Publications by authors named "Park Chul-Kee"

258 Publications

Journal Citation Report 2020 and Impact Factor of Journal of Korean Neurosurgical Society.

J Korean Neurosurg Soc 2021 Sep 1;64(5):675-676. Epub 2021 Sep 1.

Managing Editor, Journal of Korean Neurosurgical Society; Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Soonchunhayng University College of Medicine, Bucheon, Korea.

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http://dx.doi.org/10.3340/jkns.2021.0208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435650PMC
September 2021

Safety of endoscopic endonasal biopsy for the pituitary stalk-hypothalamic lesions.

Pituitary 2021 Sep 1. Epub 2021 Sep 1.

Department of Neurosurgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Purpose: The indications for and the optimal biopsy approach in pituitary stalk-hypothalamic (PsH) lesions are controversial. Biopsies through an endoscopic endonasal approach (EEA) for PsH lesions have often been considered to cause the infundibulo-tuberal syndrome. The purpose of this study was to analyze the surgical and endocrinological safety of EEA biopsies for PsH lesions.

Methods: A total of 39 consecutive patients who underwent an EEA biopsy between June 2011 and August 2020 in a single institute were retrospectively analyzed. The ophthalmological and endocrinological outcomes were assessed before and after surgery.

Results: PsH lesions were confirmed to be diverse pathological diagnoses, ranging from lymphocytic hypophysitis to diffuse midline glioma, and the most common pathologic diagnosis was a germinoma (18 patients, 46.2%). No patients developed visual deterioration after the biopsy. In patients without preoperative panhypopituitarism, 13 out of 28 patients (46.4%) developed new anterior pituitary hormonal deficiencies after the biopsy. When the tissue was collected from the stalk, the endocrinological deterioration rate was 100% (6 of 6 patients), while the rate was 31.8% (7 of 22 patients) when tissue could be harvested from an extra-stalk lesion. The rate of newly developed permanent diabetes insipidus after surgery was 40.9% (9 of 22 patients). The median surgery time was 125 min, and there was no postoperative CSF leakage or infections noted.

Conclusions: An EEA biopsy for PsH lesions is a safe and efficient surgical method unless the tissue is collected from the stalk.
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http://dx.doi.org/10.1007/s11102-021-01181-0DOI Listing
September 2021

Prognostic significance of the postoperative prognostic nutritional index in patients with glioblastoma: a retrospective study.

BMC Cancer 2021 Aug 21;21(1):942. Epub 2021 Aug 21.

Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.

Background: The prognostic nutritional index (PNI) reflects immunonutritional status. We evaluated the effects of postoperative PNI and perioperative changes in the PNI on overall survival (OS) in glioblastoma (GBM) patients.

Methods: Demographic, laboratory, and clinical data were retrospectively collected from 335 GBM patients. Preoperative and postoperative PNIs were calculated from serum albumin concentration and lymphocyte count, which were measured within 3 weeks before surgery and 1 month after surgery. Patients were classified into high (n = 206) or low (n = 129) postoperative PNI groups according to the postoperative PNI cutoff value and further classified into four groups according to the cutoff values of the preoperative and postoperative PNIs, as follows: Group HH (both high PNIs, n = 92), Group HL (high preoperative and low postoperative PNI, n = 70), Group LH (low preoperative and high postoperative PNI, n = 37), and Group LL (both low PNIs, n = 136).

Results: The median OS was significantly longer in the high postoperative PNI (PNI ≥ 50.2) group than the low postoperative PNI (PNI < 50.2) group (24.0 vs. 15.0 months, p <  0.001). In multivariate analysis, high postoperative PNI was a significant predictor of OS. OS was significantly longer in Group HH than in Group LL and seemed longer in Group HH than in Group HL and in Group LH than in Group LL. OS was not different between Groups HH and LH or between Groups HL and LL.

Conclusions: High postoperative PNI was associated with improved OS and perioperative changes in PNI may provide additional important information for prognostic prediction in GBM patients.
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http://dx.doi.org/10.1186/s12885-021-08686-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380354PMC
August 2021

Time-sequential change in immune-related gene expression after irradiation in glioblastoma: next-generation sequencing analysis.

Anim Cells Syst (Seoul) 2021 30;25(4):245-254. Epub 2021 Jul 30.

Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.

The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 h post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon- signals began to increase significantly at 24 h and were upregulated until 48 h after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon- signaling in cancer cells. In conclusions, in the glioblastoma cell line, immune-related signals were significantly upregulated at 24 and 48 h after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.
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http://dx.doi.org/10.1080/19768354.2021.1954550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366673PMC
July 2021

Revisiting vimentin: a negative surrogate marker of molecularly defined oligodendroglioma in adult type diffuse glioma.

