Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus.

Tumor interferon (IFN) signaling promotes PD-L1 expression to suppress T cell-mediated immunosurveillance. We identify the IFN-stimulated non-coding RNA 1 (INCR1) as a long noncoding RNA (lncRNA) transcribed from the PD-L1 locus and show that INCR1 controls IFNγ signaling in multiple tumor types. Silencing INCR1 decreases the expression of PD-L1, JAK2, and several other IFNγ-stimulated genes. INCR1 knockdown sensitizes tumor cells to cytotoxic T cell-mediated killing, improving CAR T cell therapy. We discover that PD-L1 and JAK2 transcripts are negatively regulated by binding to HNRNPH1, a nuclear ribonucleoprotein. The primary transcript of INCR1 binds HNRNPH1 to block its inhibitory effects on the neighboring genes PD-L1 and JAK2, enabling their expression. These findings introduce a mechanism of tumor IFNγ signaling regulation mediated by the lncRNA INCR1 and suggest a therapeutic target for cancer immunotherapy.

Treatment of Pediatric Low-Grade Gliomas.

PURPOSE OF REVIEW: Pediatric low-grade gliomas and glioneuronal tumors (pLGG) account for approximately 30% of pediatric CNS neoplasms, encompassing a heterogeneous group of tumors of primarily glial or mixed neuronal-glial histology. This article reviews the treatment of pLGG with emphasis on an individualized approach incorporating multidisciplinary input from surgery, radiation oncology, neuroradiology, neuropathology, and pediatric oncology to carefully weigh the risks and benefits of specific interventions against tumor-related morbidity. Complete surgical resection can be curative for cerebellar and hemispheric lesions, while use of radiotherapy is restricted to older patients or those refractory to medical therapy. Chemotherapy remains the preferred first-line therapy for adjuvant treatment of the majority of recurrent or progressive pLGG. RECENT FINDINGS: Technologic advances offer the potential to limit volume of normal brain exposed to low doses of radiation when treating pLGG with either conformal photon or proton RT. Recent neurosurgical techniques such as laser interstitial thermal therapy offer a "dual" diagnostic and therapeutic treatment modality for pLGG in specific surgically inaccessible anatomical locations. The emergence of novel molecular diagnostic tools has enabled scientific discoveries elucidating driver alterations in mitogen-activated protein kinase (MAPK) pathway components and enhanced our understanding of the natural history (oncogenic senescence). Molecular characterization strongly supplements the clinical risk stratification (age, extent of resection, histological grade) to improve diagnostic precision and accuracy, prognostication, and can lead to the identification of patients who stand to benefit from precision medicine treatment approaches. The success of molecular targeted therapy (BRAF inhibitors and/or MEK inhibitors) in the recurrent setting has led to a gradual and yet significant paradigm shift in the treatment of pLGG. Ongoing randomized trials comparing targeted therapy to standard of care chemotherapy are anticipated to further inform the approach to upfront management of pLGG patients.

Fourth ventricular subarachnoid stent for Chiari malformation type I-associated persistent syringomyelia.

