RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

Effects of immune checkpoint blockade on antigen-specific CD8+ T cells for use in adoptive cellular therapy.

Adoptive T-cell therapies have been successfully used as prophylaxis or treatment for immunocompromised patients at risk of viral infections or advanced cancers. Unfortunately, for some refractory cancers, they have failed. To overcome this, checkpoint inhibitors are used to rescue immune antitumor responses. We hypothesized that in vitro checkpoint blockade during T-cell stimulation and expansion with messenger RNA (mRNA)-pulsed DCs may enhance the activity of antigen-specific T cells and improve the efficacy of adoptive cellular therapy platforms. Human peripheral blood mononuclear cells were isolated from cytomegalovirus (CMV)-seropositive donors to generate DCs. These were pulsed with CMV matrix phosphoprotein 65 (CMVpp65)-mRNA to educate T cells in coculture for 15 days. Three checkpoint blockade conditions were evaluated (anti-PD1, anti-Tim3, and anti-PD1 + Tim3). IL-2 and antibodies blockades were added every 3 days. Immunophenotyping was performed on Day 0 and Day 15. Polyfunctional antigen-specific responses were evaluated upon rechallenge with CMVpp65 peptides. CMVpp65-activated CD8+ T cells upregulate Lag3 and Tim3 (P ≤ 0.0001). Tim3 antibody blockade alone or in combination led to a significant upregulation of Lag3 expression on CD8+ pp65Tetramer+ central memory, effector memory, and terminal effector memory cells re-expressing RA (TEMRA) T cells. This latter T-cell subset uniquely maintains double-positive Tim3/Lag3 expression after checkpoint blockade. By contrast, PD1 blockade had minimal effects on Tim3 or Lag3 expression. In addition, IFN-γ secretion was reduced in T cells treated with Tim3 blockade in a dose-dependent manner (P = 0.004). In this study, we have identified a potential activating component of Tim3 and linkage between Tim3 and Lag3 signaling upon blocking the Tim3 axis during T-cell-antigen-presenting cell interactions that should be considered when targeting immune checkpoints for clinical use.

Double pituitary adenomas are most commonly associated with GH- and ACTH-secreting tumors: systematic review of the literature.

INTRODUCTION: Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined. METHODS: Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: "double pituitary adenomas", "multiple pituitary adenomas" and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included. RESULTS: We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting. CONCLUSION: Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing's Disease.

mRNA-based precision targeting of neoantigens and tumor-associated antigens in malignant brain tumors.

BACKGROUND: Despite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically "cold" tumor microenvironment that hampers the generation of sustained and productive immunologic responses. The field of mRNA-based therapeutics has experienced a boon following the universal approval of COVID-19 mRNA vaccines. mRNA-based immunotherapeutics have also garnered widespread interest for their potential to revolutionize cancer treatment. In this study, we developed a novel and scalable approach for the production of personalized mRNA-based therapeutics that target multiple tumor rejection antigens in a single therapy for the treatment of refractory brain tumors. METHODS: Tumor-specific neoantigens and aberrantly overexpressed tumor-associated antigens were identified for glioblastoma and medulloblastoma tumors using our cancer immunogenomics pipeline called Open Reading Frame Antigen Network (O.R.A.N). Personalized tumor antigen-specific mRNA vaccine was developed for each individual tumor model using selective gene capture and enrichment strategy. The immunogenicity and efficacy of the personalized mRNA vaccines was evaluated in combination with anti-PD-1 immune checkpoint blockade therapy or adoptive cellular therapy with ex vivo expanded tumor antigen-specific lymphocytes in highly aggressive murine GBM models. RESULTS: Our results demonstrate the effectiveness of the antigen-specific mRNA vaccines in eliciting robust anti-tumor immune responses in GBM hosts. Our findings substantiate an increase in tumor-infiltrating lymphocytes characterized by enhanced effector function, both intratumorally and systemically, after antigen-specific mRNA-directed immunotherapy, resulting in a favorable shift in the tumor microenvironment from immunologically cold to hot. Capacity to generate personalized mRNA vaccines targeting human GBM antigens was also demonstrated. CONCLUSIONS: We have established a personalized and customizable mRNA-therapeutic approach that effectively targets a plurality of tumor antigens and demonstrated potent anti-tumor response in preclinical brain tumor models. This platform mRNA technology uniquely addresses the challenge of tumor heterogeneity and low antigen burden, two key deficiencies in targeting the classically immunotherapy-resistant CNS malignancies, and possibly other cold tumor types.

