Malignant bone tumors in children: osteosarcoma

Osteosarcoma is a rare malignant tumor of bone that produces osteoid. Most tumors arise in the metaphyses of long bones. At least 80 per cent of patients have subclinical metastases at diagnosis. Successful management of osteosarcoma requires surgical control of the primary tumor and chemotherapeutic control of systemic metastases. Wide resection of primary tumor is often compatible with limb-sparing surgery. Multiagent chemotherapy has significantly enhanced disease-free survival. Osteosarcoma metastasizes to lung and other bones. Aggressive surgical resection can sometimes control pulmonary metastases; bony metastases are almost always followed by death.     

Malignant bone tumors in children: Ewing's sarcoma

Ewing's sarcoma is a rare, malignant, small, round-cell tumor of bone. Most tumors arise in the diaphyses of long bones, but any bone can be involved. Chemotherapy is essential for long-term survival. Multiagent protocols are superior to single-agent therapies, but the ideal regimen has not been established. Both radiation therapy and surgery have been employed for local control of primary tumors. Control with either modality is significantly better when used in conjunction with effective chemotherapy. Patients who present with metastatic disease or pelvic primaries have a worse prognosis. Autologous bone marrow transplantation may improve disease-free survival for this group.     

Autologous bone marrow transplantation in solid tumors in children

Seven children with advanced solid tumors (2 rhabdomyosarcomas, 2 Ewing's sarcomas, 1 astrocytoma, 1 T cell lymphoma and 1 neuroblastoma) received high dose chemotherapy and/or radiotherapy followed by autologous bone marrow transplantation. Four patients achieved complete remissions, two had partial remissions, and one was no response. Side effect of autologous bone marrow transplantation was few compared with that of allogeneic bone marrow transplantation in which graft versus host reaction, profound posttransplantation immunodeficiency and interstitial pneumonitis were unavoidable. In this report methods of bone marrow cryopreservation and elimination of tumor cells from harvested bone marrow were also discussed.     

Absence of telomerase activity in malignant bone tumors and soft-tissue sarcomas

Purpose: Telomerase activity appears to play a crucial role in the development of many tumors. More than 80% of all malignant human tumors show an increased telomerase activity. However, conflicting results have been reported about telomerase activity in sarcomas. The aim of the study was to obtain more information about telomerase activity in sarcomas based on a large number of cases.Methods: Telomerase activity was measured in 69 different tumor samples (33 malignant bone tumors and 36 soft tissue sarcomas). Tumor samples were obtained intraoperatively and frozen immediately in liquid nitrogen. Telomerase activity was detected by the telomeric repeat amplification assay (TRAP-assay).Results: Only 7% of the samples showed telomerase activity. No correlation between staging and telomerase activity could be observed.Discussion: The fact that only five out of 69 examined tumor samples showed a telomerase activity provides experimental evidence that in sarcomas the reactivation of telomerase may play a subordinate role. Our results suggest that alternative mechanisms for cell immortalization, yet to be determined, seem to be involved in the development and/or maintenance of soft-tissue sarcomas and malignant bone tumors.     

颅内肿瘤患儿血清细胞因子高通量液态芯片检测临床应用价值的探讨

目的:探讨IL-6、IL-8、IL-10、TNF-α和IFN-γ在颅内肿瘤患儿血清中的表达和各细胞因子之间相关性,以及它们与WHO肿瘤分级的关系。方法:采用高通量液态芯片法联合检测73例颅内肿瘤患儿(5～15岁)和42例健康儿童(5～15岁)血清中上述细胞因子的水平。结果:颅内肿瘤患儿血清IL-6、IL-8、IL-10、TNF-α和IFN-γ水平均显著高于健康对照组,P<0.01;各细胞因子之间具有相关性;IL-8在低级别肿瘤患儿血清中的水平显著高于其在高级别肿瘤患儿血清中的水平,P<0.05。结论:IL-6、IL-8、IL-10、TNF-α和IFN-γ可能参与儿童颅内肿瘤发病过程,各细胞因子之间存在相互作用,IL-8可作为预测颅内肿瘤级别的一个参考指标。     

Malignant humeral bone tumors in children: Excision and reconstruction with the use of rotated clavicle

The application of intensive multimodality therapy has made possible salvage surgery in bone tumors. Reconstruction of the removed part of bone is the great problem, especially in fast-growing children. In three patients (two osteosarcomas and one Ewing's sarcoma), the tumor was confined to the proximal half part of humerus, without invasion of shoulder joint. After induction chemotherapy, reduction of tumor size was observed both clinically and radiologically. During the operation, wide resection of the tumor together with a 12- to 14-cm-long fragment of humerus, was performed. Afterward, the clavicle was rotated in the place of the removed bone, with preservation of the coracoacromial ligament. The humeral stump and clavicle were fixed with the use of metal plate. Adjuvant chemotherapy was used a few days following surgery. After 3 months, the osteosynthesis had healed. The movements in shoulder joint are limited, but functions of elbow joint remained normal. All children are alive and disease free. Reconstruction of humerus with clavicle rotation is possible when the proximal bone loss is not longer than 10–14 cm. This method seems to be an alternative to allogeneic grafts and endoprostheses. © 1996 Wiley-Liss, Inc.     

