Wataru Ishida

Use of S2-Alar-Iliac Screws Associated with Less Complications than Iliac Screws in Adult Lumbosacropelvic Fixation.

Study Design. Retrospective comparative study. Objective. To compare clinical and radiographic outcomes between the S2-alar-iliac (S2AI) and the iliac screw (IS) techniques in the adult population and clarify the clinical strength of S2AI screws. Summary of Background Data. S2AI screws have been described as an alternative method for lumbosacropelvic fixation in place of ISs. The S2AI technique has several advantages with lower prominence, increased ability to directly connect to proximal instrumentation, less extensive dissection of tissue, and enhanced biomechanical strength over the IS technique. However, the clinical significance of these advantages remains unclear. Methods. A single-center retrospective review of patients who underwent lumbosacropelvic fixation yielded 25 IS group patients and 65 S2AI group patients. Baseline demographic information, postoperative complications, pain and functional outcomes, and screw-related outcomes were collected. Results. The S2AI group had lower rates of reoperation (8.8% vs. 48.0%, P < 0.001), surgical site infection (SSI) (1.5% vs. 44.0%, P < 0.001), wound dehiscence (1.5% vs. 36.0%, P < 0.001), and symptomatic screw prominence (0.0% vs. 12.0%, P = 0.02) than the IS group, whereas rates of L5-S1 pseudarthrosis, proximal junctional failure, and sacroiliac joint pain were similar in both groups. Statistically significant pain relief and functional recovery were achieved in both groups without any significant intergroup differences. On multivariate analyses, age [odds ratio (OR) = 0.91, P = 0.004] and S2AI instrumentation (OR = 0.08, P < 0.001) were protective of reoperation, whereas diabetes mellitus (OR = 10.9, P = 0.03) and preoperative diagnosis of tumor (OR = 12.3, P = 0.04) were associated with SSI, and S2AI instrumentation (OR = 0.09, P < 0.001) was protective of SSI. Conclusion. The use of the S2AI technique over the IS technique was an independent predictor of preventing reoperation and SSI, while achieving similar clinical and functional outcomes. Level of Evidence: 4

Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis

OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3-9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5-6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

Comparison Between S2-Alar-Iliac Screw Fixation and Iliac Screw Fixation in Adult Deformity Surgery: Reoperation Rates and Spinopelvic Parameters

Study Design: Retrospective cohort study. Objective: The S2-alar-iliac (S2AI) technique has been described as an alternative method for pelvic fixation in place of iliac screws (ISs) in spinal deformity surgery. The objective of this study was to analyze the impact of S2AI screws on radiographical outcomes, including spinopelvic parameters. Methods: A retrospective review of 17 patients receiving ISs and 46 patients receiving S2AI screws for correction of adult spinal deformity between 2010 and 2015 with minimum 1-year follow-up was conducted. Patient data on postoperative complications, including reoperation rates and proximal junctional kyphosis (PJK), and radiographical parameters was collected and statistically analyzed. Results: With mean follow-up of 21.1 months, the overall reoperation rate was significantly lower in the S2AI group than in the IS group (21.7% vs 58.8%, P = .01), but the incidence of PJK was similar (32.6% vs 35.3%, P > .99). Moreover, the time to reoperation in the IS group was significantly shorter than in the S2AI group (P = .001), and the S2AI group trended toward a longer time to reoperation due to PJK (P = .08). There was a significantly higher change in pelvic incidence (PI) in the S2AI group (−6.0°) compared with the IS group (P = .001). Conclusions: Compared with the IS technique, the S2AI technique demonstrated a lower rate of overall reoperation, a similar rate of PJK, longer time to reoperation, and possible reduction in PI. Future studies may be warranted to clarify the mechanism of these results and how they can be translated into improved patient care.

Clinical outcomes following sublaminar decompression and instrumented fusion for lumbar degenerative spinal pathology

Traditional treatment for lumbar stenosis with instability is laminectomy and posterolateral arthrodesis, with or without interbody fusion. However, laminectomies remove the posterior elements and decrease the available surface area for fusion. Therefore, a sublaminar decompression may be a preferred approach for adequate decompression while preserving bone surface area for fusion. A retrospective review of 71 patients who underwent sublaminar decompression in conjunction with instrumented fusion for degenerative spinal disorders at a single institution was performed. Data collected included demographics, preoperative symptoms, operative data, and radiographical measurements of the central canal, lateral recesses, and neural foramina, and fusion outcomes. Paired t-tests were used to test significance of the outcomes. Thirty-one males and 40 females with a median age 60years underwent sublaminar decompression and fusion. A median of two levels were fused. The mean Visual Analog Scale pain score improved from 6.7 preoperatively to 2.9 at last follow-up. The fusion rate was 88%, and the median time to fusion was 11months. Preoperative and postoperative mean thecal sac cross-sectional area, right lateral recess height, left lateral recess height, right foraminal diameter, and left foraminal diameter were 153 and 209mm(2) (p<0.001), 5.9 and 5.9mm (p=0.43), 5.8 and 6.3mm (p=0.027), 4.6 and 5.2mm (p=0.008), and 4.2 and 5.2mm (p<0.001), respectively. Sublaminar decompression provided adequate decompression, with significant increases in thecal sac cross-sectional area and bilateral foraminal diameter. It may be an effective alternative to laminectomy in treating central and foraminal stenosis in conjunction with instrumented fusion.

