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Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway

  • Xu, Hong-Lin;Chen, Guang-Hong;Wu, Yu-Ting;Xie, Ling-Peng;Tan, Zhang-Bin;Liu, Bin;Fan, Hui-Jie;Chen, Hong-Mei;Huang, Gui-Qiong;Liu, Min;Zhou, Ying-Chun
    • Journal of Ginseng Research
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    • v.46 no.1
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    • pp.156-166
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    • 2022
  • Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescencelabeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/ MD2 complex and GRo (KD value of 1.16 × 10-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

Prediction of Decompensation and Death in Advanced Chronic Liver Disease Using Deep Learning Analysis of Gadoxetic Acid-Enhanced MRI

  • Subin Heo;Seung Soo Lee;So Yeon Kim;Young-Suk Lim;Hyo Jung Park;Jee Seok Yoon;Heung-Il Suk;Yu Sub Sung;Bumwoo Park;Ji Sung Lee
    • Korean Journal of Radiology
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    • v.23 no.12
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    • pp.1269-1280
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    • 2022
  • Objective: This study aimed to evaluate the usefulness of quantitative indices obtained from deep learning analysis of gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and their longitudinal changes in predicting decompensation and death in patients with advanced chronic liver disease (ACLD). Materials and Methods: We included patients who underwent baseline and 1-year follow-up MRI from a prospective cohort that underwent gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance between November 2011 and August 2012 at a tertiary medical center. Baseline liver condition was categorized as non-ACLD, compensated ACLD, and decompensated ACLD. The liver-to-spleen signal intensity ratio (LS-SIR) and liver-to-spleen volume ratio (LS-VR) were automatically measured on the HBP images using a deep learning algorithm, and their percentage changes at the 1-year follow-up (ΔLS-SIR and ΔLS-VR) were calculated. The associations of the MRI indices with hepatic decompensation and a composite endpoint of liver-related death or transplantation were evaluated using a competing risk analysis with multivariable Fine and Gray regression models, including baseline parameters alone and both baseline and follow-up parameters. Results: Our study included 280 patients (153 male; mean age ± standard deviation, 57 ± 7.95 years) with non-ACLD, compensated ACLD, and decompensated ACLD in 32, 186, and 62 patients, respectively. Patients were followed for 11-117 months (median, 104 months). In patients with compensated ACLD, baseline LS-SIR (sub-distribution hazard ratio [sHR], 0.81; p = 0.034) and LS-VR (sHR, 0.71; p = 0.01) were independently associated with hepatic decompensation. The ΔLS-VR (sHR, 0.54; p = 0.002) was predictive of hepatic decompensation after adjusting for baseline variables. ΔLS-VR was an independent predictor of liver-related death or transplantation in patients with compensated ACLD (sHR, 0.46; p = 0.026) and decompensated ACLD (sHR, 0.61; p = 0.023). Conclusion: MRI indices automatically derived from the deep learning analysis of gadoxetic acid-enhanced HBP MRI can be used as prognostic markers in patients with ACLD.

Optimization of the Flip Angle and Scan Timing in Hepatobiliary Phase Imaging Using T1-Weighted, CAIPIRINHA GRE Imaging

