Stereotactic Radio Surgery, Embolization and Conservative Management for Cerebral Arteriovenous Malformation: A New Zealand Experience of Long-Term Outcomes.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) can be treated by microsurgery, stereotactic radiosurgery (SRS) as a stand-alone procedure, or combining embolization and conservative management. This single-center, retrospective review explored the outcomes of patients treated with SRS alone, embolization before SRS (ESRS), or conservative management for cerebral AVMs. METHODS: Demographic details, Spetzler-Martin grade, SRS dose, obliteration, time to obliteration, imaging modality, rebleed, disease-specific mortality, and post-SRS complications were collected. Chi-square tests of independence and 1-way analysis of variance/Kruskal-Wallis tests were performed. RESULTS: Two-hundred and thirty-nine patients were treated with SRS alone, 37 were treated with ESRS, and 83 were conservatively managed. Obliteration rates were 78% (SRS alone) and 70% (ESRS). Rebleed rates were comparable among SRS alone (4%), ESRS (0%), and conservative management (8%). Disease-specific mortality rates were significantly lower for SRS alone (1%) and ESRS (0%) compared with conservative management (6%, X2 [2, n = 358] = 7.50, P = 0.024). Post-SRS complications occurred with SRS alone only and included radiation necrosis (n = 5), cavernous malformations (n = 2), and stroke (n = 1). Obliteration, rebleed, and disease-specific mortality rates were comparable among pediatric (<18 years), nonelderly (18-59 years), and elderly (≥60 years) age groups. CONCLUSIONS: Findings suggest that SRS and ESRS are safe and effective treatments for cerebral AVM (when quantified by obliteration, rebleed, and disease-specific mortality rates). With multinational, prospective, randomized controlled trials with long follow-up periods, the effectiveness and safety of SRS and ESRS compared with conservative management for AVM will be further clarified.

Crosstalk between ß-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells.

Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is a fast growing and highly heterogeneous tumor, often characterized by the presence of glioblastoma stem cells (GSCs). The plasticity of GSCs results in therapy resistance and impairs anti-tumor immune response by influencing immune cells in the tumor microenvironment (TME). Previously, ß-catenin was associated with stemness in GBM as well as with immune escape mechanisms. Here, we investigated the effect of ß-catenin on attracting monocytes towards GBM cells. In addition, we evaluated whether CCL2 is involved in ß-catenin crosstalk between monocytes and tumor cells. Our analysis revealed that shRNA targeting ß-catenin in GBMs reduces monocytes attraction and impacts CCL2 secretion. The addition of recombinant CCL2 restores peripheral blood mononuclear cells (PBMC) migration towards medium (TCM) conditioned by shß-catenin GBM cells. CCL2 knockdown in GBM cells shows similar effects and reduces monocyte migration to a similar extent as ß-catenin knockdown. When investigating the effect of CCL2 on ß-catenin activity, we found that CCL2 modulates components of the Wnt/ß-catenin pathway and alters the clonogenicity of GBM cells. In addition, the pharmacological ß-catenin inhibitor MSAB reduces active ß-catenin, downregulates the expression of associated genes and alters CCL2 secretion. Taken together, we showed that ß-catenin plays an important role in attracting monocytes towards GBM cells in vitro. We hypothesize that the interactions between ß-catenin and CCL2 contribute to maintenance of GSCs via modulating immune cell interaction and promoting GBM growth and recurrence.

A case report of lymphocytic hypophysitis.

BACKGROUND: Lymphocytic hypophysitis (LH) is a rare condition that mostly affects women of the reproductive age. Because it is infrequently encountered, it is not often considered as a differential diagnosis of sellar masses. The diagnosis is made clinically with the aid of magnetic resonance imaging (MRI) and should be considered if the patient has endocrine derangements in addition to a sellar mass. CASE DESCRIPTION: A 37-year-old female presents with a complaint of headaches and CT imaging showed a sellar mass. She was also being investigated simultaneously by the endocrine department and was diagnosed with panhypopituitarism. She proceeded to surgery for a presumed pituitary adenoma but histopathology returned as LH. CONCLUSION: It is important to have a wide differential diagnosis when managing pituitary masses. Clinical correlation with atypical MRI findings is useful to determine the diagnosis of LH.