Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis.

BACKGROUND: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches. METHODS: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model. RESULTS: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS. CONCLUSIONS: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

Metabolic and inflammatory parameters in relation to baseline characterization and treatment outcome in patients with prolactinoma: insights from a retrospective cohort study at a single tertiary center.

Background: Prolactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine, metabolic, and inflammatory profiles in PRL patients, aiming to identify potential prognostic markers. Methods: The study comprised data from 59 PRL patients gathered in a registry at the University Hospital of Zurich. Diagnostic criteria included MRI findings and elevated serum prolactin levels. We assessed baseline and follow-up clinical demographics, metabolic markers, serum inflammation-based scores, and endocrine parameters. Treatment outcomes were evaluated based on prolactin normalization, tumor shrinkage, and cabergoline dosage. Results: The PRL cohort exhibited a higher prevalence of overweight/obesity, prediabetes/diabetes mellitus, and dyslipidemia compared to the general population. Significant correlations were found between PRL characteristics and BMI, HbA1c, and fT4 levels. Follow-up data indicated decreases in tumor size, tumor volume, prolactin levels, and LDL-cholesterol, alongside increases in fT4 and sex hormones levels. No significant associations were observed between baseline parameters and tumor shrinkage at follow-up. A positive association was noted between PRL size/volume and the time to achieve prolactin normalization, and a negative association with baseline fT4 levels. Conclusion: This study underscores the metabolic significance of PRL, with notable correlations between PRL parameters and metabolic indices. However, inflammatory markers were not significantly correlated with patient stratification or outcome prediction. These findings highlight the necessity for standardized follow-up protocols and further research into the metabolic pathogenesis in PRL patients.

Challenges and Considerations of Preclinical Development for iPSC-Based Myogenic Cell Therapy.

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells can be manufactured to reverse the progression of muscle diseases or facilitate tissue regeneration. Despite this exciting advancement, much of the development of iPSC-based therapies for muscle diseases and tissue regeneration is limited to academic settings, with no successful clinical translation reported. The unknown differentiation process in vivo, potential tumorigenicity, and epigenetic abnormality of transplanted cells are preventing their clinical application. In this review, we give an overview on preclinical development of iPSC-derived myogenic cell transplantation therapies including processes related to iPSC-derived myogenic cells such as differentiation, scaling-up, delivery, and cGMP compliance. And we discuss the potential challenges of each step of clinical translation. Additionally, preclinical model systems for testing myogenic cells intended for clinical applications are described.

Virtual Reality Planning of Microvascular Decompression in Trigeminal Neuralgia: Technique and Clinical Outcome.

BACKGROUND: A neurovascular conflict (NVC) is considered the cause of trigeminal neuralgia (TN) in 75% of cases, and if so, a microvascular decompression (MVD) can lead to significant pain relief. A reliable preoperative detection of NVC is essential for clinical decision-making and surgical planning, making detailed neuroradiologic imaging an important component. We present our experiences and clinical outcomes with preoperative planning of the MVD procedure in a virtual reality (VR) environment, based on magnetic resonance imaging (MRI) including magnetic resonance angiography (MRA) and magnetic resonance venography (MRV) sequences. METHODS: We analyzed the data of 30 consecutive MVDs in patients treated for TN, in a retrospective single-surgeon (R.A. Kockro) study. Out of the 30 cases, 26 were included. Preoperatively, MRA/MRV and MRI series were fused and three dimensionally reconstructed in a VR environment. All critical structures such as the trigeminal nerve as well as the arteries and veins of the cerebellopontine angle, the brainstem, the neighboring cranial nerves, and the transverse and sigmoid sinus were segmented. The NVC was visualized and a simulation of a retrosigmoid approach, with varying trajectories, to the NVC was performed. The intraoperative findings were then compared with the data of the simulation. The clinical outcome was assessed by a detailed review of medical reports, and follow-up-interviews were conducted in all available patients (20/26). RESULTS: The VR planning was well integrated into the clinical workflow, and imaging processing time was 30 to 40 minutes. There was a sole arterial conflict in 13 patients, a venous conflict in 4 patients, and a combined arteriovenous conflict in 9 patients. The preoperative simulations provided a precise visualization of the anatomical relationships of the offending vessels and the trigeminal nerves as well as the surrounding structures. For each case, the approach along the most suitable surgical corridor was simulated and the exact steps of the decompression were planned. The NVC and the anatomy of the cerebellopontine angle as seen intraoperatively matched with the preoperative simulations in all cases and the MVC could be performed as planned. At follow-up, 92.3% (24/26) of patients were pain free and all the patients who completed the questionnaire would undergo the surgery again (20/20). The surgical complication rate was zero. CONCLUSION: Current imaging technology allows detailed preoperative visualization of the pathoanatomical spatial relationships in cases of TN. 3D interactive VR technology allows establishing a clear dissection and decompression strategy, resulting in safe vascular microsurgery and excellent clinical results.