OBJECTIVE: Syringomyelia (syrinx) associated with Chiari malformation type I (CM-I) is commonly managed with posterior fossa decompression, which can lead to resolution in most cases. A persistent syrinx postdecompression is therefore uncommon and challenging to address. In the setting of radiographically adequate decompression with persistent syrinx, the authors prefer placing fourth ventricular subarachnoid stents that span the craniocervical junction particularly when intraoperative observation reveals arachnoid plane scarring. The objective of this study was to evaluate the safety and efficacy of a fourth ventricle stent for CM-I-associated persistent syringomyelia, assess dynamic changes in syrinx dimensions, and report stent-reduction durability, clinical outcomes, and procedure-associated complications. METHODS: The authors performed a single-institution, retrospective review of patients who underwent fourth ventricular subarachnoid stent placement for persistent CM-I-associated syringomyelia following a prior posterior fossa decompression. The authors' institutional Chiari database contains 600 cases with 149 decompressions for CM-I-associated syringomyelia, of which 13 met criteria for inclusion. Data on patient demographics, clinical presentation and outcomes, and MRI findings were collected. The maximal syrinx diameter was estimated by calculating the area of an elliptical cross-section in the largest axial plane from preoperative, immediately postoperative, and late postoperative T2-weighted MR images. RESULTS: All 13 patients experienced a significant decrease in mean syrinx area from the preoperative to the late postoperative MRI (mean syrinx diameter 114.1 ± 81.8 mm2 vs 24.5 ± 23.8 mm2, p < 0.001). The mean time until late postoperative MRI was 19.7 months (range 2.0-70.7 months). The syrinx area reduced on average by 75.0% ± 23.9% at the time of the last postoperative scan. Syrinx resolution was variable, with 4 patients (30.8%) achieving near-complete resolution (> 90%, grade III reduction), 7 patients (50%) having 50%-90% reduction (grade II), and 2 patients (14.3%) having < 50% decrease (grade I). One patient experienced catheter migration into the left brachium pontis with an associated cyst at the tip of the catheter that decreased in size on follow-up imaging. CONCLUSIONS: Placement of fourth ventricular subarachnoid stents spanning the craniocervical junction in patients with persistent CM-I-associated syringomyelia after posterior fossa decompression is a safe therapeutic option and significantly reduced the mean syrinx area, with a greater reductive effect seen over longer follow-up periods.

Histology of high-grade glioma samples resected using 5-ALA fluorescent headlight and loupe combination.

PURPOSE: 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection of high-grade gliomas (HGG) increases the extent of resection (EOR) and progression-free survival. The headlamp/loupe combination has been introduced as a method of performing fluorescent-guided surgery. This study aims to understand the correlation between fluorescent intensity and histology and between residual fluorescence and radiographic EOR utilizing the headlamp/loupe device. METHODS: Intraoperative samples resected using the headlamp/loupe device from 14 patients were labeled as PINK, VAGUE, or NEGATIVE depending on the degree of fluorescence. Histological assessment of microvascular proliferation, necrosis, and cell density was performed, and samples were classified as histologically consistent with glioblastoma (GBM), high-grade infiltrating glioma (HGIG), IG, or non-diagnostic (NDX). The presence of intraoperative residual fluorescence was compared to EOR on post-operative MRI. RESULTS: There was a significant difference in cell density comparing PINK, VAGUE, and NEGATIVE specimens (ANOVA, p < 0.00001). The PPV of PINK for GBM or HGIG was 88.4% (38/43). The NPV of NEGATIVE for IG or NDX was 74.4% (29/39). The relationship between the degree of fluorescence determination and histological results was significant (X2 (6 degrees of freedom, N = 101) = 42.57, p < 0.00001). The PPV of intraoperative GTR for post-operative GTR on MRI was 100%, while the NPV of intraoperative STR for post-operative STR on MRI was 60%. CONCLUSION: The headlamp/loupe device provides information about histology, cell density, and necrosis with similar PPV for tumor to the operative microscope. Safe complete resection of florescence has a PPV of 100% for radiographic GTR and should be the goal of surgery.

Familial colloid cysts: not a chance occurrence.

PURPOSE: Colloid cysts are rare, benign brain tumors of the third ventricle with an estimated population prevalence of 1 in 5800. Sudden deterioration and death secondary to obstructive hydrocephalus are well-described presentations in patients with a colloid cyst. Although historically conceptualized as driven by sporadic genetic events, a growing body of literature supports the possibility of an inherited predisposition. METHODS: A prospective registry of patients with colloid cysts was maintained between 1996 and 2021. Data pertaining to a family history of colloid cyst was collected retrospectively; self-reporting was validated in each case by medical record or imaging review. Frequency of patients with a documented first-degree family member with a colloid cyst based on self-reporting was calculated. The rate of familial co-occurrence within our series was then compared to a systematic literature review and aggregation of familial case studies, as well as population-based prevalence rates of sporadic colloid cysts. RESULTS: Thirteen cases with affected first-degree relatives were identified in our series. Of the entire cohort, 19/26 were symptomatic from the lesion (73%), 12/26 (46.2%) underwent resection, and 2/26 (7.7%) had sudden death from presumed obstructive hydrocephalus. The majority of transmission patterns were between mother and child (9/13). Compared with the estimated prevalence of colloid cysts, our FCC rate of 13 cases in 383 (3.4%) estimates a greater-than-chance rate of co-occurrence. CONCLUSION: Systematic screening for FCCs may facilitate early recognition and treatment of indolent cysts, thereby preventing the rapid deterioration that can occur with an unrecognized third ventricular tumor. Furthermore, identifying a transmission pattern may yield more insight into the molecular and genetic underpinnings of colloid cysts.

