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Objective Endoscopic ipsilateral endonasal transmaxillary, contralateral endonasal transseptal transmaxillary, and Caldwell-Luc approaches can access lesions within the retromaxillary space and pterygopalatine fossa. We compared the exposure and surgical freedom of these transmaxillary approaches to assist with surgical decision making. Design Four cadaveric heads were dissected bilaterally using the three approaches just described. Prior to dissection, stereotactic computed tomography (CT) scans were obtained on each head to obtain anatomical measurements. Surgical freedom and area of exposure were determined by stereotaxis. Main Outcome Measures Area of exposure was calculated as the extent of the orbital floor, maxillary sinus floor, nasal floor, and mandibular ramus exposed through each approach. Surgical freedom was the area through which the proximal end of the endoscope could be freely moved while moving the tip of the endoscope to the edges of the exposed area. Results The mean exposed area was similar: 9.9 ± 2.5 cm² (Caldwell-Luc), 10.4 ± 2.6 cm² (ipsilateral endonasal), and 10.1 ± 2.1 cm² (contralateral transseptal) (p > 0.05). The surgical freedom of the Caldwell-Luc approach (113 ± 7 cm²) was greater than for either endonasal approach, 76 cm² ± 15 (p = 0.001) (ipsilateral endonasal) and 83 cm² ± 15 (p = 0.003) contralateral transseptal. Conclusions Our work demonstrates that the Caldwell-Luc endonasal approach offers greater surgical freedom than either approach for anterolateral skull base targets, although these approaches offer similar exposure. [ABSTRACT FROM AUTHOR]

The rich history of neurosurgical innovation served as a model for the Barrow Innovation Center's establishment in 2016. The center's accomplishments are summarized in hopes of fostering the development of similar centers and initiatives within the neurosurgical and broader medical community. A retrospective review (January 2016–July 2021) of patent filings, project proposals, and funding history was used to generate the data presented in this operational review. Through the 5-year period of analysis, 55 prior art searches were conducted on new patentable ideas. A total of 87 provisional patents, 25 Patent Cooperation Treaty applications, and 48 national stage filings were submitted. In partnership with Arizona State University, the University of Arizona, California Polytechnic State University, and Texas A&M University, a total of 27 multidisciplinary projects were conducted with input from multispecialty engineers and scientists. These efforts translated into 1 startup company and 2 licensed patents to commercial companies, with most remaining ideas and project efforts awaiting interest from industry. The multidisciplinary collaborative environment embodied by the Barrow Innovation Center has revolutionized the innovative and entrepreneurial environment of its home institution and enabled neurosurgical residents to get a unique educational experience within the realm of innovation. The bottleneck within the workflow of ideas from conception to commercialization appears to be the establishment of commercial partners; therefore, future efforts within the center will be to establish a panel of industry partnerships to enhance the exposure of ideas to interested companies. [ABSTRACT FROM AUTHOR]

(1) Background: Cushing's disease (CD) is a serious endocrine disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery. Current surgical remission rates reported in only 56% of patients depending on several criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies make CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of relevant human model systems that recapitulate the cellular composition of PitNET microenvironment. (2) Methods: human pituitary tumor tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). (3) Results: hPITOs generated from corticotroph, lactotroph, gonadotroph, and somatotroph tumors exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient's tumor was validated by comparing the neuropathology report to the expression pattern of PitNET specific markers, using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each tumor subtype. Generation of induced pluripotent stem cells (iPSCs) from a CD patient carrying germline mutation CDH23 exhibited dysregulated cell lineage commitment. (4) Conclusions: The human pituitary neuroendocrine tumor organoids represent a novel approach in how we model complex pathologies in CD patients, which will enable effective personalized medicine for these patients. [ABSTRACT FROM AUTHOR]

