SCI 발표논문

1. 12582013

   제1저자 김경희 · 교신저자 김형관

   Kim KH, Kim HK, Hwang IC, Lee SP, Cho HJ, Kang HJ, Kim YJ, Sohn DW

   ULTIMATE-SHF trial (UdenafiL Therapy to Improve symptoMAtology, exercise Tolerance and hEmodynamics in patients with chronic systolic heart failure): study protocol for a randomized, placebo-controlled, double-blind trial.

   Trials. 2013;14:188.

   Abstract

   BACKGROUND Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients.

   METHODS/DESIGN Stable, chronic SHF patients will be randomly assigned to placebo (26 patients) or udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥ 18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥ 40 mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event.

   CLINICAL TRIAL REGISTRATION Unique identifier: NCT01646515.

   PubMed IF 2.1 순환기내과
2. 12572013

   제1저자 Shaw AT, 김동완 · 교신저자 Shaw AT

   Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA

   Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.

   N Engl J Med. 2013;368(25):2385-94.

   Abstract

   BACKGROUND In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown.

   METHODS We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival.

   RESULTS The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy.

   CONCLUSIONS Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).

   PubMed IF 84.5 혈액종양내과
3. 12562013

   제1저자 이예나, 박영주 · 교신저자 이가희

   Lee Y, Park YJ, Ahn HY, Lim JA, Park KU, Choi SH, Park DJ, Oh BC, Jang HC, Yi KH

   Plasma FGF21 levels are increased in patients with hypothyroidism independently of lipid profile.

   Endocr J. 2013;60(8):977-83.

   Abstract

   Thyroid hormone is a potent regulator of metabolic and energy homeostasis implicated in various metabolic diseases. Fibroblast growth factor 21(FGF21) is a systemic metabolic regulator known to modulate various biological functions similar to the actions of thyroid hormone. We investigated the differences in plasma FGF21 concentrations in patients with varying thyroid function. Ninety drug-naïve subjects who underwent thyroid evaluation at Seoul National University Bundang Hospital were enrolled and classified into euthyroid, subclinical hypothyroid, and overtly hypothyroid groups. Biochemical markers and plasma FGF21 levels were measured and analyzed. The mean age of the subjects was 42.6 ± 9.1 years. The mean body mass index (BMI), waist circumference, and fasting glucose concentrations were similar between groups. Overtly hypothyroid subjects exhibited significantly higher concentrations of total cholesterol, triglyceride, and LDL-cholesterol than the other groups (p<0.01). Mean plasma FGF21 concentrations in euthyroid, subclinical hypothyroid and overtly hypothyroid groups were 43.2 ± 39.2 pg/mL, 63.6 ± 73.6 pg/mL, and 101.5 ± 74.9 pg/mL, respectively (p<0.01 between groups). Plasma FGF21 concentrations remained significantly higher in overtly hypothyroid subjects after adjusting for serum triglyceride concentrations (p<0.005). Multivariate analysis revealed a significant positive linear relationship between serum TSH concentrations and plasma FGF21 concentrations (β = 0.192, p = 0.002) and a significant negative linear relationship between free T4 and plasma FGF21 concentrations (β = -0.382, p = 0.037) after adjusting for gender, BMI and serum concentrations of triglycerides and glucose. Plasma FGF21 levels were significantly increased in patients with hypothyroidism independently of BMI, or lipid or glucose metabolism.

   PubMed IF 2.5 내분비대사내과
4. 12552013

   제1저자 이학모 · 교신저자 박경수

   Lee H, Park HS, Hong SH, Choi OK, Cho SD, Park J, Oh JE, Chung SS, Jung HS, Park KS

   4-Deoxypyridoxine improves the viability of isolated pancreatic islets ex vivo.

   Islets. 2013;5(3):116-21.

