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.

Endoscopic Endonasal Transpterygoid Approach and the Need for Myringotomy.

OBJECTIVE: The expanded endonasal transpterygoid approach (EETA) is used to access the middle and posterior fossa through the pterygoid process. Traditionally, the eustachian tube (ET) was resected during EETA, which often required subsequent myringotomy for inner ear drainage. Anterolateral transposition of the ET was proposed to decrease potential morbidity associated with resection. However, a comparison of resection versus transposition regarding the need for subsequent myringotomy has not been reported. METHODS: This is a retrospective cohort study of patients who underwent an EETA. Patient demographics, tumor characteristics, management of ET with resection versus transposition, and need for subsequent myringotomy were collected. Analysis was performed with JMP software in standard fashion and univariate and multivariate logistic regression analysis performed with a p < 0.05 was considered significant. RESULTS: Ninety-one patients underwent EETA for various malignant and benign tumors. Twenty-seven patients required myringotomy, with tumors of the pterygopalatine fossa accounting for the most common location (n = 8). Malignant pathology had the highest myringotomy rate compared to benign tumors (48.9% vs. 10.9%, p < 0.001), as did receiving postoperative radiation (p < 0.001), ET resection (p < 0.001), and increasing CPK class. Multivariate analysis of these variables suggests that only ET resection significantly correlated with the need for myringotomy (LR 7.97, p = 0.005). CONCLUSIONS: ET resection during EETA can lead to ET dysfunction and require myringotomy post-operatively, and patients should be counseled of this risk. Radiation treatment, malignant pathology, and CPK class, all reflecting situations where more extensive surgery was needed, were associated with the need for myringotomy on univariate analysis but did not reach significance with multivariate analysis. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1203-1207, 2024.

Identifying Tumor Microenvironment Biomarkers in Adherent and Cystic Vestibular Schwannomas.

OBJECTIVE: A subset of vestibular schwannomas (VSs), including cystic tumors, have higher postoperative morbidity because of the presence of adhesions between the tumor, facial nerve (FN), and brainstem. We identify tumor microenvironment (TME) biomarkers to better classify these tumors and predict the degree of tumor adherence. STUDY DESIGN: Retrospective case series. SETTING: Tertiary skull base referral center. METHODS: Adult patients with cystic and solid VS matched in tumor size who underwent surgical resection were included. Expressions of seven biomarkers of extracellular matrix remodeling and tumor immune response were quantified via immunohistochemistry. The distribution of CD45+ immune cells was evaluated in intratumoral and perivascular compartments. The degree of tumor adherence was categorized as none, adherent to FN, or adherent to both FN and brainstem. RESULTS: Twenty-eight patients were included. Cystic VSs were significantly more adherent than solid VSs ( p = 0.02). Patients with adherent VS had shorter duration of symptoms and were more likely to undergo subtotal resection. In solid tumors, matrix metalloproteinase (MMP)-2 expression ( p = 0.02) and CD163+ macrophage infiltration ( p = 0.007) were correlated with tumor size. Linear discriminant analyses (LDAs) demonstrated MMP-2, MMP-14, CD80, CD163, and perivascular CD45 to be individually predictive of the degree of tumor adherence (all p < 0.05), with perivascular CD45 being the best independent predictor ( p = 0.005). An LDA model including these biomarkers demonstrated 100% accurate discrimination of all three levels of tumor adherence ( p = 0.04). CONCLUSIONS: Adherent VS have a distinct proinflammatory TME characterized by elevated MMP expression, enrichment of tumor-associated macrophages, and perivascular immune cell infiltration.

Comparison of Postoperative Outcomes in Cystic Versus Solid Vestibular Schwannoma in a Multi-institutional Cohort.

