Education and employment in long-term survivors of high-grade osteosarcoma: a Japanese single-center experience.

OBJECTIVE: To investigate the status of education and employment of long-term survivors who became physically handicapped after treatment for high-grade osteosarcoma. METHODS: Of the osteosarcoma patients treated at our hospital, 41 patients aged less than 18 years at the initial presentation who were free of disease for 10 years or longer after the end of treatment were studied. The status of their education and employment was investigated via a questionnaire. RESULTS: Twenty-seven patients responded to the questionnaire (response rate, 65.9%). Of these patients, 73.1% (19/26) could return to the school they had attended before the disease, and 52% (13/25) graduated from college or university. The percentage of those who went to college or university was higher in the limb-sparing group. Seventy-two percent of the patients were engaged in clerical work, and the mean annual income was 4.01 million JPY (corresponding to about 24,000 EUR). No difference was noted in the status of employment between the amputation and limb-sparing groups. CONCLUSIONS: The percentage of patients who went to college or university was similar to the percentage in all Japanese. However, the status of the diseased limb appeared to affect school attendance. The mean annual income of the patients was comparable to that of the national average, and they experienced no major problems in their employment. Physical disabilities posed few problems in their daily living.

Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas and soft tissue sarcomas.

AIM: The control of pulmonary metastases is important for long-term survival of the patients with osteosarcomas and soft tissue sarcomas. METHODS: To evaluate the efficacy of aggressive pulmonary metastasectomy for those patients, we reviewed 105 cases (44 osteosarcomas, and 61 soft tissue sarcomas) treated in our hospital. RESULTS: The number of metastases was only the significant risk factor for the curability of the metastasectomy (logistic regression analysis, P=0.0274). The 5-year and 10-year survival rate were 43.6% and 32%. The curability was only independent prognostic factor on multivariate analysis (P=0.0008). CONCLUSIONS: Early detection of pulmonary metastasis, multimodal perioperative treatment, and design for minimizing the volume of resected lung tissues will enable complete and repeat resections for the achievement of long-term survival.

Isolation and characterization of low- and high-metastatic clones from murine RCT (Radiological, Chiba, and Toyama) sarcoma.

We have established low- and high-metastatic clones, named RCT(-) and RCT(+) cells, respectively, from the RCT (Radiological, Chiba, and Toyama) sarcoma spontaneously developed in a C3H/He male mouse by the limiting-dilution method in vitro or by the combination of the lung passages and limiting-dilution methods. After 20 serial passages in vitro, the metastatic potential of each clone did not alter. Morphologically, both cells were spindle-shaped, but RCT(+) cells were slightly thicker and larger than RCT(-) cells. The organization of actin-containing filaments was slightly poorer in RCT(+) cells than that in RCT(-) cells. Marked differences were observed in their growth characteristics and adhesiveness to plastic or collagen-coated surfaces, that is, RCT(+) cells grew more slowly but could adhere more rapidly and firmly to the surfaces than RCT(-) cells. RCT(+) cells were agglutinated by all lectins used but several lectins could not agglutinate RCT(-) cells. These results could be a reflection of the difference in oligosaccharide residues on the surface of each cell and, in part, might reflect the difference in organization of the actin-containing filaments that regulate the mobility of lectin receptors. No significant difference between these cell clones was noted in their sensitivity to natural-killer-cell-mediated cytotoxicity in vitro. RCT(-) and RCT(+) cells are considered to be the most useful experimental model for the study of the certain sarcomas.

Differentiation of Dunn osteosarcoma cells in response to dibutyryl cyclic 3',5'-adenosine monophosphate.

We investigated the effects of dibutyryl cyclic adenosine 3',5'-monophosphate (Bt2cAMP) on the differentiation of Dunn osteosarcoma cells. Flow-cytometric analysis and DNA synthesis assay showed that Bt2cAMP decreased the cell population in the S phase in a time- and dose-dependent manner. Also, the cells showed distinct morphological and functional alterations; the cell morphology changed to a fibroblast-like appearance with long and thin protoplasmic processes, the knobs or blebs on both the cell membrane and nuclear membrane disappeared and the intracellular alkaline phosphatase activity increased. Moreover, Bt2cAMP-treated cells secreted a large quantity of fibronectin, which was deposited on the extended cell surface in the culture medium. Thus, Dunn osteosarcoma cells are differentiated morphologically and functionally by Bt2cAMP, and might be transformed to benign precursor cells.

Knee rotation-plasty for malignant musculoskeletal tumors occurring around the knee joint.

