Bone Morphogenic Protein Is a Viable Adjunct for Fusion in Minimally Invasive Transforaminal Lumbar Interbody Fusion

Study DesignComparison of prospectively collected data of patients undergoing minimally invasive surgery transforaminal lumbar interbody fusion (MIS-TLIF) with and without recombinant human bone morphogenic protein 2 (BMP).PurposeTo compare the clinical, radiological outcome and complications of patients undergoing MIS-TLIF with and without BMP.Overview of LiteratureBMP is an effective fusion enhancer with potential complications. Direct comparison of MIS-TLIF with and without BMP is limited to retrospective studies with short follow-up.MethodsFrom June 2005 to February 2011, consecutive cases of MIS-TLIF performed by a single surgeon were included. North American Spine Society (NASS) score, Oswestry disability index (ODI), Short Form-36 (SF-36), and visual analogue score (VAS) were assessed preoperatively and at 6 and 24 months postoperatively. Fusion rates and complications were noted.ResultsThe 252 cases comprised 104 non-BMP and 148 BMP cases. The BMP group was significantly older (mean age, 60.2 vs. 53.9; p<0.01). Preoperative scores were similar. Immediate postoperative morphine usage was significantly lower in the BMP group (12.4 mg vs. 20.1 mg, p<0.01). At 6 months, the BMP group had lower VAS back and leg pain scores (p<0.01). At 2 years, the BMP group had better leg pain scores (p<0.01), ODI (15.4 vs. 20.3, p=0.04) and NASS scores (8.8 vs. 15.8, p<0.01). Both groups showed significant clinical improvement compared to their preoperative levels. The BMP group attained a significantly higher rate of fusion at 6 months follow-up (88.4% vs. 76.8%, p=0.016) with no difference at 2 years. The non-BMP and BMP group had 12 (11.5%) and 9 (6.1%) complications and 5 (4.8%) and 2 (1.4%) reoperations, respectively.ConclusionsThe use of BMP to augment fusion in MIS-TLIF is an acceptable alternative that has potential benefits of less pain in early and intermediate postoperative follow-up

Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion Provides Sustained Improvements in Clinical and Radiological Outcomes up to 5 Years Postoperatively in Patients with Neurogenic Symptoms Secondary to Spondylolisthesis

Study DesignRetrospective review of prospective registry data.PurposeTo determine 5-year clinical and radiological outcomes of single-level instrumented minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in patients with neurogenic symptoms secondary to spondylolisthesis.Overview of LiteratureMIS-TLIF and open approaches have been shown to yield comparable outcomes. This is the first study to assess MIS-TLIF outcomes using the minimal clinically important difference (MCID) criterion.MethodsThe outcomes of 56 patients treated by a single surgeon, including the Oswestry disability index (ODI), neurogenic symptom score, short-form 36 questionnaire (SF-36), and visual analog scale (VAS) scores for back pain (BP), and leg pain (LP), were collected prospectively for up to 5 years postoperatively. Radiological outcomes included adjacent segment degeneration, fusion, cage subsidence, and screw loosening rates.ResultsOur patients were predominantly female (71.4%) and had a mean age of 53.7±11.3 years and mean body mass index of 25.7±3.7 kg/m2. The mean operative time, blood loss, time to ambulation, and hospitalization were 167±49 minutes, 126±107 mL, 1.2±0.4 days, and 2.8±1.1 days, respectively. The mean fluoroscopic time was 58.4±33 seconds, and the mean postoperative intravenous morphine dose was 8±2 mg. Regarding outcomes, postoperative scores improved relative to preoperative scores, and this was sustained across various time points for up to 5 years (p<0.001). Improvements in ODI, SF-36, VAS-BP, and VAS-LP all met the MCID criterion. Notably, 5.4% of our patients developed clinically significant adjacent segment disease during follow-up, and 7 minor complications were reported.ConclusionsSingle-level instrumented MIS-TLIF is suitable for patients with neurogenic symptoms secondary to lumbar spondylolisthesis and is associated with an acceptable complication rate. Both clinical and radiological outcomes were sustained up to 5 years postoperatively, with many patients achieving an MCID

Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion Provides Sustained Improvements in Clinical and Radiological Outcomes up to 5 Years Postoperatively in Patients with Neurogenic Symptoms Secondary to Spondylolisthesis

