Integrating Overall Survival and Tumor Control Probability Models to Predict Local Progression After Brain Metastasis Radiosurgery.

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is frequently prescribed to the maximum tolerated dose to minimize the probability of local progression. However, many patients die from extracranial disease prior to local progression and may not require maximally aggressive treatment. Recently, improvements in models of SRS tumor control probability (TCP) and overall survival (OS) have been made. We predicted that by combining models of OS and TCP, we could better predict the true risk of local progression after SRS than by using TCP modeling alone. Methods and Materials: Records of patients undergoing SRS at a single institution were reviewed retrospectively. Using established TCP and OS models, for each patient, the probability of 1-year survival [p(OS)] was calculated, as was the probability of 1-year local progression [p(LP)]) for each treated lesion. Joint-probability was used to combine the models [p(LP,OS)=p(LP)*p(OS)]. Analyses were conducted at the individual metastasis and whole-patient levels. Fine-Gray regression was used to model p(LP) or p(LP,OS) on the risk of local progression after SRS, with death as a competing risk. Results: At the patient level, 1-year local progression was 0.08 (95% CI, 0.03-0.15), median p(LP,OS) was 0.13 (95% CI, 0.07-0.2), and median p(LP) was 0.29 (95% CI, 0.22-0.38). At the metastasis level, 1-year local progression was 0.02 (95% CI, 0.01-0.04), median p(LP,OS) was 0.05 (95% CI, 0.02-0.07), and median p(LP) was 0.10 (95% CI, 0.07-0.13). p(LP,OS) was found to be significantly associated with the risk of local progression at the patient level (P = .048) and metastasis level (P = .007); however, p(LP) was not (P = .16 and P = .28, respectively). Conclusions: Simultaneous modeling of OS and TCP more accurately predicted local progression than TCP modeling alone. Better understanding which patients with brain metastases are at risk of local progression after SRS may help personalize treatment to minimize risk without sacrificing efficacy.

Staged Resection of Difficult-to-Treat Intracranial Meningiomas: A Systematic Review of the Indications, Surgical Approaches, and Postoperative Outcomes.

Introduction Meningiomas-the most common extra-axial tumors-are benign, slow-growing dural-based lesions that can involve multiple cranial fossae and can progress insidiously for years until coming to clinical attention secondary to compression of adjacent neurovascular structures. For complex, multicompartmental lesions, multistaged surgeries have been increasingly shown to enhance maximal safe resection while minimizing adverse sequela. Here, we systematically review the extant literature to highlight the merits of staged resection. Methods PubMed, Scopus, and Web of Science databases were queried to identify articles reporting resections of intracranial meningiomas using a multistaged approach, and articles were screened for possible inclusion in a systematic process performed by two authors. Results Of 118 identified studies, 36 describing 169 patients (mean age 42.6 ± 21.3 years) met inclusion/exclusion criteria. Petroclival lesions comprised 57% of cases, with the most common indications for a multistaged approach being large size, close approximation of critical neurovascular structures, minimization of brain retraction, identification and ligation of deep vessels feeding the tumor, and resection of residual tumor found on postoperative imaging. Most second-stage surgeries occurred within 3 months of the index surgery. Few complications were reported and multistaged resections appeared to be well tolerated overall. Conclusions Current literature suggests multistaged approaches for meningioma resection are well-tolerated. However, there is insufficient comparative evidence to draw definitive conclusions about its advantages over an unstaged approach. There are similarly insufficient data to generate an evidence-based decision-making framework for when a staged approach should be employed. This highlights the need for collaborative efforts among skull base surgeons to establish an evidentiary to support the use of staged approaches and to outline those indications that merit such an approach.

The Temporoparietal Fascia Flap Transposition Technique for Ventral Skull Base Reconstruction: Anatomic Analysis and Surgical Application.

