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.

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㎤ 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.

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.

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.

Repeat Stereotactic Radiosurgery for Recurred Metastatic Brain Tumors

OBJECTIVE: We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control.METHODS: A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line.RESULTS: After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%.CONCLUSION: The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.

Repeat Stereotactic Radiosurgery for Recurred Metastatic Brain Tumors

OBJECTIVE: We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. METHODS: A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. RESULTS: After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. CONCLUSION: The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.

Recurred Intracranial Meningioma: A Retrospective Analysis for Treatment Outcome and Prognostic Factor

BACKGROUND: In this study, we aimed to compare repeated resection and radiation treatment, such as Gamma knife radiosurgery (GKRS) or conventional radiotherapy (RT), and investigate the factors influencing treatment outcome, including overall survival (OS), progression-free survival (PFS), and complication rates. METHODS: We retrospectively reviewed 67 cases of recurred intracranial meningiomas (repeated resection: 36 cases, radiation treatment: 31 cases) with 56 months of the median follow-up duration (range, 13–294 months). RESULTS: The incidence of death rate was 29.9% over follow-up period after treatment for recurred meningiomas (20/67). As independent predictable factors for OS, benign pathology [hazard ratio (HR) 0.132, 95% confidence interval (CI) 0.048–0.362, p<0.001] and tumor size <3 cm (HR 0.167, 95% CI 0.061–0.452, p<0.001) were significantly associated with a longer OS. The incidence of progression rate was 23.9% (16/67). Only treatment modality was important for PFS as an independent predictable factor (GKRS/RT vs. open resection; HR 0.117, 95% CI 0.027–0.518, p<0.005). The complication rate was 14.9% in our study (10/67). Larger tumor size (≥3 cm, HR 0.060, 95% CI 0.007–0.509, p=0.010) was significant as an independent prognostic factor for development of complications. Although treatment modality was not included for multivariate analysis, it should be considered as a predictable factor for complications (p=0.001 in univariate analysis). CONCLUSION: The role of repeated resection is questionable for recurred intracranial meningiomas, considering high progression and complication rates. Frequent and regular imaging follow-up is required to detect recurred tumor sized as small as possible, and radiation treatment can be a preferred treatment.

Ependymomas: Prognostic Factors and Outcome Analysis in a Retrospective Series of 33 Patients

BACKGROUND: The purpose of this study was to evaluate the prognostic factors and outcomes in patients with ependymoma to management plans. METHODS: Between 1997 and 2013, 33 patients with 25 ependymomas (WHO grade II) and eight anaplastic ependymomas (WHO grade III) were pathologically diagnosed. Six were pediatric patients (mean age, 6.15 years; range, 1.3–11 years), while 27 were adults (mean age, 47.5 years; range, 19–70 years). Of those, there were 12 adult patients with totally resected ependymomas without anaplastic pathology and adjuvant treatment. Prognostic factors were assessed in ependymoma patients. Prognostic factors were studied using Kaplan-Meier estimates in subgroups. RESULTS: For six pediatric patients, the progression-free survival (PFS) was 43.7±13.5 months, and the overall survival (OS) was 58.1±13.7 months. For 27 adult patients, the PFS was 125.6±14.3 months, and the OS was 151.2±12.5 months. Age demonstrated a statistically significant effect on PFS (p=0.03) and OS (p=0.03). In adult ependymomas, the extent of tumor removal significantly affected PFS (p=0.03) and trended towards an effect on OS (p=0.06). Out of 12 patients with totally resected ependymomas without anaplastic pathology and adjuvant treatment, one patient showed tumor recurrence during follow-up (mean, 93.5 months; range, 27.9–162.7 months). CONCLUSION: Adult patients with ependymomas were found to have better survival rates compared to pediatric patients. We suggest that totally resected adult ependymomas without anaplastic pathology could be observed without any adjuvant treatment, regardless of the tumor location.