Objectives  Endoscopic endonasal approaches (EEAs) for petrosectomies are evolving to reduce perioperative brain injuries and complications. Surgical terminology, techniques, landmarks, advantages, and limitations of these approaches remain ill defined. We quantitatively analyzed the anatomical relationships and differences between EEA exposures for medial, inferior, and inferomedial petrosectomies. Design  This study presents anatomical dissection and quantitative analysis. Setting  Cadaveric heads were used for dissection. EEAs were performed using the medial petrosectomy (MP), the inferior petrosectomy (IP), and the inferomedial petrosectomy (IMP) techniques. Participants  Six cadaver heads (12 sides, total) were dissected; each technique was performed on four sides. Main Outcomes and Measures  Outcomes included the area of exposure, visible distances, angles of attack, and bone resection volume. Results  The IMP technique provided a greater area of exposure (p  < 0.01) and bone resection volume (p  < 0.01) when compared with the MP and IP techniques. The IMP technique had a longer working length of the abducens nerve (cranial nerve [CN] VI) than the MP technique (p  < 0.01). The IMP technique demonstrated higher angles of attack to specific neurovascular structures when compared with the MP (midpons [ p  = 0.04], anterior inferior cerebellar artery [ p  < 0.01], proximal part of the cisternal CN VI segment [ p  = 0.02]) and IP (flocculus [ p  = 0.02] and the proximal [ p  = 0.02] and distal parts [ p  = 0.02] of the CN VII/VIII complex) techniques. Conclusion  Each of these approaches offers varying degrees of access to the petroclival region, and the surgical approach should be appropriately tailored to the pathology. Overall, the IMP technique provides greater EEA surgical exposure to vital neurovascular structures than the MP and the IP techniques. [ABSTRACT FROM AUTHOR]

Objective  This study investigated the impact of residual tumor volume (RTV) on tumor progression after subtotal resection and observation of WHO grade I skull base meningiomas. Study Design  This study is a retrospective volumetric analysis. Setting  This study was conducted at a single institution. Participants  Patients who underwent subtotal resection of a WHO grade I skull base meningioma and postsurgical observation (July 1, 2007–July 1, 2017). Main Outcome Measure  The main outcome was radiographic tumor progression. Results  Sixty patients with residual skull base meningiomas were analyzed. The median (interquartile range) RTV was 1.3 (5.3) cm 3. Tumor progression occurred in 23 patients (38.3%) at a mean duration of 28.6 months postsurgery. The 1-, 3-, and 5-year actuarial progression-free survival (PFS) rates were 98.3, 58.6, and 48.7%, respectively. The Cox multivariate analysis identified increasing RTV (p  = 0.01) and history of more than 1 previous surgery (p  = 0.03) as independent predictors of tumor progression. In a Kaplan–Meier analysis for PFS, the RTV threshold of 3 cm 3 maximized log-rank testing significance between groups of patients dichotomized at 0.5 cm 3 thresholds (p  < 0.01). The 3-year actuarial PFS rates for meningiomas with RTV ≤3 cm 3 and >3 cm 3 were 76.2 and 32.1%, respectively. When RTV >3 cm 3 was entered as a covariate in the Cox model, it was the only factor independently associated with tumor progression (p  < 0.01). Conclusion  RTV was associated with tumor progression after subtotal resection of WHO grade I skull base meningioma in this cohort. An RTV threshold of 3 cm 3 was identified that minimized progression of the residual tumor when gross total resection was not safe or feasible. [ABSTRACT FROM AUTHOR]

Objectives  To better understand the risk-benefit profile of skull base meningioma resection in older patients, we compared perioperative complications among older and younger patients. Design  Present study is based on retrospective outcomes comparison. Setting  The study was conducted at a single neurosurgery institute at a quaternary center. Participants  All older (age ≥ 65 years) and younger (<65 years) adult patients treated with World Health Organization grade 1 skull base meningiomas (2008–2017). Main Outcome Measures  Perioperative complications and patient functional status are the primary outcomes of this study. Results  The analysis included 287 patients, 102 older and 185 younger, with a mean (standard deviation [SD]) age of 72 (5) years and 51 (9) years (p  < 0.01). Older patients were more likely to have hypertension (p  < 0.01) and type 2 diabetes mellitus (p  = 0.01) but other patient and tumor factors did not differ (p ≥ 0.14). Postoperative medical complications were not significantly different in older versus younger patients (10.8 [11/102] vs. 4.3% [8/185]; p  = 0.06) nor were postoperative surgical complications (13.7 [14/102] vs. 10.8% [20/185]; p  = 0.46). Following anterior skull base meningioma resection, diabetes insipidus (DI) was more common in older versus younger patients (14 [5/37] vs. 2% [1/64]; p  = 0.01). Among older patients, a decreasing preoperative Karnofsky performance status score independently predicted perioperative complications by logistic regression analysis (p  = 0.02). Permanent neurologic deficits were not significantly different in older versus younger patients (12.7 [13/102] vs. 10.3% [19/185]; p  = 0.52). Conclusion  The overall perioperative complication profile of older and younger patients was similar after skull base meningioma resection. Older patients were more likely to experience DI after anterior skull base meningioma resection. Decreasing functional status in older patients predicted perioperative complications. [ABSTRACT FROM AUTHOR]