Brain Tumor Pathol 2021 Aug 2. Epub 2021 Aug 2.

Department of Pathology, Seoul National University Hospital, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.

Vimentin is a marker of epithelial-mesenchymal transformation and indicates poor prognosis in various cancers, but its role in diffuse gliomas remains unknown. We investigated the vimentin expression of diffuse gliomas according to the upcoming 2021 WHO classification, its variations due to mutational status, and its prognostic effects. We analyzed vimentin immunohistochemistry in 315 gliomas: a test set (n = 164) and a validation set (n = 151). RNA-seq and mutational information from The Cancer Genome Atlas (TCGA, n = 422) were also used for validation. Vimentin was diffusely positive in astrocytic tumors but negative in oligodendroglial tumors (ODGs) and its expression was significantly higher in isocitrate dehydrogenase (IDH) wild-type tumors. High vimentin expression was correlated with poor prognosis (hazard ratio [HR]: 5.99), but it was dependent on the new WHO grade which reflects both histologic features and genetics (HR: 1.28). Using the significant difference in vimentin expression between ODGs and astrocytic tumors, the positive and negative predictive values of the vimentin-based diagnosis for ODGs were 93.5% and 97.8% in the validation set. Along with additional alpha-thalassemia/mental retardation, X-linked (ATRX) immunohistostaining, the values were 98.3% and 97.8%, respectively. Vimentin is a useful ancillary marker for identifying ODGs when combined with routine histochemistry markers.
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http://dx.doi.org/10.1007/s10014-021-00411-4DOI Listing
August 2021

Development of an inside-out augmented reality technique for neurosurgical navigation.

Neurosurg Focus 2021 08;51(2):E21

3Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: With the advancement of 3D modeling techniques and visualization devices, augmented reality (AR)-based navigation (AR navigation) is being developed actively. The authors developed a pilot model of their newly developed inside-out tracking AR navigation system.

Methods: The inside-out AR navigation technique was developed based on the visual inertial odometry (VIO) algorithm. The Quick Response (QR) marker was created and used for the image feature-detection algorithm. Inside-out AR navigation works through the steps of visualization device recognition, marker recognition, AR implementation, and registration within the running environment. A virtual 3D patient model for AR rendering and a 3D-printed patient model for validating registration accuracy were created. Inside-out tracking was used for the registration. The registration accuracy was validated by using intuitive, visualization, and quantitative methods for identifying coordinates by matching errors. Fine-tuning and opacity-adjustment functions were developed.

Results: ARKit-based inside-out AR navigation was developed. The fiducial marker of the AR model and those of the 3D-printed patient model were correctly overlapped at all locations without errors. The tumor and anatomical structures of AR navigation and the tumors and structures placed in the intracranial space of the 3D-printed patient model precisely overlapped. The registration accuracy was quantified using coordinates, and the average moving errors of the x-axis and y-axis were 0.52 ± 0.35 and 0.05 ± 0.16 mm, respectively. The gradients from the x-axis and y-axis were 0.35° and 1.02°, respectively. Application of the fine-tuning and opacity-adjustment functions was proven by the videos.

Conclusions: The authors developed a novel inside-out tracking-based AR navigation system and validated its registration accuracy. This technical system could be applied in the novel navigation system for patient-specific neurosurgery.
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http://dx.doi.org/10.3171/2021.5.FOCUS21184DOI Listing
August 2021

Radiological assessment schedule for 1p/19q-codeleted gliomas during the surveillance period using parametric modeling.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab069. Epub 2021 May 20.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: There have been no evidence-based guidelines on the optimal schedule for the radiological assessment of 1p/19q-codeleted glioma. This study aimed to recommend an appropriate radiological evaluation schedule for 1p/19q-codeleted glioma during the surveillance period through parametric modeling of the progression-free survival (PFS) curve.

Methods: A total of 234 patients with 1p/19q-codeleted glioma (137 grade II and 97 grade III) who completed regular treatment were retrospectively reviewed. The patients were stratified into each layered progression risk group by recursive partitioning analysis. A piecewise exponential model was used to standardize the PFS curves. The cutoff value of the progression rate among the remaining progression-free patients was set to 10% at each scan.