Whole Spine Segmentation Using Object Detection and Semantic Segmentation.

OBJECTIVE: Virtual and augmented reality have enjoyed increased attention in spine surgery. Preoperative planning, pedicle screw placement, and surgical training are among the most studied use cases. Identifying osseous structures is a key aspect of navigating a 3-dimensional virtual reconstruction. To automate the otherwise time-consuming process of labeling vertebrae on each slice individually, we propose a fully automated pipeline that automates segmentation on computed tomography (CT) and which can form the basis for further virtual or augmented reality application and radiomic analysis. METHODS: Based on a large public dataset of annotated vertebral CT scans, we first trained a YOLOv8m (You-Only-Look-Once algorithm, Version 8 and size medium) to detect each vertebra individually. On the then cropped images, a 2D-U-Net was developed and externally validated on 2 different public datasets. RESULTS: Two hundred fourteen CT scans (cervical, thoracic, or lumbar spine) were used for model training, and 40 scans were used for external validation. Vertebra recognition achieved a mAP50 (mean average precision with Jaccard threshold of 0.5) of over 0.84, and the segmentation algorithm attained a mean Dice score of 0.75 ± 0.14 at internal, 0.77 ± 0.12 and 0.82 ± 0.14 at external validation, respectively. CONCLUSION: We propose a 2-stage approach consisting of single vertebra labeling by an object detection algorithm followed by semantic segmentation. In our externally validated pilot study, we demonstrate robust performance for our object detection network in identifying individual vertebrae, as well as for our segmentation model in precisely delineating the bony structures.

From molecular signatures to radiomics: tailoring neurooncological strategies through forecasting of glioma growth.

OBJECTIVE: Contemporary oncological paradigms for adjuvant treatment of low- and intermediate-grade gliomas are often guided by a limited array of parameters, overlooking the dynamic nature of the disease. The authors' aim was to develop a comprehensive multivariate glioma growth model based on multicentric data, to facilitate more individualized therapeutic strategies. METHODS: Random slope models with subject-specific random intercepts were fitted to a retrospective cohort of grade II and III gliomas from the database at Kepler University Hospital (n = 191) to predict future mean tumor diameters. Deep learning-based radiomics was used together with a comprehensive clinical dataset and evaluated on an external prospectively collected validation cohort from University Hospital Zurich (n = 9). Prediction quality was assessed via mean squared prediction error. RESULTS: A mean squared prediction error of 0.58 cm for the external validation cohort was achieved, indicating very good prognostic value. The mean ± SD time to adjuvant therapy was 28.7 ± 43.3 months and 16.1 ± 14.6 months for the training and validation cohort, respectively, with a mean of 6.2 ± 5 and 3.6 ± 0.7, respectively, for number of observations. The observed mean tumor diameter per year was 0.38 cm (95% CI 0.25-0.51) for the training cohort, and 1.02 cm (95% CI 0.78-2.82) for the validation cohort. Glioma of the superior frontal gyrus showed a higher rate of tumor growth than insular glioma. Oligodendroglioma showed less pronounced growth, anaplastic astrocytoma-unlike anaplastic oligodendroglioma-was associated with faster tumor growth. Unlike the impact of extent of resection, isocitrate dehydrogenase (IDH) had negligible influence on tumor growth. Inclusion of radiomics variables significantly enhanced the prediction performance of the random slope model used. CONCLUSIONS: The authors developed an advanced statistical model to predict tumor volumes both pre- and postoperatively, using comprehensive data prior to the initiation of adjuvant therapy. Using radiomics enhanced the precision of the prediction models. Whereas tumor extent of resection and topology emerged as influential factors in tumor growth, the IDH status did not. This study emphasizes the imperative of advanced computational methods in refining personalized low-grade glioma treatment, advocating a move beyond traditional paradigms.

