The RAPID Consortium: A Platform for Clinical and Translational Pituitary Tumor Research.

Objectives Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical research partnerships. Prior studies offer limited insight into the formation of a multicenter consortium. Design The authors describe the establishment of a multicenter research initiative, Registry of Adenomas of the Pituitary and Related Disorders (RAPID), to encourage quality improvement and research, promote scholarship, and apply innovative solutions in outcomes research. Methods The challenges encountered during the formation of other research registries were reviewed with those lessons applied to the development of RAPID. Setting/Participants RAPID was formed by 11 academic U.S. pituitary centers. Results A Steering Committee, bylaws, data coordination center, and leadership team have been established. Clinical modules with standardized data fields for nonfunctioning adenoma, prolactinoma, acromegaly, Cushing's disease, craniopharyngioma, and Rathke's cleft cyst were created using a Health Insurance Portability and Accountability Act-compliant cloud-based platform. Currently, RAPID has received institutional review board approval at all centers, compiled retrospective data and agreements from most centers, and begun prospective data collection at one site. Existing institutional databases are being mapped to one central repository. Conclusion The RAPID consortium has laid the foundation for a multicenter collaboration to facilitate pituitary tumor and surgical research. We sought to share our experiences so that other groups also contemplating this approach may benefit. Future studies may include outcomes benchmarking, clinically annotated biobank tissue, multicenter outcomes studies, prospective intervention studies, translational research, and health economics studies focused on value-based care questions.

Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma.

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. PATIENTS AND METHODS: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.

A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

Enhanced recovery after brain tumor surgery: pilot protocol implementation in a large healthcare system.

OBJECTIVE: Enhanced recovery after surgery (ERAS) protocols have been used in numerous specialties to improve the safety, efficiency, and cost of surgical interventions. Despite these successes, implementation of ERAS in cranial neurosurgery remains limited. In this study, a comprehensive ERAS protocol was implemented at two pilot sites within the Providence Health & Services system, and groundwork was laid for systemwide adoption. METHODS: An enhanced recovery protocol was developed and implemented through an interdisciplinary team of clinicians, executive leadership, and clinical informatics professionals across preoperative, intraoperative, and postoperative domains. Outcomes including length of stay, discharge destination, and cost were collected through systemwide databases and compared with nonprotocolized sites. RESULTS: During the study period, both pilot sites became top performers across the regional system in all evaluated metrics. The median length of stay for elective craniotomy at site 1 was reduced to 1.25 days, with a home discharge rate of > 90%. The cost per case at the pilot sites was nearly $7000 less on average than that of the nonprotocolized sites. CONCLUSIONS: Implementation of enhanced recovery protocols for brain tumor surgery is feasible and effective, resulting in marked improvements in healthcare efficiency. Future studies, including implementation of the current protocol across the entire Providence system, are needed to maximize the potential benefits of enhanced recovery programs.

An expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma.

Aim: The EMulate Therapeutics Voyager™ is a simple, wearable, home-use device that uses an alternating electromagnetic field to alter biologic signaling within cells. Objective: To assess the safety/feasibility of the Voyager in the treatment of recurrent glioblastoma (rGBM). Methods: In this study, patients with rGBM were treated with Voyager as monotherapy or in combination with standard chemotherapy at the Investigator's discretion. Safety was assessed by incidence of adverse events associated with the Voyager. Patients were followed until death. Results: A total of 75 patients were enrolled and treated for at least one day with the Voyager (safety population). Device-related adverse events were uncommon and generally did not result in interruption or withdrawal from treatment. There were no serious adverse events associated with Voyager. A total of 60 patients were treated for at least one month (clinical utility population). The median progression-free survival (PFS) was 17 weeks (4.3 months) in the Voyager only group (n = 24) and 21 weeks (5.3 months) in the Voyager + concurrent therapy group (n = 36). The median overall survival (OS) was 7 months in the Voyager only group and 9 months in the Voyager + concurrent therapy group. In patients treated with Voyager + concurrent therapy, the median OS for patients enrolled with their 1st or 2nd recurrence (n = 26) was 10 months, while in patients enrolled with their 3rd or 4th recurrence (n = 10) OS was 7 months. Conclusion: The data support the safety and feasibility of the Voyager for the treatment of rGBM. Further prospective study of the device is warranted. Trial Registration Number: NCT02296580 (ClinicalTrials.gov).

Patient Perception of Education, Care Coordination, and Psychological Distress After Developing Facial Paralysis: A Qualitative Study.