Results: Progression risk stratification resulted in 3 groups. The optimal magnetic resonance imaging (MRI) interval for patients without a residual tumor was every 91.2 weeks until 720 weeks after the end of regular treatment following the latent period for 15 weeks. For patients with a residual tumor after the completion of adjuvant radiotherapy followed by chemotherapy, the optimal MRI interval was every 37.5 weeks until week 90 and every 132.8 weeks until week 361, while it was every 33.6 weeks until week 210 and every 14.4 weeks until week 495 for patients with a residual tumor after surgery only or surgery followed by radiotherapy only.

Conclusions: The optimal radiological follow-up schedule for each progression risk stratification of 1p/19q-codeleted glioma can be established from the parametric modeling of PFS.
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http://dx.doi.org/10.1093/noajnl/vdab069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284622PMC
May 2021

Outcomes of the endoscopic endonasal approach for tumors in the third ventricle or invading the third ventricle.

J Clin Neurosci 2021 Aug 21;90:302-310. Epub 2021 Jun 21.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea.

We aimed to retrospectively analyze the surgical and clinical outcomes of the endoscopic endonasal approach (EEA) for tumors in the third ventricle or invading the third ventricle. In total, 82 patients who had undergone surgical treatment using the EEA for tumors involving the third ventricle were enrolled in this study. This cohort study comprised 46 male and 36 female patients. The median age was 37 years (range, 5-76), and the median follow-up duration was 56.5 months (range, 6-117). Seventy-six patients had craniopharyngiomas, and 6 had gangliocytomas, gangliogliomas, astrocytomas, diffuse midline gliomas and lymphomas. Gross total removal was performed in 71 (86.5%) of the 82 patients, subtotal tumor removal in 7 patients and partial removal or biopsy in 4 patients. The pituitary stalk was preserved in 20 cases. Visual function improved in 40 (81.6%) of 49 patients. Endocrine function worsened in 41 (50%) of 82 patients. Hypothalamic function improved in 16 (72.7%) of 22 cases. Postoperative obesity occurred in 3 (20.0%) of 15 children and 11 (23.9%) of 46 adult patients. The postoperative cerebrospinal fluid leakage rate was 3.6%. Postoperative meningitis occurred in 18 (21.9%) cases. Permanent diabetes insipidus was identified in 73 (89.0%) of 82 patients. Tumor recurrence was observed in 10 patients (12%). The EEA appears to be a safe and effective treatment modality for tumors in the third ventricle or involving the third ventricle. However, more cases and long-term follow-up outcomes are required to confirm the clinical efficacy of the EEA.
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http://dx.doi.org/10.1016/j.jocn.2021.06.012DOI Listing
August 2021

Prediction of Prognosis in Glioblastoma Using Radiomics Features of Dynamic Contrast-Enhanced MRI.

Korean J Radiol 2021 09 14;22(9):1514-1524. Epub 2021 Jul 14.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma.

Materials And Methods: One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (K), fractional volume of vascular plasma space (V), and fractional volume of extravascular extracellular space (V) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the "radiomics risk score" groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates.

Results: 16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; = 0.004 and hazard ratio, 0.34; = 0.022, respectively).

Conclusion: We developed and validated the "radiomics risk score" from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.
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http://dx.doi.org/10.3348/kjr.2020.1433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390822PMC
September 2021

Multiparametric magnetic resonance imaging features of a canine glioblastoma model.

PLoS One 2021 9;16(7):e0254448. Epub 2021 Jul 9.

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Purpose: To assess glioblastoma multiforme (GBM) formation with similar imaging characteristics to human GBM using multiparametric magnetic resonance imaging (MRI) in an orthotopic xenograft canine GBM model.

Materials And Methods: The canine GBM cell line J3T1 was subcutaneously injected into 6-week-old female BALB/c nude mice to obtain tumour fragments. Tumour fragments were implanted into adult male mongrel dog brains through surgery. Multiparametric MRI was performed with conventional MRI, diffusion-weighted imaging, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging at one week and two weeks after surgery in a total of 15 surgical success cases. The presence of tumour cells, the necrotic area fraction, and the microvessel density (MVD) of the tumour on the histologic specimen were assessed. Tumour volume, diffusion, and perfusion parameters were compared at each time point using Wilcoxon signed-rank tests, and the differences between tumour and normal parenchyma were compared using unpaired t-tests. Spearman correlation analysis was performed between the imaging and histologic parameters.

