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Taek-Hyun Kwon, Youn-Kwan Park, Dong-Jun Lim, Tai-Hyoung Cho, Yong-Gu Chung, Hung-Seob Chung, and Jung-Keun Suh

Object. A wide variation in postoperative drainage volumes is observed during treatment of chronic subdural hematoma (CSDH) with twist-drill or burr-hole craniostomy and closed-system drainage. In this study the authors investigate the causes of the variation, the clinical significance thereof, and its influence on treatment outcome.

Methods. A total of 175 cases were investigated between January 1991 and December 1997. Of these, 145 patients had surgery for CSDH, of whom 30 had bilateral lesions. The cases of CSDH were divided into five subtypes (low-density, isodense, high-density, mixed-density, and layering types) on the basis of the brain computerized tomography (CT) findings. Burr-hole craniostomies with closed-system drainage were performed in all patients and the drainage was maintained for 5 days, during which daily amounts of fluid were measured. The mean drainage volume over 5 days was 320 ml, with the largest volume (413 ml) seen in the low-density type and the smallest (151 ml) in the mixed-density type of CSDH. There were recurrences in six patients (seven instances, 4%). The mixed-density type had the highest recurrence rate (8.6%), whereas there was no recurrence for the low-density type. There were no recurrences in 81 patients in whom the total drainage volumes for 5 days were more than 200 ml, but there were recurrences in six (seven instances) of 94 patients in whom the total drainage volume was less than 200 ml.

Conclusions. The postoperative drainage volumes varied greatly because of differences in the outer membrane permeability of CSDH, and such variation seems to be related to the findings on the CT scans obtained preoperatively. Patients with CSDH in whom there is less postoperative drainage than expected should be carefully observed, with special attention paid to the possibility of recurrence.

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Jin Wook Kim, Hee-Won Jung, Yong Hwy Kim, Chul-Kee Park, Hyun-Tai Chung, Sun Ha Paek, Dong Gyu Kim, and Sang Hyung Lee

OBJECTIVE

A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution.

METHODS

Ninety-two patients with petroclival meningiomas were treated surgically at the authors’ institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1–368 months) and 105 months (range 1–348 months), respectively.

RESULTS

A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively.

CONCLUSIONS

The authors’ preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.

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Sung Kwon Kim, Dong Gyu Kim, Young-Bem Se, Jin Wook Kim, Yong Hwy Kim, Hyun-Tai Chung, and Sun Ha Paek

OBJECTIVE

Gamma Knife surgery (GKS) represents an alternative treatment for patients with tumor-related trigeminal neuralgia (TRTN). However, in previous studies, the primary GKS target was limited to mass lesions. The authors evaluated whether GKS could target both the tumor and the trigeminal root exit zone (REZ) in a single session while providing durable pain relief and minimizing radiation dose–related complications for TRTN patients.

METHODS

The authors' institutional review board approved the retrospective analysis of data from 15 consecutive patients (6 men and 9 women, median age 67 years, range 45–79 years) with TRTN who had undergone GKS. In all cases, the radiation was delivered in a single session targeting both the tumor and trigeminal REZ. The authors assessed the clinical outcomes, including the extent of pain relief, durability of the treatment response, and complications. Radiation doses to organs at risk (OARs), including the brainstem and the cranial nerve VII–VIII complex, were analyzed as doses received by 2% or 50% of the tissue volume and the tissue volume covered by a dose of 12 Gy (V12Gy).

RESULTS

The median length of clinical follow-up was 38 months (range 12–78 months). Pain relief with GKS was initially achieved in 14 patients (93.3%) and at the last follow-up in 13 patients (86.7%). The actuarial recurrence-free survival rates were 93%, 83%, and 69% at 1, 3, and 5 years after GKS, respectively. Persistent facial numbness was observed in 3 patients (20.0%). There were no complications such as facial weakness, altered taste function, hearing impairment, and balance difficulties indicating impaired function of the cranial nerve VII–VIII complex. The V12Gy in the brainstem was less than or equal to 0.24 cm3 in all patients. There were no significant differences in any OAR values in the brainstem between patients with and without facial numbness after GKS.

CONCLUSIONS

The strategy of performing GKS for both tumor and trigeminal REZ in a single session is a safe and effective radiosurgical approach that achieves durable pain control for TRTN patients.

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Ji Hoon Phi, Sun Ha Paek, Hyun-Tai Chung, Sang Soon Jeong, Chul-Kee Park, Hee-Won Jung, and Dong Gyu Kim

Object

The current study was undertaken to evaluate the tumor control rate and functional outcome after Gamma Knife surgery (GKS) in patients with a trigeminal schwannoma. The conditions associated with the development of cranial neuropathies after radiosurgery were scrutinized.

Methods

The authors reviewed the clinical records and radiological data in 22 consecutive patients who received GKS for a trigeminal schwannoma. The median tumor volume was 4.1 ml (0.2–12.0 ml), and the mean tumor margin dose was 13.3 ± 1.3 Gy at an isodose line of 49.9 ± 0.6% (mean ± standard deviation). The median clinical follow-up period was 46 months (range 24–89 months), and the median length of imaging follow-up was 37 months (range 24–79 months).

