Papers by Antonie Taminiau
Orphanet Journal of Rare Diseases, 2011
Background Ollier disease is a rare, non-hereditary disorder which is characterized by the presen... more Background Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown. Methods We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis using Affymetrix SNP 6.0 array on 37 tumours of 28 Ollier patients in combination with expression array using Illumina BeadArray v3.0 for 7 ECs of 6 patients. Results Non-recurrent EC specific copy number alterations were found at FAM86D, PRKG1 and ANKS1B. LOH with copy number loss of chromosome 6 was found in two ECs from two unrelated Ollier patients. One of these patients also had LOH at chromosome 3. However, no common genomic alterations were found for all ECs. Using an integration approach of SNP and expression array we i...
Journal of Cellular and Molecular Medicine, 2009
Chondrosarcoma of bone is a malignant cartilage-forming tumour that is notorious for its resistan... more Chondrosarcoma of bone is a malignant cartilage-forming tumour that is notorious for its resistance to conventional chemotherapy and radiation therapy. The majority of tumours arise in the medullar cavity of bone and are designated primary central chondrosarcomas (80-85%) [1]. For Ͻ 1% of chondrosarcomas, there is clinical evidence that they arose secondary to a pre-existing (benign) enchondroma [1, 2]. Enchondromas occur mostly as solitary lesions, although they may occur as multiple lesions in the context of non-hereditary enchondromatosis (Ollier disease). Chondrosarcomas are histologically divided into three grades, which is currently the only objective predictor of metastasis. While grade I tumours rarely metastasize and the 10-year survival rate is 83%, patients with grade III tumours develop metastatic disease in up to 71% of the cases and the 10-year survival rate decreases to 29% [3]. Marginal or intralesional excision of tumours can result in local recurrence. Thirteen percent of recurrent chondrosarcomas are of a higher grade than the primary tumour [4]. Currently, surgical removal of the tumour is the only option for curative treatment. There is no treatment to offer patients with metastatic disease or inoperable tumours in the extremities or pelvis. Elucidating the molecular background of high-grade chondrosarcomas and the involved pathways that lead to tumour Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro
Journal of Bone and Joint Surgery - British Volume, 2008
Surgery is considered to be the most effective treatment for cartilaginous tumours. In recent yea... more Surgery is considered to be the most effective treatment for cartilaginous tumours. In recent years, a trend has emerged for patients with low-grade tumours to be treated less invasively using curettage followed by various forms of adjuvant therapy. We investigated the potential for phenol to be used as an adjuvant. Using a human chondrosarcoma-derived cartilage-producing cell line OUMS-27 as an in vitro model we studied the cytotoxic effect of phenol and ethanol. Since ethanol is the standard substance used to rinse phenol out of a bone cavity, we included an assessment of ethanol to see whether this was an important secondary factor with respect to cell death. The latter was assessed by flow cytometry. A cytotoxic effect was found for concentrations of phenol of 1.5% and of ethanol of 42.5%. These results may provide a clinical rationale for the use of both phenol and ethanol as adjuvant therapy after intralesional curettage in low-grade central chondrosarcoma and justify further ...
Genes, Chromosomes and Cancer, 1999
Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarc... more Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of a hereditary or sporadic exostosis (peripheral chondrosarcoma). Loss of heterozygosity (LOH) was studied by microsatellite analysis at the loci harboring the EXT genes (implicated in hereditary multiple exostoses), the EXT-like genes, and at 9p21, 13q14, 17p13, and chromosome 10. Nineteen of 20 peripheral chondrosarcomas showed LOH at all loci tested, while only 3 of 12 central chondrosarcomas exhibited LOH, restricted to 9p21, 10, 13q14, and 17p13. LOH at 9p21 did not appear to involve the CDKN2A gene, as assessed by SSCP analysis. DNA flow cytometry demonstrated a wide variation in the ploidy status in peripheral chondrosarcomas (DNA indexes, 0.56-2.01), whereas central chondrosarcomas were predominantly peridiploid. Near-haploidy found in peripheral chondrosarcomas could explain part of the high LOH percentages. Ki-67 immunohistochemistry suggested a higher proliferation rate in peripheral chondrosarcomas. Our results indicate that peripheral chondrosarcomas, arising secondarily to an exostosis, may obtain genetic alterations during malignant transformation, with subsequent genetic instability as demonstrated by a high percentage of LOH and a wide variation in ploidy status. In contrast, peridiploidy and a low percentage of LOH in central tumors suggest that a different oncogenic molecular mechanism may be operative.
