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1.
Am J Otolaryngol ; 45(4): 104302, 2024.
Article in English | MEDLINE | ID: mdl-38678798

ABSTRACT

PURPOSE: The incidence of ageusia and dysgeusia after endoscopic endonasal (EEA) resection of olfactory groove meningioma (OGM) is not well established despite recognized impairment in olfactory function. METHODS: We retrospectively administered a validated taste and smell survey to patients undergoing EEA for resection of OGM at two institutions. Demographics and clinical characteristics were collected and survey responses were analyzed. RESULTS: Twelve patients completed the survey. The median time from surgery was 24 months. The average total complaint score was 5.5 out of 16 [0-13]. All patients reported a change in sense of smell while only 42 % reported a change in sense of taste. Taste changes did not consistently associate with laterality or size of the neoplasm. Significant heterogeneity existed when rating severity of symptoms. CONCLUSIONS: To our knowledge this is the first case series examining taste changes after EEA resection of OGM. Despite universal olfactory dysfunction, only a minority of patients reported a change in their sense of taste. Our findings may improve patient counseling and expectations after surgery.


Subject(s)
Meningeal Neoplasms , Meningioma , Postoperative Complications , Humans , Meningioma/surgery , Female , Male , Middle Aged , Retrospective Studies , Aged , Postoperative Complications/etiology , Meningeal Neoplasms/surgery , Endoscopy/methods , Endoscopy/adverse effects , Adult , Taste Disorders/etiology , Dysgeusia/etiology
2.
Pituitary ; 26(4): 488-494, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37438451

ABSTRACT

PURPOSE: Pituitary adenomas commonly arise in patients with MEN1 syndrome, an autosomal dominant condition predisposing to neuroendocrine tumor formation, and typically diagnosed in patients with a relevant family cancer history. In these patients with existing germline loss of MEN1 on one allele, somatic loss of the second MEN1 allele leads to complete loss of the MEN1 protein, menin, and subsequent tumor formation. METHODS: Whole exome sequencing was performed on the tumor and matching blood under an institutional board approved protocol. DNA extraction and analysis was conducted according to previously described methods. RESULTS: We describe a 23 year-old patient with no significant past medical history or relevant family history who underwent surgical resection of a symptomatic and medically resistant prolactinoma. Whole exome sequencing of tumor and blood samples revealed somatic loss of MEN1 at both alleles, suggesting a double hit mechanism, with no underlying germline MEN1 mutation. CONCLUSION: To our knowledge, this is the first case of pituitary adenoma to arise from somatic loss of MEN1 and in the absence of an underlying germline MEN1 mutation.


Subject(s)
Adenoma , Multiple Endocrine Neoplasia Type 1 , Pituitary Neoplasms , Prolactinoma , Humans , Young Adult , Adult , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Multiple Endocrine Neoplasia Type 1/genetics , Adenoma/genetics , Adenoma/surgery , Adenoma/pathology , Germ-Line Mutation
3.
Lancet Oncol ; 21(5): 655-663, 2020 05.
Article in English | MEDLINE | ID: mdl-32251621