Transcranial anterior petrosectomy (AP) is a classic approach; however, it is associated with adverse consequences. The endoscopic endonasal approach (EEA) has been developed as an alternative. We describe surgical techniques for AP and EEA and compare the anatomic exposures of each. Ten cadaveric heads (20 sides) were dissected. Specimens were divided into 4 groups: 1) AP, 2) EEA for medial petrosectomy (MP), 3) EEA for inferior petrosectomy (IP), and 4) EEA for inferomedial petrosectomy (IMP). Outcomes were areas of exposure, angles of attack to neurovascular structures, and bone resection volumes. AP had a greater area of exposure than did MP and IP (P = 0.30, P < 0.01) and had a higher angle of attack to the distal part of the facial nerve–vestibulocochlear nerve (cranial nerve [CN] VII/VIII) complex than did IP and IMP (P < 0.01). MP had a lower angle of attack than IMP to the midpons (P = 0.04) and to the anterior inferior cerebellar artery (P < 0.01). Compared with IMP, IP had a lower angle of attack to the proximal part of the CN VII/VIII complex (P < 0.01) and the flocculus (P < 0.01). The bone resection volume in AP was significantly less than that in MP, IP, and IMP (P < 0.01). AP and all EEA techniques had specific advantages for each specific area. We suggest AP for the ventrolateral pons and the anterior superior internal auditory canal, MP for the midline clivus, IP for the ventrolateral brainstem, and IMP to enhance the lateral corridor of the abducens nerve. [ABSTRACT FROM AUTHOR]

This study evaluates the temporal evolution of the spatial relationship between the pituitary adenoma transsphenoidal surgical cavity and the adjacent optic chiasm and discusses implications on timing and choice of radiotherapy modality. This retrospective observational review analyzed factors that might influence the postoperative relationship between the surgical cavity and the optic chiasm, including tumor type, craniocaudal tumor and resection cavity dimensions, the preoperative distance between tumor and the optic chiasm, the presence of cavernous sinus invasion, and the choice of intraoperative packing material. Changes observed on magnetic resonance imaging in the preoperative, immediate (within 72 h), and delayed (≥3 months) postoperative periods were compared. Sixty-five patient histories were analyzed. Preoperatively, the pituitary adenoma was apposed to the optic chiasm in 43 patients (66%). Postoperatively, 34 patients (52%) in the immediate postoperative period and 54 patients (83%) in the delayed postoperative period had a distance ≥2 mm between the resection cavity and the optic chiasm. This distance provides a greater margin of safety with adjuvant radiosurgery. Preoperative tumor size showed a strong association with postoperative descent of the optic chiasm. Preoperative tumor size and degree of mass effect on the optic chiasm predict postoperative changes. In this study, the distance between the resection cavity and the optic chiasm was greater at ≥3 months postoperatively than in the immediate postoperative period, regardless of preoperative mass effect, indicating radiotherapy planning should be deferred to ≥3 months postoperatively when not precluded by aggressive histological characteristics that necessitate more immediate treatment. To investigate the temporal relationship between the postoperative sellar surgical cavity and the adjacent optic apparatus after transsphenoidal resection of pituitary adenomas and the implications for radiotherapy. • MRIs were evaluated in 65 patients after transsphenoidal pituitary adenoma surgery. • A subset of these patients may require adjuvant radiotherapy. • Radiosurgery is safest when the optic chiasm is >2 mm from the resection cavity. • The surgical cavity involutes predictably, increasing distance from the optic chiasm over time. [ABSTRACT FROM AUTHOR]

