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BACKGROUND: Endoscopic endonasal surgical resection is an effective therapeutic approach for olfactory neuroblastoma (ONB). Unilateral excision of ONBs with limited extension has been reported with the purpose of preserving olfactory function. We aimed to review implications of surgical management, olfactory preservation feasibility, and survival outcomes in patients who underwent endoscopic unilateral resection of olfactory neuroblastoma. METHODS: A systematic literature review was conducted using the search terms [("Olfactory neuroblastoma") OR ("Esthesioneuroblastoma")] AND [("Unilateral resection") OR ("Olfaction preservation")]. Studies reporting cases of unilateral olfactory neuroblastoma endoscopic resection with postoperative olfaction assessment were included. Concurrently, records of patients who met inclusion criteria at our institution were reviewed retrospectively. The survival and olfactory outcomes were analyzed in both cohorts. RESULTS: Thirty-three patients were identified in the published literature. Twenty-three (69.7%) reported postoperative olfaction preservation. Olfactory function after surgery did not show an association with Kadish stage (p=0.128). No evidence of disease was observed at the latest follow-up in this group of patients. Nine patients who met inclusion criteria were identified at our institution. The extent of resection influenced the level of olfaction preservation when cribriform plate and nasal septum resection coexisted (p=0.05). A single patient at our institution developed recurrence after being lost to follow-up for 22 months. CONCLUSIONS: Olfaction preservation can be achieved in patients who undergo endoscopic unilateral resection and adjuvant radiotherapy. The extent of resection should aim for negative margins, particularly in the midline. Larger studies are required to assess the risk of contralateral microscopic disease, and, hence, close follow-up is advised.
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BACKGROUND AND OBJECTIVES: Traditional and well-established transcranial approaches to the spheno-orbital region and middle cranial fossa guarantee optimal intracranial exposure, and additional orbital and zygomatic osteotomies provide further control over extracranial components to be resected; however, these techniques come at the cost of additional morbidity. The introduction of minimally invasive endoscopic approaches and the conceptualization of the so-called "multiportal" paradigm might provide an alternative route. This preliminary study investigates the feasibility of the combined Biportal Endoscopic TransOrbital and transMaxillary Approach (bETOMA) approach to the spheno-orbital and middle cranial fossa regions. METHODS: Using 4 silicon-injected adult cadaver heads (8 sides; 16 approaches), we systematically dissected through superior eyelid ETOA and endoscopic TMA approaches. The analysis focused on pterygopalatine, infratemporal, anterior and middle cranial fossae, Meckel cave, and cavernous sinus access. We evaluated the feasibility of bETOMA using linear distances, angles of attack, and exposure areas. We also introduced volume of operative maneuverability, its standardized derivative (sVOM), target distance, visuo-operative angle, and working zone volume as novel metrics. RESULTS: The analysis revealed comparable angles of attack between approaches. ETOA and TMA exposure areas were 918.38 ± 223.93 mm2 and 257.07 ± 86.07 mm2, respectively. TMA showed a larger VOM in the greater sphenoid wing, but ETOA offered superior distal maneuverability (sVOM: 5.39 ± 1.94 vs 2.54 ± 0.79 cm3) and closer intracranial space access (27.45 vs 50.83 mm). The combined approaches yielded a mean working zone volume of 13.75 ± 3.73 cm3 in the spheno-orbital interface. CONCLUSION: The bETOMA approach provides adequate neurovascular exposure and maneuverability to the spheno-orbital region, infratemporal, and anterior and middle cranial fossae, addressing significant limitations of previously investigated monoportal techniques (ie, optic nerve decompression, hyperostotic bone resection, and infratemporal exposure). This combined minimally invasive approach might help manage lesions harbored within the cranio-orbital interface region invading the extracranial space.