OBJECTIVE: Cystic vestibular schwannomas (cVSs) have more variable and less favorable clinical outcomes after microsurgical resection compared with solid VS (sVS). This study compares the preoperative presentation and postoperative outcomes between cVS and sVS. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary skull base referral centers. METHODS: Consecutive adult patients who underwent VS resection from 2016 to 2021 were included. Univariate and multivariate analyses compared differences in baseline symptoms and postoperative outcomes between cVS and sVS. RESULTS: There were a total of 315 patients (64% female; mean age, 54 yrs) and 46 (15%) were cystic. cVS were significantly larger than sVS (maximum diameter, 28 vs. 18 mm, p < 0.001) and had higher rates of dysphagia and dysphonia preoperatively (p < 0.02). cVSs were more likely to undergo translabyrinthine resection (76 vs. 50%, p = 0.001) and have a higher rate of subtotal resection (STR) compared with sVS (30 vs. 13%, p = 0.003). At latest follow-up, fewer cVS achieved good facial nerve (FN) outcome (House-Brackmann [HB] I/II) (80 vs. 90%, p = 0.048). Subanalysis of cVS and sVS matched in tumor size, and surgical approach did not show differences in the rate of STR or FN outcomes (HB I/II, 82 vs. 78%, p = 0.79). CONCLUSION: In this large multi-institutional series, cVSs represent a distinct entity and are characterized by larger tumor size and higher incidence of atypical symptoms. Although cVSs were more likely to undergo STR and portend worse FN outcomes than sVSs, this may be due to their larger tumor size rather than the presence of the cystic component.

A modern approach to olfactory groove meningiomas.

OBJECTIVE: Management of olfactory groove meningiomas (OGMs) has changed significantly with the advances in extended endoscopic endonasal approaches (EEAs), which is an excellent approach for patients with anosmia since it allows early devascularization and minimizes retraction on the frontal lobes. Craniotomy is best suited for preservation of olfaction. However, not infrequently, a tumor presents after extending outside the reach of an EEA and a solely transcranial approach would require manipulation and retraction of the frontal lobes. These OGMs may best be treated by a staged EEA-craniotomy approach. In this study the authors' goal was to present their case series of patients with OGMs treated with their surgical approach algorithm. METHODS: The authors conducted an IRB-approved, nonrandomized historic cohort including all consecutive cases of OGMs treated surgically between 2010 and 2020. Patient demographic information, presenting symptoms, operative details, and complications data were collected. Preoperative and postoperative tumor and T2/FLAIR intensity volumes were calculated using Visage Imaging software. RESULTS: Thirty-one patients with OGMs were treated (14 craniotomy only, 11 EEA only, and 6 staged). There was a significant difference in the distribution of patients presenting with anosmia and visual disturbance by approach. Tumor size was significantly correlated with preoperative vasogenic edema. Gross-total resection was achieved in 90% of cases, with near-total resection occurring twice with EEA and once with a staged approach. T2/FLAIR hyperintensity completely resolved in 90% of cases and rates did not differ by approach. Complication rates were not significantly different by approach and included 4 CSF leaks (p = 0.68). CONCLUSIONS: A staged approach for the management of large OGMs with associated anosmia and significant lateral extension is a safe and effective option for surgical management. Through utilization of the described algorithm, the authors achieved a high rate of GTR, and this strategy may be considered for large OGMs.

Ultrasound-guided endoscopic endonasal resection of sellar and suprasellar craniopharyngiomas.

