Cusimano, Michael D.

SNAP‐25, a synaptosome associated exocytosis protein of 25 kDa plays an important role in the secretory activity of several endocrine cells. In the present study, we investigated 15 PRL, 10 GH, 5 ACTH, 5 TSH, 15 FSH/LH/ alpha subunit producing, and 5 null cell adenomas. Surgically removed, formalin‐fixed and paraffin embedded human pituitary tumors were used. Sections were immunostained by the streptavidin‐biotin‐peroxidase complex method. The results showed that 10 PRL producing adenomas were strongly immunoreactive for SNAP‐25. The immunopositive material was located mainly on the plasmalemma. The nuclei were immunonegative, the cytoplasm was mildly immunopositive in several cells. Treatment of patients with dopamine agonists before surgery decreased markedly SNAP‐25 immunopositivity in 5/10 cases. In GH producing adenomas SNAP‐25 was seen in 5 cases. Immunopositivity was mild‐ moderate, membrane bound and cytoplasmic. Somatostatin analogs caused no marked reduction in immunopositivity (5 cases). Other adenoma types were practically immunonegative. Among human pituitary adenomas only PRL producing tumors release their secretory granules via exocytosis as was demonstrated by electron microscopy. This observation is concordant with our results. In dopamine agonist treated patients, decreased SNAP‐25 expression in PRL producing adenoma cells is consistent with reduction of blood PRL levels.

BackgroundThe impact of failed cerebrospinal fluid leak (CSF) leak repair in endoscopic skull base surgery has not been adequately studied.MethodsIn this investigation we reviewed patients who had undergone endoscopic skull base surgery between 2002 and 2014 at 7 international centers. Demographic variables, comorbidities, tumor characteristics, and repair techniques were evaluated to determine association with successful repair of CSF leak. Postoperative complications and length of stay were compared among groups.ResultsData were collected on 2097 patients who were divided into 3 groups: (1) those with no intraoperative leak (n = 1533); (2) those with successful repair of their intraoperative leak (n = 452); and (3) those with failed repair (n = 112). Compared with successful repair, failed repair was associated with an increased risk of intracranial infection (odds ratio [OR], 5.6; 95% confidence interval [CI], 5.3‐13.15), pneumocephalus (OR, 16; 95% CI, 5.8‐44.4), 30‐day readmission (OR, 8.4; 95% CI, 5.3‐13.5), reoperation (OR, 115.4; 95% CI, 56.3‐236.8), and prolonged hospital stay (14.9 vs 7.0 days, p < 0.01). Outcomes in patients who had successful repairs of intraoperative leaks were similar to those who never had leakage. Intraoperative use of pedicled nasoseptal flaps was associated with successful repair (OR, 0.60; 95% CI, 0.34‐0.92).ConclusionIntraoperative CSF leaks are a frequent and expected occurrence during endoscopic skull base surgery. Failed CSF leak repair has a significant impact on patient outcomes, with increased rates of postoperative pneumocephalus, intracranial infections, reoperation, deep vein thrombosis, readmission, and prolonged hospital stay. Recognition and repair of intraoperative CSF leaks reduces postoperative complications. Use of pedicled nasoseptal flaps improves outcomes in reconstructing defects at higher risk for postoperative leak.

BackgroundIn patients undergoing transnasal endoscopic sellar surgery, an analysis of risk factors and predictors of intraoperative and postoperative cerebrospinal fluid leak (CSF) would provide important prognostic information.MethodsA retrospective review of patients undergoing endoscopic sellar surgery for pituitary adenomas or craniopharyngiomas between 2002 and 2014 at 7 international centers was performed. Demographic, comorbidity, and tumor characteristics were evaluated to determine the associations between intraoperative and postoperative CSF leaks. Correlations between reconstructive and CSF diversion techniques were associated with postoperative CSF leak rates. Odds ratios (OR) were identified using a multivariate logistic regression model.ResultsData were collected on 1108 pituitary adenomas and 53 craniopharyngiomas. Overall, 30.1% of patients had an intraoperative leak and 5.9% had a postoperative leak. Preoperative factors associated with increased intraoperative leaks were mild liver disease, craniopharyngioma, and extension into the anterior cranial fossa. In patients with intraoperative CSF leaks, postoperative leaks occurred in 10.3%, with a higher postoperative leak rate in craniopharyngiomas (20.8% vs 5.1% in pituitary adenomas). Once an intraoperative leak occurred, craniopharyngioma (OR = 4.255, p = 0.010) and higher body mass index (BMI) predicted postoperative leak (OR = 1.055, p = 0.010). In patients with an intraoperative leak, the use of septal flaps reduced the occurrence of postoperative leak (OR = 0.431, p = 0.027). Rigid reconstruction and CSF diversion techniques did not impact postoperative leak rates.ConclusionIntraoperative CSF leaks can occur during endoscopic sellar surgery, especially in larger tumors or craniopharyngiomas. Once an intraoperative leak occurs, risk factors for postoperative leaks include craniopharyngiomas and higher BMI. Use of septal flaps decreases this risk.

