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Recurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3–30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas. [ABSTRACT FROM AUTHOR]

Background: Delayed postoperative cerebrospinal fluid (CSF) leaks are uncommon and largely unstudied complications. In this study we aim to identify their etiology and understand the efficacy of various reconstruction strategies. Methods: A retrospective chart analysis of 1017 endonasal skull base surgeries performed by a single neurosurgeon was completed identifying delayed CSF leaks (occurring >1 week after surgery). Results: Seventeen cases of early (1‐2 weeks after surgery) or delayed (>2 weeks after surgery) postoperative CSF leak were identified. The most common reconstruction during the initial surgery consisted of an inlay or gasket seal collagen matrix (82.4% of patients) with an onlay pedicled flap (76.5% of patients). Presenting symptoms of delayed CSF leak included rhinorrhea (82.4%), headache (41.2%), and meningitis (23.5%). The most common causes included flap dehiscence (17.6%); provoking events such as emesis, sneezing, or fall (17.6%); flap necrosis (11.8%); flap displacement (11.8%); and inadequate apposition of the flap, that is, folded flap (11.8%). Reconstructive techniques of the delayed CSF leak included fortification of the initial reconstruction with free fat grafts (29.4% of patients), combined collagen matrix with a fat graft (23.5% of patients), repositioning of the previous flap (11.8% of patients), and repair with a new flap (11.8% of patients). CSF diversion (spinal/ventricular drain or shunt) was used in 17.6% of patients. Conclusion: This study identifies the most common etiologic factors leading to a delayed CSF leak and its initial symptoms. Furthermore, it serves as the foundation for a reconstructive algorithm based on reinforcement of the initial repair with free abdominal fat graft with or without collagen matrix. [ABSTRACT FROM AUTHOR]

Rosai-Dorfman disease (RDD) is a rare, benign histiocytosis disorder with only approximately 100 reported central nervous system cases in the literature. Even less common is skull base involvement of RDD, with about 41 reported cases. Radiographically, RDD can appear similar to a meningioma; the true diagnosis is only found with histologic analysis. Although "benign," RDD can lead to significant neurologic morbidity from the disease or unnecessary surgical and nonsurgical treatment. While rare, intracranial RDD has been treated with chemotherapy or radiotherapy, with surgery playing a limited role to relieve mass effect. Surgical approaches to the skull base are invasive and pose risk, especially for a benign and self-limiting disease like RDD. Here we present the case of a 63-year-old woman with a presumed spheno-orbital meningioma for which the patient previously underwent radiation therapy. On presentation to our facility, the patient noted pressure headaches and blurry vision, and imaging demonstrated progression of her disease. For these reasons, surgical debulking and biopsy were undertaken. This report demonstrates the role of EEA for tissue biopsy and decompression of the affected cranial nerves and orbit. This paradigm seems to provide a safe and effective way to manage patients with compressive symptoms, while also allowing for tissue sampling. [ABSTRACT FROM AUTHOR]

This article, published in the Journal of Neurological Surgery, discusses the use of repeat endoscopic transcavernous surgery for patients with residual growth hormone producing tumors and persistent acromegaly. The study analyzed 28 patients who had previously undergone pituitary tumor surgery and found that a transcavernous approach resulted in positive outcomes, with 80% of patients achieving biochemical remission with surgery alone and 90% with surgery and adjuvant therapy. The study concludes that repeat surgery with a transcavernous approach is safe and effective in achieving biochemical remission for patients with active disease who have undergone traditional transsphenoidal surgery. [Extracted from the article]