Salvage resection plus cesium-131 brachytherapy durably controls post-SRS recurrent brain metastases.

BACKGROUND: Salvage of recurrent previously irradiated brain metastases (rBrM) is a significant challenge. Resection without adjuvant re-irradiation is associated with a high local failure rate, while reirradiation only partially reduces failure but is associated with greater radiation necrosis risk. Salvage resection plus Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced normal brain dose versus re-irradiation, however data are limited. METHODS: A prospective registry of consecutive patients with post-stereotactic radiosurgery (SRS) rBrM undergoing resection plus implantation of collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60 Gy at 5 mm from the cavity was analyzed. RESULTS: Twenty patients underwent 24 operations with Cs131 implantation in 25 tumor cavities. Median maximum preoperative diameter was 3.0 cm (range 1.1-6.3). Gross- or near-total resection was achieved in 80% of lesions. A median of 16 Cs131 seeds (range 6-30), with a median air-kerma strength of 3.5 U/seed were implanted. There was one postoperative wound dehiscence. With median follow-up of 1.6 years for survivors, two tumors recurred (one in-field, one marginal) resulting in 8.4% 1-year progression incidence (95%CI = 0.0-19.9). Radiographic seed settling was identified in 7/25 cavities (28%) 1.9-11.7 months post-implantation, with 1 case of distant migration (4%), without clinical sequelae. There were 8 cases of radiation necrosis, of which 4 were symptomatic. CONCLUSIONS: With > 1.5 years of follow-up, intraoperative brachytherapy with commercially available Cs131 implants was associated with favorable local control and toxicity profiles. Weak correlation between preoperative tumor geometry and implanted tiles highlights a need to optimize planning criteria.

Barriers to Pursuing a Career in Surgery: An Institutional Survey of Harvard Medical School Students.

OBJECTIVE: This study aimed to elucidate current medical student perceptions on barriers to a career in surgery, with a particular focus on gender-specific differences. SUMMARY BACKGROUND DATA: Although gender parity in medical school composition has been reached, women continue to be underrepresented in the field of surgery. METHODS: An anonymous, single-institution, internet-based survey conducted at Harvard Medical School. RESULTS: Approximately 720 medical students were surveyed and 261 completed the questionnaire (36.3%; 58.6% women, 41% men, 0.4% transgender). Overall, there was no significant gender difference in intention to pursue surgery (27% of men, 22% of women; P = 0.38). Sixty-nine percent of all students and 75% of those pursuing surgery reported verbal discouragement from pursuing a surgical career. Women were significantly more likely to perceive that the verbal discouragement was based on gender (P < 0.0001), age (P < 0.0001), and family aspirations (P = 0.043) compared to men. Surgical work hours and time for outside interests were the greatest deterrents for both genders. Significantly more women reported concerns about time to date or marry (P = 0.042), time to spend with family (P = 0.015), finding time during residency to have a child (P < 0.0001), taking maternity/paternity leave during residency (P < 0.0001), and being too old after residency to have a child (P < 0.0001). CONCLUSIONS: Both men and women reported high rates of verbal discouragement, but more women perceived that the discouragement was gender-based. Concerns about marriage and childbearing/rearing significantly deterred more women than men. Family aspirations were also a significant factor for men to choose an alternative career path. Additional support within the surgical field is needed to mitigate these concerns and support trainees in both their career and familial aspirations.