  • Kim, Jeongjae;Kim, Bong Soo;Lee, Jeong Sub;Woo, Seung Tae;Choi, Guk Myung;Kim, Seung Hyoung;Lee, Ho Kyu;Lee, Mu Sook;Lee, Kyung Ryeol;Park, Joon Hyuk
    • Investigative Magnetic Resonance Imaging
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    • v.22 no.1
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    • pp.1-9
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    • 2018
  • Purpose: This study was designed to optimize the flip angle (FA) and scan timing of the hepatobiliary phase (HBP) using the 3D T1-weighted, gradient-echo (GRE) imaging with controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) technique on gadoxetic acid-enhanced 3T liver MR imaging. Materials and Methods: Sixty-two patients who underwent gadoxetic acid-enhanced 3T liver MR imaging were included in this study. Four 3D T1-weighted GRE imaging studies using the CAIPIRINHA technique and FAs of $9^{\circ}$ and $13^{\circ}$ were acquired during HBP at 15 and 20 min after intravenous injection of gadoxetic acid. Two abdominal radiologists, who were blinded to the FA and the timing of image acquisition, assessed the sharpness of liver edge, hepatic vessel clarity, lesion conspicuity, artifact severity, and overall image quality using a five-point scale. Quantitative analysis was performed by another radiologist to estimate the relative liver enhancement (RLE) and the signal-to-noise ratio (SNR). Statistical analyses were performed using the Wilcoxon signed rank test and one-way analysis of variance. Results: The scores of the HBP with an FA of $13^{\circ}$ during the same delayed time were significantly higher than those of the HBP with an FA of $9^{\circ}$ in all the assessment items (P < 0.01). In terms of the delay time, images at the same FA obtained with a 20-min-HBP showed better quality than those obtained with a 15-min-HBP. There was no significant difference in qualitative scores between the 20-min-HBP and the 15-min-HBP images in the non-liver cirrhosis (LC) group except for the hepatic vessel clarity score with $9^{\circ}$ FA. In the quantitative analysis, a statistically significant difference was found in the degree of RLE in the four HBP images (P = 0.012). However, in the subgroup analysis, no significant difference in RLE was found in the four HBP images in either the LC or the non-LC groups. The SNR did not differ significantly in the four HBP images. In the subgroup analysis, 20-min-HBP imaging with a $13^{\circ}$ FA showed the highest SNR value in the LC-group, whereas 15-min-HBP imaging with a $13^{\circ}$ FA showed the best value of SNR in the non-LC group. Conclusion: The use of a moderately high FA improves the image quality and lesion conspicuity on 3D, T1-weighted GRE imaging using the CAIPIRINHA technique on gadoxetic acid, 3T liver MR imaging. In patients with normal liver function, the 15-min-HBP with a $13^{\circ}$ FA represents a feasible option without a significant decrease in image quality.

Evaluation between 3.0 T vs 1.5 T MRI in Detection of Brain Metastasis using Double Dose Gd-DTPA (뇌전이 종양의 발견에 있어서 Doble dose Gd-DTPA를 이용한 3 T MRI와 1.5 T MRI간의 비교연구)

  • Chung, Woo-Suk;Kim, Hyung-Jung;Ahn, Chul-Min;Lee, Jae-Hoon;Hur, Jin;Cho, Eung-Hyuck;Chung, Tae-Sub
    • Investigative Magnetic Resonance Imaging
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    • v.9 no.2
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    • pp.101-108
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    • 2005
  • Purpose : Early detection of small brain metastases is important. The purpose of this study was to compare the detectability of brain metastases according to the size between 1.5 T and 3.0 T MRI. Materials and Methods : We reviewed 162 patients with primary lung cancer who were examined for TNM staging. After administration of double dose of Gd-DTPA, MR imaging was performed with SPGR by 3.0 T MRI and then with T1 SE sequence by 1.5 T MRI. In each patient, three readers performed qualitative assessment. Sensitivity, positive predictive value, and diagnostic accuracy were calculated in 3.0 T and 1.5 T MRI according to size. Using the signal intensity (SI) measurements between the metastatic nodules and adjacent tissue, nodule-to-adjacent tissue SI ratio was calculated. Results : Thirty-one of 162 patients had apparent metastatic nodules in the brain at either 1.5 T or 3.0 T MR imaging. 143 nodules were detected in 3.0 T MRI, whereas 137 nodules were detected at 1.5 T MRI. Six nodules, only detected in 3.0 T MRI, were smaller than 3.0 mm in dimension. Sensitivity, positive predictive value, and diagnostic accuracy in 3.0 T MRI were 100 %, 100 %, and 100 % respectively, and in 1.5 T MRI were 95.8%, 88.3%, and 85.1% respectively. SI ratio was significantly higher in the 3.0 T MRI than 1.5 T MRI (p=0.025). Conclusion : True positive rate of 3.0 T MRI with Gd-DTPA was superior to 1.5 T MRI with Gd-DTPA in detection of metastatic nodules smaller than 3.0 mm.

