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1.  Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma 
Neuro-Oncology  2012;15(3):352-359.
We assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).
From October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm2) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.
Of 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm2 without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23−82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12−68) after tandem HDCT/autoSCT were acceptable.
In children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.
PMCID: PMC3578484  PMID: 23258845
autologous stem cell transplantation; high-dose chemotherapy; late effect; medulloblastoma; radiotherapy
2.  Bromocriptine Therapy for the Treatment of Invasive Prolactinoma: The Single Institute Experience 
The objective of this study was to describe and characterize the clinical course of treatment for invasive prolactinoma patients using bromocriptine.
The study group included 23 patients who were treated with bromocriptine for their invasive prolactinomas. Clinical histories, serum prolactin level and pituitary hormone assessments, tumor diameter and signal intensity on sella magnetic resonance imaging (MRI), visual field exams and the dosage of medications were reviewed for each patient.
During 30 months (median, range 6-99) of follow-up period, 19 patients treated with bromocriptine alone achieved biochemical remission. Four patients changed the medication to cabergoline due to the adverse effects or observed resistance of bromocriptine treatment. All of five patients who had visual symptoms improved after the course of medication. Four surgically treated patients were not able to discontinue medication because they could not maintain biochemical remission state without medication. Multivariate analysis showed that decreased enhancement on the initial followed MRI after medication and longer follow-up periods were associated with higher radiologic response.
We reassure that the dopamine agonist is safe and effective for the treatment of invasive pituitary adenomas. Meanwhile, surgery has a limited role on biochemical remission. Decreased enhancement on the initial follow-up MRI after medication may reflect the treatment response. Further study is required to validate the role of MRI or other factors on the actual prognosis.
PMCID: PMC4027106  PMID: 24904895
Invasive prolactinoma; Bromocriptine; Pituitary adenoma; Cabergoline; Dopamine agonist
3.  Upward Migration of a Peritoneal Catheter Following Ventriculoperitoneal Shunt 
We present an unusual case of peritoneal catheter migration following a ventriculoperitoneal shunt operation. A 7-month-old infant, who had suffered from intraventricular hemorrhage at birth, was shunted for progressive hydrocephalus. The peritoneal catheter, connected to an 'ultra small, low pressure valve system' (Strata®; PS Medical,Gola, CA, USA) at the subgaleal space, was placed into the peritoneal cavity about 30 cm in length. The patient returned to our hospital due to scalp swelling 21 days after the surgery. Simple X-ray images revealed total upward migration and coiling of the peritoneal catheter around the valve. Possible mechanisms leading to proximal upward migration of a peritoneal catheter are discussed.
PMCID: PMC3756136  PMID: 24003378
Ventriculoperitoneal shunt; Migration; Distal catheter; Windlass effect
4.  Treatment Outcomes of Pediatric Craniopharyngioma : A 15-Year Retrospective Review of 35 Cases 
The aim of this study was to describe a single center's experience in the management of craniopharyngiomas in children over a 15-year period.
The clinical records of pediatric patients treated for craniopharyngiomas between December 1995 and February 2011 were reviewed. Thirty-five pediatric patients diagnosed with craniopharyngioma were treated, and their medical records and imaging data were analyzed retrospectively.
The mean follow-up duration was 76 months (range, 10-195). Overall survival and local control rates at 10 years were 94.7±5.1% and 37.1±11.9%, respectively. The female-to-male ratio was 16 : 19, and the mean age was 8.6 years (range, 1-17). Initially, gross total resection (GTR) was performed in 30 patients; subtotal resection (STR) followed by radiotherapy was performed in 5 patients. Of the 14 cases that showed recurrence after GTR, 5 patients were treated with GTR, 1 with radiation therapy (RT), 4 with gamma knife radiosurgery (GKRS), and 4 with subtotal resection followed by RT. No patients who underwent RT or GKRS had recurrences. Two cases with recurrence after STR followed by RT were treated with GTR. One patient died of hormonal insufficiency 64 months after the first surgery. The overall median time progression was 51.2 months (range, 3-182) : 49.7 months in the patients who underwent GTR and 60.2 months in the patients who underwent STR followed by RT.
