Chae-Yong Kim

Correlation of clinical and biological parameters with peritumoral edema in meningioma.

Peritumoral edema (PTE) in meningioma occurs variably and can adversely affect the clinical course. Moreover, the etiology of PTE in meningioma is not well documented. To examine possible correlations with PTE, the authors investigated the clinical parameters and the expressions of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) in 20 meningiomas. The estimation of tumor volume (VT) and edema volume (VE) was done using Osiris software with magnetic resonance images and the edema index (EI) was calculated. The expression of VEGF, MMP, and TIMP were estimated in all 20 meningiomas by immunohistochemical staining, Western blotting, zymography, and laser densitometry. Tumor location was closely related with PTE. Meningiomas of the frontal lobe or the frontotemporal base had large PTEs, whereas those of the occipitoparietal lobe, posterior fossa or petroclivus were small. The level of VEGF expression bore correlation with the extent of PTE but not with histologic malignancy. MMP-2 and -9 were detected in 100% of meningiomas by zymography. The levels of MMP-9 were significantly elevated in moderate to severe edema (EI > 1.0) group (p < 0.05) whereas those of MMP-2 were elevated in minimal to mild edema (EI < 1.0) group. TIMP-1 and -2 were detected in 19 (95%) and 12 (60%) of meningiomas respectively and their presence had no significant correlations statistically with PTE between two groups (p = 0.190 and 0.089, respectively). Meningiomas with severe PTE expressed high levels of VEGF and MMP-9 and low levels of MMP-2. The expressions of MMP-2, -9, and TIMPs as well as VEGF in meningioma suggests that they are strongly related with the presence of PTE in meiningiomas, and that they might play the important role in the formation of PTE in meningiomas.

Gamma knife radiosurgery for skull base meningiomas: long-term radiologic and clinical outcome.

PURPOSE To analyze the long-term outcomes in patients with skull base meningiomas (SBMNGs) treated with Gamma Knife radiosurgery (GKRS). METHODS AND MATERIALS Of the 98 consecutive patients with SBMNGs treated with GKRS between 1998 and 2002, 63 were followed up for more than 48 months. The mean (+/-SD) age of the patients was 50 +/- 12 years, the mean tumor volume was 6.5 cm(3) (range, 0.5-18.4 cm(3)), the mean marginal dose was 12.6 Gy (range, 7.0-20.0 Gy), and the mean follow-up duration was 77 +/- 18 months. The mean number of shots was 13.7 +/- 3.8. The tumor volume was decreased at the last follow-up in 28 patients (44.4%) and increased in 6 (9.6%). The actuarial tumor control rate was 90.2% at 5 years. No notable prognostic factor related to tumor control was identified. Ten patients (15.9%) with a cranial neuropathy showed unfavorable outcomes. The rate of improvement in patients with a cranial neuropathy was 45.1%. Age >70 years was likely correlated with an unfavorable outcome in patients with cranial neuropathy (odds ratio = 0.027; p = 0.025; 95% confidence interval 0.001-0.632). Cavernous sinus location was significantly associated with improvement of a cranial neuropathy (odds ratio = 7.314; p = 0.007; 95% confidence interval 1.707-31.34). CONCLUSIONS Gamma Knife radiosurgery is an effective modality for the treatment of SBMNGs and provides favorable outcomes in patients with cranial neuropathy, even in the long-term follow-up period. However, radiosurgery for patients with no or only mild symptoms should be performed cautiously because neither complication rate is low enough to be negligible, especially in elderly patients. A cranial neuropathy by MNGs involving the cavernous sinus seems to have a higher chance of improvement after radiosurgery than other SBMNGs.

Neurenteric cyst: its various presentations

Abstract Neurenteric (NE) cyst is an uncommon developmental lesion lined with epithelium of endodermal origin. To investigate the clinical manifestation and response to surgery, we retrospectively analyzed eight cases of NE cyst that has been confirmed by surgery. Four were in children. The duration of follow-up ranged from 2 to 105 (mean 38) months. One cyst was in the ventral portion of the posterior cranial fossa and the other seven were on the spinal cord. The chief complaints were motor weakness (5), pain (2), and voiding difficulty (1). In one child and three adults, the duration of symptoms was more than 3 years. Children tended to show rapid progression and excellent recovery after surgery. Although total removal of cyst was possible only in two cases, there was no recurrence. The presentation of an NE cyst may be insidious. Clinical suspicion is important for an early diagnosis and better outcome. Because of the benign course after subtotal excision, too-aggressive removal of the lesion should be avoided.