ABSTRACT

BACKGROUND: We did a phase 2 trial of pembrolizumab in patients with non-small-cell lung cancer (NSCLC) or melanoma with untreated brain metastases to determine the activity of PD-1 blockade in the CNS. Interim results were previously published, and we now report an updated analysis of the full NSCLC cohort. METHODS: This was an open-label, phase 2 study of patients from the Yale Cancer Center (CT, USA). Eligible patients were at least 18 years of age with stage IV NSCLC with at least one brain metastasis 5-20 mm in size, not previously treated or progressing after previous radiotherapy, no neurological symptoms or corticosteroid requirement, and Eastern Cooperative Oncology Group performance status less than two. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria was used to evaluate CNS disease; systemic disease was not required for participation. Patients were treated with pembrolizumab 10 mg/kg intravenously every 2 weeks. Patients were in two cohorts: cohort 1 was for those with PD-L1 expression of at least 1% and cohort 2 was patients with PD-L1 less than 1% or unevaluable. The primary endpoint was the proportion of patients achieving a brain metastasis response (partial response or complete response, according to mRECIST). All treated patients were analysed for response and safety endpoints. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT02085070. FINDINGS: Between March 31, 2014, and May 21, 2018, 42 patients were treated. Median follow-up was 8·3 months (IQR 4·5-26·2). 11 (29·7% [95% CI 15·9-47·0]) of 37 patients in cohort 1 had a brain metastasis response. There were no responses in cohort 2. Grade 3-4 adverse events related to treatment included two patients with pneumonitis, and one each with constitutional symptoms, colitis, adrenal insufficiency, hyperglycaemia, and hypokalaemia. Treatment-related serious adverse events occurred in six (14%) of 42 patients and were pneumonitis (n=2), acute kidney injury, colitis, hypokalaemia, and adrenal insufficiency (n=1 each). There were no treatment-related deaths. INTERPRETATION: Pembrolizumab has activity in brain metastases from NSCLC with PD-L1 expression at least 1% and is safe in selected patients with untreated brain metastases. Further investigation of immunotherapy in patients with CNS disease from NSCLC is warranted. FUNDING: Merck and the Yale Cancer Center.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , B7-H1 Antigen/genetics , Brain Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Aged , Antibodies, Monoclonal, Humanized/adverse effects , B7-H1 Antigen/antagonists & inhibitors , Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Middle Aged , Neoplasm Metastasis
4.
Acta Neurochir (Wien) ; 159(10): 1875-1885, 2017 10.
Article in English | MEDLINE | ID: mdl-28831590

ABSTRACT

OBJECTIVE: To review current management strategies for olfactory groove meningioma (OGM)s and the recent literature comparing endoscopic endonasal (EEA) with traditional transcranial (TCA) approaches. METHODS: A PubMed search of the recent literature (2011-2016) was performed to examine outcomes following EEA and TCA for OGM. The extent of resection, visual outcome, postoperative complications and recurrence rates were analyzed using percentages and proportions, the Fischer exact test and the Student's t-test using Graphpad PRISM 7.0Aa (San Diego, CA) software. RESULTS: There were 444 patients in the TCA group with a mean diameter of 4.61 (±1.17) cm and 101 patients in the EEA group with a mean diameter of 3.55 (± 0.58) cm (p = 0.0589). GTR was achieved in 90.9% (404/444) in the TCA group and 70.2% (71/101) in the EEA group (p < 0.0001). Of the patients with preoperative visual disturbances, 80.7% (21/26) of patients in the EEA cohort had an improvement in vision compared to 12.83%(29/226) in the TCA group (p < 0.0001). Olfaction was lost in 61% of TCA and in 100% of EEA patients. CSF leaks and meningitis occurred in 25.7% and 4.95% of EEA patients and 6.3% and 1.12% of TCA patients, respectively (p < 0.0001; p = 0.023). CONCLUSIONS: Our updated literature review demonstrates that despite more experience with endoscopic resection and skull base reconstruction, the literature still supports TCA over EEA with respect to the extent of resection and complications. EEA may be an option in selected cases where visual improvement is the main goal of surgery and postoperative anosmia is acceptable to the patient or in medium-sized tumors with existing preoperative anosmia. Nevertheless, based on our results, it seems more prudent at this time to use TCA for the majority of OGMs.


Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Natural Orifice Endoscopic Surgery/methods , Cohort Studies , Humans , Natural Orifice Endoscopic Surgery/adverse effects , Neoplasm Recurrence, Local , Olfaction Disorders/etiology , Postoperative Complications/etiology , Postoperative Period , Smell , Treatment Outcome
5.
Acta Neurochir (Wien) ; 159(9): 1589-1595, 2017 09.
Article in English | MEDLINE | ID: mdl-28688051

ABSTRACT

Stereotactic needle biopsy, a standard of care for acquiring deep-seated pathology, has limitations and risks in some situations. We present an uncommon case with basal ganglia dematiaceous mycetoma. Due to the firm consistency of the lesion, the initial stereotactic needle biopsy failed to provide a diagnosis. In a second operation, transtubular excisional biopsy was successfully performed to remove the entire mycetoma. We reviewed recent case series of transtubular approaches to deep-seated brain lesions and suggest this method could be a rescue for a non-diagnostic stereotactic needle biopsy and even may be the approach of choice in some cases.