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OBJECTIVE: Brain tumors display remarkable cellular and molecular diversity, significantly impacting the progression and outcomes of the disease. The utilization of tumor tissue acquired through surgical handheld devices for tumor characterization raises important questions regarding translational research. This study seeks to evaluate the integrity of tissue resected using a microdebrider (MD) in the context of establishing tumor organoids from glioblastomas (GBM). METHODS: Tumor samples were collected from patients with GBM using both tumor forceps (en bloc) and a MD. The time required to protocol completion and cell viability of paired samples was measured. H&E staining was performed to examine histologic morphology. RESULTS: Ten paired samples were obtained from GBM patients using tumor forceps and the MD. Samples collected with the MD demonstrated significantly shorter processing times compared to those obtained through en bloc resection, with overall means of 31.7 ± 2.4 mins and 38.8±3 mins, respectively (P < 0.001). Cell viability measured at the end of protocol completion was comparable between tissues obtained using both the MD and en bloc, with mean viabilities of 80.2 ± 12.4% and 79.1 ± 12.5%, respectively (P = 0.848). H&E examination of tissues revealed no significant differences in the cellular and histologic characteristics of paired samples obtained using both methods across GBM tumors, nor in the corresponding established organoids. CONCLUSIONS: Tumor tissues obtained using the MD and en bloc methods demonstrate a high success rate in establishing GBM organoids, with the MD offering the advantage of significantly reduced processing time. Both methods display comparable cell viability and maintain consistent histologic characteristics in the resected tissue and the corresponding organoids.
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Introduction This study highlights the relation between compound muscle action potential (CMAP) latency variations and the predictive value of facial nerve (FN) proximal-to-distal (P/D) amplitude ratio measured at the end of vestibular schwannoma resection. Methods Forty-eight patients underwent FN stimulation at the brainstem (proximal) and internal acoustic meatus (distal) using a current intensity of 2 mA. The proximal latency and the P/D amplitude ratio were assessed. House-Brackmann grades I & II indicated good FN function, and grades III to VI were considered fair/poor function. A P/D amplitude ratio > 0.6 was used as a cutoff to indicate a good FN function, while a ratio of ≤ 0.6 indicated a fair/poor FN function. Results The P/D amplitude ratio was measured for all patients, and the calculated sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) were 85.2, 85.7, 88.5, and 81.8%, respectively. The CMAPs from the mentalis muscle were then classified based on their proximal latency into group I (< 6 ms), group II (6-8 ms), and group III (> 8 ms). The SE, SP, PPV, and NPV became 90.5, 90.9, 95, and 83.3%, respectively, in group II. In group I, SE and NPV increased, whereas SP and PPV decreased. While in group III, SP and PPV increased, whereas SE and NPV decreased. Conclusion At a latency between 6 and 8 ms, the P/D amplitude ratio was predictive of outcomes with high SE and SP. When latency was < 6 ms or > 8 ms, the same predictive ability was not observed. Knowing the strengths and limitations is important for understanding the predictive value of the P/D amplitude ratio.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagen , Meningioma/patología , Meningioma/cirugía , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Pronóstico , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/cirugía , Neoplasias Orbitales/patología , Hueso Esfenoides/diagnóstico por imagen , Hueso Esfenoides/cirugíaRESUMEN
The angle of exposure (AnE) represents a metric that is particularly useful for analyzing circular bony structures during skull base dissections. The authors aimed to develop and validate a neuronavigation-based method to measure the AnE. A formula based on vectorial geometry and the coordinates of three points collected with a neuronavigation system was developed to measure the AnE. The method was validated using a plexiglass phantom head. To demonstrate its applicability, the authors measured the AnE in 6 cadaveric specimens after exposure of the hypoglossal canal using a far-medial approach (FMA) and a far-lateral transtubercular approach (FLTA) and in 6 different specimens after exposure of the jugular foramen using an FLTA and a retrosigmoid approach (RSA). The mean angles measured at 45°, 90°, and 180° using a goniometer during the validation test were 44.8° ± 1.1°, 90.8° ± 1.2°, and 179.7° ± 0.8° using the novel formula (p > 0.05). In the first illustrative application, the mean AnEs for the FMA and FLTA were 129° ± 0.9° and 243° ± 1.9°, respectively. In the second scenario, the mean AnEs were 192° ± 1.3° for the FTLA and 143° ± 2.1° for the RSA. The neuronavigation-based technique described is a highly accurate method to measure the AnE.
