Publications by authors named "Tae-Young Jung"

199 Publications

Inflammatory Brain Lesions as Omen of Primary Central Nervous System Lymphoma: A Case Report and Literature Review.

Brain Sci 2021 Feb 4;11(2). Epub 2021 Feb 4.

Department of Neurosurgery, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do 58128, Korea.

We report a rare case that was initially diagnosed as an inflammatory lesion and ultimately confirmed as primary central nervous system lymphoma (PCNSL) in an immunocompetent patient who was not treated with corticosteroid prior to the initial biopsy. A 70-year-old female patient presented with numbness in the left side of face, arm, and leg. Brain magnetic resonance imaging (MRI) revealed a lesion with intense gadolinium (Gd)-enhancement in the ventral portion of the midbrain. A stereotactic biopsy demonstrated mixed T-cell and B-cell infiltrating inflammatory lesions without demyelination. Three months after postoperative treatment with steroid, the lesion markedly decreased on follow-up MRI. Twenty-six months after the initial attack, she complained of dysarthria and urinary incontinence. Repetitive MRI showed a lesion with homogeneous enhancement, extensively involving the bilateral cerebral hemisphere, corpus callosum, and the right middle cerebellar peduncle. The confirmed diagnosis was diffuse large B-cell lymphoma on the second biopsy. Despite our best efforts, she died 38 months after disease onset. Based on review of the literature and our case, preceding inflammatory lesions are not always demyelinating and T-cell dominant inflammatory lesions. When the initial biopsy reveals an inflammatory lesion in an old-aged patient, the clinician should keep in mind the development of PCNSL and perform close clinical and radiological observations for a timely diagnosis.
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http://dx.doi.org/10.3390/brainsci11020191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913965PMC
February 2021

Branched Multipeptide-combined Adjuvants Potentially Improve the Antitumor Effects on Glioblastoma.

J Immunother 2021 Jan 27. Epub 2021 Jan 27.

Brain Tumor Research Laboratory Department of Neurosurgery Research Center for Cancer Immunotherapy Department of Internal Medicine, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Republic of Korea.

The promising immunotherapy effects of a multiple antigenic peptide on glioblastoma (GBM) in a previous study encourage the use of adjuvants to enhance its therapeutic efficacy. Among adjuvants, pan HLA-DR-binding epitope (PADRE) and anti-programmed cell death protein 1 (anti-PD1) have potentially been tested for cancer immunotherapy. Therefore, here we evaluated the ability of PADRE and anti-PD1 to enhance the function of the branched multipeptide against GBM. The potential utility of tumor-associated antigens (ErbB-2 and WT-1) targeting GBM with HLA-A24 was confirmed and a branched multipeptide was constructed from these antigens. The effects of the branched multipeptide and PADRE on immunophenotyping and polarized Th cytokine production in dendritic cells were clarified. The expression of PD1 on T cells and PDL1 on GBM cells was also investigated. The interferon-γ enzyme-linked immunospot and lactate dehydrogenase release assays were performed to determine the function of GBM peptide antigen-specific cytotoxic T cells against GBM cells. Overall, this study showed that both ErbB-2 and WT-1 are potential candidates for branched multipeptide construction. The branched multipeptide and PADRE enhanced the expression of major histocompatibility complex and co-stimulatory molecules and the production of polarized Th1 cytokines in dendritic cells. The increase in the number of interferon-γ+ effector T cells was consistent with the increase in the percentage specific lysis of GBM target cells by GBM peptide antigen-specific cytotoxic T cells in the presence of the branched multipeptide, PADRE, and anti-PD1. Our study suggests the combination of branched multipeptide and adjuvants such as PADRE and anti-PD1 can potentially enhance the effects of immunotherapy for GBM treatment.
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http://dx.doi.org/10.1097/CJI.0000000000000359DOI Listing
January 2021

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children Under the Age of 3 Years.

Cancer Res Treat 2020 Oct 28. Epub 2020 Oct 28.

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for CNS ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years.

Materials And Methods: A search of medical records from 7 centers was performed between January 2005 and December 2016.

Results: Forty-three patients were enrolled. With a median follow-up of 90 months, 27 (64.3%) patients showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3- year progression free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3- year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n = 21), treatment-related toxicity (n = 5), or unknown cause (n = 1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p<0.01).

Conclusion: Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.
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http://dx.doi.org/10.4143/crt.2020.756DOI Listing
October 2020

Case Reports of Tectal Plate Gliomas Showing Indolent Course.

Brain Tumor Res Treat 2020 Oct;8(2):109-112

Department of Neurosurgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

From 2004 to 2020, we studied three pediatric patients (age: 9-13 years, all male) and one adult patient (age: 29 years, female) with tectal plate glioma with obstructing hydrocephalus on MRI. One patient had neurofibromatosis type 1. All patients complained about headaches and vomiting, and one patient had diplopia. Endoscopic third ventriculostomy (ETV) was underwent in all patients and a biopsy was obtained from two patients. Pathologic diagnoses were a pilocytic astrocytoma and a low-grade glioma. After ETV with or without biopsy, neurological symptoms were improved in all patients. Three patients did the clinical and radiological follow-up without adjuvant treatment. One patient underwent gamma knife radiosurgery. In two pediatric patients and the adult patient, there was no clinical and radiological progression after 6.2, 6.9, and 8.0 years, respectively. One pediatric patient whose lesion had focal enhancement had radiologic progression without any neurologic symptoms after 5.1 years. Without adjuvant treatment for this lesion, there was no clinical deterioration neither further radiological progression for 6.2 years after radiological aggravation. Tectal plate gliomas showed indolent clinical courses, even after radiologic tumor progression. After the treatment of obstructing hydrocephalus, clinical and radiologic follow-up can be recommended for indolent tectal plate gliomas.
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http://dx.doi.org/10.14791/btrt.2020.8.e17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595851PMC
October 2020

Treatment Outcome of Gamma Knife Radiosurgery for Petroclival Meningiomas: Retrospective Analysis of a Single Institution Experience.