High dose chemotherapy with autologous bone marrow rescue for children with diffuse pontine brain stem tumors

Purpose. Diffuse pontine tumors are highly lethal, and there are few long-term survivors with the standard treatment of external beam irradiation. We investigated the effectiveness of high-dose thiotepa and etoposide-based chemotherapy regimens with autologous bone marrow rescue (ABMR) in children with pontine tumors. Patients and methods. Sixteen children with diffuse pontine tumors were treated. Ten had resistant or recurrent tumors. All ten had previously received irradiation; five had also received chemotherapy and one, beta-interferon. Three high-dose chemotherapy regimens were employed. Six patients received three days of thiotepa (300 mg/m²/day) and etoposide (250–500 mg/m²/day) (TE); two received three days of carmustine (BCNU) (200 mg/m²/day divided every 12 hours) followed by TE (BTE); and two received three days of carboplatin (500 mg/m²/day) followed by TE (CTE). Six other patients had newly-diagnosed tumors and had not received any prior treatment. They all received the BTE regimen and subsequently were treated with hyperfractionated irradiation (7200–7800 cGy) beginning approximately six weeks post-ABMR. Results. There were two toxic deaths (13%), both in previously treated patients, due to multiorgan system failure and Candida septicemia in one case each. Median survival of the patients with resistant or recurrent disease was 4.7 months (range 0.1–18.7) from time of ABMR. Median survival of the newly-diagnosed patients was 11.4 months (range 7.6–17.1) from the time of ABMR. Conclusion. High-dose chemotherapy utilizing these regimens followed by ABMR did not appear to prolong survival compared to conventional therapy in these children with pontine tumors. Alternative strategies need to be developed for this highly lethal disease.for the Children's Cancer Group     

儿童恶性骨肿瘤保肢手术的进展

恶性骨肿瘤患者，病骨发育成熟(14～16岁)是选择保肢手术的适应证之一。因为儿童患者实施保肢手术后，骨骺的损伤迟早会导致肢体明显不等长，引起下腰部疼痛及代偿性脊柱侧弯，步态异常等，加上患儿一般难以配合术后的功能锻炼，所以保肢术效果多不佳。按照传统的方法，这部分患者常要选择截肢治疗。     

Superoxide-neutralizing activity of blood serum in cases of primary multiple malignant tumors]

An earlier investigation of the superoxide-neutralizing activity of blood serum sampled from patients with primary multiple malignancies detected for the first time RF-proteins as well as their tropism to the target organ from which tumor was removed 2-30 years before. A possible explanation may be that a general reaction of the body presented itself. The present study has led to a conclusion that, in cases of polyneoplasia, successful complex treatment of primary malignancy, carried out however for back, might be masked by RF-protein function: the latter "indicates" the presence of foci of malignancy which are not there any longer.     

Analysis of telomerase activity and telomere length in bone and soft tissue tumors

Telomerase activation is prevalent in most epithelial tumors, and may be a critical step in cellular immortalization and carcinogenesis. However, telomerase activity in tumors of mesenchymal origin is not well understood. In the present study, we examined telomerase activity in clinical samples from osteosarcoma and soft tissue sarcoma and representative sarcoma cell lines (HOS, OST and Saos2), using the telomeric repeat amplification protocol (TRAP) assay. The cell lines HOS and OST were telomerase-positive, but Saos2 cells lacked telomerase activity and hTERT mRNA expression. Treatment of Saos2 cells with the demethylating agent 5-aza-2'-deoxy-cytidine, alone or together with the histone deacetylase inhibitor tricostatin A, did not induce hTERT mRNA expression. Twenty-six of the 83 sarcoma samples (31.3%) were telomerase-positive [bone sarcoma, 15 of 42 samples (35.7%); soft tissue sarcoma, 11 of 41 samples (26.8%)], whereas neither benign tumors nor normal bone tissue expressed telomerase activity. There was no significant correlation between histological type, tumor staging and telomerase activity. However, patients with telomerase-positive tumors had significantly shorter survival than those with telomerase-negative tumors. There was heterogeneity in telomere length (range, 6-18 kb) among the tumors examined, but there was no significant difference in length between telomerase-positive and -negative tumors. Thus, these mesenchymal tumors comprise heterologous groups, some positive and some negative for telomerase, with long and short telomeres, suggesting multiple carcinogenesis pathways. The present results indicate that telomerase activation is not prevalent in mesenchymal tumors and is not a critical determinant of telomere length, but it may be a prognostic indicator of mesenchymal tumors.