Introduction: Optimal planning and minimally invasive surgical approach are essential to complete craniopharyngiomas (CP) resection with limited postoperative morbidity. Given the nature of craniopharyngioma recurrence, complete resection of the neoplasm is crucial. Since CP arise from the pituitary stalk and may grow anteriorly or laterally, some cases require an extended endonasal craniotomy. The extension of the craniotomy is crucial to expose the whole tumor and to make its dissection from the surrounding structures feasible. In order to guide the extension of the approach, the intraoperative use of ultrasound is helpful for the surgeons. The objective of this paper is to describe and to demonstrate the applicability of the utilization of intraoperative ultrasound (US) guidance for planning and confirmation of craniopharyngioma resection in EES. Method: The authors selected one operative video of a sellar-suprassellar craniopharyngioma gross-totally resected by EES. The authors demonstrate the extended sellar craniotomy, the anatomic landmarks that guide bone drilling and dural opening, the aspect of the intraoperative real time US, tumor resection and dissection from the surrounding structures. Results: The solid component of the tumor was mostly isoechogenic in texture compared to the anterior pituitary gland, with several wide spread hyperechogenic images corresponding to calcifications and hypoechogenic vesicles corresponding to cysts inside the CF ("salt-and-pepper" pattern). Discussion: The intraoperative endonasal US is a new surgical tool that allows for real-time active imaging for skull base procedures, such as sellar region tumors. Besides tumor evaluation, the intraoperative US helps the neurosurgeon to determine the size of craniotomy, to anticipate the relation between the tumor and vascular structures and to guide the best strategy for gross-total resection of the tumor. Conclusion: The EES allows a straight access to the craniopharyngiomas located in the sellar region or that grow anteriorly or superiorly. This approach allows the surgeon to dissect the tumor with minimal manipulation of the surrounding structures, when compared to craniotomy approaches. In order to accomplish that, the use of intraoperative endonasal ultrasound helps the neurosurgeon to perform the most suitable strategy, optimizing the rate of success.

Endoscopic Multiport Approach for Exenteration of the Infratemporal Fossa.

OBJECTIVE: To demonstrate anatomic relationships pertinent to the endoscopic multiport approach to the infratemporal fossa (ITF). Discuss advantages and limitations of each individual approach. STUDY DESIGN: Cadaveric study. METHODS: Endoscopic and endoscopic-assisted endonasal transpterygoid, sublabial transmaxillary, endoscopic transorbital, and endoscopic transoral approaches to accessing the ITF were completed in five silicone-injected fresh cadaveric specimens (10 sides) with the assistance of 0, 30, and 450 rods-lens endoscopes. Image guidance was used to confirm and document the anatomical relationships encountered in each approach. RESULTS: The endonasal endoscopic transpterygoid approach provides better visualization and more direct exposure to median structures. Endoscopic-assisted sublabial transmaxillary approach enhances the field of exposure, angle of attack, and ease of instrumentation to the lateral part of the ITF. Endoscopic-assisted transorbital approach via the inferior orbital fissure provided cephalic and anterior access. Endoscopic-assisted transoral approach complements the access to lesions extending inferior to the hard palate or far lateral to the mandibular condyle. CONCLUSIONS: A combination of minimal access infratemporal approaches can provide adequate exposure of the entire ITF while avoiding some of the morbidity associated with open approaches. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1367-1374, 2023.

Intraoperative Predictor of Remission in Cushing Disease.

BACKGROUND: Cushing disease represents a challenge for neurosurgeons, with high recurrence rates reported. Characteristics associated with remission are incompletely understood; thus, an intraoperative predictor for outcome would be valuable for assessing resection of adrenocorticotropic hormone (ACTH) secreting tissue. OBJECTIVE: To evaluate whether intraoperative ACTH measurement could predict outcome after surgery for Cushing disease. METHODS: Retrospective cohort study of 55 consecutive encounters with Cushing disease who had peripheral plasma ACTH levels measured intraoperatively before, during, and after tumor resection. The primary outcome measure was remission, defined by either 2 negative 24-hour urine free cortisol or 2 negative midnight salivary cortisol measurements. A logistic regression machine learning model was generated using recursive feature elimination. RESULTS: Fifty-five operative encounters, comprising 49 unique patients, had a mean follow-up of 2.73 years (±2.11 years) and a median follow-up of 2.07 years. Remission was achieved in 69.1% (n = 38) of all operations and in 78.0% (n = 32) of those without cavernous sinus invasion. The final ACTH level measured intraoperatively correctly predicted outcome (area under the curve = 0.766; P value = .002). The odds ratio of remission in patients with the lowest quartile vs highest quartile final intraoperative ACTH was 23.4 ( P value = .002). Logistic regression machine learning model resulted in incorporating postoperative day 1 morning cortisol, final intraoperative ACTH that predicted outcome with an average area under the curve of 0.80 ( P = .0027). CONCLUSION: Intraoperative ACTH may predict outcome after surgery in Cushing disease; furthermore, investigation is warranted.