Open transcranial surgery has long served as the traditional approach for resecting tumors and other lesions in the skull base. However, endoscopic endonasal skull base surgery (EESBS) has emerged as a credible alternative. This paper provides insight on the sinonasal morbidity in patients undergoing EESBS. A literature review was performed by searches of MEDLINE database to provide further insight on sinonasal morbidity associated with EESBS, with a particular focus on published incidence rates and patterns of complication. We identified only articles that reported the incidence of sinonasal morbidity and complications as the major outcome of the studies. The most common sinonasal morbidity symptoms are nasal crusting (50.8%), nasal discharge (40.4%), nasal airflow blockage (40.1%) followed by disturbances in olfaction (26.7%). The incidence of mucocele formation is 8%, and this is significantly increased in pediatric patients up to 25% (range, 14-50%). Epistaxis appears to be a rare event, often times not found in some case series. Some studies suggested less morbidity if the middle turbinate can be preserved, a finding that must be balanced with the need for sufficient exposure on larger cases. Sinonasal morbidity following endoscopic endonasal skull base surgery has the potential to adversely impact patient quality of life, with nasal crusting and discharge being the two most common symptoms. Morbidity signs and symptoms usually resolve within 3-4 months, however symptoms can persist for longer with more complex surgeries. The rate of mucocele formation is higher in pediatric patients, with special attention required in graft positioning for this population in particular. [ABSTRACT FROM AUTHOR]

Introduction Malignancies of the clivus and petroclival region are mainly chordomas and chondrosarcomas. Although a spectrum of malignancies may present in this area, a finite group of commonly encountered malignant pathologies will be the focus of this review, as they are recognized to be formidable pathologies due to adjacent critical neurovascular structures and challenging surgical approaches. Objectives The objective is to review the literature regarding medical and surgical management of malignant tumors of the clival and petroclival region with a focus on clinical presentation, diagnostic identification, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to the skull base. Data Synthesis A literature review was conducted, searching for basic science and clinical evidence from PubMed, Medline, and the Cochrane Database. The selection criteria encompassed original articles including data from both basic science and clinical literature, case series, case reports, and review articles on the etiology, diagnosis, treatment, and management of skull base malignancies in the clival and petroclival region. Conclusions The management of petroclival malignancies requires a multidisciplinary team to deliver the most complete surgical resection, with minimal morbidity, followed by appropriate adjuvant therapy. We advocate the combination of endoscopic and open approaches (traditional or minimally invasive) as required by the particular tumor followed by radiation therapy to optimize oncologic outcomes. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to demonstrate the nuances in preoperative management, surgical technique, and reconstruction for an endoscopic endonasal odontoidectomy. Design  Assembly of an operative video demonstrating technique for endoscopic endonasal odontoidectomy. Setting  this study is a comprehensive skull base team at a tertiary care center. Participant  The patient is a 53-year-old male, with basilar invagination and myelopathy, who underwent cervical fusion, 6 years back, without ventral decompression at an outside hospital. He presented to our clinic with persistent myelopathy and generalized weakness, thus an endoscopic endonasal odontoidectomy for brainstem decompression was recommended. Main Outcome Measures  Preoperative computed tomography (CT) angiography and intraoperative CT navigation demonstrated normal carotid artery anatomic localization. An inverted U -shaped mucosal flap was reflected inferiorly and preserved. The C1 arch was identified and resected with a high speed drill. The resultant diseased soft tissue arising from retropulsion of the odontoid process was then removed and the odontoid process identified. This bone was removed centrally until a thin cap remained. After removal of the cap, the underlying ligamentous tissue was removed until dural pulsations were appreciated and brainstem decompression achieved. Hemostasis was attained and the mucosal flap mobilized into position. Results  Postoperative CT imaging demonstrated resolution of basilar invagination and brainstem decompression (Fig. 1). The patient improved both in arm dexterity and ambulation after surgery and the reconstruction demonstrated appropriate healing on nasal endoscopy 2 months postoperatively. Conclusions  This operative video demonstrates nuances in endoscopic endonasal odontoidectomy. This case also demonstrates that ventral decompression after long-term cervical fusion can improve myelopathy and that fusion in the setting of bony ventral compression, rather than rheumatoid panus, may not reduce over time with fusion only. The link to the video can be found at: https://youtu.be/370FFuBA89Y. [ABSTRACT FROM AUTHOR]

