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1.  Cancer Stem Cells in Brain Tumors and Their Lineage Hierarchy 
Despite recent advances in the development of novel targeted chemotherapies, the prognosis of malignant glioma remains dismal. The chemo-resistance of this tumor is attributed to tumor heterogeneity. To explain this unique chemo- resistance, the concept of cancer stem cells has been evoked. Cancer stem cells, a subpopulation of whole tumor cells, are now regarded as candidate therapeutic targets. Here, the author reviews and discusses the cancer stem cell concept.
PMCID: PMC3840978  PMID: 24298350
Cell of origin; Cancer stem cell; Lineage hierarchy
2.  Clinical Efficacy of Radiation-Sterilized Allografts for Sellar Reconstruction after Transsphenoidal Surgery 
The aim of this study was to assess the safety and efficacy of radiation-sterilized allografts of iliac bone and fascia lata from cadaver specimens to repair skull base defects after transsphenoidal surgery.
Between May 2009 and January 2010, 31 consecutive patients underwent endonasal transsphenoidal surgery and all patients received sellar reconstruction using allografts following tumor removal. The allografts were obtained from the local tissue bank and harvested from cadaver donors. The specimens used in our approach were tensor fascia lata and the flat area of iliac bone. For preparation, allografts were treated with gamma irradiation after routine screening by culture, and then stored at -70℃.
The mean follow-up period after surgery was 12.6 months (range, 7.4-16 months). Overall, postoperative cerebrospinal fluid (CSF) leaks occurred in three patients (9.7%) and postoperative meningitis in one patient (3.2%). There was no definitive evidence of wound infection at the routine postoperative follow-up examination or during re-do surgery in three patients. Postoperative meningitis in one patient was improved with the use of antibiotics and prolonged CSF diversion.
We suggest that allograft materials can be a feasible alternative to autologous tissue grafts for sellar reconstruction following transsphenoidal surgery under selected circumstances such as no or little intraoperative CSF leaks.
PMCID: PMC3272510  PMID: 22323936
Endoscopic endonasal approach; Transsphenoidal approach; Allograft; Sellar reconstruction; CSF leak
3.  Leukoencephalopathy and Disseminated Necrotizing Leukoencephalopathy Following Intrathecal Methotrexate Chemotherapy and Radiation Therapy for Central Nerve System Lymphoma or Leukemia 
Intrathecal methotrexate (MTX) therapy combined with whole brain radiotherapy (WBRT) is one of the major treatment modalities for leukemia and lymphoma involving the central nervous system (CNS). The purpose of this study was to retrospectively determine the incidences of leukoencephalopathy and disseminated necrotizing leukoencephalopathy (DNL) following intrathecal MTX therapy for CNS lymphoma or leukemia and to assess the potential risk factors.
Between January 2000 and August 2009, 143 patients with CNS lymphoma or leukemia received intrathecal MTX therapy alone or in combination with WBRT at a single institution. Patients were followed up clinically and radiologically at regular two- or three-month intervals. Medical records were reviewed to obtain information regarding the patients' demographics, medical histories, radiologic characteristics, treatments, and clinical courses.
On follow-up MR images, leukoencephalopathy was found in 95 of 143 patients (66.4%). The median time to develop leukoencephalopathy was 6.6 months. Among those with leukoencephalopathy, four patients showed seven extensive white-matter changes with strongly enhancing lesions demonstrating DNL. Histological confirmation was done in six lesions of three patients and radiological diagnosis alone in one patient. Four lesions spontaneously disappeared on MR images without any treatment, with a mean duration of 14 months before disappearance of DNL.
Leukoencephalopathy is a common phenomenon that occurs following intrathecal MTX therapy; however, DNL occurs at a very low incidence. For newly developed enhancing lesions, consideration for the occurrence of DNL should be taken to avoid unnecessary invasive procedures or therapies.
PMCID: PMC3243832  PMID: 22200011
Leukoencephalopathy; Methotrexate; Intrathecal; Lymphoma; Leukemia
4.  Fractionated Gamma Knife Radiosurgery for Benign Perioptic Tumors: Outcomes of 38 Patients in a Single Institute 
This study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions.
