Comparison between extended transsphenoidal and transcranial surgery for craniopharyngioma: focus on hypothalamic function and obesity.

PURPOSE: Patients suffering from craniopharyngiomas currently have good survival rates, but long-term sequelae, such as development of obesity, worsen their quality of life. Optimal treatment is still controversial and changed during the decades, becoming less aggressive. Transcranial (TC) surgery was the first approach to be used, followed by extended transsphenoidal (eTNS) access. This study aims to compare the two approaches in terms of risk of hypothalamic damage leading to obesity. METHODS: This is a monocentric retrospective analysis of post-puberal patients treated for primary craniopharyngioma. Postoperative obesity and percentual postsurgical BMI variation were considered proxy for hypothalamic function and used to fit regression models with basal BMI, type of surgery, tumor volume and hypothalamic involvement (anterior vs. anteroposterior). RESULTS: No difference in radicality was observed between the two approaches; eTNS was more effective in ameliorating visual function but was significantly associated with CSF leaks. The TC approach was associated with a higher incidence of diabetes insipidus. Regression analysis showed only tumor volume and basal BMI resulted as independent predictors for both postoperative obesity (respectively, OR 1.15, P = 0.041, and OR 1.57, P < 0.001) and percentual BMI variation (respectively, + 0.92%, P = 0.005, and - 1.49%, P = 0.001). CONCLUSIONS: Larger lesions portend a higher risk to develop postoperative obesity, independently of hypothalamic involvement. Interestingly, basal BMI is independent of lesional volume and is associated with postoperative obesity, but lesser postoperative BMI variation. The surgical approach does not influence the obesity risk. However, eTNS proves valid in managing large tumors with important hypothalamic invasion.

Enhanced SPARCL1 expression in cancer stem cells improves preclinical modeling of glioblastoma by promoting both tumor infiltration and angiogenesis.

Glioblastoma (GBM) is the most malignant brain tumor of adults and is characterized by extensive cell dissemination within the brain parenchyma and enhanced angiogenesis. Effective preclinical modeling of these key features suffers from several shortcomings. Aim of this study was to determine whether modulating the expression of extracellular matrix (ECM) modifiers in proneural (PN) and mesenchymal (MES) cancer stem cells (CSCs) and in conventional glioma cell lines (GCLs) might improve tumor invasion and vascularization. To this end, we selected secreted, acidic and rich in cysteine-like 1 (SPARCL1) as a potential mediator of ECM remodeling in GBM. SPARCL1 transcript and protein expression was assessed in PN and MES CSCs as well as GCLs, in their xenografts and in patient-derived specimens by qPCR, WB and IHC. SPARCL1 expression was then enforced in both CSCs and GCLs by lentiviral-based transduction. The effect of SPARCL1 gain-of-function on microvascular proliferation, microglia activation and advanced imaging features was tested in intracranial xenografts by IHC and MRI and validated by chorioallantoic membrane (CAM) assays. SPARCL1 expression significantly enhanced the infiltrative and neoangiogenic features of PN and MES CSC/GCL-induced tumors, with the concomitant activation of inflammatory responses associated with the tumor microenvironment, thus resulting in experimental GBMs that reproduced both the parenchymal infiltration and the increased microvascular density, typical of GBM. Overall, these results indicate that SPARCL1 overexpression might be instrumental for the generation of CSC-derived preclinical models of GBM in which the main pathognomonic hallmarks of GBMs are retrievable, making them suitable for effective preclinical testing of therapeutics.

Impact of flow and angioarchitecture on brain arteriovenous malformation outcome after gamma knife radiosurgery: the role of hemodynamics and morphology in obliteration.

