1.Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea.
Byung Sup KIM ; Ho Jun SEOL ; Do Hyun NAM ; Chul Kee PARK ; Il Han KIM ; Tae Min KIM ; Jeong Hoon KIM ; Young Hyun CHO ; Sang Min YOON ; Jong Hee CHANG ; Seok Gu KANG ; Eui Hyun KIM ; Chang Ok SUH ; Tae Young JUNG ; Kyung Hwa LEE ; Chae Yong KIM ; In Ah KIM ; Chang Ki HONG ; Heon YOO ; Jin Hee KIM ; Shin Hyuk KANG ; Min Kyu KANG ; Eun Young KIM ; Sun Hwan KIM ; Dong Sup CHUNG ; Sun Chul HWANG ; Joon Ho SONG ; Sung Jin CHO ; Sun Il LEE ; Youn Soo LEE ; Kook Jin AHN ; Se Hoon KIM ; Do Hun LIM ; Ho Shin GWAK ; Se Hoon LEE ; Yong Kil HONG
Cancer Research and Treatment 2017;49(1):193-203
PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.
Biopsy
;
Chemoradiotherapy*
;
Disease-Free Survival
;
Follow-Up Studies
;
Glioblastoma*
;
Humans
;
Korea*
;
Methylation
;
Radiotherapy
;
Retrospective Studies*
;
Survival Rate
2.Gastric Carcinogenesis in the miR-222/221 Transgenic Mouse Model.
Boram CHOI ; Jieun YU ; Tae Su HAN ; Young Kook KIM ; Keun HUR ; Byeong Cheol KANG ; Woo Ho KIM ; Dae Yong KIM ; Hyuk Joon LEE ; V Narry KIM ; Han Kwang YANG
Cancer Research and Treatment 2017;49(1):150-160
PURPOSE: MicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice over-expressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis. MATERIALS AND METHODS: At 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containing N-nitroso-N-methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed. RESULTS: Hyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia. CONCLUSION: These results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.
Adenoma
;
Animals
;
Apoptosis
;
Asian Continental Ancestry Group
;
Carcinogenesis*
;
Cell Proliferation
;
Diagnosis
;
Drinking Water
;
Heterografts
;
Humans
;
Hyperplasia
;
Incidence
;
Mice
;
Mice, Transgenic*
;
MicroRNAs
;
Oncogenes
;
Prognosis
;
Stomach Neoplasms
3.Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma.
Yongjun CHA ; Yu Jung KIM ; Se Hoon LEE ; Tae Min KIM ; Seung Hong CHOI ; Dong Wan KIM ; Chul Kee PARK ; Il Han KIM ; Jee Hyun KIM ; Eunhee KIM ; Byungse CHOI ; Chae Yong KIM ; In Ah KIM ; Dae Seog HEO
Cancer Research and Treatment 2017;49(1):129-140
PURPOSE: Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established. MATERIALS AND METHODS: Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups. RESULTS: Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups. CONCLUSION: In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.
Bevacizumab*
;
Disease Progression
;
Glioblastoma
;
Glioma*
;
Humans
4.A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer.
Ji Guang HAN ; Yong Dong JIANG ; Chun Hui ZHANG ; Yan Mei YANG ; Da PANG ; Yan Ni SONG ; Guo Qiang ZHANG
Annals of Surgical Treatment and Research 2017;92(2):55-66
PURPOSE: Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. METHODS: Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. RESULTS: Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. CONCLUSION: The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls.
Area Under Curve
;
Biomarkers
;
Breast Neoplasms*
;
Breast*
;
Humans
;
MicroRNAs
;
Real-Time Polymerase Chain Reaction
;
Receptors, Progesterone
;
ROC Curve
;
Sensitivity and Specificity
5.Associations between Soluble Receptor for Advanced Glycation End Products (sRAGE) and S100A12 (EN-RAGE) with Mortality in Long-term Hemodialysis Patients.
Eul Sik JUNG ; Wookyung CHUNG ; Ae Jin KIM ; Han RO ; Jae Hyun CHANG ; Hyun Hee LEE ; Ji Yong JUNG
Journal of Korean Medical Science 2017;32(1):54-59
Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612–2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566–1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation.
Biomarkers
;
C-Reactive Protein
;
Cardiovascular Diseases
;
Cohort Studies
;
Comorbidity
;
Glycosylation End Products, Advanced*
;
Humans
;
Incidence
;
Inflammation
;
Mortality*
;
Plasma
;
Prospective Studies
;
Renal Dialysis*
;
Risk Factors
;
S100A12 Protein*
;
Vascular Calcification
6.BRAF-Mutated Colorectal Cancer Exhibits Distinct Clinicopathological Features from Wild-Type BRAF-Expressing Cancer Independent of the Microsatellite Instability Status.
Min Hye JANG ; Sehun KIM ; Dae Yong HWANG ; Wook Youn KIM ; So Dug LIM ; Wan Seop KIM ; Tea Sook HWANG ; Hye Seung HAN
Journal of Korean Medical Science 2017;32(1):38-46
In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.
Colorectal Neoplasms*
;
Humans
;
Incidence
;
Microsatellite Instability*
;
Microsatellite Repeats*
;
Mucins
7.Biomechanical Parameters in Plantar Fasciitis Measured by Gait Analysis System With Pressure Sensor.