Thirty-eight patients with perioptic tumors were treated at our institute from May 2004 to December 2008. All patients had a lesion in close contact with the optic apparatus. Twenty-four of these patients had undergone surgical resection before fractionated GKRS. Radiation was delivered in four sessions with 12 hours intervals between sessions. The mean target volume was 3,851 mm3 and the median cumulative marginal dose was 20 Gy. The median follow-up was 38.2 months. Visual acuity and visual fields were analyzed according to visual impairment score using the German Ophthalmological Society guidelines.
Tumor control was achieved in 35 (94.6%) of the 37 patients with available follow-up images. Progressive tumor growth was observed in two craniopharyngioma patients (5.4%). Favorable visual outcomes in the postoperative period were achieved in 94.7% of cases (36/38). Sixteen patients showed visual function after fractionated GKRS, twenty cases were stationary, and two patients showed visual function deterioration after GKRS.
GKRS is a safe and effective alternative to either surgery or fractionated radiotherapy for selected benign lesions that are adjacent to the optic apparatus.
PMCID: PMC4231616  PMID: 25408926
Gamma Knife radiosurgery; Fractionated radiosurgery; Stereotactic radiosurgery; Tumor control; Visual outcome
5.  Clinical Features and Treatment Outcome of Chordoid Meningiomas in a Single Institute 
Meningioma is the second most common primary central nervous system neoplasm. In contrast, chordoid meningioma is rare; due to the paucity of cases, little is known about its clinical features or treatment outcomes. The objectives of this study were to describe the clinical characteristics and outcomes for patients with chordoid meningioma.
In total, 16 patients, with newly diagnosed chordoid meningioma who underwent surgical excision between 1999 and 2012 were included. We retrospectively evaluated the medical records, radiological findings, and pathological findings. The median follow-up period was 56.5 (range, 3-170) months. The MIB-1 labeling index ranged from 1 to 26.60% (median, 5.04).
Simpson grade I, II, and III resections were performed in four, nine, and three patients, respectively. The overall recurrence rate was 37.5%. Overall progression-free survival (PFS) after resection was 94.7 months (95% CI=62.9-126.6). Of the 4 patients with Simpson grade I resection, recurrence occurred in one patient. Among the Simpson grade II and III resection groups, eight patients underwent adjuvant radiation therapy and they showed significantly longer PFS (121 months, 95% CI=82.1-159.9) than the patients who underwent surgery alone (40.5 months, 95% CI=9.6-71.3) by the log-rank test (p<0.05).
Chordoid meningiomas are difficult to manage and have a high rate of recurrence. Complete resection of the tumor is a key determinant of better outcomes. Adjuvant radiation therapy is recommended, eparticulary when Simpson grade I resection was not achieved.
PMCID: PMC4217054  PMID: 25368760
Chordoid meningioma; MIB-1 labeling index; Adjuvant radiation therapy
6.  Endoscopic Decompression for Optic Neuropathy in McCune-Albright Syndrome 
McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including human growth hormone excess. Acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon. Surgical excision may be challenging due to the associated severe fibrous dysplasia of the skull base. Through the endoscopic procedures, we treated a case of MAS presenting with compressive optic neuropathy due to fibrous dysplasia and acromegaly caused by growth hormone secreting pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight its surgical and medical challenges.
PMCID: PMC4217071  PMID: 25368777
Fibrous dysplasia; McCune-Albright syndrome; Acromegaly
7.  Translational Validation of Personalized Treatment Strategy Based on Genetic Characteristics of Glioblastoma 
PLoS ONE  2014;9(8):e103327.
Glioblastoma (GBM) heterogeneity in the genomic and phenotypic properties has potentiated personalized approach against specific therapeutic targets of each GBM patient. The Cancer Genome Atlas (TCGA) Research Network has been established the comprehensive genomic abnormalities of GBM, which sub-classified GBMs into 4 different molecular subtypes. The molecular subtypes could be utilized to develop personalized treatment strategy for each subtype. We applied a classifying method, NTP (Nearest Template Prediction) method to determine molecular subtype of each GBM patient and corresponding orthotopic xenograft animal model. The models were derived from GBM cells dissociated from patient's surgical sample. Specific drug candidates for each subtype were selected using an integrated pharmacological network database (PharmDB), which link drugs with subtype specific genes. Treatment effects of the drug candidates were determined by in vitro limiting dilution assay using patient-derived GBM cells primarily cultured from orthotopic xenograft tumors. The consistent identification of molecular subtype by the NTP method was validated using TCGA database. When subtypes were determined by the NTP method, orthotopic xenograft animal models faithfully maintained the molecular subtypes of parental tumors. Subtype specific drugs not only showed significant inhibition effects on the in vitro clonogenicity of patient-derived GBM cells but also synergistically reversed temozolomide resistance of MGMT-unmethylated patient-derived GBM cells. However, inhibitory effects on the clonogenicity were not totally subtype-specific. Personalized treatment approach based on genetic characteristics of each GBM could make better treatment outcomes of GBMs, although more sophisticated classifying techniques and subtype specific drugs need to be further elucidated.
