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The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal was to reveal individual variability and lateralization of FAT and its structure-function correlations in language processing. The study utilized diffusion MRI data from 1065 subjects obtained from the Human Connectome Project. Automated tractography using DSI Studio software was employed to map white matter bundles, and the results were examined to study the population variation of the FAT. Additionally, anatomical dissections were performed to validate the fiber tracking results. The tract-to-region connectome, based on Human Connectome Project-MMP parcellations, was utilized to provide population probability of the tract-to-region connections. Our results showed that the left anterior FAT exhibited the most substantial individual differences, particularly in the superior and middle frontal gyrus, with greater variability in the superior than the inferior region. Furthermore, we found left lateralization in FAT, with a greater difference in coverage in the inferior and posterior portions. Additionally, our analysis revealed a significant positive correlation between the left FAT inferior coverage area and the performance on the oral reading recognition (p = .016) and picture vocabulary (p = .0026) tests. In comparison, fractional anisotropy of the right FAT exhibited marginal significance in its correlation (p = .056) with Picture Vocabulary Test. Our findings, combined with the connectivity patterns of the FAT, allowed us to segment its structure into anterior and posterior segments. We found significant variability in FAT coverage among individuals, with left lateralization observed in both macroscopic shape measures and microscopic diffusion metrics. Our findings also suggested a potential link between the size of the left FAT's inferior coverage area and language function tests. These results enhance our understanding of the FAT's role in brain connectivity and its potential implications for language and executive functions.
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Conectoma , Substância Branca , Humanos , Adulto Jovem , Imagem de Tensor de Difusão , Encéfalo/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idioma , Vias Neurais/diagnóstico por imagemRESUMO
OBJECTIVE: The mainstay of treatment for skull base chordoma (SBC) is maximal safe resection followed by radiotherapy. However, even after gross-total resection (GTR), the recurrence rate is high due to microscopic disease in the resection margins. Therefore, supramarginal resection (SMR) could be beneficial, as has been shown for sacral chordoma. The paradigm of postoperative radiation therapy for every patient has also begun to change, as molecular profiling has shown variability in the risk of recurrence. The aim of this study was to present the concept of SMR applied to SBC, along with an individualized decision for postoperative radiation therapy. METHODS: This is a retrospective analysis of all SBCs operated on by the senior author between 2018 and 2023. SMR was defined as negative histological margins of bone and/or dura mater, along with evidence of bone resection beyond the tumor margins in the craniocaudal and lateral planes on postoperative imaging. Tumors were classified into 3 molecular recurrence risk groups (group A, low risk; group B, intermediate risk; and group C, high risk). Postoperative radiation therapy was indicated in group C tumors, in group B chordomas without SMR, or in cases of patient preference. RESULTS: Twenty-two cases of SBC fulfilled the inclusion criteria. SMR was achieved in 12 (55%) cases, with a mean (range) amount of bone resection beyond the tumor margins of 10 (2-20) mm (+40%) in the craniocaudal axis and 6 (1-15) mm (+31%) in the lateral plane. GTR and near-total resection were each achieved in 5 (23%) cases. Three (19%) tumors were classified as group A, 12 (75%) as group B, and 1 (6%) as group C. Although nonsignificant due to the small sample size, the trends showed that patients in the SMR group had smaller tumor volumes (13.9 vs 19.6 cm3, p = 0.35), fewer previous treatments (33% vs 60% of patients, p = 0.39), and less use of postoperative radiotherapy (25% vs 60%, p = 0.19) compared to patients in the non-SMR group. There were no significant differences in postoperative CSF leak (0% vs 10%, p = 0.45), persistent cranial nerve palsy (8% vs 20%, p = 0.57), and tumor recurrence (8% vs 10%, p = 0.99; mean follow-up 15 months) rates between the SMR and non-SMR groups. CONCLUSIONS: In select cases, SMR of SBC appears to be feasible and safe. Larger cohorts and longer follow-up evaluations are necessary to explore the benefit of SMR and individualized postoperative radiation therapy on progression-free survival.
