Intraoperative spinal cord monitoring of C5 palsy after cervical laminoplasty.

STUDY DESIGN: Retrospective study of C5 palsy after laminoplasty for cervical myelopathy. OBJECTIVE: The objectives of this study were to investigate the morphologic characteristic of C5 palsy patients undergoing cervical laminoplasty with the intraoperative motor-evoked potential (MEP). SUMMARY OF BACKGROUND DATA: A study reported prophylactic foraminotomy for C5 paralysis after laminoplasty for cervical myelopathy. However, no indications have been established. There have been few reports on the intraoperative monitoring of the C5 palsy. This palsy is reported to happen a few days after the surgery in many cases, and the possibility of its detection by intraoperative spinal cord monitoring is unclear. METHODS: Of 153 patients with cervical myelopathy, 9 showed a decrease in upper muscle strength by 1 grade or more by postoperative manual muscle test. Of the 9 patients, 4 patients underwent segmental monitoring of upper limbs by MEP and were included in the paralysis group. Of the 153 patients, 74 (444 muscles) in whom both preoperative and postoperative manual muscle test of the upper limbs showed grade 5, and in whom the MEP monitoring of all these muscles was performed, were included in the nonparalysis group. We investigated the presence of intraoperative changes in 4 MEP parameters: amplitude, latency, duration, and waveform pattern, and the presence of foraminal stenosis in the cross-sectional view of preoperative myelographic computed tomography. RESULTS: In the paralysis group (9 muscles) and nonparalysis group (444 muscles), delay in latency was not observed in any muscle (0% and 0%), and 50% or more reduction of amplitude in 1 muscle (11%) and 22 (5%), prolongation of duration in 1 (11%) and 6 (1%), changes of waveform pattern in 3 (33%) and 40 (9%), and foraminal stenosis in 5 (56%) and 80 (18%), respectively. CONCLUSIONS: In the paralysis group, the incidences of waveform pattern change on intraoperative MEP and stenosis of the intervertebral foramen were higher than those in the nonparalysis group.

Prediction of clinical results of laminoplasty for cervical myelopathy focusing on spinal cord motion in intraoperative ultrasonography and postoperative magnetic resonance imaging.

STUDY DESIGN: Retrospective analysis of preoperative imaging and clinical data from patients undergoing cervical expansive laminoplasty for cervical myelopathy. OBJECTIVE: To investigate preoperative parameters that predict the floating status of the spinal cord at the anterior elements of the cervical spine in both intraoperative ultrasonography (US) and postoperative magnetic resonance imaging (MRI), and to evaluate the association between clinical outcome and spinal cord floating. SUMMARY OF BACKGROUND DATA: Intraoperative US has been used to evaluate the status of the spinal cord after cervical laminoplasty for cervical myelopathy. Few studies have evaluated the predictive preoperative parameters for intraoperative US results. METHODS: Imaging and clinical outcome data were collected from 101 consecutive patients who underwent cervical expansive laminoplasty for cervical myelopathy at Kaikoukai Nagoya Kyouritsu Hospital, Japan, from April 2004 to April 2008. The preoperative parameters associated with spinal cord floating in intraoperative US and postoperative MR images were investigated. Predictive parameters for the rate of recovery according to the Japanese Orthopedic Association score for cervical myelopathy at each follow-up session were also investigated. RESULTS: Predictive parameters for spinal cord floating after decompression in intraoperative US were the cervical vertebrae 2 to 7 (C2-C7) sagittal alignment in the standing neutral position on preoperative plain radiograph radiography (cut-off value=3 degrees) and the C5/6 "beak angle" in preoperative MRI (cut-off value=20 degrees). A predictive parameter for spinal cord floating in postoperative MRI was the C5/6 beak angle in preoperative MRI (cut-off value=21 degrees). The preoperative Japanese Orthopedic Association score and spinal cord floating at anterior elements of the cervical spine in intraoperative US were predictive parameters for clinical outcome. CONCLUSION: Intraoperative US was more useful than postoperative MRI for predicting the clinical outcome of cervical expansive laminoplasty. Knowledge of the predictive parameters for spinal cord floating after cervical expansive laminoplasty could help evaluate the limitations of posterior decompression.