Subject(s)
Basal Ganglia Diseases/pathology , Biopsy/methods , Mycetoma/pathology , Neurosurgical Procedures/methods , Aged , Antineoplastic Agents/adverse effects , Basal Ganglia Diseases/diagnostic imaging , Basal Ganglia Diseases/etiology , Basal Ganglia Diseases/surgery , Biopsy, Needle/methods , Female , Humans , Imaging, Three-Dimensional , Immunocompromised Host , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Magnetic Resonance Imaging , Mycetoma/diagnostic imaging , Mycetoma/etiology , Mycetoma/surgery , Purines/adverse effects , Quinazolinones/adverse effects , Stereotaxic Techniques
6.
Acta Neurochir (Wien) ; 159(8): 1379-1385, 2017 08.
Article in English | MEDLINE | ID: mdl-28643170

ABSTRACT

BACKGROUND: Orthostatic headache (OH) is a potential complication of lumbar drainage (LD) usage. The incidence and risk factors for OH with the use of lumbar drainage during endoscopic endonasal procedures have not been documented. OBJECTIVE: To investigate the incidence of post-procedure OHs associated with placement of LD in patients undergoing endoscopic endonasal procedures. METHODS: We prospectively noted the placement of LDs in a consecutive series of endoscopic endonasal skull base surgeries. Charts were retrospectively reviewed, and patients were divided into two groups: those with OH and those without. The patient demographics, drain durations, imaging findings of intracranial hypotension, pathologies and need for a blood patch were compared between the two groups. RESULTS: Two hundred forty-nine patients were included in the study. Seven patients (2.8%) suffered post-dural puncture OH, which was mild to moderate and disappeared 2-8 days (median 3 days) after treatment. Blood patches were used in four patients. Significant predisposing factors were age (33.0 vs. 53.5, P = 0.014) and a strong trend for female gender (85.7% vs. 47.9%, P = 0.062). BMI and drain duration were not significant. Postoperative intracranial hypotension was diagnosed radiographically in 43% of OH patients and in 5.4% of those without OH (P = 0.003). Four (1.6%) patients required treatment with an epidural blood patch. CONCLUSION: OH associated with intracranial hypotension in patients undergoing endoscopic endonasal procedures with LDs is an infrequent complication seen more commonly in young female patients. Radiographic signs of intracranial hypotension are a specific but not sensitive test for OH.


Subject(s)
Headache/epidemiology , Intracranial Hypotension/surgery , Neuroendoscopy/adverse effects , Postoperative Complications/epidemiology , Skull Base/surgery , Adult , Aged , Drainage/adverse effects , Female , Headache/etiology , Humans , Incidence , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Period , Retrospective Studies , Risk Factors , Treatment Outcome
7.
Neurosurg Rev ; 36(1): 21-4; discussion 24-5, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22886322

ABSTRACT

Adult patients with space-occupying hemispheric infarctions have a poor prognosis, with an associated fatality rate of 80%. Decompressive hemicraniectomy (DH) has been studied as a treatment option for patients with malignant cerebral infarction refractory to maximal medical therapy, with reasonable outcomes demonstrated in the adult population if the patient is decompressed within 48 h. However, there are no randomized controlled trials in the pediatric literature to make the same claims. In this study, we evaluated the current literature in regards to DH following malignant stroke in the pediatric population. We found that excellent recovery, with an acceptable quality of life, is possible, particularly in the pediatric patient. Our cohort suggests that pediatric intervention beyond the 48-h time interval may still lead to positive outcomes, unlike adult patients. Regardless, randomized controlled trials are needed to determine optimal timing of intervention following symptom onset, as well as to identify predictors for positive outcome in the pediatric population.


Subject(s)
Brain Ischemia/surgery , Decompression, Surgical/methods , Neurosurgical Procedures/methods , Stroke/surgery , Adolescent , Child , Child, Preschool , Cohort Studies , Dura Mater/surgery , Humans , Infant , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/surgery , Postoperative Care , Treatment Outcome
8.
Expert Opin Drug Deliv ; 20(1): 55-73, 2023 01.
Article in English | MEDLINE | ID: mdl-36420918

