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Abstract 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.

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. 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. 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[less than or equal to]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. 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.

Optimal treatment of brain metastases is often hindered by limitations in diagnostic capabilities. To meet this challenge, here we profile DNA methylomes of the three most frequent types of brain metastases: melanoma, breast, and lung cancers ( n  = 96). Using supervised machine learning and integration of DNA methylomes from normal, primary, and metastatic tumor specimens ( n  = 1860), we unravel epigenetic signatures specific to each type of metastatic brain tumor and constructed a three-step DNA methylation-based classifier (BrainMETH) that categorizes brain metastases according to the tissue of origin and therapeutically relevant subtypes. BrainMETH predictions are supported by routine histopathologic evaluation. We further characterize and validate the most predictive genomic regions in a large cohort of brain tumors ( n  = 165) using quantitative-methylation-specific PCR. Our study highlights the importance of brain tumor-defining epigenetic alterations, which can be utilized to further develop DNA methylation profiling as a critical tool in the histomolecular stratification of patients with brain metastases. The treatment of brain metastases is often limited by the ability to diagnose their origins. Here the authors generate DNA methylomes from the three most frequent types of brain metastases, identify epigenetic signatures specific to each type of metastasis and construct a DNA methylation-based classifier (BrainMETH) to advance brain metastasis diagnosis.

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. 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. 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. 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.

Genomically matched trials in primary brain tumors (PBTs) require recent tumor sequencing. We evaluated whether circulating tumor DNA (ctDNA) could facilitate genomic interrogation in these patients. Data from 419 PBT patients tested clinically with a ctDNA NGS panel at a CLIA-certified laboratory were analyzed. A total of 211 patients (50%) had ≥1 somatic alteration detected. Detection was highest in meningioma (59%) and gliobastoma (55%). Single nucleotide variants were detected in 61 genes, with amplifications detected in and others. Contrary to previous studies with very low yields, we found half of PBT patients had detectable ctDNA with genomically targetable off-label or clinical trial options for almost 50%. For those PBT patients with detectable ctDNA, plasma cfDNA genomic analysis is a clinically viable option for identifying genomically driven therapy options.

PurposeTo 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.MethodsAll 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.ResultsOf 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.ConclusionThis 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.

BACKGROUND:Three-dimensional (3-D) endoscopy is a recent addition to augment the transsphenoidal surgical approach for anterior skull-base and parasellar lesions. We describe our experience implementing this technology into regular surgical practice. OBJECTIVE:Retrospective review of clinical factors and outcomes. METHODS:All patients were analyzed who had endoscopic endonasal parasellar operations since the introduction of the 3-D endoscope to our practice. Over an 18-month period, 160 operations were performed using solely endoscopic techniques. Sixty-five of these were with the Visionsense VSII 3-D endoscope and 95 utilized 2-dimensional (2-D) high-definition (HD) Storz endoscopes. Intraoperative and postoperative findings were analyzed in a retrospective fashion. RESULTS:Comparing both groups, there was no significant difference in total or surgical operating room times comparing the 2-D HD and 3-D endoscopes (239 minutes vs 229 minutes, P = .47). Within disease-specific comparison, pituitary adenoma resection was significantly shorter utilizing the 3-D endoscope (surgical time 174 minutes vs 147 minutes, P = .03). These findings were independent of resident or fellow experience. There was no significant difference in the rate of complication, reoperation, tumor resection, or intraoperative cerebrospinal fluid leaks. Subjectively, the 3-D endoscope offered increased agility with 3-D techniques such as exposing the sphenoid rostrum, drilling sphenoidal septations, and identifying bony landmarks and suprasellar structures. CONCLUSION:The 3-D endoscope is a useful alternative to the 2-D HD endoscope for transnasal anterior skull-base surgery. Preliminary results suggest it is more efficient surgically and has a shorter learning curve. As 3-D technology and resolution improve, it should serve to be an invaluable tool for neuroendoscopy. ABBREVIATION:HD, high definition

IntroductionLonger 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.MethodsA 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.ResultsOf 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.ConclusionThis 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.

Abstract 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. Graphical Abstract Graphical Abstract

Background Most endoscopic transsphenoidal approaches jeopardize the sphenopalatine artery and septal olfactory strip (SOS), increasing the risk of postoperative anosmia and epistaxis while precluding the ability to raise pedicled nasoseptal flaps (NSF). We describe a bilateral “rescue flap” technique that preserves the mucosa containing the nasal-septal vascular pedicles and the SOS. This approach can reduce the risk of postoperative complications, including epistaxis and anosmia. Methods A retrospective analysis was conducted of all patients who underwent endoscopic transsphenoidal surgery with preservation of both sphenopalatine vascular pedicles and SOS. In a recent subset of patients, olfactory assessment was performed. Results Of 174 consecutive operations performed in 161 patients, bilateral preservation of the sphenopalatine vascular pedicle and SOS was achieved in 139 (80 %) operations, including 31 (22 %) with prior transsphenoidal surgery. Of the remaining 35 operations, 18 had a planned formal NSF and 17 had prior surgery or extensive lesions precluding use of this technique. Of pituitary adenomas, RCCs or sellar arachnoid cysts, 118 (94 %) underwent this approach, including 91 % of patients who had prior surgery. Preoperative olfaction function was maintained in 97 % of patients that were tested. None of the patients had postoperative arterial epistaxis. Conclusion Preservation of bilateral sphenopalatine vascular pedicles and the SOS is feasible in over 90 % of patients undergoing endonasal endoscopic surgery for pituitary adenomas and RCCs. This approach, while not hindering exposure or limiting instrument maneuverability, preserves the nasoseptal vasculature for future NSF use if needed and appears to minimize the risks of postoperative arterial epistaxis and anosmia.