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Cadáver , Neuronavegación , Base del Cráneo , Humanos , Neuronavegación/métodos , Base del Cráneo/cirugía , Disección/métodos , Fantasmas de Imagen , Procedimientos Neuroquirúrgicos/métodosRESUMEN
INTRODUCTION: Spheno-orbital meningiomas (SOMs) represent a distinct subtype of meningioma characterized by their unique multi-compartmental invasion pattern. Previous studies have investigated correlations between SOMs and visual manifestations. However, our comprehension of pain associated with SOMs remains limited. This study aims to provide insight into the pathophysiology underlying SOM-related pain through measurements of tumor volume and superior orbital fissure (SOF) narrowing. METHODS: This retrospective study included patients who underwent surgical resection of a SOM between 2000 and 2022. Preoperative CT and/or MRI scans were analyzed, and the tumor volume of each segment was measured. Bony 3D reconstructions were used to measure the area of the SOF, and SOF narrowing was calculated. RESULTS: The study cohort included 66 patients diagnosed with SOMs, among which 25.8% (n = 17) presented with pain. Postoperatively, 14/17 (82.4%) of patients reported pain improvement. There was no significant correlation between the total volume or the volume of tumor within each compartment and the presence of pain on presentation (p > 0.05). The median SOF narrowing was significantly different between patients presenting with and without tumor-associated pain with median of 11 mm2 (IQR 2.8-22.3) and 2 mm2 (IQR 0-6), respectively (p = 0.005). Using logistic regression, a significant correlation between the degree of SOF narrowing and the presence of SOM-associated pain on presentation was identified, with an aOR of 1.2 (95% CI 1.12-1.3, p = 0.02). CONCLUSION: While the exact cause of tumor-associated pain remains unclear, SOF narrowing seems to play a role in pain among SOM patients. Based on the radiological characteristics, SOF neurovascular decompression is recommended in SOM patients.
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Dolor en Cáncer , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/complicaciones , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Estudios Retrospectivos , Dolor , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugíaRESUMEN
BACKGROUND: Infectious intracranial aneurysms (IIAs) are a rare sequel of systemic infection and occur most commonly in patients with infective endocarditis (IE). Despite the increasing use of non-invasive screening angiography in patients with IE, the incidence remains low, yielding limited data on the management of IIAs in pediatric populations. We performed a pooled analysis of all published series of pediatric patients with IIAs to study the disease landscape including presentation, management, and outcomes. METHODS: Data included in this study were pooled from published literature on IIAs between 1960 and 2023. Abstracts were selected for full review to include only manuscripts reporting at least one case of pediatric IIA (age 0-18 years). RESULTS: A total of 145 pediatric patients with 178 IIAs were included. Patients presented with rupture in 68% of cases, of which 36% had intraparenchymal hemorrhage and 39% had subarachnoid hemorrhage. Using multivariate logistic regression, independent predictors of rupture were posterior location (aOR 10, P=0.041) and history of IE (aOR 7.2, P=0.001). Primary medical management was successful in 82% of cases with unruptured aneurysms while, in those with ruptured IIAs, medical management was successful in 26% of cases. The 90-day mortality rate was 28%. Using multivariate logistic regression, ruptured IIAs (aOR 5.4, P<0.01) and failure of medical management (aOR 11.1, P<0.05) were independent predictors of 90-day mortality. CONCLUSION: Pediatric IIAs remain a rare complication of systemic or localized CNS infection in the pediatric population. Medical management of unruptured aneurysms is highly successful, while ruptured aneurysms have a remarkably high rate of failure of medical management and should be treated by early surgical or endovascular intervention when feasible.