Intraoperative ultrasonography in microsurgical resection of vestibular schwannomas via retrosigmoid approach: surgical technique and proof-of-concept illustrative case series.

PURPOSE: Intraoperative ultrasonography (ioUS) is an established tool for the real-time intraoperative orientation and resection control in intra-axial oncological neurosurgery. Conversely, reports about its implementation in the resection of vestibular schwannomas (VS) are scarce. The aim of this study is to describe the role of ioUS in microsurgical resection of VS. METHODS: ioUS (Craniotomy Transducer N13C5, BK5000, B Freq 8 MHz, BK Medical, Burlington, MA, USA) is integrated into the surgical workflow according to a 4-step protocol (transdural preresection, intradural debulking control, intradural resection control, transdural postclosure). Illustrative cases of patients undergoing VS resection through a retrosigmoid approach with the use of ioUS are showed to illustrate advantages and pitfalls of the technique. RESULTS: ioUS allows clear transdural identification of the VS and its relationships with surgically relevant structures of the posterior fossa and of the cerebellopontine cistern prior to dural opening. Intradural ioUS reliably estimates the extent of tumor debulking, thereby helping in the choice of the right moment to start peripheral preparation and in the optimization of the extent of resection in those cases where subtotal resection is the ultimate goal of surgery. Transdural postclosure ioUS accurately depicts surgical situs. CONCLUSION: ioUS is a cost-effective, safe, and easy-to-use intraoperative adjunctive tool that can provide a significant assistance during VS surgery. It can potentially improve patient safety and reduce complication rates. Its efficacy on clinical outcomes, operative time, and complication rate should be validated in further studies.

Microsurgical management of midbrain gliomas: surgical results and long-term outcome in a large, single-surgeon, consecutive series.

OBJECTIVE: The authors report on a large, consecutive, single-surgeon series of patients undergoing microsurgical removal of midbrain gliomas. Emphasis is put on surgical indications, technique, and results as well as long-term oncological follow-up. METHODS: A retrospective analysis was performed of prospectively collected data from a consecutive series of patients undergoing microneurosurgery for midbrain gliomas from March 2006 through June 2022 at the authors' institution. According to the growth pattern and location of the lesion in the midbrain (tegmentum, central mesencephalic structures, and tectum), one of the following approaches was chosen: transsylvian (TS), extreme anterior interhemispheric transcallosal (eAIT), posterior interhemispheric transtentorial subsplenial (PITS), paramedian supracerebellar transtentorial (PST), perimedian supracerebellar (PeS), perimedian contralateral supracerebellar (PeCS), and transuvulotonsillar fissure (TUTF). Clinical and radiological data were gathered according to a standard protocol and reported according to common descriptive statistics. The main outcomes were rate of gross-total resection; extent of resection; occurrence of any complications; variation in Karnofsky Performance Status score at discharge, 3 months, and last follow-up; progression-free survival (PFS); and overall survival (OS). RESULTS: Fifty-four patients (28 of them pediatric) met the inclusion criteria (6 with high-grade and 48 with low-grade gliomas [LGGs]). Twenty-two tumors were in the tegmentum, 7 in the central mesencephalic structures, and 25 in the tectum. In no instance did the glioma originate in the cerebral peduncle. TS was performed in 2 patients, eAIT in 6, PITS in 23, PST in 16, PeS in 4, PeCS in 1, and TUTF in 2 patients. Gross-total resection was achieved in 39 patients (72%). The average extent of resection was 98.0% (median 100%, range 82%-100%). There were no deaths due to surgery. Nine patients experienced transient and 2 patients experienced permanent new neurological deficits. At a mean follow-up of 72 months (median 62, range 3-193 months), 49 of the 54 patients were still alive. All patients with LGGs (48/54) were alive with no decrease in their KPS score, whereas 42 showed improvement compared with their preoperative status. CONCLUSIONS: Microneurosurgical removal of midbrain gliomas is feasible with good surgical results and long-term clinical outcomes, particularly in patients with LGGs. As such, microneurosurgery should be considered as the first therapeutic option. Adequate microsurgical technique and anesthesiological management, along with an accurate preoperative understanding of the tumor's exact topographic origin and growth pattern, is crucial for a good surgical outcome.