Pituitary Stalk Stretch Predicts Postoperative Diabetes Insipidus After Pituitary Macroadenoma Transsphenoidal Resection.

BACKGROUND: Manipulation of the pituitary stalk, posterior pituitary gland, and hypothalamus during transsphenoidal pituitary adenoma resection can cause disruption of water electrolyte regulation leading to diabetes insipidus (DI). OBJECTIVE: To determine whether pituitary stalk stretch is an independent risk factor for postoperative DI after pituitary adenoma resection. METHODS: A retrospective review was performed of patients undergoing endoscopic endonasal resection of pituitary macroadenoma between July 2010 and December 2016 by a single neurosurgeon. We analyzed preoperative and postoperative imaging metrics to assess predictors for postoperative DI. RESULTS: Of the 234 patients undergoing resection, 41 (17.5%) developed postoperative DI. DI was permanent in 10 (4.3%) and transient in 31 (13.2%). The pituitary stalk stretch, measured as the change in stalk length from preoperative to postoperative imaging, was greater in the DI compared with the non-DI group (10.1 mm vs 5.9 mm, P < .0001). The pituitary stalk stretch was associated with DI with significant difference in mean pituitary stalk stretch between non-DI group vs DI group (5.9 mm vs 10.1 mm, P < .0001). Multivariate analysis revealed that pituitary stalk stretch >10 mm was a significant independent predictor of postoperative DI [odds ratios = 2.56 (1.10-5.96), P = .029]. When stratified into transient and permanent DI, multivariable analysis showed that pituitary stalk stretch >10 mm was a significant independent predictor of transient DI [odds ratios = 2.71 (1.0-7.1), P = .046] but not permanent DI. CONCLUSION: Postoperative pituitary stalk stretch after transsphenoidal pituitary adenoma surgery is an important factor for postoperative DI. We propose a reconstruction strategy to mitigate stalk stretch.

Comparing pre-operative versus post-operative single and multi-fraction stereotactic radiotherapy for patients with resectable brain metastases.

Background: The standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT. Methods: A multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined as patients with one of the following adverse events: 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results: 279 patients were eligible for analysis. The median follow-up time was 9 months. 87 % of patients received fractionated treatment. 29 % of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0 %, 17 %, 15 %, and 7.5 %, respectively. Conclusions: In our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.

Intraoperative Prediction of Long-Term Remission in Acromegaly.

BACKGROUND: The features of long-term remission in acromegaly adenomectomy are incompletely understood. An intraoperative predictor for long-term outcome would be valuable for assessing resection of growth hormone (GH)-secreting tumors in real-time. OBJECTIVE: To evaluate whether intraoperative GH measurement could predict long-term outcomes for acromegaly. METHODS: In 47 patients, peripheral blood GH levels were measured thrice intraoperatively: once before tumor dissection, once during tumor dissection, and once after tumor dissection. Long-term remission was defined by age-appropriate, normalized insulin-like growth factor-1 at most recent follow-up and a random GH less than 1.0 ng/mL. Patients were only considered to be in long-term remission without the use of postoperative medical therapy for acromegaly or radiation therapy. RESULTS: The median length of follow-up was 4.51 (range: 0.78-9.80) years. Long-term remission was achieved in 61.7% (29/47) of operations. Like previous studies, cavernous sinus invasion (odds ratio [OR]: 0.060; 95% CI: 0.014-0.260; P value < .01), suprasellar extension (OR: 0.191; 95% CI: 0.053-0.681; P value<.01), and tumor size greater than 1 cm (OR: 0.177; 95% CI: 0.003-0.917; P value = .03) were associated with not being in long-term remission. The minimum GH measured intraoperatively predicted long-term outcome (area under the curve: 0.7107; 95% CI: 0.537-0.884; P value < .01). The odds ratio of remission in patients with the lowest quartile minimum intraoperative GH compared with patients with the highest quartile minimum intraoperative GH was 27.0 (95% CI: 2.343-311.171; P value < .01). CONCLUSION: Minimum intraoperative GH may predict long-term outcome for acromegaly, which in principle could provide the pituitary neurosurgeon with real-time feedback and inform intraoperative decision making.

Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis.

BACKGROUND: The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD. METHODS: A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN. RESULTS: 53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24-25 Gy in 3-5 fractions. There were 0 LFs, 3 Grade 2-3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate. CONCLUSIONS: In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49-60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.

Machine Learning-Based Analysis and Prediction of Unplanned 30-Day Readmissions After Pituitary Adenoma Resection: A Multi-Institutional Retrospective Study With External Validation.

BACKGROUND: Unplanned readmission after transsphenoidal resection of pituitary adenoma can occur in up to 10% of patients but is unpredictable. OBJECTIVE: To develop a reliable system for predicting unplanned readmission and create a validated method for stratifying patients by risk. METHODS: Data sets were retrospectively collected from the National Surgical Quality Improvement Program and 2 tertiary academic medical centers. Eight machine learning classifiers were fit to the National Surgical Quality Improvement Program data, optimized using Bayesian parameter optimization and evaluated on the external data. Permutation analysis identified the relative importance of predictive variables, and a risk stratification system was built using the trained machine learning models. RESULTS: Readmissions were accurately predicted by several classification models with an area under the receiving operator characteristic curve of 0.76 (95% CI 0.68-0.83) on the external data set. Permutation analysis identified the most important variables for predicting readmission as preoperative sodium level, returning to the operating room, and total operation time. High-risk and medium-risk patients, as identified by the proposed risk stratification system, were more likely to be readmitted than low-risk patients, with relative risks of 12.2 (95% CI 5.9-26.5) and 4.2 (95% CI 2.3-8.7), respectively. Overall risk stratification showed high discriminative capability with a C-statistic of 0.73. CONCLUSION: In this multi-institutional study with outside validation, unplanned readmissions after pituitary adenoma resection were accurately predicted using machine learning techniques. The features identified in this study and the risk stratification system developed could guide clinical and surgical decision making, reduce healthcare costs, and improve the quality of patient care by better identifying high-risk patients for closer perioperative management.

Morphometric comparison of Fisch type A and endoscopic endonasal far-medial supracondylar approaches to the jugular foramen.

OBJECTIVE: The jugular foramen (JF) is one of the most complex and challenging skull base regions to approach surgically. The extreme medial approach to access the JF provides the approach angle from an anterior direction and does not require dissection and sacrifice of the jugular bulb (JB) to reach the pars nervosa. The authors compared the Fisch type A approach to the extreme medial approach to access the JF and evaluated the usefulness of the extreme medial approach. METHODS: This study was performed at the Anatomical Laboratory for Visuospatial Innovations in Otolaryngology and Neurosurgery of The Ohio State University. For the comparison of surgical maneuverability and visualization, two angles were measured: 1) the angle of attack (AoA), defined as the widest angle of movement achieved with a straight dissector; and 2) the angle of endoscopic exposure (AoEE), defined as the widest angle of movement in the nasal cavity. The differences in eustachian tube (ET) management, approach angle, surgical maneuverability, and surgical application of the Fisch type A approach to the extreme medial approach were compared. RESULTS: There was no difference between ET mobilization and transection regarding cranial-caudal (CC) or medial-lateral (ML) AoA (p = 0.646). The CC-AoA of the Fisch type A approach was significantly wider than the CC-AoA of the extreme medial approach (p = 0.001), and the CC-AoEE was significantly wider than the CC-AoA of the extreme medial approach (p < 0.001). There was no significant difference between the CC-AoA of the Fisch type A approach and the CC-AoEE. The ML-AoA of the Fisch type A approach was significantly wider than the ML-AoA of the extreme medial approach (p = 0.033), and the ML-AoEE was significantly wider than ML-AoA in the extreme medial approach (p < 0.001). The ML-AoEE was significantly wider than the ML-AoA in the Fisch type A approach (p = 0.033). CONCLUSIONS: The surgical maneuverability of the extreme medial approach was not inferior to that of the Fisch type A approach. The extreme medial approach can provide excellent surgical field visualization, while preserving the JB. Select cases of chordomas, chondrosarcomas, and JF schwannomas should be considered for an extreme medial approach. These two approaches are complementary, and a case-by-case detailed analysis should be conducted to decide the best approach.