Brain Tumor Res Treat 2020 Oct;8(2):83-92

Department of Neurosurgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

Background: Although Gamma Knife radiosurgery (GKRS) has been widely used for intracranial meningiomas as an alternative or adjuvant treatment, guidelines have not been established for the selection of patients with petroclival meningioma (PCM) for GKRS. In this study, we reported the factors related to tumor progression and postoperative complications in PCM patients treated by GKRS, with a review of the literatures.

Methods: Between 2004 and 2019, 64 patients (52 patients for alternative and 12 patients for adjuvant treatment) with PCM underwent GKRS in our institution. The clinical and radiological factors were retrospectively analyzed. The mean radiologic follow-up duration was 58.4 months (range, 6-164 months). The mean tumor volume and diameter before GKRS were 13.4 cm³ and 2.9 cm, respectively. The median marginal dose was 12 Gy (range, 10-14 Gy) with a 50% median isodose line. Fractionation was used in 19 cases (29%, two fractionations in 5 cases & three fractionations in 14 cases).

Results: Progression was noted in 7 cases (10.9%) and the progression-free survival rates were 91.1% at 5 years and 69.6% at 10 years. Although large in volume, moderate to severe peritumoral edema and male gender were somewhat related to progression, they did not reach statistical significance. Ten patients (15.6%) developed complications after GKRS. The most common complication was cranial nerve deficit (n=8), followed by hemiparesis, cognitive dysfunction, and hydrocephalus. Large size (maximal diameter ≥5 cm) [hazard ratio (HR) 0.091, 95% confidence interval (CI) 0.014-0.608; =0.013] and multiplicity (HR 0.102, 95% CI 0.018-0.573; =0.009) were independent factors for developing complications after GKRS.

Conclusion: GKRS can be considered an effective and safe treatment for large-volume PCM. However, for patients with large size or multiple masses, the treatment method should be determined with caution because the probability of complications after GKRS may increase.
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http://dx.doi.org/10.14791/btrt.2020.8.e16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595854PMC
October 2020

Relationship among symptoms, resilience, post-traumatic growth, and quality of life in patients with glioma.

Eur J Oncol Nurs 2020 Oct 12;48:101830. Epub 2020 Sep 12.

Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, South Korea. Electronic address:

Purpose: The aims of this study were to explore the relationship among symptoms, resilience, post-traumatic growth, and quality of life, and to identify the influence of these variables on quality of life in patients with glioma.

Methods: A correlational, cross-sectional research design was used. A convenience sample of 120 patients was recruited from an outpatient neurosurgery clinic. Data analyses included descriptive statistics, independent t-test, one-way ANOVA, Pearson's correlation coefficient, and hierarchical regression analysis and were performed with the SPSS WIN 25.0 program.

Results: Quality of life positively correlated with the duration of disease diagnosis and resilience and negatively correlated with age, age at onset, severity of symptoms, and interference in symptoms. Resilience was negatively correlated with severity of symptoms and interference with symptoms, and was positively correlated with post-traumatic growth. Hierarchical regression analysis showed that demographic and clinical factors explained 39.3% of the variance in quality of life in glioma patients. The explanatory power increased by 22.1% and 15.1%, respectively, when interference in symptoms and resilience were considered.

Conclusions: Assessment of quality of life in patients with glioma should consider symptoms and resilience, along with demographic and clinical factors. Interventions developed to improve quality of life in glioma patients must also consider these factors.
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http://dx.doi.org/10.1016/j.ejon.2020.101830DOI Listing
October 2020

Leiomyosarcoma of the jaw: case series.

J Korean Assoc Oral Maxillofac Surg 2020 Aug;46(4):275-281

Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Seoul, Korea.

Objectives: Leiomyosarcoma is a malignant neoplasm that affects smooth muscle tissue and it is very rare in the field of oral and maxillofcial surgery. The purpose of this study was to obtain information on diagnosis of and treatment methods for leiomyosarcoma by retrospectively reviewing of the cases.

Patients And Methods: The study included nine patients who were diagnosed with leiomyosarcoma in the Department of Oral and Maxillofacial Surgery at Seoul National University Dental Hospital. The subjects were analyzed with respect to sex, age, clinical features, primary site of disease, treatment method, recurrence, and metastasis.

Results: Particular clinical features included pain, edema, mouth-opening limitations, dysesthesia, and enlarged lymph nodes. All cases except one were surgically treated, and recurrence was found in two cases. Four of nine patients were followed up without recurrence and one patient underwent additional surgery due to recurrence.

Conclusion: In our case series, notable symptoms included pain, edema, mouth-opening limitations, and dysesthesia; however, it was difficult to label these as specific symptoms of leiomyosarcoma. Considering the aggressive characteristics of the disease and poor prognosis, surgical treatment is necessary with careful consideration of postoperative radiotherapy and chemotherapy.
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http://dx.doi.org/10.5125/jkaoms.2020.46.4.275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469964PMC
August 2020

Epidemiological Characteristics of COVID-19 Outbreak at Fitness Centers in Cheonan, Korea.

J Korean Med Sci 2020 Aug 10;35(31):e288. Epub 2020 Aug 10.

Chungnam Center for Infectious Diseases Control and Prevention, Hongseong, Korea.

Background: In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea.

Methods: From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection.

Results: A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched.

Conclusion: The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.
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http://dx.doi.org/10.3346/jkms.2020.35.e288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416003PMC
August 2020

Bevacizumab-refractory radiation necrosis with pathologic transformation of benign meningioma following adjuvant gamma knife radiosurgery: A rare case report.

Medicine (Baltimore) 2020 Jul;99(31):e21637

Department of Neurosurgery.