Automated volumetric assessment of pituitary adenoma.

PURPOSE: Assessment of pituitary adenoma (PA) volume and extent of resection (EOR) through manual segmentation is time-consuming and likely suffers from poor interrater agreement, especially postoperatively. Automated tumor segmentation and volumetry by use of deep learning techniques may provide more objective and quick volumetry. METHODS: We developed an automated volumetry pipeline for pituitary adenoma. Preoperative and three-month postoperative T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) with manual segmentations were used for model training. After adequate preprocessing, an ensemble of convolutional neural networks (CNNs) was trained and validated for preoperative and postoperative automated segmentation of tumor tissue. Generalization was evaluated on a separate holdout set. RESULTS: In total, 193 image sets were used for training and 20 were held out for validation. At validation using the holdout set, our models (preoperative / postoperative) demonstrated a median Dice score of 0.71 (0.27) / 0 (0), a mean Jaccard score of 0.53 ± 0.21/0.030 ± 0.085 and a mean 95th percentile Hausdorff distance of 3.89 ± 1.96./12.199 ± 6.684. Pearson's correlation coefficient for volume correlation was 0.85 / 0.22 and -0.14 for extent of resection. Gross total resection was detected with a sensitivity of 66.67% and specificity of 36.36%. CONCLUSIONS: Our volumetry pipeline demonstrated its ability to accurately segment pituitary adenomas. This is highly valuable for lesion detection and evaluation of progression of pituitary incidentalomas. Postoperatively, however, objective and precise detection of residual tumor remains less successful. Larger datasets, more diverse data, and more elaborate modeling could potentially improve performance.

Mixed Reality for Cranial Neurosurgical Planning: A Single-Center Applicability Study With the First 107 Subsequent Holograms.

BACKGROUND AND OBJECTIVES: Mixed reality (MxR) benefits neurosurgery by improving anatomic visualization, surgical planning and training. We aim to validate the usability of a dedicated certified system for this purpose. METHODS: All cases prepared with MxR in our center in 2022 were prospectively collected. Holographic rendering was achieved using an incorporated fully automatic algorithm in the MxR application, combined with contrast-based semiautomatic rendering and/or manual segmentation where necessary. Hologram segmentation times were documented. Visualization during surgical preparation (defined as the interval between finalized anesthesiological induction and sterile draping) was performed using MxR glasses and direct streaming to a side screen. Surgical preparation times were compared with a matched historical cohort of 2021. Modifications of the surgical approach after 3-dimensional (3D) visualization were noted. Usability was assessed by evaluating 7 neurosurgeons with more than 3 months of experience with the system using a Usefulness, Satisfaction and Ease of use (USE) questionnaire. RESULTS: One hundred-seven neurosurgical cases prepared with a 3D hologram were collected. Surgical indications were oncologic (63/107, 59%), cerebrovascular (27/107, 25%), and carotid endarterectomy (17/107, 16%). Mean hologram segmentation time was 39.4 ± 20.4 minutes. Average surgical preparation time was 48.0 ± 17.3 minutes for MxR cases vs 52 ± 17 minutes in the matched 2021 cohort without MxR (mean difference 4, 95% CI 1.7527-9.7527). Based on the 3D hologram, the surgical approach was modified in 3 cases. Good usability was found by 57% of the users. CONCLUSION: The perioperative use of 3D holograms improved direct anatomic visualization while not significantly increasing intraoperative surgical preparation time. Usability of the system was adequate. Further technological development is necessary to improve the automatic algorithms and reduce the preparation time by circumventing manual and semiautomatic segmentation. Future studies should focus on quantifying the potential benefits in teaching, training, and the impact on surgical and functional outcomes.

