Inhibitory effect of recombinant tyrosine­sulfated madanin­1, a thrombin inhibitor, on the behavior of MDA­MB­231 and SKOV3 cells in vitro.

Thrombin, which plays a crucial role in hemostasis, is also implicated in cancer progression. In the present study, the effects of the thrombin­targeting recombinant tyrosine­sulfated madanin­1 on cancer cell behavior and signaling pathways compared with madanin­1 wild­type (WT) were investigated. Recombinant madanin­1 2 sulfation (madanin­1 2S) and madanin­1 WT proteins were generated using Escherichia coli. SKOV3 and MDA­MB­231 cells were treated with purified recombinant proteins with or without thrombin stimulation. Migration and invasion of cells were analyzed by wound healing assay and Transwell assay, respectively. Thrombin markedly increased cell migration and invasion in both SKOV3 and MDA­MB­231 cells, which were significantly suppressed by madanin­1 2S (P<0.05). Madanin­1 2S also significantly suppressed thrombin­induced expression of phosphorylated (p)­Akt and p­extracellular signal­regulated kinase in both cell lines (P<0.05), whereas madanin­1 WT had no effect on the expression levels of these proteins in MDA­MB­231 cells. Furthermore, madanin­1 2S significantly reversed the effects of thrombin on E­cadherin, N­cadherin and vimentin expression in MDA­MB­231 cells (P<0.05), whereas madanin­1 WT did not show any effect. In conclusion, madanin­1 2S suppressed the migration and invasion of cancer cells more effectively than madanin­1 WT. It is hypothesized that inhibiting thrombin via the sulfated form of madanin­1 may be a potential candidate for enhanced cancer therapy; however, further in vivo validation is required.

Metastatic papillary renal cell carcinoma with portal vein tumor thrombosis confirmed on blind liver biopsy.

Portal vein tumor thrombosis (PVTT) is an uncommon condition in which tumor cells expand into the vessels, causing blood clot formation in the portal vein. PVTT is mainly associated with hepatocellular carcinoma, leading to an unfavorable prognosis; however, it can also develop in patients with other cancer types. Herein, we report a case of metastatic renal cell carcinoma diagnosed by a blind liver biopsy in a patient with dynamic computed tomography-confirmed portal vein thrombosis and cholangiopathy. This case illustrates the importance of systematic surveillance with routine laboratory tests and contrast-enhanced imaging studies on patients with cancer to detect potential liver infiltration of metastatic cancer.

Phospholipase C-γ as a Potential Therapeutic Target for Graves' Orbitopathy.

BACKGRUOUND: Phospholipase C-γ (PLC-γ) plays a crucial role in immune responses and is related to the pathogenesis of various inflammatory disorders. In this study, we investigated the role of PLC-γ and the therapeutic effect of the PLC-specific inhibitor U73122 using orbital fibroblasts from patients with Graves' orbitopathy (GO). METHODS: The expression of phospholipase C gamma 1 (PLCG1) and phospholipase C gamma 2 (PLCG2) was evaluated using polymerase chain reaction in GO and normal orbital tissues/fibroblasts. The primary cultures of orbital fibroblasts were treated with non-toxic concentrations of U73122 with or without interleukin (IL)-1ß to determine its therapeutic efficacy. The proinflammatory cytokine levels and activation of downstream signaling molecules were determined using Western blotting. RESULTS: PLCG1 and PLCG2 mRNA expression was significantly higher in GO orbital tissues than in controls (P<0.05). PLCG1 and PLCG2 mRNA expression was significantly increased (P<0.05) in IL-1ß, tumor necrosis factor-α, and a cluster of differentiation 40 ligand-stimulated GO fibroblasts. U73122 significantly inhibited the IL-1ß-induced expression of proinflammatory molecules, including IL-6, IL-8, monocyte chemoattractant protein-1, cyclooxygenase-2, and intercellular adhesion molecule-1 (ICAM-1), and phosphorylated protein kinase B (p-Akt) and p38 (p-p38) kinase in GO fibroblasts, whereas it inhibited IL-6, IL-8, and ICAM-1, and p-Akt and c-Jun N-terminal kinase (p-JNK) in normal fibroblasts (P<0.05). CONCLUSION: PLC-γ-inhibiting U73122 suppressed the production of proinflammatory cytokines and the phosphorylation of Akt and p38 kinase in GO fibroblasts. This study indicates the implications of PLC-γ in GO pathogenesis and its potential as a therapeutic target for GO.