Study DesignRetrospective review of prospective registry data.PurposeTo determine 5-year clinical and radiological outcomes of single-level instrumented minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in patients with neurogenic symptoms secondary to spondylolisthesis.Overview of LiteratureMIS-TLIF and open approaches have been shown to yield comparable outcomes. This is the first study to assess MIS-TLIF outcomes using the minimal clinically important difference (MCID) criterion.MethodsThe outcomes of 56 patients treated by a single surgeon, including the Oswestry disability index (ODI), neurogenic symptom score, short-form 36 questionnaire (SF-36), and visual analog scale (VAS) scores for back pain (BP), and leg pain (LP), were collected prospectively for up to 5 years postoperatively. Radiological outcomes included adjacent segment degeneration, fusion, cage subsidence, and screw loosening rates.ResultsOur patients were predominantly female (71.4%) and had a mean age of 53.7±11.3 years and mean body mass index of 25.7±3.7 kg/m2. The mean operative time, blood loss, time to ambulation, and hospitalization were 167±49 minutes, 126±107 mL, 1.2±0.4 days, and 2.8±1.1 days, respectively. The mean fluoroscopic time was 58.4±33 seconds, and the mean postoperative intravenous morphine dose was 8±2 mg. Regarding outcomes, postoperative scores improved relative to preoperative scores, and this was sustained across various time points for up to 5 years (p<0.001). Improvements in ODI, SF-36, VAS-BP, and VAS-LP all met the MCID criterion. Notably, 5.4% of our patients developed clinically significant adjacent segment disease during follow-up, and 7 minor complications were reported.ConclusionsSingle-level instrumented MIS-TLIF is suitable for patients with neurogenic symptoms secondary to lumbar spondylolisthesis and is associated with an acceptable complication rate. Both clinical and radiological outcomes were sustained up to 5 years postoperatively, with many patients achieving an MCID

Short segment bone-on-bone instrumentation for single curve idiopathic scoliosis.

STUDY DESIGN: Retrospective case series review. OBJECTIVES: To evaluate the outcomes of a new short segment anterior scoliosis technique with complete removal of the discs, bone-on-bone apposition of the vertebral bodies, and dual rod instrumentation. To evaluate a new preop planning technique for scoliosis instrumentation. SUMMARY OF BACKGROUND DATA: Scoliosis surgery traditionally was performed via a posterior approach, but anterior scoliosis instrumentation has proven to be superior regarding the amount of curve correction and the number of segments saved from instrumentation. METHODS: Thirty-one patients with single curve idiopathic scoliosis less than 75 degrees were operated using the bone-on-bone surgical technique with dual rod instrumentation (Kaneda Anterior Scoliosis System, Depuy AcroMed, Raynham, MA from 1996 until 2001). Average follow-up was 40 months (range 15-77 months). RESULTS: Surgical correction of the major curve averaged 73.9% over the instrumented levels and 51.4% over the entire curve. The average number of discs fused was 4.6 for thoracic curves and 3.3 for thoracolumbar and lumbar curves. There were no implant-related complications or nonunions. The compensatory curves spontaneously improved by an average of 38.6%. Uneventful healing of all fusions occurred-most within 8 to 12 weeks. One compensatory thoracic curve progressed and posterior instrumentation was done 28 months after correction of the major thoracolumbar curve. CONCLUSIONS: Surgical correction was achieved in over half the levels that would have been operated by standard posterior segmental fixation. Bony healing due to the bone-on-bone apposition was achieved uneventfully after apical correction of the spinal curvature in all patients. Use of dual rod instrumentation (Kaneda Anterior Scoliosis System) is fundamental in maintaining the correction of the curvature achieved in the operating room. The preoperative planning technique worked well

Cortical Reorganization Is Associated with Surgical Decompression of Cervical Spondylotic Myelopathy