High lactate generation and low glucose oxidation, despite normal oxygen conditions, are commonly seen in cancer cells and tumors. Historically known as the Warburg effect, this altered metabolic phenotype has long been correlated with malignant progression and poor clinical outcome. However, the mechanistic relationship between altered glucose metabolism and malignancy remains poorly understood. Here we show that inhibition of pyruvate dehydrogenase complex (PDC) activity contributes to the Warburg metabolic and malignant phenotype in human head and neck squamous cell carcinoma. PDC inhibition occurs via enhanced expression of pyruvate dehydrogenase kinase-1 (PDK-1), which results in inhibitory phosphorylation of the pyruvate dehydrogenase a (PDHα) subunit. We also demonstrate that PDC inhibition in cancer cells is associated with normoxic stabilization of the malignancy-promoting transcription factor hypoxia-inducible factor-1α (HIF-1α) by glycolytic metabolites. Knockdown of PDK-1 via short hairpin RNA lowers PDHα phosphorylation, restores PDC activity, reverts the Warburg metabolic phenotype, decreases normoxic HIF-1α expression, lowers hypoxic cell survival, decreases invasiveness, and inhibits tumor growth. PDK-1 is an HIF-1-regulated gene, and these data suggest that the buildup of glycolytic metabolites, resulting from high PDK-l expression, may in turn promote HIF-1 activation, thus sustaining a feed-forward loop for malignant progression. In addition to providing anabolic support for cancer cells, altered fuel metabolism thus supports a malignant phenotype. Correction of metabolic abnormalities offers unique opportunities for cancer treatment and may potentially synergize with other cancer therapies. [ABSTRACT FROM AUTHOR]

Erythropoietin (Epo) is used for managing anemia in cancer patients. However, recent studies have raised concerns for this practice. We investigated the expression and function of Epo and the erythropoietin receptor (EpoR) in tumor biopsies and cell lines from human head and neck cancer. Epo responsiveness of the cell lines was assessed by Epoetin-α-induced tyrosine phosphorylation of the Janus kinase 2 (JAK2) protein kinase. Transmigration assays across Matrigel-coated filters were used to examine the effects of Epoetin-α on cell invasiveness. In 32 biopsies, we observed a significant association between disease progression and expression of Epo and its receptor, EpoR. Expression was highest in malignant cells, particularly within hypoxic and infiltrating tumor regions. Although both Epo and EpoR were expressed in human head and neck carcinoma cell lines, only EpoR was upregulated by hypoxia. Epoetin-α treatment induced prominent JAK2 phosphorylation and enhanced cell invasion. Inhibition of JAK2 phosphorylation reduced both basal and Epo-induced invasiveness. Our findings support a role for autocrine or paracrine Epo signaling in the malignant progression and local invasiveness of head and neck cancer. This mechanism may also be activated by recombinant Epo therapy and could potentially produce detrimental effects in rhEpo-treated cancer patients. [ABSTRACT FROM AUTHOR]

Introduction  Understanding the anatomic features of the zygomatic nerve is critical for performing the endoscopic transmaxillary approach properly. Injury to the zygomatic nerve can result in facial numbness and corneal problems. Objective  To evaluate the surgical anatomy of the zygomatic nerve and its segments from an endoscopic endonasal perspective for clinical implications of performing the endoscopic transmaxillary approach. Methods  The origin, course, length, and segments of the zygomatic nerve were studied in four specimens from an endonasal perspective. Results  The zygomatic nerve arises 4.1 ± 1.7 mm from the foramen rotundum of the maxillary nerve in the superolateral pterygopalatine fossa (PPF). According to its anatomic region in endonasal endoscopic surgery, we divided the zygomatic nerve into two segments: the PPF segment, from origin to the point of entry under Muller's muscle, which runs superolaterally to the inferior orbital fissure (IOF) (length, 4.6 ± 1.3 mm), and the IOF segment, starting at the entry point in Muller's muscle and terminating at the exit point in the IOF, which travels between Muller's muscle and the great wing of the sphenoid bone (length, 19.6 ± 3.6 mm). In the transmaxillary approach, the zygomatic nerve is a critical landmark in the superolateral PPF. Conclusion  The zygomatic nerve travels in the PPF and the IOF; better visualization and preservation of this nerve during endonasal endoscopic surgery are crucial for successful outcomes. [ABSTRACT FROM AUTHOR]

