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Kyung Hwan Kim, So Jeong Kang, Jung-Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

This study aimed to verify the effect of proactive Gamma Knife surgery (GKS) in the treatment of asymptomatic meningioma compared with the natural course without any therapeutic intervention.

METHODS

From January 2006 to May 2017, 354 patients newly diagnosed with asymptomatic meningioma were reviewed and categorized into GKS (n = 153) and observation (n = 201) groups. Clinical and radiological progression rates were examined, and changes in volume were analyzed.

RESULTS

Clinical progression (i.e., clinician-judged progression), combining symptomatic progression (n = 43) and clinician-judged increase in size using images routinely acquired (n = 34), occurred in 4 patients (2.6%) and 73 patients (36.3%) in the GKS and observation groups, respectively (p < 0.001). The clinical progression-free survival (PFS) rates in the GKS and observation groups were 98.7% and 64.6%, respectively, at 5 years (p < 0.001), and 92.9% and 42.7%, respectively, at 10 years (p < 0.001). The radiological tumor control rate was 94.1% in the GKS group, and radiological progression was noted in 141 patients (70.1%) in the observation group. The radiological PFS rates in the GKS and observation groups were 94.4% and 38.5%, respectively, at 5 years (p < 0.001), and 88.5% and 7.9%, respectively, at 10 years (p < 0.001). Young age, absence of calcification, peritumoral edema, and high T2 signal intensity were correlated with clinical progression in the observation group. Volumetric analysis showed that untreated tumors gradually increased in size. However, GKS-treated tumors shrank gradually, although transient volume expansion was observed in the first 6 months. Adverse events developed in 26 of the 195 GKS-treated patients (13.3%), including 1 (0.5%) major event requiring microsurgery due to severe edema after GKS. Peritumoral edema was related to the development of adverse events (p = 0.004).

CONCLUSIONS

Asymptomatic meningioma is a benign disease; however, nearly two-thirds of patients experience tumor growth and one-third of untreated patients eventually require neurosurgical interventions during watchful waiting. GKS can control tumors clinically and radiologically with high probability. Although the risk of transient adverse events exists, proactive GKS may be a reasonable treatment option when there are no comorbidities limiting life expectancy.

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Yun-Sik Dho, Young Jae Kim, Kwang Gi Kim, Sung Hwan Hwang, Kyung Hyun Kim, Jin Wook Kim, Yong Hwy Kim, Seung Hong Choi and Chul-Kee Park

OBJECTIVE

The aim of this study was to analyze the positional effect of MRI on the accuracy of neuronavigational localization for posterior fossa (PF) lesions when the operation is performed with the patient in the prone position.

METHODS

Ten patients with PF tumors requiring surgery in the prone position were prospectively enrolled in the study. All patients underwent preoperative navigational MRI in both the supine and prone positions in a single session. Using simultaneous intraoperative registration of the supine and prone navigational MR images, the authors investigated the images’ accuracy, spatial deformity, and source of errors for PF lesions. Accuracy was determined in terms of differences in the ability of the supine and prone MR images to localize 64 test points in the PF by using a neuronavigation system. Spatial deformities were analyzed and visualized by in-house–developed software with a 3D reconstruction function and spatial calculation of the MRI data. To identify the source of differences, the authors investigated the accuracy of fiducial point localization in the supine and prone MR images after taking the surface anatomy and age factors into consideration.

RESULTS

Neuronavigational localization performed using prone MRI was more accurate for PF lesions than routine supine MRI prior to prone position surgery. Prone MRI more accurately localized 93.8% of the tested PF areas than supine MRI. The spatial deformities in the neuronavigation system calculated using the supine MRI tended to move in the posterior-superior direction from the actual anatomical landmarks. The average distance of the spatial differences between the prone and supine MR images was 6.3 mm. The spatial difference had a tendency to increase close to the midline. An older age (> 60 years) and fiducial markers adjacent to the cervical muscles were considered to contribute significantly to the source of differences in the positional effect of neuronavigation (p < 0.001 and p = 0.01, respectively).

CONCLUSIONS

This study demonstrated the superior accuracy of neuronavigational localization with prone-position MRI during prone-position surgery for PF lesions. The authors recommend that the scan position of the neuronavigational MRI be matched with the surgical position for more precise localization.

