[Bone and soft tissue tumours in children : Proposal for a rational diagnostic approach]. / Knochen- und Weichteiltumoren im Kindesalter : Vorschlag für ein rational-diagnostisches Vorgehen.

CLINICAL/METHODOLOGICAL ISSUE: Bone and soft tissue tumours are often incidental findings in children. Because they are usually benign tumours, nonspecialised radiologists generally have little experience in the diagnosis and differentiation from malignant tumours. Various imaging techniques are used in the diagnosis of skeletal tumours. STANDARD RADIOLOGICAL METHODS: Imaging techniques used to evaluate bone and soft tissue tumours include sonography, computed tomography (CT) and magnetic resonance imaging (MRI). METHODOLOGICAL INNOVATIONS: An algorithm to determine malignancy of bone and soft tissue tumours in children is proposed. PERFORMANCE: By using the presented algorithms, further diagnostic procedures such as biopsies can be avoided in the majority of children with bone and soft tissue tumours. Aggressive bone lesions and unclear soft tissue tumours are guided to biopsy to confirm diagnosis. ACHIEVEMENTS: The algorithms presented are based on the proposals of European professional societies and have been adapted by the authors for use in children and adolescents. PRACTICAL RECOMMENDATIONS: In the clarification of soft tissue tumours, sonography is the first diagnostic tool; depending on the sonographic findings, MRI is the technique for further clarification. Biopsy confirmation of the diagnosis in unclear cases or in cases of probable malignancy should be carried out in a paediatric oncology centre.

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid.

Recent findings link increased expression of the structurally complex 'b' pathway gangliosides GD1b, GT1b, GQ1b (CbG) to a favourable clinical and biological behaviour in human neuroblastoma (NB). Seeking a model to probe these observations, we evaluated four human NB cell lines. Very low CbG content (4-10%) in three of the four cell lines (LAN-5, LAN-1, SMS-KCNR) reflected the ganglioside pattern observed in the most aggressive NB tumours. Pharmacological alterations of complex ganglioside synthesis in vitro by a 5-7 day exposure to 5-10 microM retinoic acid, which is employed in maintenance therapy of disseminated NB, included markedly increased (i) relative expression of CbG (6.6+/-2.0-fold increase, P=0.037), (ii) relative expression of the analogous 'a' pathway gangliosides, termed CaG (6.4+/-1.4-fold increase in GM1a and GD1a; P=0.010), and (iii) total cellular ganglioside content (2.0-6.3-fold), which in turn amplified the accumulation of structurally complex gangliosides. Substantial increases (2.7-2.9-fold) in the activity of GD1b/GM1a synthase (beta-1,3-galactosyltransferase), which initiates the synthesis of CbG and CaG, accompanied the all-trans retinoic acid (ATRA)-induced ganglioside changes. Thus, increased CbG synthesis in NB cell lines is attributable to a specific effect of ATRA, namely induction of GD1b/GM1a synthase activity. Since the shift towards higher expression of CbG and CaG during retinoic acid-induced cellular differentiation reflects a ganglioside pattern found in clinically less-aggressive tumours, our studies suggest that complex gangliosides may play a role in the biological and clinical behaviour of NB.

Intracranial manifestation of osteosarcoma.

Involvement of the central nervous system in osteosarcoma is uncommon. These neoplasms are most often located at the metaphyses of tubular bones and rarely in flat bones of vertebra, ribs, pelvis, facial bones, or skull. Tumors of the latter bones may obviously spread into the cerebrum. Osteosarcomas primarily metastasize hematogenously to the lungs. Bone, lymph node, or brain metastases are mostly seen following or concomitantly with pulmonary metastatic disease. However, there are single cases of primary osteosarcoma of the brain parenchyma without bone association or tumor manifestation at other locations. Three illustrative cases highlight the diversity of the clinical presentation of cerebral osteosarcoma: a 22-year-old man with multiple brain metastases following late pulmonary relapse of an osteosarcoma of the tibia, a 31-year-old woman with an osteosarcoma of the left anterior cranial fossa arising from the skull base, and a 78-year-old man presenting with primary osteogenic sarcoma of the left frontal cerebral hemisphere. According to the current literature, 10-15% of all osteosarcoma patients experiencing relapse may beat risk for central nervous system metastases. To the authors' best knowledge, there are 11 cases of primary intracerebral or meningeal osteogenic sarcoma, including this case report, without any skeletal attachment.

Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours.

As the systemic administration of etoposide is effective in the treatment of relapsed and metastatic brain tumours, a pilot trial was designed to study the feasibility of intraventricular administration of etoposide in such patients. 14 patients aged 2.1 to 33.2 years were treated with intraventricular etoposide simultaneously with either oral or intravenous chemotherapy with trofosfamide or carboplatin and etoposide. In 59 courses (1-12/patient) 0.5 mg etoposide was administered daily via an indwelling subcutaneous reservoir for 5 consecutive days every 2-5 weeks over a period of 0-11 months. During 15 courses in 5 patients serial CSF samples were obtained and etoposide levels were determined by reversed-phase HPLC. Side effects included transient headache and bacterial meningitis, each during 2 courses. Pharmacokinetic data analysis in the CSF (11 courses, 4 patients) revealed a terminal half-life of 7.4+/-1.2 hours and an AUC of 25.0 +/- 9.5 microg h ml(-1)(mean +/- standard deviation). The volume of distribution at steady state and total clearance exhibited a large interindividual variability with mean values of 0.16 l and 0.46 ml min(-1)respectively. Intraventricularly administered etoposide is well tolerated. CSF peak levels exceed more than 100-fold those achieved with intravenous infusions. Further studies should be focused on optimizing the dose and schedule and on determining the effectiveness of intraventricularly administered etoposide.

Activation-dependent expression of the insulin-like growth factor binding protein-2 in human lymphocytes.

The expression of the insulin-like growth factor binding protein-2 (IGFBP-2) was assayed in mononuclear cells originating from different organs of the immune system. All mononuclear cells studied did express IGFBP-2, but the expression level was found to be dependent on the cell type and origin of the cell. T cells showed a higher expression of IGFBP-2 mRNA than did B cells, and CD34+ stem cells expressed IGFBP-2 mRNA at a high level. Expression was highest in bone marrow and thymus. Stimulation of peripheral mononuclear cells resulted in a marked increase of IGFBP-2 mRNA and also intracellular IGFBP-2, as analysed by fluorescence staining. This increase parallels the increase of other known T-cell activation markers. Furthermore, the increase of intracellular IGFBP-2 seems to precede T-cell blast formation and all T cells in active phases of the cell cycle have high levels of IGFBP-2. Our results provide a basis for further investigations on the contribution of the IGF-system to the regulation of T-cell proliferation and differentiation. IGFBP-2, in particular, may have an important influence in the regulation of T-cell activation and proliferation.

On the down-regulation of cross-bridges occurring as changes in the cycling rate during tonic smooth muscle contractions.

As regards cross-bridge down-regulation, the following statements may summarize the results of our experiments: 1) The time course of cross-bridge down-regulation is the initial high turn-over rate followed by a continuous retardation without any distinct loss in force generation. These mechanisms allowed a rapid force development and an improvement in force maintenance. 2) Cross-bridge down-regulation was seen in the tracheal preparation of both the rat and the guinea pig. As indicated by the greater time constants of the post-vibration force recovery, the cross-bridge cycling rate seems to be distinctly lower in the guinea pig than in the rat trachea. 3) Cross-bridge down-regulation only occurs in smooth muscle preparations with intact cell membranes. This result would seem to hint that the sarcoplasmatic calcium concentration and/or the intactness of the cell membrane might be essential for producing cross-bridge down-regulation. 4) The recovery from cross-bridge down-regulation requires a rest period of more than 10s. The cross-bridges remain down-regulated during this time even after an increase in the sarcoplasmatic calcium concentration which was induced by a subsequent stimulus. This result indicates that changes in the sarcoplasmatic calcium cannot explain all the problems arising during cross-bridge down-regulation.