Guidelines for Manufacturing and Application of Organoids: Brain.

This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.

A new DNA aptamer which binds to SARS-CoV-2 spike protein and reduces pro-inflammatory response.

COVID-19 caused by SARS-CoV-2 spread rapidly around the world, endangering the health of people globally. The SARS-CoV-2 spike protein initiates entry into target cells by binding to human angiotensin-converting enzyme 2 (ACE2). In this study, we developed DNA aptamers that specifically bind to the SARS-CoV-2 spike protein, thereby inhibiting its binding to ACE2. DNA aptamers are small nucleic acid fragments with random structures that selectively bind to various target molecules. We identified nine aptamers targeting the SARS-CoV-2 spike protein using the systematic evolution of ligands by exponential enrichment (SELEX) method and selected three optimal aptamers by comparing their binding affinities. Additionally, we confirmed that the DNA aptamers suppressed pro-inflammatory cytokines induced by the SARS-CoV-2 spike protein in ACE2-overexpressing HEK293 cells. Overall, the DNA aptamer developed in this study has the potential to bind to the SARS-CoV-2 spike protein and inhibit or block its interaction with ACE2. Thus, our DNA aptamers can be used as new biological tools for the prevention and diagnosis of SARS-CoV-2 infection.

Temporal Analysis of Postoperative Outcomes With or Without Intraoperative Motor Evoked Potentials and Somatosensory Evoked Potentials Monitoring for Intracranial Meningioma Surgery.

BACKGROUND: This study aimed to retrospectively assess results of intracranial meningioma surgery with or without intraoperative neuromonitoring (IONM) in a single institution. METHODS: Two cohorts (a historical cohort and a monitoring cohort) were collected for the analysis. Before IONM was introduced, a total of 107 patients underwent intracranial meningioma operation without IONM from January 2000 to December 2008 by one neurosurgeon (historical cohort). After IONM was introduced, a total of 99 patients with intracranial meningioma were operated under IONM between November 2018 and February 2023 by two neurosurgeons (monitoring cohort). A retrospective comparison was made on the complications from meningioma surgery between the two groups. RESULTS: In the monitoring cohort, warning signals of motor evoked potential (MEPs) or somatosensory evoked potential (SSEPs) were alarmed in 10 patients. Two of these 10 patients aborted the operation and eight of these 10 patients with warning signals underwent tumor resection. Of these eight patients, five showed postoperative morbidity. Five of 89 patients without warning signals developed neurological deficits. In the historical cohort, 14 of 107 patients showed postoperative morbidity or mortality. CONCLUSION: Even after successful resection of intracranial meningiomas prior to the advent of IONM, integration of MEPs and SSEPs monitoring yielded valuable insights for surgical teams during operative procedures.

Noggin contributes to brain metastatic colonization of lung cancer cells.

BACKGROUND: Brain metastasis is a common complication among patients with lung cancer, yet the underlying mechanisms remain unclear. In this study, we aimed to investigate the pathogenesis of brain metastasis in lung cancer. METHODS: We established highly colonizing metastatic lung cancer cells, A549-M2, through multiple implantations of A549 human lung cancer cells in the carotid artery of athymic nude mice. RESULTS: Compared to parental cells (M0), M2 cells demonstrated slower growth in culture plates and soft agar, as well as lower motility and higher adhesion, key characteristics of mesenchymal-epithelial transition (MET). Further analysis revealed that M2 cells exhibited decreased expression of epithelial-mesenchymal transition markers, including ZEB1 and Vimentin. M2 cells also demonstrated reduced invasiveness in co-culture systems. RNA sequencing and gene set enrichment analysis confirmed that M2 cells underwent MET. Intriguingly, depletion of Noggin, a BMP antagonist, was observed in M2 cells, and replenishment of Noggin restored suppressed migration and invasion of M2 cells. In addition, Noggin knockdown in control M0 cells promoted cell attachment and suppressed cell migration, suggesting that Noggin reduction during brain colonization causes inhibition of migration and invasion of metastatic lung cancer cells. CONCLUSIONS: Our results suggest that lung cancer cells undergo MET and lose their motility and invasiveness during brain metastatic colonization, which is dependent on Noggin.