Expanded specific T cells to hypomutated regions of the SARS-CoV-2 using mRNA electroporated antigen-presenting cells.

The COVID-19 pandemic has caused about seven million deaths worldwide. Preventative vaccines have been developed including Spike gp mRNA-based vaccines that provide protection to immunocompetent patients. However, patients with primary immunodeficiencies, patients with cancer, or hematopoietic stem cell transplant recipients are not able to mount robust immune responses against current vaccine approaches. We propose to target structural SARS-CoV-2 antigens (i.e., Spike gp, Membrane, Nucleocapsid, and Envelope) using circulating human antigen-presenting cells electroporated with full length SARS-CoV-2 structural protein-encoding mRNAs to activate and expand specific T cells. Based on the Th1-type cytokine and cytolytic enzyme secretion upon antigen rechallenge, we were able to generate SARS-CoV-2 specific T cells in up to 70% of unexposed unvaccinated healthy donors (HDs) after 3 subsequent stimulations and in 100% of recovered patients (RPs) after 2 stimulations. By means of SARS-CoV-2 specific TCRß repertoire analysis, T cells specific to Spike gp-derived hypomutated regions were identified in HDs and RPs despite viral genomic evolution. Hence, we demonstrated that SARS-CoV-2 mRNA-loaded antigen-presenting cells are effective activating and expanding COVID19-specific T cells. This approach represents an alternative to patients who are not able to mount adaptive immune responses to current COVID-19 vaccines with potential protection across new variants that have conserved genetic regions.

Reducing the Gap in Neurosurgical Education in LMICs: A Report of a Non-Profit Educational Program.

INTRODUCTION: Central to neurosurgical care, neurosurgical education is particularly needed in low- and middle-income countries (LMICs), where opportunities for neurosurgical training are limited due to social and economic constraints and an inadequate workforce. The present paper aims (1) to evaluate the validity and usability of a cadaver-free hybrid system in the context of LMICs and (2) to report their learning needs and whether the courses meet those needs via a comprehensive survey. METHODS: From April to November 2021, a non-profit initiative consisting of a series of innovative cadaver-free courses based on virtual and practical training was organized. This project emerged from a collaboration between the Young Neurosurgeons Forum of the World Federation of Neurological Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and UpSurgeOn, an Italian hi-tech company specialized in simulation technologies, creator of the UpSurgeOn Box, a hyper-realistic simulator of cranial approaches fused with augmented reality. Over that period, 11 cadaver-free courses were held in LMICs using remote hands-on Box simulators. RESULTS: One hundred sixty-eight participants completed an online survey after course completion of the course. The anatomical accuracy of simulators was overall rated high by the participant. The simulator provided a challenging but manageable learning curve, and 86% of participants found the Box to be very intuitive to use. When asked if the sequence of mental training (app), hybrid training (Augmented Reality), and manual training (the Box) was an effective method of training to fill the gap between theoretical knowledge and practice on a real patient/cadaver, 83% of participants agreed. Overall, the hands-on activities on the simulators have been satisfactory, as well as the integration between physical and digital simulation. CONCLUSIONS: This project demonstrated that a cadaver-free hybrid (virtual/hands-on) training system could potentially participate in accelerating the learning curve of neurosurgical residents, especially in the setting of limited training possibilities such as LMICs, which were only worsened during the COVID-19 pandemic.

Needs, Roles, and Challenges of Young Latin American and Caribbean Neurosurgeons.