Results: All animals showed a peripheral enhancing lesion on MRI and confirmed the presence of a tumour through histologic analysis (92.3%). The normalized perfusion values did not show significant decreases through at least 2 weeks after the surgery (P > 0.05). There was greater cerebral blood volume and flow in the GBM than in the normal-appearing white matter (1.46 ± 0.25 vs. 1.13 ± 0.16 and 1.30 ± 0.22 vs. 1.02 ± 0.14; P < 0.001 and P < 0.001, respectively). The MVD in the histologic specimens was correlated with the cerebral blood volume in the GBM tissue (r = 0.850, P = 0.004).

Conclusion: Our results suggest that the canine GBM model showed perfusion imaging characteristics similar to those of humans, and it might have potential as a model to assess novel technical developments for GBM treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254448PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270200PMC
July 2021

Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study).

Cancer Res Treat 2021 Jul 6. Epub 2021 Jul 6.

Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Purpose: The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL).

Materials And Methods: In this randomized, open-label, phase II trial, 90 patients with WHO grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to CCRT with temozolomide followed by 6 cycles of adjuvant temozolomide (Arm A) and radiotherapy (RT) alone (Arm B).

Results: Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between Arm A and Arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33).

Conclusion: The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.
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http://dx.doi.org/10.4143/crt.2021.393DOI Listing
July 2021

A Deep Dive: SIWV Tetra-Peptide Enhancing the Penetration of Nanotherapeutics into the Glioblastoma.

ACS Biomater Sci Eng 2021 Jul 1. Epub 2021 Jul 1.

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor. It is difficult to regulate GBM using conventional chemotherapy-based methods due to its anatomical structure specificity, low drug targeting ability, and limited penetration depth capability to reach the tumor interior. Numerous approaches have been proposed to overcome such issues, including nanoparticle-based drug delivery system (DDS) with the development of GBM site targeting and penetration depth enhancing moieties (e.g., peptides, sugars, proteins, etc.). In this study, we prepared four different types of nanoparticles, which are based on porous silicon nanoparticles (pSiNPs) incorporating polyethylene glycol (PEG), iRGD peptide (well-known cancer targeting peptide), and SIWV tetra-peptide (a recently disclosed GBM-targeting peptide), and analyzed their deep-tumor penetration abilities in cell spheroids, in GBM patient-derived tumoroids, and in GBM xenograft mice. We found that SIWV tetra-peptide significantly enhanced the penetration depth of pSiNPs, and its therapeutic formulation (temozolomide-loaded/SIWV-functionalized pSiNPs) showed a higher anticancer efficacy compared with other formulations. These findings hold great promise for the development of nanotherapeutics and peptide-conjugated drugs for GBM.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00653DOI Listing
July 2021

The substantial loss of H3K27me3 can stratify risk in grade 2, but not in grade 3 meningioma.

Hum Pathol 2021 Sep 26;115:96-103. Epub 2021 Jun 26.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. Electronic address:

Trimethylation of lysine 27 of histone H3 (H3K27me3) has recently emerged as a crucial epigenetic marker in meningioma. The loss of H3K27me3 expression might predict the early recurrence of grade 1 and 2 meningiomas. However, this is controversial in terms of grade 3 meningioma and the effects of H3K27me3 on the overall survival (OS) of patients with low low-grade meningioma have not been studied. Therefore, we immunohistochemically assessed the prognostic implications of H3K27me3 expression in grade 2 and 3 meningiomas. Whole-slide H3K27me3 immunostaining was evaluated for strict quality control and to confirm a significant correlation (P < .0001) with tissue microarray results. The effects of tissue age on H3K27me3 immunostaining were also evaluated, to select an appropriate cohort for survival analysis. Log-rank tests of 115 grade 2 meningiomas and 26 grade 3 meningiomas showed that the loss of H3K27me3 expression was a prognostic factor for early recurrence (P < .0001) and death (P = .00012) in grade 2, but not in grade 3 meningioma. Multivariate analysis revealed that age, recurrent tumor, and loss of H3K27me3 expression (hazard ratio, 1.264-7.510; P = .0133) were significant for recurrentrecurrence-free survival (RFS), and that recurrent tumor and loss of H3K27me3 expression (hazard ratio, 1.717-120.621; P = .0140) were significant for OS. We concluded that H3K27me3 expression is a significant prognostic factor for the RFS and OS of patients with grade 2 meningioma; it should be considered as an ancillary test for risk stratification of this meningioma.
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http://dx.doi.org/10.1016/j.humpath.2021.06.005DOI Listing
September 2021

Human Glioblastoma Visualization: Triple Receptor-Targeting Fluorescent Complex of Dye, SIWV Tetra-Peptide, and Serum Albumin Protein.

