Comparative Analysis of Endoscope Obscuration With Utilization of an Endonasal Access Guide for Endonasal Skull Base Surgery.

BACKGROUND AND OBJECTIVES: In endoscopic endonasal approaches (EEAs) for skull base pathologies, endoscope view obscuration remains a persistent, time-consuming, and distracting issue for surgeons and may result in increased operative time. The endonasal access guide (EAG) has been demonstrated as a possible adjunct to minimize these events. However, to date, there have been no comparative studies performed and the potential time savings by using EAGs have yet to be quantified. This cohort study aimed to determine the operative efficiency benefits of the EAG in EEA operations. METHODS: Analysis of EEA operative videos from an EAG cohort (n = 20) and a control cohort (n = 20) was performed, assessing 12-minute segments in the first, middle, and last third of each operation. The first segment in each cohort was selected before EAG placement, serving as an internal control. Every endoscope lens soiling instance was counted (measured as cleaning actions per minute), timed (obscuration time %), and identified as a withdrawal, irrigation, or other cleaning action. Perioperative variables including skull base repair and postoperative cerebrospinal fluid leakage were assessed. RESULTS: Within the EAG cohort, obscuration time was reduced in the middle and last third compared with the first third (3.73% [CI: 2.39-5.07] vs 12.97% [CI: 10.24-15.70], P < .001; 4.19% [CI: 2.83-5.55] vs 12.97% [CI: 10.24-15.70], P < .001) and cleaning actions were also significantly reduced by EAG (0.69/min [CI: 0.39-0.99] vs 1.67/min [CI: 1.34-2.00], P = .001; 0.66/min [CI: 0.35-0.97] vs 1.67/min [CI: 1.34-2.00], P < .001). Between the control and EAG cohorts, there was no significant difference between obscuration time and cleaning actions in the first third (9.33% vs 12.97%, P = .086; 1.34/min vs 1.67/min, P = .151) or in the middle third (6.24% vs 3.73%, P = .140; 0.80/min vs 0.69/min, P = .335), but there was a significant difference in the last third (9.25% [CI: 6.95-11.55] vs 4.19% [CI: 2.83-5.55], P < .001; 0.95/min [CI: 0.73-1.17] vs 0.66/min [CI: 0.35-0.97], P = .018). CONCLUSION: EAG significantly reduces lens obscurations and cleaning events, particularly during the intradural portion of operations. This technology may offer a greater time-saving impact with patients undergoing long EEA operations.

American Association of Neurological Surgeons/Congress of the Neurological Surgeons Section on Tumors Guidelines: Assessing Their Impact on Brain Tumor Clinical Practice.

Clinical guidelines direct healthcare professionals toward evidence-based practices. Evaluating guideline impact can elucidate information penetration, relevance, effectiveness, and alignment with evolving medical knowledge and technological advancements. As the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors marks its 40th anniversary in 2024, this article reflects on the tumor guidelines established by the Section over the past decade and explores their impact on other publications, patents, and information dissemination. Six tumor guideline categories were reviewed: low-grade glioma, newly diagnosed glioblastoma, progressive glioblastoma, metastatic brain tumors, vestibular schwannoma, and pituitary adenomas. Citation data were collected from Google Scholar and PubMed. Further online statistics, such as social media reach, and features in policy, news, and patents were sourced from Altmetric. Online engagement was assessed through website and CNS+ mobile application visits. Data were normalized to time since publication. Metastatic Tumor guidelines (2019) had the highest PubMed citation rate at 26.1 per year and webpage visits (29 100 page views 1/1/2019-9/30/2023). Notably, this guideline had two endorsement publications by partner societies, the Society of Neuro-Oncology and American Society of Clinical Oncology, concerning antiepileptic prophylaxis and steroid use, and the greatest reach on X (19.7 mentions/y). Citation rates on Google Scholar were led by Vestibular Schwannoma (2018). Non-Functioning Pituitary Adenoma led Mendeley reads. News, patent, or policy publications were led by low-grade glioma at 1.5/year. Our study shows that the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors guidelines go beyond citations in peer-reviewed publications to include patents, online engagement, and information dissemination to the public.

Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

BACKGROUND AND OBJECTIVE: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated. METHODS: Patients with treated CD from 2011 to 2023 were included. The perioperative and long-term characteristics of CD patients with and without recurrence were assessed using univariable and multivariable analyses. RESULTS: Of 383 patients with CD from 26 surgeons achieving postoperative remission, 288 (75.2%) maintained remission at last follow-up while 95 (24.8%) showed recurrence (median time to recurrence 9.99 ± 1.34 years). Patients with recurrence required longer postoperative hospital stays (5 ± 3 vs 4 ± 2 days, P = .002), had larger average tumor volumes (1.76 ± 2.53 cm3 vs 0.49 ± 1.17 cm3, P = .0001), and more often previously failed prior treatment (31.1% vs 14.9%, P = .001) mostly being prior surgery. Multivariable hazard prediction models for tumor recurrence found younger age (odds ratio [OR] = 0.95, P = .002) and Knosp grade of 0 (OR = 0.09, reference Knosp grade 4, P = .03) to be protective against recurrence. Comparison of Knosp grade 0 to 2 vs 3 to 4 showed that lower grades had reduced risk of recurrence (OR = 0.27, P = .04). Other factors such as length of stay, surgeon experience, prior tumor treatment, and Knosp grades 1, 2, or 3 failed to reach levels of statistical significance in multivariable analysis. CONCLUSION: This multicenter study centers suggests that the strongest predictors of recurrence include tumor size/invasion and age. This insight can help with patient counseling and prognostication. Long-term follow-up is necessary for patients, and early treatment of small tumors may improve outcomes.

A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer.

Background: Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase II dose in patients with progressive or recurrent brain cancers. Methods: Afatinib was taken orally once every 4 days or once every 7 days depending on dose cohort, until disease progression or unacceptable toxicity. Results: A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase II dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, 2 patients (9.5%) exhibited partial response based on Response Assessment in Neuro-Oncology criteria and disease stabilization was seen in 3 patients (14.3%). Conclusions: Afatinib taken orally was safe and well-tolerated up to 280 mg every 7 days in brain cancer patients.

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.

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.

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.

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.

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.

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.

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.