Seung Don YOO ; Hee Sang KIM ; Jong Ha LEE ; Dong Hwan YUN ; Dong Hwan KIM ; Jinmann CHON ; Seung Ah LEE ; Yoo Jin HAN ; Yun Soo SOH ; Yong KIM ; Seonyoung HAN ; Woojin LEE ; Young Rok HAN
Annals of Rehabilitation Medicine 2017;41(6):979-989
OBJECTIVE: To investigate the differences in biomechanical parameters measured by gait analysis systems between healthy subjects and subjects with plantar fasciitis (PF), and to compare biomechanical parameters between ‘normal, barefooted’ gait and arch building gait in the participants. METHODS: The researchers evaluated 15 subjects (30 feet) with bilateral foot pain and 15 subjects (15 feet) with unilateral foot pain who had a clinical diagnosis of PF. Additionally, 17 subjects (34 feet) who had no heel pain were recruited. Subjects were excluded if they had a traumatic event, prior surgery or fractures of the lower limbs, a leg length discrepancy of 1 cm or greater, a body mass index greater than 35 kg/m2, or had musculoskeletal disorders. The participants were asked to walk with an arch building gait on a treadmill at 2.3 km/hr for 5 minutes. Various gait parameters were measured. RESULTS: With the arch building gait, the PF group proved that gait line length and single support line were significantly decreased, and lateral symmetry of the PF group was increased compared to that of the control group. The subjects with bilateral PF displayed significantly increased maximum pressure over the heel and the forefoot during arch building gait. In addition, the subjects with unilateral PF showed significantly increased maximum pressure over the forefoot with arch building gait. CONCLUSION: The researchers show that various biomechanical differences exist between healthy subjects and those with PF. Employing an arch building gait in patients with PF could be helpful in changing gait patterns to normal biomechanics.
Body Mass Index
;
Diagnosis
;
Fasciitis, Plantar*
;
Foot
;
Gait*
;
Healthy Volunteers
;
Heel
;
Humans
;
Leg
;
Lower Extremity
8.Size of Non-lepidic Invasive Pattern Predicts Recurrence in Pulmonary Mucinous Adenocarcinoma: Morphologic Analysis of 188 Resected Cases with Reappraisal of Invasion Criteria.
Soohyun HWANG ; Joungho HAN ; Misun CHOI ; Myung Ju AHN ; Yong Soo CHOI
Journal of Pathology and Translational Medicine 2017;51(1):56-68
BACKGROUND: We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns. METHODS: Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3). RESULTS: The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121). CONCLUSIONS: This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.
Adenocarcinoma in Situ
;
Adenocarcinoma, Mucinous*
;
Disease-Free Survival
;
Humans
;
Lung
;
Male
;
Mucins*
;
Multivariate Analysis
;
Recurrence*
9.Radial Artery Occlusion after Transradial Artery Cannulation.
Hyung Youn GONG ; Sang Hyun PARK ; Yong Han SEO ; Jin Hun CHUNG
Soonchunhyang Medical Science 2017;23(1):71-73
Percutaneous arterial catheterization is a widely used technique for continuous hemodynamic monitoring and arterial blood gas analysis. There are various complications such as hemorrhage, hematoma, infection, and thrombosis. We performed a catheterization procedure to confirm that the lateral circulation of the radial artery was sufficient. The arterial blood pressure waveform was damped after catheterization. Immediately after removal of the catheter, ultrasonography and Doppler were used to confirm the formation of total thrombus in the radial artery. A thrombus was found in the radial artery and disappeared at 3 days postoperatively.
Arterial Pressure
;
Arteries*
;
Blood Gas Analysis
;
Catheterization*
;
Catheters
;
Hematoma
;
Hemodynamics
;
Hemorrhage
;
Radial Artery*
;
Thrombosis
;
Ultrasonography
10.Heating of infusion fluids through heated breathing circuits.
Myoung Hun KIM ; Ji Hoon KIM ; Dong Ki HUR ; Su Bin KIM ; Yong Hyun CHO ; Se Hun LIM ; Jeong Han LEE ; Wonjin LEE ; Kwangrae CHO
Anesthesia and Pain Medicine 2017;12(1):28-31
BACKGROUND: Hypothermia is a common physiological condition that occurs during surgical operations. The goal of this experiment is to measure the temperature of the fluids flowing through heated breathing circuits with respect to changes in infusion speed. METHODS: The infusion pump was connected to the intravenous inlet of a heated breathing circuit with two 50 cm extension lines connected to the outlet. Fluids were injected through the heated breathing circuit at 100, 200, 300, 400, 500, 600, and 700 ml/h, with measurement of the fluid temperature immediately after transit (OP 20), 70 cm after transit (OP 70), and 120 cm after transit (OP 120). RESULTS: The mean fluid temperatures at OP 20, OP 70, and OP 120 were 40.7 ± 4.8℃, 35.1 ± 3.22℃, and 31.7 ± 2.5℃, respectively. CONCLUSIONS: The heated breathing circuit was effective to heat the fluid. After passing out the heated breathing circuit, the temperature of the fluid continuously reduced. A length of 70 cm can be used to efficiently supply heated fluid to the patient. From this experiment, it is expected that supplying heated fluid to a patient using the heated breathing circuit will help maintain the patient's body temperature.
Anesthesia
;
Bays
;
Body Temperature
;
Heating*
;
Hot Temperature*
;
Humans
;
Hypothermia
;
Infusion Pumps
;
Respiration*

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