PMCID: PMC4118874  PMID: 25084005
8.  Gamma Knife Radiosurgery for Brain Metastases from Breast Cancer 
The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS).
Pathologic and clinical features, and outcomes were analyzed in a cohort of 62 patients with BM from BC treated by GKS. The Kaplan-Meier method, the log-rank test, and Cox's proportional hazards model were used to assess prognostic factors.
Median survival after GKS was 73.0 weeks (95% confidence interval, 46.0-100.1). HER2+ [hazard ratio (HR) 0.441; p=0.045], Karnofsky performance scale (KPS) ≥70 (RR 0.416; p=0.050) and systemic chemotherapy after GKS (RR 0.282; p=0.001) were found to be a favorable prognostic factor of overall survival. Actuarial local control (LC) rate were 89.5±4.5% and 70.5±6.9% at 6 and 12 months after GKS, respectively. No prognostic factors were found to affect LC rate. Uni- and multivariate analysis revealed that the distant control (DC) rate was higher in patients with; a small number (≤3) of metastasis (HR 0.300; p=0.045), no known extracranial metastasis (p=0.013, log-rank test), or the HER2+ subtype (HR 0.267; p=0.027). Additional whole brain radiation therapy and metastasis volume were not found to be significantly associated with LC, DC, or overall survival.
The treatment outcomes of patients with newly diagnosed BM from BC treated with GKS could be affected primarily by intrinsic subtype, KPS, and systemic chemotherapy. Therapeutic strategy and prognosis scoring system should be individualized based on considerations of intrinsic subtype in addition to traditionally known parameters related to stereotactic radiosurgery.
PMCID: PMC3873352  PMID: 24379946
Brain metastasis; Breast cancer; Gamma Knife radiosurgery; Intrinsic subtype; Treatment outcomes
9.  Delayed Cranial Nerve Palsy after Microvascular Decompression for Hemifacial Spasm 
Microvascular decompression (MVD) for hemifacial spasm (HFS) is a safe and effective treatment with favorable outcomes. The purpose of this study was to evaluate the incidence of delayed cranirve ( VI, VII, and VIII ) palsy following MVD and its clinical courses.
Between January 1998 and December 2009, 1354 patients underwent MVD for HFS at our institution. Of them, 100 patients (7.4%) experienced delayed facial palsy (DFP), one developed sixth nerve palsy, and one patient had delayed hearing loss.
DFP occurred between postoperative day number 2 and 23 (average 11 days). Ninety-two patients (92%) completely recovered; however, House-Brackmann grade II facial weakness remained in eight other patients (8%). The time to recovery averaged 64 days (range, 16 days to 9 months). Delayed isolated sixth nerve palsy recovered spontaneously without any medical or surgical treatment after 8 weeks, while delayed hearing loss did not improve.
Delayed cranial nerve (VI, VII, and VIII) palsies can occur following uncomplicated MVD for HFS. DFP is not an unusual complication after MVD, and prognosis is fairly good. Delayed sixth nerve palsy and delayed hearing loss are extremely rare complications after MVD for HFS. We should consider the possibility of development of these complications during the follow up for MVD.
PMCID: PMC3488634  PMID: 23133714
Delayed facial palsy; Microvascular decompression; Delayed cranial palsy; Delayed hearing loss; Delayed abducens palsy
10.  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
11.  Identification of prognostic biomarkers for glioblastomas using protein expression profiling 
International Journal of Oncology  2011;40(4):1122-1132.