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BACKGROUND: Endovascular thrombectomy (EVT) remains the standard of care for acute large vessel occlusion (LVO) stroke. However, the safety and efficacy of repeat thrombectomy (rEVT) in recurrent LVO remains unclear. This study uses a large real-world patient cohort to study technical and clinical outcomes after rEVT. METHODS: This is a retrospective cohort study including patients who underwent thrombectomy between January 2013 and December 2022. Data were included from 21 comprehensive stroke centers globally through the Stroke Thrombectomy and Aneurysm Registry (STAR). Patients undergoing single EVT or rEVT within 30 days of LVO stroke were included in the study. Propensity score matching was used to compare patients undergoing single EVT versus rEVT. RESULTS: Out of a total of 7387 patients who underwent thrombectomy for LVO stroke, 90 (1.2%) patients underwent rEVT for the same vascular territory within 30 days. The median (IQR) time to re-occlusion was 2 (1-7) days. Compared with a matched cohort of patients undergoing a single EVT procedure, patients undergoing rEVT had a comparable rate of good functional outcome and mortality rate, but a higher rate of symptomatic intracranial hemorrhage (sICH). There was a significant reduction in the National Institutes of Health Stroke Scale (NIHSS) score of patients who underwent rEVT at discharge compared with baseline (-4.8±11.4; P=0.006). The rate of successful recanalization was similar in the single thrombectomy and rEVT groups (78% vs 80%, P=0.171) and between index and rEVT performed on the same patient (79% vs 80%; P=0.593). CONCLUSION: Short-interval rEVT is associated with an improvement in the NIHSS score following large vessel re-occlusion. Compared with single thrombectomy, there was a higher rate of sICH with rEVT, but without a significant impact on rates of functional independence or mortality.
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BACKGROUND: Cavernous malformations (CMs) are clusters of thin-walled sinusoidal vessels without well-defined walls. Though they can occur anywhere in the neuroaxis, cranial nerve (CN) CMs are rare. METHOD: We report a 47-year-old male with gradual CN III palsy. Initial imaging showed no significant findings, but a follow-up MRI revealed a growing lesion along CN III. Intraoperative findings confirmed a CN III CM. Diagnosing and treating CN III CM are complex. Radiological findings lack specificity, requiring consideration of various diagnoses for patients with isolated CN III palsy and abnormal radiological findings. CONCLUSION: Surgery is the gold standard, aiming for complete lesion removal while minimizing neurological complications.
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Enfermedades del Nervio Oculomotor , Nervio Oculomotor , Humanos , Masculino , Persona de Mediana Edad , Nervios Craneales , Enfermedades del Nervio Oculomotor/etiología , Enfermedades del Nervio Oculomotor/cirugía , ParálisisRESUMEN
Skull base malignancies arising from the parotid gland, skin, or external auditory canal (EAC) can potentially involve the temporal bone. Management of these invasive tumors represents a true challenge considering the critical neurovascular relationships. Exoscope-assisted temporal bone resection (TBR) plays a crucial role in addressing such malignancies. The extent of disease is evaluated using the Pittsburgh staging system, which then guides the boundaries of resection. Lateral TBR (LTBR) relies on removal of the EAC and lateral ossicles and is generally appropriate for stage T1 and T2 tumors. Total TBR (TTBR) is reserved for high-grade tumors involving the petrous apex. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23135.
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BACKGROUND AND OBJECTIVES: Spheno-orbital meningiomas arise from the arachnoid villi cap cells at the sphenoid ridge and have the ability to spread through soft tissue extension and cranial bone invasion. Owing to their orbital hyperostosis and intraorbital soft tissue extension, they commonly present with ophthalmologic manifestations. This study aims to investigate the correlation between tumor volume with the presenting symptoms and postoperative outcomes. METHODS: This retrospective study analyzed patients who underwent surgical resection of spheno-orbital meningiomas. Tumor volumes in different compartments were measured using preoperative and postoperative imaging. Linear and logistic regression analyses were used to identify correlations between tumor volumes and presenting symptoms preoperatively and postoperative outcomes. RESULTS: Sixty-six patients were included in this study, of whom 86.4% had proptosis, 80.3% had decreased visual acuity (VA), 30.3% had visual field defects, and 13.6% had periorbital edema. Preoperatively, proptosis linearly correlated with intraosseous tumor volume (coefficient = 0.6, P < .001), while the decrease in baseline VA correlated with the intraorbital tumor volume (coefficient = 0.3, P = .01). The odds of periorbital edema were found to increase with an increase in intraosseous tumor volume with an adjusted odds ratio of 1.4 (95% CI, 1.1-1.7, P = .003), while the odds of visual field defects were found to increase with an increase in intraorbital tumor volume with an adjusted odds ratio of 2.7 (95% CI, 1.3-5.6, P = .01). Postoperatively, the volume of intraosseous tumor resected linearly correlated with the improvement in proptosis (coefficient = 0.7, P < .001), while the volume of intraorbital tumor resected linearly correlated with improvement in VA (coefficient = 0.5, P < .001) and with a larger effect size in patients presenting with moderate-to-severe decrease in VA preoperatively (coefficient = 0.8). CONCLUSION: Underscoring the importance of each tumor compartment relative to the patient's symptomatology serves as a valuable guide in implementing a compartmentalized resection approach tailored to the surgical objectives.