BACKGROUND AND OBJECTIVES: The temporoparietal fascia (TPF) flap is an alternative for revision endoscopic skull base reconstruction in the absence of the nasoseptal flap, and we aimed to investigate the anatomy and surgical application of TPF flap transposition in endoscopic endonasal surgery. METHODS: Six lightly embalmed postmortem human heads and 30 computed tomography angiography imaging scans were used to analyze the anatomic features of the TPF flap transposition technique. Three cases selected from a 512 endoscopic endonasal cases database were presented for the clinical application of the TPF flap. RESULTS: The TPF flap, composed by the deepest 3 scalp layers (galea aponeurotica, loose areolar connective tissue, and pericranium), can be harvested and then transposed through the infratemporal-maxillary-pterygoid tunnel to the ventral skull base. The superficial temporal artery as its feeding artery, gives frontal and parietal branches with similar diameter (1.5 ± 0.3 mm) at its bifurcation. The typical bifurcation was present in 50 sides (83.3%), with single (frontal) branch in 5 sides (8.3%), single (parietal) branch in 2 sides (3.3%), and multiple branches (>2) in 3 sides (5%). The transposed TPF flap was divided into 3 parts according to its anatomic location: (1) infratemporal part with an area of 19.5 ± 2.5 cm2, (2) maxillary part with an area of 23.7 ± 2.8 cm2, and (3) skull base part with an area of 44.2 ± 4 cm2. Compared with the nasoseptal flap, nasal floor flap, inferior turbinate flap, and extended septal flap, the coverage area of the skull base part of the TPF flap was significantly larger than any of them (P < .0001). CONCLUSION: The TPF flap technique is an effective alternative for endoscopic endonasal skull base reconstruction. The TPF flap could successfully cover large skull base defects through the infratemporal-maxillary-pterygoid tunnel.

Resection of corticotroph microadenomas invading the medial wall of the cavernous sinus in two cases of a primary and recurrent case of Cushing's disease.

Emerging evidence from multiple highly specialized groups continues to support a role for resection of the medial wall of the cavernous sinus when it is invaded by functional pituitary adenomas, to offer durable biochemical remission. The authors present two cases of Cushing's disease that underscore the power of this surgical technique in achieving remission in microadenomas that ectopically present in the cavernous sinus or have invaded the medial wall of the sinus. This video demonstrates key steps in the safe removal of the medial wall of the cavernous sinus and successful resection of tumor burden in the cavernous sinus for sustained postoperative remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2323.

Cytodifferentiation of pituitary tumors influences pathogenesis and cavernous sinus invasion.

OBJECTIVE: Pituitary tumors (PTs) continue to present unique challenges given their proximity to the cavernous sinus, whereby invasive behavior can limit the extent of resection and surgical outcome, especially in functional tumors. The aim of this study was to elucidate patterns of cavernoinvasive behavior by PT subtype. METHODS: A total of 169 consecutive first-time surgeries for PTs were analyzed; 45% of the tumors were functional. There were 64 pituitary transcription factor-1 (PIT-1)-expressing, 62 steroidogenic factor-1 (SF-1)-expressing, 38 T-box transcription factor (TPIT)-expressing, and 5 nonstaining PTs. The gold standard for cavernous sinus invasion (CSI) was based on histopathological examination of the cavernous sinus medial wall and intraoperative exploration. RESULTS: Cavernous sinus disease was present in 33% of patients. Of the Knosp grade 3 and 4 tumors, 12 (19%) expressed PIT-1, 7 (11%) expressed SF-1, 8 (21%) expressed TPIT, and 2 (40%), were nonstaining (p = 0.36). PIT-1 tumors had a significantly higher predilection for CSI: 53% versus 24% and 18% for TPIT and SF-1 tumors, respectively (OR 6.08, 95% CI 2.86-13.55; p < 0.001). Microscopic CSI-defined as Knosp grade 0-2 tumors with confirmed invasion-was present in 44% of PIT-1 tumors compared with 7% and 13% of TPIT and SF-1 tumors, respectively (OR 11.72, 95% CI 4.35-35.50; p < 0.001). Using the transcavernous approach to excise cavernous sinus disease, surgical biochemical remission rates for patients with acromegaly, prolactinoma, and Cushing disease were 88%, 87%, and 100%, respectively. The granule density of PIT-1 tumors and corticotroph functional status did not influence CSI. CONCLUSIONS: The likelihood of CSI differed by transcription factor expression; PIT-1-expressing tumors had a higher predilection for invading the cavernous sinus, particularly microscopically, compared with the other tumor subtypes. This elucidates a unique cavernoinvasive behavior absent in cells from other lineages. Innovative surgical techniques, however, can mitigate tumor behavior and achieve robust, reproducible biochemical remission and gross-total resection rates. These findings can have considerable implications on the surgical management and study of PT biology and behavior.