Rationale: Bevacizumab has shown good efficacy in radiation necrosis (RN) following gamma knife radiosurgery (GKRS) and associated peritumoral edema. However, few studies have reported bevacizumab failure. Moreover, the pathologic transformation of benign meningioma following GKRS has never been reported.

Patients Concerns: A 41-year-old man was admitted with focal seizure on the right arm.

Diagnoses: Magnetic resonance imaging (MRI) demonstrated a 4.7 cm-sized convexity meningioma involving left motor cortex.

Interventions: Subtotally resected tumor was confirmed as a meningothelial meningioma and subsequently treated by GKRS. During 4-year follow-up after GKRS, seizure and hemiparesis had persisted with progressively worsened peritumoral edema regardless of steroid and bevacizumab treatment. Radical debulking of tumor was achieved and immunohistopathological examination revealed angiomatous meningioma with necrotic core presenting scanty VEGF expression.

Outcomes: A follow-up MRI at 4 months after debulking surgery showed a marked reduction of peritumoral edema with improvement of symptoms.

Lessons: This is the first report of pathologically confirmed angiomatous transformation following GKRS. Although the pathogenesis is not fully understood, this rare pathologic transformation may be closely related to RN. Also, if bevacizumab is resistant, debulking surgery for reducing tumor burden could be an effective treatment option to control the RN.
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http://dx.doi.org/10.1097/MD.0000000000021637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402780PMC
July 2020

Peptide Vaccine Combined Adjuvants Modulate Anti-tumor Effects of Radiation in Glioblastoma Mouse Model.

Front Immunol 2020 11;11:1165. Epub 2020 Jun 11.

Brain Tumor Research Laboratory, Chonnam National University Medical School and Hwasun Hospital, Chonnam National University, Hwasun, South Korea.

Glioblastoma, the most common aggressive cancer, has a poor prognosis. Among the current standard treatment strategies, radiation therapy is the most commonly recommended. However, it is often unsuccessful at completely eliminating the cancer from the brain. A combination of radiation with other treatment methods should therefore be considered. It has been reported that radiotherapy in combination with immunotherapy might show a synergistic effect; however, this still needs to be investigated. In the current study, a "branched multipeptide and peptide adjuvants [such as pan DR epitope (PADRE) and polyinosinic-polycytidylic acid-stabilized with polylysine and carboxymethylcellulose-(poly-ICLC)]," namely vaccine and anti-PD1, were used as components of immunotherapy to assist in the anti-tumor effects of radiotherapy against glioblastomas. With regard to experimental design, immunological characterization of GL261 cells was performed and the effects of radiation on this cell line were also evaluated. An intracranial GL261 mouse glioma model was established, and therapeutic effects were observed based on tumor size and survival time. The distribution of effector immune cells in the spleen, based on cytotoxic T lymphocyte (CTL) and natural killer (NK) cell function, was determined. The pro-inflammatory and anti-inflammatory cytokine production from re-stimulated splenocytes and single tumor cells were also evaluated. As GL261 cells demonstrated both immunological characteristics and radiation sensitivity, they were found to be promising candidates for testing this combination treatment. Combinatorial treatment with radiation, vaccine, and anti-PD1 prolonged mouse survival by delaying tumor growth. Although this combination treatment led to an increase in the functional activity of both CTLs and NK cells, as evidenced by the increased percentage of these cells in the spleen, there was a greater shift toward CTL rather than NK cell activity. Moreover, the released cytokines from re-stimulated splenocytes and single tumor cells also showed a shift toward the pro-inflammatory response. This study suggests that immunotherapy comprising a branched multipeptide plus PADRE, poly-ICLC, and anti-PD1 could potentially enhance the anti-tumor effects of radiotherapy in a glioblastoma mouse model.
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http://dx.doi.org/10.3389/fimmu.2020.01165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358653PMC
June 2020

What Clinicians Should Consider to Determine a More Beneficial Treatment Strategy for Small to Medium Sized Vestibular Schwannoma With Serviceable Hearing: A Single Surgeon's Long-term Outcome of Microsurgery and Gamma Knife Radiosurgery.

Otol Neurotol 2020 Sep;41(8):1122-1130

Brain Tumor Clinic and Gamma Knife Center, Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Jeollanamdo, South Korea.

Objective: The number of small to medium sized vestibular schwannoma (VS) patients presenting with serviceable hearing has steadily increased. There are various treatment strategies for small to medium sized VS, including microsurgery (MS), gamma knife radiosurgery (GKS), and serial observations using magnetic resonance imaging. In this study, we presented the long-term outcomes of patients with small to medium sized VS with serviceable hearing. We also evaluated the potential prognostic factors for hearing preservation and discussed appropriate treatment strategies.

Methods: A retrospective review of 504 cases of all VS patients who underwent MS or GKS between 1993 and July 2019 was conducted. Surgical resection was performed on 267 patients using the retro-sigmoid approach and 55 (20.6%) of them were small to medium sized VS. GKS was performed on 237 patients and 175 (73.8%) of them were small to medium sized VS. Small to medium sized VS was defined as less than 25 mm in the greatest dimension. After applying the inclusion and exclusion criteria, 51 patients with small to medium sized VS with serviceable hearing were enrolled in this study and underwent either MS (n = 21) or GKS (n = 30). To define the clinical characteristics of the patients, clinical data at the time of treatment, age, sex, presenting symptoms, tumor location type, preoperative hearing status, posttreatment related complications, recurrence, and hearing loss progression-free survival data were collected.

Results: In the MS group, the hearing preservation rate was 71.4% and the tumor control rate was 100%. In the GKS group, the tumor control rate was 93.3% and two patients experienced recurrence at a median interval of 41.5 months. Kaplan-Meier curves showed that the hearing progression-free survival rates at 1-, 3-, and 5-years following GKS were 80, 66.7, and 53.3%, respectively. The MS group had a higher hearing preservation rate at 5 years (71.4 versus 53.3%), but the difference did not reach statistical significance (p = 0.173). Hearing preservation was statistically significant when the preoperative hearing status was class A in the GKS group (p = 0.016), but it was not statistically significant in the MS group (p = 0.777). In the MS group, medial type VS had a higher hearing preservation rate (80%) than the lateral fundal extended type VS (63.6%), and this difference was almost close to statistical significance (p = 0.058). The GKS group had a higher occurrence of postoperative tinnitus (23.3%) than the MS group (9.5%).