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Exoftalmia , Neoplasias Meníngeas , Meningioma , Neoplasias Orbitales , Humanos , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Meningioma/patología , Pronóstico , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/cirugía , Neoplasias Orbitales/patología , Resultado del Tratamiento , Estudios Retrospectivos , Exoftalmia/patología , Exoftalmia/cirugía , Hueso Esfenoides/diagnóstico por imagen , Hueso Esfenoides/cirugía , Trastornos de la Visión/patología , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Edema/patologíaRESUMEN
INTRODUCTION: Brain tumors display significant inter and intratumoral heterogeneity, impacting disease progression and outcomes. Preserving surgically resected tissue is vital for ensuring accurate research results to enhance understanding of tumor pathophysiology. This study evaluates tissue integrity and viability of tissue resected using 2 surgical devices for tumor resection: a mechanical microdebrider (MD) and an ultrasonic aspirator (UA). METHODS: Tumor samples were obtained from patients undergoing surgical resection of primary and secondary intracranial tumors. Cell viability was assessed, and histopathological analysis of Hematoxylin and Eosin -stained tissues was performed. Adherent monolayer and neurospheres cell cultures were established from paired samples. RNA isolation and quantitative polymerase chain reaction of housekeeping genes were conducted to compare genetic integrity. RESULTS: The cellular viability was comparable between samples obtained using both the MD and the UA, with a mean viability of 75.2% ± 15.6 and 70.7% ± 16.8, respectively (P = 0.318). Histopathological evaluation indicated no discernible differences in cellular integrity between the devices. Cell culture success rates and growth characteristics were similar for both devices. RNA concentration and integrity were well-maintained in both MD and UA samples, with no significant differences (P = 0.855). Quantitative polymerase chain reaction analysis of housekeeping genes showed consistent results across matched tissues from both devices and different tumor pathologies. CONCLUSIONS: Surgical handheld devices provide valuable, high-quality tissue samples for research. Surgeon preference, tumor pathology, and anatomical location dictate device choice. Both MD and UA devices are reliable for obtaining quality tissue specimens, facilitating translational neuro-oncology research.
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Neoplasias Encefálicas , Terapia por Ultrasonido , Humanos , Ultrasonido , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Encéfalo/patología , ARNRESUMEN
BACKGROUND AND OBJECTIVES: The emergence of machine learning models has significantly improved the accuracy of surgical outcome predictions. This study aims to develop and validate an artificial neural network (ANN) model for predicting facial nerve (FN) outcomes after vestibular schwannoma (VS) surgery using the proximal-to-distal amplitude ratio (P/D) along with clinical variables. METHODS: This retrospective study included 71 patients who underwent VS resection between 2018 and 2022. At the end of surgery, the FN was stimulated at the brainstem (proximal) and internal acoustic meatus (distal) and the P/D was calculated. Postoperative FN function was assessed using the House-Brackmann grading system at discharge (short-term) and after 9-12 months (long-term). House-Brackmann grades I-II were considered good outcome, whereas grades III-VI were considered fair/poor. An ANN model was constructed, and the performance of the model was evaluated using the area under the ROC curve for internal validation and accuracy, sensitivity, specificity, and positive and negative predictive values for external validation. RESULTS: The short-term FN outcome was grades I-II in 57.7% and grades III-VI in 42.3% of patients. Initially, a model using P/D had an area under the curve of 0.906 (internal validation) and an accuracy of 89.1% (95% CI: 68.3%-98.8%) (external validation) for predicting good vs fair/poor short-term FN outcomes. The model was then refined to include only muscles with a P/D with a proximal latency between 6 and 8 ms. This improved the accuracy to 100% (95% CI: 79%-100%). Integrating clinical variables (patient's age, tumor size, and preoperative HB grade) in addition to P/D into the model did not significantly improve the predative value. A model was then created to predict the long-term FN outcome using P/D with latencies between 6 and 8 ms and had an accuracy of 90.9% (95% CI: 58.7%-99.8%). CONCLUSION: ANN models incorporating P/D can be a valuable tool for predicting FN outcomes after VS surgery. Refining the model to include P/D with latencies between 6 and 8 ms further improves the model's prediction. A user-friendly interface is provided to facilitate the implementation of this model.