Impact of the COVID-19 pandemic on neuro-oncology outcomes.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic has uprooted healthcare systems worldwide, disrupting care and increasing dependence on alternative forms of health care delivery. It is yet to be determined how the pandemic affected neuro-oncology patient outcomes, given that the majority of even "elective" neurosurgical oncology procedures are time-sensitive. This study quantifies changes in neuro-oncological care during the height of the pandemic and investigates patient outcomes in 2020 compared to a historical control. METHODS: We performed a retrospective review of patients with malignant brain tumor diagnoses who were seen at our institution between March 13 and May 1 of 2020 and 2019. Alterations in care, including shift from in-person to telehealth, delays in evaluation and intervention, and treatment modifications were evaluated. These variables were analyzed with respect to brain tumor control and mortality. RESULTS: 112 patients from 2020 to 166 patients from 2019 were included. There was no significant difference in outcomes between the cohorts, despite significantly more treatment delays (p = 0.0160) and use of telehealth (p < 0.0001) in 2020. Patients in 2020 who utilized telehealth visits had significantly more stable tumor control than those who had office visits (p = 0.0124), consistent with appropriate use of in-person visits for patients with progression. CONCLUSIONS: Our study showed that use of telehealth and selective alterations in neuro-oncological care during the COVID-19 pandemic did not lead to adverse patient outcomes. This suggests that adaptive physician-led changes were successful and may inform management during the ongoing pandemic, especially with the emergence of the Delta variant.

Interdisciplinary data science to advance environmental health research and improve birth outcomes.

Rates of preterm birth and low birthweight continue to rise in the United States and pose a significant public health problem. Although a variety of environmental exposures are known to contribute to these and other adverse birth outcomes, there has been a limited success in developing policies to prevent these outcomes. A better characterization of the complexities between multiple exposures and their biological responses can provide the evidence needed to inform public health policy and strengthen preventative population-level interventions. In order to achieve this, we encourage the establishment of an interdisciplinary data science framework that integrates epidemiology, toxicology and bioinformatics with biomarker-based research to better define how population-level exposures contribute to these adverse birth outcomes. The proposed interdisciplinary research framework would 1) facilitate data-driven analyses using existing data from health registries and environmental monitoring programs; 2) develop novel algorithms with the ability to predict which exposures are driving, in this case, adverse birth outcomes in the context of simultaneous exposures; and 3) refine biomarker-based research, ultimately leading to new policies and interventions to reduce the incidence of adverse birth outcomes.

Immune profiling of pituitary tumors reveals variations in immune infiltration and checkpoint molecule expression.

PURPOSE: Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities. METHODS: 72 pituitary tumors were evaluated for expression of the immune regulatory markers programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and tumor necrosis factor receptor superfamily member 4 (OX40) by immunohistochemistry (IHC). Lymphocyte infiltration, macrophage infiltration, and angiogenesis were analyzed using IHC. Expression of pituitary tumor initiating cell marker CD15 and mismatch repair proteins MutS protein homolog 2 (MSH2) and MutS protein homolog 6 (MSH6) was also assessed. RESULTS: Pituitary tumors were infiltrated by macrophages and T cells, and they expressed varying levels of PD-L1, PD-L2, VISTA, LAG3, and OX40. Functional tumors and tumors with high expression of tumor stem cell markers had higher immune cell infiltration and greater expression of immunosuppressive checkpoint regulators. Increased PD-L1 and LAG3 and reduced VISTA were observed in primary tumors compared to recurrent tumors. CONCLUSION: Immune cell infiltration and checkpoint regulator expression vary depending on functional status and presence of pituitary tumor initiating cells. Functional tumors may have a particularly immunosuppressive microenvironment. Further studies of immune checkpoint blockade of pituitary tumors, particularly functional tumors, are warranted, though combination therapy may be required.

Eyebrow supraorbital keyhole craniotomy for olfactory groove meningiomas with endoscope assistance: case series and systematic review of extent of resection, quantification of postoperative frontal lobe injury, anosmia, and recurrence.