BACKGROUND: Few studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR). METHODS: A prospectively enrolled single-center cohort of patients with bAVMs treated by GKSR has been studied to define independent predictors of obliteration with particular attention to angioarchitectural variables. Only patients older than 18 years old (y.o.), who underwent baseline digital subtraction angiography (DSA) and clinico-radiological follow-up of at least 36 months, were included in the study. RESULTS: Data of 191 patients were evaluated. After a mean follow-up of 80 months (range 37-173), total obliteration rate after first GKSR treatment was 66%. Mean dose higher than 22 Gy (P = .019, OR = 2.39, 95% CI 1.15-4.97) and flow rate dichotomized into high vs non-high (P < .001, OR = 0.23, 95% CI 0.11-0.51) resulted to be independent predictors of obliteration. Flow-surrogate angioarchitectural features did not emerge as independent outcome predictors. CONCLUSIONS: Flow rate seems to be associated in predicting outcome after GKSR conferring high-flow AVM a lower occlusion rate. Its role should be considered when planning radiosurgical treatment of bAVM, and it could be added to other parameters used in GKRS outcome predicting scales.

Radiosurgical treatment of arteriovenous malformations in a retrospective study group of 33 children: the importance of radiobiological scores.

PURPOSE: Arteriovenous malformations' (AVMs) obliteration depends on several factors; among the many factors that must be considered to obtain a high rate of obliteration and a low rate of complications, Flickinger-Pollock Score (FPS) seems to have an important role but still have to be validated in the pediatric population while Paddick-Conformity Index (PCI) still has no demonstration of its utility on the outcome and is considered only as a treatment quality marker. METHODS: We retrospectively analyzed 33 consecutive children (2-18 years) with an AVM, treated with stereotactic radiosurgery Gamma Knife (SRS-GK) from 2001 to 2014 in our institution. We assess angiographic (DSA) Obliteration Rate (OR) as well FPS and PCI to draw conclusions. RESULTS: DSA-OR was 60.6% with a rate of hemorrhage of 0%. median target volume (TV) was 3.60 cc (mean 4.32 ± 3.63; range 0.15-14.2), median PD was 22 Gy (mean 21.4 ± 2.6; range 16.5-25). Median percentage of coverage was 98% (mean 97 ± 3; range 84-100). The median modified FPS was 0.78 (mean 0.89 ± 0.52; range 0.21-2.1) and highly correlate with OR (p = 0.01). The median PCI was 0.65 (mean 0.65 ± 0.14; range 0.34-0.95) A PCI lower than 0.57 highly correlates with final OR (p = 0.02). CONCLUSION: SRS-GK was safe and gradually effective in children. A prescription dose-like that used in adult population (i.e. > 18 and between 20 and 25 Gy) is essential to achieve obliteration. A PD of 23 Gy and 22 Gy did impact OR, respectively (p = 0.02) and (p = 0.05). FPS and PCI are valuable scores that seem to correlate with the OR also in the pediatric population although further prospective studies are needed to confirm these observations.

A novel composite type I collagen scaffold with micropatterned porosity regulates the entrance of phagocytes in a severe model of spinal cord injury.

Traumatic spinal cord injury (SCI) is a damage to the spinal cord that results in loss or impaired motor and/or sensory function. SCI is a sudden and unexpected event characterized by high morbidity and mortality rate during both acute and chronic stages, and it can be devastating in human, social and economical terms. Despite significant progresses in the clinical management of SCI, there remain no effective treatments to improve neurological outcomes. Among experimental strategies, bioengineered scaffolds have the potential to support and guide injured axons contributing to neural repair. The major aim of this study was to investigate a novel composite type I collagen scaffold with micropatterned porosity in a rodent model of severe spinal cord injury. After segment resection of the thoracic spinal cord we implanted the scaffold in female Sprague-Dawley rats. Controls were injured without receiving implantation. Behavioral analysis of the locomotor performance was monitored up to 55 days postinjury. Two months after injury histopathological analysis were performed to evaluate the extent of scar and demyelination, the presence of connective tissue and axonal regrowth through the scaffold and to evaluate inflammatory cell infiltration at the injured site. We provided evidence that the new collagen scaffold was well integrated with the host tissue, slightly ameliorated locomotor function, and limited the robust recruitment of the inflammatory cells at the injury site during both the acute and chronic stage in spinal cord injured rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1040-1053, 2017.