Introduction Meningiomas—the most common extra-axial tumors—are benign, slow-growing dural-based lesions that can involve multiple cranial fossae and can progress insidiously for years until coming to clinical attention secondary to compression of adjacent neurovascular structures. For complex, multicompartmental lesions, multistaged surgeries have been increasingly shown to enhance maximal safe resection while minimizing adverse sequela. Here, we systematically review the extant literature to highlight the merits of staged resection. Methods PubMed, Scopus, and Web of Science databases were queried to identify articles reporting resections of intracranial meningiomas using a multistaged approach, and articles were screened for possible inclusion in a systematic process performed by two authors. Results Of 118 identified studies, 36 describing 169 patients (mean age 42.6 ± 21.3 years) met inclusion/exclusion criteria. Petroclival lesions comprised 57% of cases, with the most common indications for a multistaged approach being large size, close approximation of critical neurovascular structures, minimization of brain retraction, identification and ligation of deep vessels feeding the tumor, and resection of residual tumor found on postoperative imaging. Most second-stage surgeries occurred within 3 months of the index surgery. Few complications were reported and multistaged resections appeared to be well tolerated overall. Conclusions Current literature suggests multistaged approaches for meningioma resection are well-tolerated. However, there is insufficient comparative evidence to draw definitive conclusions about its advantages over an unstaged approach. There are similarly insufficient data to generate an evidence-based decision-making framework for when a staged approach should be employed. This highlights the need for collaborative efforts among skull base surgeons to establish an evidentiary to support the use of staged approaches and to outline those indications that merit such an approach. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a patient who presented with headaches and diplopia and was initially diagnosed with a radiographic cavernous hemangioma in the cavernous sinus. However, further evaluation revealed that the lesion was actually an ectopic functional corticotroph adenoma. The patient underwent endoscopic endonasal resection, resulting in biochemical remission. The article emphasizes the challenges in diagnosing and treating cavernous sinus lesions and highlights the importance of comprehensive endocrine evaluation and precise imaging in achieving successful treatment. [Extracted from the article]

This article discusses the outcomes of endoscopic endonasal transcavernous surgery for pituitary adenomas. The study analyzed data from patients who underwent this surgery between 2018 and 2023. The results showed that transcavernous surgery was more common in repeat surgery patients and those with functioning adenomas. The study also examined the invasion patterns of the cavernous sinus compartments and found that the medial wall was the most frequently involved. The authors concluded that the outcomes of transcavernous surgery can vary depending on the specific compartments involved. [Extracted from the article]

Radiofrequency ablation (RFA) focally destroys abnormal or dysfunctional tissue using thermal energy generated from alternating current. The utilization of RFA has gained popularity as a minimally invasive procedure for the treatment of skeletal metastases with a particular focus on palliative pain treatments to the spine, pelvis, long bones, sternum, and glenoid. More recently, single-session procedures that combine RFA with vertebral augmentation techniques have allowed treatment to areas of pain associated with pathologic fractures secondary to metastatic disease. Although many studies have been done to investigate the safety and efficacy of RFA, there have been no reported cases to date in which the use of RFA for the treatment of spinal metastases has led to any major permanent neurological injury. This report describes a case of a 61-year-old woman who underwent RFA and kyphoplasty for spinal metastases and noted the immediate onset of lower extremity paralysis after the procedure. To the best of our knowledge, this is the first documented case of permanent lower extremity paralysis in the medical literature after radiofrequency thermal ablation of spine metastases. Postoperative magnetic resonance imaging and physical examination suggest RFA-induced thermal injury as the most likely mechanism of paralysis. In this report, a review of previous in vivo models used in studying the efficacy and safety of spine RFA is conducted. Additionally, the literature has been reviewed for any neurological events reported with the use of RFA in the treatment of patients with vertebral pathology. [ABSTRACT FROM AUTHOR]