Supramaximal Resection for Glioblastoma: Redefining the Extent of Resection Criteria and Its Impact on Survival.

Glioblastomas (GBMs) are the most common and aggressive primary brain tumors, and despite advances in treatment, prognosis remains poor. The extent of resection has been widely recognized as a key factor affecting survival outcomes in GBM patients. The surgical principle of "maximal safe resection" has been widely applied to balance tumor removal and neurological function preservation. Historically, T1-contrast enhanced (T1CE) extent of resection has been the focus of research; however, the "supramaximal resection" concept has emerged, advocating for even greater tumor resection while maintaining neurological function. Recent studies have demonstrated potential survival benefits associated with resection beyond T1CE extent in GBMs. This review explores the developing consensus and newly established criteria for "supramaximal resection" in GBMs, with a focus on T2-extent of resection. Systematic reviews and meta-analyses on supramaximal resection are summarized, and the Response Assessment in Neuro-Oncology (RANO) resect group classification for extent of resection is introduced. The evolving understanding of the role of supramaximal resection in GBMs may lead to improved patient outcomes and more objective criteria for evaluating the extent of tumor resection.

Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach.

There is a strong association between intracranial hypertension (IH) that occurs following the acute phase of traumatic brain injury (TBI) and negative outcomes. This study proposes a pressure-time dose (PTD)-based parameter that may specify a possible serious IH (SIH) event and develops a model to predict SIH. The minute-by-minute signals of arterial blood pressure (ABP) and intracranial pressure (ICP) of 117 TBI patients were utilized as the internal validation dataset. The SIH event was explored through the prognostic power of the IH event variables for the outcome after 6 months, and an IH event with thresholds that included an ICP of 20 mmHg and PTD > 130 mmHg * minutes was considered an SIH event. The physiological characteristics of normal, IH and SIH events were investigated. LightGBM was employed to forecast an SIH event from various time intervals using physiological parameters derived from the ABP and ICP. Training and validation were conducted on 1,921 SIH events. External validation was performed on two multi-center datasets containing 26 and 382 SIH events. The SIH parameters could be used to predict mortality (AUROC = 0.893, p < 0.001) and favorability (AUROC = 0.858, p < 0.001). The trained model robustly forecasted SIH after 5 and 480 minutes with an accuracy of 86.95% and 72.18% in internal validation. External validation also revealed a similar performance. This study demonstrated that the proposed SIH prediction model has reasonable predictive capacities. A future intervention study is required to investigate whether the definition of SIH is maintained in multi-center data and to ensure the effects of the predictive system on TBI patient outcomes at the bedside.

Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury.

PURPOSE: Glymphatic system dysfunction has been reported in animal models of traumatic brain injury (TBI). This study aimed to evaluate the activity of the human glymphatic system using the non-invasive Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS) method in patients with TBI. METHODS: A total of 89 patients with TBI (June 2018 to May 2020) were retrospectively enrolled, and 34 healthy volunteers were included who had no previous medical or neurological disease. Magnetic resonance imaging (MRI) with DTI was performed, and the ALPS index was calculated to evaluate the glymphatic system's activity. Wilcoxon rank-sum test was used to compare the ALPS index between patients with TBI and healthy controls. ANOVA was done to compare the ALPS index among controls and patients with mild/moderate-to-severe TBI. Multivariate logistic regression analyses were used to identify independent clinical and radiological factors associated with the ALPS index. The correlation between Glasgow Coma Scale (GCS) score and the ALPS index was also assessed. RESULTS: The ALPS index was significantly lower in patients with TBI than in healthy controls (median, 1.317 vs. 1.456, P < 0.0001). There were significant differences in the ALPS index between healthy controls and patients with mild/moderate-to-severe TBI (ANOVA, P < 0.001). The presence of subarachnoid hemorrhage (P = 0.004) and diffuse axonal injury (P = 0.001) was correlated with a lower ALPS index in the multivariate analysis. There was a weak positive correlation between the ALPS index and GCS scores (r = 0.242, P = 0.023). CONCLUSIONS: The DTI-ALPS method is useful for evaluating glymphatic system impairment and quantifying its activity in patients with TBI.