Hereditary cancer in clinical practice, Jan 15, 2004
Multiple Osteochondromas is an autosomal dominant disorder characterised by the presence of multi... more Multiple Osteochondromas is an autosomal dominant disorder characterised by the presence of multiple osteochondromas and a variety of orthopaedic deformities. Two genes causative of Multiple Osteochondromas, Exostosin-1 (EXT1) and Exostosin-2 (EXT2), have been identified, which act as tumour suppressor genes. Osteochondroma can progress towards its malignant counterpart, secondary peripheral chondrosarcoma and therefore adequate follow-up of Multiple Osteochondroma patients is important in order to detect malignant transformation early.This review summarizes the considerable recent basic scientific and clinical understanding resulting in a multi-step genetic model for peripheral cartilaginous tumorigenesis. This enabled us to suggest guidelines for clinical management of Multiple Osteochondroma patients. When a patient is suspected to have Multiple Osteochondroma, the radiologic documentation, histology and patient history have to be carefully reviewed, preferably by experts and if ...
Surgical Oncology, 2012
To systematically review published studies comparing Quality of Life (QoL), functional ability an... more To systematically review published studies comparing Quality of Life (QoL), functional ability and/ or physical activity between different surgical interventions due to a malignant bone tumour of the leg. Methods: A systematic literature search, covering the years 2000e2010 was performed using the PubMed, Embase, Web of science and Cochrane databases. Studies were included if they described and statistically compared QoL, functional ability and/or physical activity of at least two surgical interventions for lower extremity bone cancer. In addition, the methodological quality of the selected studies was evaluated by using a 24-point scale. Where appropriate, a qualitative analysis or meta-analysis was performed. Results: The search strategy resulted in a list of 246 citations. Based on titles and abstracts 50 full-text articles were selected, of which 13 articles describing 12 studies, were finally included. Overall, the methodological quality of the studies was moderate. Studies were heterogeneous with respect to their categorisation of surgical interventions, average age of patients and average duration of follow-up. Overall, results regarding differences between ablative and limb-sparing surgery varied largely. Metaanalysis was considered to be not appropriate due to clinical heterogeneity, methodological differences and flaws. Conclusion: Twelve studies comparing the outcomes of QoL, functional ability and physical activity between limb-sparing and ablative surgery groups were identified, with an overall moderate methodological quality. Their largely varying outcomes suggest that no general conclusions on the advantage of either limb-sparing or ablative surgery in patients with malignant bone tumours of the lower extremity can be drawn.
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Nederlands tijdschrift voor geneeskunde, 2010
Two male and one female patient, aged 64, 70 and 51 respectively, were surgically treated for pat... more Two male and one female patient, aged 64, 70 and 51 respectively, were surgically treated for pathological fracture of the proximal femur without preoperative biopsy. In contrast to their benign radiological diagnosis, all three patients were finally diagnosed as having a malignant primary bone tumour. The proximal femur is the primary location of pathological fractures in the appendicular skeleton. Metastases to bone are the most common cause of a destructive lesion of the skeleton in an adult. Although rare, a primary bone tumour must be included in differential diagnosis of a pathological fracture. A systematic diagnostic strategy is critical to avoid complications that make curative treatment impossible. A solitary bone lesion seen on radiography should never be assumed to be a bone metastasis. Without further diagnostic research, surgical treatment for a pathological fracture should never be commenced before a definitive diagnosis is made.