Objective Visual field (VF) outcomes are commonly reported in neurosurgical case series; however, substantial variability can exist in VF testing and outcome reporting. We aimed to evaluate the challenges of VF testing and to develop detailed recommendations for VF outcome reporting by analyzing results from an ongoing, multicenter study of transsphenoidal pituitary surgery. Methods VF testing results were collected during a prospective, multicenter clinical trial evaluating patient outcomes after transsphenoidal surgery for nonfunctioning pituitary adenomas (TRANSSPHER). Two independent ophthalmologists reviewed reliability and outcomes of all VF studies. Preoperative and postoperative VF studies were evaluated individually and as preoperative/postoperative pairs. Results Suboptimal perimetry field settings were reported in 37% of VF studies. Automated reliability criteria flagged 25%–29% of VF studies as unreliable, whereas evaluation by 2 independent ophthalmologists flagged 16%–28%. Agreement between automated criteria and raters for VF reliability was inconsistent (κ coefficients = 0.55–0.83), whereas agreement between the 2 raters was substantial to almost perfect (κ coefficients = 0.78–0.83). Most patients demonstrated improvement after surgery (rater 1, 67%; rater 2, 60%), with substantial rater agreement on outcomes for paired examinations (κ coefficient = 0.62). Conclusions VF outcome studies demonstrated significant variability of test parameters and patient performance. Perimetry field settings varied among patients and for some patients varied preoperatively versus postoperatively. Reliance on automated criteria alone could not substitute for independent ophthalmologist review of test reliability. Standardized guidelines for VF data collection and reporting could increase reliability of results and allow better comparisons of outcomes in future studies. Highlights • In a multicenter trial, 30% of VF studies were unreliable. • Neurosurgeons and researchers should consider the potential unreliability of VF data. • We review sources of unreliable VF testing in a transsphenoidal surgery cohort. • We propose guidelines to improve VF reporting in future neurosurgical studies. [ABSTRACT FROM AUTHOR]

Chordoma is a rare, radiation-resistant, skull-base and spinal tumor with high local recurrence containing mixed cell-adhesion phenotypes. We characterized DNA damage response (DDR) signaling (γH2AX, pKAP1, pATM) and survival response to ionizing radiation (IR) in human chordoma samples (42 resections, 23 patients) to test if blocking cell adhesion sensitizes U-CH1 tumor cells to IR. U-CH1 cells expressed brachyury, YAP, and laminin adhesion receptors (CD49c, CD49f, CD44), and approximately 15% to 20% of U-CH1 cells featured an α6 integrindependent (CD49f) cohesive cluster phenotype, which confers therapeutic resistance and aids metastasis. DDR to IR in U-CH1 cells was compared to normal prostate epithelial (PrEC) and tumor cells (DU145). Flow cytometry showed a dose- and time-dependent increase in γH2AX and pKAP1 expression in all cell lines. However, nearly 50% of U-CH1 cells exhibited nonresponsive phenotype to IR (measured by γH2AX and pKAP1) independent of cell cycle status. Immunofluorescence microscopy verified that only 15% of U-CH1 clustered cells were γH2AX or pKAP1 positive (versus 80% of nonclustered cells) 2 hours following 2-Gy IR. Conversely, both tumor cell lines were uniformly defective in pATM response. HYD1, a synthetic ECM ligand, inhibited DDR through an unresolved γH2AX response. β1 integrin-blocking antibody (AIIB2) decreased cell survival 50% itself and approximately doubled the IR-induced cell kill at all IR doses observed at 2 and 4 weeks posttreatment. These results suggest that a heterogeneity of DDR to IR exists within a chordoma population. Blocking integrin function alone and/or as an adjuvant to IR may eradicate chordomas containing the cohesive cluster phenotype. [ABSTRACT FROM AUTHOR]