Endoscopic transorbital approach to the cavernous sinus: Cadaveric anatomy study and clinical application (‡SevEN-009).

Objective: Cavernous sinus (CS) invasion is frequently encountered in the management of skull base tumors. Surgical treatment of tumors in the CS is technically demanding, and selection of an optimal surgical approach is critical for maximal tumor removal and patient safety. We aimed to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the CS based on a cadaveric study. Methods: Five cadaveric heads were used for dissection under the ETOA in the comparison with the endoscopic endonasal approach (EEA) and the microscopic transcranial approach (TCA). The CS was exposed, accessed, and explored, first using the ETOA, followed by the EEA and TCA. A dedicated endoscopic system aided by neuronavigation guidance was used for the procedures. During the ETOA, neurovascular structures inside the CS were approached through different surgical triangles. Results: After completing the ETOA with interdural dissection, the lateral wall of the CS was fully exposed. The lateral and posterior compartments of the CS, of which accessibility is greatly limited under the EEA, were effectively approached and explored under the ETOA. The anteromedial triangle was the largest window via which most of the lateral compartment was freely approached. The internal carotid artery and abducens nerve were also observed through the anteromedial triangle and just behind V1. During the ETOA, the approaching view through the supratrochlear and infratrochlear triangles was more directed towards the posterior compartment. After validation of the feasibility and safety based on the cadaveric study, ETOA was successfully performed in a patient with a pituitary adenoma with extensive CS invasion. Conclusions: Based on the cadaveric study, we demonstrated that the lateral CS wall was reliably accessed under the ETOA. The lateral and posterior compartments of the CS were effectively explored via surgical triangles under the ETOA. ETOA provides a unique and valuable surgical route to the CS with a promising synergy when used with EEA and TCA. Our experience with a clinical case convinces us of the efficacy of the ETOA during surgical management of skull base tumors with CS-invasion.

Pedicled frontal periosteal rescue flap via eyebrow incision for skull base reconstruction (SevEN-002).

PURPOSE: Cerebrospinal fluid (CSF) leakage is one of the major complications after endoscopic endonasal surgery. The reconstructive nasoseptal flap is widely used to repair CSF leakage. However, it could not be utilized in all cases; thus, there was a need for an alternative. We developed a pericranial rescue flap that could cover both sellar and anterior skull base defects via the endonasal approach. A modified surgical technique that did not violate the frontal sinus and cause cosmetic problems was designed using the pericranial rescue flap. METHODS: We performed 12 cadaveric dissections to investigate the applicability of the lateral pericranial rescue flap. An incision was made, extending from the middle to the lateral part of the eyebrow. The pericranium layer was dissected away from the galea layer, from the supraorbital region towards the frontoparietal region. With endoscopic assistance, the periosteal flap was raised, the flap base was the pericranium layer at the eyebrow incision. After a burr-hole was made in the supraorbital bone, the pericranial flap was inserted via the intradural or extradural pathway. RESULTS: The mean size of the pericranial flap was 11.5 cm × 3.2 cm. It was large enough to cross the midline and cover the dural defects of the anterior skull base, including the sellar region. CONCLUSION: We demonstrated a modified endoscopic technique to repair the anterior skull base defects. This minimally invasive pericranial flap may resolve neurosurgical complications, such as CSF leakage.

The efficacy of EGFR-tyrosine kinase inhibitor in non-small cell lung cancer patients with synchronous brain metastasis: a real-world study.

BACKGROUND/AIMS: The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. METHODS: A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. RESULTS: Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. CONCLUSION: This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.

A novel biguanide (IM1761065) inhibits bioenergetics of glioblastoma tumorspheres.