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Surface characteristics and stability of implants treated with alkali and heat (알칼리와 열처리에 의한 임플란트의 표면 특성 및 골유착 안정성에 관한 연구)

  • Song, Yun-Seok;Cho, In-Ho
    • The Journal of Korean Academy of Prosthodontics
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    • v.46 no.5
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    • pp.490-499
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    • 2008
  • Statement of problem: Bioactive materials must have the ability to spontaneously form a bone like apatite layer on their surface and induce direct biochemical bonding to bone. A simple chemical treatment via alkali and heat has been revealed to induce bioactivity in titanium. Purpose: The purpose of this study was to evaluate the surface characteristics and stability of alkali and heat treated implants. Material and methods: Specimens were divided into three groups; group 1 was the control group with machined surface implants, groups 2 and 3 were treated with alkali solutions and heat treated in the atmosphere and vacuum conditions respectively. The surface characteristics were observed with FESEM, XPS, TF-XRD and AFM. Stability was evaluated with the resonance frequency analysis, periotest and removal torque values. One-way ANOVA and Duncan test were used for statistical analysis. Results: 1. Groups treated with alkali and heat showed similar characteristics. Groups 2 and 3 showed high compositions of Na ions on the surface with sub-micron sized pores compared to group 1. Group 2 showed mixed compositions of anatase and rutile with superior contents of rutile. 2. Resonance frequency analysis : The ISQ of group 2 showed significantly higher values than that of groups 1 and 3 at 12 weeks. The ISQ of groups 1 and 2 showed significant increase after 4 weeks, and the ISQ of group 3 increased significantly after 2 and 4 weeks respectively (P < .05). 3. Periotest: The PTV of groups 1 and 2 showed significant decrease after 4 weeks, and the PTV of group 3 showed significant decrease after 2 and 4 weeks respectively (P < .05). 4. Removal torque analysis: The removal torque value of group 2 was significantly higher than those of groups 1 and 3 at 2, 4 and 8 weeks. The removal torque values of groups 1 and 3 showed increase at 4 and 12 weeks, but the removal torque value of group 2 showed increase after 4 weeks (P < .05). Conclusion: An oxide layer with appropriate crystal structure and amorphous sodium titanate layer can be obtained on titanium implants through alkali and heat treatment in the atmosphere, and even alkali and heat treatment in vacuum conditions, provided a bioactive surface containing sodium. These surface layers can be considered to be effective for enhancement of osseointegration and reduction of healing period for implant treatment.

Usefulness of Acoustic Noise Reduction in Brain MRI Using Quiet-T2 (뇌 자기공명영상에서 Quiet-T2 기법을 이용한 소음감소의 유용성)

  • Lee, SeJy;Kim, Young-Keun
    • Journal of radiological science and technology
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    • v.39 no.1
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    • pp.51-57
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    • 2016
  • Acoustic noise during magnetic resonance imaging (MRI) is the main source for patient discomfort. we report our preliminary experience with this technique in neuroimaging with regard to subjective and objective noise levels and image quality. 60 patients(29 males, 31 females, average age of 60.1) underwent routine brain MRI with 3.0 Tesla (MAGNETOM Tim Trio; Siemens, Germany) system and 12-channel head coil. Q-$T_2$ and $T_2$ sequence were performed. Measurement of sound pressure levels (SPL) and heart rate on Q-$T_2$ and $T_2$ was performed respectively. Quantitative analysis was carried out by measuring the SNR, CNR, and SIR values of Q-$T_2$, $T_2$ and a statistical analysis was performed using independent sample T-test. Qualitative analysis was evaluated by the eyes for the overall quality image of Q-$T_2$ and $T_2$. A 5-point evaluation scale was used, including excellent(5), good(4), fair(3), poor(2), and unacceptable(1). The average noise and peak noise decreased by $15dB_A$ and $10dB_A$ on $T_2$ and Q-$T_2$ test. Also, the average value of heartbeat rate was lower in Q-$T_2$ for 120 seconds in each test, but there was no statistical significance. The quantitative analysis showed that there was no significant difference between CNR and SIR, and there was a significant difference (p<0.05) as SNR had a lower average value on Q-$T_2$. According to the qualitative analysis, the overall quality image of 59 case $T_2$ and Q-$T_2$ was evaluated as excellent at 5 points, and 1 case was evaluated as good at 4 points due to a motion artifact. Q-$T_2$ is a promising technique for acoustic noise reduction and improved patient comfort.