If safe resection is possible, GTR at the initial treatment should be attempted to reduce the tumor recurrence. However, if the tumor recurs after the first surgery, RT or GKRS with/without reoperation may be an effective salvage treatment for recurrent craniopharyngioma.
PMCID: PMC3440501  PMID: 22993676
Craniopharyngioma; Microsurgery; Radiotherapy
5.  Moyamoya Syndrome Precipitated by Cranial Irradiation for Craniopharyngioma in Children 
Recently, combination of surgery and radiation therapy (RT) has been recommended in the treatment of craniopharyngioma. RT could be associated with late complications, including vasculopathy. We report two cases of the moyamoya syndrome seen in children with craniopharyngioma who received RT after surgical resection. Thirty-five patients in pediatric age with craniopharyngioma were surgically treated. Fifteen out of 35 patients underwent surgical resection followed by RT or gamma knife surgery. Two of the 15 were found to have symptoms of transient ischemic attack and were diagnosed as moyamoya syndrome through the cerebral angiography. Age at RT was 4 and 13 years, respectively. The latent period for development of the moyamoya syndrome was 27 months and 3 years, respectively, after RT. The RT dose of both patients was 54 Gy. These two patients received bilateral encephaloduroarteriosynangiosis procedures. We report here these two cases of radiation-induced moyamoya syndrome in pediatric craniopharyngioma. Pediatric patients with craniopharyngioma who received RT should be reminded, during follow-up, about the risk of development of the moyamoya syndrome.
PMCID: PMC3272518  PMID: 22323944
Moyamoya syndrome; Craniopharyngioma; Radiation; Vasculopathy
6.  Endoscopic Third Ventriculostomy in Patients with Shunt Malfunction 
This paper presents data from a retrospective study of endoscopic third ventriculostomy (ETV) in patients with shunt malfunction and proposes a simple and reasonable post-operative protocol that can detect ETV failure.
We enrolled 19 consecutive hydrocephalus patients (11 male and 8 female) who were treated with ETV between April 2001 and July 2010 after failure of previously placed shunts. We evaluated for correlations between the success rate of ETV and the following parameters : age at the time of surgery, etiology of hydrocephalus, number of shunt revisions, interval between the initial diagnosis of hydrocephalus or the last shunt placement and ETV, and the indwelling time of external ventricular drainage.
At the time of ETV after shunt failure, 14 of the 19 patients were in the pediatric age group and 5 were adults, with ages ranging from 14 months to 42 years (median age, 12 years). The patients had initially been diagnosed with hydrocephalus between the ages of 1 month 24 days and 32 years (median age, 6 years 3 months). The etiology of hydrocephalus was neoplasm in 7 patients; infection in 5; malformation, such as aqueductal stenosis or megacisterna magna in 3; trauma in 1; and unknown in 3. The overall success rate during the median follow-up duration of 1.4 years (9 days to 8.7 years) after secondary ETV was 68.4%. None of the possible contributing factors for successful ETV, including age (p=0.97) and the etiology of hydrocephalus (p=0.79), were statistically correlated with outcomes in our series.
The use of ETV in patients with shunt malfunction resulted in shunt independence in 68.4% of cases. Age, etiology of hydrocephalus, and other contributing factors were not statistically correlated with ETV success. External ventricular drainage management during the immediate post-ETV period is a good means of detecting ETV failure.
PMCID: PMC3098424  PMID: 21607179
Shunt failure; Secondary endoscopic third ventriculostomy; Hydrocephalus
7.  Transventricular Biopsy of Brain Tumor without Hydrocephalus Using Neuroendoscopy with Navigation 
It is usually difficult to perform the neuroendoscopic procedure in patients without hydrocephalus due to difficulties with ventricular cannulation. The purpose of this study was to find out the value of navigation guided neuroendoscopic biopsy in patients with peri- or intraventricular tumors without hydrocephalus.