BACKGROUND: Barriers to neurosurgery training and practice in Latin American and Caribbean countries (LACs) have been scarcely documented. The World Federation of Neurosurgical Societies Young Neurosurgeons Forum survey sought to identify young neurosurgeons' needs, roles, and challenges. We present the results focused on Latin America and the Caribbean. METHODS: In this cross-sectional study, we analyzed the Young Neurosurgeons Forum survey responses from LACs, following online survey dissemination through personal contacts, social media, and neurosurgical societies' e-mailing lists between April and November 2018. Data analysis was performed using Jamovi version 2.0 and STATA version 16. RESULTS: There were 91 respondents from LACs. Three (3.3%) respondents practiced in high-income countries, 77 (84.6%) in upper middle-income countries, 10 (11%) in lower middle-income countries, and 1 (1.1%) in an unclassified country. The majority (77, or 84.6%) of respondents were male, and 71 (90.2%) were younger than 40. Access to basic imaging modalities was high, with access to computed tomography scan universal among the survey respondents. However, only 25 (27.5%) of respondents reported having access to imaging guidance systems (navigation), and 73 (80.2%) reported having access to high-speed drills. A high GDP per capita was associated with increased availability of high-speed drills and more time dedicated to educational endeavors in neurosurgery, such as didactic teaching and topic presentation (P < 0.05). CONCLUSIONS: This survey found that neurosurgery trainees and practitioners of Latin America and the Caribbean face many barriers to practice. These include inadequate state-of-the-art neurosurgical equipment, a lack of standardized training curricula, few research opportunities, and long working hours.

Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. STATEMENT OF SIGNIFICANCE: The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors.

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell interactions.

Cancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable the mechanistic studies of tumor-immune interactions hampers the identification of new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), enable CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific CAR T cells cocultured with the CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, and killing of cancer cells. The anti-tumor activity was clearly captured via longterm in situ imaging and supported by upregulation of cytokines and chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, and CCL4. Interestingly, target cancer cells, upon an immune attack, initiated an "immune escape" response by frantically invading the surrounding microenvironment. This phenomenon however was not observed for the wild-type tumor samples which remained intact and produced no relevant cytokine response. Single cells collection and transcriptomic profiling of CAR T cells at regions of interest revealed feasibility of identifying differential gene expression amongst the immune subpopulations. Complimentary 3D in vitro platforms are necessary to uncover cancer immune biology mechanisms, as emphasized by the significant roles of the TME and its heterogeneity.

mRNA aggregates harness danger response for potent cancer immunotherapy.

Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA). Intravenous administration of RNA-LPAs mimics infectious emboli and elicits massive DC/T cell mobilization into lymphoid tissues provoking cancer immunogenicity and mediating rejection of both early and late-stage murine tumor models. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for toll-like receptor engagement, RNA-LPAs stimulate intracellular pathogen recognition receptors (RIG-I) and reprogram the TME thus enabling therapeutic T cell activity. RNA-LPAs were safe in acute/chronic murine GLP toxicology studies and immunologically active in client-owned canines with terminal gliomas. In an early phase first-in-human trial for patients with glioblastoma, we show that RNA-LPAs encoding for tumor-associated antigens elicit rapid induction of pro-inflammatory cytokines, mobilization/activation of monocytes and lymphocytes, and expansion of antigen-specific T cell immunity. These data support the use of RNA-LPAs as novel tools to elicit and sustain immune responses against poorly immunogenic tumors.

Evolution and Revolution of Imaging Technologies in Neurosurgery.

We understand only a small fraction of the events happening in our brains; therefore, despite all the progress made thus far, a whole array of questions remains. Nonetheless, neurosurgeons invented new tools to circumvent the challenges that had plagued their predecessors. With the manufacturing boom of the 20th century, technological innovations blossomed enabling the neuroscientific community to study and operate upon the living brain in finer detail and with greater precision while avoiding harm to the nervous system. The purpose of this chronological review is to 1) raise awareness among future neurosurgeons about the latest advances in the field, 2) become familiar with innovations such as augmented reality (AR) that should be included in education given their ready applicability in surgical training, and 3) be comfortable with customizing these technologies to real-life cases like in the case of mixed reality.

CAR T Cell Locomotion in Solid Tumor Microenvironment.