Transcranial application of magnetic pulses for improving brain drug delivery efficiency via intranasal injection of magnetic nanoparticles.

As the blood-brain barrier (BBB) hinders efficient drug delivery to the brain, drug delivery via the intranasal pathway, bypassing the BBB, has received considerable attention. However, intranasal administration still has anatomical and physiological limitations, necessitating further solutions to enhance effectiveness. In this study, we used transcranial magnetic stimulation (TMS) on fluorescent magnetic nanoparticles (MNPs) of different sizes (50, 100, and 300 nm) to facilitate MNP's transportation and delivery to the brain parenchyma. To validate this concept, anesthetized rats were intranasally injected with the MNPs, and TMS was applied to the center of the head. As the result, a two-fold increase in brain MNP delivery was achieved using TMS compared with passive intranasal administration. In addition, histological analysis that was performed to investigate the safety revealed no gross or microscopic damages to major organs caused by the nanoparticles. While future studies should establish the delivery conditions in humans, we expect an easy clinical translation in terms of device safety, similar to the use of conventional TMS. The strategy reported herein is the first critical step towards effective drug transportation to the brain.

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

What is the optimal prolactin cutoff for predicting the presence of a pituitary adenoma in patients with polycystic ovary syndrome?

Objective: Hyperprolactinemia (HPRL) and polycystic ovary syndrome (PCOS) are common causes of infertility in women of reproductive age. A pituitary adenoma (PA) is the most common type of brain tumor that causes HPRL. In the neurosurgical field, the co-existence of PA and PCOS is not common. However, neurosurgeons often treat patients who are referred from gynecology. Because most of these patients are young and reproductive-aged, it is difficult for a neurosurgeon to come up with a treatment plan alone. In this study, we investigated the prevalence of PAs in PCOS patients, the cutoff prolactin (PRL) level to detect PAs, and the treatment strategy, then assessed the relationship between these diseases via a literature review. Methods: Medical records from November 2009 to March 2020 were reviewed at our institute. A total of 657 PCOS patients were enrolled. Initial prolactin levels were investigated and hyperprolactinemic patients were selected. As a result of sella magnetic resonance imaging (MRI), patients were divided into 2 groups of those with hyperprolactinemia but without PAs (group A) and those with both hyperprolactinemia and PAs (group B), respectively. We then compared and analyzed each group to find the characteristics and statistical differences. Receiver operating characteristic (ROC) curve analysis was performed to determine a cutoff value of the serum PRL level that could detect PAs in hyperprolactinemic PCOS patients. Results: Of 657 patients diagnosed with PCOS, 76 patients had hyperprolactinemia (76/657, 11.6%). Sella MRI was performed in 56 patients, excluding 20 patients for various reasons. Patients in groups A and B numbered 43 and 13, respectively, and the mean serum prolactin level significantly differed between the groups (39.89 ± 41.64 vs. 108.59 ± 60.70 ng/mL, P < 0.001). Based on the ROC curve analysis of the prolactin threshold level for predicting PAs in PCOS patients, the area under the ROC curve was 0.853 (95% confidence interval, 0.733-0.934; P < 0.001), and the sensitivity and specificity were 76.9% and 86.1%, respectively. Ultimately, the cutoff value for prolactin level was 52.9 ng/mL. Conclusion: PCOS and hyperprolactinemia are common causes of infertility in reproductive-age women. PCOS patients with a PRL level of ≥ 52.9 ng/mL may need to undergo sella MRI for detecting PAs. To help ensure a favorable clinical course for these patients, systematic diagnosis, treatment, and follow-up plan should be established. Therefore, a multidisciplinary approach involving both neurosurgery and gynecology is essential.