The Pterygosphenoidal Triangle: Surgical Anatomy and Case Series in Endoscopic Endonasal Skull Base Surgery.

BACKGROUND: Safe exposure of the lacerum segment of the carotid artery remains a challenge in endoscopic endonasal surgery. OBJECTIVE: To introduce the pterygosphenoidal triangle as a novel and reliable landmark for facilitating access to the foramen lacerum. METHODS: Fifteen colored silicone-injected anatomic specimens were dissected using an endoscopic endonasal approach to the foramen lacerum region in a stepwise manner. Twelve dried skulls were studied and 30 high-resolution computed tomography scans were analyzed to measure the borders and angles of the pterygosphenoidal triangle. Surgical cases incorporating the foramen lacerum exposure between July 2018 and December 2021 were reviewed to provide surgical outcomes of the proposed surgical technique. RESULTS: The pterygosphenoidal triangle is delineated by the pterygosphenoidal fissure medially and the vidian nerve laterally. The palatovaginal artery is located at the base of the triangle anteriorly, while the apex is formed by the pterygoid tubercle posteriorly, which leads to the anterior wall of the foramen lacerum and lacerum internal carotid artery. In the reviewed surgical cases, 39 patients underwent 46 foramen lacerum approaches for resection of pituitary adenoma (12 patients), meningioma (6 patients), chondrosarcoma (5 patients), chordoma (5 patients), or other lesions (11 patients). There were no carotid injuries or ischemic events. Near-total resection was achieved in 33 (85%) of 39 patients (gross-total in 20 [51%]). CONCLUSION: This study details the pterygosphenoidal triangle as a novel and practical anatomic surgical landmark for safe and effective exposure of the foramen lacerum in endoscopic endonasal surgery.

Knowledge and Awareness Regarding Osteoarthritis and Its Factors in Hail Region, Saudi Arabia.

Objectives Osteoarthritis (OA) is a common chronic degenerative joint disease linked to age, joint overuse abnormalities, and previous trauma. This research aims to assess the awareness levels, as well as the knowledge gap and misconceptions, about OA and its risk factors among the general population in Hail, Saudi Arabia. Methods The research adopted an observational cross-sectional method. Participants from Hail, Saudi Arabia, were recruited and then interviewed between 1 April and 15 July 2022. Adult males and females aged 18 or more were recruited via an online questionnaire using a Google Form link, inviting them to take part in a study concerning their knowledge of OA. The questionnaire was split into three sections. The first section covered demographic data, the second section contained general knowledge regarding OA, and the third section was made up of a 20-item quiz. The collected data was reviewed and then analyzed using the Statistical Package for Social Sciences (SPSS) Version 21 (IBM Corp., Armonk, NY, USA). The statistical methods employed were all two-tailed, with an alpha level of 0.05 considered significant if the P value was less than, or equal to, 0.05. Results Nine hundred six (906) eligible respondents completed the questionnaire. Participants ranged from 18 to 65 in age. More than 66% were female, while 77.5% had a university level of education or above. 13.6% had been diagnosed with OA. Overall, 40.9% of the study participants demonstrated a good knowledge level regarding OA, while 59.1% showed a poor knowledge level. Conclusion The study revealed that the awareness and knowledge levels of the general population in Hail about OA are unsatisfactory. Efforts are recommended to increase the awareness and knowledge of the population through public education, which in turn can lead to a reduction in risk factors and improved early detection of the disease.

Reappraisal of the anatomy of the frontotemporal branches of the facial nerve.