Results

Tumor growth control was achieved in 21 (95%) of the 22 patients. Facial pain responded best to radio-surgery, with two thirds of patients showing improvement. However, only one third of patients with facial hypesthesia improved. Six patients (27%) experienced new or worsening cranial neuropathies after GKS. Ten patients (46%) showed tumor expansion after radiosurgery, and nine of these also showed central enhancement loss. Loss of central enhancement, tumor expansion, and a tumor in a cavernous sinus were found to be significantly related to the emergence of cranial neuropathies.

Conclusions

The use of GKS to treat trigeminal schwannoma resulted in a high rate of tumor control and functional improvement. Cranial neuropathies are bothersome complications of radiosurgery, and tumor expansion in a cavernous sinus after radiosurgery appears to be the proximate cause of the complication. Loss of central enhancement could be used as a warning sign of cranial neuropathies, and for this vigilant patient monitoring is required.

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Jung Ho Han, Dong Gyu Kim, Hyun-Tai Chung, Chul-Kee Park, Sun Ha Paek, Jeong Eun Kim, Hee-Won Jung, and Dae Hee Han

Object

In this paper the authors analyzed the clinical and neuroimaging outcomes of patients with cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS), focusing on the analysis of the radiation injury rate depending on the AVM volume.

Methods

Between 1997 and 2004, 277 consecutive patients with cerebral AVMs were treated with GKS. Of these patients, 218 were followed up for ≥ 2 years. The mean age was 31 ± 15 years, the median AVM volume was 3.4 cm3 (range 0.17–35.2 cm3), the median marginal dose was 18.0 Gy (range 10.0–25.0 Gy), and the mean follow-up duration was 44 ± 20 months. The authors reduced the prescription dose by various amounts, depending on the AVM volume and location as prescribed in the classic guideline to avoid irreversible radiation injuries.

Results

The angiographic obliteration rate was 66.4% overall, and it was 81.7, 53.1, and 12.5% for small, medium, and large AVMs, respectively. The overall annual bleeding rate was 1.9%. The annual bleeding rate was 0.44 and 4.64% for small and large AVMs, respectively. Approximately 20% of the patients showed severe postradiosurgery imaging (PRI) changes. The rate of PRI change was 11.4, 33.3, and 9.5% for small, medium, and large AVM volume groups, respectively, and a permanent radiation injury developed in 5.1% of patients.

Conclusions

By using the reduced dose from what is usually prescribed, the authors were able to obtain outcomes in small AVMs that were comparable to the outcomes described in previous reports. However, medium AVMs appear to still be at risk for adverse radiation effects. Last, in large AVMs, the authors were able to attain a tolerable rate of radiation injury; however, the clinical outcomes were quite disappointing following administration of a reduced dose of GKS for large AVMs.

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Dong Gyu Kim, Chi Heon Kim, Hyun-Tai Chung, Sun Ha Paek, Sang Soon Jeong, Dae Hee Han, and Hee-Won Jung

Object. The authors analyzed tumor control rates and complications in patients with superficially located meningiomas after gamma knife surgery (GKS).

Methods. Between 1998 and 2003, GKS was performed in 23 patients with 26 lesions in whom follow-up imaging for 1 year or more was available. The male/female ratio was 1:22. The mean age was 59 years. The median tumor volume was 4.7 cm3, and the mean margin dose was 16 Gy at the 50% isodose line. Peritumoral edema was revealed on magnetic resonance (MR) imaging in four patients before GKS. Magnetic resonance imaging and clinical examinations were performed every 6 months after GKS. The mean follow-up duration was 32 months.

The tumor shrank in eight cases, was stable in 17, and enlarged in one; thus 25 (95%) of 26 tumors were controlled. A peritumoral high signal on T2-weighted MR images was found in eight lesions and preexisting edema was aggravated in three lesions after GKS. Ten of these 11 patients complained of severe headache, and three patients experienced neurological deficits at the same time after a mean latency of 3 months; however, high signal was not demonstrated on imaging before 6 months on average. Steroid agents, when required, gave relief to all patients. The complication rate was 43% (10 of 23 cases). High signal disappeared in nine patients and decreased in the remaining two. High signal was associated with a high integral dose and a large tumor volume. Tumor shrinkage at the last follow-up examination was more prominent in the patients with symptomatic high signal (p = 0.03).

Conclusions. There was a good tumor control rate with a high complication rate. Longer follow up of more patients is needed. Adjusting the dose—volume relationship should be considered to reduce complications.

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Ben A. Strickland, Michelle Wedemeyer, Saman Sizdahkhani, and Steven L. Giannotta

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Dong Gyu Kim, Hyun-Tai Chung, Ho-Shin Gwak, Sun Ha Paek, Hee-Won Jung, and Dae Hee Han

Object. The authors conducted an analysis of prognostic factors for patient survival and local control of brain metastases after gamma knife radiosurgery.