   Abstract

   The successful islet transplantation, for the treatment of type 1 diabetes, depends on the quantity and the quality of transplanted islets. Previously, it has reported that the significant loss of isolated islet mass could be prevented by sphingolipid metabolite, sphinogosine 1-phophate (S1P). This study was performed to elucidate whether the beneficial effects of S1P maintaining isolated pancreatic islets ex vivo are mimicked by modulation of intracellular S1P. We tested the in vitro effect of various agents that modulate intracellular S1P levels in insulinoma cell lines and isolated islets to compare their anti-apoptotic effects with that of S1P. As results, we discovered that 4-deoxypyridoxine (DOP), which inhibits the degradation of intracellular S1P by inhibiting S1P lyase (SPL) activity, minimized the chemically induced apoptosis of insulinoma cell lines as S1P did. Also, supplementation of DOP in the culture media protected the regression of isolated islets that have been maintained ex vivo at least for 18 h providing the evidence of increasing viability of isolated islets with DOP, which impaired SPL activity. In conclusion, these results suggest that the application of SPL inhibitors could be considered as a supplement for the maintenance of viable islets isolated from donor sources in the process of islet transplantation.

   PubMed IF 1.4 내분비대사내과
5. 12542013

   제1저자 임수 · 교신저자 고광곤

   Lim S, Park YM, Sakuma I, Koh KK

   How to control residual cardiovascular risk despite statin treatment: focusing on HDL-cholesterol.

   Int J Cardiol. 2013;166(1):8-14.

   Abstract

   Lowering low-density lipoprotein-cholesterol (LDL-C) is the primary target in the management of dyslipidemia in patients at high risk of cardiovascular disease. However, patients who have achieved LDL-C levels below the currently recommended targets may still experience cardiovascular events. This may result, in part, from elevated triglyceride (TG) levels and low levels of high-density lipoprotein-cholesterol (HDL-C). Low HDL-C and high TG levels are common and are recognized as independent risk factors for cardiovascular morbidity and mortality. Furthermore, atherogenic dyslipidemia, characterized by low levels of HDL-C, high TG, and small, dense LDL particles, is a typical phenotype of dyslipidemia in subjects with insulin resistance and metabolic syndrome. Therefore, to reduce further the risk of coronary heart disease (CHD), raising HDL-C and lowering TG may be the secondary therapeutic target for patients who achieve LDL-C levels below the currently recommended targets but are still at risk of CHD. However, whether increasing HDL-C levels alone reduces CHD has not yet been confirmed in large randomized clinical trials, and whether functional HDL is more important than HDL-C in reducing CHD remains controversial. Large CHD endpoint trials that include many patients with diabetes are underway to compare combination treatments with statin and niacin, fibrates, or cholesteryl ester transfer protein inhibitors with statin alone treatments. In this review, we discuss the rationale and importance of increasing HDL-C levels with and without lowering TG levels in the treatment and prevention of cardiovascular events.

   PubMed IF 3.3 내분비대사내과
6. 12532013

   제1저자 박경우 · 교신저자 김효수

   Park KW, Lim WH, Kim JH, Kang SH, Seo JW, Song YB, Hahn JY, Lee HY, Kang HJ, Cho YS, Youn TJ, Koo BK, Choi SH, Chae IH, Gwon HC, Choi DJ, Kim HS

   Comparison between zotarolimus-eluting stents and first generation drug-eluting stents in the treatment of patients with acute ST-segment elevation myocardial infarction.

   Int J Cardiol. 2013;166(1):118-25.

   Abstract

   BACKGROUND The purpose of this study was to compare the two year efficacy and safety of zotarolimus-eluting stents (ZES) and first-generation DES, sirolimus- (SES) and paclitaxel-eluting stents (PES), in an all-comer registry receiving primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI).

   METHODS A total of 711 consecutive STEMI patients (ZES: 135, SES: 427, and PES: 149), who underwent primary PCI between January 2005 and June 2008 were enrolled from three centers. In our study, the efficacy analysis endpoint was target vessel failure (cardiac death, target vessel related myocardial infarction, and ischemia-driven target vessel revascularization) at 2 years. The safety analysis endpoint was a composite of all cause death, non-fatal myocardial infarction, and stent thrombosis within 2 years.

   RESULTS At 2 years, the rates of target vessel failure in the ZES, SES, and PES groups were 14.8%, 12.9%, and 19.5%, respectively (p=0.141). The rates of composite safety endpoints at 2 years were not different among the three groups (ZES 8.1% vs. SES 13.1% vs. PES 16.8%, p=0.102). However, when comparing the two groups, ZES was safer than PES (adjusted HR 0.48, 95% CI 0.24-0.98, p=0.046). There was also a non-significant trend in favor of ZES in the rate of stent thrombosis (ZES 1.5% vs. SES 2.3% vs. PES 4.7%, p=0.186).