ABSTRACT

INTRODUCTION: Traumatic brain injuries (TBIs) impact the breadth of society and remain without any approved pharmacological treatments. Despite successful Phase II clinical trials, the failure of many Phase III clinical trials may be explained by insufficient drug targeting and retention, preventing the proper attainment of an observable dosage threshold. To address this challenge, nanoparticles can be functionalized to protect pharmacological payloads, improve targeted drug delivery to sites of injury, and can be combined with supportive scaffolding to improve secondary outcomes. AREAS COVERED: This review briefly covers the pathophysiology of TBIs and their subtypes, the current pre-clinical and clinical management strategies, explores the common models of focal, diffuse, and mixed traumatic brain injury employed in experimental animals, and surveys the existing literature on nanoparticles developed to treat TBIs. EXPERT OPINION: Nanoparticles are well suited to improve secondary outcomes as their multifunctionality and customizability enhance their potential for efficient targeted delivery, payload protection, increased brain penetration, low off-target toxicity, and biocompatibility in both acute and chronic timescales.


Subject(s)
Brain Injuries, Traumatic , Nanoparticles , Animals , Brain Injuries, Traumatic/drug therapy , Brain , Drug Delivery Systems
9.
J Neurosurg Case Lessons ; 5(8)2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36806010

ABSTRACT

BACKGROUND: Superimposed intracranial infection is an uncommon but clinically significant complication in patients with active coronavirus disease 2019 (COVID-19), particularly in those with predisposing immunocompromising conditions. OBSERVATIONS: The authors describe a case of subdural empyema, secondary to extension from pansinusitis, in a 20-year-old otherwise healthy immunocompetent male who was recently diagnosed with COVID-19. Despite his critical condition at time of presentation, he made a full clinical recovery with aggressive multidisciplinary surgical management between neurosurgery and otolaryngology, despite negative cultures to guide directed antimicrobial therapy. Ultimately, use of molecular-based polymerase chain reaction testing diagnosed Aspergillus fumigatus as the offending pathogen after the patient had already recovered and was discharged from the hospital. LESSONS: This case demonstrates the potential for significant superimposed intracranial infection even in young, healthy individuals, infected by COVID-19 and suggests an aggressive surgical approach to achieve source control, particularly in the absence of positive cultures to guide antimicrobial therapies, may lead to rapid clinical improvement.

10.
Int Forum Allergy Rhinol ; 13(11): 2073-2075, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37026426

ABSTRACT

KEY POINTS: 3D printing for virtual surgical planning of nasoseptal flap skull base reconstruction is a viable approach. Results indicate improved mucosal preservation but further research is needed to define impact on quality of life.

11.
J Neurosurg ; 139(6): 1664-1670, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37347618

ABSTRACT

OBJECTIVE: Low-field portable MRI (pMRI) is a recent technological advancement with potential for broad applications. Compared with conventional MRI, pMRI is less resource-intensive with regard to operational costs and scan time. The application of pMRI in neurosurgical oncology has not been previously described. The goal of this study was to demonstrate the efficacy of pMRI in assessing optic nerve decompression after endoscopic endonasal surgery for sellar and suprasellar pathologies. METHODS: Patients who underwent endoscopic endonasal surgery for sellar and suprasellar lesions at a single institution and for whom pMRI and routine MRI were performed postoperatively were retrospectively reviewed to compare the two imaging systems. To assess the relative resolution of pMRI compared with MRI, the distance from the optic chiasm to the top of the third ventricle was measured, and the measurements were compared between paired equivalent slices on T2-weighted coronal images. The inter- and intrarater correlations were analyzed. RESULTS: Twelve patients were included in this study (10 with pituitary adenomas and 2 with craniopharyngiomas) with varying degrees of optic chiasm compression on preoperative imaging. Measurements were averaged across raters before calculating agreement between pMRI and MRI, which demonstrated significant interrater reliability (intraclass correlation coefficient [ICC] = 0.78, p < 0.01). Agreement between raters within the pMRI measurements was also significantly reliable (ICC = 0.93, p < 0.01). Finally, a linear mixed-effects model was specified to demonstrate that MRI measurement could be predicted using the pMRI measurement with the patient and rater set as random effects (pMRI ß coefficient = 0.80, p < 0.01). CONCLUSIONS: The results of this study suggest that resolution of pMRI is comparable to that of conventional MRI in assessing the optic chiasm position in relation to the third ventricle. Portable MRI sufficiently demonstrates decompression of the optic chiasm after endoscopic endonasal surgery. It can be an alternative strategy in cases in which cost, scan-time considerations, or lack of intraoperative MRI availability may preclude the ability to assess adequate optic nerve decompression after endoscopic endonasal surgery for sellar and suprasellar lesions.