Safety of microneurosurgical interventions for superficial and deep-seated brain metastases: single-center cohort study of 637 consecutive cases.

PURPOSE: Microneurosurgical techniques have greatly improved over the past years due to the introduction of new technology and surgical concepts. To reevaluate the role of micro-neurosurgery in brain metastases (BM) resection in the era of new systemic and local treatment options, its safety profile needs to be reassessed. The aim of this study was to analyze the rate of adverse events (AEs) according to a systematic, comprehensive and reliably reproducible grading system after microneurosurgical BM resection in a large and modern microneurosurgical series with special emphasis on anatomical location. METHODS: Prospectively collected cases of BM resection between 2013 and 2022 were retrospectively analyzed. Number of AEs, defined as any deviations from the expected postoperative course according to Clavien-Dindo-Grade (CDG) were evaluated. Patient, surgical, and lesion characteristics, including exact anatomic tumor locations, were analyzed using uni- and multivariate logistic regression and survival analysis to identify predictive factors for AEs. RESULTS: We identified 664 eligible patients with lung cancer being the most common primary tumor (44%), followed by melanoma (25%) and breast cancer (11%). 29 patients (4%) underwent biopsy only whereas BM were resected in 637 (96%) of cases. The overall rate of AEs was 8% at discharge. However, severe AEs (≥ CDG 3a; requiring surgical intervention under local/general anesthesia or ICU treatment) occurred in only 1.9% (n = 12) of cases with a perioperative mortality of 0.6% (n = 4). Infratentorial tumor location (OR 5.46, 95% 2.31-13.8, p = .001), reoperation (OR 2.31, 95% 1.07-4.81, p = .033) and central region tumor location (OR 3.03, 95% 1.03-8.60) showed to be significant predictors in a multivariate analysis for major AEs (CDG ≥ 2 or new neurological deficits). Neither deep supratentorial nor central region tumors were associated with more major AEs compared to convexity lesions. CONCLUSIONS: Modern microneurosurgical resection can be considered an excellent option in the management of BM in terms of safety, as the overall rate of major AEs are very rare even in eloquent and deep-seated lesions.

Development and external validation of clinical prediction models for pituitary surgery.

Introduction: Gross total resection (GTR), Biochemical Remission (BR) and restitution of a priorly disrupted hypothalamus pituitary axis (new improvement, IMP) are important factors in pituitary adenoma (PA) resection surgery. Prediction of these metrics using simple and preoperatively available data might help improve patient care and contribute to a more personalized medicine. Research question: This study aims to develop machine learning models predicting GTR, BR, and IMP in PA resection surgery, using preoperatively available data. Material and methods: With data from patients undergoing endoscopic transsphenoidal surgery for PAs machine learning models for prediction of GTR, BR and IMP were developed and externally validated. Development was carried out on a registry from Bologna, Italy while external validation was conducted using patient data from Zurich, Switzerland. Results: The model development cohort consisted of 1203 patients. GTR was achieved in 207 (17.2%, 945 (78.6%) missing), BR in 173 (14.4%, 992 (82.5%) missing) and IMP in 208 (17.3%, 167 (13.9%) missing) cases. In the external validation cohort 206 patients were included and GTR was achieved in 121 (58.7%, 32 (15.5%) missing), BR in 46 (22.3%, 145 (70.4%) missing) and IMP in 42 (20.4%, 7 (3.4%) missing) cases. The AUC at external validation amounted to 0.72 (95% CI: 0.63-0.80) for GTR, 0.69 (0.52-0.83) for BR, as well as 0.82 (0.76-0.89) for IMP. Discussion and conclusion: All models showed adequate generalizability, performing similarly in training and external validation, confirming the possible potentials of machine learning in helping to adapt surgical therapy to the individual patient.