BACKGROUND: In addition to the wide excision of malignant musculoskeletal tumor around the knee joint, surgical methods, such as total knee arthroplasty and knee rotation-plasty are available. Therefore, this study was undertaken to clarify the usefulness of knee rotation-plasty. MATERIALS AND METHODS: At the Chiba Cancer Center, knee rotation-plasty was performed in 27 patients with malignant musculoskeletal tumor around the knee joint. Patients were divided into two groups: Group S, in which operations were performed as salvage surgery (8 patients), and Group I, in which operations were performed as initial surgery (19 patients). The lower limb function was investigated in 17 patients (7 patients in Group S and 10 patients in Group I). The lower limb function was assessed by the Knee Evaluation System of International Symposium on Limb Salvage and the Knahr's assessment. RESULTS: Lower limb function in Group S measured an average of 25.7 points (85.6%), while the lower limb function in Group I measured an average of 23.6 points (78.7%). The majority of patients in both groups were capable of walking without a cane or doing light exercise with below-the-knee prosthesis, revealing good lower limb function. CONCLUSION: Whether it is performed as salvage or initial surgery, knee rotation-plasty can be useful method for reconstruction of the knee after wide excision of malignant musculoskeletal tumor around the knee joint.

Two cases of osteosarcoma occurring as second malignancy of childhood cancer.

We report on two patients in whom osteosarcoma occurred as second malignancy of childhood cancer. One patient had a malignant teratoma and the other adrenocortical carcinoma as the primary cancer. The emergence of cancer in cured cases and long-term survival cases of childhood cancer may result in an increase in the number of osteosarcomas seen in adolescence occurring as second malignancy. Anti-cancer drugs in large does were used for the treatment of a malignant teratoma in the former. These anti-cancer drugs may be involved in the occurrence of the second malignancy. In the latter, the patient has the germ-line mutation of p53 tumor suppressor gene, so genetic factors are presumably related to the occurrence of the second malignancy.

Surgical treatment for pancreatic metastasis from soft-tissue sarcoma: report of two cases.

We present two cases in which a soft-tissue sarcoma metastasized to the pancreas, but both patients survived as a result of repetitive surgical treatment during a 6- to 10-year period. The first case was a 29-year-old man who had a history of removal of mesenchymal chondrosarcoma in the left thigh in 1986 and who underwent distal pancreatectomy and the enucleation of a tumor in the head of the pancreas because of the development of three metastatic lesions in 1989. Afterward, although metastases were found in other organs, they were resected each time (for a total of five times) and the patient has survived over 10 years. The second case was a 40-year-old woman who had a history of the removal of synovial sarcoma in the right thigh and had 6 surgical resections of local or pulmonary recurrent tumors. She underwent pylorus-preserving pancreaticoduodenectomy in 1993 because of the development of a solitary metastatic lesion in the pancreas and survived more than 6 years after the pancreatectomy. Our report suggests, in selected cases, that long-term survival from pancreatic metastasis of soft-tissue sarcoma is expected as a result of curative resection. However, because pancreatic metastasis has a potential to recur in other organs, it is necessary to take aggressive surgical procedures repeatedly for the treatment of recurrences to improve prognosis after pancreatectomy.

Redundant nerve roots in patients with degenerative lumbar spinal stenosis.

Extensive fundamental and clinical investigations have been performed concerning redundant nerve roots (RNR) and the pathogenesis of cauda equina claudication (CEC) in degenerative lumbar canal stenosis (DLCS). These investigations consisted of (1) anatomic observations on RNR in 117 fixed cadaveric specimens, (2) myelographic study in 117 patients with or without DLCS, (3) operative observation on neural elements with special reference to the cauda equina in 56 DLCS patients (including a postoperative follow-up), and (4) electrophysiologic tests using spinal cord action potential recording under walking load preoperatively and intraoperative measurement of nerve conduction velocity of RNR. The RNR have neuronal losses resulting from a longer duration stenosis that suggests a sort of friction neuritis. Complicated factors contribute to the pathogenesis of CEC and the development of root gripping, such as the magnitude of RNR, the extent of the stenosis, a narrowed sac, age-dependent axial shortening of the spinal canal, and dynamic or postural factors. In cases with severe RNR, satisfactory operative results can be obtained only after thorough decompression with dural incision.

Effects of ethane-1-hydroxy-1, 1 diphosphonate on Dunn osteosarcoma cells.

We investigated the effects of ethane-1-hydroxy-1, 1 diphosphonate (EHDP) on Dunn osteosarcoma cells in vivo and in vitro. In in vivo study, an increase of tumor volume was significantly suppressed in the EHDP administered groups compared with the control group. Histologically, Dunn osteosarcoma cells' viability was maintained after EHDP administration. However, fatty degeneration of tumor tissue was suspected in two of eight mice in the 5.0 mg/kg EHDP administered group. In vitro study, EHDP inhibited DNA synthesis and induced morphological changes, such as pycnotic cells. These findings show that the growth of Dunn osteosarcoma cells is inhibited by EHDP.

