Distinct Specialized Center of Excellence, the Story of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital.

The paper provides a comprehensive overview of the growth and development of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital over the past 18 years. As the first brain tumor center in Korea when it was established in April 2004, Hwasun Neurosurgery has since become one of the leading institutions in brain tumor education and research in the country. Its impressive clinical and basic research capabilities, dedication to professional education, and numerous academic achievements have all contributed to its reputation as a top-tier institution. We hope this will become a useful guide for other brain tumor centers or educational institutions by sharing the story of Hwasun Neurosurgery.

Contralateral subfrontal approach for tuberculum sellae meningioma: techniques and clinical outcomes.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) present a burdensome surgical challenge because of their adjacency to vital neurovascular structures. The contralateral subfrontal approach provides an outstanding corridor for removing a TSM with an excellent visual outcome and limited complications. The authors present their long-term surgical experience in treating TSMs via the contralateral subfrontal approach and discuss patient selection, surgical techniques, and clinical outcomes. METHODS: Between 2005 and 2021, the authors used the contralateral subfrontal approach in 74 consecutive patients presenting with TSMs. The surgical decision-making process and surgical techniques are described, and the clinical outcomes were retrospectively analyzed. RESULTS: The mean patient age was 54.4 years, with a female predominance (n = 61, 82%). Preoperatively, 61 patients (82%) had vision symptoms and 73 (99%) had optic canal invasion by tumor. Gross-total resection was achieved in almost all patients (n = 70, 95%). The visual function improvement and stabilization rate was 91% (67/74). Eight patients (11%) showed a worsening of visual function on the less-compromised (approach-side) optic nerve. There was no occurrence of cerebrospinal fluid leakage. Four patients (5%) experienced recurrences after the initial operation (mean follow-up duration 63 months). There were no deaths in this study. CONCLUSIONS: The contralateral subfrontal approach provides a high chance of complete tumor removal and visual improvement with limited complications and recurrences, especially when the tumor is in a unilateral or midline location causing unilateral visual symptoms or bilateral asymmetrical visual symptoms, regardless of tumor size or encasement of major vessels. With the appropriate patient selection, surgical technique, and familiarity with surrounding neurovascular structures, this approach is reliable for TSM surgery.

Multiple craniospinal tumors in a pediatric patient with neurofibromatosis type 2: a case report.

INTRODUCTION: Neurofibromatosis type 2 (NF-2) is an inherited disease, linked with abnormalities in the NF-2 gene, which is located on chromosome 22 and involved in merlin production. Many craniospinal tumors are common in individuals with NF-2. We present a case of NF-2 with the rapid symptomatic progression of multiple craniospinal tumors. CASE REPORT: A 12-year-old male complained of headache and hearing impairment in the right ear for 7 months. Brain magnetic resonance imaging (MRI) revealed a right frontal meningioma, bilateral vestibular and trigeminal schwannomas, and a brainstem tumor. He was diagnosed with NF-2 and underwent brain surgery and radiotherapy for chordoid meningioma. He complained of right leg motor weakness 5 months post-surgery. The spine MRI showed multiple heterogeneously enhanced masses spreading over the entire spinal cord. The symptomatic intradural extramedullary mass at the cervicothoracic area was removed and the histological finding was schwannoma. His leg motor weakness was relieved after surgery. At the 6-month follow-up, brain MRI revealed the progression of the vestibular schwannoma, trigeminal schwannoma, and brainstem tumor. The patient was treated with bevacizumab (5 mg/kg) every 2 weeks for 6 months. For 2 years, all of the craniospinal tumors were stable without neurological deterioration after the completion of chemotherapy. CONCLUSION: Meningiomas and schwannomas grow slowly in most patients with NF-2, but these multiple craniospinal tumors can show sudden rapid growth and manifest as neurological symptoms in a pediatric patient. These tumors could be controlled with local symptomatic and systemic bevacizumab treatments.

Sellar plasmacytoma with massive bleeding during surgery.