PURPOSE: Glioblastoma (GBM) is a rapidly growing tumor in the central nervous system with altered metabolism. Depleting the bioenergetics of tumors with biguanides have been suggested as an effective therapeutic approach for treating GBMs. The purpose of this study was to determine the effects of IM1761065, a novel biguanide with improved pharmacokinetics, on GBM-tumorspheres (TSs). METHODS: The biological activities of IM1761065 on GBM-TSs, including their effects on viability, ATP levels, cell cycle, stemness, invasive properties, and transcriptomes were examined. The in vivo efficacy of IM1761065 was tested in a mouse orthotopic xenograft model. RESULTS: IM1761065 decreased the viability and ATP levels of GBM-TSs in a dose-dependent manner, and reduced basal and spare respiratory capacity in patient-derived GBM-TS, as measured by the oxygen consumption rate. Sphere formation, expression of stemness-related proteins, and invasive capacity of GBM-TSs were also significantly suppressed by IM1761065. A gene-ontology comparison of IM1761065-treated groups showed that the expression levels of stemness-related, epithelial mesenchymal transition-related, and mitochondrial complex I genes were also significantly downregulated by IM1761065. An orthotopic xenograft mouse model showed decreased bioluminescence in IM1761065-treated cell-injected mice at 5 weeks. IM1761065-treated group showed longer survival than the control group (P = 0.0289, log-rank test). CONCLUSION: IM1761065 is a potent inhibitor of oxidative phosphorylation. The inhibitory effect of IM1761065 on the bioenergetics of GBM-TS suggests that this novel compound could be used as a new drug for the treatment of GBM.

Patterns of recurrence according to the extent of resection in patients with IDH-wild-type glioblastoma: a retrospective study.

OBJECTIVE: In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis. METHODS: This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)-wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed. RESULTS: Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p < 0.0001). CONCLUSIONS: In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH-wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.

Extended endoscopic transorbital approach with superior-lateral orbital rim osteotomy: cadaveric feasibility study and clinical implications (SevEN-007).

OBJECTIVE: The endoscopic transorbital approach (ETOA) has been developed, permitting a new surgical corridor. Due to the vertical limitation of the ETOA, some lesions of the anterior cranial fossa are difficult to access. The ETOA with superior-lateral orbital rim (SLOR) osteotomy can achieve surgical freedom of vertical as well as horizontal movement. The purpose of this study was to confirm the feasibility of the ETOA with SLOR osteotomy. METHODS: Anatomical dissections were performed in 5 cadaveric heads with a neuroendoscope and neuronavigation system. ETOA with SLOR osteotomy was performed on one side of the head, and ETOA with lateral orbital rim (LOR) osteotomy was performed on the other side. After analysis of the results of the cadaveric study, the ETOA with SLOR osteotomy was applied in 6 clinical cases. RESULTS: The horizontal and vertical movement range through ETOA with SLOR osteotomy (43.8° ± 7.49° and 36.1° ± 3.32°, respectively) was improved over ETOA with LOR osteotomy (31.8° ± 5.49° and 23.3° ± 1.34°, respectively) (p < 0.01). Surgical freedom through ETOA with SLOR osteotomy (6025.1 ± 220.1 mm3) was increased relative to ETOA with LOR osteotomy (4191.3 ± 57.2 mm3) (p < 0.01); these values are expressed as the mean ± SD. Access levels of ETOA with SLOR osteotomy were comfortable, including anterior skull base lesion and superior orbital area. The view range of the endoscope for anterior skull base lesions was increased through ETOA with SLOR osteotomy. After SLOR osteotomy, the space for moving surgical instruments and the endoscope was widened. Anterior clinoidectomy could be achieved successfully using ETOA with SLOR osteotomy. The authors performed ETOA with SLOR osteotomy in 6 cases of brain tumor. In all 6 cases, complete removal of the tumor was successfully accomplished. In the 3 cases of anterior clinoidal meningioma, anterior clinoidectomy was performed easily and safely, and manipulation of the extended dural margin and origin dura mater was possible. There was no complication related to this approach. CONCLUSIONS: The authors evaluated the clinical feasibility of ETOA with SLOR osteotomy based on a cadaveric study. ETOA with SLOR osteotomy could be applied to more diverse disease groups that do not permit conventional ETOA or to cases in which surgical application is challenging. ETOA with SLOR osteotomy might serve as an opportunity to broaden the indication for the ETOA.

Endoscopic Transorbital Approach to Mesial Temporal Lobe for Intra-Axial Lesions: Cadaveric Study and Case Series (SevEN-008).