The promising outcomes of chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies potentiates its capability in the fight against many cancers. Nevertheless, this immunotherapy modality needs significant improvements for the treatment of solid tumors. Researchers have incrementally identified limitations and constantly pursued better CAR designs. However, even if CAR T cells are armed with optimal killer functions, they must overcome and survive suppressive barriers imposed by the tumor microenvironment (TME). In this review, we will discuss in detail the important role of TME in CAR T cell trafficking and how the intrinsic barriers contribute to an immunosuppressive phenotype and cancer progression. It is of critical importance that preclinical models can closely recapitulate the in vivo TME to better predict CAR T activity. Animal models have contributed immensely to our understanding of human diseases, but the intensive care for the animals and unreliable representation of human biology suggest in vivo models cannot be the sole approach to CAR T cell therapy. On the other hand, in vitro models for CAR T cytotoxic assessment offer valuable insights to mechanistic studies at the single cell level, but they often lack in vivo complexities, inter-individual heterogeneity, or physiologically relevant spatial dimension. Understanding the advantages and limitations of preclinical models and their applications would enable more reliable prediction of better clinical outcomes.

Women in Neurosurgery: First Neurosurgeon in Latin America and Current Mexican Leaders.

BACKGROUND: History has taught us that Mexican culture has been largely supported by women, despite gender prejudice from the society. Neurosurgery has not been the exception. Therefore, we investigated the challenges and influence of female neurosurgeons in Mexico. METHODS: We conducted a review of the literature and an analysis of the internal database of the Mexican Society of Neurological Surgery focusing on 3 topics: 1) the historical presence of women and gender inequality in Mexico; 2) the life and legacy of the woman who became the first neurosurgeon in Mexico and in Latin America; and 3) the participation of women in neurosurgery in the past 3 decades. RESULTS: In Latin America, the first woman in neurosurgery was María Cristina García-Sancho, who completed her neurosurgical training in 1951. Currently, women represent 6.2% of the total members of the Mexican Society of Neurological Surgery (MSNS). This percentage is still low, although data collected in this study suggest that it might increase in the next few years because 16.7% of Board Directors of the MSNS are women, the next elected president is a female neurosurgeon, and 14.5% of neurosurgery residents are women. CONCLUSIONS: Although a steady increase has occurred of women in neurosurgery in Mexico, there is still work to do, especially to overcome the barriers related to the old assumptions of the cultural and social roles of women.

An Affordable and Feasible Technique for Minimally Invasive Tubular Lumbar Discectomy.

BACKGROUND: The benefits of minimally invasive spine surgery are attainable only if hospitals have the financial resources to acquire essential equipment. We present a surgical approach readily available to countries where unacceptably expensive materials are the main limitation for use of minimally invasive spine surgery. METHODS: This retrospective study included 30 patients who underwent minimally invasive spine surgery using syringes as dilators and retractors for posterior lumbar approaches. Inclusion criteria were lumbar radicular/back pain, degenerative disc, spondylolysis, unilateral approach, and maximum of 2 affected spine levels. Demographic characteristics, affected radicular level, diagnosis, type and length of surgery, hospital length of stay, MacNab criteria, complications, and resumption of daily activities were analyzed. RESULTS: Of 30 patients, 17 (56.6%) presented with S1 radicular pain. Pain was mainly due to posterolateral hernia (70%; n = 21) requiring 1-level discectomy. In 6 patients (20%), discectomy and an interspinous process device were required. One patient (3.33%) underwent 2-level discectomy. All surgeries were performed using syringes as dilators and retractors. Maximum syringe diameter used was 2 cm (20-mL syringes) in 29 patients (96.6%) and 3 cm (60-mL syringe) in 1 patient. Average length of surgery was 1.5 hours, and average hospital stay was 1.8 days. Based on MacNab criteria, excellent, good, and fair outcomes were achieved in 25 patients (83%), 3 patients (10%), and 2 patients (6.7%). Complications were observed in 5 patients (16.7%). CONCLUSIONS: This is a safe and feasible technique with excellent results obtained at low cost and is becoming an attractive surgical option in developing countries.