Subject(s)
Optic Chiasm , Pituitary Neoplasms , Humans , Optic Chiasm/diagnostic imaging , Optic Chiasm/surgery , Optic Chiasm/pathology , Retrospective Studies , Reproducibility of Results , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/surgery , Pituitary Neoplasms/pathology , Magnetic Resonance Imaging , Decompression
12.
J Neurosurg ; 139(6): 1648-1656, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37243548

ABSTRACT

OBJECTIVE: Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium. METHODS: Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed. RESULTS: A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade-i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival. CONCLUSIONS: Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.


Subject(s)
Meningeal Neoplasms , Meningioma , Supratentorial Neoplasms , Humans , Meningioma/genetics , Meningioma/surgery , Meningioma/complications , Meningeal Neoplasms/genetics , Meningeal Neoplasms/surgery , Meningeal Neoplasms/complications , Mutation/genetics , Genomics , Supratentorial Neoplasms/genetics , Supratentorial Neoplasms/surgery
13.
Curr Oncol ; 29(3): 1408-1421, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35323318

ABSTRACT

Craniopharyngiomas are rare, benign primary brain tumors that arise from remnants of the craniopharyngeal duct epithelium within the sellar and suprasellar region. Despite their benign biology, they may cause significant morbidity, secondary to involvement of nearby eloquent neural structures, such as the pituitary gland, hypothalamus, and optic apparatus. Historically, aggressive surgical resection was the treatment goal to minimize risk of tumor recurrence via open transcranial midline, anterolateral, and lateral approaches, but could lead to clinical sequela of visual, endocrine, and hypothalamic dysfunction. However, recent advances in the endoscopic endonasal approach over the last decade have mostly supplanted transcranial surgery as the optimal surgical approach for these tumors. With viable options for adjuvant radiation therapy, targeted medical treatment, and alternative minimally invasive surgical approaches, the management paradigm for craniopharyngiomas has shifted from aggressive open resection to more minimally invasive but maximally safe resection, emphasizing quality of life issues, particularly in regards to visual, endocrine, and hypothalamic function. This review provides an update on current multi-modal approaches for craniopharyngiomas, highlighting the modern surgical treatment paradigm for this disease entity.


Subject(s)
Craniopharyngioma , Pituitary Neoplasms , Adult , Craniopharyngioma/pathology , Craniopharyngioma/surgery , Humans , Neoplasm Recurrence, Local , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Quality of Life
14.
J Neurol Surg B Skull Base ; 83(2): 105-115, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35433188

ABSTRACT

Introduction Spontaneous cerebrospinal fluid (CSF) leaks represent a unique clinical presentation of idiopathic intracranial hypertension (IIH), lacking classical features of IIH, including severe headaches, papilledema, and markedly elevated opening pressures. Methods Following a single-institution retrospective review of patients undergoing spontaneous CSF leak repair, we performed a literature review of spontaneous CSF leak in patients previously undiagnosed with IIH, querying PubMed. Results Our literature review yielded 26 studies, comprising 716 patients. Average age was 51 years with 80.8% female predominance, and average body mass index was 35.5. Presenting symptoms included headaches (32.5%), visual disturbances (4.2%), and a history of meningitis (15.3%). Papilledema occurred in 14.1%. An empty sella was present in 77.7%. Slit ventricles and venous sinus stenosis comprised 7.7 and 31.8%, respectively. CSF leak most commonly originated from the sphenoid sinus (41.1%), cribriform plate (25.4%), and ethmoid skull base (20.4%). Preoperative opening pressures were normal at 22.4 cm H 2 O and elevated postoperatively to 30.8 cm H 2 O. 19.1% of patients underwent shunt placement. CSF leak recurred after repair in 10.5% of patients, 78.6% involving the initial site. A total of 85.7% of these patients were managed with repeat surgical intervention, and 23.2% underwent a shunting procedure. Conclusion Spontaneous CSF leaks represent a distinct variant of IIH, distinguished by decreased prevalence of headaches, lack of visual deficits, and normal opening pressures. Delayed measurement of opening pressure after leak repair may be helpful to diagnose IIH. Permanent CSF diversion may be indicated in patients exhibiting significantly elevated opening pressures postoperatively, refractory symptoms of IIH, or recurrent CSF leak.