Plasmacytoma in the sellar region is an extremely rare occurrence. Sellar plasmacytoma is often difficult to differentiate from pituitary tumors both clinically and radiologically. The occurrence of cranial nerve palsy, the preservation of pituitary hormone function, the presence of sellar floor destruction, and better contrast enhancement are regarded as the differentiating factors between sellar plasmacytoma and pituitary tumors. We recommend adding the massive bleeding properties of sellar plasmacytoma as another characteristic which differentiates it from a pituitary tumor.

Surgery is a safe, effective first-line treatment modality for noninvasive prolactinomas.

PURPOSE: Dopamine agonists (DAs) have long been the recommended first-line treatment for prolactinoma. Given the remarkable developments in surgical techniques, however, surgery is on the rise. We compared the treatment outcomes of patients with noninvasive prolactinomas receiving two different initial treatments (DAs and transsphenoidal surgery). METHODS: We reviewed 745 patients with hyperprolactinemia or pituitary tumors treated from 2004 to 2020 at Chonnam National University Hwasun Hospital and identified 310 with prolactinomas. After selecting patients who had pituitary tumors with Knosp grade 0 to 1 with follow-up period over 1 year, 70 patients (29 who underwent surgery and 41 who received DAs as the initial treatment) were finally included for a comparative study. RESULTS: The surgery group exhibited better outcomes in terms of DA-free remission and the structural response, although the tumor size was significantly larger than in the DA group. The groups exhibited comparable results in terms of symptom control and the biochemical response. Univariate and multivariate analyses indicated that surgery as the initial treatment modality provided significantly better clinical outcomes in terms of DA-free remission. In the surgery group, a postoperative prolactin level < 10 ng/mL was the only significant predictor of DA-free remission. CONCLUSIONS: Transsphenoidal surgery showed comparable clinical outcomes in patients with prolactinomas, and low complication rates. The decision regarding the first-line treatment modality for non-invasive prolactinomas should be made on an individual basis.

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

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

Type-D personality and quality of life in patients with primary brain tumours.

OBJECTIVE: To investigate the influence of type-D personality on quality of life (QoL) in patients with primary brain tumours. METHODS: We performed descriptive cross-sectional study between July 2018 and March 2019. A convenience sample of 293 patients was recruited from an outpatient neurosurgery clinic. RESULTS: Type-D personality was identified in 34.1% of subjects. Type-D patients had poorer QoL and experienced more severe symptoms and interference with life. Poor QoL was associated with lower education, no spouse and lower family income. Symptoms were the most significant factor affecting QoL, followed by type-D personality, income and education. CONCLUSION: Symptoms, type-D personality and demographic factors should be considered when assessing QoL in patients with primary brain tumours. Interventions that reflect these characteristics, including type-D personality, may help improve QoL for patients with primary brain tumours.

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

BACKGROUND: Although Gamma Knife radiosurgery (GKRS) has been widely used for intracranial meningiomas as an alternative or adjuvant treatment, guidelines have not been established for the selection of patients with petroclival meningioma (PCM) for GKRS. In this study, we reported the factors related to tumor progression and postoperative complications in PCM patients treated by GKRS, with a review of the literatures. METHODS: Between 2004 and 2019, 64 patients (52 patients for alternative and 12 patients for adjuvant treatment) with PCM underwent GKRS in our institution. The clinical and radiological factors were retrospectively analyzed. The mean radiologic follow-up duration was 58.4 months (range, 6-164 months). The mean tumor volume and diameter before GKRS were 13.4 cm³ and 2.9 cm, respectively. The median marginal dose was 12 Gy (range, 10-14 Gy) with a 50% median isodose line. Fractionation was used in 19 cases (29%, two fractionations in 5 cases & three fractionations in 14 cases). RESULTS: Progression was noted in 7 cases (10.9%) and the progression-free survival rates were 91.1% at 5 years and 69.6% at 10 years. Although large in volume, moderate to severe peritumoral edema and male gender were somewhat related to progression, they did not reach statistical significance. Ten patients (15.6%) developed complications after GKRS. The most common complication was cranial nerve deficit (n=8), followed by hemiparesis, cognitive dysfunction, and hydrocephalus. Large size (maximal diameter ≥5 cm) [hazard ratio (HR) 0.091, 95% confidence interval (CI) 0.014-0.608; p=0.013] and multiplicity (HR 0.102, 95% CI 0.018-0.573; p=0.009) were independent factors for developing complications after GKRS. CONCLUSION: GKRS can be considered an effective and safe treatment for large-volume PCM. However, for patients with large size or multiple masses, the treatment method should be determined with caution because the probability of complications after GKRS may increase.