Dose-escalated accelerated hypofractionation for elderly or frail patients with a newly diagnosed glioblastoma.

BACKGROUND: The standard of care for elderly glioblastoma patients is 40 Gy in 15 fraction radiotherapy with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions. METHODS: Elderly patients (≥ 65 years old) who received hypofractionated radiation with TMZ from 2010 to 2020 were included in this analysis. Overall survival (OS) and progression free survival were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared between patients who received 40 and 52.5 Gy. Univariable and multivariable analyses were performed. RESULTS: Sixty-six newly diagnosed patients were eligible for analysis. Thirty-nine patients were treated with 40 Gy in 15 fractions while twenty-seven were treated with 52.5 Gy in 15 fractions. Patients had no significant differences in age, sex, methylation status, or performance status. OS was superior in the 52.5 Gy group (14.1 months) when compared to the 40 Gy group (7.9 months, p = 0.011). Isoeffective dosing to 52.5 Gy was shown to be an independent prognostic factor for improved OS on multivariable analysis. CONCLUSIONS: Isoeffective dosing to 52.5 Gy in 15 fractions was associated with superior OS compared to standard of care 40 Gy in 15 fractions. These hypothesis generating data support accelerated hypofractionation in future prospective trials.

Complications after 1002 endoscopic endonasal approach procedures at a single center: lessons learned, 2010-2018.

OBJECTIVE: The endoscopic endonasal approach (EEA) has evolved into a mainstay of skull base surgery over the last two decades, but publications examining the intraoperative and perioperative complications of this technique remain scarce. A prior landmark series of 800 patients reported complications during the first era of EEA (1998-2007), parallel to the development of many now-routine techniques and technologies. The authors examined a single-institution series of more than 1000 consecutive EEA neurosurgical procedures performed since 2010, to elucidate the safety and risk factors associated with surgical and postoperative complications in this modern era. METHODS: After obtaining institutional review board approval, the authors retrospectively reviewed intraoperative and postoperative complications and their outcomes in patients who underwent EEA between July 2010 and June 2018 at a single institution. RESULTS: The authors identified 1002 EEA operations that met the inclusion criteria. Pituitary adenoma was the most common pathology (n = 392 [39%]), followed by meningioma (n = 109 [11%]). No patients died intraoperatively. Two (0.2%) patients had an intraoperative carotid artery injury: 1 had no neurological sequelae, and 1 had permanent hemiplegia. Sixty-one (6.1%) cases of postoperative cerebrospinal fluid leak occurred, of which 45 occurred during the original surgical hospitalization. Transient postoperative sodium dysregulation was noted after 87 (8.7%) operations. Six (0.6%) patients were treated for meningitis, and 1 (0.1%) patient died of a fungal skull base infection. Three (0.3%) patients died of medical complications, thereby yielding a perioperative 90-day mortality rate of 0.4% (4 deaths). High-grade (Clavien-Dindo grade III-V) complications were identified after 103 (10%) EEA procedures, and multivariate analysis was performed to determine the associations between factors and these more serious complications. Extradural EEA was significantly associated with decreased rates of these high-grade complications (OR [95% CI] 0.323 [0.153-0.698], p = 0.0039), whereas meningioma pathology (OR [95% CI] 2.39 [1.30-4.40], p = 0.0053), expanded-approach intradural surgery (OR [95% CI] 2.54 [1.46-4.42], p = 0.0009), and chordoma pathology (OR [95% CI] 9.31 [3.87-22.4], p < 0.0001) were independently associated with significantly increased rates of high-grade complications. CONCLUSIONS: The authors have reported a large 1002-operation cohort of EEA procedures and associated complications. Modern EEA surgery for skull base pathologies has an acceptable safety profile with low morbidity and mortality rates. Nevertheless, significant intraoperative and postoperative complications were correlated with complex intradural procedures and meningioma and chordoma pathologies.