Six patients with brain tumors without hydrocephalus underwent navigation-guided neuroendoscopic biopsy. The procedure was indicated for verification of the histological diagnosis of the neoplasm, which was planned to be treated by chemotherapy and/or radiotherapy as the first line treatment, or establishment of the pathological diagnosis for further choice of the most appropriate treatment strategy.
Under the guidance of navigation, targeted lesion was successfully approached in all patients. Navigational tracking was especially helpful in entering small ventricles and in approaching the third ventricle through narrow foramen Monro. The histopathologic diagnosis was established in all of 6 patients : 2 germinomas, 2 astrocytomas, 1 dysembryoplastic neuroepithelial tumor and 1 pineocytoma. The tumor biopsy sites were pineal gland (n = 2), suprasellar area (n = 2), subcallosal area (n = 1) and thalamus (n = 1). There were no operative complications related to the endoscopic procedure.
Endoscopic biopsy or resection of peri- or intraventricular tumors in patients without hydrocephalus is feasible. Image-guided neuroendoscopic procedure improved the accuracy of the endoscopic approach and minimized brain trauma. The absence of ventriculomegaly in patients with brain tumor may not be served as a contraindication to endoscopic tumor biopsy.
PMCID: PMC2899026  PMID: 20617084
Neuroendoscopy; Navigation; Without hydrocephalus
8.  Improved Outcome of Central Nervous System Germ Cell Tumors: Implications for the Role of Risk-adapted Intensive Chemotherapy 
Journal of Korean Medical Science  2010;25(3):458-465.
To determine the impact of treatment protocols on the outcome of central nervous system germ cell tumors (CNS-GCTs), we reviewed the medical records of 53 patients who received front-line chemotherapy from September 1997 to September 2006. Pure germinoma, normal alpha-fetoprotein level and beta-human chorionic gonadotropin level <50 mIU/mL were regarded as low-risk features and the others as high-risk. Patients from different time periods were divided into 3 groups according to the chemotherapy protocols. Group 1 (n=19) received 4 cycles of chemotherapy comprising cisplatin, etoposide and bleomycin. Group 2 (n=16) and group 3 (n=18) received 4 cycles of chemotherapy with cisplatin, etoposide, cyclophosphamide and vincristine in the former and with carboplatin, etoposide, cyclophosphamide and bleomycin in the latter. In group 2 and group 3, high-risk patients received double doses of cisplatin, carboplatin and cyclophosphamide. Radiotherapy was given after chemotherapy according to the clinical requirements. The event-free survivals of groups 1, 2, and 3 were 67.0%, 93.8%, and 100%, respectively (group 1 vs. 2, P=0.06; group 2 vs. 3, P=0.29; group 1 vs. 3, P=0.02). Our data suggest that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs.
PMCID: PMC2826748  PMID: 20191048
Neoplasms, Germ Cell and Embryonal; Central Nervous System; Drug Therapy; Survival
9.  The Frequency of Reexpansion Pulmonary Edema after Trocar and Hemostat Assisted Thoracostomy in Patients with Spontaneous Pneumothorax 
Yonsei Medical Journal  2012;54(1):166-171.
Several risk factors for development of reexpansion pulmonary edema (REPE) after drainage of pneumothoraces have been reported, but the association between the method of thoracostomy and the development of REPE is unknown. The aim of this study was to compare the frequency of REPE after treatment of spontaneous pneumothorax with trocar or hemostat assisted closed thoracostomy.
Materials and Methods
We performed a prospective, observational study including 173 patients with spontaneous pneumothorax who visited the emergency department from January 2007 to December 2008. In 2007, patients were treated with hemostat-assisted drainage, whereas patients in 2008 were treated with trocar-assisted drainage. The main outcome was the development of REPE, determined by computed tomography of the chest 8 hours after closed thoracostomy. Outcomes in both groups were compared using univariate and multivariate analyses.