OBJECTIVE: The anatomy of the temporal branches of the facial nerve (FN) has been widely described in the neurosurgical literature because of its relevance in anterolateral approaches to the skull base and implication in frontalis palsies from these approaches. In this study, the authors attempted to describe the anatomy of the temporal branches of the FN and identify whether there are any FN branches that cross the interfascial space of the superficial and deep leaflets of the temporalis fascia. METHODS: The surgical anatomy of the temporal branches of the FN was studied bilaterally in 5 embalmed heads (n = 10 extracranial FNs). Exquisite dissections were performed to preserve the relationships of the branches of the FN and their relationship to the surrounding fascia of the temporalis muscle, the interfascial fat pad, the surrounding nerve branches, and their final terminal endpoints near the frontalis and temporalis muscles. The authors correlated their findings intraoperatively with 6 consecutive patients with interfascial dissection in which neuromonitoring was performed to stimulate the FN and associated twigs that were observed to be interfascial in 2 of them. RESULTS: The temporal branches of the FN stay predominantly superficial to the superficial leaflet of the temporal fascia in the loose areolar tissue near the superficial fat pad. As they course over the frontotemporal region, they give off a twig that anastomoses with the zygomaticotemporal branch of the trigeminal nerve, which crosses the superficial layer of the temporalis muscle, spanning the interfascial fat pad, and then pierces the deep temporalis fascial layer. This anatomy was observed in 10 of the 10 FNs dissected. Intraoperatively, stimulation of this interfascial segment yielded no facial muscle response up to 1 mA in any of the patients. CONCLUSIONS: The temporal branch of the FN gives off a twig that anastomoses with the zygomaticotemporal nerve, which crosses the superficial and deep leaflets of the temporal fascia. Interfascial surgical techniques aimed at protecting the frontalis branch of the FN are safe in their efforts to protect against frontalis palsy with no clinical sequelae when executed properly.

Impact of esthesioneuroblastoma treatment delays on overall patient survival.

OBJECTIVES: To characterize clinical factors associated with esthesioneuroblastoma treatment delays and determine the impact of these delays on overall survival. STUDY DESIGN: Retrospective database analysis. METHODS: The 2004-2016 National Cancer Database was queried for patients with esthesioneuroblastoma managed by primary surgery and adjuvant radiation. Durations of diagnosis-to-treatment initiation (DTI), diagnosis-to-treatment end (DTE), surgery-to-RT initiation (SRT), radiotherapy treatment (RTD), and total treatment package (TTP) were analyzed. The cohort was split into two groups for each delay interval using the median time as the threshold. RESULTS: A total of 814 patients (39.6% female, 88.5% white) with mean ± SD age of 52.6 ± 15.1 years who underwent both esthesioneuroblastoma surgery and adjuvant radiotherapy were queried. Median DTI, DTE, SRT, RTD, and TTP were 34, 140, 55, 45, and 101 days, respectively. A significant association was identified between increased regional radiation dose above 66 Gy and decreased DTI (OR = 0.54, 95% CI 0.35-0.83, p = 0.01) and increased RTD (OR = 3.94, 95% CI 2.36-6.58, p < 0.001) durations. Chemotherapy administration was linked with decreased SRT (OR = 0.64, 95% CI 0.47-0.89, p = 0.01) and TTP (OR = 0.59, 95% CI 0.43-0.82, p = 0.001) durations. Cox proportional-hazards analysis revealed that increased RTD was associated with decreased survival (HR = 1.80, 95% CI 1.26-2.57, p < 0.005), independent of age, sex, race, regional radiation dose, facility volume, facility type, insurance status, modified Kadish stage, chemotherapy status, Charlson-Deyo comorbidity index, and surgical margins. CONCLUSIONS: Delays during, and prolongation of radiotherapy for esthesioneuroblastoma appears to be associated with decreased survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:764-772, 2023.

Surgical management of petrous apex cholesteatomas in the pediatric population: A systematic review.