ACS Sens 2021 06 8;6(6):2270-2280. Epub 2021 Jun 8.

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Fluorescence guided surgery (FGS) has been highlighted in the clinical site for guiding surgical procedures and providing the surgeon with a real-time visualization of the operating field. FGS is a powerful technique for precise surgery, particularly tumor resection; however, clinically approved fluorescent dyes have often shown several limitations during FGS, such as non-tumor-targeting, low in vivo stability, insufficient emission intensity, and low blood-brain barrier penetration. In this study, we disclose a fluorescent dye complex, peptide, and protein for the targeted visualization of human glioblastoma (GBM) cells and tissues. Our noble triple receptor-targeting fluorescent complex (named ) consists of (i) dipolar oxazepine dye (), which has high stability, low cytotoxicity, bright fluorescence, and two-photon excitable, (ii) tetra-peptide (SIWV) for the targeting of the caveolin-1 receptor, and (iii) bovine serum-albumin (BSA) protein for the targeting of albondin (gp60) and secreted protein acidic and rich in cysteine receptor. The photophysical properties and binding mode of were analyzed, and the imaging of GBM cell lines and human clinical GBM tissues were successfully demonstrated in this study. Our findings hold great promise for the application of to GBM identification and the surgery at clinical sites, as a new FGS agent.
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http://dx.doi.org/10.1021/acssensors.1c00320DOI Listing
June 2021

Clinical application of 3D virtual and printed models for cerebrovascular diseases.

Clin Neurol Neurosurg 2021 Jul 29;206:106719. Epub 2021 May 29.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Objective: Three-dimensional (3D) printing techniques are rapidly advancing in the medical industry and in clinical practice. We aimed to evaluate the usefulness of 3D virtual and printed models of 6 representative cerebrovascular diseases using the software we developed.

Methods: Six cases consisted of 4 intracranial aneurysms (IAs) including complex ones with intrasaccular thrombosis, large size and a skull base location; 1 cavernous malformation in the pons; and 1 arteriovenous malformation in the parietal lobe. The 3D modeling process was performed retrospectively in 3 cases and prospectively in 1 IA. Segmentation of raw data and rendering and modification for 3D virtual models were processed mostly automatically.

Results: Most intracranial structures were satisfactorily made, including the skull, brain, vessels, thrombus, tentorium and major cranial nerves. Based on 3D modeling, surgical plan was changed in 1 prospective IA case. However, it was still difficult to discriminate small vessels and cranial nerves, to feel a realistic tactile sense and to directly perform presurgical simulations, such as dissection, removal, clipping and microanastomosis.

Conclusions: The 3D modeling was thought to be very helpful in experiencing the operative views from various directions in advance, in selecting an appropriate surgical approach, and in educating physicians and patients. With advancements in radiological resolution, processing techniques and material properties, 3D modeling is expected to simulate real brain tissues more closely.
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http://dx.doi.org/10.1016/j.clineuro.2021.106719DOI Listing
July 2021

Differentiation between glioblastoma and primary CNS lymphoma: application of DCE-MRI parameters based on arterial input function obtained from DSC-MRI.

Eur Radiol 2021 May 18. Epub 2021 May 18.

Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: This study aimed to evaluate whether arterial input functions (AIFs) obtained from dynamic susceptibility contrast (DSC)-MRI (AIF) improve the reliability and diagnostic accuracy of dynamic contrast-enhanced (DCE)-derived pharmacokinetic (PK) parameters for differentiating glioblastoma from primary CNS lymphoma (PCNSL) compared with AIFs derived from DCE-MRI (AIF).

Methods: This retrospective study included 172 patients with glioblastoma (n = 147) and PCNSL (n = 25). All patients had undergone preoperative DSC- and DCE-MRI. The volume transfer constant (K), volume of the vascular plasma space (v), and volume of the extravascular extracellular space (v) were acquired using AIF and AIF. The relative cerebral blood volume (rCBV) was obtained from DSC-MRI. Intraclass correlation coefficients (ICC) and ROC curves were used to assess the reliability and diagnostic accuracy of individual parameters.

Results: The mean K, v, and v values revealed better ICCs with AIF than with AIF (K, 0.911 vs 0.355; v, 0.766 vs 0.503; v, 0.758 vs 0.657, respectively). For differentiating all glioblastomas from PCNSL, the mean rCBV (AUC = 0.856) was more accurate than the AIF-driven mean K, which had the largest AUC (0.711) among the DCE-derived parameters (p = 0.02). However, for glioblastomas with low rCBV (≤ 75th percentile of PCNSL; n = 30), the AIF-driven mean K and v were more accurate than rCBV (AUC: K, 0.807 vs rCBV, 0.515, p = 0.004; v, 0.715 vs rCBV, p = 0.045).

