• Journal of Korean Neurosurgical Society
• /
• 제64권4호
• /
• pp.631-643
• /
• 2021

Objective : Here, we evaluated whether cerebrospinal fluid (CSF) profiles and their changes after intraventricular chemotherapy for leptomeningeal carcinomatosis (LMC) could predict the treatment response or be prognostic for patient overall survival (OS) along with clinical factors. Methods : Paired 1) pretreatment lumbar, 2) pretreatment ventricular, and 3) posttreatment ventricular samples and their CSF profiles were collected retrospectively from 148 LMC patients who received Ommaya reservoir installation and intraventricular chemotherapy. CSF profile changes were assessed by calculating the differences between posttreatment and pretreatment samples from the same ventricular compartment. CSF cell counts were further differentiated into total and other based on clinical laboratory reports. Results : For the treatment response, a decreased CSF 'total' cell count tended to be associated with a 'controlled' increase in intracranial pressure (ICP) (p=0.059), but other profile changes were not associated with either the control of increased ICP or the cytology response. Among the pretreatment CSF profiles, lumbar protein level and ventricular cell count were significantly correlated with OS in univariable analysis, but they were not significant in multi-variable analysis. Among CSF profile changes, a decrease in 'other' cell count showed worse OS than 'no change' or increased groups (p=0.001). The cytological response was significant for OS, but the hazard ratio of partial remission was paradoxically higher than that of 'no response'. Conclusion : A decrease in other cell count of CSF after intraventricular chemotherapy was associated with poor OS in LMC patients. We suggest that more specific CSF biomarkers of cancer cell origin are needed.

• Journal of Korean Neurosurgical Society
• /
• 제64권3호
• /
• pp.386-405
• /
• 2021

Recent advancements in basic research on the process of secondary neurulation and increased clinical experience with caudal spinal anomalies with associated abnormalities in the surrounding and distal structures shed light on further understanding of the pathoembryogenesis of the lesions and led to the new classification of these dysraphic entities. We summarized the changing concepts of lesions developed from the disordered secondary neurulation shown during the last decade. In addition, we suggested our new pathoembryogenetic explanations for a few entities based on the literature and the data from our previous animal research. Disordered secondary neurulation at each phase of development may cause corresponding lesions, such as failed junction with the primary neural tube (junctional neural tube defect and segmental spinal dysgenesis), dysgenesis or duplication of the caudal cell mass associated with disturbed activity of caudal mesenchymal tissue (caudal agenesis and caudal duplication syndrome), failed ingression of the primitive streak to the caudal cell mass (myelomeningocele), focal limited dorsal neuro-cutaneous nondisjunction (limited dorsal myeloschisis and congenital dermal sinus), neuro-mesenchymal adhesion (lumbosacral lipomatous malformation), and regression failure spectrum of the medullary cord (thickened filum and filar cyst, low-lying conus, retained medullary cord, terminal myelocele and terminal myelocystocele). It seems that almost every anomalous entity of the primary neural tube may occur in the area of secondary neurulation. Furthermore, the close association with the activity of caudal mesenchymal tissue in secondary neurulation involves a wider range of surrounding structures than in primary neurulation. Although the majority of the data are from animals, not from humans and many theories are still conjectural, these changing concepts of normal and disordered secondary neurulation will provoke further advancements in our management strategies as well as in the pathoembryogenetic understanding of anomalous lesions in this area.

• Journal of Korean Neurosurgical Society
• /
• 제55권1호
• /
• pp.5-11
• /
• 2014

Objective : We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Methods : Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Results : Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Conclusion : Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

• Radiation Oncology Journal
• /
• 제36권3호
• /
• pp.182-191
• /
• 2018

Purpose: To investigate the clinical outcome of proton therapy (PT) in patients with chordoma. Materials and Methods: Fifty-eight patients with chordoma treated with PT between June 2007 and December 2015 at the National Cancer Center, Korea, were retrospectively analyzed. The median total dose was 69.6 cobalt gray equivalent (CGE; range, 64.8 to 79.2 CGE). Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method. Results: With the median follow-up of 42.8 months (range, 4 to 174 months), the 5-year LPFS, DMFS, OS, and DSS rates were 87.9%, 86.7%, 88.3%, and 92.9%, respectively. The tumor location was associated with the patterns of failure: the LPFS rates were lower for cervical tumors (57.1%) than for non-cervical tumors (93.1%) (p = 0.02), and the DMFS rates were lower for sacral tumors (53.5%) than for non-sacral tumors (100%) (p = 0.001). The total dose was associated with both the LPFS rate and DMFS rate. The initial tumor size was associated with the DMFS rate, but was not associated with the LPFS rate. Three patients had grade 3 late toxicity with none ≥grade 4. Conclusion: PT is an effective and safe treatment in patients with chordomas. The tumor location was associated with the patterns of failure: local failure was common in cervical tumors, and distant failure was common in sacral tumors. Further refinement of PT, such as the utilization of intensity modulated PT for cervical tumors, is warranted to improve the outcome.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2004년도 Annual Meeting of the Korean Society ofApplied Pharmacology
• /
• pp.95-99
• /
• 2004