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Cordoma , Neoplasias da Base do Crânio , Humanos , Cordoma/cirurgia , Cordoma/radioterapia , Cordoma/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Base do Crânio/radioterapia , Neoplasias da Base do Crânio/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodos , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Adulto Jovem , Margens de ExcisãoRESUMO
BACKGROUND: Understanding and teaching the three-dimensional architecture of the brain remains difficult because of the intricate arrangement of grey nuclei within white matter tracts. Although cortical area functions have been well studied, educational and three-dimensional descriptions of the organization of deep nuclei and white matter tracts are still missing. OBJECTIVE: We propose herein a detailed step-by-step dissection of the lateral aspect of a left hemisphere using the Klingler method and provide high-quality stereoscopic views with the aim to help teach medical students or surgeons the three-dimensional anatomy of the brain. METHODS: Three left hemispheres were extracted and prepared. Then, according to the Klingler method, dissections were carried out from the lateral aspect. Photographs were taken at each step and were modified to provide stereoscopic three-dimensional views. RESULTS: Gray and white structures were described: cortex, claustrum, putamen, pallidum, caudate nucleus, amygdala; U-fibers, external and internal capsules, superior longitudinal fasciculus, frontal aslant fasciculus, uncinate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, corticospinal fasciculus, corona radiata, anterior commissure, and optic radiations. CONCLUSION: This educational stereoscopic presentation of an expert dissection of brain white fibers and basal ganglia would be of value for theoretical or hands-on teaching of brain anatomy; labeling and stereoscopy could, moreover, improve the teaching, understanding, and memorizing of brain anatomy. In addition, this could be also used for the creation of a mental map by neurosurgeons for the preoperative planning of brain tumor surgery.
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Cérebro , Substância Branca , Humanos , Encéfalo/anatomia & histologia , Substância Branca/diagnóstico por imagem , Substância Branca/anatomia & histologia , Cérebro/anatomia & histologia , Dissecação/métodos , Fibras NervosasRESUMO
This research studies the dose-plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into "standard PL" and "high PL" (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose-PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted.
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OBJECTIVE: Recurrent cerebrospinal fluid (CSF) rhinorrhea caused by sequential, anatomically separated skull base defects is rarely reported in the literature. Neither management nor etiology has been sufficiently investigated. We present an illustrative case and a systematic review of the literature regarding etiology, diagnostics, and management of this rare phenomenon. METHODS: A systematic literature search looking for articles reporting sequential CSF leaks with multiple skull base defects was performed. Data from included articles were descriptively reported, and the quality of the included studies was assessed with Grading of Recommendations Assessment, Development and Evaluation. RESULTS: A 71-year-old woman with posttraumatic CSF rhinorrhea and left-sided CSF otorrhea due to a left-sided horizontal fracture of the petrous bone presented at our institution. After initial surgical repair and a 10-week symptom-free interval, CSF rhinorrhea recurred. Imaging revealed a preexisting contralateral meningoencephalocele of the lateral sphenoid recess causing recurrent CSF rhinorrhea most likely after initial traumatic laceration. The defect was successfully treated. A literature search identified 366 reports, 6 of which were included in the systematic review with a total of 10 cases. Quality was deemed good in 8 of 10 cases. The most common location for primary and sequential CSF leaks was along the sphenoid bone (4/10 and 5/10 patients, respectively). All publications except one reported the presence of a meningo (encephalo)cele as cause of the sequential CSF leak. CONCLUSIONS: Occurrence of recurrent CSF rhinorrhea due to an anatomically separated sequential skull base lesion remains a rare phenomenon. Reassessment of imaging studies and a structured diagnostic workup to detect sequential CSF leaks independent of the primary lesion should is recommended.