BACKGROUND: Olfactory groove meningiomas (OGMs) are commonly treated with open craniotomy. Endonasal approaches have also been described. OBJECTIVE: To present clinical and radiographic outcomes for the minimally invasive eyebrow incision supraorbital keyhole approach with endoscopic assistance for OGMs. METHODS: We performed a retrospective single-center cohort study and a systematic literature review. RESULTS: Fifteen patients were identified, all with Grade I meningiomas. Radiographic gross total resection of enhancing tumor was achieved in all patients. Mean frontal lobe fluid-attenuated inversion recovery volume decreased from 11.1 ± 18.3 cm3 preoperatively to 9.9 ± 11.4 cm3 immediately postoperatively, and there was minimal new restricted diffusion (3.2 ± 2.2 cm3; max 7.5 cm3). Median length of stay was 3 days (range 2-8). Vision was improved in 4 (80%) and stable in 1 (20%) of 5 patients with a preoperative deficit. New postoperative anosmia occurred in 3 (23%) of 13 patients with any preoperative olfaction. All patients were satisfied with their cosmetic result at 3 months. After a median follow-up of 32.2 months, there were 2 (13.3%) asymptomatic radiographic recurrences, 1 treated with radiosurgery and the other with endoscopic endonasal approach (EEA). No patients required further craniotomy. Systematic review revealed the present series to be the largest to date reporting disaggregated outcomes for the eyebrow approach to OGM. CONCLUSION: The eyebrow incision supraorbital keyhole craniotomy with endoscopic assistance is a safe and effective approach to OGM with tumor control rates similar to more invasive open approaches and better than the endonasal approach. Rates of frontal lobe injury, CSF leak and anosmia are comparatively low.

Genomic Alterations in Sporadic Pituitary Tumors.

PURPOSE OF REVIEW: Pituitary tumors are undergoing a transformation in histopathologic and molecular classification, coincident with the continued refinement of increasingly powerful methods of genomic annotation and discovery. We highlight novel genomic alterations identified in pituitary adenomas and craniopharyngiomas and discuss their clinical implications. RECENT FINDINGS: Sporadic pituitary adenomas are associated with relatively few recurrent somatic mutations. Recurrent mutations occur largely in subsets of hormone-producing tumors, including GNAS and GPR101 in somatotroph adenomas and USP8 in corticotroph adenomas. Additionally, they manifest with a dichotomous signature of copy number alterations, ranging from almost none to widespread genome instability, while microduplication of chromosome Xq26.3, containing the GNAS gene, defines X-linked acrogigantism. Papillary craniopharyngiomas are defined by BRAF V600E mutations while ß-catenin alterations characterize adamantinomatous craniopharyngiomas. Genomic annotation of pituitary tumors is defining increasing subsets of neuroendocrine adenohypophyseal tumors and craniopharyngiomas, offering rationale-based pharmacologic targets and potential biomarkers for clinical outcome.

Craniopharyngioma: a roadmap for scientific translation.

OBJECTIVE Craniopharyngiomas are among the most challenging of intracranial tumors to manage because of their pattern of growth, associated morbidities, and high recurrence rate. Complete resection on initial encounter can be curative, but it may be impeded by the risks posed by the involved neurovascular structures. Recurrent craniopharyngiomas, in turn, are frequently refractory to additional surgery and adjuvant radiation or chemotherapy. METHODS The authors conducted a review of primary literature. RESULTS Recent advances in the understanding of craniopharyngioma biology have illuminated potential oncogenic targets for pharmacotherapy. Specifically, distinct molecular profiles define two histological subtypes of craniopharyngioma: adamantinomatous and papillary. The discovery of overactive B-Raf signaling in the adult papillary subtype has led to reports of targeted inhibitors, with a growing acceptance for refractory cases. An expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies that are personalized to the molecular signature of each individual tumor. CONCLUSIONS The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.

Risk factors for post-operative respiratory failure among 94,621 neurosurgical patients from 2006 to 2013: a NSQIP analysis.