• Journal of Korean Neurosurgical Society
• /
• 제48권2호
• /
• pp.145-152
• /
• 2010

Objective : The aim of this report is to provide accurate nationwide epidemiologic data on primary central nervous system (CNS) tumors in Korea. Despite its importance, there are no accurate statistics on primary CNS tumors in Korea. We analyzed primary CNS tumors diagnosed in 2005 from the nationwide registry. Methods : Data on primary CNS tumors diagnosed in 2005 were collected from the Korean Central Cancer Registry and the Korean Brain Tumor Society. Crude and age-standardized rates were calculated in terms of gender, age, and histological type. Tumors of uncertain histology were investigated individually at the corresponding hospitals and had their diagnoses confirmed. Results : A total of 5,692 patients diagnosed with primary CNS tumors in 2005 were included in this study. CNS tumors occurred in females more often than in males (female to male, 1.43 : 1). The most common tumor was meningioma (31.2%). Glioblastoma accounted for 30.7% of all gliomas, and 19.3% of all malignant primary CNS tumors. In children under 19 years of age, both germ cell tumor and embryonal/primitive/medulloblastoma were the most common tumors. Conclusion : This article is the first nationwide primary CNS tumor epidemiology report in Korea. Data from this study should provide valuable information regarding the understanding of primary CNS tumors epidemiology in Korea.

• 한국멀티미디어학회논문지
• /
• 제18권12호
• /
• pp.1445-1452
• /
• 2015

In these days, fluorescent materials such as ICG or 5-ALA is used for the brain surgery. The patients who underwent brain tumor surgery has been increased during last 30 years and the survivorship rate increased 22∼33% in 5 years. Recently, the Fluorescence induction surgery is developed for more safety and improved the resection rate for the glioma in the neurosurgery field. In this study, we proposed fluorescence area detection method for ICG and 5-ALA fluorescence induced surgery using acquired images from image processing. Accuracy was 99.21% from ICG images, and 99.51% from 5-ALA images. Matthews correlation coefficient was 88.67% from ICG images, and 90.49% from 5-ALA images.

• Journal of Korean Neurosurgical Society
• /
• 제52권3호
• /
• pp.193-199
• /
• 2012

Objective : The objective of study is to evaluate the incidence of leptomeningeal carcinomatosis (LMC) in breast cancer patients with parenchymal brain metastases (PBM) and clinical risk factors for the development of LMC. Methods : We retrospectively analyzed 27 patients who had undergone surgical resection (SR) and 156 patients with whole brain radiation therapy (WBRT) as an initial treatment for their PBM from breast cancer in our institution and compared the difference of incidence of LMC according to clinical factors. The diagnosis of LMC was made by cerebrospinal fluid cytology and/or magnetic resonance imaging. Results : A total of 27 patients (14%) in the study population developed LMC at a median of 6.0 months (range, 1.0-50). Ten of 27 patients (37%) developed LMC after SR, whereas 17 of 156 (11%) patients who received WBRT were diagnosed with LMC after the index procedure. The incidence of LMC was significantly higher in the SR group compared with the WBRT group and the hazard ratio was 2.95 (95% confidence interval; 1.33-6.54, p<0.01). Three additional factors were identified in the multivariable analysis : the younger age group (<40 years old), the progressing systemic disease showed significantly increased incidence of LMC, whereas the adjuvant chemotherapy reduce the incidence. Conclusion : There is an increased risk of LMC after SR for PBM from breast cancer compared with WBRT. The young age (<40) and systemic burden of cancer in terms of progressing systemic disease without adjuvant chemotherapy could be additional risk factors for the development of LMC.

• Journal of Korean Neurosurgical Society
• /
• 제63권5호
• /
• pp.566-578
• /
• 2020

Objective : Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective. Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. Methods : We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC₅₀ radiation dose was determined. Dexamethasone dose (10 μM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. Results : Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. Conclusion : Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTEN-mutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.

• Journal of Korean Neurosurgical Society
• /
• 제64권3호
• /
• pp.380-385
• /
• 2021

Caudal agenesis refers to the congenital malformation with the essential feature of the agenesis of the sacrococcygeal bone. It is associated with various types of spinal cord anomaly as well as with complex anomalies of genitourinary or gastrointestinal system. The wide spectrum of the disease can be attributed to its pathoembryological origin, the secondary neurulation. This review presents the definition, etiology, classification, and clinical features of the disease.