   CONCLUSION In the treatment of STEMI patients, ZES showed similar and acceptable efficacy compared to first-generation DES (SES and PES) up to 2 years. In addition, ZES seems to be more favorable than PES in terms of safety.

   PubMed IF 3.3 순환기내과
7. 12522013

   제1저자 이해영 · 교신저자 차명진

   Cha MJ, Lee HY, Cho HJ, Hwang HY, Kim KB, Oh BH

   Under-utilization of donor hearts in the initial era of the heart transplant program in Korea- review of 13 years’ experience from the Korea national registry.

   Circ J. 2013;77(8):2056-63.

   Abstract

   BACKGROUND Heart transplantation (HTPL) is the effective treatment option to improve quality of life as well as survival of terminal heart failure patients. Shortage of donors, however, limits HTPL to all indicated cases. The temporal trend and clinical characteristics of HTPL donors in Korea were therefore investigated.

   METHODS AND RESULTS Among 2,001 brain-death donors registered in Korean Network for Organ Sharing from February 2000 to May 2012, a total of 28% of hearts (n=552) were utilized for HTPL. The mean age of Korean heart donors was 10 years younger than that of heart recipients (33.2 ± 12 years vs. 43.2 ± 17 years, respectively). The oldest was 56 years old, and donors aged over 50 accounted for only 6.2% (n=34) of total cases. Female donors were utilized less than male donors (23.6% vs. 29.6%, respectively). To determine characteristics of declined donor heart candidates, subgroup analysis of echocardiographic data was done, and 74.6% had normal ventricular function and structure, although only 42.3% were actually transplanted. The utilization rate of donor hearts with minor echocardiography abnormalities was only 15.2%. Clinical outcomes of marginal heart donors were not different from non-marginal donors.

   CONCLUSIONS Although shortage of donor organs is an emerging issue, most donor hearts have been under-utilized in the past in Korea. In particular, aged and female donor hearts with minor echocardiographic abnormalities had a low rate of utilization.

   PubMed IF 5.8 순환기내과
8. 12512013

   제1저자 오태정 · 교신저자 정혜승

   Oh TJ, Jung HS, Bae JH, Kim YG, Park KS, Cho YM, Park KS, Kim SY

   Clinical characteristics of the responders to dipeptidyl peptidase-4 inhibitors in Korean subjects with type 2 diabetes.

   J Korean Med Sci. 2013;28(6):881-7.

   Abstract

   We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (ΔHbA1c). The Student's t-test between good responders (GR: ΔHbA1c > 1.0%) and poor responders (PR: ΔHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with ΔHbA1c. In the multivariate analysis, age (r(2) = 0.006), duration of diabetes (r(2) = 0.019), HbA1c (r(2) = 0.296), and creatinine levels (r(2) = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.

   PubMed IF 3.2 내분비대사내과
9. 12502013

   제1저자 김덕겸 · 교신저자 정희순

   Kim DK, Jin KN, Park SS, Heo EY, Chang MS, Lee CH, Chung HS

   A woman with progressive dyspnea with multiple lung cavitations.

   Am J Respir Crit Care Med. 2013;187(11):e21-2.

   PubMed IF 21.7 호흡기내과
10. 12492013

    제1저자 이세원 · 교신저자 이춘택

    Lee SW, Leem CS, Kim TJ, Lee KW, Chung JH, Jheon S, Lee JH, Lee CT

    The long-term course of ground-glass opacities detected on thin-section computed tomography.

    Respir Med. 2013;107(6):904-10.

    Abstract

    BACKGROUND Focal ground-glass opacity (GGO) is becoming a major concern because of its possible association with lung cancer. In this study, we analyzed the long-term progression of GGOs that persisted for more than 2 years.

    METHODS We reviewed focal GGOs identified by thin-section computed tomography that persisted for more than 2 years.

    RESULTS We enrolled a total of 114 patients with 175 GGO lesions. The median patient age was 61 years (range, 37-92 years) and 42 (36.8%) patients were male. Mean initial GGO size was 7.8 ± 4.4 mm. Median follow-up duration was 45 months. Forty-six (26.3%) GGOs had significant size increases (≥2 mm in the longest diameter) with a mean volume doubling time of 1041 days. In a multivariate analysis, large size (≥10 mm), the presence of a solid portion (mixed GGO) and old age (≥65 years) were risk factors for significant size increase, with odds ratios (95% CI) of 6.46 (2.69-15.6), 2.69 (1.11-6.95) and 2.55 (1.13-5.77), respectively. GGOs with character changes from pure to mixed or mixed to solid showed more rapid volume expansion.