BACKGROUND: Endoscopic transorbital approach (ETOA) has been proposed as a minimally invasive technique for the treatment of skull base lesions located around mesial temporal lobe (MTL), mostly extra-axial pathology. OBJECTIVE: To explore the feasibility of ETOA in accessing intraparenchymal MTL with cadaveric specimens and describe our initial clinical experience of ETOA for intra-axial lesions in MTL. METHODS: Anatomic dissections were performed in 4 adult cadaveric heads using a 0° endoscope. First, a stepwise anatomical investigation of ETOA to intraparenchymal MTL was explored. Then, ETOA was applied clinically for 7 patients with intra-axial lesions in MTL, predominantly high-grade gliomas (HGGs) and low-grade gliomas (LGGs). RESULTS: The extradural stage of ETOA entailed a superior eyelid incision followed by orbital retraction, drilling of orbital roof, greater and lesser wing of sphenoid bone, and cutting of the meningo-orbital band. For the intradural stage, the brain tissue medial to the occipito-temporal gyrus was aspirated until the temporal horn was opened. The structures of MTL could be aspirated selectively in a subpial manner without injury to the neurovascular structures of the ambient and sylvian cisterns, and the lateral neocortex. After cadaveric validation, ETOA was successfully performed for 4 patients with HGGs and 3 patients with LGGs. Gross total resection was achieved in 6 patients (85.7%) without significant surgical morbidities including visual field deficits. CONCLUSION: ETOA provides a logical line of access for intra-axial lesions in MTL. The safe and natural surgical trajectory of ETOA can spare brain retraction, neurovascular injury, and disruption of the lateral neocortex.

Whole-Brain Radiotherapy vs. Localized Radiotherapy after Resection of Brain Metastases in the Era of Targeted Therapy: A Retrospective Study.

Whether targeted therapy (TT) and radiotherapy impact survival after resection of brain metastases (BM) is unknown. The purpose of this study was to analyze the factors affecting overall survival (OS), local control (LC), distant control (DC), and leptomeningeal metastases (LMM) in patients who had undergone resection of BM. We retrospectively analyzed 124 consecutive patients who had undergone resection of BM between 2004 and 2020. Patient information about age, sex, Karnofsky Performance Scale (KPS), origin of cancer, synchronicity, tumor size, status of primary cancer, use of TT, extent of resection, and postoperative radiotherapy was collected. Radiation therapy was categorized into whole-brain radiotherapy (WBRT), localized radiotherapy (local brain radiotherapy or stereotactic radiosurgery (LBRT/SRS)), and no radiation. We identified factors that affect OS, LC, DC, and LMM. In multivariable analysis, significant factors for OS were higher KPS score (≥90) (HR 0.53, p = 0.011), use of TT (HR 0.43, p = 0.001), controlled primary disease (HR 0.63, p = 0.047), and single BM (HR 0.55, p = 0.016). Significant factors for LC were gross total resection (HR 0.29, p = 0.014) and origin of cancer (p = 0.041). Both WBRT and LBRT/SRS showed superior LC than no radiation (HR 0.32, p = 0.034 and HR 0.38, p = 0.018, respectively). Significant factors for DC were use of TT (HR 0.54, p = 0.022) and single BM (HR 0.47, p = 0.004). Reduced incidence of LMM was associated with use of TT (HR 0.42, p = 0.038), synchronicity (HR 0.25, p = 0.028), and controlled primary cancer (HR 0.44, p = 0.047). TT was associated with prolonged OS, improved DC, and reduced LMM in resected BM patients. WBRT and LBRT/SRS showed similar benefits on LC. Considering the extended survival of cancer patients and the long-term effect of WBRT on cognitive function, LBRT/SRS appears to be a good option after resection of BM.

Virtual dissection of the real brain: integration of photographic 3D models into virtual reality and its effect on neurosurgical resident education.