Influence of gender and sexual hormones on outcomes after pituitary surgery: a systematic review and meta-analysis.

BACKGROUND: Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA), gender differences regarding outcome of patients who underwent transsphenoidal resection of PA are poorly understood. The aim of this study was to identify gender differences in PA surgery. METHODS: The PubMed/MEDLINE database was searched up to April 2023 to identify eligible articles. Quality appraisal and extraction were performed in duplicate. RESULTS: A total of 40 studies including 4989 patients were included in this systematic review and meta-analysis. Our analysis showed odds ratio of postoperative biochemical remission in males vs. females of 0.83 (95% CI 0.59-1.15, P = 0.26), odds ratio of gross total resection in male vs. female patients of 0.68 (95% CI 0.34-1.39, P = 0.30), odds ratio of postoperative diabetes insipidus in male vs. female patients of 0.40 (95% CI 0.26-0.64, P < 0.0001), and a mean difference of preoperative level of prolactin in male vs. female patients of 11.62 (95% CI - 119.04-142.27, P = 0.86). CONCLUSIONS: There was a significantly higher rate of postoperative DI in female patients after endoscopic or microscopic transsphenoidal PA surgery, and although there was some data in isolated studies suggesting influence of gender on postoperative biochemical remission, rate of GTR, and preoperative prolactin levels, these findings could not be confirmed in this meta-analysis and demonstrated no statistically significant effect. Further research is needed and future studies concerning PA surgery should report their data by gender or sexual hormones and ideally further assess their impact on PA surgery.

Rhinologic outcome of endoscopic transnasal-transsphenoidal pituitary surgery: an institutional series, systematic review, and meta-analysis.

PURPOSE: We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery. METHODS: Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed. RESULTS: The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher's exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0-2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1-3.0), a postoperative synechiae rate of 7.5% (IQR 1.8-19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5-5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting. CONCLUSION: Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care.

Meta-topologies define distinct anatomical classes of brain tumours linked to histology and survival.

The current World Health Organization classification integrates histological and molecular features of brain tumours. The aim of this study was to identify generalizable topological patterns with the potential to add an anatomical dimension to the classification of brain tumours. We applied non-negative matrix factorization as an unsupervised pattern discovery strategy to the fine-grained topographic tumour profiles of 936 patients with neuroepithelial tumours and brain metastases. From the anatomical features alone, this machine learning algorithm enabled the extraction of latent topological tumour patterns, termed meta-topologies. The optimal part-based representation was automatically determined in 10 000 split-half iterations. We further characterized each meta-topology's unique histopathologic profile and survival probability, thus linking important biological and clinical information to the underlying anatomical patterns. In neuroepithelial tumours, six meta-topologies were extracted, each detailing a transpallial pattern with distinct parenchymal and ventricular compositions. We identified one infratentorial, one allopallial, three neopallial (parieto-occipital, frontal, temporal) and one unisegmental meta-topology. Each meta-topology mapped to distinct histopathologic and molecular profiles. The unisegmental meta-topology showed the strongest anatomical-clinical link demonstrating a survival advantage in histologically identical tumours. Brain metastases separated to an infra- and supratentorial meta-topology with anatomical patterns highlighting their affinity to the cortico-subcortical boundary of arterial watershed areas.Using a novel data-driven approach, we identified generalizable topological patterns in both neuroepithelial tumours and brain metastases. Differences in the histopathologic profiles and prognosis of these anatomical tumour classes provide insights into the heterogeneity of tumour biology and might add to personalized clinical decision-making.