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

RATIONALE: Bevacizumab has shown good efficacy in radiation necrosis (RN) following gamma knife radiosurgery (GKRS) and associated peritumoral edema. However, few studies have reported bevacizumab failure. Moreover, the pathologic transformation of benign meningioma following GKRS has never been reported. PATIENTS CONCERNS: A 41-year-old man was admitted with focal seizure on the right arm. DIAGNOSES: Magnetic resonance imaging (MRI) demonstrated a 4.7 cm-sized convexity meningioma involving left motor cortex. INTERVENTIONS: Subtotally resected tumor was confirmed as a meningothelial meningioma and subsequently treated by GKRS. During 4-year follow-up after GKRS, seizure and hemiparesis had persisted with progressively worsened peritumoral edema regardless of steroid and bevacizumab treatment. Radical debulking of tumor was achieved and immunohistopathological examination revealed angiomatous meningioma with necrotic core presenting scanty VEGF expression. OUTCOMES: A follow-up MRI at 4 months after debulking surgery showed a marked reduction of peritumoral edema with improvement of symptoms. LESSONS: This is the first report of pathologically confirmed angiomatous transformation following GKRS. Although the pathogenesis is not fully understood, this rare pathologic transformation may be closely related to RN. Also, if bevacizumab is resistant, debulking surgery for reducing tumor burden could be an effective treatment option to control the RN.

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

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

Artificial intelligence and lung cancer treatment decision: agreement with recommendation of multidisciplinary tumor board.

BACKGROUND: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients. METHODS: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value. RESULTS: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients. CONCLUSIONS: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage.

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

OBJECTIVE: The number of small to medium sized vestibular schwannoma (VS) patients presenting with serviceable hearing has steadily increased. There are various treatment strategies for small to medium sized VS, including microsurgery (MS), gamma knife radiosurgery (GKS), and serial observations using magnetic resonance imaging. In this study, we presented the long-term outcomes of patients with small to medium sized VS with serviceable hearing. We also evaluated the potential prognostic factors for hearing preservation and discussed appropriate treatment strategies. METHODS: A retrospective review of 504 cases of all VS patients who underwent MS or GKS between 1993 and July 2019 was conducted. Surgical resection was performed on 267 patients using the retro-sigmoid approach and 55 (20.6%) of them were small to medium sized VS. GKS was performed on 237 patients and 175 (73.8%) of them were small to medium sized VS. Small to medium sized VS was defined as less than 25 mm in the greatest dimension. After applying the inclusion and exclusion criteria, 51 patients with small to medium sized VS with serviceable hearing were enrolled in this study and underwent either MS (n = 21) or GKS (n = 30). To define the clinical characteristics of the patients, clinical data at the time of treatment, age, sex, presenting symptoms, tumor location type, preoperative hearing status, posttreatment related complications, recurrence, and hearing loss progression-free survival data were collected. RESULTS: In the MS group, the hearing preservation rate was 71.4% and the tumor control rate was 100%. In the GKS group, the tumor control rate was 93.3% and two patients experienced recurrence at a median interval of 41.5 months. Kaplan-Meier curves showed that the hearing progression-free survival rates at 1-, 3-, and 5-years following GKS were 80, 66.7, and 53.3%, respectively. The MS group had a higher hearing preservation rate at 5 years (71.4 versus 53.3%), but the difference did not reach statistical significance (p = 0.173). Hearing preservation was statistically significant when the preoperative hearing status was class A in the GKS group (p = 0.016), but it was not statistically significant in the MS group (p = 0.777). In the MS group, medial type VS had a higher hearing preservation rate (80%) than the lateral fundal extended type VS (63.6%), and this difference was almost close to statistical significance (p = 0.058). The GKS group had a higher occurrence of postoperative tinnitus (23.3%) than the MS group (9.5%). CONCLUSION: MS was more suitable for patients who are younger, have good physical status, good preoperative hearing status including AAO-HNS class B, and medial type VS. GKS was more suitable for patients who are elderly, have poor physical status, preoperative AAO-HNS class A hearing.