Combined HDAC and Bromodomain Protein Inhibition Reprograms Tumor Cell Metabolism and elicits Synthetic Lethality in Glioblastoma

Purpose: Glioblastoma remains a challenge in oncology, in part due to tumor heterogeneity. Experimental Design: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. Results: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that the combination of histone deacetylase (HDAC) inhibition and bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells. Transcriptome-based GSEA analysis suggests that metabolic reprogramming is involved with synergistic reduction of oxidative and glycolytic pathways in the combination treatment. Extracellular flux analysis confirms that combined HDAC inhibition and BRD inhibition blunts oxidative and glycolytic metabolism of cancer cells, leading to a depletion of intracellular ATP production and total ATP levels. In turn, energy deprivation drives an integrated stress response, originating from the endoplasmic reticulum. This results in an increase in proapoptotic Noxa. Aside from Noxa, we encounter a compensatory increase of antiapoptotic Mcl-1 protein. Pharmacologic, utilizing the FDA-approved drug sorafenib, and genetic inhibition of Mcl-1 enhanced the effects of the combination therapy. Finally, we show in orthotopic patient-derived xenografts of GBM, that the combination treatment reduces tumor growth, and that triple therapy involving the clinically validated compounds panobinostat, OTX015, and sorafenib further enhances these effects, culminating in a significant regression of tumors in vivo. Conclusions: Overall, these results warrant clinical testing of this novel, efficacious combination therapy. Clin Cancer Res; 24(16); 3941–54. ©2018 AACR.

The Effects of High-Dose Parathyroid Hormone Treatment on Fusion Outcomes in a Rabbit Model of Posterolateral Lumbar Spinal Fusion Alone and in Combination with Bone Morphogenetic Protein 2 Treatment

BACKGROUND Parathyroid hormone (PTH) (1-34) treatment reduces fracture risk in osteoporotic patients. Previously, we demonstrated in a rabbit model that low-dose PTH treatment resulted in increased fusion mass volume. As effects of PTH on bone are dose-dependent, we aimed to evaluate whether increasing dosage of PTH increases both volume and biomechanical stiffness of the resulting fusion masses and/or exhibits synergistic effects with low-dose bone morphogenetic protein 2 (BMP-2). METHODS Posterolateral lumbar spinal fusion surgery was performed on 60 New Zealand White rabbits divided into 6 experimental groups: iliac crest autograft alone, autograft plus 20 μg/kg/day PTH, autograft plus 40 μg/kg/day PTH, BMP-2 alone, BMP-2 plus 20 μg/kg/day PTH, and BMP-2 plus 40 μg/kg PTH. Fusion was assessed at postoperative week 6 via manual palpation, volumetric computed tomography analysis, and 4-point bending biomechanical testing. RESULTS All groups treated with BMP-2 fused. Increasing doses of PTH resulted in increased fusion mass volume compared with autograft alone. Autograft plus 40 μg/kg/day PTH yielded fusion mass volumes comparable to BMP-2. When the autograft groups were considered alone, increased mechanical stiffness was observed only in the 20 μg/kg/day group. No significant stiffness differences were observed between BMP-2 groups. CONCLUSIONS Treatment with the highest dose of PTH resulted in fusion mass volumes similar to those obtained with BMP-2. When the autograft groups were considered alone, significant increases in mechanical stiffness were observed at a dosage of 20 μg/kg/day, suggesting there may be an optimal dose of PTH in the rabbit model. Effects of BMP-2 on fusion were dominant.

Indications and Techniques for Anterior Thoracolumbar Resections and Reconstructions

Metastatic spinal tumors are the most common spinal neoplasms and often lead to significant morbidity due to neurological dysfunction and axial pain. Indications for resection and subsequent reconstruction of thoracolumbar spine tumors include intractable pain, impending spinal instability, progressive compression of the spinal cord by bony elements, and symptomatic compression of those neural structures by radio-resistant tumors. When deciding on a surgical approach, the location of the pathology and any neural compression should be considered first. The predicted life expectancy of each patient (Tokuhashi score) should also be strongly considered when considering indications for surgery as well as determining a specific reconstruction method. Although posterior approaches are often used for spinal tumor resection, there are anterior approaches to the cervical spine, cervicothoracic junction, thoracic spine, thoracolumbar junction, and lumbar spine that will be reviewed in detail below. Each surgical approach has its advantages and disadvantages and should be carefully tailored for each patient, with the deciding focus on the location of the pathology within the spinal column.