Ninety-two patients were included, 48 (42 males) of which underwent hemostat-assisted drainage and 44 (41 males) underwent trocar-assisted drainage. The groups were similar in mean age (24±10 vs. 26±14 respectively). The frequencies of REPE after hemostat- and trocar-assisted drainage were 63% (30 patients) and 86% (38 patients) respectively (p=0.009). In multivariate analysis, trocar-assisted drainage was the major contributing factor for developing REPE (odds ratio=5.7, 95% confidence interval, 1.5-21). Age, gender, size of pneumothorax, symptom duration and laboratory results were similar between the groups.
Closed thoracostomy using a trocar is associated with an increased risk of REPE compared with hemostat-assisted drainage in patients with spontaneous pneumothorax.
PMCID: PMC3521265  PMID: 23225814
Pneumothorax; thoracostomy; pulmonary edema
10.  Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study 
Journal of Korean Medical Science  2010;25(8):1160-1166.
The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates ±95% confidence intervals (CI) were 33.3±12.2% and 26.7% ±11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates ±95% CI was 40.0±15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.
PMCID: PMC2908784  PMID: 20676326
Recurrence; Medulloblastoma; Transplantation, Autologous; Tandem; Hematopoietic Stem Cell Transplantation
11.  Reduced-dose craniospinal radiotherapy followed by high-dose chemotherapy and autologous stem cell rescue for children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuroectodermal tumor 
The Korean Journal of Hematology  2010;45(2):120-126.
In this study, we investigated the effects of reduced-dose craniospinal radiotherapy (CSRT) followed by tandem high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in children with a newly diagnosed high-risk medulloblastoma (MB) or supratentorial primitive neuroectodermal tumor (sPNET).
Between March 2005 and April 2007, patients older than 3 years with a newly diagnosed high-risk MB or sPNET were enrolled. The patients received two cycles of pre-RT chemotherapy consisting of cisplatin, etoposide, vincristine, and cyclophosphamide (cycle A), and carboplatin, etoposide, vincristine, and ifosphamide (cycle B), followed by CSRT with 23.4 Gy and local RT with 30.6 Gy. After four cycles of post-RT chemotherapy (cycles A, B, A, and B), tandem double HDCT with ASCR was performed.
A total of 13 patients (MB=11, sPNET=2) were enrolled. Of these, one patient progressed, one patient died of septic shock after the second cycle of B, and one patient relapsed after the third cycle of B. The 3-year event-free survival (EFS) rate of the patients intended for HDCT was 76.9%, whereas the 3-year EFS rate of the patients who received HDCT was 100%. No treatment-related mortality occurred during HDCT.
Although the follow-up period was short and the patient cohort was small in size, the results of this study are encouraging. The limited toxicity and favorable EFS rate observed in children treated with reduced-dose CSRT followed by HDCT and ASCR warrant further exploration in a larger study population.
PMCID: PMC2983022  PMID: 21120191
Radiotherapy; High-dose chemotherapy; Autologous stem cell transplantation; Medulloblastoma; Supratentorial primitive neuroectodermal tumor; Children
12.  Brain abscess in Korean children: A 15-year single center study 
Korean Journal of Pediatrics  2010;53(5):648-652.
A brain abscess is a serious disease of the central nerve system. We conducted this study to summarize the clinical manifestations and outcomes of brain abscesses.
A retrospective chart review of pediatric patients diagnosed with brain abscesses from November 1994 to June 2009 was performed at Samsung Medical Center, Seoul, Korea.
Twenty-five patients were included in this study. On average, 1.67 cases per year were identified and the median age was 4.3 years. The common presenting clinical manifestations were fever (18/25, 72%), seizure (12/25, 48%), altered mental status (11/25, 44%), and signs of increased intracranial pressure (9/25, 36%). A total of 14 (56%) patients had underlying illnesses, with congenital heart disease (8/25, 32%) as the most common cause. Predisposing factors were identified in 15 patients (60%). The common predisposing factors were otogenic infection (3/25, 12%) and penetrating head trauma (3/25, 12%). Causative organisms were identified in 64% of patients (16/25). The causative agents were S. intermedius (n=3), S. aureus (n=3), S. pneumoniae (n=1), Group B streptococcus (n=2), E. coli (n=1), P. aeruginosa (n=1), and suspected fungal infection (n=5). Seven patients received medical treatment only while the other 18 patients also required surgical intervention. The overall fatality rate was 16% and 20% of patients had neurologic sequelae. There was no statistical association between outcomes and the factors studied.