While surgery is a critical treatment option for craniopharyngiomas, the optimal surgical approach remains under debate. Herein, we studied a large cohort of craniopharyngioma patients to identify predictors of endoscopic surgery (ES) and to compare survival outcomes between patients undergoing ES versus nonendoscopic surgery (NES). The National Cancer Database was queried for patients receiving definitive surgical treatment in 2010–2016. Cox proportional hazards and propensity score-adjusted Kaplan–Meier analyses assessed mortality risk and overall survival, respectively. Predictors of surgical approach were evaluated via logistic regression. Of 1721 patients, 508 (29.5%) underwent ES, 877 (50.9%) were female, and the average age was 41.8 ± 21.3 years. Matched ES and NES cohorts exhibited 5-year overall survival rates of 88.0% and 79.8%, respectively (P = 0.004). ES was associated with reduced mortality (Hazard Ratio = 0.634; 95% confidence interval [CI], 0.439–0.914; P = 0.015). Patients treated at academic facilities (Odds Ratio [OR] = 2.095; 95% CI, 1.529–2.904; P < 0.001) or diagnosed recently (OR = 1.132; 95% CI, 1.058–1.211; P < 0.001) were more likely to undergo ES, while those with tumor sizes >3 cm (OR = 0.604; 95% CI, 0.451–0.804; P < 0.001) or receiving adjuvant radiotherapy (OR = 0.641; 95% CI, 0.454–0.894; P = 0.010) were more likely to receive NES. Surgical inpatient stays were significantly shorter with ES compared to NES (8.0 vs. 10.5 days, P < 0.001). On linear regression, ES usage increased by 82.4% and NES usage decreased by 23.4% between 2010 and 2016 (R2 = 0.575, P = 0.031). ES of craniopharyngioma was associated with reduced mortality and shorter inpatient stays compared to NES. Factors including tumor size, extent of resection, facility type, and year of diagnosis may predict receiving ES. There is a trend towards increased usage of ES for surgical management of craniopharyngiomas. [ABSTRACT FROM AUTHOR]

Medical complications were independently predicted by ASA 4-5 compared with ASA 1-2 (OR = 4.09, 95% CI 1.94-8.64, I p i < 0.001). This study aims to evaluate the value of frailty, age, and American Society of Anesthesiologists (ASA) classification in predicting postoperative outcomes after minimally invasive pituitary surgery. Keywords: age; ASA; frailty; pituitary surgery EN age ASA frailty pituitary surgery 780 783 4 04/28/22 20220501 NES 220501 INTRODUCTION Pituitary adenomas are common intracranial tumors, with an estimated prevalence of 16.7%.1 Minimally invasive pituitary surgery is the standard of care in the treatment of most pituitary neoplasms and often requires a complex and multidisciplinary management plan. [Extracted from the article]

Purpose: Diagnosing and operating pediatric patients with intracranial lesions posed a greater diagnostic challenge for physicians during the early twentieth century. At the time, an intracranial neoplasm was indistinctively diagnosed as a glioma, encompassing a broad category of brain tumor pathologies. The treatment and surgical interventions followed for children diagnosed with gliomas is not well-described in the literature from this time. Methods: Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, we reviewed the Johns Hopkins Hospital surgical files from 1896-1912. Patients 18 years or younger, who underwent surgical intervention by Cushing for suspected intracranial tumors, were selected. Results: Of the eight pediatric cases diagnosed with gliomas by Cushing, four cases were later diagnosed as medulloblastomas by Dr. Cushing in 1925. Of the remaining four pediatric cases, one was diagnosed as a brainstem glioma and another as a ventricular glioma. We describe the remaining two cases. Conclusion: These examples illustrate Cushing's approach to treating brain tumors diagnosed as gliomas in pediatric patients, focusing on an initial decompression and followed by a thorough surgical exploration for tumor. Furthermore, these cases demonstrate Cushing's early attempts to manage such lesions in children and highlight the challenges faced in diagnosing and localizing intracranial lesions within this group of patients. [ABSTRACT FROM AUTHOR]