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

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

Intracranial Inflammatory Pseudotumor Associated with Idiopathic Hypertrophic Pachymeningitis Mimicking Malignant Tumor or High-Grade Meningioma.

BACKGROUND: Idiopathic hypertrophic pachymeningitis (IHP) is a rare clinical disease characterized by inflammatory fibrosis, which causes diffuse thickening of the dura mater. The inflammatory fibrosis will be locally invasive in nature but will be characterized by a benign histological appearance, known as an inflammatory pseudotumor. We present the case of a patient with an infiltrative lesion involving the right frontal convexity diagnosed as IHP, which had been suspected to be a malignant tumor or high-grade meningioma from the preoperative radiological findings. CASE DESCRIPTION: A 59-year-old man was admitted to our hospital because of a temporary loss of consciousness. Contrast-enhanced magnetic resonance imaging (MRI) of the brain showed a 30-mm × 12-mm mass located in the right frontal convexity. The lesion had an isointensity to high-intensity signal with moderate periregional edema on T2-weighted MRI, and homogeneous enhancement, including a necrotic portion with a long dural tail along the right frontal convexity, after contrast-enhanced MRI. Thus, our preliminary diagnosis was high-grade meningioma or a malignant tumor. We decided to surgically remove the tumor. Intraoperatively, the lesion appeared as a dural-based yellowish mass with partial infiltration of the cortex. Histopathological examination of the lesion revealed thickened meninges with marked fibroinflammatory changes. The inflammatory changes extended into the underlying brain parenchyma and were centered in the perivascular spaces. The lesion showed abundant lymphoplasmacytic infiltration with fibrosis. Immunohistochemistry revealed mixed T and B lymphocytes and plasma cells. Only a small number of IgG4-positive cells were identified. From these findings, we finally concluded that the diagnosis was IHP. The patient did not receive any further steroid therapy, because the patient had no evidence of systemic autoimmune disease. A follow-up brain MRI scan was performed 6 month after surgery, which revealed no recurrence of the lesion. CONCLUSIONS: Surgical treatment can be the first treatment option when the lesion is not localized to a critical portion of the brain. Thus, it might be possible to arrive at a definitive diagnosis histologically and determine additional treatment strategies. Also, if the surgeons are confident that the IHP has been removed completely, additional steroid therapy might not be necessary.

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

BACKGROUND: Although 11C-methionine positron emission tomography (MET-PET) images can be fused with magnetic resonance (MR) images using planning software for gamma knife radiosurgery (GKR), the stereotactic information has limited value in patients with recurrent malignant brain tumor due to the difference in imaging protocols between MET-PET and MR images. The aim of this study was to evaluate the clinical application of MR imaging (MRI)-deformed MET-PET images in GKR using a deformable registration tool. METHODS: We examined the enhanced MR stereotactic images, MET-PET and MRI-deformed MET-PET images without stereotactic information for 12 newly developed metastatic brain tumors. MET-PET and MRI-deformed MET-PET images were co-registered with the MR stereotactic images using radiosurgery planning software. Visual analysis was performed to determine whether the MET-PET and MR images matched better after using the deformable registration tool. In addition, the matching volume between MR and MET-PET images was compared before and after applying this tool. The matching volume was calculated as the metabolic tumor volume on the MET-PET images, including the MR-enhanced volume. The matching percentage was calculated as the matching volume divided by the MR-enhanced volume, multiplied by 100. RESULTS: Visual analysis revealed that the MRI-deformed MET-PET images provided the same axial plane as that of the MR images, with the same window level, enabling easy identification of the tumor with the radiosurgery planning software. The mean matching percentage of the MET-PET/MR fusion images was 61.1% (range 24.7-94.7) and that of the MRI-deformed MET-PET/MR fusion images was 63.4% (range 20.8-94.3). No significant difference was found in the matching percentage between the two types of fusion images (p = 0.754). CONCLUSIONS: The MRI-deformed MET-PET images enable utilization of the functional information when planning a treatment in GKR without significant volume change.