Importance: The management of vestibular schwannoma may include observation, microsurgical resection, or radiation of a tumor near the facial nerve. Injury to the facial nerve can result in facial paralysis with major functional, social, and psychological sequelae, and the experiences of patients after paralysis are not well studied. Objective: To (1) identify patient preparedness for developing facial paralysis and how well their care is coordinated following its development and (2) present in their own words outcomes of facial paralysis in terms of physical health, emotional health, self-perception, and social interactions. Design, Setting, and Participants: A qualitative observational study was performed using semistructured interviews at a tertiary care academic medical center. Semistructured interviews were conducted between January 1, 2018, and June 30, 2019, with adults aged 25 to 70 years who developed facial paralysis after treatment for vestibular schwannoma. Data were analyzed from July 2019 to June 2020. Main Outcomes and Measures: Perceptions of the educational and emotional experiences of individuals who developed complete facial paralysis after surgical treatment of vestibular schwannoma. Results: Overall, 12 participants were interviewed (median age, 54 years [range, 25-70 years]; 11 were female). Saturation was achieved after 12 interviews, indicating that no further information could be elicited from additional interviews. Four major themes were identified: (1) lack of sufficient patient education about the diagnosis of facial paralysis; (2) lack of appropriate care coordination related to facial paralysis; (3) changes in physical and emotional health following facial paralysis; and (4) changes in social interactions and external support following facial paralysis. Conclusions and Relevance: It is well-known that patients with facial paralysis have reduced quality of life, severe psychological and emotional sequelae. However, little is currently done to help prepare patients for this undesirable outcome. In this qualitative study of facial paralysis, patients express, in their own words, their feeling that the education and management of facial paralysis by their clinicians was inadequate. Before patients undergo surgery, and certainly after injury to the facial nerve, clinicians should consider the patient's goals, preferences, and values to ensure that a comprehensive educational program and psychosocial support system are implemented. Facial reanimation research has not adequately captured these key patient factors associated with the quality of communication.

Treatment of Cushing Disease With Pituitary-Targeting Seliciclib.

CONTEXT: Preclinical studies show seliciclib (R-roscovitine) suppresses neoplastic corticotroph proliferation and pituitary adrenocorticotrophic hormone (ACTH) production. OBJECTIVE: To evaluate seliciclib as an effective pituitary-targeting treatment for patients with Cushing disease (CD). METHODS: Two prospective, open-label, phase 2 trials, conducted at a tertiary referral pituitary center, included adult patients with de novo, persistent, or recurrent CD who received oral seliciclib 400 mg twice daily for 4 consecutive days each week for 4 weeks. The primary endpoint in the proof-of-concept single-center study was normalization of 24-hour urinary free cortisol (UFC; ≤ 50 µg/24 hours) at study end; in the pilot multicenter study, primary endpoint was UFC normalization or ≥ 50% reduction in UFC from baseline to study end. RESULTS: Sixteen patients were consented and 9 were treated. Mean UFC decreased by 42%, from 226.4 ± 140.3 µg/24 hours at baseline to 131.3 ± 114.3 µg/24 hours by study end. Longitudinal model showed significant UFC reductions from baseline to each treatment week. Three patients achieved ≥ 50% UFC reduction (range, 55%-75%), and 2 patients exhibited 48% reduction; none achieved UFC normalization. Plasma ACTH decreased by 19% (P = 0.01) in patients who achieved ≥ 48% UFC reduction. Three patients developed grade ≤ 2 elevated liver enzymes, anemia, and/or elevated creatinine, which resolved with dose interruption/reduction. Two patients developed grade 4 liver-related serious adverse events that resolved within 4 weeks of seliciclib discontinuation. CONCLUSION: Seliciclib may directly target pituitary corticotrophs in CD and reverse hypercortisolism. Potential liver toxicity of seliciclib resolves with treatment withdrawal. The lowest effective dose requires further determination.

Critical appraisal of minimally invasive keyhole surgery for intracranial meningioma in a large case series.