Conclusion: DCE-derived PK parameters using the AIF showed improved reliability and diagnostic accuracy for differentiating glioblastoma with low rCBV from PCNSL.

Key Points: • An accurate differential diagnosis of glioblastoma and PCNSL is crucial because of different therapeutic strategies. • In contrast to the rCBV from DSC-MRI, another perfusion imaging technique, the DCE parameters for the differential diagnosis have been limited because of the low reliability of AIFs from DCE-MRI. • When we analyzed DCE-MRI data using AIFs from DSC-MRI (AIF), AIF-driven DCE parameters showed improved reliability and better diagnostic accuracy than rCBV for differentiating glioblastoma with low rCBV from PCNSL.
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http://dx.doi.org/10.1007/s00330-021-08044-zDOI Listing
May 2021

Radiomics-based neural network predicts recurrence patterns in glioblastoma using dynamic susceptibility contrast-enhanced MRI.

Sci Rep 2021 May 11;11(1):9974. Epub 2021 May 11.

Seoul National University College of Medicine, Seoul, Republic of Korea.

Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903-1.000) for local recurrence; 0.864 (0.726-0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or "radiomic risk score", increased risk of recurrence/progression (hazard ratio, 1.61; p = 0.03) in multivariate Cox regression on progression-free survival.
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http://dx.doi.org/10.1038/s41598-021-89218-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113258PMC
May 2021

The Korean Society for Neuro-Oncology (KSNO) Guideline for Antiepileptic Drug Usage of Brain Tumor: Version 2021.1.

Brain Tumor Res Treat 2021 Apr;9(1):9-15

Department of Cancer Control, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

Background: To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019.

Methods: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords.

Results: The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year.

Conclusion: The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.
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http://dx.doi.org/10.14791/btrt.2021.9.e7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082286PMC
April 2021

The Korean Society for Neuro-Oncology (KSNO) Guideline for Adult Diffuse Midline Glioma: Version 2021.1.

Brain Tumor Res Treat 2021 Apr;9(1):1-8

Department of Cancer Control, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

Background: There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019.

Methods: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As 'diffuse midline glioma' was recently defined, and there was no international guideline, trials and guidelines of 'diffuse intrinsic pontine glioma' or 'brain stem glioma' were thoroughly reviewed first.

Results: The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma's protocol is recommended.

Conclusion: The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.
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http://dx.doi.org/10.14791/btrt.2021.9.e8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082289PMC
April 2021

The Role of Postoperative Radiotherapy in Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Multi-Institutional Retrospective Study (KROG 18-11).

Cancer Res Treat 2021 Mar 24. Epub 2021 Mar 24.

Department of Radiation Oncology, Seoul National University Hospital, Seoul National University, College of Medicine, Seoul, Korea.

Purpose: To evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).

Methods And Materials: A total of 133 patients with histologically confirmed HPC were included from 8 institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 (64%) patients. The prognostic effects of sex, age, performance, WHO grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.

Results: The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p<0.001) and PFS (p<0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001) , or STR (p<0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).

Conclusion: This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.
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http://dx.doi.org/10.4143/crt.2021.142DOI Listing
March 2021

Clinical application of patient-specific 3D printing brain tumor model production system for neurosurgery.

Sci Rep 2021 03 26;11(1):7005. Epub 2021 Mar 26.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Daehak-ro 101, Jongno-gu, Seoul, 03080, Republic of Korea.

The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture (p = 0.0147) and craniotomy design (p = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.
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http://dx.doi.org/10.1038/s41598-021-86546-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998007PMC
March 2021

Safety and Efficacy of Endoscopic Dorsum Sellar Resection for Access to Retroinfundibular or Upper Clival Tumors (Korean Society of Endoscopic Neurosurgery-008).

World Neurosurg 2021 06 23;150:e675-e680. Epub 2021 Mar 23.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Pituitary Center, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Objective: The retroinfundibular and upper clival regions are challenging to access using the endoscopic endonasal approach because these regions are obstructed by the dorsum sellae and posterior clinoid processes. We evaluated the safety and clinical efficacy of endoscopic dorsum sellar resection (DSR) and identified the optimal indications for endoscopic DSR in patients with craniopharyngioma.