OBJECTIVE: Virtual reality (VR) is increasingly being used for education and surgical simulation in neurosurgery. So far, the 3D sources for VR simulation have been derived from medical images, which lack real color. The authors made photographic 3D models from dissected cadavers and integrated them into the VR platform. This study aimed to introduce a method of developing a photograph-integrated VR and to evaluate the educational effect of these models. METHODS: A silicone-injected cadaver head was prepared. A CT scan of the specimen was taken, and the soft tissue and skull were segmented to 3D objects. The cadaver was dissected layer by layer, and each layer was 3D scanned by a photogrammetric method. The objects were imported to a free VR application and layered. Using the head-mounted display and controllers, the various neurosurgical approaches were demonstrated to neurosurgical residents. After performing hands-on virtual surgery with photographic 3D models, a feedback survey was collected from 31 participants. RESULTS: Photographic 3D models were seamlessly integrated into the VR platform. Various skull base approaches were successfully performed with photograph-integrated VR. During virtual dissection, the landmark anatomical structures were identified based on their color and shape. Respondents rated a higher score for photographic 3D models than for conventional 3D models (4.3 ± 0.8 vs 3.2 ± 1.1, respectively; p = 0.001). They responded that performing virtual surgery with photographic 3D models would help to improve their surgical skills and to develop and study new surgical approaches. CONCLUSIONS: The authors introduced photographic 3D models to the virtual surgery platform for the first time. Integrating photographs with the 3D model and layering technique enhanced the educational effect of the 3D models. In the future, as computer technology advances, more realistic simulations will be possible.

Correlation Between 18F-FDG Uptake and Immune Cell Infiltration in Metastatic Brain Lesions.

BACKGROUND: The purpose of this study was to investigate the correlation between 18F-fluorodeoxyglucose (FDG) uptake and infiltrating immune cells in metastatic brain lesions. METHODS: This retrospective study included 34 patients with metastatic brain lesions who underwent brain 18F-FDG positron emission tomography (PET)/computed tomography (CT) followed by surgery. 18F-FDG uptake ratio was calculated by dividing the standardized uptake value (SUV) of the metastatic brain lesion by the contralateral normal white matter uptake value. We investigated the clinicopathological characteristics of the patients and analyzed the correlation between 18F-FDG uptake and infiltration of various immune cells. In addition, we evaluated immune-expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and Ki-67 in metastatic brain lesions. RESULTS: The degree of 18F-FDG uptake of metastatic brain lesions was not significantly correlated with clinical parameters. There was no significant relationship between the 18F-FDG uptake and degree of immune cell infiltration in brain metastasis. Furthermore, other markers, such as GLUT1, HK2, and Ki-67, were not correlated with degree of 18F-FDG uptake. In metastatic brain lesions that originated from breast cancer, a higher degree of 18F-FDG uptake was observed in those with high expression of CD68. CONCLUSIONS: In metastatic brain lesions, the degree of 18F-FDG uptake was not significantly associated with infiltration of immune cells. The 18F-FDG uptake of metastatic brain lesions from breast cancer, however, might be associated with macrophage activity.

Importance of Sufficient Petrosectomy in an Anterior Petrosal Approach: Relightening of the Kawase Pyramid.

BACKGROUND: In 1985, Kawase published an anterior petrosal approach to expose the posterior cranial fossa and to minimize retraction of the temporal lobe. However, some neurosurgeons still have difficulty with removing tumors through an anterior petrosal approach because a complete understanding of the Kawase pyramid has not been achieved. We hypothesized that if anterior petrosectomy were performed with three-dimensional understanding of the Kawase pyramid, it would have a positive effect on extent of tumor resection. METHODS: We performed a retrospective study of patients who underwent surgical treatment for meningioma through an anterior petrosal approach. Patients were divided into total resection and subtotal resection groups, and statistical differences between the groups were analyzed. To identify factors predictive of complete tumor removal, univariable and multivariable logistic regression analyses were performed. RESULTS: Width and height of the drilled internal auditory canal of the total resection group were significantly larger than those of the subtotal resection group (P = 0.001, P = 0.033). The operative angle of the total resection group was significantly larger than that of the subtotal resection group (P < 0.001). Regression analyses showed only drilled internal auditory canal width to be predictive of complete tumor removal, increasing the likelihood of complete tumor removal by 2.778-fold with an increase in drilled internal auditory canal width by 1 mm (P = 0.023). CONCLUSIONS: Insufficient petrosectomy during an anterior petrosal approach adversely affects the extent of tumor resection. Furthering three-dimensional understanding of the Kawase pyramid could aid in complete tumor resection and better outcomes without causing damage to the surrounding organs.

Endoscopic transorbital approach to the insular region: cadaveric feasibility study and clinical application (SevEN-005).