Methods. In the survival analysis, 53 consecutive patients with 121 lesions treated in the last 2 years were examined. Common primary sites were lung (26 patients), kidney (seven), breast (three), and colon (three). Patient age ranged from 28 to 75 years (median 58 years) and the female/male ratio was 1:0.9. The median tumor volume was 2.1 cm3 (range 0.02–45.5cm3) and the average prescription dose was 15.4 Gy to the 50% isodose. The median follow up was 12 months (range 1–23 months) and the median survival was 46 weeks.

Six-month and 1-year survival rates were 63% and 39%, respectively. Karnofsky Performance Scale score, tumor volume, and presence of extracranial disease were statistically significant prognostic factors (p < 0.05) for survival in multivariate analysis. Number of lesions, patient age, and adjuvant whole-brain radiation therapy were not statistically significant. Ninety-one of 121 lesions with follow-up images were included in the local control analysis. The 1-year actuarial local control rate was 48%. In multivariate analysis smaller volume was associated with better control (p = 0.0043), and, control period of renal cell carcinoma was shorter than that of the other tumor types (p = 0.0070).

Conclusions. Karnofsky Performance Scale score, tumor volume, controlled primary cancer, and absence of extracranial metastases were associated with longer survival in the present study. For local control, tumor volume was a statistically significant factor.

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Seung-Ki Kim, Kyu-Chang Wang, Byung-Kyu Cho, Hyun-Tai Chung, Young-Yim Kim, Su-Young Lim, Choon-Taek Lee, and Hyun Jib Kim

Object. Multiple gene replacements have been examined as a potential treatment modality for malignant gliomas. Nevertheless, no reports are available that detail the synergy, additivity, or antagonism of multiple genes. The aim of this study was to assess the interaction between p53 and p16 genes in the growth of glioma cell lines.

Methods. The human glioma cell lines U87MG and U373MG were transduced using an adenoviral vector with Ad-p53, Ad-p16, or both. Western blotting was performed to determine the expression of the protein products of the transduced p53 and p16 genes. To establish whether the combination of Ad-p53 and Ad-p16 would be beneficial, the effects of gene combinations at the median inhibitory concentration level were analyzed using the isobologram method. Annexin assays and cell cycle analyses were performed on the transduced cells. Western blotting demonstrated the expression of p53 and p16 in transduced cells. Simultaneous exposure to Ad-p53 and Ad-p16 produced additive effects in both glioma cell lines. Experimental data points in U373MG lay near the Mode I line, indicating that the vectors had a different mode of action. The restoration of normal p53-encoded protein in the mutant cell lines induced apoptosis, whereas in the wild-type p53 cell lines, the overexpression of wild-type p53 resulted in a moderate degree of apoptosis and G1 arrest. Furthermore, Ad-p16 induced more marked G1 arrest than Ad-p53 in cells with wild-type p53.

Conclusions. The results show that interaction between Ad-p53 and Ad-p16 is additive, regardless of p53 gene status.

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Jin Pyeong Jeon, Jeong Eun Kim, Jun Hyong Ahn, Won-Sang Cho, Young Dae Cho, Young-Je Son, Jae Seung Bang, Hyun-Seung Kang, Chul-Ho Sohn, Hyun-Tai Chung, Chang Wan Oh, and Dong Gyu Kim

OBJECT

Treatment strategies for venous-predominant arteriovenous malformation (vp-AVM) remain unclear due to the limited number of cases and a lack of long-term outcomes. The purpose of this study was to report the authors’ experience with treatment outcomes with a review of the pertinent literature in patients with vp-AVM.

METHODS

Medical and radiological data from 1998 to 2011 were retrospectively evaluated. The degree of the arteriovenous (AV) shunt was categorized into 2 groups, a high- and low-flow AV shunt based on the angiographic findings.

RESULTS

Sixteen patients with a mean age of 45.3 years (range 16–78 years) and a mean follow-up of 79.9 months (range 25–264 months) were examined. Symptomatic lesions were noted in 13 patients: intracranial hemorrhage (ICH) in 9, seizure in 1, and headache in 3. A high-flow shunt was observed on angiography in 13 patients. Among these 13 patients, 12 patients were symptomatic. Nine patients presenting with ICH underwent hematoma removal with additional Gamma Knife surgery (GKS; n = 4), GKS only (n = 2), or conservative treatment (n = 3). The 3 asymptomatic patients received conservative treatment, and 1 rebleeding episode was observed. Seven of 8 patients who underwent GKS as an initial or secondary treatment modality experienced a marked reduction in the AV shunt on follow-up angiography, but complete obliteration was not observed.

CONCLUSIONS

Poor lesion localization makes a vp-AVM challenging to treat. Symptomatic patients with a high-flow shunt are supposedly best treated with GKS, despite the fact that only 87.5% of the vp-AVMs treated this way showed a reduction in the malformation volume, and none were cured.