Background: Cholesteatomas are growths of squamous epithelium that can form inside the middle ear and mastoid cavity and damage nearby structures causing hearing loss when located at the petrous apex. The primary goal of petrous apex cholesteatoma resection is gross total removal with tympanoplasty and canal-wall up or canal-wall down tympanomastoidectomy. At present, there is no definitive surgical approach supported by greater than level 4 evidence in the literature to date. Methods: A systematic review was conducted utilizing PubMed, Embase, and Scopus databases. Articles were screened and selected to be reviewed in full text. The articles that met inclusion criteria were reviewed for relevant data. Data analysis, means, and standard deviations were calculated using Microsoft Excel. Results: After screening, five articles were included in the systematic review. There were a total of eight pediatric patients with nine total cholesteatomas removed. Conductive hearing loss was the most common (77%) presenting symptom. Perforations were noted in seven ears (86%). Recurrence was noted in 50% of patients with an average recurrence rate of 3.5 years (SD = 1.73). Average length of follow-up was 32.6 months (SD = 21.7). Canal-wall up was the most utilized technique (60%) and there were zero noted surgical complications. Five of the seven (71%) patients that experienced hearing loss from perforation noted improved hearing. Conclusion: Due to its rarity, diagnostic evaluation and treatment can vary. Further, multi-institutional investigation is necessary to develop population-level management protocols for pediatric patients affected by petrous apex cholesteatomas.

Endoscopic versus Nonendoscopic Surgery for Resection of Craniopharyngiomas.

OBJECTIVE: While surgery is a critical treatment option for craniopharyngiomas, the optimal surgical approach remains under debate. Herein, we studied a large cohort of craniopharyngioma patients to identify predictors of endoscopic surgery (ES) and to compare survival outcomes between patients undergoing ES versus nonendoscopic surgery (NES). METHODS: The National Cancer Database was queried for patients receiving definitive surgical treatment in 2010-2016. Cox proportional hazards and propensity score-adjusted Kaplan-Meier analyses assessed mortality risk and overall survival, respectively. Predictors of surgical approach were evaluated via logistic regression. RESULTS: Of 1721 patients, 508 (29.5%) underwent ES, 877 (50.9%) were female, and the average age was 41.8 ± 21.3 years. Matched ES and NES cohorts exhibited 5-year overall survival rates of 88.0% and 79.8%, respectively (P = 0.004). ES was associated with reduced mortality (Hazard Ratio = 0.634; 95% confidence interval [CI], 0.439-0.914; P = 0.015). Patients treated at academic facilities (Odds Ratio [OR] = 2.095; 95% CI, 1.529-2.904; P < 0.001) or diagnosed recently (OR = 1.132; 95% CI, 1.058-1.211; P < 0.001) were more likely to undergo ES, while those with tumor sizes >3 cm (OR = 0.604; 95% CI, 0.451-0.804; P < 0.001) or receiving adjuvant radiotherapy (OR = 0.641; 95% CI, 0.454-0.894; P = 0.010) were more likely to receive NES. Surgical inpatient stays were significantly shorter with ES compared to NES (8.0 vs. 10.5 days, P < 0.001). On linear regression, ES usage increased by 82.4% and NES usage decreased by 23.4% between 2010 and 2016 (R2 = 0.575, P = 0.031). CONCLUSIONS: ES of craniopharyngioma was associated with reduced mortality and shorter inpatient stays compared to NES. Factors including tumor size, extent of resection, facility type, and year of diagnosis may predict receiving ES. There is a trend towards increased usage of ES for surgical management of craniopharyngiomas.

Endoscopic Anatomy of the Zygomatic Nerve: Implications for the Endoscopic Transmaxillary Approach.

Introduction Understanding the anatomic features of the zygomatic nerve is critical for performing the endoscopic transmaxillary approach properly. Injury to the zygomatic nerve can result in facial numbness and corneal problems. Objective To evaluate the surgical anatomy of the zygomatic nerve and its segments from an endoscopic endonasal perspective for clinical implications of performing the endoscopic transmaxillary approach. Methods The origin, course, length, and segments of the zygomatic nerve were studied in four specimens from an endonasal perspective. Results The zygomatic nerve arises 4.1 ± 1.7 mm from the foramen rotundum of the maxillary nerve in the superolateral pterygopalatine fossa (PPF). According to its anatomic region in endonasal endoscopic surgery, we divided the zygomatic nerve into two segments: the PPF segment, from origin to the point of entry under Muller's muscle, which runs superolaterally to the inferior orbital fissure (IOF) (length, 4.6 ± 1.3 mm), and the IOF segment, starting at the entry point in Muller's muscle and terminating at the exit point in the IOF, which travels between Muller's muscle and the great wing of the sphenoid bone (length, 19.6 ± 3.6 mm). In the transmaxillary approach, the zygomatic nerve is a critical landmark in the superolateral PPF. Conclusion The zygomatic nerve travels in the PPF and the IOF; better visualization and preservation of this nerve during endonasal endoscopic surgery are crucial for successful outcomes.