Resection and Observation for Brain Metastasis without Prompt Postoperative Radiation Therapy

OBJECTIVE: Total resection without consecutive postoperative whole brain radiation therapy is indicated for patients with a single or two sites of brain metastasis, with close follow-up by serial magnetic resonance imaging (MRI). In this study, we explored the effectiveness, usefulness, and safety of this follow-up regimen. METHODS: From January 2006 to December 2015, a total of 109 patients (76 males, 33 females) underwent tumor resection as the first treatment for brain metastases (97 patients with single metastases, 12 with two metastases). The mean age was 59.8 years (range 27–80). The location of the 121 tumors in the 109 patients was supratentorial (n=98) and in the cerebellum (n=23). The origin of the primary cancers was lung (n=45), breast (n=17), gastrointestinal tract (n=18), hepatobiliary system (n=8), kidney (n=7), others (n=11), and unknown origin (n=3). The 121 tumors were totally resected. Follow-up involved regular clinical and MRI assessments. Recurrence-free survival (RFS) and overall survival (OS) after tumor resection were analyzed by Kaplan-Meier methods based on clinical prognostic factors. RESULTS: During the follow-up, MRI scans were done for 85 patients (78%) with 97 tumors. Fifty-six of the 97 tumors showed no recurrence without adjuvant local treatment, representing a numerical tumor recurrence-free rate of 57.7%. Mean and median RFS was 13.6 and 5.3 months, respectively. Kaplan-Meier analysis revealed the cerebellar location of the tumor as the only statistically significant prognostic factor related to RFS (p=0.020). Mean and median OS was 15.2 and 8.1 months, respectively. There were no significant prognostic factors related to OS. The survival rate at one year was 8.2% (9 of 109). CONCLUSION: With close and regular clinical and image follow-up, initial postoperative observation without prompt postoperative radiation therapy can be applied in patients of brain metastasi(e)s when both the tumor(s) are completely resected.

Metallothinein 1E Enhances Glioma Invasion through Modulation Matrix Metalloproteinases-2 and 9 in U87MG Mouse Brain Tumor Model

Malignant glioma cells invading surrounding normal brain are inoperable and resistant to radio- and chemotherapy, and eventually lead to tumor regrowth. Identification of genes related to motility is important for understanding the molecular biological behavior of invasive gliomas. According to our previous studies, Metallothionein 1E (MT1E) was identified to enhance migration of human malignant glioma cells. The purpose of this study was to confirm that MT1E could modulate glioma invasion in vivo. Firstly we established 2 cell lines; MTS23, overexpressed by MT1E complementary DNA construct and pV12 as control. The expression of matrix metalloproteinases (MMP)-2, -9 and a disintegrin and metalloproteinase 17 were increased in MTS23 compared with pV12. Furthermore it was confirmed that MT1E could modulate MMPs secretion and translocation of NFkB p50 and B-cell lymphoma-3 through small interfering ribonucleic acid knocked U87MG cells. Then MTS23 and pV12 were injected into intracranial region of 5 week old male nude mouse. After 4 weeks, for brain tissues of these two groups, histological analysis, and immunohistochemical stain of MMP-2, 9 and Nestin were performed. As results, the group injected with MTS23 showed irregular margin and tumor cells infiltrating the surrounding normal brain, while that of pV12 (control) had round and clear margin. And regrowth of tumor cells in MTS23 group was observed in another site apart from tumor cell inoculation. MT1E could enhance tumor proliferation and invasion of malignant glioma through regulation of activation and expression of MMPs.

Bacitracin Inhibits the Migration of U87-MG Glioma Cells via Interferences of the Integrin Outside-in Signaling Pathway

OBJECTIVE: Protein disulfide isomerase (PDI) acts as a chaperone on the cell surface, and it has been reported that PDI is associated with the tumor cell migration and invasion. The aims of this study are to investigate the anti-migration effect of bacitracin, which is an inhibitor of PDI, and the associated factor in this process. METHODS: U87-MG glioma cells were treated with bacitracin in 1.25, 2.5, 3.75, and 5.0 mM concentrations. Western blot with caspase-3 was applied to evaluate the cytotoxicity of bacitracin. Adhesion, morphology, migration assays, and organotypic brain-slice culture were performed to evaluate the effect of bacitracin to the tumor cell. Western blot, PCR, and gelatin zymography were performed to investigate the associated factors. Thirty glioma tissues were collected following immunohistochemistry and Western blot. RESULTS: Bacitracin showed a cytotoxicity in 3rd (p<0.05) and 4th (p<0.001) days, in 5.0 Mm concentration. The cell adhesion significantly decreased and the cells became a round shape after treated with bacitracin. The migration ability, the expression of phosphorylated focal adhesion kinase (p-FAK) and matrix metalloproteinase-2 (MMP-2) decreased in a bacitracin dose- and time-dependent manner. The U87-MG cells exhibited low-invasiveness in the 2.5 mM, compared with the untreated in organotypic brain-slice culture. PDI was expressed in the tumor margin, and significantly increased with histological glioma grades (p<0.001). CONCLUSION: Bacitracin, as a functional inhibitor of PDI, decreased the phosphorylated FAK and the secreted MMP-2, which are the downstream of integrin and play a major role in cell migration and invasion, might become one of the feasible therapeutic strategies for glioblastoma.

