Tumor characteristics and surgical outcomes of intracranial subependymomas: a systematic review and meta-analysis.

OBJECTIVE: The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies. METHODS: A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted. RESULTS: Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39-7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03-7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78-2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35-1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27-2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%). CONCLUSIONS: Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.

Current and future applications for stem cell therapies in spine surgery.

Spinal surgery involves the bone-cartilage-neural interface. It is a field of surgery that is rapidly changing and evolving; not only through the development of novel techniques, approaches and devices but also through evidence from large clinical trials assessing indications, efficacy and outcomes. The use of biologics in spine surgery has now become widespread. Biologics in the form of autologous or allogeneic stem cells or progenitor cells are not yet in routine clinical use in spine surgery. However it is likely that they will have a significant role in the future, since increasing numbers of preclinical and clinical studies have demonstrated the safety and efficacy of progenitor cells to treat a variety of spinal conditions. Such studies have paved the way to larger clinical trials. Cell therapies encompass a wide range of stem cell and progenitor cell types. Stem cells subtypes differ in their lineage potential often being described as pluripotent or multipotent, some of which have potential application in therapies to treat diseases of the spine having the ability to differentiate into tissues including bone and cartilage and to secrete factors that promote matrix repair and regeneration. Furthermore, studies have shown that some cells, particularly mesenchymal stromal cells, modulate oxidative stress and secrete cytokines and growth factors that have immunomodulatory, antiinflammatory, angiogenic and antiapoptotic effects. It is these combined characteristics that make cell based therapies prime candidates for advancing current techniques in spine surgery and for providing new strategies directed at targeting the underlying causes of spinal diseases and disorders to promote repair and regeneration. This review will explore the characteristics of various stem cells and other progenitor cells derived from different sources. The authors are not suggesting that all these cells are necessarily suitable clinically. The review will thus focus on their application to both current and potentially future areas of spine surgery based on results of the available evidence and clinical trials. This review will not address spinal cord injury.

A comparison of mesenchymal precursor cells and amnion epithelial cells for enhancing cervical interbody fusion in an ovine model.

BACKGROUND: Rapid, reliable fusion is the goal in anterior cervical diskectomy and fusion. Iliac crest autograft has a high rate of donor-site morbidity. Alternatives such as bone graft substitutes lack osteoinductivity, and recombinant bone morphogenetic proteins risk life-threatening complications. Both allogeneic mesenchymal precursor cells (MPCs) and amnion derived epithelial cells (AECs) have osteogenic potential. OBJECTIVE: To compare for the first time the capacity of MPCs and AECs to promote osteogenesis in an ovine model. METHODS: Five groups of 2-year-old ewes were subjected to C3-4 anterior cervical diskectomy and fusion with a Fidji interbody cage packed with iliac crest autograft alone (group A; n = 6), hydroxyapatite-tricalcium phosphate Mastergraft granules (HA/TCP) alone (group B; n = 6), HA/TCP containing 5 million MPCs (group C; n = 6), or HA/TCP containing 5 million AECs (group D; n = 5); group E was made up of age-matched nonoperative controls (n = 6). At 3 months, animals were euthanized and quantitative multislice computed tomography, functional radiography, biomechanics, histology, and histomorphometry were performed. RESULTS: No procedure- or cell-related adverse events were observed. There was significantly more fusion in the MPC group (C) than in group A, B, or D. Computed tomography scan at 3 months revealed that 5 of 6 MPC-treated animals (83%) had continuous bony bridging compared with 0 of 5 AEC-treated and only 1 of 6 autograft- and 2 of 6 HA/TCP-treated animals (P = .01). CONCLUSION: Implantation of allogeneic MPCs in combination with HA/TCP within an interbody spacer facilitates interbody fusion after diskectomy. The earlier, more robust fusion observed with MPCs relative to autograft and HA/TCP bone substitute indicates that this approach may offer a therapeutic benefit.

Potential applications for using stem cells in spine surgery.

While the use of biologics as adjuncts for spine surgery is growing annually stem cells have yet to be approved for this clinical application. Stem cells have the unique ability to differentiate into a variety of musculoskeletal tissues including bone or cartilage. Moreover they have been shown to secrete growth factors that promote matrix repair and regeneration and can down regulate inflammation and immune cell functions. It is these combined activities that make stem cells attractive candidates for advancing current techniques in spine surgery and possibly mitigating those pathologies responsible for tissue degeneration and failure thereby minimising the need for surgical intervention at a later date. This review focuses on the characteristics of progenitor cells from different sources and explores their potential as adjuncts for both current and future applications in spine surgery. Where possible we draw on the experimental outcomes from our own preclinical studies using adult mesenchymal progenitor stem cells, as well as related studies by others to support our contention that stem cell based therapies will play a significant role in spine surgery in the future.