Intracranial Breakthrough Through Cavernous Sinus Compartments: Anatomic Study and Implications for Pituitary Adenoma Surgery.

BACKGROUND: Pituitary adenomas (PAs) with cavernous sinus (CS) invasion can extend into the intradural space by breaking through the CS walls. OBJECTIVE: To elaborate on the potential breakthrough route through CS compartments for invasive PAs and describe relevant surgical anatomy and technical nuances, with an aim to improve resection rates. METHODS: Twelve colored silicon-injected human head specimens were used for endonasal and transcranial dissection of the CS walls; ligaments, dural folds, and cranial nerves on each compartment were inspected. Two illustrative cases of invasive PA are also presented. RESULTS: The potential breakthrough routes through the CS compartments had unique anatomic features. The superior compartment breakthrough was delimited by the anterior petroclinoidal ligament laterally, posterior petroclinoidal ligament posteriorly, and interclinoidal ligament medially; tumor extended into the parapeduncular space with an intimate spatial relationship with the oculomotor nerve and posterior communicating artery. The lateral compartment breakthrough was limited by the anterior petroclinoidal ligament superiorly and ophthalmic nerve inferiorly; tumor extended into the middle fossa, displacing the trochlear nerve and inferolateral trunk to reach the medial temporal lobe. The posterior compartment breakthrough delineated by the Gruber ligament, petrosal process of the sphenoid bone, and petrous apex inferiorly, posterior petroclinoidal ligament superiorly, and dorsum sellae medially; tumor displaced or encased the abducens nerve and inferior hypophyseal artery and compressed the cerebral peduncle. CONCLUSION: The superior lateral and posterior components of the CS are potential routes for invasion by PAs. Better identification of CS breakthrough patterns is crucial for achieving higher gross total resection and remission rates.

Prospective intraoperative and histologic evaluation of cavernous sinus medial wall invasion by pituitary adenomas and its implications for acromegaly remission outcomes.

Recurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3-30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas.

Microsurgical anatomy and the importance of the petrosal process of the sphenoid bone in endonasal surgery.

OBJECTIVE: The petrosal process of the sphenoid bone (PPsb) is a relevant skull base osseous prominence present bilaterally that can be used as a key surgical landmark, especially for identifying the abducens nerve. The authors investigated the surgical anatomy of the PPsb, its relationship with adjacent neurovascular structures, and its practical application in endoscopic endonasal surgery. METHODS: Twenty-one dried skulls were used to analyze the osseous anatomy of the PPsb. A total of 16 fixed silicone-injected postmortem heads were used to expose the PPsb through both endonasal and transcranial approaches. Dimensions and distances of the PPsb from the foramen lacerum (inferiorly) and top of the posterior clinoid process (PCP; superiorly) were measured. Moreover, anatomical variations and the relationship of the PPsb with the surrounding crucial structures were recorded. Three representative cases were selected to illustrate the clinical applications of the findings. RESULTS: The PPsb presented as a triangular bony prominence, with its base medially adjacent to the dorsum sellae and its apex pointing posterolaterally toward the petrous apex. The mean width of the PPsb was 3.5 ± 1 mm, and the mean distances from the PPsb to the foramen lacerum and the PCP were 5 ± 1 and 11 ± 2.5 mm, respectively. The PPsb is anterior to the petroclival venous confluence, superomedial to the inferior petrosal sinus, and inferomedial to the superior petrosal sinus; constitutes the inferomedial limit of the cavernous sinus; and delimits the upper limit of the paraclival internal carotid artery (ICA) before the artery enters the cavernous sinus. The PPsb is anterior and medial to and below the sixth cranial nerve, forming the floor of Dorello's canal. During surgery, gentle mobilization of the paraclival ICA reveals the petrosal process, serving as an accurate landmark for the location of the abducens nerve. CONCLUSIONS: This investigation revealed details of the microsurgical anatomy of the PPsb, its anatomical relationships, and its application as a surgical landmark for identifying the abducens nerve. This novel landmark may help in minimizing the risk of abducens nerve injury during transclival approaches, which extend laterally toward the petrous apex and cavernous sinus region.