Advances in Brain Metastasis Models.

To obtain achievements in addressing the clinical challenges of brain metastasis, we need a clear understanding of its biological mechanisms. Brain metastasis research is challenged by many practical scientific barriers. Depending on the purpose of the study, experimental brain metastasis models in vivo can be used. It is now possible to re-create the architecture and physiology of human organs. Human organoids provide unique opportunities for the study of human disease and complement animal models. The translation of experimental findings to clinical application has several barriers in the development of treatment for brain metastasis. A variety of models have provided significant contributions to the knowledge of brain metastasis pathology and remain pivotal tools for examining novel therapeutic strategies.

Comparison of Single- and Multi-Echo Susceptibility-Weighted Imaging in Detecting Cerebral Arteriovenous Shunts: A Preliminary Study.

Purpose: To compare the sensitivities of T2-weighted image (T2WI) and susceptibility-weighted imaging (SWI) in detecting cerebral arteriovenous fistula (AVF), cerebral arteriovenous malformation (AVM), and carotid-cavernous sinus fistula (CCF), and to qualitatively evaluate single-echo SWI (s-SWI) and multi-echo SWI (m-SWI) in characterizing vascular lesions. Materials and Methods: From January 2016 to December 2021, cerebral angiography-proven lesions were recruited. The sensitivities of T2WI and SWI in detecting vascular lesions were compared using McNemar's test. Qualitative evaluations of s-SWI and m-SWI were categorized to be of poor, average, or good quality and compared using Fisher's exact test. Results: A total of 24 patients (mean age: 61 years, 12 female, and 12 male) were enrolled. Twenty patients underwent s-SWI or m-SWI, and four patients underwent both. AVF, AVM, and CCF were diagnosed in 10, 11, and 3 patients, respectively. SWI demonstrated higher sensitivity compared to that of T2WI (82.1% vs. 53.6%, p = 0.013). m-SWI showed better image quality compared to that of s-SWI (good quality, 83.3% vs. 25.0%, p = 0.009). Conclusion: SWI demonstrated a higher sensitivity for detecting cerebral arteriovenous shunts compared to that of T2WI. m-SWI exhibited better image quality compared to that of s-SWI in characterizing vascular lesions.

Lipid Accumulation Product Index Predicts New-Onset Type 2 Diabetes Among Non-Obese Koreans: A 12-Year Longitudinal Study.

Purpose: The lipid accumulation product (LAP) has been a potential indicator of central lipid accumulation status. This study aimed to assess the longitudinal association between LAP index and incident type 2 diabetes among non-obese Korean adults using a large, community-based Korean cohort observed over 12 years. Patients and Methods: This study included 4281 non-diabetic adults without generalized obesity and abdominal obesity and aged 40-69 years from the Korean Genome and Epidemiology Study. The participants were divided into four groups according to LAP index quartiles, calculated as (waist circumference [cm] - 65) x (triglycerides [mmol/L]) in men and (waist circumference [cm] - 58) x (triglycerides [mmol/L]) in women. We prospectively assessed hazard ratios (HRs) with 95% confidential intervals (CIs) for incident type 2 diabetes using multivariate Cox proportional hazard regression models. Results: Overall, 608 (14.2%) participants developed type 2 diabetes during the follow-up period. HRs for incident type 2 diabetes in the second, third, and fourth LAP quartile were 1.32 (95% CI: 0.97-1.79), 1.51 (95% CI: 1.11-2.06), and 2.14 (95% CI: 1.56-2.94), respectively, after adjusting for age, sex, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and impaired glucose tolerance. Conclusion: A high LAP index can be an additional indicator for new-onset T2DM among middle-aged and elderly non-obese Koreans.

Association between Temporal Muscle Thickness and Overall Survival in Non-Small Cell Lung Cancer Patients with Brain Metastasis.