Role of Craniofacial Resection for Malignant Tumors Involving the Anterior Skull Base: Surgical Experience in a Single Institution

BACKGROUND: Craniofacial resection (CFR) has been regarded as a standard treatment for various tumors involving the anterior skull base. The purpose of this study was to evaluate the results of CFR for the patients with anterior skull base malignancies in our hospital. METHODS: We retrospectively analyzed 17 patients with anterior skull base malignancies treated with CFR between 2001 and 2012. Mean follow-up duration was 41 months (range, 2-103 months). RESULTS: Intracranial involvement was found in 11 patients (65%) and orbital extension in 6 patients (35%). Classical bifrontal craniotomy was combined with endoscopic endonasal approach in 14 patients and external approach in 3 patients. Vascularized flap was used for reconstruction of the anterior fossa floor in 16 patients (94%). The most common pathological type was squamous cell carcinoma (6 patients). Gross total resection was achieved in all cases. Postoperative complications developed in 4 patients (24%) and included local wound problem and brain abscess. One patient with liver cirrhosis died from unexpected varix bleeding after the operation. Although postoperative treatment, such as radiotherapy or chemotherapy, was performed in 14 patients, local recurrence was seen in 6 patients. The mean overall survival time after the operation was 69.0 months (95% confidence interval: 47.5-90.5 months) with a 1-, 2-, and 5-year survival rate of 82.3%, 76.5%, and 64.7%, respectively. Postoperative radiotherapy was found to be the powerful prognostic factor for favorable survival. CONCLUSION: Considering the higher local control rate and acceptable complication or mortality rate, CFR with adjuvant radiotherapy is a gold standard treatment option for malignant tumors involving anterior skull base, especially with extensive intracranial involvement.

Surgical Experience of Infratentorial Meningiomas : Clinical Series at a Single Institution during the 20-Year Period

OBJECTIVE: Based on surgical outcomes of patients with infratentorial meningiomas surgically treated at our institution, we analyzed the predictors for surgical resection, recurrence, complication, and survival. METHODS: Of surgically treated 782 patients with intracranial meningioma, 158 (20.2%) consecutive cases of infratentorial location operated on between April 1993 and May 2013 at out institute were reviewed retrospectively. The patients had a median age of 57.1 years (range, 16--77 years), a female predominance of 79.7%, and a mean follow-up duration of 48.4 months (range, 0.8--242.2 months). RESULTS: Gross total resection (Simpson's grade I & II) was achieved in 81.6% (129/158) of patients. Non-skull base location was an independent factor for complete resection. The recurrence rate was 13.3% (21/158) and the 5-, 10-, and 15-year recurrence rates were 8.2%, 12.0%, and 13.3%, respectively. Benign pathology, postoperative KPS over than 90, low peritumoral edema, and complete resection were significantly associated with longer recurrence-free survival rate. The 5-, 10-, and 15-year survival rates were 96.2%, 94.9%, and 94.9%, respectively. Benign pathology, postoperative KPS over than 90 and complete resection were significantly associated with a longer survival rate. The permanent complication rate was 13% (21/158). Skull base location and postoperative KPS less than 90 were independent factors for the occurrence of permanent complication. CONCLUSION: Our experience shows that infratentorial meningiomas represent a continuing challenge for contemporary neurosurgeons. Various factors are related with resection degree, complications, recurrence and survival.