Conclusion: MS was more suitable for patients who are younger, have good physical status, good preoperative hearing status including AAO-HNS class B, and medial type VS. GKS was more suitable for patients who are elderly, have poor physical status, preoperative AAO-HNS class A hearing.
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http://dx.doi.org/10.1097/MAO.0000000000002721DOI Listing
September 2020

Salvage surgery with second free flap reconstruction for recurrent oral squamous cell carcinoma.

Heliyon 2020 Jun 11;6(6):e04014. Epub 2020 Jun 11.

Oral Cancer Center, Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea.

Purpose: The purpose of this study was to evaluate the results of the reconstruction using the second free flap following resection of recurrent oral squamous cell carcinoma(OSCC).

Patients And Methods: A total of 25 patients from 2005 to 2018 who had undergone salvage surgery and reconstruction using the second free flap for recurrent OSCC were included in this study. Medical records were reviewed to obtain demographic data, stages of the primary cancer, region of recurrent OSCC, the period until recurrence, type of the second reconstruction flaps, recipient vessels, survival rate of the flaps and 2- and 5-year survival rates.

Results: The patients were 13 males and 12 females. The average age was 64.1 years. Of the stages of primary cancer, stage IV patients accounted for the largest number with 13 patients (52.0%). The region of recurrent OSCC was the largest in the mandible with 13 patients, followed by 5 patients in the tongue and 4 patients in the buccal mucosa and maxilla. The mean time interval between the first and second reconstruction was about 34.1 months. Latissimus dorsi free flap and radial forearm free flap used in the second reconstruction were most frequently used in 11 patients (35.5%), followed by fibular composite free flap with 6 patients (19.4%). Facial artery in the recipient arteries of the second reconstruction was most frequently used with 13 cases (43.3%), followed by superior thyroid artery with 8 cases (26.7%) and lingual artery with 7 cases (23.3%). In the second free flap reconstruction, survival rate of the flaps was 96.8%. The 2- and 5-year survival rates in the patients were 70.0% and 62.5%, respectively.

Conclusion: The study showed that the second free flap reconstruction with salvage surgery in resectable recurrent OSCC is a safe and reliable method with a high success rate of the flap and improvement of the 5-year survival rate.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298410PMC
June 2020

Postoperative radiotherapy for WHO grade II-III intracranial ependymoma in adults: An intergroup collaborative study (KROG 18-06/KNOG 18-01).

Radiother Oncol 2020 Sep 2;150:4-11. Epub 2020 Jun 2.

Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

Background And Purpose: To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II-III intracranial ependymoma (IEPN).

Materials And Methods: A total of 172 pathologically confirmed adult grade II-III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis.

Results: The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P = 0.002), PFS (P = 0.002), and OS (P = 0.043). Older age (P < 0.001), WHO grade III (P < 0.001), larger tumor size (P = 0.004), and lesser surgical extent (P < 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P = 0.010), PFS (P = 0.007), and OS (P = 0.069) on multivariate analysis for grade II IEPNs.

Conclusion: This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II-III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.
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http://dx.doi.org/10.1016/j.radonc.2020.05.045DOI Listing
September 2020

Feasibility of dendritic cell-based vaccine against glioblastoma by using cytoplasmic transduction peptide (CTP)-fused protein antigens combined with anti-PD1.

Hum Vaccin Immunother 2020 Nov 13;16(11):2840-2848. Epub 2020 May 13.

Brain Tumor Research Laboratory.

Recent clinical trials utilizing antigen-pulsed dendritic cells (DCs) have demonstrated increased survival of vaccinated cancer patients. Besides, the cytoplasmic transduction peptide (CTP) not only has an excellent transcellular efficiency but also shows a strong tendency to remain in the cytoplasm after transduction, without migrating into the nucleus. In this study, we investigated the effectiveness of immunotherapy against malignant gliomas using DCs pulsed with CTP-fused protein antigens combined with programmed cell death protein 1 blockade (anti-PD1). The expression of tumor associated antigen (WT1 and BIRC5) and PDL1 on glioblastoma (GBM) target cells was confirmed by western blot. The effect of CTP-fused protein antigens on mature DCs (VaxDCs) was determined. The immunophenotypes of VaxDCs pulsed with CTP-fused protein antigens was confirmed by flow cytometry and the cytokine production levels of T helper polarization were measured by enzyme-linked immunosorbent (ELISA) assay. The IFN-γ-enzyme linked immunospot and lactate dehydrogenase release assays were performed to estimate the cytotoxic activity of antigen-specific cytotoxic T lymphocytes (CTLs), stimulated by VaxDCs pulsed with CTP-fused protein antigens and anti-PD1, against malignant glioma cells expressing target antigens. VaxDCs pulsed with CTP-fused protein antigens showed enhanced expression of major histocompatibility complex (MHC) and co-stimulatory markers of DCs and resulted in Th1 cytokine polarization. The increase in the number of IFN-γ effector T cells paralleled with the enhanced percent specific lysis of GBM targets cells by antigen-specific CTLs. Our study suggested that using CTP-fused protein antigens for DC vaccine preparation along with PD1 blockade could be an effective immunotherapy strategy for GBM.
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http://dx.doi.org/10.1080/21645515.2020.1732165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734070PMC
November 2020

Dural-Based Primary Central Nervous System Lymphoma with Bone Invasion.

World Neurosurg 2020 07 30;139:415-418. Epub 2020 Apr 30.