BACKGROUND: Meningioma surgery has evolved over the last 20 years with increased use of minimally invasive approaches including the endoscopic endonasal route and endoscope-assisted and gravity-assisted transcranial approaches. As the "keyhole" concept remains controversial, we present detailed outcomes in a cohort series. METHODS: Retrospective analysis was done for all patients undergoing meningioma removal at a tertiary brain tumor referral center from 2008-2021. Keyhole approaches were defined as: use of a minimally invasive "retractorless" approach for a given meningioma in which a traditional larger approach is often used instead. The surgical goal was maximal safe removal including conservative (subtotal) removal for some invasive locations. Primary outcomes were resection rates, complications, length of stay and Karnofsky Performance Scale (KPS). Secondary outcomes were endoscopy use, perioperative treatments, tumor control and acute MRI FLAIR/T2 changes to assess for brain manipulation and retraction injury. RESULTS: Of 329 patients, keyhole approaches were utilized in 193(59%) patients (mean age 59±13; 30 (15.5%) had prior surgery) who underwent 213 operations; 205(96%) were skull base location. Approaches included: endoscopic endonasal (n = 74,35%), supraorbital (n = 73,34%), retromastoid (n = 38,18%), mini-pterional (n = 20,9%), suboccipital (n = 4,2%), and contralateral transfalcine (n = 4,2%). Primary outcomes: Gross total/near total (>90%) resection was achieved in 125(59%) (5% for petroclival, cavernous sinus/Meckel's cave, spheno-cavernous locations vs 77% for all other locations). Major complications included: permanent neurological worsening 12(6%), CSF leak 2(1%) meningitis 2(1%). There were no DVTs, PEs, MIs or 30-day mortality. Median LOS decreased from 3 to 2 days in the last 2 years; 94% were discharged to home with favorable 90-day KPS in 176(96%) patients. Secondary outcomes: Increased FLAIR/T2 changes were noted on POD#1/2 MRI in 36/213(17%) cases, resolving in all but 11 (5.2%). Endoscopy was used in 87/139(63%) craniotomies, facilitating additional tumor removal in 55%. Tumor progression occurred in 26(13%) patients, mean follow-up 42±36 months. CONCLUSIONS & RELEVANCE: Our experience suggests minimally invasive keyhole transcranial and endoscopic endonasal meningioma removal is associated with comparable resection rates and low complication rates, short hospitalizations and high 90-day performance scores in comparison to prior reports using traditional skull base approaches. Subtotal removal may be appropriate for invasive/adherent meningiomas to avoid neurological deficits and other post-operative complications, although longer follow-up is needed. With careful patient selection and requisite experience, these approaches may be considered reasonable alternatives to traditional transcranial approaches.

Minimally invasive pericranial flap harvest through a supraorbital eyebrow craniotomy: Technical note in salvage skull base reconstruction.

BACKGROUND AND IMPORTANCE: The supraorbital eyebrow craniotomy is a minimally invasive approach that provides access to pathologies of the anterior and middle cranial fossae. Vascularized flaps are preferred when considering reconstructive options, however, small incisions may not provide adequate access to vascularized tissue. We present two cases demonstrating a modified technique for harvesting pericranium through an eyebrow supraorbital craniotomy for reconstruction of large skull base defects. CLINICAL PRESENTATION: The first case is of a 62-year-old woman with an invasive esthesioneuroblastoma. Multiple resections and reconstructions, including a large frontal craniectomy and titanium mesh cranioplasty, resulted in refractory tension pneumocephalus. A supraorbital craniotomy was performed with endoscope-assisted harvesting of a pericranial flap through a coronal plane stab incision for definitive repair. The second case is a 44-year-old woman with a high-grade neuroendocrine tumor transgressing the anterior cranial fossa. Resection was achieved via combined supraorbital eyebrow craniotomy and endoscopic endonasal approach. A multilayered reconstruction including a pericranial flap from above and a nasoseptal flap from below was used to reconstruct the defect. The pericranial flap was again harvested with endoscope assistance through a coronal plane stab incision. Both cases had excellent outcomes with no post-operative cerebrospinal fluid leak. CONCLUSION: Repair of large anterior cranial fossa defects with a vascularized pericranial flap can be performed through a supraorbital eyebrow craniotomy. Utilizing small, strategically placed transverse (coronal plane) incisions behind the hairline allows for the endoscope-assisted harvesting of a highly customized flap. This modified technique increases the flexibility of the minimally invasive supraorbital craniotomy.

Cell-free plasma microRNAs that identify patients with glioblastoma.

Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with pGBM and rGBM tumors. 2,083 miRs were assessed using the HTG miRNA whole transcriptome assay (WTA). CfmiRs detection was compared in pre-operative plasma samples from patients with pGBM (n = 32) and rGBM (n = 13) to control plasma samples from normal healthy donors (n = 73). 265 cfmiRs were found differentially expressed in plasma samples from pGBM patients compared to normal healthy donors (FDR < 0.05). Of those 193 miRs were also detected in pGBM tumor tissues (n = 15). Additionally, we found 179 cfmiRs differentially expressed in rGBM, of which 68 cfmiRs were commonly differentially expressed in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC = 98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC = 90.2%). This study demonstrated that plasma samples from pGBM and rGBM patients have specific miR signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM and rGBM tumors using a minimally invasive blood assay.

Supraorbital and mini-pterional keyhole craniotomies for brain tumors: a clinical and anatomical comparison of indications and outcomes in 204 cases.

OBJECTIVE: The authors' objective was to compare the indications, outcomes, and anatomical limits of supraorbital (SO) and mini-pterional (MP) craniotomies in patients with intra- and extraaxial brain tumors, and to assess approach selection, utility of endoscopy, and surgical field overlap. METHODS: A retrospective analysis was conducted of all brain tumor patients who underwent an SO or MP approach. The analyzed characteristics included pathology, endoscopy use, extent of resection, length of stay (LOS), and complications. On the basis of preoperative MRI data, tumor heatmaps were constructed to compare surgical access provided by both routes, including coronal projection heatmaps for parasellar tumors. RESULTS: From 2007 to 2020, 158 patients underwent 173 (84.8%) SO craniotomies and 30 patients underwent 31 (15.2%) MP craniotomies; 71 (34.8%) procedures were reoperations. Of these 204 operations, 110 (63.6%) SO and 21 (67.7%) MP approaches were for extraaxial tumors (meningiomas in 65% and 76.2%, respectively). Gliomas and metastases together represented 84.1% and 70% of intraaxial tumors accessed with SO and MP approaches, respectively. Overall, 56.1% of tumors accessed with the SO approach and 41.9% of those accessed with the MP approach were in the parasellar region. Axial projection heatmaps showed that SO access extended along the entire ipsilateral and medial contralateral anterior cranial fossa, parasellar region, ipsilateral sylvian fissure, medial middle cranial fossa, and anterior midbrain, whereas MP access was limited to the ipsilateral middle cranial fossa, sylvian fissure, lateral parasellar region, and posterior aspect of anterior cranial fossa. Coronal projection heatmaps showed that parasellar access extended further superiorly with the SO approach compared with that of the MP approach. Endoscopy was utilized in 98 (56.6%) SO craniotomies and 7 (22.6%) MP craniotomies, with further tumor resection in 48 (49%) and 5 (71.4%) cases, respectively. Endoscope-assisted tumor removal was clustered in areas that were generally at farther distances from the craniotomy or in angled locations such as the cribriform plate region where microscopic visualization is limited. Gross-total or near-total resection was achieved in 120/173 (69%) SO approaches and 21/31 (68%) MP approaches. Major complications occurred in 11 (6.4%) SO approaches and 1 (3.2%) MP approach (p = 0.49). The median LOS decreased to 2 days in the last 2 years of the study. CONCLUSIONS: This clinical experience suggests the SO and MP craniotomies are versatile, safe, and complementary approaches for tumors located in the anterior and middle cranial fossae and perisylvian and parasellar regions. The SO route, used in 85% of cases, achieved greater overall reach than the MP route. Both approaches may benefit from expanded visualization with endoscopy.

Diagnostic Pitfalls in Cushing Disease: Surgical Remission Rates, Test Thresholds, and Lessons Learned in 105 Patients.

