The effect of a prostaglandin E-1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis

Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D). QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after a parts per thousand yen6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0-100). Leg pain, leg numbness, and low back pain while walking (VAS a parts per thousand yen25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time 30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by a parts per thousand yen10 min and the EQ-5D utility value was improved by a parts per thousand yen0.1 points in significantly more patients in the limaprost group than in the control group. According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.ArticleJOURNAL OF ORTHOPAEDIC SCIENCE. 18(2):208-215 (2013)journal articl

The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

Neuroblastoma (NB), which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2). In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB

Union versus nonunion after posterolateral lumbar fusion: a comparison of long-term surgical outcomes in patients with degenerative lumbar spondylolisthesis

It has been reported that in patients undergoing posterolateral lumbar fusion (PLF), the fusion status is not related to the short-term operative results. To determine whether the fusion status influences the long-term operative results of PLF, we retrospectively examined the surgical outcomes of uninstrumented PLF for a minimum of 8 years (average, 9.5 years), by comparing cases exhibiting union with those exhibiting nonunion. Uninstrumented PLF was performed for the treatment of lumbar canal stenosis (LCS) with degenerative spondylolisthesis. Since nine patients were lost to final follow-up, the study included 42 patients, and the follow-up rate was 82.4%. The mean age of the patients was 64.1 years (range 46–77 years). Eight patients exhibited fusion at the L3–4 level and 34 patients, at the L4–5 level. The fusion status was assessed using plain radiographs. The clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scores. Nonunion was noted in 26% (11/42) of the patients. There were no statistically significant differences between the groups exhibiting union and nonunion with respect to age, sex, preoperative JOA score, or preoperative lumbar instability. The union group achieved better operative results than the nonunion group at the 5-year and final follow-up (P = 0.006 and 0.008, respectively) although there was no significant difference in the percent recovery at 1 and 3-year follow-up (P = 0.515 and 0.506, respectively). A stepwise regression analysis revealed that the best combination of predictors for percent recovery at the time of final follow-up included the fusion status and the presence of comorbid disease. The results indicate that the fusion status following PLF is a critical factor influencing the long-term but not short-term operative results in the treatment of LCS with degenerative spondylolisthesis