• Journal of Korean Neurosurgical Society
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• 제61권3호
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• pp.376-385
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• 2018

Recent discoveries of brain tumor-related genes and fast advances in genomic testing technologies have led to the era of molecular diagnosis of brain tumor. Molecular profiling of brain tumor became the significant step in the diagnosis, the prediction of prognosis and the treatment of brain tumor. Because traditional molecular testing methods have limitations in time and cost for multiple gene tests, next-generation sequencing technologies are rapidly introduced into clinical practice. Targeted sequencing panels using these technologies have been developed for brain tumors. In this article, focused on pediatric brain tumor, key discoveries of brain tumor-related genes are reviewed and cancer panels used in the molecular profiling of brain tumor are discussed.

• Clinical and Experimental Pediatrics
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• 제65권2호
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• pp.56-64
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• 2022

Cerebrospinal fluid (CSF) is a dynamic metabolically active body fluid that has many important roles and is commonly analyzed in pediatric patients, mainly to diagnose central nervous system infection and inflammation disorders. CSF components have been extensively evaluated as biomarkers of neurological disorders in adult patients. Circulating microRNAs in CSF are a promising class of biomarkers for various neurological diseases. Due to the complexity of pediatric neurological disorders and difficulty in acquiring CSF samples from pediatric patients, there are challenges in developing CSF biomarkers of pediatric neurological disorders. This review aimed to provide an overview of novel CSF biomarkers of seizure disorders, infection, inflammation, tumor, traumatic brain injuries, intraventricular hemorrhage, and congenital hydrocephalus exclusively observed in pediatric patients.

• Clinical and Experimental Pediatrics
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• 제59권sup1호
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• pp.139-144
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• 2016

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome that affects ectomesodermal tissues (skin, eyes, adipose tissue, and brain). The neurologic manifestations associated with ECCL are various including seizures. However, ECCL patients very rarely develop brain tumors that originate from the neuroepithelium. This is the first described case of ECCL in combination with dysembryoplastic neuroepithelial tumor (DNET) that presented with intractable seizures. A 7-year-old girl was admitted to our center because of ECCL and associated uncontrolled seizures. She was born with right anophthalmia and lipomatosis in the right temporal area and endured right temporal lipoma excision at 3 years of age. Seizures began when she was 3 years old, but did not respond to multiple antiepileptic drugs. Brain magnetic resonance (MR) imaging performed at 8 and 10 years of age revealed an interval increase of multifocal hyperintense lesions in the basal ganglia, thalamus, cerebellum, periventricular white matter, and, especially, the right temporal area. A nodular mass near the right hippocampus demonstrated the absence of N-acetylaspartate decrease on brain MR spectroscopy and mildly increased methionine uptake on brain positron emission tomography, suggesting low-grade tumor. Twenty-four-hour video electroencephalographic monitoring also indicated seizures originating from the right temporal area. Right temporal lobectomy was performed without complications, and the nodular lesion was pathologically identified as DNET. The patient has been seizure-free for 14 months since surgery. Although ECCL-associated brain tumors are very rare, careful follow-up imaging and surgical resection is recommended for patients with intractable seizures.

• Clinical and Experimental Pediatrics
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• 제59권sup1호
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• pp.96-98
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• 2016

Wilms' tumor is the most common malignant renal tumor in childhood. The brain metastasis of a Wilms' tumor with anaplastic histopathology is rare. We present the case of an 8-year-old girl with Wilms' tumor, who presented with multiple brain metastases 5 years after her primary diagnosis. The brain masses were diagnosed after a generalized tonic-clonic seizure attack. The big solid mass in the cerebellum was resected, and whole-brain radiotherapy was performed, after which, she succumbed to her disease. In the case of clinical suspicion, cranial surveillance should be included in the routine clinical work-up for Wilms' tumor. Combined aggressive therapy (surgery+radiotherapy+chemotherapy) should be applied whenever possible, for both better survival and palliative aspects.

• Journal of Korean Neurosurgical Society
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• 제62권3호
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• pp.313-320
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• 2019

Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.

• Clinical and Experimental Pediatrics
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• 제57권10호
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• pp.434-439
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• 2014

Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered.

• Journal of Korean Neurosurgical Society
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• 제40권3호
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• pp.154-158
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• 2006

Objective : We treated 10 pediatric diffuse intrinsic brain stem glioma[BSG] patients with Novalis system [linac based radiotherapy unit, Germany] and examined the efficacy of the Fractionated Stereotactic Radiotherapy[FSRT]. Methods : A retrospective review was conducted on 10 pediatric diffuse intrinsic BSG patients who were treated with FSRT between May, 2001 and August, 2004. The mean age of the patient group was 7.7 years old. Male to female ratio was 4 to 1. The mean dose of FSRT was 38.7Gy, mean fractionated dose was 2.6Gy, mean fractionation size was 16.6, and target volume was $42.78cm^3$. The mean follow up period was 14 months. Results : Four weeks after completion of FSRT, improvements on neurological status and Karnofsky performance scale[KPS] score were recorded in 9/10 (90%] patients and magnetic resonance imaging[MRI] showed decrease in target tumor volume in 8 pediatric patients. The median survival period was 13.5 months after FSRT and treatment toxicity was mild. Conclusion : It is difficult for surgeons to choose surgical treatment for diffuse intrinsic BSG due to its dangerous anatomical structures. FSRT made it possible to control the tumor volume to improve neurological symptoms with minimal complications. We expect that FSRT is a feasible treatment modality for pediatric diffuse intrinsic BSG with tolerable toxicities.