Microsurgical anatomy of the dorsal clinoidal space: implications for endoscopic endonasal parasellar surgery.

OBJECTIVE: The clinoidal venous space dorsal to the internal carotid artery (ICA) has not been well studied given its inaccessibility due to obstruction by the ICA during transcranial surgery. The evolution of endoscopic endonasal surgery has provided a new perspective into the clinoidal space and a new route for paraclinoidal lesions. Understanding the dorsal clinoidal space (DCS) is vital in planning and performing endoscopic endonasal surgery in the parasellar region. A detailed and precise description of the DCS from the endonasal perspective has not yet been provided. The authors' goal in this study was to delineate the microsurgical anatomy of the DCS from an endoscopic endonasal perspective, emphasizing its surgical implications when treating invasive pituitary adenomas and other parasellar lesions. METHODS: An endoscopic endonasal transsellar approach was performed in 15 silicone-injected postmortem heads. Afterward, the sellar region was dissected through a transcranial approach using magnification ×3 to ×40 microscopy. The osseous, dural, and arterial relationships of the DCS and its architecture were investigated. The DCS's length, width, and depth were measured and its anatomical variations recorded. RESULTS: The DCS was identified in 90% of the specimens, and in most cases, its shape was a narrow rectangular pyramid, with its base oriented toward the sphenoid sinus and its apex toward the posterior clinoid process. It is delimited superiorly by the distal ring, inferiorly by the medial aspect of the proximal dural ring or caroticoclinoid ligament, laterally by the clinoidal ICA, and medially by the superior continuation of the medial wall of the cavernous sinus. The width, height, and length of the DCS were 4 ± 1, 4.5 ± 1.5, and 7 ± 2 mm, respectively. A fenestrated caroticoclinoid ligament is a potential route for tumor invasion from the cavernous sinus into the DCS. CONCLUSIONS: This report provides important anatomical descriptions of the DCS from endoscopic endonasal and transcranial perspectives that may facilitate the space's safe exposure for the removal of invasive adenomas, increasing total resection rates and minimizing the risk of injury to neurovascular structures.

Microvascular anatomy of the medial temporal region.

OBJECTIVE: The authors investigated the microvascular anatomy of the hippocampus and its implications for medial temporal tumor surgery. They aimed to reveal the anatomical variability of the arterial supply and venous drainage of the hippocampus, emphasizing its clinical implications for the removal of associated tumors. METHODS: Forty-seven silicon-injected cerebral hemispheres were examined using microscopy. The origin, course, irrigation territory, spatial relationships, and anastomosis of the hippocampal arteries and veins were investigated. Illustrative cases of hippocampectomy for medial temporal tumor surgery are also provided. RESULTS: The hippocampal arteries can be divided into 3 segments, the anterior (AHA), middle (MHA), and posterior (PHA) hippocampal artery complexes, which correspond to irrigation of the hippocampal head, body, and tail, respectively. The uncal hippocampal and anterior hippocampal-parahippocampal arteries contribute to the AHA complex, the posterior hippocampal-parahippocampal arteries serve as the MHA complex, and the PHA and splenial artery compose the PHA complex. Rich anastomoses between hippocampal arteries were observed, and in 11 (23%) hemispheres, anastomoses between each segment formed a complete vascular arcade at the hippocampal sulcus. Three veins were involved in hippocampal drainage-the anterior hippocampal, anterior longitudinal hippocampal, and posterior longitudinal hippocampal veins-which drain the hippocampal head, body, and tail, respectively, into the basal and internal cerebral veins. CONCLUSIONS: An understanding of the vascular variability and network of the hippocampus is essential for medial temporal tumor surgery via anterior temporal lobectomy with amygdalohippocampectomy and transsylvian selective amygdalohippocampectomy. Stereotactic procedures in this region should also consider the anatomy of the vascular arcade at the hippocampal sulcus.

TOP2B Enzymatic Activity on Promoters and Introns Modulates Multiple Oncogenes in Human Gliomas.