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OBJECTIVE: The anterior transpetrosal approach using a microscope to provide wider access to the petrous apex region has been described for radical resection of lesions of the middle and posterior skull base. The microscopic anterior transpetrosal approach (mATPA) requires a wide craniotomy and meticulous epidural procedures to minimize temporal lobe retraction. Recently, the clinical application of transcranial endoscopic keyhole approaches for minimally invasive surgery has been steadily expanding. In this study, the details of the purely endoscopic subtemporal keyhole ATPA (eATPA) for petrous apex lesions are described and its initial results are reported. METHODS: Between May 2022 and May 2023, the authors performed eATPA in 10 patients with petrous apex lesions, of which 6 were meningiomas, 3 were trigeminal schwannomas, and 1 was epidermoid cyst. The surgical procedure of the purely eATPA is as follows. After a small temporal craniotomy, the endoscopic procedure is started. The anterior rim of the petrous bone and Meckel's cave are exposed via an intradural subtemporal approach. The lesion is removed with additional drilling of Kawase's triangle, cutting the superior petrosal sinus, opening Meckel's cave, and cutting the tentorium. The authors also compared the outcomes of mATPA versus eATPA for consecutive cases of petrous apex lesions. RESULTS: Gross-total resection was achieved in 8 of the 10 patients. The average operative time was 4 hours 13 minutes. There were 3 cases of transient abducens nerve palsy and 1 case of trochlear nerve palsy in the postoperative period. No new-onset motor deficits or CSF leakage was noted in any of these patients. Only 1 patient exhibited postoperative asymptomatic temporal lobe edema. The Karnofsky Performance Scale (KPS) scores remained unchanged or improved for all patients postoperatively. Compared with mATPA, eATPA achieved a similar extent of resection and comparable postoperative KPS scores with a significantly shorter mean operative time, much smaller temporal craniotomy, and thus less mean blood loss during surgery with lower rates of new-onset temporal lobe edema in the postoperative period. CONCLUSIONS: An eATPA allows a direct route to access Meckel's cave and posterior cranial fossa lesions similar to conventional mATPA, with shortening the operative time and reducing the risk of postoperative temporal lobe edema. This eATPA is considered one of the new surgical techniques that can be expected to develop in the future.
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Objective The endoscopic endonasal approach has emerged as an excellent option for the treatment of lesions involving the petroclival fissure (PCF). Here, we investigate the surgical anatomy of the ventral PCF and its application in endoscopic endonasal surgery. Methods Sixteen head specimens were used to investigate the anatomical features of PCF and relevant technical nuances in translacerum, extreme medial, and contralateral transmaxillary (CTM) approaches. Two representative endoscopic endonasal surgeries involving the PCF were selected to illustrate the clinical application. Results From the endoscopic endonasal view, the ventral PCF is presented as a lazy L sign, which is divided into two distinct segments: (1) upper (or petrosphenoidal) segment, which extends vertically from the foramen lacerum inferiorly to the junction of the petrosal process of sphenoid bone and petrous apex superiorly, and (2) lower (or petroclival) segment, which extends inferolaterally from the foramen lacerum to the ventral jugular foramen. Approaching both segments of the ventral PCF first requires full exposure of the foramen lacerum, followed either by exposure of the anterior wall of cavernous sinus and paraclival internal carotid artery for upper segment access, or transection of pterygosphenoidal fissure and Eustachian tube mobilization for lower segment access. Combined with a CTM approach, the lateral extension of the surgical access can be improved for both upper and lower segment PCF approaches. Conclusion This study provides a detailed investigation of the microsurgical anatomy of the ventral part of PCF, relevant surgical approaches, and technical nuances that may facilitate its safe exposure intraoperatively.
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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.
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Thyroid-stimulating hormone-secreting adenomas (TSH-oma) are exceptionally rare.1 The primary treatment is surgical resection with radiation and pharmacotherapy postoperatively if subtotal resection, especially with cavernous sinus invasion.2 We present the case of a 29-year-old man with TSH-oma with cavernous sinus medial wall invasion. This is the first documented case with selective resection of the cavernous sinus medial wall to achieve a complete resection and biochemical remission in TSH-oma through endoscopic endonasal approach. The patient had elevated TSH and thyroid hormones with symptoms of weight loss, palpitations, excess sweating, and decreased endurance. MRI revealed a 1.3 × 2.1 × 1.2 cm contrast-enhancing sellar mass with rightward pituitary gland displacement without evidence of cavernous sinus invasion (Knosp 2). The patient consented to procedure/publication. No institutional review board approval needed per institution. We performed standard resection of the firm sellar tumor portion and noted that there was tumor invasion into the left cavernous sinus medial wall dura. The bony opening was expanded to expose the anterior wall of the cavernous sinus, which was opened to identify the cavernous internal carotid artery and the medial wall attachments. The thickened medial wall was completely resected. We achieved a complete tumor resection, and the patient's TSH and thyroid hormone dropped to a desired threshold.3 Tumor stained for GATA3 and PIT1, characterizing the TSH-oma.4,5 Understanding cavernous sinus vascular and ligamentous anatomy allows for safe separation of invaded medial wall dura from the cavernous internal carotid artery,6 allowing for a more complete tumor resection, improving surgical cure rates, and sparing the patient from future radiation and pharmacotherapy.