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Kyung Hwan Kim, Doo-Sik Kong, Kyung Rae Cho, Min Ho Lee, Jung-Won Choi, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM.

METHODS

The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival.

RESULTS

Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5–25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%–29%) in the 9-Gy group, and 37% (95% CI 1%–58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1–51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1–29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups.

CONCLUSIONS

In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

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Min Ho Lee, Kyung Hwan Kim, Kyung Rae Cho, Jung Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife surgery (FGKS) has recently been used to treat large brain metastases. However, little is known about specific volume changes of lesions during the course of treatment. The authors investigated short-term volume changes of metastatic lesions during FGKS.

METHODS

The authors analyzed 33 patients with 40 lesions who underwent FGKS for intracranial metastases of non–small-cell lung cancer (NSCLC; 25 patients with 32 lesions) and breast cancer (8 patients with 8 lesions). FGKS was performed in 3–5 fractions. Baseline MRI was performed before the first fraction. MRI was repeated after 1 or 2 fractions. Adaptive planning was executed based on new images. The median prescription dose was 8 Gy (range 6–10 Gy) with a 50% isodose line.

RESULTS

On follow-up MRI, 18 of 40 lesions (45.0%) showed decreased tumor volumes (TVs). A significant difference was observed between baseline (median 15.8 cm3) and follow-up (median 14.2 cm3) volumes (p < 0.001). A conformity index was significantly decreased when it was assumed that adaptive planning was not implemented, from baseline (mean 0.96) to follow-up (mean 0.90, p < 0.001). The average reduction rate was 1.5% per day. The median follow-up duration was 29.5 weeks (range 9–94 weeks). During the follow-up period, local recurrence occurred in 5 lesions.

CONCLUSIONS

The TV showed changes with a high dose of radiation during the course of FGKS. Volumetric change caused a significant difference in the clinical parameters. It is expected that adaptive planning would be helpful in the case of radiosensitive tumors such as NSCLCs or breast cancer to ensure an adequate dose to the target area and reduce unnecessary exposure of normal tissue to radiation.

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Jinhyung Kim, Sang Baek Ryu, Sung Eun Lee, Jaewoo Shin, Hyun Ho Jung, Sung June Kim, Kyung Hwan Kim and Jin Woo Chang

OBJECT

Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways.

METHODS

Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity.

RESULTS

MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS.

CONCLUSIONS

This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

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Sook Young Sim, Yong Sam Shin, Kyung Gi Cho, Sun Yong Kim, Se Hyuk Kim, Young Hwan Ahn, Soo Han Yoon and Ki Hong Cho

Object

The clinical features of blood blister–like aneurysms (BBAs) that arise at nonbranching sites of the internal carotid artery (ICA) differ from those of saccular aneurysms. In this study, the authors attempt to describe optimal treatments for BBAs, which have yet to be clearly established.

Methods

Ten of 483 patients with aneurysmal subarachnoid hemorrhage who had been seen at the authors’ institution between March 2001 and June 2005 had intraoperatively confirmed BBAs at nonbranching sites of the ICA. All ten patients were women between the ages of 37 and 64 years (mean age 49.3 years); five had a history of hypertension. The BBAs were localized to the right side of the ICA in seven cases. All patients were successfully treated; clipping was undertaken in six, clipping combined with wrapping in three, and trapping in one. These methods were used in conjunction with various other surgical techniques such as brain relaxation by draining cerebrospinal fluid, anterior clinoidectomy, exposing the cervical ICA, gentle subpial dissection (for aneurysms that adhered to the frontal lobe), complete trapping of the ICA before clipping, and protecting the brain. Clip slippage occurred at the end of dural closing in two cases; the aneurysm was completely obliterated using multiple clips combined with ICA stenosis in one of these cases and ICA trapping with good collateral flow in the other. An excellent clinical outcome was achieved in eight patients, whereas two patients were disabled from massive vasospasm. The authors retrospectively reviewed radiological and surgical data in all cases to determine which treatment methods produced a favorable outcome.

Conclusions

Blood blister–like aneurysms located at nonbranching sites of the ICA are difficult to treat. Preoperative awareness and careful consideration of these lesions during surgery can prevent poor clinical outcomes.