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

Following the introduction of the molecular classification of gliomas by the WHO in 2016, molecularly-proven lineage conversion during glioma recurrence has never been reported. The reported two cases were initially diagnosed as oligodendroglioma with 1p/19q-codeletion and mutation of isocitrate dehydrogenase 1 (IDH1)-R132H. The recurrent tumors showed loss of alpha-thalassemia/mental retardation X-linked (ATRX) expression, strong P53 positivity, and 1p/19q-nondeletion. Next generation sequencing analysis performed on the first case confirmed the transition of molecular traits from oligodendroglioma to astrocytoma. An IDH mutation of R132H was preserved in the episodes of recurrence, but ATRX and TP53 mutations were newly acquired and TERT promoter mutation C228T was lost at the most recent recurrence. The issue in question for the presented cases is whether the original tumors were pure oligodendrogliomas that then transdifferentiated into astrocytomas, or whether the original tumor was an oligoastrocytoma having oligodendroglioma cells that outnumbered the astrocytoma cells and where the astrocytoma cells becoming more dominant over the episodes of recurrence. With the recognition of the possibility of lineage conversion, our study suggests that molecular examination should be performed to adjust therapeutic strategies in recurrent gliomas. Indeed, our observation of lineage conversion in glioma recurrence calls into question the current distinction drawn between oligodendroglioma, astrocytoma and oligoastrocytoma, rather than simply bidding "farewell to oligoastrocytoma."

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

BACKGROUND: Hemifacial spasm (HFS), one of the most common hyperactive cranial rhizopathies, is a disorder characterized by spontaneous, intermittent, and repetitive contraction of unilateral facial muscle. The most common cause of HFS is a mechanical compression of the facial nerve at the root exit zone (REZ) by blood vessels located in the brainstem. The incidence of cerebellopontine angle (CPA) tumor-induced HFS ranges from 0.3%-2.5% of all patients with HFS, and the incidence of epidermoid cyst among such tumors is extremely rare (0.2% to 0.25%). We present a patient manifesting HFS induced by a small epidermoid cyst who underwent Gamma Knife surgery (GKS) for ipsilateral vestibular schwannoma (VS) more than 10 years ago. CLINICAL DESCRIPTION: A 59-year-old female was admitted to our hospital with HFS. Ten years before admission, the patient underwent GKS for ipsilateral VS. Enhanced brain magnetic resonance imaging demonstrated that the volume of VS was not increased. Also, no definitive mechanical compression of the facial nerve REZ by blood vessels was detected. We concluded that HFS was secondary to the VS treatment by GKS and decided to operate to remove the tumor and identify REZ. A standardized lateral suboccipital retrosigmoid approach was performed. The cochlear nerve was encased by a tumor mass, and the posterior inferior cerebellar artery (PICA) was displaced by the mass. During tumor excision, we ensured that the VS and displaced PICA did not directly compress the REZ. Interestingly, an unexpected lesion was found with a yellowish viscous mass located between the sixth nerve and ventral side of the seventh nerve REZ. After the tumor removal, a small piece of Teflon was inserted between the PICA and REZ of the facial nerve. Postoperatively, the patient experienced no HFS or facial nerve dysfunction. Histopathologic examination of the lesion revealed an epidermoid cyst. CONCLUSIONS: We should consider various possibilities for the cause of HFS and review brain imaging meticulously if patients were treated for CPA tumor with GKS a long time ago and the delayed HFS occurred without changes in tumor volume. HFS induced by epidermoid cyst is rare. Therefore it is critical for the neurosurgeon to ensure the absence of any abnormal contact with the REZ of the facial nerve during surgery for HFS induced by CPA tumors.