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OBJECTIVE: The cavernous sinus (CS) has 4 compartments: superior, inferior, posterior, and lateral. Among these, the lateral compartment is the most common location for residual tumor, given the risk of neurovascular injury. The authors' study aimed to delineate the anatomical landmarks in this area and illustrate the technical nuances of the lateral transcavernous approach. METHODS: Twenty-two colored silicone-injected specimens were dissected via an endoscopic endonasal approach to the lateral compartment of the CS. The anatomical landmarks and the internal carotid artery (ICA) mobilization technique were investigated. Two illustrative cases are provided. RESULTS: The lateral compartment of the CS is bounded by the carotid-oculomotor membrane (COM) and optic strut as the roof and the petrolingual ligament and lingual process as the floor. It is divided into 2 asymmetrical subcompartments: the upper, larger subcompartment, located superior to the abducens nerve, accommodates the lateral parasellar ligament (LPL), inferolateral trunk (ILT), and branches of the tentorial artery; and the lower, smaller subcompartment, inferior to the abducens nerve, accommodates only the sympathetic nerve branches as they join the abducens nerve. The LPL is a well-defined ligamentous band and was identified in 38 (86%) hemispheres with 2 distinct configurations: 1) robust LPL (59%), with highly compacted ligamentous bands tightly adherent to the ICA; and 2) dispersed LPL (27%), with less compaction and adherence to ICA. The main attachment of the LPL to the cavernous ICA was most commonly observed at the horizontal ICA segment (55%), followed by the anterior (18%) and posterior (14%) genua. The ILT, as the main vessel in the lateral compartment, was identified in 41 (93%) hemispheres and originated from the horizontal ICA segment (80%) or the anterior genu (14%), from either the lateral (52%) or inferior (41%) aspect of the cross-section of the ICA. In 64% of hemispheres, the LPL wrapped the ILT, abducens nerve, and sympathetic nerve to form a broad and firm neurovascular-ligamental complex. Transection of the LPL, ILT, and COM enables medial ICA mobilization and enhances access to the lateral compartment of the CS, potentially increasing the exposure width by 6 ± 1 mm. CONCLUSIONS: This study provides valuable insights into the anatomical intricacies of the lateral compartment of the CS and underscores the potential benefits of the endoscopic endonasal lateral transcavernous approach. Further clinical applications are essential for validating these findings and optimizing surgical outcomes.
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Background: Post-operative fluid restriction after transsphenoidal surgery (TSS) for pituitary tumors may effectively prevent delayed hyponatremia, the most common cause of readmission. However, implementation of individualized fluid restriction interventions after discharge is often complex and poses challenges for provider and patient. The purpose of this study was to understand the factors necessary for successful implementation of fluid restriction and discharge care protocols following TSS. Methods: Semi-structured interviews with fifteen patients and four caregivers on fluid discharge protocols were conducted following TSS. Patients and caregivers who had surgery before and after the implementation of updated discharge protocols were interviewed. Data were analyzed inductively using a procedure informed by rapid and thematic analysis. Results: Most patients and caregivers perceived fluid restriction protocols as acceptable and feasible when indicated. Facilitators to the protocols included clear communication about the purpose of and strategies for fluid restriction, access to the care team, and involvement of patients' caregivers in care discussions. Barriers included patient confusion about differences in the care plan between teams, physical discomfort of fluid restriction, increased burden of tracking fluids during recovery, and lack of clarity surrounding desmopressin prescriptions. Conclusion: Outpatient fluid restriction protocols are a feasible intervention following pituitary surgery but requires frequent patient communication and education. This evaluation highlights the importance of patient engagement and feedback to effectively develop and implement complex clinical interventions.