INTRODUCTION: Post-operative respiratory failure can occur after neurosurgical operations. Identification of risk factors for respiratory failure after neurosurgery may help guide clinical decision-making, decrease length of stay, improve patient outcomes, and lower costs. METHODS: We performed a search of the ACS-NSQIP database for all patients undergoing operations with a neurosurgeon from 2006 to 2013. We analyzed demographics, past medical history, and post-operative respiratory failure, defined as unplanned intubation and/or ventilator dependence for more than 48 h post-operatively. RESULTS: Of 94,621 NSQIP-reported neurosurgical patients from 2006 to 2013, 2325 (2.5 %) developed post-operative respiratory failure. Of these patients, 1270 (54.6 %) were male, with an overall mean age of 60.59 years; 571 (24.56 %) were current smokers and 756 (32.52 %) were ventilator-dependent. Past medical history included dyspnea in 204 patients (8.8 %), COPD in 198 (8.5 %), and congestive heart failure in 66 (2.8 %). The rate of post-operative respiratory failure decreased from 4.1 % in 2006 to 2.1 % in 2013 (p < 0.001). Of the 2325 patients with respiratory failure, 1061 (45.6 %) underwent unplanned intubation post-operatively and 1900 (81.7 %) were ventilator-dependent for more than 48 h. The rate of both unplanned intubation (p < 0.001) and ventilator dependence (p < 0.001) decreased significantly from 2006 to 2013. Multivariate analysis demonstrated that significant risk factors for respiratory failure included inpatient status (p < 0.001, OR = 0.165), age (p < 0.001, OR = 1.014), diabetes (p = 0.001, OR = 1.489), functional dependence prior to surgery (p < 0.001, OR = 2.081), ventilator dependence (p < 0.001, OR = 10.304), hypertension requiring medication (p = 0.005, OR = 1.287), impaired sensorium (p < 0.001, OR = 2.054), CVA/stroke with or without neurological deficit (p < 0.001, OR = 2.662; p = 0.002, OR = 1.816), systemic sepsis (p < 0.001, OR = 1.916), prior operation within 30 days (p = 0.026, OR = 1.439), and operation type (cranial relative to spine, p < 0.001, OR = 4.344, Table 4). CONCLUSIONS: Based on the NSQIP database, risk factors for respiratory failure after neurosurgery include pre-operative ventilator dependence, alcohol use, functional dependence prior to surgery, stroke, and recent operation. The overall rate of respiratory failure decreased from 4.1 % in 2006 to 2.1 % in 2013 according to these data.

Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary.

PURPOSE: Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. METHODS: The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. RESULTS: GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (p < 0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (p < 0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (p < 0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke's remnant, the putative pituitary stem cell niche, and in corticotropes. CONCLUSION: Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis.

Separation surgery for metastatic spine tumors: How less became more.

Metastatic epidural spinal cord compression (MESCC) is an increasingly common clinical entity in cancer patients and is associated with significant morbidity and neurologic sequalae. Management of MESCC has undergone many significant paradigms shifts over the past 50 years and was at times managed exclusively with either surgery or radiation. Historically, aggressive surgical techniques to achieve en bloc or intralesional gross tumor resections were pursued but were associated with significant morbidity and poor tumor control rates when combined with conventional external beam radiation. However, improvements in radiation treatment delivery in the form of stereotactic body radiation therapy have allowed for the safe delivery of high-dose conformal photon beam radiation providing histology-independent ablative responses. This shifted the goals of surgery away from maximal tumor resection toward simple spinal cord decompression with reconstitution of the thecal to create a tumor target volume capable of being irradiated within the constraints of spinal cord tolerance. This new approach of creating space between the thecal sac and the tumor was termed separation surgery and when combined with postoperative SBRT, it is referred to as hybrid therapy. Herein, we will describe the evolution of the management of MESCC, the technique of separation surgery and its outcomes, and finish with an illustrative case example.

Compliance With Federal Price Transparency Rules and Cost Estimation at United States Hospitals With Neurosurgical Training Programs.