    CONCLUSIONS GGOs which persisted for several years showed an indolent course. Large lesions with a solid portion and GGOs in male or elderly individuals may be cause for more concern, as these factors were associated with size increase. Resection should be considered if GGOs show character changes, as these may be associated with rapid size progression.

    PubMed IF 3.3 호흡기내과
11. 12482013

    제1저자 민아름 · 교신저자 임석아/방영주

    Min A, Im SA, Yoon YK, Song SH, Nam HJ, Hur HS, Kim HP, Lee KH, Han SW, Oh DY, Kim TY, O'Connor MJ, Kim WH, Bang YJ

    RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib.

    Mol Cancer Ther. 2013;12(6):865-77.

    Abstract

    A PARP inhibitor is a rationally designed targeted therapy for cancers with impaired DNA repair abilities. RAD51C is a paralog of RAD51 that has an important role in the DNA damage response. We found that cell lines sensitive to a novel oral PARP inhibitor, olaparib, had low levels of RAD51C expression using microarray analysis, and we therefore hypothesized that low expression of RAD51C may hamper the DNA repair process, resulting in increased sensitivity to olaparib. Compared with the cells with normal RAD51C expression levels, RAD51C-deficient cancer cells were more sensitive to olaparib, and a higher proportion underwent cell death by inducing G2-M cell-cycle arrest and apoptosis. The restoration of RAD51C in a sensitive cell line caused attenuation of olaparib sensitivity. In contrast, silencing of RAD51C in a resistant cell line enhanced the sensitivity to olaparib, and the number of RAD51 foci decreased with ablated RAD51C expression. We also found the expression of RAD51C was downregulated in cancer cells due to epigenetic changes and RAD51C expression was low in some gastric cancer tissues. Furthermore, olaparib significantly suppressed RAD51C-deficient tumor growth in a xenograft model. In summary, RAD51C-deficient cancer cells are highly sensitive to olaparib and offer preclinical proof-of-principle that RAD51C deficiency may be considered a biomarker for predicting the antitumor effects of olaparib.

    PubMed IF 6.9 혈액종양내과
12. 12472013

    제1저자 문민경 · 교신저자 박영주/장학철

    Moon MK, Hong ES, Lim JA, Cho SW, Soo L, Choi SH, Yi KH, Park DJ, Park YJ, Jang HC

    Associations between thyroid hormone levels and regional fat accumulation in euthyroid men.

    Eur J Endocrinol. 2013;168(6):805-10.

    Abstract

    OBJECTIVE Body adiposity, especially ectopic fat accumulation, has a range of metabolic and cardiovascular effects. This study aimed to investigate whether thyroid function is associated with various regional fat quantities in euthyroid subjects.

    METHODS A total of 100 euthyroid men (free triiodothyronine (fT3), 4.77±1.21 pg/ml; free thyroxine (fT4), 1.38±0.21 ng/dl; and TSH, 2.09±0.91 μIU/ml) were enrolled in this cross-sectional study. We measured accumulated regional fat using 64-slice multi-detector computed tomography. Multiple linear regression analysis was used to determine whether accumulated fat in each region was associated with clinical parameters after adjusting for age.

    RESULTS FT3 was inversely correlated with BMI (R=0.232, P=0.029) and LDL cholesterol level (R=0.277, P=0.019). FT4 was inversely correlated with waist circumference (R=0.350, P=0.008) and BMI (R=0.355, P0.001). In multiple linear regression analysis, fT3 and fT4 levels were significantly associated with pericardial fat volume (fT3: B=-0.079, 95% CI -0.142 to -0.017, P=0.013; fT4: B=-0.411, 95% CI -0.780 to -0.042, P=0.030) in euthyroid men, independent of age. FT3 level was inversely associated with intramuscular fat area (B=-0.059, 95% CI -0.106 to -0.011, P=0.016) and hepatic fat quantity (B=-0.237, 95% CI -0.441 to -0.033, P=0.024) in euthyroid men, independent of age.