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OBJECTIVE: Tumors located in the retrochiasmatic region with extension to the third ventricle might be difficult to access when the pituitary-chiasmatic corridor is narrow. Similarly, tumor extension into the interpeduncular and retrosellar space poses a major surgical challenge. Pituitary transposition techniques have been developed to gain additional access. However, when preoperative pituitary function is already impaired or the risk of postoperative panhypopituitarism (PH) is considered to be particularly high, removal of the pituitary gland (PG) might be the preferred option to increase the working corridor. The aim of this study was to describe the relevant surgical anatomy, operative steps, and clinical experience with the endoscopic endonasal pituitary sacrifice (EEPS) and transsellar approach. METHODS: This study comprised anatomical dissections to highlight the relevant surgical steps and a retrospective case series reporting clinical characteristics, indications, and outcomes of patients who underwent EEPS. The surgical technique is as follows: both lateral opticocarotid recesses are exposed laterally, the limbus sphenoidale superiorly, and the sellar floor inferiorly. After opening the dura, the PG is detached circumferentially and mobilized off the medial walls of the cavernous sinuses. The descending branches of the superior hypophyseal artery are coagulated, and the stalk is transected. After removal of the PG, drilling of the dorsum sellae and bilateral posterior clinoidectomies are performed to gain access to the hypothalamic region, interpeduncular, and prepontine cisterns. RESULTS: From 2018 to 2023, 11 patients underwent EEPS. The cohort comprised mostly tuberoinfundibular craniopharyngiomas (n = 8, 73%). Seven (64%) patients had partial or complete anterior PG dysfunction preoperatively, while 4 (36%) had preoperative diabetes insipidus. Because of the specific tumor configuration, the chance of preserving endocrine function was estimated to be very low in patients with intact function. The main reasons for pituitary sacrifice were impaired visibility and surgical accessibility to the retrochiasmatic and retrosellar spaces. Gross-total tumor resection was achieved in 10 (91%) patients and near-total resection in 1 (9%) patient. Two (18%) patients experienced a postoperative CSF leak, requiring surgical revision. CONCLUSIONS: When preoperative pituitary function is already impaired or the risk for postoperative PH is considered particularly high, the EEPS and transsellar approach appears to be a feasible surgical option to improve visibility and accessibility to the retrochiasmatic hypothalamic and retrosellar spaces, thus increasing tumor resectability.
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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.
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Background Sinonasal debridement is typically performed in the weeks following endonasal skull base surgery (ESBS). In the pediatric population, this second-look procedure may require general anesthesia; however, there is currently little evidence assessing the benefit of this practice. Methods This was a multicenter retrospective study of pediatric patients (age <18 years) undergoing a planned second-look debridement under general anesthesia following ESBS. Intraoperative findings, interventions performed, and perioperative complications were reviewed. Multivariate regression analysis was performed to identify associations between intraoperative findings and clinical factors. Results We reviewed 69 cases of second-look debridements (age mean 8.6 ± 4.2 years, range: 2-18 years), occurring a mean of 18.3 ± 10.3 days following ESBS. All abnormal findings were noted in patients age ≤12 years. Synechiae were noted in 8.7% of cases, bacterial rhinosinusitis in 2.9%, and failed reconstruction with cerebrospinal fluid leak in 4.5% (two cases of flap malposition and one case of flap necrosis). All failed reconstructions were noted following expanded endonasal cases for craniopharyngioma, and in each case, a revision reconstruction was performed during the second-look surgery. Synechiae were not significantly associated with younger age, revision cases, or cases with reconstructive flaps. There were no perioperative complications. Conclusion Second-look debridement under general anesthesia may be useful in the identification and intervention of sinonasal pathology following endoscopic skull base surgery, particularly in children ≤12 years old or those with pedicled flap reconstructions. Larger controlled studies are warranted to validate this practice and refine indications and timing of this second procedure.