Soft Gasket Seal Reconstruction After Endoscopic Endonasal Transtuberculum Resection of Craniopharyngiomas.

BACKGROUND: The expanded endoscopic endonasal approach (EEA) is currently well accepted for a variety of ventral skull base tumors. Such an approach often results in a transdural defect and intraoperative cerebrospinal fluid (CSF) leak, and adequate reconstruction is necessary to prevent postoperative CSF leak and its complications. Reconstruction is usually performed using a variety of materials along with the nasoseptal flap. OBJECTIVE: This work's aim is to describe a new reconstructive technique called the "soft gasket seal" (SGS) in detail and compare it with the standard reconstructive technique at our institution for craniopharyngiomas operated via transtuberculum EEA. METHODS: A retrospective chart review was achieved to identify patients who underwent transtubercular EEA for craniopharyngioma between 2010 and 2018, by the same neurosurgical and otolaryngology team using either the SGS or standard reconstructive technique. RESULTS: Of 36 patients who met criteria and were considered for analysis, 15 of them underwent SGS reconstruction and 21 had standard reconstruction. There were 16 female (44%) and 20 male (56%) patients. The median age was 42.2 ± 20.9 years. The rate of postoperative CSF leak in the group of patients treated with the standard technique was 14.2% and 6.6% in the SGS group (odds ratio 0.43 [confidence interval 95% 0.007-6.15], P = 0.62). CONCLUSIONS: The SGS technique provides a simple reconstructive technique in conjunction with the nasoseptal flap, showing a tendency of lower complications when compared with our standard technique while avoiding donor site morbidity. Such results are encouraging, but further studies are necessary to confirm these findings.

Simultaneous Endoscopic and Microscopic Visualization in Microvascular Decompression for Hemifacial Spasm.

BACKGROUND: Hemifacial spasm (HFS) is a socially limiting condition leading to decreased quality of life that can be treated with microvascular decompression (MVD). Endoscopy has been described as an adjunct to traditional microscopy for MVD, although the best visualization technique is debated. OBJECTIVE: To review the current literature on use of endoscopy in MVD for HFS and to describe the simultaneous microscopic and endoscopic visualization technique along with a video illustration. METHODS: Patients who underwent MVD for HFS were retrospectively reviewed from January 2011 to December 2019. The first set of patients in the series were done using traditional endoscopic assisted visualization, followed by a change in technique in the subsequent patients using the simultaneous endoscopic technique. The surgical technique is described as well as illustrated with a video. RESULTS: In total, 21 patients underwent 24 MVDs to treat HFS. The simultaneous endoscopic/microscopic technique was used in 48% of cases for visualization. All but one patient had resolution of their symptoms immediately after the procedure. In total, 7 patients had recurrence of HFS, with 4 (17%) resolving spontaneously and 3 (13%) ultimately undergoing redo MVD. Postoperatively 7 patients (29%) had transient complications that all resolved completely. There was no significant difference between the traditional alternating microscopic and endoscopic technique with the simultaneous endoscopic microscopic technique. CONCLUSION: Endoscopic assistance during MVD for HFS is beneficial and may be streamlined by using the simultaneous microscope and endoscope visualization technique.