Although uncommon, a brain abscess is a serious disease. A high level of suspicion is very important for early diagnosis and to prevent serious consequences.
PMCID: PMC2994128  PMID: 21189932
Brain; Abscess; Child; Korea
13.  Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn 
Korean Journal of Radiology  2008;9(Suppl):S26-S29.
We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor.
PMCID: PMC2627202  PMID: 18607121
Congenital cerebellar tumor; Mixed germ cell tumor; Posterior fossa tumor; Neonatal cerebellar hemorrhage
14.  Retrospective Analysis on 76 Cases of Cerebral Arteriovenous Malformations Treated by Gamma Knife Radiosurgery 
Outcome of gamma knife radiosurgery (GKS) in the consecutive 100 cases with cerebral arteriovenous malformations (AVMs) was analyzed.
Data from initial 100 patients treated with GKS in the authors' institute were reviewed retrospectively. Spetzler-Martin grade at diagnosis were I in 18 patients, II in 27, III in 36, IV in 11, and V in 8. Thirty-five patients had experienced previous bleeding, 27 patients presented with seizure, and 31 patients presented with headache. The mean volume of the lesion was 4.3 cm3 (0.1-29.3 cm3). The median radiation dose delivered to the margin was 20.0 Gy (13-32 Gy). Mean follow-up period was 37.5 months (5-63 months).
Angiographic follow-up was performed in 48 patients at least 2 years after GKS. Sixteen patients were lost in follow up following 2 years from GKS. Twenty-eight of 48 patients (58%) showed complete obliteration and 20 patients (42%) showed partial obliteration. Seven patients presented with post-GKS hemorrhage. Adverse radiation effect (ARE) was observed at follow-up MRI in 25 of 76 patients, and it was symptomatic in 5 patients. Complete obliteration was confirmed in 24 of 31 (77%) patients with volume less than 4 cm3, meanwhile only 4 of 17 (24%) patients with volume of 4 cm3 or more showed complete obliteration. Complete obliteration rate was 67% with 20 Gy or higher marginal dose, 63% with 15-20 Gy, and 17% with less than 15 Gy.
GKS can provide high rates of obliteration with acceptable risk of morbidity in a subgroup of small AVMs. However, overall outcome in whole spectrum of AVMs, in which large proportion of cases have unfavorable characteristics for radiosurgery, is much worse. More effective therapeutic strategy needs to be developed for large AVMs that are difficult to be managed with current available treatment modalities.
PMCID: PMC2588252  PMID: 19096630
Gamma knife radiosurgery; Arteriovenous malformation; Outcome
15.  Trilateral retinoblastoma: a case report. 
Journal of Korean Medical Science  2002;17(1):137-140.
Trilateral retinoblastoma is a rare, but well recognized syndrome. These tumors usually occur in the pineal, parasellar, or suprasellar regions several years after successful management of ocular retinoblastomas without evidence of direct extension or distant metastasis. Here we report a case of trilateral retinoblastoma presenting initially with a sellar tumor and with concurrent unilateral retinoblastoma. The patient was a 5-month-old baby girl showing poor eye contact and nystagmus for several days. She had no family history of retinoblastoma. Brain MRI revealed a midline suprasellar tumor without evidence of cerebrospinal fluid seeding or extracranial metastasis. A pathologic diagnosis of retinoblastoma was made for her brain tumor, and a small, intraocular retinoblastoma was detected in the left eye by thorough examination of the fundus. If a retinoblastoma occurs in the midline of the brain, including the pineal and sellar regions, a careful screening to detect any additional retinal tumors should be performed. Moreover, since these tumors are often hereditary and harbor a worse prognosis, the diagnosis has implications for genetic counseling. This is the first report on a case of trilateral retinoblastoma in Korea presented with a sellar mass.
PMCID: PMC3054828  PMID: 11850605

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