A reversed-flow latissimus dorsi musculocutaneous flap based on the serratus branch in primary shoulder reconstruction.

We report a case using the latissimus dorsi musculocutaneous flap based on the serratus branch in primary shoulder reconstruction. The reversed flow of the serratus branch maintained the circulation of the flap following acute disruption of the thoracodorsal vessels. Although our case was unusual, the reversed-flow latissimus dorsi flap based on its serratus branch may add a useful option in some cases.

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for refractory bone and soft tissue sarcomas].

High-dose chemotherapy with autologous peripheral blood stem cell transplantation was administered to 10 patients with refractory bone and soft tissue sarcoma (2 patients with primitive neuroectodermal tumor, 4 patients with Ewing's sarcoma, 3 patients with synovial sarcoma and one patient with osteosarcoma). Busulfan 4 mg/kg x 4, melphalan 140 mg/m2 and thiotepa 200 mg/m2 x 3 were used in the high-dose chemotherapy. Complications related to the treatment were limited to one patient who developed hepatic veno-occlusive disease, no serious complications were seen in the other patients. Four patients died of their disease, one patient was alive with the disease and 5 patients were alive with no evidence of disease. The prognosis for non-resectable primitive neuroectodermal tumor and Ewing's sarcoma is said to be very poor. However, there are some patients in whom the disease is kept in remission by high-dose chemotherapy with autologous peripheral blood stem cell transplantation, so this therapy may be a possible substitute for radical operation. With spindle cell sarcomas, the efficacy of this treatment was temporary, so it will be necessary to investigate frequent high-dose chemotherapy and to change the high-dose chemotherapy regimen.

[Toxic effects of ifosfamide in the treatment of bone and soft tissue sarcomas].

A total of 64 courses of ifosfamide (IFM) treatments for sarcoma patients were evaluated for toxic effects. A dose of 100 ml of 1/2 diluted Maalox by normal saline was instilled into urinary bladder with clump of catheter for 15 min for uroprotection instead of Mesna that was not available in Japan at that time. Forty-six courses of ifosfamide treatment in 12-16 g/m2 doses with daily Maalox instillation resulted only one hemorrhagic cystitis, while 18 courses at a dose of 6-10 g/m2 of IFM without Maalox eventuated in 5 cases of hemorrhagic cystitis. Forty-six courses of ifosfamide treatment at a dose of 12-16 g/m2 (mean dose of 14.4 g/m2) for 5 to 6 day continuous infusion were evaluated also for myelosuppression, nephrotoxicity, neurotoxicity, and other toxicities. Myelosuppression was acceptable, although the absolute neutrophil count of the 80% course was below 500. No patient showed neurotoxicity characterized by confusion or somnolence. No course resulted in abnormal serum creatinine elevation, although two of 46 courses caused an abnormal decrease of creatinine clearance. One patient had arrhythmia that required medical treatment after 5 courses of IFM treatment.

[The effects of high-dose ifosfamide in the treatment of bone and soft tissue sarcomas].

From January 1990 to December 1995 we treated 35 patients (pts) with bone and soft tissue sarcoma with ifosfamide (IFM). Sixteen patients had measurable metastatic pulmonary lesion and 9 had primary lesion. Histology of the tumor included osteosarcoma in 13 pts, Ewing sarcoma in 5 pts, malignant fibrous histiocytoma of bone in 2 pts, synovial sarcoma in 7pts, primitive neuroectodermal tumor in 2 pts, and other in 7 pts. The IFM at the dose of 12-18g/m2 (mean 15. 4g/m2) for 5 to 8 days continuous infusion was administered to patients in each treatment course. The uroprotector, mesna, was also given concomitantly in 60-100% dose of IFM. Eighteen pts received one course of IFM treatment. Other pts received 2 to 8 courses of IFM treatment at three to four week intervals. The overall response rate was 40% (PR in 14 pts, NC in 18 pts, and PD in 3 pts). The response rate of 13 pts with osteosarcoma was 54% (PR in 7 pts) and 30% in 15 pts with soft tissue sarcoma (PR in 5 pts).

Extraskeletal mesenchymal chondrosarcoma: an imaging review of ten new patients.

