Shinsuke Sugihara

Total sacrectomy and reconstruction: Oncologic and functional outcome

The oncologic and functional outcomes of nine patients who were treated by total sacrectomy through L5 (three cases) or L5-S1 (six cases) were reviewed. Histologic diagnoses were one osteosarcoma, two giant cell tumors, two chondrosarcomas, and four chordomas. Patients’ ages ranged from 17 to 70 years (mean age, 44.5 years). Resection margins were intralesional (giant cell tumors) in two, marginal in one, and wide in six patients (one contaminated). Reconstruction was performed using polymethylmethacrylate in two, screw and plate fixation in one, and a custom-made device in one. In five patients no reconstruction was performed. Five patients (45.5%) had wound complications: one had a wound dehiscence and two had deep infection; all needed surgical reintervention. In addition, in one a ventral and in another a dorsal hernia developed; only the ventral hernia was revised successfully. One patient had a deep vein thrombosis that was treated with a Coumadin derivate. Three patients (33%) died after 14, 18, and 50 months postoperatively respectively. One died of lung and widespread metastases, and two died of local recurrence and metastases. One patient with a giant cell tumor had a solitary lung metastasis. After resection the patient has been disease-free more than 90 months. At followup, six patients had no evidence of disease (mean followup, 73 months; range, 30–120 months). Functionally, there was no correlation between patients who had a reconstruction and those who had not. Total sacrectomy is a valuable procedure to secure local tumor control and overall survival, despite potential complications and neurologic and sexual dysfunction.

The effect of cage stiffness on the rate of lumbar interbody fusion: an in vivo model using poly(l-lactic Acid) and titanium cages.

Study Design. A goat interbody fusion model using poly-(L-lactic acid) and titanium cages was designed to evaluate the effect of cage stiffness on lumbar interbody fusion. Objective. To investigate the effect of cage stiffness on the rate of interbody fusion. Summary of Background Data. Various types of cages considerably exceed the stiffness of vertebral bone, which ultimately may lead to postoperative complications. To avoid these complications, poly-(L-lactic acid) cages with limited stiffness have been designed. The mechanical integrity of the cages remains intact for at least 6 months. Methods. Interbody fusions were performed at L3–L4 of 15 Dutch milk goats, and one of three cages was randomly implanted: 1) a titanium cage (n = 3), 2) a stiff poly-(L-lactic acid) cage (n = 6), or 3) a flexible poly-(L-lactic acid) cage (n = 6). Interbody fusion was assessed radiographically by three independent observers 3 and 6 months after surgery. Results. At 3 months, all the poly-(L-lactic acid) specimens showed ingrowth of new bone, but with radiolucency in the fusion mass. At 6 months, solid arthrodesis was observed in four of six poly-(L-lactic acid) specimens, advanced ingrowth in one specimen, and infection in one specimen. Titanium cages showed ingrowth of bone, but with radiolucency in the fusion mass. Interbody fusion using poly-(L-lactic acid) cages showed a significantly higher rate statistically (P = 0.016) and more complete fusion than titanium cages of the same design. Conclusions. The reduced stiffness of poly-(L-lactic acid) cages showed enhanced interbody fusion, as compared with titanium cages after 6 months. Bioabsorbable poly-(L-lactic acid) cages thus may be a viable alternative to current interbody cage devices, thereby avoiding the concomitant problems related to their excessive stiffness. However, the bioabsorbability of the poly-(L-lactic acid) cages awaits investigation in a long-term study currently underway.

Telomere elongation observed in immortalized human fibroblasts by treatment with 60Co gamma rays or 4-nitroquinoline 1-oxide.

Telomeres are the tandemly repeated (TTAGGG)n sequences that make up the structural and functional ends of all chromosomes in mammals. Many lines of evidence indicate that telomeres stabilize chromosomes, prevent aberrant recombination, and direct chromosome attachment to the nuclear membrane. Since DNA polymerase requires a labile primer to initiate unidirectional 5′-3′ DNA synthesis, some bases at the 3′ end of each template strand are not copied unless special mechanisms bypass this end-replication problem. To overcome this problem, most eukaryotic cells use telomerase, an enzyme that elongates telomeres. However, this enzyme has not been detected in normal human cells, and these cells lose telomeres with cell division. Cellular senescence might be the result of this loss. Thus, activation of telomerase seems to be critical for the immortalization of human cell lines. In addition, substantial evidence indicates that immortalization in itself is a rate-limiting step for the malignant transformation of human cells. We have treated normal human fibroblasts (AD387, KMS-6, and OUMS-24 lines) intermittently with either 60Co gamma rays or 4-nitroquinoline 1-oxide (4NQO) during serial subcultivations, and have obtained three immortalized cell lines, SUSM-1, KMST-6, and OUMS-24F. In KMS-6 and OUMS-24, the mean terminal restriction fragment length significantly decreased as the population-doubling level increased. The rate of telomere loss was 40 and 50 bp/ population doubling in the KMS-6 and OUMS-24 cell lines, respectively. Once these normal cell lines were immortalized, their telomeres became elongated. Similar data were obtained for AD387 cells and their immortalized SUSM-1 cells. These results suggest that telomeres play a critical role in cellular senescence and in the immortalization processes of human cells.

