlated with marginal margins (P< 0.05). Fifteen patients had major complications (44%) mainly deep infection in proximal tibia resections and aseptic loosening in distal femur resections. Aseptic loosening was significantly correlated with non HA-coated stems (P< 0.05). Functional outcome scores according to MSTS (mean 81, (65–93)) and TESS (mean 85, (56–98)) of survivors are good.

Our results suggest that extra-articular tumour resections of the knee-joint can provide a functional endoprosthesis and can be an alternative for primary amputation. However it is a technical demanding procedure with acceptable local recurrence and high complication rates in patients with, in general, poor survival.

Purpose: Surgery is the only treatment option for chondrosarcoma grade I. Because this cartilage tumour is found by coincidence, patients feel unsafe, are anxious and very emotional. The purpose of this study was to evaluate the psychological and social impact of a chondrosarcoma grade I and to optimize the care of these patients.

Patients and methods: Eighty-two patients with a mean age of 50 years (22 – 80), who underwent surgery because of a chondrosarcoma grade I between 1990 and 2007, participated in this retrospective multi-method study. Assessment followed using, the Short Form-36, the MSTS and a special developed semi-structured questionnaire. The mean follow-up time was 4,8 year. 66 patients had a curettage, fenolisation and bonegraft. Sixteen patients had a resection. Five of them underwent a reconstruction with an allograft and another five a reconstruction with prosthesis.

Results: The majority of the patients (77%) were satisfied with our information. For mortgage and life/health insurance there were consequences in 18% of the patients. The SF-36 displayed slight lower scores in all domains except for mental health. Satisfaction with the operation is connected to emotional acceptance.

Conclusions: For patients afflicted by chondrosarcoma grade I the psychological impact is enormous. Three-quarter of the patients think often about the diagnosis and 40% was concerned about the waiting time before operation. To a lesser extent, patients were concerned about the impact of the chondrosarcoma on their lives. Within both domains, psychological as well social, there is a task for the nurse practitioner or a social worker in improving care of these patients. The extent of the surgical procedure does not influence patient satisfaction. The emotional acceptance of the disease decides the level of patient satisfaction.