Department of Pathology, Chonnam National University Medical School, Chonnam National University Hospital and Chonnam National University Hwasun Hospital, Gwangju, Republic of Korea.

Background: Primary central nervous system lymphoma (PCNSL) occurs frequently in a deep intraparenchymal location. It rarely occurs in the meninges, and bone invasion is uncommon.

Case Description: A 12-year-old boy was admitted to our hospital with a history of headache and seizures. Magnetic resonance imaging showed a 4-cm-sized dural-based mass with osteolytic bone change. Craniotomy and tumor removal were performed. Operative findings showed a dural-based hard tumor, including necrosis and hemorrhage, and the skull was focally destroyed by tumor cells. The tumor was completely removed. Pathologically, large atypical cells with pleomorphic nuclei and frequent mitoses were found. The tumor cells were immune-positive for CD30, epithelial cell antigen, and anaplastic lymphoma kinase. The final diagnosis was anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALCL). There was no evidence of systemic cancer. The boy underwent chemotherapy following the Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster protocol. There was no recurrence after a 16-month chemotherapy-off period.

Conclusions: ALCL is not a common type of PCNSL, and central nervous system ALCL frequently involves the dura and meninges compared with PCNSL in general. However, osteolytic bone lesions are rarely seen in ALCL. This case thus represents a rare case of dural-based ALCL with bone invasion.
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http://dx.doi.org/10.1016/j.wneu.2020.04.164DOI Listing
July 2020

The Application of Magnetic Resonance Imaging-Deformed 11C-Methionine-Positron Emission Tomography Images in Stereotactic Radiosurgery.

Stereotact Funct Neurosurg 2019 6;97(4):217-224. Epub 2019 Nov 6.

Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun-gun, Republic of Korea,

Background: Although 11C-methionine positron emission tomography (MET-PET) images can be fused with magnetic resonance (MR) images using planning software for gamma knife radiosurgery (GKR), the stereotactic information has limited value in patients with recurrent malignant brain tumor due to the difference in imaging protocols between MET-PET and MR images. The aim of this study was to evaluate the clinical application of MR imaging (MRI)-deformed MET-PET images in GKR using a deformable registration tool.

Methods: We examined the enhanced MR stereotactic images, MET-PET and MRI-deformed MET-PET images without stereotactic information for 12 newly developed metastatic brain tumors. MET-PET and MRI-deformed MET-PET images were co-registered with the MR stereotactic images using radiosurgery planning software. Visual analysis was performed to determine whether the MET-PET and MR images matched better after using the deformable registration tool. In addition, the matching volume between MR and MET-PET images was compared before and after applying this tool. The matching volume was calculated as the metabolic tumor volume on the MET-PET images, including the MR-enhanced volume. The matching percentage was calculated as the matching volume divided by the MR-enhanced volume, multiplied by 100.

Results: Visual analysis revealed that the MRI-deformed MET-PET images provided the same axial plane as that of the MR images, with the same window level, enabling easy identification of the tumor with the radiosurgery planning software. The mean matching percentage of the MET-PET/MR fusion images was 61.1% (range 24.7-94.7) and that of the MRI-deformed MET-PET/MR fusion images was 63.4% (range 20.8-94.3). No significant difference was found in the matching percentage between the two types of fusion images (p = 0.754).

Conclusions: The MRI-deformed MET-PET images enable utilization of the functional information when planning a treatment in GKR without significant volume change.
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http://dx.doi.org/10.1159/000503732DOI Listing
March 2020

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade II Cerebral Gliomas in Adults: Version 2019.01.

Brain Tumor Res Treat 2019 Oct;7(2):74-84

Department of Neurosurgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.

Background: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established.

Methods: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults.

Results: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase ()-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, -mutant and oligodendroglioma (-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group.

Conclusion: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
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http://dx.doi.org/10.14791/btrt.2019.7.e43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829081PMC
October 2019

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade III Cerebral Gliomas in Adults: Version 2019.01.

Brain Tumor Res Treat 2019 Oct;7(2):63-73

Department of Neurosurgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.

Background: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in , the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established.

Methods: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults.

Results: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase ()-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, -wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, -mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy.

Conclusion: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
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http://dx.doi.org/10.14791/btrt.2019.7.e42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829084PMC
October 2019

Concurrent and Adjuvant Temozolomide for Newly Diagnosed Grade III Gliomas without 1p/19q Co-deletion: A Randomized, Open-Label, Phase 2 Study (KNOG-1101 Study).

Cancer Res Treat 2020 Apr 28;52(2):505-515. Epub 2019 Oct 28.

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

Purpose: We investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.

Materials And Methods: This was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary end-point was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.

Results: The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.

Conclusion: Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.
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http://dx.doi.org/10.4143/crt.2019.421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176949PMC
April 2020

Does the Time Interval from Biopsy to Radical Prostatectomy Affect the Postoperative Oncologic Outcomes in Korean Men?

J Korean Med Sci 2019 Sep 30;34(37):e234. Epub 2019 Sep 30.

Department of Urology, Veterans Health Service Medical Center, Seoul, Korea.

Background: Prostate cancer (PC) is the second most common type of cancer in men worldwide and the fifth most common cancer among Korean men. Although most PCs grow slowly, it is unclear whether a longer time interval from diagnosis to treatment causes worse outcomes. This study aimed to investigate whether the time interval from diagnosis to radical prostatectomy (RP) in men with clinically localized PC affects postoperative oncologic outcomes.

Methods: We retrospectively analyzed data of 427 men who underwent RP for localized PC between January 2005 and June 2016. The patients were divided into two groups based on the cutoff median time interval (100 days) from biopsy to surgery. The associations between time interval from biopsy to surgery (< 100 vs. ≥ 100 days) and adverse pathologic outcomes such as positive surgical margin, pathologic upgrading, and upstaging were evaluated. Biochemical recurrence (BCR)-free survival rates were analyzed and compared based on the time interval from biopsy to surgery.