A set of proteins reflecting the prognosis of patients have clinical significance since they could be utilized as predictive biomarkers and/or potential therapeutic targets. With the aim of finding novel diagnostic and prognostic markers for glioblastoma (GBM), a tissue microarray (TMA) library consisting of 62 GBMs and 28 GBM-associated normal spots was constructed. Immunohistochemistry against 78 GBM-associated proteins was performed. Expression levels of each protein for each patient were analyzed using an image analysis program and converted to H-score [summation of the intensity grade of staining (0–3) multiplied by the percentage of positive cells corresponding to each grade]. Based on H-score and hierarchical clustering methods, we divided the GBMs into two groups (n=19 and 37) that had significantly different survival lengths (p<0.05). In the two groups, expression of nine proteins (survivin, cyclin E, DCC, TGF-β, CDC25B, histone H1, p-EGFR, p-VEGFR2/3, p16) was significantly changed (q<0.05). Prognosis-predicting potential of these proteins were validated with another independent library of 82 GBM TMAs and a public GBM DNA microarray dataset. In addition, we determined 32 aberrant or mislocalized subcellular protein expression patterns in GBMs compared with relatively normal brain tissues, which could be useful for diagnostic biomarkers of GBM. We therefore suggest that these proteins can be used as predictive biomarkers and/or potential therapeutic targets for GBM.
PMCID: PMC3584590  PMID: 22179774
biomarker; therapeutic target; glioblastoma; tissue micro-array; bioinformatics; automated image analysis
12.  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
13.  The Role of Radiosurgery in Patients with Brain Metastasis from Small Cell Lung Carcinoma 
The purpose of this retrospective study was to evaluate the outcome of gamma knife radiosurgery (GKRS) and/or whole brain radiation therapy (WBRT) for the treatment of small cell lung carcinoma (SCLC) metastasis to the brain.
From 2000 to 2010, 50 patients underwent GKRS for metastatic brain lesions originating from SCLC. Among these patients, 11 received prophylactic cranial irradiation (PCI) before the development of metastatic lesions (PCI group), and GKRS was performed as an initial treatment for newly diagnosed lesions in 12 patients who had not received PCI (primary GKRS group). In addition, GKRS was performed as a salvage treatment for progressive lesions after WBRT in 27 patients (salvage GKRS group). The medical records and imaging data of all patients were retrospectively analyzed.
The overall survival of the 50 patients was 20.8 months (range 1-53) after the diagnosis of primary tumor and 12.0 months (range 1-47) after the development of cerebral metastasis. Median survival after GKRS was 4.8 months (range 1-15) in the PCI group, 4.6 months (range 0-18) in the primary GKRS group, and 7.6 months (range 0-33) in the salvage GKRS group. Further treatment for progressive lesions after GKRS was necessary in 15 patients, after a mean interval of 3.8 months. Causes of death were systemic organ failure in 15 patients, deterioration of neurological state in 13 patients, and unknown or combined causes in 16 patients. The local control rate of the lesions treated with GKRS was 76.4% (decreased in 13 patients and stable in 16 patients at the final imaging follow-up (mean 5.60 months).
GKRS is an effective local treatment for brain metastasis from SCLC both as an initial treatment for newly diagnosed lesions after PCI and as a salvage treatment for recurrent or progressive lesions. However, the survival benefit is not significant because most patients die of systemic multi-organ failure with a short life expectancy.
PMCID: PMC3206286  PMID: 22053227
Small cell lung carcinoma; Radiosurgery; Gamma knife; Metastasis
14.  Concurrent Nocardia Related Brain Abscess and Semi-Invasive Pulmonary Aspergillosis in an Immunocompetent Patient 
We describe here the first case of a concurrent brain abscess caused by Norcardia spp. and semi-invasive pulmonary aspergillosis in an immunocompetent patient. After one year of appropriate antimicrobial therapy and surgical drainage of the brain abscess, the nocardia brain abscess and pulmonary aspergillosis have resolved.
PMCID: PMC3115156  PMID: 21716631
Brain nocardiosis; Semi-invasive pulmonary aspergillosis; Immunocompetent
15.  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
16.  Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma 
Neuro-Oncology  2010;12(3):289-296.