Intracranial Meningiomas, WHO Grade Il : Prognostic Implications of Clinicopathologic Features

OBJECTIVE: Intracranial meningiomas are primarily benign tumors with a good prognosis. Although WHO grade II meningiomas are rare (2-10%), WHO grade II meningiomas have higher recurrence and mortality rates than benign. We evaluated the patient recurrence rate and investigated the prognostic factors of WHO grade II meningiomas. METHODS: Between 1993 and 2005, 55 patients were diagnosed with WHO grade II meningiomas in our hospital. WHO grade II meningiomas (n=55) were compared with other WHO grades meningiomas (I, n=373; and III, n=20). The patients had a median age of 48.4 years (range, 14-17 years), a male-to-female ratio of 26 : 29, and a mean follow-up time of 45 months (range, 3-175 months). RESULTS: In WHO grade II meningiomas, only the extent of resection was a significant prognostic factor. Post-operative radiotherapy had no significant influence on tumor recurrence (p=0.053). The relative risk of recurrence was significantly higher in WHO grade II meningiomas with incomplete resection (10/27, RR=37%) than in WHO grade II meningiomas with complete resection (4/28, RR=14%) regardless of post-operative radiotherapy. In the incomplete resection group, Simpson grade III or IV had a significantly high risk of recurrence regardless of post-operative RT (n=3, RR=100%) However, if the degree of resection was Simpson grade II, the recurrence rate was similar to the complete resection group even though post-operative RT was not performed. CONCLUSION: Complete resection was the most powerful independent predictive factor of the recurrence rate in WHO grade II meningiomas. Post-operative adjuvant RT was not a significant factor in this study.

Leptomeningeal Dissemination of a Low-Grade Brainstem Glioma without Local Recurrence

It is rare for low-grade gliomas to disseminate to the leptomeninges. However, low-grade gliomas with dissemination to the leptomeninges have been occasionally reported in children, and have generally been associated with local recurrence. A 16-year-old boy sought evaluation for diplopia and gait disturbance. A brain magnetic resonance imaging (MRI) revealed pontine mass, which was proved to be fibrillary astrocytoma on biopsy, later. Radiation therapy (5400 cGy) was given and the patient's symptoms were improved. He was followed-up radiologically for brain lesion. Seven months after diagnosis he complained of back pain and gait disturbance. A brain MRI showed a newly-developed lesion at the left cerebellopontine angle without an interval change in the primary lesion. A spinal MRI demonstrated leptomeningeal dissemination of the entire spine. Radiation therapy (3750 cGy) to the spine, and adjuvant chemotherapy with a carboplatin plus vincristine regimen were administered. However, he had a progressive course with tumoral hemorrhage and expired 13 months after diagnosis. We report an unusual case of a low-grade brainstem glioma with spinal dissemination, but without local recurrence, and a progressive course associated with hemorrhage.

Characterization of Invading Glioma Cells Using Molecular Analysis of Leading-Edge Tissue

OBJECTIVE: We have introduced a method of characterization of invading glioma cells by using molecular analysis of marginal invading tumor cells and molecular profiles of glioma tumor margin. METHODS: Each of tumor core and marginal tissues was obtained in 22 glioma patients. Tumor core cells and marginal cells from each glial tumor were collected by laser capture microdissection or intraoperative microdissection under the operating microscope. Expression of MMP-2, MMP-9, CD44 and RHAMM mRNA by invading glioma cells compared with tumor core was confirmed by realtime-PCR of twenty-four glioma specimens. Clinical data also were reviewed for invasion and recurrence pattern of the gliomas radiologically and invasive rim pattern microscopically. RESULTS: Overall results of the molecular analysis showed that relative overexpression of MMP-2, MMP-9 and RHAMM were noted at the invasive edge of human glioma specimens comparing to the tumor core but CD44 was highly expressed in the tumor core comparing to the margin. High marginal expression of MMP-2 and MMP-9 were noted in poorly ill-defined margin on the pathological finding. High marginal expression of CD44 and MMP-2 were demonstrated in the midline cross group on the radiological review, and that of RHAMM and MMP-2 were showed in the aggressive recurrence group. High expression of MMP-2 seems to be involved in the various invasion-related phenomenons. CONCLUSION: Up-regulation of MMP-2, MMP-9, CD44 and RHAMM was noted in invasive edge of gliomas according to the various clinical situations.