Temporal muscle thickness (TMT) has recently been suggested as a novel biomarker of sarcopenia in head and neck malignancies. However, few studies have evaluated TMT as a prognostic marker in patients with brain metastasis. This study investigated the association of TMT with overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastasis. The records of all NSCLC patients with brain metastasis between 2009 and 2018 at St. Vincent's Hospital were reviewed retrospectively. A total of 221 patients met our eligibility criteria. In the group with TMT thicker than the median, OS was longer than the group with TMT thinner than the median (240 days versus 139 days, p = 0.014). In multivariate analysis, the thicker TMT group had longer survival (HR 0.73 CI 0.56−0.96, p = 0.024). Male (HR 1.58 CI 1.19−2.09, p = 0.002) and older age (≥65 years) (HR 2.05 CI 1.53−2.74, p < 0.001) also showed statistical significance. We also performed subgroup analysis in older patients (≥65 years). In this subgroup of 107 patients, the thicker TMT group also showed longer OS than the thinner TMT group (209 days versus 82 days, p = 0.009). Our findings suggest that TMT can be a useful biomarker for OS in NSCLC patients with brain metastasis.

Human Palatine Tonsils Are Linked to Alzheimer's Disease through Function of Reservoir of Amyloid Beta Protein Associated with Bacterial Infection.

Amyloid-ß (Aß)-peptide production or deposition in the neuropathology of Alzheimer's disease (AD) was shown to be caused by chronic inflammation that may be induced by infection, but the role of pathogenic-bacteria-related AD-associated Aß is not yet clearly understood. In this study, we validated the hypothesis that there is a correlation between the Aß-protein load and bacterial infection and that there are effects of bacteria, Staphylococcus aureus (S. aureus), on the Aß load in the inflammatory environment of human tonsils. Here, we detected Aß-peptide deposits in human tonsil tissue as well as tissue similar to tonsilloliths found in the olfactory cleft. Interestingly, we demonstrated for the first time the presence of Staphylococcus aureus (S. aureus) clustered around or embedded in the Aß deposits. Notably, we showed that treatment with S. aureus upregulated the Aß-protein load in cultures of human tonsil organoids and brain organoids, showing the new role of S. aureus in Aß-protein aggregation. These findings suggest that a reservoir of Aß and pathogenic bacteria may be a possible therapeutic target in human tonsils, supporting the treatment of antibiotics to prevent the deposition of Aß peptides via the removal of pathogens in the intervention of AD pathogenesis.

[Corrigendum] Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Subsequently to the publication of the above article, the authors have realized that Fig. 3 on p. 6, showing the results of bioluminescence imaging of U87 and U373 cells after applying tumor­treating fields for 72 h, was published containing an erroneous image. Essentially, the data analysis panel for the U87 / U87TTF experiment was inadvertently copied across for the U373 / U373TTF experiment for the '75% Duty' experimental condition. The revised version of Fig. 3, now showing the correct data analysis panel for the '75% Duty' U373 / U373TTF experiment, is shown below. The authors confirm that the error made in the presentation of Fig. 3 did not adversely affect the conclusions reported in this paper, and they are grateful to the Editor of International Journal of Oncology for granting them this opportunity to publish a Corrigendum. All the authors agree to the publication of this Corrigendum; they also apologize to the readership for any inconvenience caused. [International Journal of Oncology 60: 8, 2022; DOI: 10.3892/ijo.2021.5298].

Assessment of Bacterial Communities Within the Biofilm of Bladder Calculi in the Neurogenic Bladder Rat Model Following Spinal Cord Injury.