BACKGROUND AND OBJECTIVES: The Centers for Medicare & Medicaid Services implemented federal requirements on January 1, 2021, under the Public Health Service Act that require hospitals to provide a list of payer-negotiated prices or "standard charges" in a machine-readable file and in a patient-friendly online estimator for standard services. We sought to assess compliance by United States hospitals associated with neurosurgical training programs with these federal requirements for 11 common neurosurgical procedures. METHODS: We performed a cross-sectional analysis in March 2023 of 116 United States hospitals associated with a neurosurgical training program to assess compliance with the new federal requirements to have a machine-readable, downloadable file with standard charges and a patient-friendly online estimator for two spinal procedures. RESULTS: A total of 110/114 (96.5%) hospitals were compliant with the requirement for a machine-readable file with payer-negotiated prices. A total of 47/110 hospitals (42.7%) were compliant with downloadable machine-readable files and reported at least one payer-negotiated price for 1 of the 11 common neurosurgical procedures. A total of 45/110 (40.9%) used bundled Diagnosis-Related Group codes, and 18/110 (16.4%) did not contain any price information for neurosurgical procedures. For neurosurgical procedures, the percent difference between the average negotiated private insurance and Medicare price per procedure ranged from 17.5% to 77.6%. Medicare and private insurance data for each procedure were available on average for 10.3 states (SD = 3.8) and 15.6 states (SD = 4.8), respectively. CONCLUSION: While hospital compliance with federal requirements for machine-readable files with payer-negotiated prices was high, availability of payer-negotiated prices for 4 major insurance types across 11 common neurosurgical procedures based on Current Procedural Terminology codes was sparce. Consequently, meaningful conclusions on procedure-related charges for elective procedures are difficult for patients to make because of the unintelligible format of data and a lack of reporting of charges per Current Procedural Terminology code in a comprehensive manner.

Treatment and outcomes of IDH1-mutant gliomas in elderly patients.

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutations in both high- and low-grade gliomas are associated with an increase in survival compared with IDH-wild-type (IDHwt) tumors. A rare and understudied population is elderly individuals, ≥ 65 years of age, who have IDH1-R132H-mutant (IDHmt) gliomas. The objective of this paper was to characterize the institutions' experience with IDHmt gliomas in a patient population ≥ 65 years of age over the last 10 years. METHODS: A retrospective study of individuals ≥ 65 years of age with IDHmt gliomas treated between 2010 and 2020 at Memorial Sloan Kettering was performed. RESULTS: Twenty-five patients ≥ 65 years of age underwent resection or biopsy with a diagnosis of IDHmt glioma (52% WHO grade II, 32% WHO grade III, and 16% WHO grade IV). The most common presenting symptoms were seizure (28%) and motor or sensory deficits (24%). On preoperative MRI, 56% of tumors demonstrated contrast enhancement and 44% had no enhancement. Most patients underwent craniotomy for resection (n = 23, 92%), with subtotal resection achieved in the majority (16/23, 69.6%). Postoperative discharge location included home (64%), acute rehabilitation (16%), subacute rehabilitation (8%), and unknown (12%). Most patients received postoperative chemotherapy (72%) and radiation therapy (68%). The 2- and 5-year survival rates for the overall cohort were 83.1% (95% CI 69.3%-99.7%) and 69.7% (95% CI 53.2%-91.3%), respectively, with gross-total resection or near-total resection, contrast enhancement, and WHO grade significantly associated with survival. From the clinical sequencing data, no significant differences were identified between younger and older IDHmt cohorts. CONCLUSIONS: While IDH mutation in elderly patients may be rare, these patients have favorable survival relative to their IDHwt counterparts. Age at diagnosis should not be used in isolation to suggest a molecular IDHwt status or poor prognosis when guiding patient treatment decisions.

Cerebrospinal Fluid Leaks: Challenges in Localizing Spontaneous Spinal Leak Sites and Minimally Invasive Treatment.

The confirmation of cerebrospinal fluid (CSF) leaks in the setting of spontaneous intracranial hypotension (SIH) by imaging involves a growing toolset of multimodal advanced spinal and skull base imaging techniques, for which exists a unique set of challenges for each CSF leak type. Furthermore, the repertoire of minimally invasive CSF leak treatment beyond nontargeted epidural blood patch administration has grown widely, with varied practices across institutions. This review describes current diagnostic imaging and treatment modalities as they apply to the challenges of CSF leak localization and management.