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OBJECTIVE Internal carotid artery injury (ICAI) is a rare, life-threatening complication of endoscopic endonasal approaches that will be encountered by most skull base neurosurgeons and otolaryngologists. Rates of surgical proficiency for managing ICAI are not known, and the role of simulation to improve performance has not been studied on a nationwide scale. METHODS Attending and resident neurosurgery and otorhinolaryngology surgeons (n = 177) were recruited from multicenter regional and national training courses to assess training outcomes and validity at scale of a prospective educational intervention to improve surgeon technical skills using a previously validated, perfused human cadaveric simulator. Participants attempted an initial trial (T1) of simulated ICAI control using their preferred technique. An educational intervention including personalized instruction was performed. Participants attempted a second trial (T2). Task success (dichotomous), time to hemostasis (TTH), estimated blood loss (EBL), and surgeon heart rate were measured. RESULTS Participant rating scales confirmed that the simulation retained face and construct validity across eight instructional settings. Trial success (ICAI control) improved from 56% in T1 to 90% in T2 (p < 0.0001). EBL and TTH decreased by 37% and 38%, respectively (p < 0.0001). Postintervention resident surgeon performance (TTH, EBL, and success rate) was superior to preintervention attending surgeon performance. The most improved quartile of participants achieved 62% improvement in TTH and 73% improvement in EBL, with trial success improvement from 25.6% in T1 to 100% in T2 (p < 0.0001). Baseline surgeon confidence was uncorrelated with T1 success, while posttraining confidence correlated with T2 success. Tachycardia was measured in 57% of surgeon participants, but was attenuated during T2, consistent with development of resiliency. CONCLUSIONS Prior to training, many attending and most resident surgeons could not manage the rare, life-threatening intraoperative complication of ICAI. A simulated educational intervention significantly improved surgeon performance and remained valid when deployed at scale. Simulation also promoted the development of favorable cognitive skills (accurate perception of skill and resiliency). Rare, life-threatening intraoperative complications may be optimal targets for educational interventions using surgical simulation.

OBJECTIVE Pituitary adenomas (PAs) are among the most common intracranial tumors. Understanding the clinical effects of various modifiable risk factors (MRFs) and nonmodifiable risk factors (NMRFs) is important in guiding proper treatment, yet there is limited evidence outlining the influence of MRFs and NMRFs on outcomes of PA resection. The aim of this study was to analyze MRFs and NMRFs in patients undergoing resection for PAs. METHODS Using the 2016 and 2017 National Readmission Database, the authors identified a cohort of 9472 patients undergoing microscopic or endoscopic resection of a PA. Patients with nonoverlapping MRFs and NMRFs were analyzed for length of stay (LOS), hospital cost, readmission rates, and postoperative complications. From the original cohort, a subset of 373 frail patients (as defined by the Johns Hopkins Frailty Index) were identified and propensity matched to nonfrail patients. Statistical analysis included 1-way ANOVA, Tukey multiple comparisons of means, odds ratios, Wald testing, and unpaired Welch 2-sample t-tests to compare complications, outcomes, and costs between each cohort. Perioperative outcomes and hospital readmission rates were tracked, and predictive algorithms were developed to establish precise relationships between relevant risk factors and neurosurgical outcomes. RESULTS Malnourished patients had significantly longer LOSs when compared to nonmalnourished patients (p < 0.001). There was a significant positive correlation between the number of MRFs and readmission at 90 days (p = 0.012) and 180 days (p = 0.020). Obese patients had higher rates of postoperative neurological injury at the 30-day follow-up (p = 0.048) compared to patients with normal BMI. Within this NMRF cohort, frail patients were found to have significantly increased hospital LOS (p < 0.001) and total inpatient costs compared to nonfrail patients (p < 0.001). Predictive analytics showed that frail patients had significantly higher readmission rates at both 90-day (p < 0.001) and 180-day follow-ups (p < 0.001). Lastly, rates of acute postsurgical infection were higher in frail patients compared to nonfrail patients (p < 0.001). CONCLUSIONS These findings suggest that both MRFs and NMRFs negatively affect the perioperative outcomes following PA resection. Notable risk factors including malnutrition, obesity, elevated lipid panels, and frailty make patients more prone to prolonged LOS, higher inpatient costs, and readmission. Further prospective research with longitudinal data is required to precisely pinpoint the effects of various risk factors on the outcomes of pituitary surgery.

