Taketoshi Yasuda

Surgical outcome of cervical expansive laminoplasty in patients with diabetes mellitus.

STUDY DESIGN The results from cervical laminoplasty in 18 patients with diabetes mellitus were compared with results from the same procedure in 34 nondiabetic patients matched for age, gender, and disease. OBJECTIVE To analyze the effects of diabetes mellitus on the surgical outcome after cervical laminoplasty. SUMMARY OF BACKGROUND DATA There have been no reports on the results of cervical laminoplasty patients with diabetes. METHODS A retrospective analysis of 18 patients with diabetes mellitus who underwent cervical laminoplasty and 34 nondiabetic patients who underwent the same surgical procedure was undertaken. The postoperative score, intra- and postoperative findings, complications, and radiologic factors were compared between the two groups. In the group with diabetes, the correlation between the recovery rate of the Japanese Orthopedic Association score and the factors indicating the severity of diabetes was assessed. RESULTS There was no statistical difference between the total Japanese Orthopedic Association scores of the two groups. However, the group with diabetes mellitus showed a poor recovery of sensory function of the lower extremities. Three patients in the group with diabetes had superficial wound complication after surgery. In contrast, none of the patients in the control group had a wound problem. Furthermore, a negative correlation was observed between the recovery rate and the preoperative HbA1 level in the group with diabetes. CONCLUSIONS Although patients with diabetes mellitus who had cervical myelopathy experienced benefits from cervical laminoplasty similar to those of nondiabetic patients, the patients with diabetes were more likely to have wound complication. Furthermore, the negative correlation between the recovery rate and the preoperative HbA1 value might suggest that long-term diabetes control of more than 2 to 3 months before surgery at least is recommended for a favorable surgical outcome.

SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: A study from the Japanese Musculoskeletal Oncology Group†

In the present study, we evaluated the safety and effectiveness of SYT‐SSX‐derived peptide vaccines in patients with advanced synovial sarcoma. A 9‐mer peptide spanning the SYT‐SSX fusion region (B peptide) and its HLA‐A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14‐day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freunds adjuvant and then administered subcutaneously six times at 14‐day intervals. In addition, interferon‐α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six‐injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed‐type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.

Development of a new technique for pedicle screw and Magerl screw insertion using a 3-dimensional image guide.

Study Design. We developed a new technique for cervical pedicle screw and Magerl screw insertion using a 3-dimensional image guide. Objective. In posterior cervical spinal fusion surgery, instrumentation with screws is virtually routine. However, malpositioning of screws is not rare. To avoid complications during cervical pedicle screw and Magerl screw insertion, the authors developed a new technique which is a mold shaped to fit the lamina. Summary of Background Data. Cervical pedicle screw fixation and Magerl screw fixation provide good correction of cervical alignment, rigid fixation, and a high fusion rate. However, malpositioning of screws is not a rare occurrence, and thus the insertion of screws has a potential risk of neurovascular injury. It is necessary to determine a safe insertion procedure for these screws. Methods. Preoperative computed tomographic (CT) scans of 1-mm slice thickness were obtained of the whole surgical area. The CT data were imported into a computer navigation system. We developed a 3-dimensional full-scale model of the patients spine using a rapid prototyping technique from the CT data. Molds of the left and right sides at each vertebra were also constructed. One hole (2.0 mm in diameter and 2.0 cm in length) was made in each mold for the insertion of a screw guide. We performed a simulated surgery using the bone model and the mold before operation in all patients. The mold was firmly attached to the surface of the lamina and the guide wire was inserted using the intraoperative image of lateral vertebra. The proper insertion point, direction, and length of the guide were also confirmed both with the model bone and the image intensifier in the operative field. Then, drilling using a cannulated drill and tapping using a cannulated tapping device were carried out. Eleven consecutive patients who underwent posterior spinal fusion surgery using this technique since 2009 are included. The screw positions in the sagittal and axial planes were evaluated by postoperative CT scan to check for malpositioning. Results. The screw insertion was done in the same manner as the simulated surgery. With the aid of this guide the pedicle screws and Magerl screws could be easily inserted even at the level where the pedicle seemed to be very thin and sclerotic on the CT scan. Postoperative CT scan showed that there were no critical breaches of the screws. Conclusion. This method employing the device using a 3-dimensional image guide seems to be easy and safe to use. The technique may improve the safety of pedicle screw and Magerl screw insertion even in difficult cases with narrow sclerotic pedicles.

The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study.

Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large‐scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real‐life, postmarketing surveillance data.

Nutlin-3 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulation of death receptor 5 (DR5) in human sarcoma HOS cells and human colon cancer HCT116 cells.

MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Recently, nutlins, small-molecule antagonists of MDM2, have been developed to inhibit the p53-MDM2 interaction and activate p53 signaling. The expressions of DR4 and DR5, Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors, are regulated by p53. In this study, the combined effects of nutlin-3 and TRAIL on apoptosis were investigated in HOS and HCT116 cells, which express wild-type p53. Nutlin-3 and TRAIL synergistically enhanced apoptosis owing to their intrinsic and extrinsic pathway signals, respectively. The increase in the Bid expression level and the decrease in the expression levels of anti-apoptotic proteins, c-FLIP and XIAP, were involved in this apoptosis enhancement. Furthermore, nutlin-3 activated the DR5 promoter and increased the expression levels of DR5 at mRNA and protein levels. These results indicate that the combination, treated with nutlin-3 and TRAIL, is useful for apoptosis induction in malignant cells expressing wild-type p53.

Molecular mechanism of apoptosis and gene expressions in human lymphoma U937 cells treated with anisomycin.