• Advances in pediatric surgery
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• 제8권2호
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• pp.101-106
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• 2002

The antiangiogenic effects of novel agent KJ3, Betulinic acid, and Fumagillin on the neovascularization were studied by examining ultrastructural alterations in the vasculature of synthetic gelform and mouse neuroblastoma C1300. Small pieces of gelform with 0.4% agar were introduced subcutaneously (s.c.) in 7 week old male CH3/HeJ mice. After the $LD_{50}s$ were determined by FACS analysis, a third of $LD_{50}$ of three drugs were injected either locally or intraperitoneally every other day for 14 days. A/J mice were inoculated s.c. with the C1300 neuroblastoma cell line, then either saline or three drugs were injected in the same manner. The antiangiogenic effects of three drugs were studied by measuring the histologic changes in tumors, and immunostaining for CD34, VIII/vWF, CD105, and thymidine phosphorylase. In the drug treated groups, the number of vessels in gelform experiments and C1300 neuroblastoma experiments were lower than the corresponding values in the control. The histologic findings were significantly different in drug treated groups on day 7, but these were not significant on day 14. These results imply that antiangiogenic agents were effective when the tumor burden is minimal.

• Clinical and Experimental Pediatrics
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• 제45권8호
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• pp.1016-1023
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• 2002

목 적: 뇌종양은 소아에서 가장 흔한 고형암종이다. 이번 연구는 15년간의 임상적 고찰을 통해 나이, 성별, 종양의 위치에 따라 소아 뇌종양을 분류해 보았고, 각각의 총생존율을 조사해 보았으며 또한 일부 질환에서는 항암제 추가여부가 생존율에 미치는 영향에 대해서도 조사해 보았다. 방 법 : 1985년 1월부터 2001년 9월까지 세브란스병원에서 진단받고 치료받은 354명의 소아 뇌종양 환자를 대상으로 임상적 기록에 의거하여 후향조사하였다. 결 과 : 소아 뇌종양의 호발 연령은 5-10세와 10-15세가 큰 차이 없이 모두 높았고 남녀비에서는 남자가 조금 우세하였다. 위치별 빈도는 천막상종양(52%)과 천막하종양(48%)에서 비슷하였으나 천막상종양이 근소하게 많았다. 가장 호발하는 종양의 종류는 수모세포종/원시신경외배엽성종양으로 87례(24.6%)였고 다음으로는 소뇌 성상세포종으로 50례(14.1%)였다. 수모세포종, 소뇌 성상세포종, 대뇌 성상세포종은 10년 생존율이 59.4%, 79.3%, 71%로 비교적 예후가 양호하였다. 뇌간교종과 다형성아교모세포종은 10년 생존율이 12.7%, 13.3%로 예후가 불량하였다. 수모세포종의 고위험군에서는 항암제를 사용한 경우에서 사용하지 않은 경우보다 10년 생존율이 유의하게 높았다(54.5%와 40%, P<0.05). 결 론 : 본 연구는 단일기관의 다수의 환자를 대상으로 15년간의 장기간동안 치료 결과를 추적 관찰하여 기타 문헌과의 비교를 해보았다. 수술기법과 방사선, 항암제의 병합요법으로 뇌종양의 생존율 향상이 보고되고 있는바 본 연구에서도 최근 보고처럼 생존율의 향상을 볼 수 있었다. 특히 고위험군 수모세포종의 경우에서는 추가로 항암제를 사용한 경우 생존율이 높아짐을 볼 수 있었다.

• 한국환경보건학회지
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• 제41권3호
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• pp.182-190
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• 2015

Objectives: To introduce a protocol of Mobi-kids study which was aimed to examine an association between radiofrequency (RF) radiation exposure by mobile phone use and brain tumor risk in children and adolescents. Methods: The Mobi-kids study was a multinational matched case control study using a standardized protocol with the number of subjects targeted about 1,000 cases and 2,000 controls aged 10 to 24. In Mobi-Kids Korea, the source population was restricted to Seoul, Incheon, and Gyeonggi-do province. Eligible cases of primary brain tumor (glioma, meningioma, and others) were diagnosed from January 2012 to June 2015. Eligible controls were appendicitis patients operated during the study period. Two controls were matched on age, gender, and study region for 1 case. Information about pattern and history of mobile phone use and other covariates were obtained by face to face interview by trained interviewer. The Mobi-kids study has been involved in Mobi-expo as a validation study about mobile phone use, XGridmaster to localize tumor in the brain for RF energy calculation, and histological review for validation of diagnosis. Results: The Mobi-kids was the first and largest study in children and adolescents to estimate risk of brain tumor in association with the RF energy absorption in the brain estimated by mobile phone use. Forty-six-cases and 54 controls were collected as of September 2014 in Korea. Conclusions: The meaningful results of the study were expected because of the largest sample size, high validity of EMF exposure assessment as well as the susceptible study populationof children and adolescents.