Methods: A retrospective study was conducted of patients who had undergone treatment with an endoscopic endonasal approach from January 2014 to January 2019. We identified a total of 50 patients who had undergone DSR. The indications for DSR included the following: 1) a tumor involving the upper clivus; 2) a tumor located behind the dorsum sellae; and 3) a tumor involving the interpeduncular or prepontine cistern. We evaluated the clinical outcomes, postoperative endocrinological status, and surgical morbidities.

Results: Of the 50 patients, 16 had been treated for craniopharyngioma, 30 for chordoma, 2 for pituitary adenoma, 1 for schwannoma, and 1 for chondrosarcoma. An extradural approach for DSR with posterior clinoidectomy was performed in 33 patients (66.0%) and an interdural transcavernous approach in 17 patients (34.0%). The overall gross total tumor resection rate was 92.0% (46 of 50 patients). Postoperatively, 28 of 33 patients (84.8%) with normal pituitary function preoperatively showed preservation of hormonal function postoperatively.

Conclusions: DSR with or without posterior clinoidectomy is a challenging procedure that requires considerable effort and advanced surgical techniques. However, it can be safely performed with accumulating experience and a thorough knowledge of the surrounding anatomical structures.
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http://dx.doi.org/10.1016/j.wneu.2021.03.085DOI Listing
June 2021

Methylation and molecular profiles of ependymoma: Influence of patient age and tumor anatomic location.

Mol Clin Oncol 2021 May 5;14(5):88. Epub 2021 Mar 5.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Ependymomas are tumors of the central nervous system that can occur in patients of all ages. Guidelines from the World Health Organization (WHO) for the grading of ependymomas consider patient age, tumor resection range, tumor location and histopathological grade. However, recent studies have suggested that a greater focus on both tumor location and patient age in terms of transcriptomic, genetic, and epigenetic analyses may provide a more accurate assessment of clinical prognosis than the grading system proposed by WHO guidelines. The current study identified the differences and similarities in ependymoma characteristics using three different molecular analyses and methylation arrays. Primary intracranial ependymoma tissues were obtained from 13 Korean patients (9 adults and 4 children), after which whole-exome sequencing (WES), ion-proton comprehensive cancer panel (CCP) analysis, RNA sequencing, and Infinium HumanMethylation450 BeadChip array analysis was performed. Somatic mutations, copy number variations, and fusion genes were identified. It was observed that the methylation status and differentially expressed genes were significantly different according to tumor location and patient age. Several novel gene fusions and somatic mutations were identified, including a fusion mutation in a child with a good prognosis. Moreover, the methylation microarray revealed that genes associated with neurogenesis and neuron differentiation were hypermethylated in the adult group, whereas genes in the homeobox gene family were hypermethylated in the supratentorial (ST) group. The results confirmed the existence of significantly differentially expressed tumor-specific genes based on tumor location and patient age. These results provided valuable insight into the epigenetic and genetic profiles of intracranial ependymomas and uncovered potential strategies for the identification of location- and age-based ependymoma-related prognostic factors.
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http://dx.doi.org/10.3892/mco.2021.2250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976387PMC
May 2021

Adjuvant radiotherapy versus observation following gross total resection for atypical meningioma: a systematic review and meta-analysis.

Radiat Oncol 2021 Feb 17;16(1):34. Epub 2021 Feb 17.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Background: The impact of adjuvant radiotherapy (RT) on atypical meningioma (AM) underwent a gross total resection (GTR) remains unclear, showing conflicting results from various studies. The objective of this study was to perform an updated meta-analysis for observational studies to determine the effect of adjuvant RT after GTR on local recurrence and survival outcomes compared to observation after GTR.

Methods: PubMed, Embase, and Web of Science were searched to identify comparative studies that reported outcomes of adjuvant RT versus observation for AM patients after GTR. Local recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicities related to RT were considered as outcomes of interest. Differences between two cohorts were estimated by calculating odds ratios (OR) for LR rate and hazard ratios (HR) for survival outcomes with 95% confidence intervals (CIs) for meta-analysis, using R version 4.0.3 software. Included studies were appraised with the Risk of Bias Assessment tool for Non-Randomized Studies. Outcome ratios were combined with the Mantel-Haenszel method and the inverse variance-weighted method, appropriately.

Results: Data from 30 studies involving 2904 patients (adjuvant RT: n = 737; observation: n = 2167) were eventually included. Significant reduction of local recurrence rate was seen in the adjuvant RT cohort compare to that in the observation cohort (OR 0.50; 95% CI 0.36-0.68; p < 0.0001). Pooled HRs of PFS at 1-year, 3-year, 5-year, and > 5-year revealed that adjuvant RT was superior to observation. There was no significant difference in OS between the two cohorts during any period. Most toxicities were tolerable with grade 1 or 2. There was no documented grade 5 toxicity.

