Imatinib Inhibits GH Secretion From Somatotropinomas

Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line.Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/β) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways.Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-β (PDGFR-β; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-β pathway.Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas

How Safe and Effective Is Shifting from Pterional to Supraorbital Keyhole Approach for Clipping Ruptured Anterior Circulation Aneurysms? A Surgeon’s Transition Phase Comparative Study

Background Comparative studies between standard pterional and supraorbital keyhole approaches for aneurysms had potential biases with the heterogeneity of patient selection, differences among surgeons, or varying expertise across the surgeon’s learning curve. This is a study of a surgeon’s transition from pterional to keyhole approach for early clipping of selected consecutive ruptured anterior circulation aneurysms. Methods Patients more than 18 years, presenting within 72 hours of ictus, in good clinical grades 1 to 3, no midline shift, with saccular aneurysms less than 25 mm at either communicating segment of internal carotid artery, anterior communicating artery, or middle cerebral artery segment till bifurcation were studied between the last 25 cases of pterional and first 25 cases of the keyhole, for the intraoperative and postoperative surgical outcome parameters. Results There was no significant difference among baseline parameters, including the location of aneurysms across both groups. While only four cases of pterional had an intraoperative ventricular puncture, the lumbar drain was electively inserted in all keyhole patients. The intraoperative parameters, such as a dural tear, adequate parent vessel exposure, temporary clipping, and intraoperative rupture, did not show any significant difference. None had immediate postoperative deficits. While delayed cerebral ischemia and wound complaints were similar in both groups, temporal hollowing and chewing difficulty were significantly more in pterional patients(p = 0.01). Conclusion A surgeon experienced in pterional approach can comfortably and safely shift to the keyhole for early clipping of selected ruptured aneurysms less than 25 mm, with a comparable surgical outcome but better cosmesis and mastication