CONTEXT: Confirming a diagnosis of Cushing disease (CD) remains challenging, yet is critically important before recommending transsphenoidal surgery for adenoma resection. OBJECTIVE: To describe predictive performance of preoperative biochemical and imaging data relative to post-operative remission and clinical characteristics in patients with presumed CD. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Patients (n = 105; 86% female) who underwent surgery from 2007 through 2020 were classified into 3 groups: group A (n = 84) pathology-proven ACTH adenoma; group B (n = 6) pathology-unproven but with postoperative hypocortisolemia consistent with CD; and group C (n = 15) pathology-unproven, without postoperative hypocortisolemia. Group A + B were combined as confirmed CD and group C as unconfirmed CD. MAIN OUTCOMES: Group A + B was compared with group C regarding predictive performance of preoperative 24-hour urinary free cortisol (UFC), late night salivary cortisol (LNSC), 1-mg dexamethasone suppression test (DST), plasma ACTH, and pituitary magnetic resonance imaging (MRI). RESULTS: All groups had a similar clinical phenotype. Compared with group C, group A + B had higher mean UFC (P < 0.001), LNSC (P = 0.003), DST (P = 0.06), and ACTH (P = 0.03) and larger MRI-defined lesions (P < 0.001). The highest accuracy thresholds were: UFC 72 µg/24 hours; LNSC 0.122 µg/dL, DST 2.70 µg/dL, and ACTH 39.1 pg/mL. Early (3-month) biochemical remission was achieved in 76/105 (72%) patients: 76/90(84%) and 0/15(0%) of group A + B vs group C, respectively, P < 0.0001. In group A + B, nonremission was strongly associated with adenoma cavernous sinus invasion. CONCLUSIONS: Use of strict biochemical thresholds may help avoid offering transsphenoidal surgery to presumed CD patients with equivocal data and improve surgical remission rates. Patients with Cushingoid phenotype but equivocal biochemical data warrant additional rigorous testing.

Characterization of outcomes and practices utilized in the management of internal carotid artery injury not requiring definitive endovascular management.

BACKGROUND: After internal carotid artery (ICA) injury during endoscopic skull base surgery, the majority of patients undergo ICA embolization or stenting to treat active extravasation or pseudoaneurysm development. However, management practices when embolization or stenting is not required have not been well described. The objective of this study was to determine how patients with ICA injury but no embolization, stenting, or ligation do long-term and ascertain the reconstruction methods utilized. METHODS: Twenty-nine cases of ICA injury were identified in an international multi-institutional retrospective review. Of these, we identified six cases that were not treated with embolization, stenting, or ICA sacrifice. Information was available for five cases. RESULTS: A muscle patch was used in the immediate repair of each case. A nasoseptal flap was used in one case. Prefabricated nasal tampons were used in all cases. Nasal packing was initially left in for a median of 7 days prior to removal. The initial muscle patch was reinforced with a second muscle graft in one case. One case demonstrated ICA bleeding at the time of packing removal and was repacked an additional week. Follow-up for each of these cases was at least 2 years. No cases of subsequent carotid rupture were found and none of these cases ultimately underwent endovascular stenting. Radiation or proton therapy has not been subsequently used in any of these patients. CONCLUSIONS: This study details the reconstruction, lessons learned, and long-term follow-up for five cases of ICA injury not treated with embolization, stenting, or ligation.

Streamlining brain tumor surgery care during the COVID-19 pandemic: A case-control study.

BACKGROUND: The COVID-19 pandemic forced a reconsideration of surgical patient management in the setting of scarce resources and risk of viral transmission. Herein we assess the impact of implementing a protocol of more rigorous patient education, recovery room assessment for non-ICU admission, earlier mobilization and post-discharge communication for patients undergoing brain tumor surgery. METHODS: A case-control retrospective review was undertaken at a community hospital with a dedicated neurosurgery and otolaryngology team using minimally invasive surgical techniques, total intravenous anesthesia (TIVA) and early post-operative imaging protocols. All patients undergoing craniotomy or endoscopic endonasal removal of a brain, skull base or pituitary tumor were included during two non-overlapping periods: March 2019-January 2020 (pre-pandemic epoch) versus March 2020-January 2021 (pandemic epoch with streamlined care protocol implemented). Data collection included demographics, preoperative American Society of Anesthesiologists (ASA) status, tumor pathology, and tumor resection and remission rates. Primary outcomes were ICU utilization and hospital length of stay (LOS). Secondary outcomes were complications, readmissions and reoperations. FINDINGS: Of 295 patients, 163 patients were treated pre-pandemic (58% women, mean age 53.2±16 years) and 132 were treated during the pandemic (52% women, mean age 52.3±17 years). From pre-pandemic to pandemic, ICU utilization decreased from 92(54%) to 43(29%) of operations (p<0.001) and hospital LOS≤1 day increased from 21(12.2%) to 60(41.4%), p<0.001, respectively. For craniotomy cohort, median LOS was 2 days for both epochs; median ICU LOS decreased from 1 to 0 days (p<0.001), ICU use decreased from 73(80%) to 29(33%),(p<0.001). For endonasal cohort, median LOS decreased from 2 to 1 days; median ICU LOS was 0 days for both epochs; (p<0.001). There were no differences pre-pandemic versus pandemic in ASA scores, resection/remission rates, readmissions or reoperations. CONCLUSION: This experience suggests the COVID-19 pandemic provided an opportunity for implementing a brain tumor care protocol to facilitate safely decreasing ICU utilization and accelerating discharge home without an increase in complications, readmission or reoperations. More rigorous patient education, recovery room assessment for non-ICU admission, earlier mobilization and post-discharge communication, layered upon a foundation of minimally invasive surgery, TIVA anesthesia and early post-operative imaging are possible contributors to these favorable trends.