Anisomycin is known as a potent apoptosis inducer by activating JNK/SAPK and inhibiting protein synthesis during translation. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by anisomycin using DNA microarrays and computational gene-expression analysis tools in human lymphoma U937 cells. Anisomycin was found to induce apoptosis in time- and concentration-dependent manner as confirmed by phosphatidylserine externalization and DNA fragmentation analysis. Furthermore, anisomycin-treated cells also showed caspase-8 activation, mitochondrial membrane potential collapse, Bid activation, caspase-3 cleavage and cytochrome c release into the cytosol. In the gene-expression analysis, six gene clusters were detected. From clusters I and II, three significant genetic networks were identified. Interestingly, many bZIP family transcription factors were observed in the up-regulated genetic networks. Moreover, the expression of protein-synthesis-related genes, such as EIF4 family proteins and ribosomal proteins, were inhibited. This finding could explain the reason why anisomycin inhibits the protein synthesis at the translation steps. These results provide novel information for understanding the molecular mechanism of apoptosis induced by anisomycin.

Effects of Vascular Endothelial Growth Factor and E-Selectin on Angiogenesis in the Murine Metastatic RCT Sarcoma

The relationship between vascular endothelial growth factor (VEGF) and induction of angiogenesis in high-metastatic RCT(+) or low-metastatic RCT(–) clones of the poorly differentiated murine RCT sarcoma was investigated. The association with E-selectin in VEGF-induced angiogenesis was also evaluated. RCT(+) cells produced significantly larger amounts of VEGF than RCT(–) cells. In a tube formation assay with murine lung microvascular endothelial (MLE) cells, conditioned medium from RCT(+) cells showed a significantly greater effect on tube formation than that from RCT(–) cells. Induction of tube formation was suppressed by anti-mouse VEGF monoclonal antibody. Furthermore, anti-mouse E-selectin monoclonal antibody suppressed the tube formation induced by recombinant mouse VEGF. In a flow-cytometric analysis, the expression of E-selectin on MLE cells was upregulated after pretreatment with conditioned medium from RCT(+) and RCT(–) cells. Conditioned medium from RCT(+) cells induced a higher expression of E-selectin compared to medium from RCT(–) cells. Anti-VEGF monoclonal antibody prevented the upregulation of E-selectin by the RCT cell-conditioned medium. These findings suggest that E-selectin plays an important role in the angiogenesis induced by VEGF. VEGF derived from tumor cells may enhance angiogenesis by upregulating the expression of E-selectin on vascular endothelial cells.

Ionizing Radiation Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis through Up-Regulations of Death Receptor 4 (DR4) and Death Receptor 5 (DR5) in Human Osteosarcoma Cells

Despite improvements in chemotherapy and surgery in the treatment of osteosarcoma (OS), satisfactory results are still difficult to achieve. Novel therapeutic modalities need to be developed for osteosarcoma treatment. The combined effects of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and ionizing radiation (IR) on human OS cells were investigated. IR and TRAIL treatment synergistically decreased the cell viability and enhanced apoptosis in OS cell lines. IR pretreatment enhances TRAIL‐induced Bid and caspase‐3 activations. Decreases in the expression levels of the antiapoptotic proteins c‐FLIP and XIAP also associated with apoptosis enhancement. Furthermore, IR pretreatment enhanced DR4 and DR5 expressions at the transcription stage. These results can become the basic lines of evidence for the future treatment of OS using TRAIL with IR.

Ossification of the posterior longitudinal ligament in not only the cervical spine, but also other spinal regions: analysis using multidetector computed tomography of the whole spine.

Study Design. A prospective cohort study. Objective. To evaluate ossification of the posterior longitudinal ligament (OPLL) of the whole spine in patients with cervical OPLL and to analyze which types of cervical OPLL were associated with the other lesions in the thoracic and/or lumbar spine. Summary of Background Data. OPLL is most frequently seen in the cervical spine. The coexisting ossified lesions are sometimes observed in other spinal regions. However, coexisting OPLL in other spinal regions have not yet been precisely evaluated in patients with cervical OPLL. Methods. One hundred seventy-eight patients with a diagnosis of cervical OPLL whose plain radiographs were obtained were included. Computed tomographic images of the whole spine were obtained. The ossification index (OS index) was newly determined according to the sum of the levels of vertebral bodies and intervertebral discs with OPLL. The patients were divided into 2 groups, the group that had OPLL only in the cervical spine (C group) and the group that had OPLL in multilevel spinal regions other than the cervical spine (M group). Results. Ninety-five (53.4%) had OPLL not only in the cervical spine, but also in other spinal regions. The M group had more females than the C group. The incidence of bridge formation in the cervical spine was higher in M group than in C group. More females had a high OS index. A positive correlation was found between the OS index of the cervical spine and the OS index of the thoracic and lumbar spine; however, the r value was small. Conclusion. This study demonstrated that more than half of the patients with cervical OPLL had coexisting OPLL in the thoracic and/or lumbar spine. We strongly recommend computed tomographic analysis of the whole spine for patients with radiographical evidence of OPLL in the cervical spine for the early detection of additional sites of ossification. Level of Evidence: 4

Cystic spinal cord tumors : Magnetic resonance imaging correlated to histopathological findings

We report the characteristics of magnetic resonance imaging (MRI) of cystic intradural extramedullary spinal cord tumors (cystic neurilemmoma, epidermoid cyst, and enterogeneous cyst). T1-weighted MRI enhanced with gadolinium-DTPA clearly demonstrated the rim morphology of these tumors. The comparison between the rim enhancement pattern and histopathological findings offered possible qualitative diagnosis of these cystic spinal cord tumors by MRI.