Cyclooxygenase-2 overexpression predicts poor survival in patients with high-grade extremity osteosarcoma: a pilot study.

UNLABELLED: Several lines of evidence suggest cyclooxygenase-2 (COX-2) overexpression may be a causal factor for tumor growth and metastasis. However, there is no evidence COX-2 expression in a primary tumor correlates with clinical outcome of osteosarcoma. We examined expression levels of COX-2 immunohistochemically in 51 patients with extremity osteosarcoma who completed standard therapy and obtained complete initial regression of the tumor. Correlation of the positivity of staining with prognosis was analyzed. COX-2 was expressed in most of the cases. We found no correlation between COX-2 staining intensity and variables such as gender, age, anatomic site, necrosis after chemotherapy, and surgical stage. Strong COX-2 expression was associated with low metastasis-free survival. Age older than 20 years and strong COX-2 expression independently predicted increased risk of metastasis. Among seven patients with resectable lung metastasis, all three with greater COX-2 expression in the metastatic lesion than that in a primary site died of the disease. Our preliminary data suggest COX-2 overexpression in the primary tumor correlates with the occurrence of distant metastasis in patients with osteosarcoma and also may affect postmetastatic survival. LEVEL OF EVIDENCE: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Pericellular matrix formation alters the efficiency of intracellular uptake of oligonucleotides in osteosarcoma cells.

One of the crucial roles of tumor extracellular matrix is to act as a barrier to drug delivery. In this study, we analyzed the relationship between the formation of tumor extracellular matrix and the efficiency of intracellular uptake of oligonucleotides in human osteosarcoma cell lines, HOS, and MG-63. Oligonucleotides used in this study were nuclear factor-kappa B (NF-kappaB) decoy, which might be a therapeutic tool for neoplasms. Pericellular matrix formation was examined by particle exclusion assay. Cellular uptake of fluorescein isothiocyanate-labeled NF-kappaB decoy was evaluated by fluorescent microscopy and flow cytometry. Effects of NF-kappaB decoy on cell viability and cell cycle arrest in MG-63 cells were determined by MTT assay and flow cytometry, respectively. MG-63 cells exhibited abundant pericellular matrix with time compared with HOS cells. Uptake of fluorescein isothiocyanate-labeled NF-kappaB decoy decreased in MG-63 cells with time but not in HOS cells in both monolayer and three-dimensional culture using matrigel. However, after enzymatic removal of pericellular matrix, the uptake markedly recovered in MG-63 cells. NF-kappaB decoy inhibited cell proliferation and induced G0/G1 cell cycle arrest in MG-63 cells. These results suggest that abundant pericellular matrix might disturb the uptake of NF-kappaB decoy, and modification of pericellular matrix composition would increase the efficacy of exogenous oligonucleotides treatment for neoplasms.

Hyaluronan oligosaccharides inhibit tumorigenicity of osteosarcoma cell lines MG-63 and LM-8 in vitro and in vivo via perturbation of hyaluronan-rich pericellular matrix of the cells.

Numerous studies have demonstrated a correlation between hyaluronan expression and the malignant properties of various kinds of cancer, and inhibition of hyaluronan production causes decreased tumor growth. Hyaluronan oligosaccharides have been shown to inhibit several tumor cell types via disruption of receptor-hyaluronan interaction. However, few studies have addressed hyaluronan with respect to osteosarcoma. In this study, we examined the effects of exogenously added hyaluronan oligosaccharides on tumorigenicity of murine osteosarcoma cells, LM-8, and human osteoblastic osteosarcoma cells, MG-63. Moreover, the critical size of oligomers needed to inhibit malignant properties was defined. Fluorescent hyaluronan oligosaccharides accumulated both on the surface of cells and in the cytoplasm, and this retention was blocked by pretreatment with an anti-CD44 monoclonal antibody. Hyaluronan octasaccharides significantly inhibited cell viability and induced apoptosis as defined by cell proliferation and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays, respectively. Octasaccharides also abrogated functional cell-associated matrices and significantly reduced the retention of endogenous hyaluronan. Further, octasaccharide treatment affected an inhibition of cell motility as well as cell invasiveness. Pretreatment of the cells with anti-CD44 antibody reduced the antitumor effect of the octasaccharides. In vivo, intratumoral injection of hyaluronan octasaccharides reduced the hyaluronan accumulation in local tumors, resulting in significant suppression of the formation of distant lung metastasis. Together these data suggest that hyaluronan oligosaccharides have potent antitumor effects functioning in part by the abrogation of hyaluronan-rich cell-associated matrices.