Pediatric Blood & Cancer, 2009
Background. To examine the practical applicability, internal consistency, and validity of the Bt-... more Background. To examine the practical applicability, internal consistency, and validity of the Bt-DUX, a disease-specific Health Related Quality of Life (HRQoL) instrument. The Bt-Dux was developed to examine patients' individual values of their life after a malignant bone tumor of the lower extremity at four domains (cosmetic, social, emotional, and functional). Procedure. Patients were eligible for this cross-sectional, multicenter study if they underwent surgery for a malignant tumor of the leg in a period ranging between 12 and 60 months before the recruitment. Assessments included: Bt-DUX, Toronto Extremity Salvage Score (TESS) Short Form (SF)-36, TNO-AZL Questionnaire for Adult's Quality of Life (TAAQOL), and TNO-AZL Children's Quality of Life Questionnaire (TACQOL). Results. Seventy-two patients (35 male, 37 female), mean age 17 (SD 4) years were included. Limb sparing surgery took place in 32 patients and ablative surgery in 40 patients. The Bt-DUX was completed in less than 5 min and easy to comprehend. The mean Bt-DUX score was 69.8 (SD 15.5), with Cronbach's alpha being 0.92. Domain-total correlations ranged between 0.84 and 0.88 (P < 0.01). Correlations between Bt-DUX Total score and TESS, SF-36 Physical and Mental Component Summary scales and selected TACQOL and TAAQOL scores were statistically significant (P < 0.05), except for the social scale of the TACQOL. The Bt-DUX was able to discriminate between patients with higher and lower TESS scores (P < 0.05). Conclusion. The Bt-DUX was found to be a practical and valid instrument. Its added value compared with existing HRQoL measures needs to be further established.
Skeletal radiology, 1994
A uniform classification of response to chemotherapy is essential to allow comparison of local ef... more A uniform classification of response to chemotherapy is essential to allow comparison of local effect and ultimate prognosis between different therapy schedules. We define a histological grading system for assessment of the response to chemotherapy in Ewing's sarcoma, based on the amount and architectural pattern of residual histologically viable-appearing tumour, the preferential sites of minimal residual tumour and the amount of tumour necrosis. Twenty-six consecutive patients with a biopsy-proven Ewing's sarcoma were treated with chemotherapy prior to surgery. The effect of chemotherapy was evaluated microscopically on the specimens obtained after surgery. Response to chemotherapy was classified as minimal or no effect (< 10% tumour necrosis), moderate effect (solid areas of remnant viable tumour), minimal residual disease, and no evidence of disease (100% tumour necrosis or well-vascularized fibrous tissue). The subperiosteal area in particular and, less frequently, s...
Skeletal radiology, 1994
Magnetic resonance (MR) imaging was performed in 26 patients with Ewing's sarcoma of bone pre... more Magnetic resonance (MR) imaging was performed in 26 patients with Ewing's sarcoma of bone preceding and following neoadjuvant chemotherapy, to assess tumour response non-invasively prior to surgery. T1- and T2-weighted spin echo images were obtained. Changes including intra- and extramedullary signal intensities, tumour demarcation, tumour volume and the appearance of residual extramedullary tumour were compared with histopathology of the resected specimens. Reduction of tumour volume was significantly higher in good responders. Other single parameters did not correlate with histologic tumour response. However, when several MR parameters summarized in a classification system were combined, a positive correlation with histopathologic response was found. A limited decrease of tumour volume (< 25%) and/or residual soft tissue mass following chemotherapy correlated with a poor response. An inhomogeneous, well-defined cuff of abnormal tissue encircling the bone and/or radiological...
Sarcoma, 1997
Purpose. To report the outcome of 37 patients with metastatic osteosarcoma entered into a large r... more Purpose. To report the outcome of 37 patients with metastatic osteosarcoma entered into a large randomized trial (EOI 80831/MRC B002) comparing two different regimens of chemotherapy in patients with osteosarcoma.Methods. Patients with biopsy-proven osteosarcoma localized and metastatic, age 40 years or younger, were randomized to receive either two-drug treatment with doxorubicin/cisplatin (DOX 25 mg m−2day−1× 3 + DDP 100 mg m−2on day 1 q 3 weeks × 6 courses) or three-drug treatment comprising high-dose methotrexate (HDMTX 8 mg m−2administered every412weeks × 4 courses) given 10 days before DOX/DDP.Results. Twenty-four patients with metastatic disease received the two-drug arm treatment and 13 received three-drug treatment. Despite chance imbalance in numbers, there were no major differences in age, sex, primary site or performance status. Baseline alkaline phosphatase (AP) was elevated more frequently (96 vs 42%) in the two-drug arm. Twenty-one of 24 patients in the two-drug arm a...