OBJECT Concussions typically resolve within several days, but in a few cases the symptoms last for a month or longer and are termed persistent postconcussive symptoms (PPCS). These persisting symptoms may also be associated with more serious brain trauma similar to subdural hematoma (SDH). The objective of this study was to investigate the head dynamic and brain tissue responses of injury reconstructions resulting in concussion, PPCS, and SDH. METHODS Reconstruction cases were obtained from sports medicine clinics and hospitals. All subjects received a direct blow to the head resulting in symptoms. Those symptoms that resolved in 9 days or fewer were defined as concussions (n = 3). Those with symptoms lasting longer than 18 months were defined as PPCS (n = 3), and 3 patients presented with SDHs (n = 3). A Hybrid III headform was used in reconstruction to obtain linear and rotational accelerations of the head. These dynamic response data were then input into the University College Dublin Brain Trauma Model to calculate maximum principal strain and von Mises stress. A Kruskal-Wallis test followed by Tukey post hoc tests were used to compare head dynamic and brain tissue responses between injury groups. Statistical significance was set at p < 0.05. RESULTS A significant difference was identified for peak resultant linear and rotational acceleration between injury groups. Post hoc analyses revealed the SDH group had higher linear and rotational acceleration responses (316 g and 23,181 rad/sec2, respectively) than the concussion group (149 g and 8111 rad/sec2, respectively; p < 0.05). No significant differences were found between groups for either brain tissue measures of maximum principal strain or von Mises stress. CONCLUSIONS The reconstruction of accidents resulting in a concussion with transient symptoms (low severity) and SDHs revealed a positive relationship between an increase in head dynamic response and the risk for more serious brain injury. This type of relationship was not found for brain tissue stress and strain results derived by finite element analysis. Future research should be undertaken using a larger sample size to confirm these initial findings. Understanding the relationship between the head dynamic and brain tissue response and the nature of the injury provides important information for developing strategies for injury prevention.

Objective. We investigated the correlation between immunohistochemical expression of the pituitary tumor transforming gene (PTTG) and pituitary adenoma subtype. Methods. Pituitary adenomas (n = 89) were stained for PTTG using the streptavidin—biotin—peroxidase complex method and a monoclonal PTTG antibody. Results. PTTG staining was found to be cytoplasmic with a pronounced paranuclear expression pattern. Reactivity was highest in growth hormone (GH) adenomas as compared with other tumors, including prolactin (PRL), follicle-stimulating hormone/luteinizing hormone/α subunit, as well as adrenocorticotrophic hormone—secreting adenomas. PRL adenomas exhibited the lowest expression levels. Among GH adenomas, untreated tumors demonstrated significantly higher PTTG levels than octreotide-treated examples. Although dopamine agonist—treated PRL adenomas tended to show lower expression levels, statistical significance was not reached. Conclusions. Our finding that PTTG was differentially expressed in pituitary adenoma subtypes suggests a cell-specific function for PTTG. Moreover, treatment of GH adenomas with somatostatin analogues lowered PTTG expression. Further investigation into mechanisms mediating cell-specific expression of PTTG is warranted.

Object The aim of this work was to investigate the immunohistochemical expression of nestin, a member of the intermediate filament family, in adenohypophysial vasculature during development and progression of pituitary infarction. Methods Forty-five nontumorous adenohypophyses and 34 pituitary adenomas of various types, all exhibiting acute or healing infarcts, were examined immunohistochemically using the streptavidin-biotin-peroxidase complex method. Results In both adenohypophyses and pituitary adenomas without infarction, nestin was expressed in only a few capillaries and endothelial cells. In acute infarcts without a vascular response, no nestin was demonstrable within necrotic capillaries (50 cases). In organizing infarcts, newly formed vessels spreading into necrotic zones showed nestin expression in all capillaries and practically every endothelial cell (25 cases). In the hypocellular, fibrotic scar phase, only a few vessels (4) were apparent, and immunoreactivity was focal and mild. Conclusions Nestin is strongly expressed in newly formed capillaries and is downregulated when infarcts transform to fibrous tissue. Nestin expression may provide valuable insight into the process of pituitary angiogenesis.