Ex vivo and in vivo evaluation of transsphenoidal Liqoseal application to prevent cerebrospinal fluid leakage.

BACKGROUND: Despite improvements in closure techniques by using a vital nasoseptal flap, the use of sealing materials, and improved neurosurgical techniques, cerebrospinal fluid (CSF) leak after transsphenoidal surgery still is a clinically relevant problem. Liqoseal® (Polyganics bv, Groningen, The Netherlands) is a CE-approved bioresorbable sealant patch for use as an adjunct to standard methods of cranial dural closure to prevent CSF leakage. This study aims to evaluate the application of Liqoseal in transsphenoidal surgery ex vivo and in vivo. METHODS: 1. We created an ex vivo setup simulating the sphenoidal anatomy, using a fluid pump and porcine dura positioned on a conus with the anatomical dimensions of the sella to evaluate whether the burst pressure of Liqoseal applied to a bulging surface was above physiological intracranial pressure. Burst pressure was measured with a probe connected to dedicated computer software. Because of the challenging transsphenoidal environment, we tested in 4 groups with varying compression weight and time for the application of Liqoseal. 2. We subsequently describe the application of Liqoseal® in 3 patients during transsphenoidal procedures with intraoperative CSF leakage to prevent postoperative CSF leakage. RESULTS: 1. Ex vivo: The overall mean burst pressure in the transsphenoidal setup was 231 (± 103) mmHg. There was no significant difference in mean burst pressure between groups based on application weight and time (p = 0.227). 2. In Vivo: None of the patients had a postoperative CSF leak. No nose passage problems were observed. One patient had a postoperative meningitis and ventriculitis, most likely related to preoperative extensive CSF leakage. Postoperative imaging did not show any local infection, swelling, or other device-related adverse effects. CONCLUSIONS: We assess the use of Liqoseal® to seal a dural defect during an endoscopic transsphenoidal procedure as to be likely safe and potentially effective.

DeepEOR: automated perioperative volumetric assessment of variable grade gliomas using deep learning.

PURPOSE: Volumetric assessments, such as extent of resection (EOR) or residual tumor volume, are essential criterions in glioma resection surgery. Our goal is to develop and validate segmentation machine learning models for pre- and postoperative magnetic resonance imaging scans, allowing us to assess the percentagewise tumor reduction after intracranial surgery for gliomas. METHODS: For the development of the preoperative segmentation model (U-Net), MRI scans of 1053 patients from the Multimodal Brain Tumor Segmentation Challenge (BraTS) 2021 as well as from patients who underwent surgery at the University Hospital in Zurich were used. Subsequently, the model was evaluated on a holdout set containing 285 images from the same sources. The postoperative model was developed using 72 scans and validated on 45 scans obtained from the BraTS 2015 and Zurich dataset. Performance is evaluated using Dice Similarity score, Jaccard coefficient and Hausdorff 95%. RESULTS: We were able to achieve an overall mean Dice Similarity Score of 0.59 and 0.29 on the pre- and postoperative holdout sets, respectively. Our algorithm managed to determine correct EOR in 44.1%. CONCLUSION: Although our models are not suitable for clinical use at this point, the possible applications are vast, going from automated lesion detection to disease progression evaluation. Precise determination of EOR is a challenging task, but we managed to show that deep learning can provide fast and objective estimates.

Early versus delayed mobilization after aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of efficacy and safety.