PURPOSE: The epigenetic mechanisms involved in transcriptional regulation leading to malignant phenotype in gliomas remains poorly understood. Topoisomerase IIB (TOP2B), an enzyme that decoils and releases torsional forces in DNA, is overexpressed in a subset of gliomas. Therefore, we investigated its role in epigenetic regulation in these tumors. EXPERIMENTAL DESIGN: To investigate the role of TOP2B in epigenetic regulation in gliomas, we performed paired chromatin immunoprecipitation sequencing for TOP2B and RNA-sequencing analysis of glioma cell lines with and without TOP2B inhibition and in human glioma specimens. These experiments were complemented with assay for transposase-accessible chromatin using sequencing, gene silencing, and mouse xenograft experiments to investigate the function of TOP2B and its role in glioma phenotypes. RESULTS: We discovered that TOP2B modulates transcription of multiple oncogenes in human gliomas. TOP2B regulated transcription only at sites where it was enzymatically active, but not at all native binding sites. In particular, TOP2B activity localized in enhancers, promoters, and introns of PDGFRA and MYC, facilitating their expression. TOP2B levels and genomic localization was associated with PDGFRA and MYC expression across glioma specimens, which was not seen in nontumoral human brain tissue. In vivo, TOP2B knockdown of human glioma intracranial implants prolonged survival and downregulated PDGFRA. CONCLUSIONS: Our results indicate that TOP2B activity exerts a pleiotropic role in transcriptional regulation of oncogenes in a subset of gliomas promoting a proliferative phenotype.

Microsurgical anatomy of the lateral posterior choroidal artery: implications for intraventricular surgery involving the choroid plexus.

OBJECTIVE: The lateral posterior choroidal artery (LPChA) should be a major surgical consideration in the microsurgical management of lateral ventricular tumors. Here the authors aim to delineate the microsurgical anatomy of the LPChA by using anatomical microdissections. They describe the trajectory, segments, and variations of the LPChA and discuss the surgical implications when approaching the choroid plexus using different routes. METHODS: Twelve colored silicone-injected, lightly fixed, postmortem human head specimens were prepared for dissection. The origin, diameter, trunk, course, segment, length, spatial relationships, and anastomosis of the LPChA were investigated. The surgical landmarks of 4 different approaches to the LPChA were also examined thoroughly. RESULTS: The LPChA was present in 23 hemispheres (96%), and in 14 (61%) it originated from the posterior segment of the P2 (i.e., P2P); most commonly (61%) the LPChA had 2 trunks, and in 17 hemispheres (74%) it had a C-shaped trajectory. According to its course, the authors divided the LPChA into 3 segments: 1) cisternal, from PCA to choroidal fissure (length 10.6 ± 2.5 mm); 2) forniceal, starting at the choroidal fissure, 8.2 ± 5.7 mm posterior to the inferior choroidal point, and terminating at the posterior level of the choroidal fissure (length 28.7 ± 6.8 mm); and 3) pulvinar, starting at the posterior choroidal fissure and terminating in the pulvinar (length 5.9 ± 2.2 mm). The LPChA was divided into 3 patterns according to its entrance into the choroidal fissure: A (anterior) 78%; B (posterior) 13%; and C (mixed) 9%. The transsylvian trans-limen insulae approach provided the best exposure for cisternal and proximal forniceal segments; the lateral transtemporal approach facilitated a more direct approach to the forniceal segment, including cases with posterior entrance; the transparietal transcortical and contralateral posterior interhemispheric transfalcine transprecuneus approaches provided direct access to the pulvinar segment of the LPChA and to the posterior forniceal segment, including cases with posterior choroidal entrance. CONCLUSIONS: The LPChA typically runs in the medial border of the choroid plexus, which may facilitate its recognition during surgery. The distance between the AChA at the inferior choroidal point and the LPChA is a valuable reference during surgery, but there are cases of posterior choroidal entrance. Most frequently, there are 2 or more LPChA trunks, which makes possible the sacrifice of one trunk feeding the tumor while preserving the other that provides supply to relevant structures. The intraventricular approaches can be selected based on the tumor location and the LPChA anatomy.