Gamma knife radiosurgery for central neurocytoma: primary and secondary treatment.

Little is known about long‐term results of gamma knife (GK) stereotactic radiosurgery (SRS) as a primary or a secondary postoperative therapy for central neurocytomas (CNs). The authors retrospectively reviewed long‐term outcomes of 13 patients with CN treated with GK SRS.

Usefulness of MS-MLPA for detection of MGMT promoter methylation in the evaluation of pseudoprogression in glioblastoma patients.

Pseudoprogression is a major diagnostic dilemma in current treatment protocols for malignant gliomas that involve concurrent chemoradiotherapy. We hypothesized that methylation-specific multiplex ligation probe amplification (MS-MLPA), an assay that permits semiquantitative evaluation of promoter methylation, may be used to diagnose pseudoprogression based on the quantification of the methylation status of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter. We examined the methylation ratio of the MGMT promoter with MS-MLPA in 48 samples from glioblastoma patients. The results were compared with those from methylation-specific polymerase chain reaction (MSP), and protein levels were confirmed by immunohistochemical staining. We then evaluated the correlation between those molecular signatures and clinical outcomes. With regard to radiological progression after chemoradiotherapy, the diagnostic accuracy of the MS-MLPA method was 80% (using a cut-off value of 0.2). These results are better than those obtained with MSP (diagnostic accuracy of 68%). Combining the MS-MLPA and MSP methods resulted in a diagnostic accuracy of 93% for the identification of pseudoprogression among patients to whom these results were coherent. These results demonstrate that MS-MLPA is a useful method to predict radiological progression vs pseudoprogression in glioblastoma patients and that the interpretation of these results in combination with MSP results will provide good practical guidelines for clinical decision making in glioblastoma treatment.

Long-Term Outcome of Gamma Knife Radiosurgery for Treatment of Typical Trigeminal Neuralgia

PURPOSE To analyze the long-term outcomes of patients with typical trigeminal neuralgia treated with gamma knife radiosurgery (GKRS). PATIENTS AND METHODS A total of 62 consecutive patients with typical trigeminal neuralgia were treated with GKRS between 1998 and 2004. Of the 62 patients, 2 were lost to follow-up; the remaining 60 patients were followed for >12 months. The mean prescribed maximal dose was 79.7 Gy (range, 75-80), using a 4-mm shot. RESULTS Of the 60 patients, 48 were followed for >4 years. An additional 3 patients, followed for <4 years, experienced recurrent pain after a favorable initial response and were incorporated into the long-term response analysis. Of these 51 patients (mean age, 61 +/- 11 years; 37 women [72.5%]; and mean follow-up duration, 58 +/- 14 months), 46 (90.2%) responded to GKRS, as demonstrated by an improvement in their Barrow Neurological Institute pain intensity score. Of the 46 patients, 24 (52.2%) had pain recurrence. The actuarial recurrence-free survival rate was 84.8%, 76.1%, 69.6%, 63.0%, and 45.8% at 1, 2, 3, 4, and 5 years after radiosurgery, respectively. Patient age >70 years correlated with a favorable outcome in terms of pain recurrence after radiosurgery (hazard ratio, 0.125; 95% confidence interval, 0.016-0.975; p = .047) on multivariate analysis. CONCLUSION GKRS seems to be an effective treatment modality for patients with typical trigeminal neuralgia considering the initial response rate; however, fewer than one-half of patients might continue to benefit from GKRS after long-term follow-up. Elderly patients might be good candidates for radiosurgery considering the long-term durability of efficacy.

Survival benefit of levetiracetam in patients treated with concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma multiforme.

A chemosensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O‐6 methylguanine‐DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. The objective of this study was to assess the survival benefit of LEV compared with other antiepileptic drugs as a chemosensitizer to temozolomide for patients with glioblastoma.