Complication avoidance protocols in endoscopic pituitary adenoma surgery: a retrospective cohort study in 514 patients.

PURPOSE: To evaluate the impact of using consistent complication-avoidance protocols in patients undergoing endoscopic pituitary adenoma surgery including techniques for avoiding anosmia, epistaxis, carotid artery injury, hypopituitarism, cerebrospinal fluid leaks and meningitis. METHODS: All patients undergoing endoscopic adenoma resection from 2010 to 2020 were included. Primary outcomes included 90-day complication rates, gland function outcomes, reoperations, readmissions and length of stay. Secondary outcomes were extent of resection, short-term endocrine remission, vision recovery. RESULTS: Of 514 patients, (mean age 51 ± 16 years; 78% macroadenomas, 19% prior surgery) major complications occurred in 18(3.5%) patients, most commonly CSF leak (9, 1.7%) and meningitis (4, 0.8%). In 14 of 18 patients, complications were deemed preventable. Four (0.8%) had complications with permanent sequelae (3 before 2016): one unexplained mortality, one stroke, one oculomotor nerve palsy, one oculoparesis. There were no internal carotid artery injuries, permanent visual worsening or permanent anosmia. New hypopituitarism occurred in 23/485(4.7%). Partial or complete hypopituitarism resolution occurred in 102/193(52.8%) patients. Median LOS was 2 days; 98.3% of patients were discharged home. Comparing 18 patients with major complications versus 496 without, median LOS was 7 versus 2 days, respectively p < 0.001. Readmissions occurred in 6%(31/535), mostly for hyponatremia (18/31). Gross total resection was achieved in 214/312(69%) endocrine-inactive adenomas; biochemical remission was achieved in 148/209(71%) endocrine-active adenomas. Visual field or acuity defects improved in 126/138(91.3%) patients. CONCLUSION: This study suggests that conformance to established protocols for endoscopic pituitary surgery may minimize complications, re-admissions and LOS while enhancing the likelihood of preserving gland function, although there remains opportunity for further improvements.

Endoscopic Endonasal and Supraorbital Removal of Tuberculum Sellae Meningiomas: Anatomic Guides and Operative Nuances for Keyhole Approach Selection.

BACKGROUND: With growing worldwide endoscopy experience, endonasal and supraorbital removal of tuberculum sellae meningiomas (TSM) has increased. OBJECTIVE: To describe anatomic factors for guiding approach selection and outcomes. METHODS: Retrospective analysis of patients undergoing endonasal or supraorbital TSM resection: approach criteria, clinical outcomes, acute magnetic resonance imaging (MRI) fluid-attenuated inversion-recovery (FLAIR)/T2 changes. RESULTS: From 2008 to 2020, 33 patients (mean age 55 ± 11 yr) were identified: 20 (61%) had endonasal and 13 (39%) supraorbital removal. Comparing endonasal and supraorbital approaches, mean tumor volume (3.7 ± 3.5 cm3 vs 7.7 ± 8.5 cm3, P = .07); percent tumor above planum (42% vs 65%, P = .02), and lateral tumor beyond supraclinoid internal carotid arteries (1.4 ± 2.0 mm vs 4.0 ± 3.2 mm, P = .006) were greater for supraorbital route. Sellar depth was greater for endonasal route tumors (12.2 ± 2.6 mm vs 9.3 ± 2.4 mm, P = .003). Endoscopy, used in 10/13(77%) supraorbital cases, was helpful in additional tumor removal in 4/10(40%). Gross total removal and mean volumetric tumor resection were 16/20(80%) and 97.5% by endonasal, and 5/13(39%) and 96% by supraorbital route. Vision improved in 12/17 (71%) endonasal, 6/8 (75%) supraorbital operations, and worsened in 1 (3%) supraorbital case. Endonasal approach with optic canal decompression increased over study period: 15/20 (75%) endonasal patients vs 1/13(8%) supraorbital (P < .001). Postoperative FLAIR/T2 MRI changes occurred in 2/12 supraorbital and 0/20 endonasal cases. CONCLUSION: In our experience, both endonasal and supraorbital routes are safe and effective for TSM removal. Greater tumor extension below planum and medial optic canal invasion favor endonasal route, while larger size and lateral extension favor supraorbital route. Given high frequency of TSM growth into optic canals and better access for medial optic canal tumor removal, endonasal route may be preferred for most TSMs.