15.
Article in English | MEDLINE | ID: mdl-34667073

ABSTRACT

Glomangiopericytomas are rare, primary sinonasal tumors. The existing literature is mostly limited to reports describing the clinicopathologic characteristics of these tumors. Comprehensive genetic characterization of glomangiopericytomas remains lacking. Whole-exome sequencing of a case of glomangiopericytoma was performed under an institutional review board-approved protocol. A 69-yr-old female underwent surgical resection of a glomangiopericytoma. Whole-exome sequencing revealed somatic mutations in CTNNB1 and PIK3CA, the former previously associated with this pathology but the latter not described. Concurrent dysregulation of Wnt/ß-catenin and PI3K/AKT/mTOR signaling, secondary to mutations in these two oncogenes, may be amenable to targeted treatment with existing clinically approved drugs. Genomic characterization of glomangiopericytomas remains lacking. This study reports novel coexistence of PIK3CA and CTNNB1 mutations in a case of glomangiopericytoma that may offer insight into the pathogenesis and potential for targeted medical therapies of this rare tumor.


Subject(s)
Class I Phosphatidylinositol 3-Kinases , Glomus Tumor/genetics , beta Catenin , Aged , Class I Phosphatidylinositol 3-Kinases/genetics , Female , Humans , Mutation , Oncogenes , beta Catenin/genetics
16.
World Neurosurg ; 162: e251-e263, 2022 06.
Article in English | MEDLINE | ID: mdl-35276399

ABSTRACT

OBJECTIVE: To determine whether baseline frailty is an independent predictor of extended hospital length of stay (LOS), nonroutine discharge, and in-hospital mortality after evacuation of an acute traumatic subdural hematoma (SDH). METHODS: A retrospective cohort study was performed. All adult patients who underwent surgery for an acute traumatic SDH were identified using the National Trauma Database from the year 2017. Patients were categorized into 3 cohorts based on the criteria of the 5-item modified frailty index (mFI-5): mFI = 0, mFI = 1, or mFI = 2+. A multivariate logistic regression analysis was used to identify independent predictors of extended LOS, nonroutine discharge, and in-hospital mortality. RESULTS: Of the 2620 patients identified, 41.7% were classified as mFI = 0, 32.7% as mFI = 1, and 25.6% as mFI = 2+. Rates of extended LOS and in-hospital mortality did differ significantly between the cohorts, with the mFI = 0 cohort most often experiencing a prolonged LOS (mFI = 0: 29.41% vs. mFI = 1: 19.45% vs. mFI = 2+: 19.73%, P < 0.001) and in-hospital mortality (mFI = 0: 24.66% vs. mFI = 1: 18.11% vs. mFI = 2+: 21.58%, P = 0.002). On multivariate regression analysis, when compared with mFI = 0, mFI = 2+ (odds ratio 1.4, P = 0.03) predicted extended LOS and nonroutine discharge (odds ratio 1.61, P = 0.001). CONCLUSIONS: Our study demonstrates that baseline frailty may be an independent predictor of extended LOS and nonroutine discharge, but not in-hospital mortality, in patients undergoing evacuation for an acute traumatic SDH. Further investigations are warranted as they may guide treatment plans and reduce health care expenditures for frail patients with SDH.


Subject(s)
Frailty , Hematoma, Subdural, Acute , Hematoma, Subdural, Intracranial , Adult , Frailty/complications , Hematoma, Subdural/surgery , Hematoma, Subdural, Acute/surgery , Humans , Morbidity , Postoperative Complications/epidemiology , Retrospective Studies
17.
Case Rep Genet ; 2021: 5586072, 2021.
Article in English | MEDLINE | ID: mdl-33747576

ABSTRACT

Intracranial undifferentiated pleomorphic sarcoma remains a rare pathology within the sarcoma literature that may arise primarily or secondary after radiation therapy. Despite first-line treatment with maximal surgical resection, followed by nonstandardized adjuvant chemotherapy/radiation regimens, clinical prognosis remains exceedingly poor. Furthermore, there is a lack of genetic or molecular characterization to guide potential for targeted therapies. We present genomic analysis of a radiation-induced intracranial undifferentiated pleomorphic sarcoma in an 83-year-old woman with notable KIT and PDGFRA alterations. Further similar genomic studies of intracranial pleomorphic sarcoma are needed to develop better therapies for this rare but challenging disease entity.