The prognosis for patients with recurrent glioblastomas (GBMs) is dismal, with a median survival of 3–6 months. We performed a phase II trial of low-dose continuous (metronomic) treatment using temozolomide (TMZ) for recurrent GBMs. TMZ-refractory patients with GBM who experienced disease recurrence or progression during or after the cyclic treatment schedule of TMZ after surgery and standard radiotherapy were eligible. This phase II trial included 2 cohorts of patients. The initial cohort, comprising 10 patients, received TMZ at 40 mg/m2 everyday. After this regimen seemed safe and effective, the metronomic schedule was changed to 50 mg/m2 everyday. The second cohort, comprising 28 patients, received TMZ at 50 mg/m2 everyday. The 6-month progression-free survival in all 38 patients was 32.5% (95% CI: 29.3%–35.8%) and the 6-month overall survival was 56.0% (95% CI: 36.2%–75.8%). One patient developed a grade III neutropenia, grade II thrombocytopenia in 3 patients, and grade II increase of liver enzyme (GOT/GPT) in 3 patients. Of all patients included in this study, 4 patients were withdrawn from this study because of side effects including sustained hematological disorders, cryptococcal infection, and cellulitis. In a response group, quality of life measured with short form-36 was well preserved, when compared with the pretreatment status. Metronomic treatment of TMZ is an effective treatment for recurrent GBM that is even refractory to conventional treatment of TMZ and has acceptable toxicity.
PMCID: PMC2940595  PMID: 20167817
glioblastoma; metronomic; recurrent
17.  Impact of adjuvant chemotherapy for gliomatosis cerebri 
BMC Cancer  2010;10:424.
Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC.
Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy.
Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008).
Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.
PMCID: PMC2933624  PMID: 20704759
18.  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
19.  The Efficacy and Safety of Microvascular Decompression for Hemifacial Spasm in Elderly Patients 
The purpose of this study was to examine the efficacy and safety of microvascular decompression (MVD) for hemifacial spasm (HFS) in elderly patients.
Between 1997 and June 2008, 1,174 patients had undergone MVD for HFS at our institute. Among these, 53 patients were older than 65 years. We retrospectively reviewed and compared the complication and the cure rates of these patients with those of younger patients.
There were 38 females and 15 males. The mean duration of symptoms of HFS of these patients was 94.6 months (range, 12-360 months), compared with 67.2 months (range, 3-360 months) in the younger group. The overall cure rate in elderly patients who underwent MVD for HFS during this period was 96.2%. Permanent cranial nerve dysfunctions, such as hearing loss and facial palsy, were seen in 2 patients (3.8%, 2/53) in the elderly group and 19 patients (1.7%, 19/1121) in the younger group. The difference in permanent cranial nerve dysfunction between the two groups was not statistically significant. There was no operative mortality in either group.
Microvascular decompression is the most effective surgical modality available for the treatment of HFS. Results of this study indicate that such technique can be performed in the elderly without higher rates of morbidity or mortality. Any patient with HFS, whose general health is acceptable for undergoing general anesthesia, should be considered as a candidate for MVD.
PMCID: PMC2899032  PMID: 20617090
Microvascular decompression; Hemifacial spasm; Elderly patients
20.  Combined Hyperactive Dysfunction Syndrome of the Cranial Nerves 
Combined hyperative dysfunction syndrome (HDS) defined as the combination of HDSs such as trigeminal neuralgia (TN), hemifacial spasm (HFS) and glossopharyngeal neuralgia (GPN), which may or may not occur simultaneously on one or both sides. We reviewed patients with combined HDS and demonstrated their demographic characteristics by comparing them with those of patients with a single HDS.
Between October 1994 and February 2006, we retrospectively studied a series of 1,720 patients who suffered from HDS and found 51 patients with combined HDSs. We analyzed several independent variables in order to evaluate the prevalence and etiologic factors of combined HDS.
The combined HDS group accounted for 51 of 1,720 (2.97%) patients with HDS; 27 cases of bilateral HFS, 10 cases of bilateral TN and 14 cases of HFS with TN. Their mean age was 52.1 years (range, 26-79 years). There were 5 men and 46 women. Seven patients had synchronous and 44 patients metachronous onset of HDSs. By comparison of combined and single HDS groups, we found that age and hypertension were closely associated with the prevalence of combined HDS (p < 0.05).
This study revealed that combined HDS was very rare. Hypertension and age might be the most important causative factors to evoke combined HDS.
PMCID: PMC2773393  PMID: 19893725
Combined hyperactive dysfunction syndrome; Prevalence; Hemifacial spasm; Trigeminal neuralgia; Etiology
21.  Prognostic Factors of Hemifacial Spasm after Microvascular Decompression 
The factors that influence the prognosis of patients with hemifacial spasm (HFS) treated by microvascular decompression (MVD) have not been definitely established. We report a prospective study evaluating the prognostic factors in patients undergoing MVD for HFS.