Cyclooxygenase-2 expression in ependymoma of the spinal cord.

OBJECT: Cyclooxygenase-2 (COX-2), also known as prostaglandin endoperoxide synthase, has been reported to play an important role in the tumorigenicity of many types of tumors. The expression of COX-2 in spinal ependymomas, however, has not been studied. The authors evaluated COX-2 expression in ependymoma of the spinal cord. METHODS: Sixteen ependymoma samples obtained in patients undergoing surgery between 1995 and 2004 were utilized for immunohistochemical studies to evaluate COX-2 and vascular endothelial growth factor (VEGF) expression. Intratumoral microvessels were also stained immunohistochemically using anti-human von Willebrand factor antibody and were quantified to determine the microvessel density (MVD). The clinical features were reviewed and recorded and the association with COX-2 expression was assessed. Seven (43.8%) of the 16 ependymoma specimens expressed COX-2. All three of the myxopapillary-type ependymomas exhibited COX-2-positive staining. Excluding the three myxopapillary-type cases, COX-2 expression was identified in four (30.8%) of 13 cellular-type ependymomas. The COX-2-positive samples exhibited a significant increase in VEGF-positive staining cells and MVD compared with COX-2-negative samples. The clinical features were not associated with COX-2 expression. CONCLUSIONS: The results of the present study indicate that COX-2 expression may promote angiogenesis through VEGF expression in ependymomas of the spinal cord. It is suggested that the use of selective COX-2 inhibitors may provide a new therapeutic strategy for spinal cord ependymomas due to their inhibition of the COX-2-mediated angiogenesis.

Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes.

Cyclooxygenase-2 (COX-2) inhibitors exert antitumor activity via COX-2-dependent and independent pathways. We wished to evaluate the antitumor activity of meloxicam, a preferential COX-2 inhibitor, in osteosarcoma, the most common primary malignant bone tumor, and determine whether its antitumor effect is COX-2-dependent. COX-2 expression in the osteosarcoma cell lines MG-63, HOS and U2-OS was determined by real-time RT-PCR and western blotting. Subsequently, the inhibitory effects of meloxicam on osteosarcoma cell growth and invasiveness were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and matrigel invasion assays, respectively. Apoptotic activity was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining and semi-quantification of Bax and Bcl-2 expression by real time RT-PCR and western blotting. Prostaglandin-E(2) (PGE(2)) production in the presence and absence of meloxicam was analyzed by enzyme immunoassay, and to determine whether the effects of meloxicam are COX-2-dependent or independent, PGE(2) was added to see if it reversed the effects of meloxicam. In addition, the effects of meloxicam on tumor growth and metastasis were evaluated in an in vivo mouse model using grafted LM-8 mouse osteosarcoma cells, together with immunohistochemical analysis for vascular endothelial growth factor in lung metastatic lesion. Meloxicam inhibited PGE(2) production, proliferation and invasiveness especially in MG-63 cells, which express relatively high levels of COX-2. Only high concentrations of meloxicam caused apoptosis and upregulated Bax mRNA and protein in MG-63 cell culture. In contrast, meloxicam did not induce apoptosis in HOS and U2-OS cells, expressing relatively low levels of COX-2. Exogenous PGE(2) reduced the effects of meloxicam on cell viability and invasiveness, but not its effect on Bax mRNA. In vivo, high doses of meloxicam suppressed LM-8 tumor growth and lung metastasis. Meloxicam, may have both COX-2-dependent and independent inhibitory actions on osteosarcoma. Its effects are more prominent in osteosarcoma cells that have relatively high levels of COX-2.