Continuous hydroxylation of the HIF-1 transcription factor a subunit by oxygen and 2-oxoglutarate-dependent dioxygenases promotes decay of this protein and thus prevents the transcriptional activation of many genes involved in energy metabolism, angiogenesis, cell survival, and matrix modification. Hypoxia blocks HIF-1α hydroxylation and thus activates HIF-1α-mediated gene expression. Several nonhypoxic stimuli can also activate HIF-1, although the mechanisms involved are not well known. Here we show that the glucose metabolites pyruvate and oxaloacetate inactivate HIF-1α decay in a manner selectively reversible by ascorbate, cysteine, histidine, and ferrous iron but not by 2-oxoglutarate or oxygen. Pyruvate and oxaloacetate bind to the 2-oxoglutarate site of HIF-1α prolyl hydroxylases, but their effects on HIF-1 are not mimicked by other Krebs cycle intermediates, including succinate and fumarate. We show that inactivation of HIF-1 hydroxylation by glucose-derived 2-oxoacids underlies the prominent basal HIF-1 activity commonly seen in many highly glycolytic cancer cells. Since HIF-1 itself promotes glycolytic metabolism, enhancement of HIF-1 by glucose metabolites may constitute a novel feed-forward signaling mechanism involved in malignant progression. [ABSTRACT FROM AUTHOR]

Minimally invasive transcranial approaches (MITAs) continue to expand in popularity in neurosurgery. Only few MITAs allow sufficient sylvian exposure to enable wide use of the transsylvian corridor. In this study, we aim to compare the transsylvian corridor in two MITAs: the minipterional (MPTa) and the extended supraorbital eyebrow approaches (XSEa). Eight cadaver heads were used to quantify the surgical exposure and maneuverability along the sylvian fissure and the insular lobe provided by the MPTa and the XSEa. Surgical exposure was calculated by means of the exposed length of the sylvian fissure and by the area framed within three extreme points in the insular lobe. Maneuverability was assessed by means of the surgical freedom along the sylvian cistern. XSEa provides twice the frontal exposure and half of the temporal exposure in comparison to the MPTa (p < 0.001 and p = 0.02, respectively). No significant differences were found between the two craniotomies in the length of the exposure of the sylvian fissure, area of insular exposure, or surgical freedom. Both the MPTa and the XSEa afford sufficient grades of exposure along the sylvian fissure and the insular lobe, although the viewing angle is significantly different between the two approaches. Such properties allow either to be used for microsurgery deep within the sylvian cistern. The use of additional corridors, such as the subfrontal route (XSEa) and pretemporal route (MPTa), may influence selection of either the minipterional or the extended supraorbital approaches according to the origin of the surgical pathology addressed. [ABSTRACT FROM AUTHOR]

Background: Craniopharyngioma has historically been recognized to be a formidable pathology primarily due to its proximity to critical neurovascular structures and the challenging surgical corridors that surgeons have tried to reach this lesion. Focus of review: In this work, we review the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to craniopharyngiomas. Summary: The management of craniopharyngiomas requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver the most comprehensive and safest surgical resection with minimal postoperative morbidity. [ABSTRACT FROM AUTHOR]

Background: Pediatric pituitary adenomas are a rare medical entity that makes up a small portion of intracranial tumors in children and adolescents. Although benign, the majority of these lesions are secreting functional tumors with the potential for physiological sequela that can profoundly affect a child's development. Focus of Review: In this review, we discuss the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to treat these tumors. Summary: The management of pituitary tumors requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver comprehensive care. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance. Mechanistically, the formation of a protein complex comprising NEK2 and EZH2 in glioma spheres phosphorylated and then protected EZH2 from ubiquitination-dependent protein degradation in a NEK2 kinase activity-dependent manner. Clinically, NEK2 expression in patients with glioma was closely associated with EZH2 expression and correlated with a poor prognosis. NEK2 expression was also substantially elevated in recurrent tumors after therapeutic failure compared with primary untreated tumors in matched GBM patients. We designed a NEK2 kinase inhibitor, compound 3a (CMP3a), which efficiently attenuated GBM growth in a mouse model and exhibited a synergistic effect with radiotherapy. These data demonstrate a key role for NEK2 in maintaining GSCs in GBM by stabilizing the EZH2 protein and introduce the small-molecule inhibitor CMP3a as a potential therapeutic agent for GBM. [ABSTRACT FROM AUTHOR]

