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Somatotropinomas are pituitary tumors with a heterogenous clinical behavior. The tumor microenvironment regulates the interaction between tumor cells and the host immune system, potentially modulating tumor behavior. Here, we aimed to investigate the tumor immune infiltration in a cohort of medically naïve acromegaly patients. A retrospective, monocenter study was designed to analyze the presence of CD3+, CD20+, CD138+, CD4+, CD8+, CD68+ immune cells in samples of somatotropinomas and their prognostic significance on tumor behavior and response to first generation somatostatin analogs (fg-SSA). Thirty-six patients (23 females) were included in the study. Macroadenomas were identified in 23 cases: 12 with cavernous sinus invasion. The number of CD8+ lymphocytes positively correlated with CD4+ lymphocytes (p = .05, r:0.245) and with CD68+ macrophages (p = .01, r = 0.291). The CD8+/CD4+ ratio inversely correlated with CD68+/CD8+ ratio (p < .001, r = -0.626). CD68+ macrophages positively correlated with tumor size (maximum diameter p = .003, r = 0.574; volume p = .009, r = 0.566) and were more numerous in somatotropinomas with Ki-67 > 3% (median 65/HPF, IQR:15), compared to cases with Ki67 < 3% (median 50/HPF, IQR:22, p < .001). CD8+ and CD138+ lymphocytes were more numerous in cases responsive to fg-SSA (respectively median 18/HPF IQR:18 and median 8/HPF IQR: 6.5) as compared to fg-SSA nonresponsive cases (median 14.5/HPF IQR:40 p = .03; median 3.5/HPF IQR: 14 p = .03). CD8+ lymphocytes act as single predictor of response to fg-SSA, independently from age, GH and IGF-I levels, tumor dimension and invasion. Our results support that lymphocytes and macrophages generate an immune network in somatotropinomas and the characteristic of the immune infiltrate may predict treatment outcome.

The prognostic role of epidermal growth factor receptor variant III (EGFRvIII), a constitutively activated oncogenic receptor, in glioblastoma is controversial. We performed a prospective study enrolling 355 patients operated on for de novo glioblastoma at a large academic center. The molecular profile, including EGFRvIII status, MGMT promoter methylation, and VEGF expression, was assessed. Standard parameters (age, clinical status and extent of surgical resection) were confirmed to hold prognostic value. MGMT promoter methylation portended a slightly improved survival. In the whole series, confirming previous results, EGFRvIII was not associated with worsened prognosis. Interestingly, female sex was associated with a better outcome. Such findings are of interest for the design of future trials.

Background: Trans-sphenoidal endoscopic surgery has drawn huge benefits from advances in surgical visualization. The Ultra-HD "4K" endoscope has improved 4-fold image resolution compared with HD, but its actual advantages are unclear. Aim of the present study was to assess its usefulness in the early outcome of trans-sphenoidal surgery. Methods: We analyzed a series of 199 trans-sphenoidal pituitary adenoma procedures performed by an experienced team using alternatively HD (n=102) or 4K (n=97) endoscopes. We evaluated extent of resection both subjectively, based on intraoperative surgeon's impression, and objectively based on post-operative MR scan. Results: Baseline patients' characteristics were balanced. Objective near-total and total resection rates were comparable between 4K and HD groups (91.5% vs 86.3% and 64.9% vs 56.9%, respectively). 4K endoscope slightly improved resection rate in recurrent adenoma. At multivariate analysis, the only independent prognosticator of total resection was cavernous sinus invasion. Importantly, 4K endoscope enhanced the reliability of intraoperative judgement on extent of resection, significantly reducing unexpected residuals (12.8% vs 33.3% for HD). Operative features and clinical outcomes were similar. Conclusions: The HD endoscope remains the standard-of-care for pituitary surgery. The 4K enhanced, "immersive" visualization significantly improved the reliability of surgeon's judgment on resection and might be useful in surgically difficult cases.

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BACKGROUND: In transsphenoidal endoscopic cranial base surgery, a precise navigational support may be crucial. This is particularly evident when tumors extend to the parasellar region or in recurrent tumors whereas normal anatomy has been altered by previous surgery/radiotherapy. - METHODS: Previous unsatisfactory experiences with various navigation techniques in this type of surgery encouraged us to perform an endoscopic endonasal approach with an O-arm (Medtronic, Inc., Minneapolis, Minnesota, USA) assisted technique for the surgical treatment of 4 patients affected respectively by an orbital tumor and 3 cases of relapse of nonfunctioning pituitary adenoma, 1 of them localized in the infrasellar-clival region. - RESULTS: The system O-arm-StealthStation allows for merging intraoperative bone 3-D acquisition with preoperative computed tomography/magnetic resonance imaging and provides the surgeon with an extremely reliable operative navigational tool. - CONCLUSIONS: This is the first report of an O-armassisted endoscopic surgery for cranial base tumors. Here we report on the feasibility and usefulness of such a new application of the O-arm: technical details, setting of the operating room, advantages, and limits of the method are also described. Our overall impression, considering the limited number of patients, is that use of the O-arm may be successfully extended to selected cases of cranial base tumors operated through an endoscopic endonasal approach.