Results: Pathologic upgrading of Gleason score in surgical specimens was more frequent in the longer time interval group and showed marginal significance (38.8% vs. 30.0%; = 0.057). Based on multivariable analysis, an association was observed between time interval from biopsy to surgery and pathologic upgrading (odds ratio, 2.211; 95% confidence interval [CI], 1.342-3.645; = 0.002). BCR-free survival did not differ based on time interval from biopsy to surgery, and significant association was not observed between time interval from biopsy to surgery and BCR on multivariable analysis (hazard ratio, 1.285; 95% CI, 0.795-2.077; = 0.305).

Conclusion: Time interval ≥ 100 days from biopsy to RP in clinically localized PC increased the risk of pathologic upgrading but did not affect long-term BCR-free survival rates in Korean men.
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http://dx.doi.org/10.3346/jkms.2019.34.e234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763398PMC
September 2019

Multiple Brain Biopsies for Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma with Extensive Necrosis in a Posttransplant Patient.

World Neurosurg 2020 Jan 21;133:10-13. Epub 2019 Sep 21.

Department of Pathology, Chonnam National University Hospital and Chonnam National University Hwasun and Medical School, Gwangju, Republic of Korea.

Background: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in an immunocompromised patient with organ transplantation demonstrated unusual brain magnetic resonance imaging (MRI) findings. Recognition of EBV-positive DLBCL by radiologists on MRI may prevent unnecessary neurosurgical resection, and it could be important to obtain viable cells for accurate diagnosis on stereotactic biopsy because of extensive necrosis.

Case Description: A 62-year-old woman presented to the emergency department with left hemiparesis grade III and dysarthria lasting for 3 weeks. She underwent kidney transplantation in 2007 and was taking immunosuppressants and had hypothyroidism. Brain MRI showed a 3.8-cm peripheral enhancing lesion with extensive central necrosis in association with marked perilesional edema. The irregular ringlike enhancing lesion showed diffusion restriction and mildly increased regional cerebral blood volume in the rim portion of the mass. 11C-Methionine positron emission tomography revealed slightly increased uptake in the peripheral lesion. The provisional diagnosis was a high-grade glioma. Stereotactic multiple biopsies were performed for the central necrotic area and peripheral enhancing lesion. The nonenhancing areas showed only necrotic material, without viable cells, and the enhancing portion showed viable cells for an accurate diagnosis in a frozen biopsy specimen. The pathologic diagnosis was EBV-positive DLBCL with extensive necrosis. Positron emission tomography of the chest, abdomen, pelvis, and neck soft tissues ruled out systemic diseases. She underwent whole-brain radiotherapy at a dose of 30.6 Gy. Eight months later, her neurologic symptoms had improved, with a stable brain lesion and improved perilesional edema.

Conclusions: We report an immunocompromised patient with EBV-positive DLBCL, which showed atypical MRI findings, including extensive necrosis. Multiple biopsies were required for final diagnosis.
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http://dx.doi.org/10.1016/j.wneu.2019.09.084DOI Listing
January 2020

Recurrent Glioma With Lineage Conversion From Oligodendroglioma to Astrocytoma in Two Cases.

Front Oncol 2019 27;9:828. Epub 2019 Aug 27.

Department of Pathology, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Hwasun, South Korea.

Following the introduction of the molecular classification of gliomas by the WHO in 2016, molecularly-proven lineage conversion during glioma recurrence has never been reported. The reported two cases were initially diagnosed as oligodendroglioma with 1p/19q-codeletion and mutation of -R132H. The recurrent tumors showed loss of alpha-thalassemia/mental retardation X-linked (ATRX) expression, strong P53 positivity, and 1p/19q-nondeletion. Next generation sequencing analysis performed on the first case confirmed the transition of molecular traits from oligodendroglioma to astrocytoma. An mutation of R132H was preserved in the episodes of recurrence, but and mutations were newly acquired and promoter mutation C228T was lost at the most recent recurrence. The issue in question for the presented cases is whether the original tumors were pure oligodendrogliomas that then transdifferentiated into astrocytomas, or whether the original tumor was an oligoastrocytoma having oligodendroglioma cells that outnumbered the astrocytoma cells and where the astrocytoma cells becoming more dominant over the episodes of recurrence. With the recognition of the possibility of lineage conversion, our study suggests that molecular examination should be performed to adjust therapeutic strategies in recurrent gliomas. Indeed, our observation of lineage conversion in glioma recurrence calls into question the current distinction drawn between oligodendroglioma, astrocytoma and oligoastrocytoma, rather than simply bidding "farewell to oligoastrocytoma."
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http://dx.doi.org/10.3389/fonc.2019.00828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719522PMC
August 2019

Hemifacial Spasm Caused by Small Epidermoid Tumor, Misinterpreted as Delayed Secondary Hemifacial Spasm Caused by Vestibular Schwannoma Treated with Gamma Knife Surgery.

World Neurosurg 2019 Oct 23;130:410-414. Epub 2019 Jul 23.

Brain Tumor Clinic and Gamma Knife Center, Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Jeollanam-do, South Korea.

Background: Hemifacial spasm (HFS), one of the most common hyperactive cranial rhizopathies, is a disorder characterized by spontaneous, intermittent, and repetitive contraction of unilateral facial muscle. The most common cause of HFS is a mechanical compression of the facial nerve at the root exit zone (REZ) by blood vessels located in the brainstem. The incidence of cerebellopontine angle (CPA) tumor-induced HFS ranges from 0.3%-2.5% of all patients with HFS, and the incidence of epidermoid cyst among such tumors is extremely rare (0.2% to 0.25%). We present a patient manifesting HFS induced by a small epidermoid cyst who underwent Gamma Knife surgery (GKS) for ipsilateral vestibular schwannoma (VS) more than 10 years ago.