Conclusions: For AM patients who underwent GTR, evidence suggested that adjuvant RT could potentially decrease local recurrence and improve PFS better than observation.
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http://dx.doi.org/10.1186/s13014-021-01759-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890913PMC
February 2021

Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae.

Cancer Res Treat 2021 Jan 13. Epub 2021 Jan 13.

Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Purpose: We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.

Materials And Methods: Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole-brain (WB), and whole-ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.

Results: The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in ten patients (5.3 %) with a latency of 20 years (range, 4-26) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.

Conclusion: Reduced dose and volume of extended-field rather than total dose or involved-field will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.
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http://dx.doi.org/10.4143/crt.2020.1052DOI Listing
January 2021

Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.

Brain 2021 03;144(2):636-654

Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.
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http://dx.doi.org/10.1093/brain/awaa408DOI Listing
March 2021

Editorial Statistics and Best Reviewer Awards 2020 for the Journal of Korean Neurosurgical Society.

J Korean Neurosurg Soc 2021 Jan 1;64(1):1-3. Epub 2021 Jan 1.

Editor in Chief, Journal of Korean Neurosurgical Society; Department of Neurosurgery, Seoul National University Boramae Hospital, Seoul, Korea.

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http://dx.doi.org/10.3340/jkns.2020.0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819797PMC
January 2021

Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values.

Cancer Immunol Immunother 2021 Jul 8;70(7):1995-2008. Epub 2021 Jan 8.

Department of Neurosurgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Purpose: To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures.

Methods: The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications.

Results: The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps.

Conclusions: Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.
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http://dx.doi.org/10.1007/s00262-020-02836-wDOI Listing
July 2021

The prognostic significance of p16 expression pattern in diffuse gliomas.

J Pathol Transl Med 2021 Mar 23;55(2):102-111. Epub 2020 Dec 23.

Department of Pathology, Seoul National University Hospital, Seoul, Korea.

Background: CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)-mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas.

Methods: p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression.

Results: A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n=326, p<.001), in the IDH-mutant glioma patients (n=103, p=.010), and in the IDH-mutant astrocytoma patients (n=73, p=.032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n=223, p=.121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n=30, p=.457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p=.008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p=.001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p< .001) and in IDH-mutant glioma groups. (p=.046).

Conclusions: This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.
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http://dx.doi.org/10.4132/jptm.2020.10.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987518PMC
March 2021

Superselective pseudocontinuous arterial spin labeling in patients with meningioma: utility in prediction of feeding arteries and preoperative embolization feasibility.

J Neurosurg 2020 Nov 13:1-7. Epub 2020 Nov 13.

3Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.

Objective: Superselective pseudocontinuous arterial spin labeling (ss-pCASL) is an MRI technique in which individual vessels are labeled to trace their perfusion territories. In this study, the authors assessed its merit in defining feeding vessels and gauging preoperative embolization feasibility for patients with meningioma, using digital subtraction angiography (DSA) as the reference method.

Methods: Thirty-one consecutive patients with meningiomas were prospectively recruited, each undergoing DSA (and embolization, if feasible) before resection. All ss-pCASL imaging studies were performed 1 day prior to DSA. Two neuroradiologists independently reviewed ss-pCASL images, rating the contribution of each labeled vessel to tumor blood supply as none, minor, or major. Two neuroradiologists also gauged the feasibility of embolization in each patient, based on ss-pCASL images. Interobserver and intermodality agreement were determined using Cohen's kappa statistic. The diagnostic performance of ss-pCASL was assessed in terms of discerning tumor blood supply and the potential for embolization.

Results: Interobserver agreement in the rating of blood supply by ss-pCASL was very good (κ = 0.817, 95% CI 0.771-0.863), and intermodality agreement (consensus ss-pCASL readings vs DSA findings) was good (κ = 0.688, 95% CI 0.632-0.744). In delineating tumor blood supply, ss-pCASL showed high sensitivity (87.1%) and specificity (87.2%). The positive and negative predictive values for embolization feasibility were 85.2% and 100%, respectively.

Conclusions: In patients with meningiomas, feeding vessels are reliably predicted by ss-pCASL. This noninvasive approach, involving no iodinated contrast or radiation exposure, is particularly beneficial if there are no prospects of embolization.
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http://dx.doi.org/10.3171/2020.7.JNS201915DOI Listing
November 2020
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