Pituitary adenomas in older adults (≥ 65 years): 90-day outcomes and readmissions: a 10-year endoscopic endonasal surgical experience.

INTRODUCTION: Longer lifespan and newer imaging protocols have led to more older adults being diagnosed with pituitary adenomas. Herein, we describe outcomes of patients ≥ 65 years undergoing endoscopic adenoma removal. To address selection criteria, we also assess a conservatively managed cohort. METHODS: A retrospective analysis of 90-day outcomes of patients undergoing endoscopic pituitary adenomectomy from 2010 to 2019 by a neurosurgical/ENT team was performed. Tumor subtype, cavernous sinus invasion, extent of resection/early remission, endocrinology outcomes, complications, re-operations and readmissions were analyzed. A comparator cohort ≥ 65 years undergoing clinical surveillance without surgery was also analyzed. RESULTS: Of 468 patients operated on for pituitary adenoma, 123 (26%) were ≥ 65 years (range 65-93 years); 106 (86.2%) had endocrine-inactive adenomas; 18 (14.6%) had prior surgery. Of 106 patients with endocrine-inactive adenomas, GTR was achieved in 70/106 (66%). Of 17 patients with endocrine-active adenomas, early biochemical remission was: Cushing's 6/8; acromegaly 1/4; prolactinomas 1/5. Gland function recovery occurred in 28/58 (48.3%) patients with various degrees of preoperative hypopituitarism. New anterior hypopituitarism occurred in 3/110 (2.4%) patients; permanent DI in none. Major complications in 123 patients were: CSF leak 2 (1.6%), meningitis 1 (0.8%), vision decline 1 (0.8%). There were no vascular injuries, operative hematomas, anosmia, deaths, MIs, or thromboembolic events. Median length of stay was 2 days. Readmissions occurred in 14/123 (11.3%) patients, 57% for delayed hyponatremia. Intra-cohort analysis by age (65-69, 70-74, 75-79, ≥ 80 years) revealed no outcome differences. Cavernous sinus invasion (OR 7.7, CI 1.37-44.8; p = 0.02) and redo-surgery (OR 8.5, CI 1.7-42.8; p = 0.009) were negative predictors for GTR/NTR. Of 105 patients evaluated for presumed pituitary adenoma beginning in 2015, 72 (69%) underwent surgery, 8 (7%) had prolactinomas treated with cabergoline and 25 (24%) continue clinical surveillance without surgery, including two on new hormone replacement. CONCLUSION: This study suggests that elderly patients carefully selected for endoscopic adenoma removal can have excellent short-term outcomes including high resection rates, low complication rates and short length of stay. Our experience supports a multidisciplinary approach and the concept of pituitary centers of excellence. Based on our observations, approximately 25% of elderly patients with pituitary adenomas referred for possible surgery can be monitored closely without surgery.

Virtual education in neurosurgery during the COVID-19 pandemic.

OBJECTIVE: Neurosurgical education in the US has changed significantly as a consequence of the novel coronavirus (COVID-19) pandemic. Institutional social distancing requirements have resulted in many neurosurgical programs utilizing video conferencing for educational activities. However, it is unclear how or if these practices should continue after the pandemic. The objective of this study was to characterize virtual education in neurosurgery and understand how it should be utilized after COVID-19. METHODS: A 24-question, 3-part online survey was administered anonymously to all 117 US neurosurgical residency programs from May 15, 2020, to June 15, 2020. Questions pertained to the current use of virtual conferencing, preferences over traditional conferences, and future inclinations. The Likert scale (1 = strongly disagree, 3 = neutral, 5 = strongly agree) was used. Comparisons were calculated using the Mann-Whitney U-test. Statistical significance was set at 0.05. RESULTS: One-hundred eight responses were recorded. Overall, 38 respondents (35.2%) were attendings and 70 (64.8%) were trainees. Forty-one respondents (38.0%) indicated attending 5-6 conferences per week and 70 (64.8%) attend national virtual conferences. When considering different conference types, there was no overall preference (scores < 3) for virtual conferences over traditional conferences. In regard to future use, respondents strongly agreed that they would continue the practice at some capacity after the pandemic (median score 5). Overall, respondents agreed that virtual conferences would partially replace traditional conferences (median score 4), whereas they strongly disagreed with the complete replacement of traditional conferences (median score 1). The most common choices for the partial replacement of tradition conferences were case conferences (59/108, 55%) and board preparation (64/108, 59%). Lastly, there was a significant difference in scores for continued use of virtual conferencing in those who attend nationally sponsored conferences (median score 5, n = 70) and those who do not (median score 4, n = 38; U = 1762.50, z = 2.97, r = 0.29, p = 0.003). CONCLUSIONS: Virtual conferences will likely remain an integral part of neurosurgical education after the COVID-19 pandemic has abated. Across the country, residents and faculty report a preference for continued use of virtual conferencing, especially virtual case conferences and board preparation. Some traditional conferences may even be replaced with virtual conferences, in particular those that are more didactic. Furthermore, nationally sponsored virtual conferences have a positive effect on the preferences for continued use of virtual conferences.