PURPOSE: To develop a rat model of bladder calculi in the neurogenic bladder following spinal cord injury (SCI) and assess bacterial communities within the biofilm of bladder calculi using denaturing gradient gel electrophoresis (DGGE). METHODS: The silk tied to a small segment of the Teflon IV catheter was implanted through the urethra into the bladder of rats with SCI induced by T9 laminectomy. After 6 months, the rats were sacrificed and their bladder calculi were collected by opening the bladders through the low-midline incision. Genomic DNA was extracted from the biofilm of bladder calculi followed by DGGE to obtain bacterial DNA. The DNA sequences were compared and analyzed using BLAST (Basic Local Alignment Search Tool) to identify bacteria. RESULTS: After placing silk nidus in the bladder for 6 months, all 6 rats developed bladder calculi. According to DGGE analysis, Pseudomonas aeruginosa was the most dominant strain, while Clostridium sp. and Lactobacillus sp. were relatively dominant strains within the biofilm of bladder calculi in the rats with SCI. CONCLUSION: DGGE analysis showed various microorganisms in the biofilm of calculi arising from a neurogenic bladder rat model. This research design can be the basis for clinical studies and may be applied to calculi in patients with neurogenic bladder following SCI.

Clinical feasibility of modified procarbazine and lomustine chemotherapy without vincristine as a salvage treatment for recurrent adult glioma.

Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose reduction or discontinuation in patients with recurrent glioma. The current study evaluated the safety and efficacy of modified procarbazine and lomustine (PC) chemotherapy that omits vincristine and reduces the lomustine dose compared with those of conventional PCV chemotherapy. Using electronic medical records, all patients with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary's Hospital or St. Vincent's Hospital were examined retrospectively. A total of 59 patients met the eligibility criteria. Among them, 15 patients received modified PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). The PC group presented a significantly lower hematology toxicity (anemia, 6.7 vs. 45.5%, P=0.02; thrombocytopenia 20.0 vs. 70.4%, P<0.001). Additionally, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s) or total cessation of chemotherapy, were significantly less frequent compared with the PCV group (26.7 vs. 68.2%, P=0.012). The overall survival of the PC group was also significantly longer than that of PCV group (396 vs. 232 days, P=0.042), while there was no significant difference in progression-free survival between the two groups (284.5 vs. 131 days, P=0.077). The results suggested that modified PC chemotherapy may be an alternative chemotherapeutic regimen with tolerable toxicity and without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are required to validate our findings.

Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-ß Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer's Disease.

The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer's disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-ß peptide (Aß1-42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aß1-42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aß1-42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aß1-42. Silencing OPN via siRNA suppressed Aß-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.

Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Tumor­treating fields (TTFields) are emerging cancer therapies based on alternating low­intensity electric fields that interfere with dividing cells and induce cancer cell apoptosis. However, to date, there is limited knowledge of their effects on normal cells, as well as the effects of different duty cycles on outcomes. The present study evaluated the effects of TTFields with different duty cycles on glioma spheroid cells and normal brain organoids. A customized TTFields system was developed to perform in vitro experiments with varying duty cycles. Three duty cycles were applied to three types of glioma spheroid cells and brain organoids. The efficacy and safety of the TTFields were evaluated by analyzing the cell cycle of glioma cells, and markers of neural stem cells (NSCs) and astrocytes in brain organoids. The application of the TTFields at the 75 and 100% duty cycle markedly inhibited the proliferation of the U87 and U373 compared with the control. FACS analysis revealed that the higher the duty cycle of the applied fields, the greater the increase in apoptosis detected. Exposure to a higher duty cycle resulted in a greater decrease in NSC markers and a greater increase in glial fibrillary acidic protein expression in normal brain organoids. These results suggest that TTFields at the 75 and 100% duty cycle induced cancer cell death, and that the neurotoxicity of the TTFields at 75% was less prominent than that at 100%. Although clinical studies with endpoints related to safety and efficacy need to be performed before this strategy may be adopted clinically, the findings of the present study provide meaningful evidence for the further advancement of TTFields in the treatment of various types of cancer.

Association between height and the risk of primary brain malignancy in adults: a nationwide population-based cohort study.