Rathke cleft cysts (RCCs) are benign sellar lesions originating from remnants of primitive ectoderm. They have not been previously linked to other cystic lesions, such as pineal cysts (PCs). Our objective was to perform a multicenter cross-sectional neuroimaging study to examine prevalence rates of coexisting RCC and PC.We retrospectively queried prospectively maintained, institutional review board-approved, databases from the authors' centers. All patients undergoing transsphenoidal surgery for RCC between the years of 2011 and 2020 were included for analysis. Preoperative magnetic resonance imaging was reviewed to identify the coexistence of a PC. Patient demographics and neuroimaging characteristics were recorded. A control cohort comprised of 100 age- and sex-matched patients with nonfunctional pituitary adenoma (NFPA) who also underwent surgical intervention was utilized.Eighty-four patients with RCC were identified for analysis. A coexistent PC was identified in 40.5% (n = 34) of patients with RCC compared with 14.3% (n = 12) in the NFPA cohort (P0.001). There was no significant difference in PC size between patients with RCC and PA (8 vs. 8.8 mm, respectively; P = 0.77). Although the majority (85.7%; n = 72) of the RCC cohort were female patients, there was no sex predominance with respect to coexisting PC in either the RCC or PA cohort.This is the first study to report an increased prevalence of coexisting PC and RCC, possibly because of an embryologic link or other propensity for intracranial cyst formation. Additional studies in more generalizable populations can further explore the relation between RCC and PC, or other cyst formation.

Background The direct endoscopic endonasal approach (EEA) has become the primary technique used for resection of sellar pathology, meriting investigation into the risk factors for complications and predictors of postoperative outcomes after direct EEA. Methods We retrospectively analyzed the patient and tumor characteristics from 404 patients who had undergone direct EEA for sellar pathology at the USC Pituitary Center from September 2011 to December 2019. Results Of the 404 pathologic entities included, 349 (86%) were pituitary adenomas (PAs), 29 (7%) were Rathke cleft cysts, and 26 (6%) were other sellar lesions. The mean lesion diameter was 2.3 cm, with 34 microadenomas (10%) and 315 macroadenomas (90%). Cavernous sinus invasion was present in 39% of the PAs. No patient died. The surgical complications included internal carotid artery injury without neurological sequelae (0.2%), vision loss (0.7%), meningitis (0.7%), cerebrospinal fluid leak (4%), epistaxis (4%), sinusitis (1%), transient cranial nerve paresis (0.5%), and postoperative abscess (0.25%). New hypopituitarism developed in 3%. Gross total resection was achieved in 208 PA cases (58%). Clinical improvement of headaches and visual deficits were reported for 67% and 76% of cases, respectively. Hormonal remission was achieved in 82% of patients with functional PAs. The median hospital stay was 2 days, with 34 patients (8%) readmitted within 30 days and 10 (3%) undergoing early reoperation. Disease recurrence or progression developed in 10% and was less likely in the case of gross total resection and apoplexy. Conclusion In the present, large, consecutive, mostly single-surgeon series, the patients experienced clinical improvement in most preoperative symptoms and had low rates of perioperative morbidity. We have demonstrated that direct EEA can be efficiently, safely, and successfully performed by a neurosurgical team.

In patients with residual or recurrent nonfunctioning pituitary adenomas (NFPAs) after transsphenoidal resection, both GammaKnife (GKRS) and CyberKnife (CKRS) stereotactic radiosurgery (SRS) are viable treatment options.We report a retrospective single center series comparing assessing the effectiveness and complications from of these 2 commonly used SRS techniques.A total of 53 patients with prior surgical resection and residual or recurrent NFPAs who underwent GKRS or CKRS and minimum 3-month follow-up between January 2002 and February 2017 at a single center were identified.A total of 34 patients underwent GKRS and 19 received CKRS. CKRS patients had a larger maximal tumor diameter (P = 0.005) and tumor volume treated (P = 0.001). Differences between GKRS and CKRS treatment parameters included target volume, target volume treated, prescribed dose, maximum dose, prescription isodose line, and conformity index (P0.05). The mean follow-up time was 53.74 months for GKRS and 41.48 months for CKRS patients. Tumor progression developed in 6% of cases after GKRS versus 5% after CKRS. The mean progression-free survival was 48.44 months after GKRS and 38.57 months after CKRS (P = 0.61). Five-year actuarial tumor control rates were 91% after GKRS versus 89% after CKRS (P0.99). There were no differences in worsened vision or rates of hypopituitarism.In patients undergoing single fraction GKRS versus fractionated CKRS for NFPAs, both modalities had similar rates of tumor control, new hypopituitarism, and visual morbidity despite varying indications. This study validates the versatile use of these 2 SRS modalities for patients meeting their relative criteria, especially based on proximity to the optic apparatus and normal pituitary gland.