The Comparison of Susceptibility Changes in 1.5T and3.0T MRIs due to TE Change in Functional MRI (뇌 기능영상에서의 TE값의 변화에 따른 1.5T와 3.0T MRI의 자화율 변화 비교)

  • Kim, Tae;Choe, Bo-Young;Kim, Euy-Neyng;Suh, Tae-Suk;Lee, Heung-Kyu;Shinn, Kyung-Sub
    • Investigative Magnetic Resonance Imaging
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    • v.3 no.2
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    • pp.154-158
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    • 1999
  • Purpose : The purpose of this study was to find the optimum TE value for enhancing $T_2^{*}$ weighting effect and minimizing the SNR degradation and to compare the BOLD effects according to the changes of TE in 1.5T and 3.0T MRI systems. Materials and Methods : Healthy normal volunteers (eight males and two females with 24-38 years old) participated in this study. Each volunteer was asked to perform a simple finger-tapping task (sequential opposition of thumb to each of the other four fingers) with right hand with a mean frequency of about 2Hz. The stimulus was initially off for 3 images and was then alternatively switched on and off for 2 cycles of 6 images. Images were acquired on the 1.5T and 3.0T MRI with the FLASH (fast low angle shot) pulse sequence (TR : 100ms, FA : $20^{\circ}$, FOV : 230mm) that was used with 26, 36, 46, 56, 66, 76ms of TE times in 1.5T and 16, 26, 36, 46, 56, 66ms of TE in 3.0T MRI system. After the completion of scan, MR images were transferred into a PC and processed with a home-made analysis program based on the correlation coefficient method with the threshold value of 0.45. To search for the optimum TE value in fMRI, the difference between the activation and the rest by the susceptibility change for each TE was used in 1.5T and 3.0T respectively. In addition, the functional $T_2^{*}$ map was calculated to quantify susceptibility change. Results : The calculated optimum TE for fMRI was $61.89{\pm}2.68$ at 1.5T and $47.64{\pm}13.34$ at 3.0T. The maximum percentage of signal intensity change due to the susceptibility effect inactivation region was 3.36% at TE 66ms in 1.5T 10.05% at TE 46ms in 3.0T, respectively. The signal intensity change of 3.0T was about 3 times bigger than of 1.5T. The calculated optimum TE value was consistent with TE values which were obtained from the maximum signal change for each TE. Conclusion : In this study, the 3.0T MRI was clearly more sensitive, about three times bigger than the 1.5T in detecting the susceptibility due to the deoxyhemoglobin level change in the functional MR imaging. So the 3.0T fMRI I ore useful than 1.5T.