Methylation status of the MGMT gene promoter fails to predict the clinical outcome of glioblastoma patients treated with ACNU plus cisplatin.

We analyzed the methylation status of the O6‐methylguanine‐DNA methyltransferase (MGMT) promoter using a methylation‐specific polymerase chain reaction (MSP) in glioblastoma patients treated with 1‐(4‐amino‐2‐methyl‐5‐pyrimidinyl)methyl‐3‐(2‐chloroethyl)‐3‐nitrosourea (ACNU) plus cisplatin followed by radiation therapy. Forty‐eight patients with interpretable MSP results were included in this study. The MGMT promoter was methylated in 26 patients (54.2%, methylated group) and unmethylated in 22 patients (45.8%, unmethylated group). Comparison of clinical outcomes between the two groups revealed that the methylation status of the MGMT gene promoter was not a prognostic factor for overall survival (P = 0.516) or a predictive factor for radiological response to ACNU plus cisplatin treatment (P = 0.529). The most noteworthy explanation for the result is that the synergistic antitumor effects of ACNU and cisplatin resulting from inactivation of MGMT by cisplatin in MGMT active tumors offset the drug resistance.

A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma

BACKGROUND To determine the benefit of surgical management in recurrent glioblastoma, we analyzed a series of patients with recurrent glioblastoma who had undergone surgery, and we devised a new scale to predict their survival. METHODS Clinical data from 55 consecutive patients with recurrent glioblastoma were evaluated after surgical management. Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were used to identify prognostic variables for the development of a predictive scale. After the multivariate analysis, performance status (P = .078) and ependymal involvement (P = .025) were selected for inclusion in the new prognostic scale. The devised scale was validated with a separate set of 96 patients from 3 different institutes. RESULTS A 3-tier scale (scoring range, 0-2 points) composed of additive scores for the Karnofsky performance status (KPS) (0 for KPS ≥ 70 and 1 for KPS < 70) and ependymal involvement (0 for no enhancement and 1 for enhancement of the ventricle wall in the magnetic resonance imaging) significantly distinguished groups with good (0 points; median survival, 18.0 months), intermediate (1 point; median survival, 10.0 months), and poor prognoses (2 points; median survival, 4.0 months). The new scale was successfully applied to the validation cohort of patients showing distinct prognosis among the groups (median survivals of 11.0, 9.0, and 4.0 months for the 0-, 1-, and 2-point groups, respectively). CONCLUSIONS We developed a practical scale to facilitate deciding whether to proceed with surgical management in patients with recurrent glioblastoma. This scale was useful for the diagnosis of prognostic groups and can be used to develop guidelines for patient treatment.

Hearing Outcomes After Stereotactic Radiosurgery for Unilateral Intracanalicular Vestibular Schwannomas: Implication of Transient Volume Expansion

PURPOSE We evaluated the prognostic factors for hearing outcomes after stereotactic radiosurgery (SRS) for unilateral sporadic intracanalicular vestibular schwannomas (IC-VSs) as a clinical homogeneous group of VSs. METHODS AND MATERIALS Sixty consecutive patients with unilateral sporadic IC-VSs, defined as tumors in the internal acoustic canal, and serviceable hearing (Gardner-Roberson grade 1 or 2) were treated with SRS as an initial treatment. The mean tumor volume was 0.34±0.03 cm3 (range, 0.03-1.00 cm3), and the mean marginal dose was 12.2±0.1 Gy (range, 11.5-13.0 Gy). The median follow-up duration was 62 months (range, 36-141 months). RESULTS The actuarial rates of serviceable hearing preservation were 70%, 63%, and 55% at 1, 2, and 5 years after SRS, respectively. In multivariate analysis, transient volume expansion of ≥20% from initial tumor size was a statistically significant risk factor for loss of serviceable hearing and hearing deterioration (increase of pure tone average≥20 dB) (odds ratio=7.638; 95% confidence interval, 2.317-25.181; P=.001 and odds ratio=3.507; 95% confidence interval, 1.228-10.018; P=.019, respectively). The cochlear radiation dose did not reach statistical significance. CONCLUSIONS Transient volume expansion after SRS for VSs seems to be correlated with hearing deterioration when defined properly in a clinically homogeneous group of patients.