Silent thyrotropin pituitary adenomas (TSHomas) are defined by absence of hyperthyroidism despite TSH immunopositivity. Data pertaining to clinical and surgical characteristics of silent TSHomas remains limited. We aim to describe the clinical presentation, pathological characteristics, and outcomes in silent TSHoma patients treated at a tertiary pituitary center. We retrospectively identified patients with histologically-proven silent TSHoma who underwent transsphenoidal resection at our center between 2000 and 2016 (n = 1244 total patients). Patients with preoperative hyperthyroidism or thyroidectomy were excluded. Twenty patients with silent TSHomas were included (1.6% of surgically treated PAs), of which 35% were reoperations. Presenting symptoms included vision loss (45%) and headache (40%). Preoperative pituitary dysfunction included hypothyroidism (40%), hypogonadotropic hypogonadism (30%), and panhypopituitarism (15%). Nineteen patients (95%) had macroadenomas (mean diameter 29.9 mm). Extrasellar growth was identified in 17 patients (85%) and 65% had cavernous sinus invasion. Immunostaining for alpha-subunit was positive in 19 patients (95%), and 75% of tumors expressed immunopositivity for hormones other than TSH. Gross total tumor resection was achieved in 9 patients (45%) on follow-up MRI. Major postoperative complications included hydrocephalus (1 patient) and cerebrospinal fluid leak with meningitis (1 patient). Tumor progression and recurrence occurred in 1 patient each (10% total) over the follow-up period (median 18.5 months). Silent TSHomas tend to be large, invasive tumors. In addition to TSH, a majority express immunopositivity for alpha-subunit and gonadotropins, thereby potentially supporting a primitive adenoma lineage and subtype. Despite reoperation in several patients, good overall outcomes with low complication rates were achieved.

Introduction Complementary and alternative medicine (CAM) are highly used among those diagnosed with glioma. Further research is warranted, however, as it remains important to clearly delineate CAM practices that are unproven, disproven, or promising for future research and implementation. Methods A systematic review was conducted to identify all articles that investigated the effect of any CAM therapy on survival of patients with newly diagnosed or recurrent glioma. Results Eighteen papers and 4 abstracts pertaining to the effects of ketogenic diet (4), antioxidants (3), hyperbaric oxygen (4), cannabinoids (2), carbogen and nicotinamide (3), mistletoe extract (2), hypocupremia and penicillamine (1), and overall CAM use (3) on overall and progression-free survival in patients with low- and high-grade glioma were identified (Levels of Evidence I-IV). Ketogenic diets, hyperbaric oxygen therapy, and cannabinoids appear to be safe and well tolerated by patients; preliminary studies demonstrate tumor response and increased progression-free survival and overall survival when combined with standard of care therapies. Antioxidant usage exhibit mixed results perhaps associated with glioma grade with greater effect on low-grade gliomas; vitamin D intake was associated with prolonged survival. Conversely, carbogen breathing and hypocupremia were found to have no effect on the survival of patients with glioma, with associated significant toxicity. Most modalities under the CAM umbrella have not been appropriately studied and require further investigation. Conclusions Despite widespread use, Level I or II evidence for CAM for the treatment of glioma is lacking, representing future research directions to optimally counsel and treat glioma patients.

OBJECTIVEIncomplete resection of skull base pathology may result in local tumor recurrence. This study investigates the utility of 5-aminolevulinic acid (5-ALA) fluorescence during endoscopic endonasal approaches (EEAs) to increase visibility of pathologic tissue.METHODSThis retrospective multicenter series comprises patients with planned resection of an anterior skull base lesion who received preoperative 5-ALA at two tertiary care centers. Diagnostic use of a blue light endoscope was performed during EEA for all cases. Demographic and tumor characteristics as well as fluorescence status, quality, and homogeneity were assessed for each skull base pathology.RESULTSTwenty-eight skull base pathologies underwent blue-light EEA with preoperative 5-ALA, including 15 pituitary adenomas (54%), 4 meningiomas (14%), 3 craniopharyngiomas (11%), 2 Rathke’s cleft cysts (7%), as well as plasmacytoma, esthesioneuroblastoma, and sinonasal squamous cell carcinoma. Of these, 6 (21%) of 28 showed invasive growth into surrounding structures such as dura, bone, or compartments of the cavernous sinus. Tumor fluorescence was detected in 2 cases (7%), with strong fluorescence in 1 tuberculum sellae meningioma and vague fluorescence in 1 pituicytoma. In all other cases fluorescence was absent. Faint fluorescence of the normal pituitary gland was seen in 1 (7%) of 15 cases. A comparison between the particular tumor entities as well as a correlation between invasiveness, WHO grade, Ki-67, and positive fluorescence did not show any significant association.CONCLUSIONSWith the possible exception of meningiomas, 5-ALA fluorescence has limited utility in the majority of endonasal skull base surgeries, although other pathology may be worth investigating.