Background. Cervical spondylotic myelopathy (CSM) results in sensorimotor limb deficits, bladder, and bowel dysfunction, but mechanisms underlying motor plasticity changes before and after surgery are unclear. Methods. We studied 24 patients who underwent decompression surgery and 15 healthy controls. Patients with mixed upper and lower limb dysfunction (Group A) and only lower limb dysfunction (Group B) were then analysed separately. Results. The sum amplitude of motor evoked potentials sMEP (p<0.01) and number of focal points where MEPs were elicited (N) (p<0.001) were significantly larger in CSM patients compared with controls. For Group A (16 patients), sMEP (p<0.01) and N (p<0.001) showed similar findings. However, for Group B (8 patients), only N (p=0.03) was significantly larger in patients than controls. Group A had significantly increased grip strength (p=0.02) and reduced sMEP (p=0.001) and N (p=0.003) after surgery. Changes in sMEP (cMEP) significantly correlated inversely with improved feeding (p=0.03) and stacking (p=0.04) times as was the change in number of focal points (NDiff) with improved writing times (p=0.03). Group B did not show significant reduction in sMEP or N after surgery, or significant correlation of cMEP or NDiff with all hand function tests. No significant differences in H reflex parameters obtained from the flexor carpi radialis, or central motor conduction time changes, were noted after surgery. Discussion. Compensatory expansion of motor cortical representation occurs largely at cortical rather than spinal levels, with a tendency to normalization after surgery. These mirrored improvements in relevant tasks requiring utilization of intrinsic hand muscles

Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 -9 ), but was less obvious in other types of solid tumors except for prostate and Epstein-Barr virus (EBV)-positive gastric cancer (FDR < 10 -3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection.Link_to_subscribed_fulltex

Nuclear Localization of DNAJB6 Is Associated with Survival of Patients with Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells

© 2015 AGA Institute. Background & Aims The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is part of a family of proteins that regulates chaperone activities. One of its isoforms, DNAJB6a, contains a nuclear localization signal and regulates β-catenin signaling during breast cancer development. We investigated the role of DNAJB6 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Methods We performed immunohistochemical analyses of primary ESCC samples and lymph node metastases from a cohort of 160 patients who underwent esophagectomy with no preoperative chemoradiotherapy at Hong Kong Queen Mary Hospital. Data were collected on patient outcomes over a median time of 12.1 ± 2.9 months. Retrospective survival association analyses were performed. Wild-type and mutant forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI, KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs, or by genome engineering. Bimolecular fluorescence complementation was used to study interactions between proteins in living cells. Results In primary ESCC samples, patients whose tumors had high nuclear levels of DNAJB6 had longer overall survival times (19.2 ± 1.8 months; 95% confidence interval [CI], 15.6-22.8 mo) than patients whose tumors had low nuclear levels of DNAJB6 (12.6 ± 1.4 mo; 95% CI, 9.8-15.4 mo; P =.004, log-rank test). Based on Cox regression analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower risk of death than patients with low levels (hazard ratio, 0.562; 95% CI, 0.379-0.834; P =.004). Based on log-rank analysis and Cox regression analysis, the combination of the nuclear level of DNAJB6 and the presence of lymph node metastases at diagnosis could be used to stratify patients into groups with good or bad outcomes (P < .0005 for both analyses). There was a negative association between the nuclear level of DNAJB6 and the presence of lymph node metastases (P =.022; Pearson Ï 2 test). Cancer cell lines that overexpressed DNAJB6a formed tumors more slowly in nude mice than control cells or cells that expressed a mutant form of DNAJB6a that did not localize to the nucleus. DNAJB6 knockdown in cancer cell lines promoted their growth as xenograft tumors in mice. A motif of histidine, proline, and aspartic acid in the J domain of DNAJB6a was required for its tumor-suppressive effects and signaling via AKT1. Loss of DNAJB6a resulted in up-regulation of AKT signaling in cancer cell lines and immortalized esophageal epithelial cells. Expression of a constitutively active form of AKT1 restored proliferation to tumor cells that overexpressed DNAJB6a, and DNAJB6a formed a complex with AKT1 in living cells. The expression of DNAJB6a reduced the sensitivity of ESCC to AKT inhibitors; the expression level of DNAJB6a affected AKT signaling in multiple cancer cell lines. Conclusions Nuclear localization of DNAJB6 is associated with longer survival times of patients with ESCC. DNAJB6a reduces AKT signaling, and DNAJB6 expression in cancer cells reduces their proliferation and growth of xenograft tumors in mice. DNAJB6a might be developed as a biomarker for progression of ESCC.Link_to_subscribed_fulltex

Supplementary Figure 7 from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma

Uncropped western blot images</p

Supplementary Figure 2 from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma

EBV in NPC268 can be induced into lytic phase using various chemical inducers.</p