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

OBJECTIVE: The functional information of 11C-methionine positron emission tomography (MET-PET) images can be applied for Gamma knife radiosurgery (GKR) and its image quality may affect defining the tumor. This study conducted the phantom-based evaluation for geometric accuracy and functional characteristic of diagnostic MET-PET image co-registered with stereotactic image in Leksell GammaPlan® (LGP) and also investigated clinical application of these images in metastatic brain tumors. METHODS: Two types of cylindrical acrylic phantoms fabricated in-house were used for this study : the phantom with an array-shaped axial rod insert and the phantom with different sized tube indicators. The phantoms were mounted on the stereotactic frame and scanned using computed tomography (CT), magnetic resonance imaging (MRI), and PET system. Three-dimensional coordinate values on co-registered MET-PET images were compared with those on stereotactic CT image in LGP. MET uptake values of different sized indicators inside phantom were evaluated. We also evaluated the CT and MRI co-registered stereotactic MET-PET images with MR-enhancing volume and PET-metabolic tumor volume (MTV) in 14 metastatic brain tumors. RESULTS: Imaging distortion of MET-PET was maintained stable at less than approximately 3% on mean value. There was no statistical difference in the geometric accuracy according to co-registered reference stereotactic images. In functional characteristic study for MET-PET image, the indicator on the lateral side of the phantom exhibited higher uptake than that on the medial side. This effect decreased as the size of the object increased. In 14 metastatic tumors, the median matching percentage between MR-enhancing volume and PET-MTV was 36.8% on PET/MR fusion images and 39.9% on PET/CT fusion images. CONCLUSION: The geometric accuracy of the diagnostic MET-PET co-registered with stereotactic MR in LGP is acceptable on phantom-based study. However, the MET-PET images could the limitations in providing exact stereotactic information in clinical study.

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

OBJECTIVE: Indocyanine green videoangiography (ICGVA) has been used in many neurosurgical operations, including vascular and brain tumor fields. In this study, the authors applied ICGVA to intracranial meningioma surgery and evaluated it usefulness with attention to collateral venous flow. METHODS: Forty-two patients with intracranial meningioma who underwent ICGVA during microsurgical resection were retrospectively analyzed. For ICGVA, the ICG was injected intravenously at the standard dose of 12.5 mg before and/or after tumor resection. Intravascular fluorescence from blood vessels was imaged through a microscope with a special filter and infrared excitation light to illuminate the operating field. The authors assessed the benefits of ICGVA and analyzed its findings with preoperative radiological findings on MRI. RESULTS: ICGVA allowed real-time assessment of the patency and flow direction in very small peritumoral vessels in all cases. A safe dural incision could also be done based on information from ICGVA. The collateral venous channel due to venous obstruction of tumoral compression was found in 10 cases, and venous flow restoration after tumor resection was observed promptly after tumor resection in 4 cases. Peritumoral brain edema (PTBE) was observed on preoperative T2-weighted MRI in 19 patients. The presence of collateral venous circulation or flow restoration was significantly related to PTBE formation in multivariate analysis (p = 0.001; HR 0.027, 95% CI 0.003-0.242). CONCLUSIONS: ICGVA, an excellent method for monitoring blood flow during meningioma resection, provides valuable information as to the presence of venous collaterals and flow restoration. Furthermore, the fact that the presence of venous collaterals was found to be associated with PTBE may directly support the venous theory as the pathogenesis of PTBE formation.

The Cornerstone Technique of Microvascular Decompression for Hemifacial Spasm with Vertebral Artery Offender.

BACKGROUND: Microvascular decompression surgery is the most effective treatment for hemifacial spasm (HFS). The vertebral artery (VA) is a larger and more elastic vessel, which makes surgical management more difficult. We introduce a surgical technique of proximal Teflon transposition with interposition (PTTI) in the vertebromedullary space for HFS with a VA offender. METHODS: In 112 patients with HFS, 22 patients had a VA offender on the facial nerve exit zone. Six of 22 patients with a VA offender underwent surgery by traditional microvascular decompression at the facial nerve exit zone, and 16 patients underwent the PTTI technique. We compared surgical outcomes of the PTTI technique and the conventional technique for HFS associated with the VA. We also compared surgical outcomes of the PTTI technique with outcomes of other alternative techniques. RESULTS: The PTTI technique was associated with a good operative prognosis and fewer complications. The PTTI technique is an easy, safe, and effective method for treatment of patients with HFS with a VA offender. CONCLUSIONS: The PTTI technique can be considered as another treatment option in addition to the transposition technique reported previously.