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Traumatismos del Nervio Facial , Neuroma Acústico , Humanos , Nervio Facial/cirugía , Neuroma Acústico/cirugía , Estudios Retrospectivos , Traumatismos del Nervio Facial/etiología , Traumatismos del Nervio Facial/prevención & control , Pronóstico , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Atypical teratoid/rhabdoid tumor (ATRT) is a rare, highly aggressive central nervous system tumor predominantly found in children. Limited information exists on ATRT in adults, posing challenges in diagnosis and treatment. This study presents the case of an adult patient with ATRT in the sellar region and explores the impact of different treatment regimens on patient survival. OBSERVATIONS: A 60-year-old female with an ATRT underwent resection of the tumor, followed by adjuvant chemoradiotherapy. Molecular genetic analysis revealed compound heterozygous SMARCB1 point mutations. Survival analysis was performed on previously published adult ATRT cases, comparing treatment approaches. The cohort's overall median survival was 6 months, with patients receiving combined chemoradiotherapy showing the longest median survival of 23.5 months. Statistical analysis demonstrated a significant difference in survival between patients treated with surgery alone and those receiving surgery followed by chemoradiotherapy (p < 0.001). However, no significant difference was observed between patients treated with surgery alone and those with postoperative radiotherapy (p = 0.105). LESSONS: Early initiation of adjuvant chemoradiotherapy following surgery improves survival outcomes in adult patients with ATRT. Because of limited data on standardized treatment protocols for adults with ATRT, further research and larger-scale studies are needed to establish effective treatment guidelines for this population.
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BACKGROUND: Although unplanned readmission is a postoperative outcome metric associated with significant morbidity and financial burden, precise assessment tools for its prediction have not yet been developed. The Risk Analysis Index (RAI) could potentially be used to help improve the prediction of unplanned readmissions for patients undergoing intracranial tumor resection (ITR). In the present study, we evaluate the predictive accuracy of frailty on 30-day unplanned readmission after ITR using the RAI. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program database. The baseline characteristics, preoperative clinical status, and outcomes were compared between patients with and without unplanned readmission. Frailty was calculated using the RAI. Univariate and multivariate logistic regression analyses were performed to identify independent associations between unplanned readmissions and patient characteristics. RESULTS: The unplanned readmission rate for this cohort (n = 31,776) was 10.8% (n = 3420). Of the 3420 readmitted patients, 958 required unplanned reoperation. Multiple characteristics were significantly different between the 2 groups, including age, body mass index, comorbidities, and RAI groups (P < 0.05). The common causes of unplanned readmission included infection (9.4%), seizures (6%), and pulmonary embolism (4%). The patient characteristics identified as reliable predictors of unplanned readmission included age, body mass index, functional status, diabetes, hypertension, hyponatremia, and the patient's RAI score (P < 0.05). Frail status, hyponatremia, leukocytosis, hypertension, and thrombocytosis were significant predictors of unplanned readmissions. CONCLUSIONS: The RAI is a reliable preoperative frailty index for predicting unplanned readmissions after ITR. Using the RAI could decrease unplanned readmissions by identifying high-risk patients and enabling future implementation of appropriate management guidelines.