    CONCLUSIONS In euthyroid men, low levels of fT3 and fT4 were significantly associated with increased pericardial fat volume and BMI.

    PubMed IF 6.7 내분비대사내과
13. 12462013

    제1저자 이정원 · 교신저자 김나영

    Lee JW, Kim N, Kim JM, Nam RH, Chang H, Kim JY, Shin CM, Park YS, Lee DH, Jung HC

    Prevalence of primary and secondary antimicrobial resistance of Helicobacter pylori in Korea from 2003 through 2012.

    Helicobacter. 2013;18(3):206-14.

    Abstract

    BACKGROUND Antimicrobial resistance of Helicobacter pylori (H. pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H. pylori isolates to antibiotics and to characterize the risk factors associated with antimicrobial resistance in Korea.

    MATERIALS AND METHODS This study was performed during the period of 2003-2012. Primary resistance was evaluated from 347 patients without any history of eradication, and secondary resistance was evaluated in 86 patients from whom H. pylori was cultured after failure of eradication. Minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, levofloxacin, and moxifloxacin using agar dilution method. Primary and secondary resistance rates of H. pylori to 7 antibiotics were evaluated and risk factors for the antibiotic resistance were analyzed.

    RESULTS Increase in the primary resistance rate was found in amoxicillin (6.3-14.9%, p = .051), clarithromycin (17.2-23.7%, p = .323), and both of levofloxacin and moxifloxacin (4.7-28.1%, p = .002) during the study period. Secondary resistance rate significantly increased in metronidazole, levofloxacin, and moxifloxacin. Increase of resistance occurred after initial failure of eradication therapy in case of clarithromycin (p < .001), azithromycin (p < .001), levofloxacin (p = .011), and moxifloxacin (p = .020). Multivariable analyses showed that clarithromycin, azithromycin, levofloxacin, and moxifloxacin resistance was associated with previous eradication treatment history.

    CONCLUSIONS The increased primary and secondary antibiotic resistance of H. pylori in Korea is ongoing, and it will become a significant limitation for effective eradication of H. pylori in the future.

    PubMed IF 4.6 소화기내과
14. 12452013

    제1저자 최윤진 · 교신저자 김나영

    Choi YJ, Kim N, Paik JH, Kim JM, Lee SH, Park YS, Hwang JH, Kim JW, Jeong SH, Lee DH, Jung HC

    Characteristics of Helicobacter pylori-positive and Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma and their influence on clinical outcome.

    Helicobacter. 2013;18(3):197-205.

    Abstract

    BACKGROUND To compare clinicopathologic and molecular characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma depending on Helicobacter pylori positivity and to find out a predictive factor for unresponsiveness to Helicobacter pylori eradication therapy in Korea.

    METHODS A total of 53 Helicobacter pylori-positive and 13 negative mucosa-associated lymphoid tissue lymphoma patients were enrolled, and tissues from 21 patients were investigated to examine the presence of t(11;18)(q21;q21) with fluorescence in situ hybridization. Clinicopathologic features such as the endoscopic appearance, dominant site of lesion, depth of invasion, clinical stage, and the existence of MALT1 gene rearrangement were compared between these two groups. Fifty-six patients who underwent H. pylori eradication therapy were divided into responder and nonresponder groups. The two groups were analyzed to calculate odds ratios for resistance to the eradication.

    RESULTS Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma patients averaged a more advanced clinical stage than H. pylori-positive (p = .023) patients. The frequency of t(11;18)/API2-MALT1 did not differ between H. pylori-positive (45.5%) and H. pylori-negative cases (55.6%). Thirty-eight of 51 (74.5%) H. pylori-positive patients achieved complete regression after the eradication, while 2 of 5 (40%) H. pylori-negative patients obtained regression. Presence of lesions in both distal and proximal parts of stomach (p = .041) and bearing of t(11;18)(q21;q21) (p = .007) were predictors for nonresponsiveness for H. pylori eradication.

    CONCLUSIONS Helicobacter pylori eradication could be performed as a primary therapy regardless of H. pylori status, and assessing t(11;18)/API2-MALT1 would be considered after failure to remission by H. pylori eradication.