Modified Trans-Middle Temporal Gyrus Approach for Trigonal Tumor to Preserve Visual Field

OBJECTIVE: We evaluated a modified trans-middle temporal gyrus (MTG) approach with good postoperative visual preservation for patients with trigonal tumors. METHODS: Three patients with a trigonal tumor were treated via the modified trans-MTG approach guided by a neuro-navigator. Modified trans-MTG approach involve the incision at the MTG within 5 mm to the superior temporal sulcus. This approach makes a proper trajectory to the trigone but also reduces the retraction injury of MTG as little as possible to prevent postoperative visual field defect. Preoperative and postoperative visual field examination using perimetry was performed to evaluate the visual field. RESULTS: Three patients underwent surgery for lymphoma in the right trigone, meningioma in the left trigone, and focal enhancing nodule in the right paratrigonal area, respectively. In case of lymphoma, preoperative examination showed a left homonymous hemianopsia : one week later after surgery, a visual field examination was performed and revealed improvement of the visual field defect. In case of the meningioma, the preoperative examination showed no visual field defect : one month later, the visual field had no defect. In case of the enhancing nodule, preoperative visual field testing revealed a partial left homonymous hemianopsia. Visual examination within one month after surgery showed no visual field defect. All three patients treated with the modified trans-MTG approach showed no visual deterioration after surgery. CONCLUSION: The modified trans-MTG approach provides a safe and useful technique for trigonal tumors without postoperative visual field deterioration and affords adequate exposure of the trigonal tumor with a short trajectory.

Intramedullary Subependymoma of the Thoracic Spinal Cord

An Intramedullary subependymoma of the spinal cord is a rare tumor with only 43 reported cases in the literature. Most of them are reported to be localized within the cervical spinal cord. We report a rare case of a thoracic spine intramedullary subependymoma in a 37-year-old female who presented with back pain and radiating leg pain. Subtotal resection and post-operative radiotherapy were performed. Subependymomas developing in the spinal cord are benign with a low proliferative potential. Complete resection of the tumor appears to be the optimal method for a complete cure. However aggressive surgery may cause severe neurological deficit. Therefore, if severe neurological deficits are expected after complete removal, a partial removal and postoperative radiation therapy is an alternative method for treatment in selected cases. A large-scale randomized study is mandatory to clarify the effectiveness of radiotherapy and to establish the recurrence rate and prognosis with respect to the surgical removal of these tumors.

Serum S-100B Protein as a Prognostic Factor in Patients with Severe Head Injury

OBJECTIVE: Despite the recent progress that has been made in intracerebral monitoring, it is still difficult to quantify the exact extent of primary brain damage after severe head injury. In this work, we investigate the role of S-100B protein as a serum marker of brain damage after severe head injury. METHODS: 21 patients with severe head injury (GCS score <9) were selected for this prospective study. A venous blood sample was taken as soon as possible after head injury and the serum concentration of S-100B protein was measured daily for five consecutive days. The serum level of S-100B protein was compared with the patients' outcome. The outcome was measured twice, at hospital discharge and after 6 months of follow-up using the Glasgow Outcome Scale(GOS). RESULTS: Those patients who died within two weeks (after head injury) had a significantly higher serum S-100B value than those who survived (median, 9.64 ug/L versus 2.91 ug/L). Seven (78%) of the nine patients who died had a maximum S-100B value of 2 ug/L or higher, while three (25%) of the twelve surviving patients showed a maximum S-100B protein value of more than 2 ug/L (P<0.05). CONCLUSION: These results indicate that S-100B protein appears to be the most reliable index for estimating the extent of brain damage.

An Aneurysm Developing on the Infundibulum of Posterior Communicating Artery: Case Report and Literature Review

Infundibular dilatation is funnel-shaped symmetrical enlargement that occurs at the origin of cerebral arteries and which is apparent on 7 to 25% of normal angiograms 3,4,7,10,12,13,15). Infundibular dilatation is frequently considered a normal anatomic variation of no pathologic significance. The authors report a case in which an aneurysm developed on an infundibular dilatation of the posterior communicating artery (PComA). A 72-year-old woman presented with severe headache, nausea, and vomiting. Digital subtraction angiography showed a saccular aneurysm arising from the origin of the left PComA. Operative findings revealed the aneurysm and infundibular widening of the right PComA. The aneurysm was successfully obliterated. Whether infundibular dilatation is a pre-aneurysmal state or a benign dilatation is controversial. However, we believe infundibular dilatation of the PComA in this case may have served as a pre-aneurysmal lesion.