Minimally invasive surgical treatment of intracranial meningiomas in elderly patients (≥ 65 years): outcomes, readmissions, and tumor control.

OBJECTIVE: Increased lifespan has led to more elderly patients being diagnosed with meningiomas. In this study, the authors sought to analyze and compare patients ≥ 65 years old with those < 65 years old who underwent minimally invasive surgery for meningioma. To address surgical selection criteria, the authors also assessed a cohort of patients managed without surgery. METHODS: In a retrospective analysis, consecutive patients with meningiomas who underwent minimally invasive (endonasal, supraorbital, minipterional, transfalcine, or retromastoid) and conventional surgical treatment approaches during the period from 2008 to 2019 were dichotomized into those ≥ 65 and those < 65 years old to compare resection rates, endoscopy use, complications, and length of hospital stay (LOS). A comparator meningioma cohort of patients ≥ 65 years old who were observed without surgery during the period from 2015 to 2019 was also analyzed. RESULTS: Of 291 patients (median age 60 years, 71.5% females, mean follow-up 36 months) undergoing meningioma resection, 118 (40.5%) were aged ≥ 65 years and underwent 126 surgeries, including 20% redo operations, as follows: age 65-69 years, 46 operations; 70-74 years, 40 operations; 75-79 years, 17 operations; and ≥ 80 years, 23 operations. During 2015-2019, of 98 patients referred for meningioma, 67 (68%) had surgery, 1 (1%) had radiosurgery, and 31 (32%) were observed. In the 11-year surgical cohort, comparing 173 patients < 65 years versus 118 patients ≥ 65 years old, there were no significant differences in tumor location, size, or outcomes. Of 126 cases of surgery in 118 elderly patients, the approach was a minimally invasive approach to skull base meningioma (SBM) in 64 cases (51%) as follows: endonasal 18, supraorbital 28, minipterional 6, and retrosigmoid 12. Endoscope-assisted surgery was performed in 59.5% of patients. A conventional approach to SBM was performed in 15 cases (12%) (endoscope-assisted 13.3%), and convexity craniotomy for non-skull base meningioma (NSBM) in 47 cases (37%) (endoscope-assisted 17%). In these three cohorts (minimally invasive SBM, conventional SBM, and NSBM), the gross-total/near-total resection rates were 59.5%, 60%, and 91.5%, respectively, and an improved or stable Karnofsky Performance Status score occurred in 88.6%, 86.7%, and 87.2% of cases, respectively. For these 118 elderly patients, the median LOS was 3 days, and major complications occurred in 10 patients (8%) as follows: stroke 4%, vision decline 3%, systemic complications 0.7%, and wound infection or death 0. Eighty-three percent of patients were discharged home, and readmissions occurred in 5 patients (4%). Meningioma recurrence occurred in 4 patients (3%) and progression in 11 (9%). Multivariate regression analysis showed no significance of American Society of Anesthesiologists physical status score, comorbidities, or age subgroups on outcomes; patients aged ≥ 80 years showed a trend of longer hospitalization. CONCLUSIONS: This analysis suggests that elderly patients with meningiomas, when carefully selected, generally have excellent surgical outcomes and tumor control. When applied appropriately, use of minimally invasive approaches and endoscopy may be helpful in achieving maximal safe resection, reducing complications, and promoting short hospitalizations. Notably, one-third of our elderly meningioma patients referred for possible surgery from 2015 to 2019 were managed nonoperatively.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.