    PubMed IF 4.6 소화기내과
15. 12442013

    제1저자 정은숙 · 교신저자 주권욱

    Jung ES, Lee J, Lee JW, Yoon HJ, Kim DK, Oh KH, Kim YS, Han JS, Joo KW

    Increasing the dialysate sodium concentration based on serum sodium concentrations exacerbates weight gain and thirst in hemodialysis patients.

    Tohoku J Exp Med. 2013;230(2):117-21.

    Abstract

    Most dialysis centers adopt a standard dialysate sodium prescription. While pre-hemodialysis (HD) serum sodium levels remain relatively constant in each individual patient on chronic HD, these levels can vary between different patients. Therefore, a single dialysate sodium prescription may not be appropriate for all patients. Nineteen stable patients on maintenance HD were dialyzed for 9 HD sessions with their current dialysis solutions, followed by another 9 sessions using individualized prescriptions created by aligning dialysate sodium levels to each patient's serum sodium concentration. Patients were divided into 2 groups according to whether the average pre-HD serum sodium concentration was higher than (higher serum sodium group, n = 13) or equal to (equal sodium group, n = 5) the standard dialysate sodium concentration. Pre-HD serum sodium levels remained constant during entire study period in both groups. In higher serum sodium group, interdialytic weight gain increased after implementation of the sodium alignment (2.0 ± 0.3 kg vs. 2.3 ± 0.4 kg; P = 0.008). Thirst scores also increased in patients whose dialysate sodium was increased by 4 mmol/L (n = 7) (6.4 ± 1.5 vs. 7.6 ± 1.5, P = 0.015). There were no significant changes in blood pressure and intradialytic complications. In equal sodium group, significant differences were not observed in any parameters. Our results suggest that alignment of dialysate sodium levels to each patient's serum sodium concentration is of little benefit in hemodynamically stable patients who have pre-HD serum sodium concentrations higher than dialysate sodium concentration.

    PubMed IF 1.5 신장내과
16. 12432013

    제1저자 이경희 · 교신저자 유철규

    Lee KH, Yoo CG

    Simultaneous inactivation of GSK-3β suppresses quercetin-induced apoptosis by inhibiting the JNK pathway.

    Am J Physiol Lung Cell Mol Physiol. 2013;304(11):L782-9.

    Abstract

    Quercetin, a ubiquitous bioactive plant flavonoid, has shown to exert a broad range of activities, such as apoptotic, antioxidant, and anti-inflammatory effects. Thus, flavonoids can mediate both cell protection and cell injury. Recently, quercetin has been reported to prevent the progression of emphysema in animal models through antioxidant and anti-inflammatory actions. These findings suggest that quercetin could be a potential treatment option for chronic obstructive pulmonary disease. Its clinical application, however, could be limited by the cytotoxicity of quercetin, and understanding of the apoptotic mechanisms of quercetin is a prerequisite to develop a therapeutic strategy with minimal cytotoxicity. We evaluated the apoptotic effect of quercetin and its molecular mechanisms in normal bronchial epithelial cells (BEAS-2B cells). Quercetin decreased the viability of BEAS-2B cells via apoptosis in a dose- and time-dependent manner. Quercetin activated JNK and increased the expression levels of c-Jun and p53-dependent Bax. Blockade of JNK activation by overexpression of dominant negative JNK1 suppressed apoptosis by quercetin via inhibition of caspase-3 activation and reduction of p53 and Bax expression. Simultaneously, quercetin inactivated glycogen synthase kinase (GSK)-3β, which is phosphatidylinositol 3-kinase/Akt dependent. Overexpression of a constitutively active GSK-3β mutant enhanced quercetin-induced JNK activation. In contrast, overexpression of enzymatically inert GSK-3β inhibited JNK activation, resulting in a suppression of apoptosis by quercetin. Taken together, the JNK-p53 pathway is involved in quercetin-induced apoptosis, and simultaneous inactivation of GSK-3β can attenuate apoptosis in normal bronchial epithelial cells.

    PubMed IF 3.8 호흡기내과
17. 12422013

    제1저자 김진원 · 교신저자 임석아

    Kim JW, Cho HJ, Kim M, Lee KH, Kim MA, Han SW, Oh DY, Lee HJ, Im SA, Kim TY, Yang HK, Kim WH, Bang YJ

    Differing effects of adjuvant chemotherapy according to BRCA1 nuclear expression in gastric cancer.

    Cancer Chemother Pharmacol. 2013;71(6):1435-43.