From January 2004 to September 2006, the authors prospectively studied a series of 293 patients who underwent MVD for HFS. We prospectively analyzed a number of variables in order to evaluate the predictive value of independent variables for the prognosis of patients undergoing MVD. The patients were followed-up at regular intervals and divided into as cured and unsatisfactory groups based on symptom relief. Uni- and multivariate analyses were performed using logistic regression models.
A total 273 of 293 (94.2%) patients achieved symptom relief within one year after the operation. Intraoperatively, the indentation of the root exit zone was observed in 259 (88.5%) patients. Uni- and multivariate analyses revealed that the symptoms at postoperative 3 months (p<0.001) and indentation of the root exit zone (p=0.036) were associated with good outcomes.
The intraoperative finding of root exit zone indentation will help physicians determine the prognosis in patients with HFS. To predict the prognosis of HFS, a regular follow-up period of at least 3 months following MVD should be required.
PMCID: PMC2711230  PMID: 19609416
Hemifacial spasm; Microvascular decompression; Prognosis; Chronology
22.  Hemifacial Spasm: A Neurosurgical Perspective 
Hemifacial spasm (HFS) is characterized by tonic clonic contractions of the muscles innervated by the ipsilateral facial nerve. Compression of the facial nerve by an ectatic vessel is widely recognized as the most common underlying etiology. HFS needs to be differentiated from other causes of facial spasms, such as facial tic, ocular myokymia, and blepharospasm. To understand the overall craniofacial abnormalities and to perform the optimal surgical procedures for HFS, we are to review the prevalence, pathophysiology, differential diagnosis, details of each treatment modality, usefulness of brainstem auditory evoked potentials monitoring, debates on the facial EMG, clinical course, and complications from the literature published from 1995 to the present time.
PMCID: PMC2588188  PMID: 19096569
Hemifacial spasm; Microvascular decompression; Craniofacial abnormalities
23.  One-year Outcome Evaluation after Interspinous Implantation for Degenerative Spinal Stenosis with Segmental Instability 
Journal of Korean Medical Science  2007;22(2):330-335.
The authors hypothesized that the placement of the interspinous implant would show a similar clinical outcome to the posterior lumbar interbody fusion (PLIF) in patients having spinal stenosis with mild segmental instability and that this method would be superior to PLIF without significantly affecting degeneration at the adjacent segments. Forty two adult patients having degenerative spinal stenosis with mild segmental instabilit who underwent implantation of Coflex™ (Spine motion, Germany) or PLIF at L4-5 between January 2000 and December 2003 were consecutively selected and studied for one-year clinical outcome. At 12 months after surgery, both groups showed a significant improvement in the visual analogue scale score and Oswestry disability index score for both lower extremity pain and low back pain. However, the range of motion at the upper adjacent segments (L3-4) increased significantly after surgery in the PLIF group, which was not manifested in the Coflex™ group during the follow-up. The authors assumed that interspinous implantation can be an alternative treatment for the spinal stenosis with segmental instability in selected conditions posing less stress on the superior adjacent level than PLIF.
PMCID: PMC2693603  PMID: 17449945
Spinal Stenosis; Outcome
24.  Prognosis of Non-Small Cell Lung Cancer with Synchronous Brain Metastases Treated with Gamma Knife Radiosurgery 
Journal of Korean Medical Science  2006;21(3):527-532.
The clinical outcome and prognostic factors of patients with synchronous brain metastases from non-small cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKS) were analyzed. A total of 35 patients with NSCLC underwent GKS as an initial treatment for metastatic brain lesions of synchronous onset. The period of survival and various prognostic factors such as age, gender, performance status, multiplicity of the brain lesions, intracranial tumor volume, and extent of the primary tumor were analyzed. The overall median survival time for this series was 12 months (range 0.75 to 43 months) from the diagnosis. Of the 21 patients who were no longer alive at the conclusion of this study, only 7 (33.3%) died of neurological causes. Multivariate analysis of these data revealed that N stage, whole-brain radiotherapy (WBRT), and chemotherapy were significant predictors for survival (p<0.05). Survival of patients with NSCLC and synchronous brain metastases is mainly dependent upon the progression of the systemic disease, provided that the cerebral lesions are treated adequately with local treatment modalities including radiosurgery. Application of radiosurgery as an initial treatment option and aggressive local and systemic modalities to control extracranial disease may improve survival.
PMCID: PMC2729962  PMID: 16778400
Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Radiosurgery

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