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The Comparison between Single Shot Turbo Spin Echo and B-FFE (Balanced Turbo Field-echo) in the Differentiation of Focal Liver Lesions (국소 간병변 감별에서 단발고속스핀에코 기법과 균형항정상 태세차를 이용한 고속영역 기법간의 비교)

  • Kim, Young-Chul;Kim, Myeong-Jin;Cha, Seung-Whan;Chung, Yong-Eun;Han, Kwang-Hyup;Choi, Jin-Sub
    • Investigative Magnetic Resonance Imaging
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    • v.11 no.1
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    • pp.39-48
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    • 2007
  • Purpose : To determine the diagnostic accuracy of four different sequences : moderately T2 weighted, two heavily T2-weighted single shot turbo spin-echo sequence and breath-hold axial-2D balanced turbo field-echo sequence(bFFE) for characterization of focal lesions. Materials and Methods : During the 3-month period between June and August 2005, seventy-six patients were proved to have ninety-three focal hepatic lesions on MR imaging. The patients consisted of 49 men and 27 women (age range, 15-75 years; mean age, 56.23 years). All MR images were acquired on a 1.5-T MR using the following sequences: 1. A breath-hold axial T2-weighted single shot turbo spin-echo sequence, 2. a breath-hold axial-2D balanced turbo field-echo sequence. Two radiologists performed quantitative analysis. Another radiologist measured the lesion-to-liver contrast-to-noise ratio at the region-of-interest in the four sequences. Results : There was no significant difference in inter-observer variability between the four sequences. The accuracy for both cyst and malignancy of moderate T2 weighted MRI (echo time: 80 msec) was also highest. There was significant difference for lesion characterization between moderate T2 weighted MRI and balanced steady state procession (p-value: 0.004) in the second reader. For longer echo time, the CNR of cystic lesions were markedly increased in comparison to lesions of other component. Conclusion : The accuracy and inter-observer variability of single shot turbo spin echo T2 weighted sequence was higher than bFFE. Although there was no statically significant difference, moderate T2 weighted MRI (echo time: 80 msec) was more accurate than heavily T2 weighted sequence (echo time: 300 msec). If the results for lesion characterization is equivocal in TE 80, the addition of heavily T2 weighted MRI (echo time: 180 msec) can be helpful.

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Optimal Localization through DSA Distortion Correction for SRS

  • Shin, Dong-Hoon;Suh, Tae-Suk;Huh, Soon-Nyung;Son, Byung-Chul;Lee, Hyung-Koo;Choe, Bo-Young;Shinn, Kyung-Sub
    • Progress in Medical Physics
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    • v.11 no.1
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    • pp.39-47
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    • 2000
  • In Stereotactic Radiosurgery (SRS), there are three imaging methods of target localization, such as digital subtraction Angiography (DSA), computed tomography (CT), magnetic resonance imaging (MRI). Especially, DSA and MR images have a distortion effect generated by each modality. In this research, image properties of DSA were studied. A first essential condition in SRS is an accurate information of target locations, since high dose used to treat a patient may give a complication on critical organ and normal tissue. Hut previous localization program did not consider distortion effect which was caused by image intensifier (II) of DSA. A neurosurgeon could not have an accurate information of target locations to operate a patient. In this research, through distortion correction, we tried to calculate accurate target locations. We made a grid phantom to correct distortion, and a target phantom to evaluate localization algorithm. The grid phantom was set on the front of II, and DSA images were obtained. Distortion correction methods consist of two parts: 1. Bilinear transform for geometrical correction and bilinear interpolation for gray level correction. 2. Automatic detection method for calculating locations of grid crosses, fiducial markers, and target balls. Distortion was corrected by applying bilinear transform and bilinear interpolation to anterior-posterior and left-right image, and locations of target and fiducial markers were calculated by the program developed in this study. Localization errors were estimated by comparing target locations calculated in DSA images with absolute locations of target phantom. In the result, the error in average with and without distortion correction is $\pm$0.34 mm and $\pm$0.41 mm respectively. In conclusion, it could be verified that our localization algorithm has an improved accuracy and acceptability to patient treatment.

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Resection and Observation for Brain Metastasis without Prompt Postoperative Radiation Therapy

  • Song, Tae-Wook;Kim, In-Young;Jung, Shin;Jung, Tae-Young;Moon, Kyung-Sub;Jang, Woo-Youl
    • Journal of Korean Neurosurgical Society
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    • v.60 no.6
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    • pp.667-675
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    • 2017
  • 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.