Method Development for a Short-Term 7-Day Toxicity Test with Unionid Mussels.

The US Environmental Protection Agency's short-term freshwater effluent test methods include a fish (Pimephales promelas), a cladoceran (Ceriodaphnia dubia), and a green alga (Raphidocelis subcapitata). There is a recognized need for additional taxa to accompany the three standard species for effluent testing. An appropriate additional taxon is unionid mussels because mussels are widely distributed, live burrowed in sediment and filter particles from the water column for food, and exhibit high sensitivity to a variety of contaminants. Multiple studies were conducted to develop a relevant and robust short-term test method for mussels. We first evaluated the comparative sensitivity of two mussel species (Villosa constricta and Lampsilis siliquoidea) and two standard species (P. promelas and C. dubia) using two mock effluents prepared by mixing ammonia and five metals (cadmium, copper, nickel, lead, and zinc) or a field-collected effluent in 7-day exposures. Both mussel species were equally or more sensitive (more than two-fold) to effluents compared with the standard species. Next, we refined the mussel test method by first determining the best feeding rate of a commercial algal mixture for three age groups (1, 2, and 3 weeks old) of L. siliquoidea in a 7-day feeding experiment, and then used the derived optimal feeding rates to assess the sensitivity of the three ages of juveniles in a 7-day reference toxicant (sodium chloride [NaCl]) test. Juvenile mussels grew substantially (30%-52% length increase) when the 1- or 2-week-old mussels were fed 2 ml twice daily and the 3-week-old mussels were fed 3 ml twice daily. The 25% inhibition concentrations (IC25s) for NaCl were similar (314-520 mg Cl/L) among the three age groups, indicating that an age range of 1- to 3-week-old mussels can be used for a 7-day test. Finally, using the refined test method, we conducted an interlaboratory study among 13 laboratories to evaluate the performance of a 7-day NaCl test with L. siliquoidea. Eleven laboratories successfully completed the test, with more than 80% control survival and reliable growth data. The IC25s ranged from 296 to 1076 mg Cl/L, with a low (34%) coefficient of variation, indicating that the proposed method for L. siliquoidea has acceptable precision. Environ Toxicol Chem 2021;40:3392-3409. © 2021 SETAC.

Endoscopic Endonasal Transtubercular Approach for Resection of Giant Pituitary Adenomas With Subarachnoid Extension: The "Second Floor" Strategy to Avoid Postoperative Apoplexy.

BACKGROUND: Giant pituitary adenomas (GPAs) with subarachnoid extension can be challenging to achieve a gross total resection through a single endonasal or transcranial approach, and any residual tumor is at risk for postoperative apoplexy. Intraoperative venous congestion of the suprasellar tumor can occur following resection of the sellar tumor, limiting tumor descent, and leading to suprasellar residual. We propose a technique for resecting the suprasellar component first, which we call the "second floor" strategy (SFS) for GPA. METHODS: A retrospective review of cases from 2010-2020 identified 586 endoscopic endonasal approaches (EEAs) for pituitary adenoma resection. We report the rate of postoperative apoplexy and describe the SFS technique used in 2 cases. RESULTS: Of 586 cases, 2 developed symptomatic postoperative apoplexy (0.3%), and a third transferred to our care after undergoing postoperative apoplexy. All 3 cases had subarachnoid extension of a pituitary adenoma, underwent EEA, and had residual suprasellar tumor. All 3 had permanent morbidity due to the postoperative apoplexy including blindness, stroke, or death, despite undergoing reoperation. The SFS was used for reoperation on 1 of these patients and as a primary strategy in a fourth patient who presented with a GPA with subarachnoid extension. We describe the SFS technique and demonstrate it with a 2-dimensional operative video. CONCLUSIONS: Postoperative apoplexy of residual adenoma is a rare but serious complication after GPA resection. The proposed SFS allows early access to the suprasellar tumor and may improve the ability to safely achieve a gross total resection without need for additional procedures.