Lazy Glass Microsurgical Trainer: A Frugal Solution for Microsurgical Training.

BACKGROUND: The art of surgery is becoming increasingly complex and dependent on scopes, screens, and technology, inviting a complex learning curve and development of hand-eye coordination and dexterity among other skills. We introduce an affordable, do-it-yourself microsurgical simulator that can be set up using a smartphone and a pair of reflective prism glasses. The glasses employ periscopic prisms on either side that reflect light perpendicularly. When the visual input is combined with the magnification of a smartphone camera, a real-time microsurgical experience can be simulated. METHODS: We analyzed the performance of 2 trainee residents in performing their first 5 successful sutures with 5-0 polypropylene thread on the cut ends of a glove over the course of 3 months. The module was also assessed in a survey at an international conference of neurosurgeons. RESULTS: A significant improvement was observed in both residents at the end of each month versus baseline (P < 0.05). Of 27 survey participants, 3 (11%) reported access to a training laboratory in their institute. The module was rated 4/5 in terms of hand-eye coordination, 3.5/5 in management of microsurgical field, and 3.5/5 in depth perception. CONCLUSIONS: The microsurgical simulation technique proved to be useful in performing complex microsurgical tasks. A significant improvement in microsurgical skills was observed among our trainees. The cost of building the module can be as low as U.S. $5. We endorse the use of this technique for resident training and skill development, especially in resource-challenged environments.

A Dual Approach for the Management of Complex Craniovertebral Junction Abnormalities: Endoscopic Endonasal Odontoidectomy and Posterior Decompression with Fusion.

BACKGROUND: Ventral brainstem compression secondary to complex craniovertebral junction abnormality is an infrequent cause of neurologic deterioration in pediatric patients. However, in cases of symptomatic, irreducible ventral compression, 360° decompression of the brainstem supported by posterior stabilization may provide the best opportunity for improvement in symptoms. More recently, the endoscopic endonasal corridor has been proposed as an alternative method of odontoidectomy associated with less morbidity. We report the largest single case series of pediatric patients using this dual-intervention surgical technique. The purpose of this study was to evaluate the surgical outcomes of pediatric patients who underwent posterior occipitocervical decompression and instrumentation followed by endoscopic endonasal odontoidectomy performed to relieve neurologic impingement involving the ventral brainstem and craniocervical junction. METHODS: Between January 2011 and February 2017, 7 patients underwent posterior instrumented fusion followed by endonasal endoscopic odontoidectomy at our unit. Standardized clinical and radiological parameters were assessed before and after surgery. A univariate analysis was performed to assess clinical and radiologic improvement after surgery. RESULTS: A total of 14 operations were performed on 7 pediatric patients. One patient had Ehlers-Danlos syndrome, 1 patient had a Chiari 1 malformation, and the remaining 5 patients had Chiari 1.5 malformations. Average extubation day was postoperative day 0.9. Average day of initiation of postoperative feeds was postoperative day 1.0. CONCLUSIONS: The combined endoscopic endonasal odontoidectomy and posterior decompression and fusion for complex craniovertebral compression is a safe and effective procedure that appears to be well tolerated in the pediatric population.

Suprasellar and recurrent pediatric craniopharyngiomas: expanding indications for the extended endoscopic transsphenoidal approach.