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Introduction: Aggressive prolactinomas (APRLs) pose a significant clinical challenge due to their high rate of regrowth and potentially life-threatening complications. In this study, we present a case of a patient with an APRL who had a trial of multiple therapeutic modalities with the aim to provide a review of molecular abnormalities and management of APRLs by corroborating our experience with previous literature. Methods: A total of 268 articles were reviewed and 46 were included. Case reports and series, and studies that investigated the molecular and/or genetic analysis of APRLs were included. Special care was taken to include studies describing prolactinomas that would fall under the APRL subtype according to the European Society of Endocrinology guidelines; however, the author did not label the tumor as "aggressive" or "atypical". Addiontionally, we present a case report of a 56-year-old man presented with an invasive APRL that was resistant to multiple treatment modalities. Results: Literature review revealed multiple molecular abnormalities of APRLs including mutations in and/or deregulation of ADAMTS6, MMP-9, PITX1, VEGF, POU6F2, CDKN2A, and Rb genes. Mismatch repair genes, downregulation of microRNAs, and hypermethylation of specific genes including RASSF1A, p27, and MGMT were found to be directly associated with the aggressiveness of prolactinomas. APRL receptor analysis showed that low levels of estrogen receptor (ER) and an increase in somatostatin receptors (SSTR5) and epidermal growth factor receptors (EGFR) were associated with increased invasiveness and higher proliferation activity. Our patient had positive immunohistochemistry staining for PD-L1, MSH2, and MSH6, while microarray analysis revealed mutations in the CDKN2A and POU6F2 genes. Despite undergoing two surgical resections, radiotherapy, and taking dopamine agonists, the tumor continued to progress. The patient was administered pazopanib, which resulted in a positive response and the patient remained progression-free for six months. However, subsequent observations revealed tumor progression. The patient was started on PD-L1 inhibitor pembrolizumab, yet the tumor continued to progress. Conclusion: APRLs are complex tumors that require a multidisciplinary management approach. Knowledge of the molecular underpinnings of these tumors is critical for understanding their pathogenesis and identifying potential targets for precision medical therapy.
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Neoplasias Hipofisarias , Prolactinoma , Masculino , Humanos , Persona de Mediana Edad , Prolactinoma/tratamiento farmacológico , Prolactinoma/genética , Prolactinoma/metabolismo , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Indazoles/uso terapéutico , Factores del Dominio POURESUMEN
OBJECTIVE: Surgery plays a key role in the management of brain metastases. Stratifying surgical risk and individualizing treatment will help optimize outcomes because there is clinical equipoise between radiation and resection as treatment options for many patients. Here, the authors used a multicenter database to assess the prognostic utility of baseline frailty, calculated with the Risk Analysis Index (RAI), for prediction of mortality within 30 days after surgery for brain metastasis. METHODS: The authors pooled patients who had been surgically treated for brain metastasis from the American College of Surgeons National Surgical Quality Improvement Program database (2012-2020). The authors studied the relationship between preoperative calculated RAI score and 30-day mortality after surgery for brain metastasis by using linear-by-linear proportional trend tests and binary logistic regression. The authors calculated C-statistics (with 95% CIs) in receiver operating characteristic (ROC) curve analysis to assess discriminative accuracy. RESULTS: The authors identified 11,038 patients who underwent brain metastasis resection with a median (interquartile range) age of 62 (54-69) years. The authors categorized patients into four groups on the basis of RAI: robust (RAI 0-20), 8.1% of patients; normal (RAI 21-30), 9.2%; frail (RAI 31-40), 75%; and severely frail (RAI ≥ 41), 8.1%. The authors found a positive correlation between 30-day mortality and frailty. RAI demonstrated superior predictive discrimination for 30-day mortality as compared with the 5-factor modified frailty index (mFI-5) on ROC analysis (C-statistic 0.65, 95% CI 0.65-0.66). CONCLUSIONS: The RAI frailty score accurately estimates 30-day mortality after brain metastasis resection and can be calculated online with an open-access software tool: https://nsgyfrailtyoutcomeslab.shinyapps.io/BrainMetsResection/. Accordingly, RAI can be utilized to measure surgical risk, guide treatment options, and optimize outcomes for patients with brain metastases. RAI has superior discrimination for predicting 30-day mortality compared with mFI-5.