Summary Activation of nuclear factor κB (NF-κB) induces mesenchymal (MES) transdifferentiation and radioresistance in glioma stem cells (GSCs), but molecular mechanisms for NF-κB activation in GSCs are currently unknown. Here, we report that mixed lineage kinase 4 (MLK4) is overexpressed in MES but not proneural (PN) GSCs. Silencing MLK4 suppresses self-renewal, motility, tumorigenesis, and radioresistance of MES GSCs via a loss of the MES signature. MLK4 binds and phosphorylates the NF-κB regulator IKKα, leading to activation of NF-κB signaling in GSCs. MLK4 expression is inversely correlated with patient prognosis in MES, but not PN high-grade gliomas. Collectively, our results uncover MLK4 as an upstream regulator of NF-κB signaling and a potential molecular target for the MES subtype of glioblastomas. [ABSTRACT FROM AUTHOR]

Summary: Chordoma is a rare bone cancer that is aggressive, locally invasive, and has a poor prognosis. Chordomas are thought to arise from transformed remnants of notochord and have a predilection for the axial skeleton, with the most common sites being the sacrum, skull base, and spine. The gold standard treatment for chordomas of the mobile spine and sacrum is en-bloc excision with wide margins and postoperative external-beam radiation therapy. Treatment of clival chordomas is unique from other locations with an enhanced emphasis on preservation of neurological function, typified by a general paradigm of maximally safe cytoreductive surgery and advanced radiation delivery techniques. In this Review, we highlight current standards in diagnosis, clinical management, and molecular characterisation of chordomas, and discuss current research. [ABSTRACT FROM AUTHOR]

Objective.: Our objectives were to determine if the erythropoietin receptor (EpoR) has increased expression in epithelial ovarian carcinoma, and if erythropoietin (Epo) confers malignant properties to ovarian cancer cell lines. Methods.: A Western blot analysis of protein lysates from normal ovarian surface epithelial cells and ovarian cancer cell lines was performed. In addition, immunohistochemical (IHC) staining for EpoR in tissue specimens of normal, low malignant potential tumor, and epithelial ovarian carcinoma was performed. Epo effect on ovarian cancer cell lines was investigated by a cytotoxicity assay using a cell line with high (OVCAR3) and low (SKOV3) EpoR expression. Results.: Western blot analysis revealed increased expression of EpoR in multiple ovarian cancer cell lines. IHC staining revealed limited EpoR expression in benign ovarian tissue and increased levels in ovarian low malignant potential (LMP) tumor and carcinoma. This difference between benign ovarian tissue and carcinoma was found to be statistically significant using a quantitative scoring system. In addition, a cytotoxicity assay with paclitaxel and cisplatin revealed an attenuation of cytotoxic effects. Conclusion.: Increased EpoR expression in ovarian LMP tumors and carcinoma is demonstrated by Western blot analysis and IHC staining. Furthermore, adversely effects sensitivity to cisplatin in the ovarian cancer cell lines. These data add to the growing body of evidence suggesting possible detrimental effects of erythropoietin. [Copyright &y& Elsevier]

A correction is presented to the article Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2.

The article focuses on targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2.

Summary Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter RNA splicing in recipient cells, thereby promoting their therapy resistance and aggressive migratory phenotype. Mechanistically, we identified RBM11 as a representative splicing factor that is upregulated in tumors after therapy and shed in extracellular vesicles upon induction of apoptosis. Once internalized in recipient cells, exogenous RBM11 switches splicing of MDM4 and Cyclin D1 toward the expression of more oncogenic isoforms. [ABSTRACT FROM AUTHOR]