Clinical and Radiological Outcomes after Microscopic Bilateral Decompression via a Unilateral Approach for Degenerative Lumbar Disease: Minimum 5-Year Follow-Up

Study DesignA retrospective study.PurposeTo assess postoperative bone regrowth at surgical sites after lumbar decompression with >5 years of follow-up. Postoperative preservation of facet joints and segmental spinal instability following surgery were also evaluated.Overview of LiteraturePrevious reports have documented bone regrowth after conventional laminectomy or laminotomy and several factors associated with new bone formation.MethodsForty-nine patients who underwent microscopic bilateral decompression via a unilateral approach at L4–5 were reviewed. Primary outcomes included correlations among postoperative bone regrowth, preservation of facet joints, radiographic parameters, and clinical outcomes. Secondary outcomes included comparative analyses of radiographic parameters and clinical outcomes among preoperative diagnoses (lumbar spinal stenosis, degenerative spondylolisthesis, and degenerative lumbar scoliosis).ResultsThe average value of bone regrowth at the latest follow-up was significantly higher on the dorsal side of the facet joint (3.4 mm) than on the ventral side (1.3 mm). Percent facet joint preservation was significantly smaller on the approach side (79.2%) than on the contralateral side (95.2%). Bone regrowth showed a significant inverse correlation with age, but no significant correlation was observed with facet joint preservation, gender, postoperative segmental spinal motion, or clinical outcomes. Subanalysis of these data revealed that bone regrowth at the latest follow-up was significantly greater in patients with degenerative lumbar scoliosis than in those with lumbar spinal stenosis. Postoperative segmental spinal motion at L4–L5 did not progress significantly in patients with degenerative spondylolisthesis or degenerative lumbar scoliosis compared with those with lumbar spinal stenosis.ConclusionsMicroscopic bilateral decompression via a unilateral approach prevents postoperative spinal instability because of satisfactory preservation of facet joints, which may be the primary reason for inadequate bone regrowth. Postoperative bone regrowth was not related to clinical outcomes and postoperative segmental spinal instability

Identification of RNA biomarkers for chemical safety screening in mouse embryonic stem cells using RNA deep sequencing analysis

Although it is not yet possible to replace in vivo animal testing completely, the need for a more efficient method for toxicity testing, such as an in vitro cell-based assay, has been widely acknowledged. Previous studies have focused on mRNAs as biomarkers; however, recent studies have revealed that non-coding RNAs (ncRNAs) are also efficient novel biomarkers for toxicity testing. Here, we used deep sequencing analysis (RNA-seq) to identify novel RNA biomarkers, including ncRNAs, that exhibited a substantial response to general chemical toxicity from nine chemicals, and to benzene toxicity specifically. The nine chemicals are listed in the Japan Pollutant Release and Transfer Register as class I designated chemical substances. We used undifferentiated mouse embryonic stem cells (mESCs) as a simplified cell-based toxicity assay. RNA-seq revealed that many mRNAs and ncRNAs responded substantially to the chemical compounds in mESCs. This finding indicates that ncRNAs can be used as novel RNA biomarkers for chemical safety screening

Classification of chemical compounds based on the correlation between \textit{in vitro} gene expression profiles

Toxicity evaluation of chemical compounds has traditionally relied on animal experiments;however, the demand for non-animal-based prediction methods for toxicology of compounds is increasing worldwide. Our aim was to provide a classification method for compounds based on \textit{in vitro} gene expression profiles. The \textit{in vitro} gene expression data analyzed in the present study was obtained from our previous study. The data concerned nine compounds typically employed in chemical management.We used agglomerative hierarchical clustering to classify the compounds;however, there was a statistical difficulty to be overcome.We needed to properly extract RNAs for clustering from more than 30,000 RNAs. In order to overcome this difficulty, we introduced a combinatorial optimization problem with respect to both gene expression levels and the correlation between gene expression profiles. Then, the simulated annealing algorithm was used to obtain a good solution for the problem. As a result, the nine compounds were divided into two groups using 1,000 extracted RNAs. Our proposed methodology enables read-across, one of the frameworks for predicting toxicology, based on \textit{in vitro} gene expression profiles.Comment: 13pages, 7 figure

Compression Myelopathy Caused by Anterolisthesis and Hypertrophic Ligamentumflavum in the Adjacent Segment 11years after Cervical Laminoplasty-A Case Report and Review of the Literature

Introduction: Symptomatic adjacent segment disease after anterior cervical decompression and fusion has been well described, but there have been few reports of symptomatic adjacent segment disease after cervical laminoplasty.&nbsp;Case report: The authors report on a 69-year-old female gradually developed gait disturbance due to C7 anterolisthesis and ligamentumflavum thickening with an onset 11 years after conventional C3-7 laminoplasty. The patient underwent laminectomy from C6 to T1 and was able to return to ambulation. However, she experienced further deterioration in her ambulatory status four years after the second surgery, due to further anterior slippage of C7.Finally; she underwent posterior decompression and fusion from C5 to T3. The patient was able to return to ambulation with the assistance of a cane despite some level of spasticity.&nbsp;Conclusion: Compression myelopathy may occur as a late effect adjacent segment disease that produces a deteriorated condition after conventional cervical laminoplasty. Anterolisthesis with thickened ligamentumflavum at the cervico-thoracic junction needs to be fused and instrumented.</p

Pharmacokinetic study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy (KHBO1101)

Background: Biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1, 000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1, 000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and pharmacodynamics of gemcitabine in these subjects. Methods: We evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by gemcitabine therapy. A pharmacokinetic evaluation of gemcitabine and its main metabolite, 2′, 2′-difluorodeoxyuridine (dFdU), was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800-1, 000 mg/m2. Physical examination and adverse events were monitored for 12 weeks. Results: Thirteen patients were enrolled from August 2011 to January 2013, with 12 ultimately completing the pharmacokinetic study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had superficial spreading type cholangiocarcinoma. The median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43-83 days). We observed the following toxicities: neutropenia (n = 11, 91.7%), leukopenia (n = 10, 83.3%), thrombocytopenia (n = 6, 50.0%), and infection (n = 5, 41.7%). Grade 3 or 4 neutropenia was observed in 25% (n = 3) of patients. There were differences in clearance of gemcitabine and dFdU between our subjects and the subjects who had not undergone hepatectomy. Conclusion: Major hepatectomy did not affect the pharmacokinetics of gemcitabine or dFdU. Trial Registration: UMIN-CTR in (JPRN) UMIN000005109