European Instructional Lectures, 2011
European Surgical Orthopaedics and Traumatology, 2014
ABSTRACT Cartilaginous tumours form the second largest group of primary bone tumours. They all sh... more ABSTRACT Cartilaginous tumours form the second largest group of primary bone tumours. They all share the characteristic production of chondroid matrix by tumour cells. Cartilage tumours range from completely benign lesions to highly malignant and are sub-divided by location in intramedullary, central and surface or peripheral sites. Most cartilage lesions can be diagnosed using plain radiographs or MRI. Differentiation between benign and malignant can be very difficult, for example enchondroma versus low-grade chondrosarcoma, osteochondroma versus peripheral chondrosarcoma and chondroblastoma versus clear-cell chondrosarcoma. Biopsy of malignant lesions can be false negative due to sample error as most cartilage lesions have grades of malignancy and can even present benign sections. Benign lesions are best left untouched if free of symptoms and radiologically inactive such as enchondroma of the phalanges. En bloc resection of osteochondroma including the pseudocapsule is curative and results in a very low recurrence rate. Malignant cartilage tumours, if low-grade central chondrosarcoma of the long bones, can be treated with intralesional surgery in combination with some adjuvant (phenol, cryosurgery). High grade chondrosarcoma (including clear-cell chondrosarcoma) and all chondrosarcoma of the axial skeleton should be surgically resected with wide margins with an intermediate risk of local recurrence.
New Developments for Limb Salvage in Musculoskeletal Tumors, 1989
The Oncologist, 2011
Background. Enchondromatosis is characterized by the presence of multiple benign cartilage lesion... more Background. Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. Method. A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Results. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p ؍ 0.00l). Conclusions. Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with
Spine, 2000
Two cases are reported in which an osteoid osteoma of the lumbar spine was treated with CT-guided... more Two cases are reported in which an osteoid osteoma of the lumbar spine was treated with CT-guided thermocoagulation. To review an alternative and minimally invasive treatment for spinal osteoid osteomas. Surgical resection of a spinal osteoid osteoma can, depending on the location, be a formidable undertaking. Bone scintigraphy can be helpful in intraoperative identification. More recently, resection through a computed tomography-guided drill hole was found to minimize exposure. Using a thermocoagulation probe, as has been used in osteoid osteoma of the extremities, may be technically easier and cause less morbidity. With the patient under general anesthesia, a bone biopsy cannula was introduced into the center of the osteoid osteoma. Material was subjected to histologic examination. A thermocoagulation probe was then inserted and heated to 90 C for 4 minutes. The two patients were kept overnight for observation. Both patients had complete pain relief and no evidence of recurrence after 2 years&#39; follow-up. There were no complications. Scoliosis resolved in one patient and persisted in the other. Percutaneous computed tomography-guided thermocoagulation is a minimally invasive and technically straightforward method to achieve ablation of a spinal osteoid osteoma. No complications were encountered in these two patients. Future research should focus on the safety of thermocoagulation, especially cephalad to the level of the conus medullaris.
Skeletal Radiology, 1996
Objective. The objective of this study was to assess the effectiveness of conventional radiograph... more Objective. The objective of this study was to assess the effectiveness of conventional radiography in predicting histopathologic response in patients with osteogenic sarcoma who were treated with preoperative chemotherapy. Design and patients. The radiographs of 22 patients with an osteogenic sarcoma, taken before and after neoadjuvant chemotherapy, were reviewed. Tumour location, size, radiographic appearance, margination, cortical destruction and periosteal reaction
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Papers by Antonie Taminiau