18.
Cancers (Basel) ; 13(5)2021 Mar 02.
Article in English | MEDLINE | ID: mdl-33801444

ABSTRACT

Little is known about the subcellular localization and function of programmed cell death 4 (PDCD4) in melanoma. Our past studies suggest PDCD4 interacts with Pleckstrin Homology Domain Containing A5 (PLEKHA5) to influence melanoma brain metastasis outcomes, as high intracranial PDCD4 expression leads to improved survival. We aimed to define the subcellular distribution of PDCD4 in melanoma and in the tumor microenvironment during neoplastic progression and its impact on clinical outcomes. We analyzed multiple tissue microarrays with well-annotated clinicopathological variables using quantitative immunofluorescence and evaluated single-cell RNA-sequencing on a brain metastasis sample to characterize PDCD4+ immune cell subsets. We demonstrate differences in PDCD4 expression during neoplastic progression, with high tumor and stromal PDCD4 levels associated with improved survival in primary melanomas and in intracranial metastases, but not in extracranial metastatic disease. While the expression of PDCD4 is well-documented on CD8+ T cells and natural killer cells, we show that it is also found on B cells and mast cells. PDCD4 expression in the tumor microenvironment is associated with increased immune cell infiltration. Further studies are needed to define the interaction of PDCD4 and PLEKHA5 and to evaluate the utility of this pathway as a therapeutic target in melanoma brain metastasis.

19.
J Clin Neurosci ; 78: 420-422, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32336638

ABSTRACT

Gigantism (early-onset acromegaly) is a rare pediatric disorder caused by a growth hormone (GH)-secreting pituitary adenoma. Approximately 50% patients of gigantism have a germline mutation, most commonly an inactivating mutation in the aryl-hydrocarbon interacting receptor protein (AIP) gene on chromosome 11q13.2. We present an 11-year-old male patient with a GH-secreting pituitary macroadenoma who presented with excessive growth spurts, behavioral changes, and frontal headaches. He was successfully treated with an endoscopic endonasal gross total resection and subsequently demonstrated biochemical cure. Whole-exome sequencing showed a heterozygous germline mutation in the AIP gene suggesting pituitary adenoma predisposition. Analysis of the tumor tissue revealed a large-scale deletion on chromosome 11 overlapping with AIP leading to bi-allelic AIP loss. Coincident germline and somatic AIP mutations were likely causal in formation of a GH-secreting adenoma with an aggressive phenotype. This case exemplifies the need for early diagnosis and curative surgery in the management of AIP-mutated pituitary adenomas.


Subject(s)
Germ-Line Mutation , Gigantism/etiology , Growth Hormone-Secreting Pituitary Adenoma/complications , Intracellular Signaling Peptides and Proteins/genetics , Pituitary Neoplasms/pathology , Child , Chromosomes, Human, Pair 11/genetics , Gigantism/genetics , Growth Hormone-Secreting Pituitary Adenoma/pathology , Growth Hormone-Secreting Pituitary Adenoma/surgery , Heterozygote , Humans , Male , Phenotype , Pituitary Neoplasms/genetics , Sequence Deletion
20.
Endocrine ; 68(3): 489-501, 2020 06.
Article in English | MEDLINE | ID: mdl-32162185

ABSTRACT

Magnetic resonance (MR) imaging is an essential tool in the diagnosis and management of pituitary diseases, indispensable for making correct treatment decisions. Successful management and follow-up of pituitary pathology requires an understanding of the MR appearance of normal and abnormal structures in the sellar region. This review will describe the MR appearance of the normal and abnormal pituitary gland and proposes an algorithm for the management strategy of some of the most common abnormalities in or around the sella.


Subject(s)
Pituitary Diseases , Pituitary Neoplasms , Humans , Magnetic Resonance Imaging , Pituitary Diseases/diagnostic imaging , Pituitary Diseases/therapy , Pituitary Gland/diagnostic imaging , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/therapy , Sella Turcica
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