OBJECTIVE Pituitary adenoma (PA) consistency, or texture, is an important intraoperative characteristic that may dictate operative dissection techniques and/or instruments used for tumor removal during endoscopic endonasal approaches (EEAs). The impact of PA consistency on surgical outcomes has yet to be elucidated. METHODS The authors developed an objective 5-point grading scale for PA consistency based on intraoperative characteristics, including ease of tumor debulking, manipulation, and instrument selection, ranging from cystic/hemorrhagic tumors (grade 1) to calcified tumors (grade 5). The proposed grading system was prospectively assessed in 306 consecutive patients who underwent an EEA for PAs, and who were subsequently analyzed for associations with surgical outcomes, including extent of resection (EOR) and complication profiles. RESULTS Institutional database review identified 306 patients who underwent intraoperative assessment of PA consistency, of which 96% were macroadenomas, 70% had suprasellar extension, and 44% had cavernous sinus invasion (CSI). There were 214 (69.9%) nonfunctional PAs and 92 functional PAs (31.1%). Distribution of scores included 15 grade 1 tumors (4.9%), 112 grade 2 tumors (36.6%), 125 grade 3 tumors (40.8%), 52 grade 4 tumors (17%), and 2 grade 5 tumors (0.7%). Compared to grade 1/2 and grade 3 PAs, grade 4/5 PAs were significantly larger (22.5 vs 26.6 vs 27.4 mm, p < 0.01), more likely to exhibit CSI (39% vs 42% vs 59%, p < 0.05), and trended toward nonfunctionality (67% vs 68% vs 82%, p = 0.086). Although there was no association between PA consistency and preoperative headaches or visual dysfunction, grade 4/5 PAs trended toward preoperative (p = 0.058) and postoperative panhypopituitarism (p = 0.066). Patients with preoperative visual dysfunction experienced greater improvement if they had a grade 1/2 PA (p < 0.05). Intraoperative CSF leaks were noted in 32% of cases and were more common with higher-consistency-grade tumors (p = 0.048), although this difference did not translate to postoperative CSF leaks. Gross-total resection (%) was more likely with lower PA consistency score as follows: grade 1/2 (60%), grade 3 (50%), grade 4/5 (44%; p = 0.045). Extracapsular techniques were almost exclusively performed in grade 4/5 PAs. Assignment of scores showed low variance and high reproducibility, with an intraclass correlation coefficient of 0.905 (95% CI 0.815–0.958), indicating excellent interrater reliability. CONCLUSIONS These findings demonstrate clinical validity of the proposed intraoperative grading scale with respect to PA subtype, neuroimaging features, EOR, and endocrine complications. Future studies will assess the relation of PA consistency to preoperative MRI findings to accurately predict consistency, thereby allowing the surgeon to tailor the exposure and prepare for varying resection strategies.

Cavernous malformations are angiographically occult vascular hamartomas without intervening neural tissue that represent an estimated 10% of central nervous system vascular pathologies.1 Management is often dictated by lesion location, intranidal versus extranidal hemorrhage, presenting symptoms, acuity of onset, and surgical accessibility. Deep-seated cavernous malformations are often adjacent to eloquent structures, including functional white matter tracts that must be accounted for during surgical planning and respected during resection of the cavernoma. Exoscopic-guided channel-based approaches can help minimize retraction of brain tissue while providing a navigated, direct path to the target lesion.2 We report a case of an 18-year-old man who presented with seizures and was found to have a hemorrhagic third ventricular cavernous malformation resulting in hydrocephalus. A right frontal trans-sulcal approach using an exoscope and channel-based retractor was performed and directed along the long axis of the lesion to minimize displacement of surrounding eloquent structures and manipulation of the fornix. An uneventful gross total resection was achieved and confirmed using an angled endoscope to inspect the cavity walls, the "exoscopic to endoscopic or E2E approach" (Video 1). The patient developed transient short-term memory dysfunction in the immediate postoperative period, likely due to retraction of the fornix, which dramatically improved with speech therapy and rehabilitation. The patient provided informed consent for surgery and video recording.