Clinical Description: A 59-year-old female was admitted to our hospital with HFS. Ten years before admission, the patient underwent GKS for ipsilateral VS. Enhanced brain magnetic resonance imaging demonstrated that the volume of VS was not increased. Also, no definitive mechanical compression of the facial nerve REZ by blood vessels was detected. We concluded that HFS was secondary to the VS treatment by GKS and decided to operate to remove the tumor and identify REZ. A standardized lateral suboccipital retrosigmoid approach was performed. The cochlear nerve was encased by a tumor mass, and the posterior inferior cerebellar artery (PICA) was displaced by the mass. During tumor excision, we ensured that the VS and displaced PICA did not directly compress the REZ. Interestingly, an unexpected lesion was found with a yellowish viscous mass located between the sixth nerve and ventral side of the seventh nerve REZ. After the tumor removal, a small piece of Teflon was inserted between the PICA and REZ of the facial nerve. Postoperatively, the patient experienced no HFS or facial nerve dysfunction. Histopathologic examination of the lesion revealed an epidermoid cyst.

Conclusions: We should consider various possibilities for the cause of HFS and review brain imaging meticulously if patients were treated for CPA tumor with GKS a long time ago and the delayed HFS occurred without changes in tumor volume. HFS induced by epidermoid cyst is rare. Therefore it is critical for the neurosurgeon to ensure the absence of any abnormal contact with the REZ of the facial nerve during surgery for HFS induced by CPA tumors.
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http://dx.doi.org/10.1016/j.wneu.2019.07.119DOI Listing
October 2019

Herstory of the Korean Women Neurosurgical Society since 2008.

J Korean Neurosurg Soc 2019 Nov 15;62(6):619-625. Epub 2019 Jul 15.

Korean Women Neurosurgical Society, Seoul, Korea.

The Korean Women Neurosurgical Society (KWNS) was founded in 2008. To commemorate its 10th anniversary, herein we review its history and the status of Korean Neurosurgical Society (KNS)-certified women neurosurgeons. Based on the academic and social activity of the KWNS, we can expect to promote professional work as members of the KNS, facilitate interaction among neurosurgeons, and sustain professional careers.
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http://dx.doi.org/10.3340/jkns.2019.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835153PMC
November 2019

Quantitative Feasibility Evaluation of 11C-Methionine Positron Emission Tomography Images in Gamma Knife Radiosurgery : Phantom-Based Study and Clinical Application.

J Korean Neurosurg Soc 2019 Jul 4;62(4):476-486. Epub 2019 Jun 4.

Department of Neurosurgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

Objective: The functional information of 11C-methionine positron emission tomography (MET-PET) images can be applied for Gamma knife radiosurgery (GKR) and its image quality may affect defining the tumor. This study conducted the phantom-based evaluation for geometric accuracy and functional characteristic of diagnostic MET-PET image co-registered with stereotactic image in Leksell GammaPlan® (LGP) and also investigated clinical application of these images in metastatic brain tumors.

Methods: Two types of cylindrical acrylic phantoms fabricated in-house were used for this study : the phantom with an array-shaped axial rod insert and the phantom with different sized tube indicators. The phantoms were mounted on the stereotactic frame and scanned using computed tomography (CT), magnetic resonance imaging (MRI), and PET system. Three-dimensional coordinate values on co-registered MET-PET images were compared with those on stereotactic CT image in LGP. MET uptake values of different sized indicators inside phantom were evaluated. We also evaluated the CT and MRI co-registered stereotactic MET-PET images with MR-enhancing volume and PET-metabolic tumor volume (MTV) in 14 metastatic brain tumors.

Results: Imaging distortion of MET-PET was maintained stable at less than approximately 3% on mean value. There was no statistical difference in the geometric accuracy according to co-registered reference stereotactic images. In functional characteristic study for MET-PET image, the indicator on the lateral side of the phantom exhibited higher uptake than that on the medial side. This effect decreased as the size of the object increased. In 14 metastatic tumors, the median matching percentage between MR-enhancing volume and PET-MTV was 36.8% on PET/MR fusion images and 39.9% on PET/CT fusion images.

Conclusion: The geometric accuracy of the diagnostic MET-PET co-registered with stereotactic MR in LGP is acceptable on phantom-based study. However, the MET-PET images could the limitations in providing exact stereotactic information in clinical study.
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http://dx.doi.org/10.3340/jkns.2019.0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616987PMC
July 2019

Importance of collateral venous circulation on indocyanine green videoangiography in intracranial meningioma resection: direct evidence for venous compression theory in peritumoral edema formation.

J Neurosurg 2019 May 24;132(6):1715-1723. Epub 2019 May 24.

Departments of1Neurosurgery and.

Objective: Indocyanine green videoangiography (ICGVA) has been used in many neurosurgical operations, including vascular and brain tumor fields. In this study, the authors applied ICGVA to intracranial meningioma surgery and evaluated it usefulness with attention to collateral venous flow.

Methods: Forty-two patients with intracranial meningioma who underwent ICGVA during microsurgical resection were retrospectively analyzed. For ICGVA, the ICG was injected intravenously at the standard dose of 12.5 mg before and/or after tumor resection. Intravascular fluorescence from blood vessels was imaged through a microscope with a special filter and infrared excitation light to illuminate the operating field. The authors assessed the benefits of ICGVA and analyzed its findings with preoperative radiological findings on MRI.

Results: ICGVA allowed real-time assessment of the patency and flow direction in very small peritumoral vessels in all cases. A safe dural incision could also be done based on information from ICGVA. The collateral venous channel due to venous obstruction of tumoral compression was found in 10 cases, and venous flow restoration after tumor resection was observed promptly after tumor resection in 4 cases. Peritumoral brain edema (PTBE) was observed on preoperative T2-weighted MRI in 19 patients. The presence of collateral venous circulation or flow restoration was significantly related to PTBE formation in multivariate analysis (p = 0.001; HR 0.027, 95% CI 0.003-0.242).