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BACKGROUND AND OBJECTIVE: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated. METHODS: Patients with treated CD from 2011 to 2023 were included. The perioperative and long-term characteristics of CD patients with and without recurrence were assessed using univariable and multivariable analyses. RESULTS: Of 383 patients with CD from 26 surgeons achieving postoperative remission, 288 (75.2%) maintained remission at last follow-up while 95 (24.8%) showed recurrence (median time to recurrence 9.99 ± 1.34 years). Patients with recurrence required longer postoperative hospital stays (5 ± 3 vs 4 ± 2 days, P = .002), had larger average tumor volumes (1.76 ± 2.53 cm3 vs 0.49 ± 1.17 cm3, P = .0001), and more often previously failed prior treatment (31.1% vs 14.9%, P = .001) mostly being prior surgery. Multivariable hazard prediction models for tumor recurrence found younger age (odds ratio [OR] = 0.95, P = .002) and Knosp grade of 0 (OR = 0.09, reference Knosp grade 4, P = .03) to be protective against recurrence. Comparison of Knosp grade 0 to 2 vs 3 to 4 showed that lower grades had reduced risk of recurrence (OR = 0.27, P = .04). Other factors such as length of stay, surgeon experience, prior tumor treatment, and Knosp grades 1, 2, or 3 failed to reach levels of statistical significance in multivariable analysis. CONCLUSION: This multicenter study centers suggests that the strongest predictors of recurrence include tumor size/invasion and age. This insight can help with patient counseling and prognostication. Long-term follow-up is necessary for patients, and early treatment of small tumors may improve outcomes.
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BACKGROUND: With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence. METHODS: A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses. RESULTS: A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation ±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p < 0.001), overall stage (p < 0.001), and modified Kadish scores (p < 0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio = 5.62; p = 0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence. CONCLUSIONS: Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning.
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BACKGROUND AND OBJECTIVES: Despite growing interest in how patient frailty affects outcomes (eg, in neuro-oncology), its role after transsphenoidal surgery for Cushing disease (CD) remains unclear. We evaluated the effect of frailty on CD outcomes using the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) data set from a collaboration of US academic pituitary centers. METHODS: Data on consecutive surgically treated patients with CD (2011-2023) were compiled using the 11-factor modified frailty index. Patients were classified as fit (score, 0-1), managing well (score, 2-3), and mildly frail (score, 4-5). Univariable and multivariable analyses were conducted to examine outcomes. RESULTS: Data were analyzed for 318 patients (193 fit, 113 managing well, 12 mildly frail). Compared with fit and managing well patients, mildly frail patients were older (mean ± SD 39.7 ± 14.2 and 48.9 ± 12.2 vs 49.4 ± 8.9 years, P < .001) but did not different by sex, race, and other factors. They had significantly longer hospitalizations (3.7 ± 2.0 and 4.5 ± 3.5 vs 5.3 ± 3.5 days, P = .02), even after multivariable analysis (ß = 1.01, P = .007) adjusted for known predictors of prolonged hospitalization (age, Knosp grade, surgeon experience, American Society of Anesthesiologists grade, complications, frailty). Patients with mild frailty were more commonly discharged to skilled nursing facilities (0.5% [1/192] and 4.5% [5/112] vs 25% [3/12], P < .001). Most patients underwent gross total resection (84.4% [163/193] and 79.6% [90/113] vs 83% [10/12]). No difference in overall complications was observed; however, venous thromboembolism was more common in mildly frail (8%, 1/12) than in fit (0.5%, 1/193) and managing well (2.7%, 3/113) patients (P = .04). No difference was found in 90-day readmission rates. CONCLUSION: These results demonstrate that mild frailty predicts CD surgical outcomes and may inform preoperative risk stratification. Frailty-influenced outcomes other than age and tumor characteristics may be useful for prognostication. Future studies can help identify strategies to reduce disease burden for frail patients with hypercortisolemia.
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BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.