OBJECTIVE: The insula is a complex anatomical structure. Accessing tumors in the insula remains a challenge due to its anatomical complexity and the high chance of morbidity. The goal of this study was to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the insular region based on a cadaveric study. METHODS: One cadaveric head was used to study the anatomy of the insula and surrounding vessels. Then, anatomical dissection was performed in 4 human cadaveric heads using a dedicated endoscopic system with the aid of neuronavigation guidance. To assess the extent of resection, CT scanning was performed before and after dissection. The insular region was directly exposed by a classic transcranial approach to check the extent of resection from the side with a classic transcranial approach. RESULTS: The entire procedure consisted of two phases: an extradural orbital phase and an intradural sylvian phase. After eyelid incision, the sphenoid bone and orbital roof were extensively drilled out with exposure of the frontal and temporal dural layers. After making a dural window, the anterior ramus of the sylvian fissure was opened and dissected. The M2 segment of the middle cerebral artery (MCA) was identified and traced posterolaterally. A small corticectomy was performed on the posterior orbital gyrus. Through the window between the lateral lenticulostriate arteries and M2, the cortex and medulla of the insula were resected in an anteroposterior direction without violation of the M2 segment of the MCA or its major branches. When confirmed by pterional craniotomy, the sylvian fissure and the MCA were found to be anatomically preserved. After validation of the feasibility and safety based on a cadaveric study, the ETOA was successfully performed in a patient with a high-grade glioma (WHO grade III) in the right insula. CONCLUSIONS: The transorbital route can be considered a potential option to access tumors located in the insula. Using an ETOA, the MCA and its major branches were identified and preserved while removal was performed along the long axis of the insula. In particular, lesions in the anterior part of the insula are most benefited by this approach. Because this approach was implemented in only one patient, additional discussion and further verification is required.

Association between survival and levetiracetam use in glioblastoma patients treated with temozolomide chemoradiotherapy.

This study was conducted to assess whether levetiracetam (LEV) affects the survival of patients with glioblastoma (GBM) treated with concurrent temozolomide (TMZ) chemotherapy. To this end, from 2004 to 2016, 322 patients with surgically resected and pathologically confirmed isocitrate dehydrogenase (IDH)-wildtype GBM who received TMZ-based chemoradiotherapy were analysed. The patients were divided into two groups based on whether LEV was used as an anticonvulsant both at the time of surgery and the first visit thereafter. The median overall survival (OS) and progression-free survival (PFS) were compared between the groups. The OS was 21.1 and 17.5 months in the LEV (+) and LEV (-) groups, respectively (P = 0.003); the corresponding PFS was 12.3 and 11.2 months (P = 0.017). The other prognostic factors included age, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and Karnofsky Performance Status (KPS) score. The multivariate analysis showed age (hazard ratio [HR], 1.02; P < 0.001), postoperative KPS score (HR 0.99; P = 0.002), complete tumour resection (HR 0.52; P < 0.001), MGMT promoter methylation (HR 0.75; P < 0.001), and LEV use (HR 0.72; P = 0.011) were significantly associated with OS. In conclusion, LEV use was associated with prolonged survival in patients with GBM treated with concurrent TMZ chemoradiotherapy.

Biportal endoscopic transorbital approach: a quantitative anatomical study and clinical application.

BACKGROUND: We devised a biportal endoscopic transorbital approach (BiETOA) to gain surgical freedom by making a port for the endoscope and investigated the benefits and limitations of BiETOA. METHODS: A cylindrical port was designed and 3-D printed using biocompatible material. The port was inserted through a keyhole between the superolateral side of the orbital rim and the temporal muscle. An endoscope was inserted through the port, and other instruments were inserted through the conventional transorbital route. BiETOA was used to dissect eight cadaveric heads, and the angle of attack and surgical freedom were assessed. RESULTS: The mean maximal angle of attack was significantly different in BiETOA and endoscopic transorbital approach (ETOA) (P < 0.01) but not in BiETOA and ETOA lateral orbital rim (LOR) osteotomy (P = 0.207, P = 0.21). The mean surgical freedom was significantly different in BiETOA and ETOA (P < 0.01) and in BiETOA and ETOA LOR osteotomy (P < 0.01). In the clinical cases, tumors were removed successfully without any complications. CONCLUSIONS: BiETOA provided increased surgical freedom and better visibility of deep target lesion and resulted in good surgical and cosmetic outcomes.