Treatment outcome of osteofibrous dysplasia

The disease course of six tibial lesions in five patients with osteofibrous dysplasia who were followed longer than 10 years (average: 16.8 years) was analyzed retrospectively. Three patients had a lesion of the unilateral tibia; one patient had lesions of the unilateral tibia and fibula; and one patient had lesions of the bilateral tibiae and ulnae. Curettage and autogeneic bone graft were performed on two lesions, which then healed. Of four lesions on which curettage and xenogeneic bone grafts were performed, three lesions healed, and one developed local recurrence. Curettage and xenogeneic bone graft were performed on the recurrent lesion, which finally healed and the deformity stopped. Three lesions healed without surgical treatment. During the long-term follow-up, this disease showed a clear tendency of healing. Surgical treatment should be considered in patients with disease uncontrollable by conservative treatment or those who have a high possibility of impending fracture and progressing deformity.

Imaging assessment of the response of bone tumors to preoperative chemotherapy

Assessment of the response of bone tumors to preoperative chemotherapy is of clinical importance. The authors determined the value of 3 imaging techniques (digital subtraction angiography, thallium scintigraphy, and dynamic magnetic resonance imaging) in guiding patient management by assessing the response of 17 bone sarcomas to preoperative chemotherapy compared with histologic evaluation of the resected specimens. Digital subtraction angiography showed a sensitivity of 87.5%, specificity of 57.1%, and accuracy of 73.3%. Thallium scintigraphy (sensitivity, 85.7%; specificity, 85.7%; accuracy, 85.7%) was superior to angiography in predicting tumor responses. The results of dynamic magnetic resonance imaging were analyzed on the basis of the value of slopes, which represents the percent increase in signal intensity per minute. The differences in slope before and after chemotherapy and the postchemotherapy slope values correlated with the histologic responses. The assessment by dynamic magnetic resonance imaging showed a sensitivity of 100%, specificity of 85.7%, and accuracy of 90.9%. Thallium scintigraphy and dynamic magnetic resonance imaging were considered noninvasive, reliable techniques that had about equal ability to assess the response of bone sarcomas to preoperative chemotherapy. Dynamic magnetic resonance imaging offers major advantages in the spatial resolution and can be more readily quantitated when compared with thallium scintigraphy.

Influence of telomerase activity on bone and soft tissue tumors

PurposeTelomeres consisting of a repeating nucleotide sequence (TTAGGG)n are shortened in normal somatic cells. Telomerase is an enzyme that elongates the telomere sequence and is detected in most human cancers and usually not in normal somatic cells. Little is known about telomerase activity in bone and soft tissue tumors. The aim of this study was to investigate the relationship between telomerase activity and clinical factors in bone and soft tissue tumors.MethodsTelomerase activity was measured using the modified telomeric repeat amplification protocol (TRAP) assay in 115 bone and soft tissue tumors obtained through open biopsy or resection.ResultsTelomerase activity was detected in 10% of benign tumors and 44% of malignant tumors (p<0.001). A higher incidence of telomerase activity was detected in high-grade tumors than in low-grade tumors (p=0.002). The cumulative metastasis-free and overall survival in telomerase-positive patients was significantly worse than in telomerase-negative patients (p=0.045 and p=0.048).ConclusionOur study suggests that telomerase activity is associated with tumor aggressiveness and may be a useful parameter to predict the prognosis of patients with malignant bone and soft tissue tumors.

The importance of doxorubicin and methotrexate dose intensity in the chemotherapy of osteosarcoma

The relationship between dose intensity of cytotoxic agents and therapeutic results was examined in a retrospective analysis of 32 patients with non-metastatic high-grade osteosarcoma of the extremities. The average dose intensities of individual agents were 9.8 mg/m2/week for doxorubicin, 1.2 g/m2/week for methotrexate, and 10.5 mg/m2/week for cisplatinum. The dose intensities of doxorubicin and methotrexate were significantly correlated with the clinical results, while that of cisplatinum was not. These results indicate that maximal dose intensification of doxorubicin and methotrexate is an important determinant of treatment outcome for patients with osteosarcoma.

Multiple osteocartilaginous exostosis. A follow-up study.

Deformity of the lower extremities in 26 patients with multiple cartilaginous exostosis was examined radiologically. Follow-up periods ranged between 3 and 33 years (mean 10.3 years). Twenty-four patients had deformity of the joints. A femoral neck-shaft angle (FNA) of more than 150° was noted in 14 patients (26 of 51 hip joints) at diagnosis. After approximately 10 years of age, the FNA tended to decrease. Eleven patients (22 of 52 knee joints) had genu valgum (the femorotibial angle < mean −2 SD of normal control) which was caused by valgus deformity of the distal femur in one-third of the patients and that of the proximal tibia in two-thirds. Fifteen of 21 patients (29 of 42 joints) had valgus deformity of the ankle (antero-posterior mortise angle of the ankle > 94c), and in half of them, the valgus deformity progressed with growth. Two patients (aged 10 and 11 years) underwent varus osteotomy of the tibia with partial excision of the fibula. However, their deformity relapsed. Surgical treatment for hip deformity is unnecessary during the growth stage. Progressive deformity of the knee and ankle should be detected in an early stage, and the surgical indication has to be examined.

Massive osteolysis in the pelvis—a case report

In 1985, a 42-year-old woman felt pain in her left hip while playing volleyball, but continued to play occasionally because her symptoms were mild. In 1987, the pain worsened. Past and family histories showed no remarkable findings.

Polyostotic lesions compatible with osteofibrous dysplasia - A case report

An 18-month-old girl with lesions in the cortex of the bilateral tibiae and ulnae and right fibula is reported. The lesion in the right tibia disappeared after curettage and xenogeneic bone grafting, and the other lesions disappeared spontaneously by the age of 12 years. All lesions involved the bone cortex. The right tibial lesion exhibited the histopathological features of “zonal architecture” and a osteoblast rim formation around the trabeculae. We consider that osteofibrous dysplasia can involve systemically any long bone.