OBJECTIVE: A central tenet of Enhanced Recovery After Surgery (ERAS) is evidence-based medicine. Survivors of aneurysmal subarachnoid hemorrhage (aSAH) constitute a fragile patient population prone to prolonged hospitalization within neurointensive care units (NICUs), prolonged immobilization, and a range of nosocomial adverse events. Potentially, well-monitored early mobilization (EM) could constitute a beneficial element of ERAS protocols in this population. Therefore, the objective was to summarize the available evidence on EM strategies in patients with aSAH. METHODS: The authors retrieved prospective and retrospective studies that reported efficacy or safety data on EM (defined as EM in the NICU starting ≤ 7 days after ictus) versus delayed mobilization (DM) (any strategy that comparatively delayed mobilization) after aSAH and were published after January 1, 2000, in PubMed/MEDLINE, Embase, and the Cochrane Library. Random-effects meta-analysis was performed. RESULTS: Ten studies analyzing 1292 patients were included for quantitative synthesis, including 1 randomized, 1 prospective nonrandomized, and 8 retrospective studies. Modified Rankin Scale scores at discharge were not different between the EM and DM groups (mean difference [MD] [95% CI] -0.86 [-2.93 to 1.20] points, p = 0.41). Hospital length of stay in days was markedly reduced in the EM group (MD [95% CI] -6.56 [-10.64 to -2.47] days, p = 0.002). Although there was a statistically significant reduction in radiological vasospasms (OR [95% CI] 0.65 [0.44-0.97], p = 0.03), the reduction in clinically relevant vasospasms was nonsignificant (OR [95% CI] 0.63 [0.31-1.26], p = 0.19). The odds of shunting were significantly lower in the EM group (OR [95% CI] 0.61 [0.39-0.95], p = 0.03). The rates of mortality, pneumonia, and thrombosis were similar among groups (p > 0.05). CONCLUSIONS: Due to a lack of high-quality studies, vastly varying protocols, and resulting statistical clinical and statistical heterogeneity, the level of evidence for recommendations regarding EM in patients with aSAH remains low. The currently available data indicated that mobilization within the first 5 days after aneurysm repair was feasible and safe without significant excessive adverse events, that neurological outcome with EM was almost certainly not worse than with prolonged immobilization, and that there was likely at least some reduction in length of hospital stay. Radiological and clinical vasospasms were not more frequent-with signals even trending toward a decrease-in patients who mobilized early. Higher-quality studies and implementation of full ERAS protocols are necessary to evaluate efficacy and safety with a higher level of evidence and to guide practical implementation through increased standardization. Clinical trial registration no.: CRD42023432828 (www.crd.york.ac.uk/prospero).

Maximal surgical tumour load reduction in immune-checkpoint inhibitor naïve patients with melanoma brain metastases correlates with prolonged survival.

BACKGROUND: Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients. METHODS: Retrospective single-centre analysis of a prospective registry of resected melanoma BM from 2013 to 2021. Correlations of residual tumour volume and outcome were determined with respect to patient, tumour and treatment regimens characteristics. RESULTS: 121 individual patients (66% male, mean age 59.9 years) were identified and included in the study. Pre- and postoperative systemic treatments included BRAF/MEK inhibitors, as well as combination or monotherapy of immune-checkpoint inhibitors (ICIs). Median OS of the entire cohort was 20 months. Cox proportional-hazard analysis revealed postoperative anti-CTLA4+anti-PD-1 therapy (HR 0.07, p = .01) and postoperative residual intracranial tumour burden (HR 1.4, p = .027) as significant predictors for OS. Further analysis revealed that ICI-naïve patients with residual tumour volume ≤3.5 cm3 and postoperative ICI showed significantly prolonged OS compared to patients with residual volume >3.5 cm3 (p < .0001). Subgroup analysis of ICI-naïve patients showed steroid intake postoperatively to be negatively associated with OS, however residual tumour volume ≤3.5 cm3 remained independently correlated with superior OS (HR 0.14, p < .001). CONCLUSION: Besides known predictive factors like postoperative ICI, a maximal intracranial tumour burden reduction seems to be beneficial, especially in ICI-naïve patients. This highlights the importance of local CNS control and the need to further investigating the role of initial surgical tumour load reduction in randomised clinical trials.