Conclusions: ICGVA, an excellent method for monitoring blood flow during meningioma resection, provides valuable information as to the presence of venous collaterals and flow restoration. Furthermore, the fact that the presence of venous collaterals was found to be associated with PTBE may directly support the venous theory as the pathogenesis of PTBE formation.
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http://dx.doi.org/10.3171/2019.3.JNS182308DOI Listing
May 2019

Primary Intraparenchymal Central Nervous System Solitary Fibrous Tumor/Hemangiopericytoma Presenting with Intracerebral Hemorrhage: A Case Report.

Brain Tumor Res Treat 2019 Apr;7(1):53-56

Department of Pathology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun, Korea.

A 53-year old man who had a left hemiparesis from head injury of traffic accident 20 years ago visited an emergency room with suddenly developed semi-comatose mental status. Brain CT showed 8.6-cm sized solid and cystic mass on right temporal lobe that was associated with hemorrhage. Solid lesion showed a strong enhancement after an administration of contrast media. Because of severe mass effect, emergency operation was performed. The mass was an intraparenchymal lesion with yellowish cystic fluid and the firm reddish-brown solid lesion was hemorrhagic. The lesion was totally resected. Pathologically, anaplastic solitary fibrous tumor/hemangiopericytoma was diagnosed with 70/10 high power fields. Postoperative radiotherapy of 50 Gy was done. Postoperative 2 months later, the patient was recovered to alert mental state. We report this unusual case of non-dural based intraparenchymal solitary fibrous tumor/hemangiopericytoma with high mitotic index and acute massive hemorrhage. Rapid tumor growth of hypervascular tumor might have a chance of bleeding.
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http://dx.doi.org/10.14791/btrt.2019.7.e27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504755PMC
April 2019

The Korean Society for Neuro-Oncology (KSNO) Guideline for Glioblastomas: Version 2018.01.

Brain Tumor Res Treat 2019 Apr;7(1):1-9

Department of Neurosurgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.

Background: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018.

Methods: The Working Group was composed of 35 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.

Results: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment.

Conclusion: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
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http://dx.doi.org/10.14791/btrt.2019.7.e25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504754PMC
April 2019

The Role Played by SLUG, an Epithelial-Mesenchymal Transition Factor, in Invasion and Therapeutic Resistance of Malignant Glioma.

Cell Mol Neurobiol 2019 Aug 22;39(6):769-782. Epub 2019 Apr 22.

Department of Neurosurgery, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, 58128, South Korea.

In malignant gliomas, invasive phenotype and cancer stemness promoting resurgence of residual tumor cells render treatment very difficult. Hence, identification of epithelial-mesenchymal transition (EMT) factors associated with invasion and stemness of glioma cells is critical. To address the issue, we investigated several EMT factors in hypermotile U87MG and U251 cells, orthotopic mouse glioma model, and human glioma samples. Of several EMT markers, SLUG expression was notably increased at the invasive fronts of gliomas, both in mouse tumor grafts and human glioma samples. The biological role played by SLUG was investigated using a colony-forming assay after chemotherapy and irradiation, and by employing a neurosphere culture assay. The effect of SLUG on glioma progression was examined in our patient cohort and samples, and compared to large public data from the REMBRANDT and TCGA. Genetic upregulation of SLUG was associated with increased levels of stemness factors and enhanced resistance to radiation and temozolomide. In our cohort, patients exhibiting lower-level SLUG expression evidenced longer progression-free survival (P = 0.042). Also, in the REMBRANDT dataset, a group in which SLUG was downregulated exhibited a significant survival benefit (P < 0.001). Although paired glioblastoma samples from our patients did not show a significant increase of SLUG expression, increased mRNA levels of SLUG were found in recurrent glioblastoma from TCGA (P = 0.052), and in temozolomide-treated glioma cells and mouse tumor grafts. SLUG may contribute to glioma progression by controlling invasion at infiltrating margins, associated with increased stemness and therapeutic resistance.
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http://dx.doi.org/10.1007/s10571-019-00677-5DOI Listing
August 2019

Nutritional status regulates algicidal activity of Aeromonas sp. L23 against cyanobacteria and green algae.

PLoS One 2019 12;14(3):e0213370. Epub 2019 Mar 12.

Department of Environmental Engineering, Yonsei University, Wonju, Republic of Korea.

Algicidal bacteria have received broad acceptance as an ecofriendly tool for controlling harmful algal blooms. However, their practical application is still limited to the lab-scale tests due to the complex alga-bacterium interactions in different nutrient statuses. In this study, the Aeromonas sp. L23 that exhibit relatively wide-spectrum in algicidal activity was isolated from a eutrophic agricultural lake. The physiological response of cyanobacteria and green to the algicidal activity under varied nutritional status were studied in an alga-bacterial co-culture. The algicidal activities of L23 against Microcystis aeruginosa UTEX LB 2385, Microcystis aeruginosa NHSB, Anabaena variabilis AG10064, Scenedesmus quadricauda AG10003, and Chlorella vulgaris AG10034 were 88 ± 1.2%, 94 ± 2.6%, 93 ± 0.5%, 82 ± 1.1%, and 47 ± 0.9%, respectively. The L23 cells had low algicidal activity in cell pellet (3%-9%) compared with the cell-free supernatant (78%-93%), indicating that the activity is induced by extracellular substances. Adding glucose, NaNO3, NH4Cl, and KH2PO4 to the co-culture raised the algicidal activity of the L23 against green algae by 5%-50%. Conversely, a 10%-20% decrease in activity occurred against the target cyanobacteria except M. aeruginosa UTEX LB 2385. These results indicated that the interspecific algicidal activity changes according to the nutritional status, which means that the alga-bacterium interaction will be more complex in the field where the nutritional status changes from time to time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213370PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413897PMC
December 2019