OBJECTIVE: Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare soft-tissue tumor that most arises in young adults. Because of its rarity, few imaging studies have been reported to date. The purpose of this study was to elucidate the imaging features of this tumor. DESIGN: We conducted a multi-institutional study in cooperation with five referral cancer centers in Japan. Imaging findings of ten new EMC cases, including conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI), performed at each institute, were reviewed along with clinical features. PATIENTS: Ten patients with EMC, who had been treated at each hospital from 1990 to 2001, participated in this study. RESULTS AND CONCLUSIONS: Soft-tissue masses with well-demarcated, dense and granular calcification were most frequently observed on plain radiographs and CT scans. T2-weighted MR images most clearly depicted a two-component structure composed of calcified and uncalcified areas, and enhanced MRI showed inhomogeneous enhancement in both areas. Although the sensitivity and specificity of these findings are unknown, they might be characteristic and have diagnostic value for this rare tumor.

Systematic multi-modal treatment of osteosarcoma, with special reference to the role of fast neutron radiotherapy.

Sixty-one patients with osteosarcoma were treated. Twenty-four of these patients were managed with our systematic multi-modal treatment. Overall survival rate was markedly improved chiefly by intensive systemic chemotherapy with multiple drugs, especially adriamycin and high dose methotrexate. Preoperative regional intra-arterial infusion of anti-tumor drugs and fast neutron radiotherapy were employed and it was suggested that fast neutron had a higher relative biological effectiveness and a greater therapeutic gain factor as compared with X-rays. Fast neutron radiotherapy can play a significant role in the very systematic treatment of osteosarcoma and is specifically useful for preservation of the affected limbs.

[Characteristics of high- and low-metastatic clones isolated from murine undifferentiated sarcoma (RCT sarcoma)].

We have established low- and high-metastatic clones from the undifferentiated RCT (Radiological Science-Chiba Cancer Center-Toyama Medical and Pharmaceutical University) sarcoma spontaneously developed in a C3H/He male mouse. Metastatic lesions of RCT sarcoma at the lung were inoculated into the subcutaneous tissue which was then cultured and cloned. Clones potential of low- and high-metastatic were named RCT(-) and RCT(+), respectively. RCT(-) cells were cloned by the limiting dilution method in vitro and RCT(+) cells were cloned by the combination of lung passages and limiting dilution methods. After 20 serial passages in vitro, the metastatic potential of each clone remained unchanged. Significant differences were noted in their growing property and adhesiveness to plastic or collagen-coated surfaces; RCT(+) cells grew more slowly, adhered more rapidly and firmly to the surfaces than those of RCT(-) cells. RCT(+) cells were agglutinated by all types of lectins used in this study, while several types of lectins could not agglutinate RCT(-) cells. These results would indicate that there was the difference in oligosaccharide residues on the surface of each cell. No significant difference between these cell clones in their sensitivity to natural killer cell-mediated cytotoxicity in vitro. We believe that RCT(-) and RCT(+) cells are very useful experimental model to study the mechanism of sarcoma metastasis.

Ceramic vertebral body replacement for metastatic spine tumors.

A modular ceramic spacer system was developed and used for vertebral body replacement in 21 patients with metastatic spine tumor in cervical (n = 10 cases), thoracic (n = 9), and lumbar spines (n = 2). All cases of cervical and lumbar spinal tumors underwent simultaneous use of a ceramic spacer and plate-screw fixation, and eight patients received additional posterior interventions in the thoracic spine. Postoperative radiation therapy was performed in all cases except two, which involved prostatic carcinoma. Complete or moderate pain relief was obtained in 19 patients, and 17 patients were able to walk after surgery. The average bed rest period was 11 days. Radiologically, a clear zone at the spacer-vertebral body interfaces and migration of the spacer was observed in four cases and one case, respectively. However, satisfactory pain relief and stabilization of the spine was obtained in an average follow-up time of 22.3 months. In all four autopsy specimens studied, the ceramic spacer showed firm connection with the vertebral body. This modular ceramic spacer system facilitates a relatively easy procedure, maintenance of spinal stability, early ambulation, and no interference with local radiation therapy.

[Diagnosis of malignant bone and soft part tumors].

In most bone tumors, the patient's local symptoms, which are usually pain and/or swelling, are nonspecific. Laboratory studies are of little significance in the diagnosis of the bone tumors, except myeloma and metastatic prostatic carcinoma. Though a definitive diagnosis must be made histologically, roentgenograms afford practically conclusive evidence of the malignant or benign nature of bony lesions and often indicate the histologic type. Differential diagnosis of malignant bone tumors which were misled as benign conditions were mainly described, and advantages and disadvantages of radiologic imaging methods such as RI, CT, and MRI, were also discussed. In the diagnosis of malignant soft part tumors, aspiration biopsy was strongly recommended but this necessitates experts' hand to avoid dissemination of the tumor cells to the normal tissue.