Objectives/Hypotheses  The endoscopic endonasal approach (EEA) is the workhorse endoscopic procedure for sellar and parasellar pathology. Various reconstruction techniques have been reported following EEA surgery, ranging from no reconstruction to vascularized flaps. We review our institution's experience with sellar reconstruction following EEA and propose an evidence-based algorithm. Design  Retrospective review. Setting  Tertiary academic medical center. Participants  Patients who underwent endoscopic EEA surgery for sellar or parasellar pathology between March 1, 2013 and August 31, 2016. Main Outcome Measures  Patient demographic and clinicopathologic data were collected. Outcome measures included intraoperative and postoperative cerebrospinal fluid (CSF) leak rates and extent of resection (gross or subtotal). Results  Three hundred consecutive patients were included. Depending on the presence and grade of intraoperative CSF leak, cases were reconstructed using either a free mucosal graft (FMG) or nasoseptal flap (NSF). Intraoperative and postoperative CSF leak rates were 30.7% and 2.3%, respectively. Multivariable logistic regression found that intraoperative CSF leak was associated with recurrent disease (odds ratio [OR] 2.47, p  = 0.004), with no apparent predictors of postoperative CSF leak. Conclusions  Based on this large series, we propose the following algorithm for sellar reconstruction: FMG for no CSF leak; fat graft + FMG ± rigid fixation for low-grade leaks; and fat graft + NSF ± rigid fixation for high-grade leaks.

Objectives/Hypotheses  The endoscopic endonasal approach (EEA) is the workhorse endoscopic procedure for sellar and parasellar pathology. Various reconstruction techniques have been reported following EEA surgery, ranging from no reconstruction to vascularized flaps. We review our institutions experience with sellar reconstruction following EEA and propose an evidence-based algorithm. Design  Retrospective review. Setting  Tertiary academic medical center. Participants  Patients who underwent endoscopic EEA surgery for sellar or parasellar pathology between March 1, 2013 and August 31, 2016. Main Outcome Measures  Patient demographic and clinicopathologic data were collected. Outcome measures included intraoperative and postoperative cerebrospinal fluid (CSF) leak rates and extent of resection (gross or subtotal). Results  Three hundred consecutive patients were included. Depending on the presence and grade of intraoperative CSF leak, cases were reconstructed using either a free mucosal graft (FMG) or nasoseptal flap (NSF). Intraoperative and postoperative CSF leak rates were 30.7% and 2.3%, respectively. Multivariable logistic regression found that intraoperative CSF leak was associated with recurrent disease (odds ratio [OR] 2.47, p  = 0.004), with no apparent predictors of postoperative CSF leak. Conclusions  Based on this large series, we propose the following algorithm for sellar reconstruction: FMG for no CSF leak; fat graft + FMG ± rigid fixation for low-grade leaks; and fat graft + NSF ± rigid fixation for high-grade leaks.

Plasma membrane function requires distinct leaflet lipid compositions. Two of the P-type ATPases (flippases) in yeast, Dnf1 and Dnf2, translocate aminoglycerophospholipids from the outer to the inner leaflet, stimulated via phosphorylation by cortically localized protein kinase Fpk1. By monitoring Fpk1 activity in vivo, we found that Fpk1 was hyperactive in cells lacking Gin4, a protein kinase previously implicated in septin collar assembly. Gin4 colocalized with Fpk1 at the cortical site of future bud emergence and phosphorylated Fpk1 at multiple sites, which we mapped. As judged by biochemical and phenotypic criteria, a mutant (Fpk1(11A)), in which 11 sites were mutated to Ala, was hyperactive, causing increased inward transport of phosphatidylethanolamine. Thus, Gin4 is a negative regulator of Fpk1 and therefore an indirect negative regulator of flippase function. Moreover, we found that decreasing flippase function rescued the growth deficiency of four different cytokinesis mutants, which suggests that the primary function of Gin4 is highly localized control of membrane lipid asymmetry and is necessary for optimal cytokinesis.