OBJECTIVE The expanded endonasal endoscopic transsphenoidal approach has become increasingly used for craniopharyngioma surgery in the pediatric population, but questions still persist regarding its utility in younger children, in recurrent and irradiated tumors, and in masses primarily located in the suprasellar region. The narrow corridor, incomplete pneumatization, and fear of hypothalamic injury have traditionally relegated this approach to application in older children with mostly cystic craniopharyngiomas centered in the sella. The authors present a series of consecutive pediatric patients in whom the endonasal endoscopic approach was used to remove craniopharyngiomas from patients of varied ages, regardless of the location of the tumor and previous treatments or surgeries, to ascertain if the traditional concerns about limitations of this approach are worth reevaluating METHODS Eleven consecutive pediatric patients (age ≤ 18 years) underwent surgery via an endoscopic transsphenoidal approach at NewYork-Presbyterian/Weill Cornell Medical Center from 2007 to 2016. The authors recorded the location, consistency, and size of the lesion, assessed for hypothalamic invasion radiographically, calculated skull base measurements, and assessed parameters such as extent of resection, visual function, endocrinological function, weight gain, and return-to-school status. RESULTS The average age at the time of surgery was 7.9 years (range 4-17 years) and the tumor sizes ranged from 1.3 to 41.7 cm3. Five cases were purely suprasellar, 5 had solid components, 4 were reoperations, and 5 had a conchal sphenoid aeration. Nevertheless, gross-total resection was achieved in 45% of the patients and 50% of those in whom it was the goal of surgery, without any correlation with the location, tumor consistency, or the age of the patient. Near-total resection, subtotal resection, or biopsy was performed intentionally in the remaining patients to avoid hypothalamic injury. Anterior pituitary dysfunction occurred in 81.8% of the patients, and 63.3% developed diabetes insipidus . Two patients (18%) had a greater than 9% increase in body mass index. Visual function was stable or improved in 73%. All children returned to an academic environment, with 10 of them in the grade appropriate for their age. There was a single case of each of the following: CSF leak, loss of vision unilaterally, and abscess. CONCLUSIONS The endoscopic transsphenoidal approach is suitable for removing pediatric craniopharyngiomas even in young children with suprasellar tumors, conchal sphenoid sinus, recurrent tumors, and tumors with solid components. The extent of resection is dictated by intrinsic hypothalamic tumor invasiveness rather than the approach. The endoscopic transsphenoidal approach affords the ability to directly inspect the hypothalamus to determine invasion, which may help spare the patient from hypothalamic injury. Irrespective of approach, the rates of postoperative endocrinopathy remain high and the learning curve for the approach to a relatively rare tumor is steep.

Astrocytic Tumors in Mexico: An Overview of Characteristics and Prognosis in an Open Reference Center for Low-Income Population.

OBJECTIVE: The authors aimed to analyze the current epidemiology of high- and low-grade gliomas, follow-up strategies, and prognosis in a national reference center of a developing country. MATERIALS AND METHODS: Medical records of patients diagnosed with intracranial gliomas from January 2012 to January 2016 were reviewed. Data were classified by age, symptoms, Karnofsky functional scale (KFS), tumor location, extent of resection (EOR), histopathology, hospital stay, Glasgow outcome scale (GOS), adjuvant treatments, overall survival (OS), and mortality. RESULTS: Astrocytomas accounted for 28.2% of the intracranial tumors and 53.5% were male. Headache was the most common symptom, while sensory disturbance was the least frequent. The right cerebral hemisphere was involved in 56.5% of cases and frontal lobe in 31.3%. Gross total resection (GTR) was achieved in 18.1% cases, 35.3% subtotal resection, and 46.4% biopsy. Regarding the astrocytomas, 43.3% were low grade and 56.4% high grade. Low-grade tumors had the highest frequency in the fourth decade of life, while Grade III and IV in the fifth and seventh decades of life, respectively. In high-grade lesions, there was a slight male predominance (~1.4:1). The initial KFS was regularly 80 for low-grade gliomas and 60 for high-grade. By 1-month postdischarge, the score decreased by 10 points. About half of the patients (47.5%) received adjuvant therapy after surgery. From the Glasgow Outcome Scale (GOS), the majority had a form of disability and 30-month OS was above 88% for Grade I-II and 0% for Grade III and IV. CONCLUSIONS: Astrocytic tumors were the most frequently noted intra-axial tumors. Age, histological grade, and EOR are important prognostic factors. These results are similar to other reports; however, increased variability was noted when treatment-related factors were considered. Additional studies are necessary to identify the factors related to these treatment results. HIGHLIGHTS: There are no data describing the basic epidemiology and prognosis of high-grade and low-grade gliomas in Mexico.Intracranial astrocytomas account for 28.2% tumors in our institution.Age, histological grade, and EOR are important prognostic factors.Poor overall survival was achieved in our target population.