BACKGROUND: The association between height and the risk of developing primary brain malignancy remains unclear. We evaluated the association between height and risk of primary brain malignancy based on a nationwide population-based database of Koreans. METHODS: Using data from the Korean National Health Insurance System cohort, 6 833 744 people over 20 years of age that underwent regular national health examination were followed from January 2009 until the end of 2017. We documented 4771 cases of primary brain malignancy based on an ICD-10 code of C71 during the median follow-up period of 7.30 years and 49 877 983 person-years. RESULTS: When dividing the population into quartiles of height for each age group and sex, people within the highest height quartile had a significantly higher risk of brain malignancy, compared to those within the lowest height quartile (HR 1.21 CI 1.18-1.32) after adjusting for potential confounders. We also found that the risk of primary brain malignancy increased in proportion with the quartile increase in height. After analyzing subgroups based on older age (≥ 65) and sex, we found positive relationships between height and primary brain malignancy in all subgroups. CONCLUSIONS: This study is the first to suggest that height is associated with an increased risk of primary brain malignancy in the East-Asian population. Further prospective and larger studies with precise designs are needed to validate our findings.

Modified Orbitozygomatic Approach for Resecting a Parasellar Tumor in a Single Institution.

BACKGROUND: Modified orbitozygomatic craniotomy is characterized by simplicity and wide exposure. The purpose of the present study was to describe a modified orbitozygomatic approach without resecting the zygomatic arch for large parasellar tumor surgeries. METHODS: Between April 2016 and December 2019, seven patients with parasellar tumor underwent surgiest with a modified orbitozygomatic approach. Surgical procedures, clinical outcomes, and complications were analyzed. RESULTS: This study included 3 meningiomas, 2 pituitary adenomas, 1 chondrosarcoma, and 1 schwannoma. Modified orbitozygomatic craniotomy provides a wider surgical freedom in the opticocarotid and prechiasmatic cistern than frontotemporal craniotomy without orbitotomy, Total, subtotal, and partial resections were achieved for 3, 2, and 2 patients, respectively. Reasons for partial resections were tight adhesion to the carotid artery and encasing of the carotid artery. Permanent morbidities developed in one patient with 3rd nerve palsy and one patient with hemiparesis. CONCLUSION: Modified orbitozygomatic approach can provide the shortest access to the interpeduncular cistern with a minimum brain retraction. Surgeons who experience surgical challenge during the conventional approach for parasellar tumor resection are recommended to learn the modified orbitozygomatic approach.

Associations of General and Abdominal Obesity with the Risk of Glioma Development.

The association between obesity and the risk of glioma remains unclear. We sought to evaluate the potential association between general and abdominal obesity and the risk of glioma based on a nationwide population-based cohort study of Koreans. Using data from the Korean National Health Insurance System cohort, 6,833,744 people older than 20 years who underwent regular national health examination in both 2009 and 2011 were followed until the end of 2017. We documented 4771 glioma cases based on an ICD-10 code of C71 during the median follow-up period of 7.30 years. Individuals with a body mass index (BMI) ≥ 25.0 kg/m2 were at significantly higher risk of developing glioma than those with a BMI < 25.0 kg/m2 (HR 1.08 CI 1.02-1.15). Individuals with a waist circumference (WC) ≥ 90 cm (males)/85 cm (females) also had a significantly higher risk of glioma than those with a WC < 90 cm (males)/85 cm (females) (HR 1.16 CI 1.09-1.24). In the group with a BMI ≥ 25.0 kg/m2, individuals with abdominal obesity were at significantly higher risk of developing glioma (HR 1.18 CI 1.09-1.27) than those without abdominal obesity. The role of abdominal obesity in this association was stronger in women than in men. To the best of our knowledge, this is the first demonstration that obese people may be at higher risk of glioma, especially centrally obese people from an Asian population with a BMI ≥ 25.0 kg/m2. Loss of visceral fat in people with abdominal obesity may reduce their risk of developing glioma.