    Abstract

    BACKGROUND We aimed to investigate the role of BRCA1 nuclear expression in sporadic gastric cancer; currently, the role remains unknown.

    METHODS Patients with gastric cancer who received curative operation with D2 dissection were enrolled in this study. Adjuvant chemotherapy was administered at the discretion of the physician. According to BRCA1 nuclear expression analysis by immunohistochemistry (IHC) on tissue microarrays using anti-BRCA1 antibody MS110, BRCA1 expression was classified as negative, low expression, and high expression.

    RESULTS Among 318 cases, 155 cases (48.7 %) were identified as BRCA1-negative by IHC and 96 cases (30.2 %) revealed BRCA1 low expression, 67 cases (21.0 %) showed BRCA1 high expression. The negative or reduced expression of BRCA1 was more frequent in more advanced-stage disease (p < 0.001) and was associated with perineural invasion (p = 0.032). Disease-free survival (DFS) was significantly decreased with reduced BRCA1 expression (p = 0.027). This tendency was also observed in overall survival (OS), although the difference was not significant. The poorer prognosis of BRCA1-negative tumors was overcome through adjuvant chemotherapy. The benefit of adjuvant chemotherapy for DFS and OS in stage III was enhanced only in BRCA1-negative tumors (p < 0.001, p < 0.001, respectively), but not in BRCA1-positive tumors (p = 0.236, p = 0.148, respectively).

    CONCLUSION The reduction of BRCA1 nuclear expression is associated with advanced stage and perineural invasion. Moreover, negative BRCA1 nuclear expression is a predictive marker regarding the benefit of adjuvant chemotherapy in sporadic gastric cancer; these novel findings are of great importance, and further, larger studies are warranted.

    PubMed IF 2.5 혈액종양내과
18. 12412013

    제1저자 정용진 · 교신저자 김진욱

    Jung YJ, Kim JW, Park SJ, Min BY, Jang ES, Kim NY, Jeong SH, Shin CM, Lee SH, Park YS, Hwang JH, Kim N, Lee DH

    c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B virus in human hepatoma cells.

    J Med Virol. 2013;85(6):969-78.

    Abstract

    MicroRNAs (miRNAs) regulate post-transcriptional gene expression in various physiological and pathological processes, including viral infections. The miR-17-92 cluster encodes six miRNAs (miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a-1) which are transactivated by c-Myc. Because hepatitis B virus transactivates c-Myc, the interaction between the miR-17-92 cluster and HBV replication was examined in this study. Inducing HBV replication in a human hepatoma cell line increased miR-17-5p, miR-20a and miR-92a-1 expression. HBV-induced overexpression of miR-17-92 was reversed by c-Myc knockdown. Antisense peptide nucleic acids against miR-20a and miR-92a-1 augmented HBV replication. A computational analysis yielded potential binding sites for miR-20a and miR-92a-1 in the HBV genome. The direct interaction between these two miRNAs and target regions in HBV transcripts was confirmed by luciferase reporter analysis. These results demonstrated negative feedback suppression of HBV replication by the miR-17-92 polycistron.

    PubMed IF 3.7 소화기내과
19. 12402013

    제1저자 차병효 · 교신저자 황진혁

    Cha BH, Lee SH, Kim JE, Yoo JY, Park YS, Kim JW, Jeong SH, Kim N, Lee DH, Hwang JH

    Endoscopic self-expandable metallic stent placement in malignant pyloric or duodenal obstruction: does chemotherapy affect stent patency?

    Asia Pac J Clin Oncol. 2013;9(2):162-8.

    Abstract

    AIM Self-expandable metallic stents (SEMS) have been used for palliation in patients with malignant gastroduodenal obstructions. We evaluated clinical outcomes after SEMS placement and identified prognostic factors of SEMS patency, including chemotherapy.

    METHODS A review of records of 85 patients with unresectable gastric or pancreatic cancer who underwent endoscopic SEMS insertion for gastroduodenal obstructions at Seoul National University Bundang Hospital.

    RESULTS From August 2003 to October 2009, 85 patients with gastroduodenal obstruction were managed with endoscopic SEMS placement. Technical success was achieved in 82 patients (96%) and clinical success in 68 patients (80%). Of 49 patients who had clinical success, 19 underwent chemotherapy (chemoTx group), and 30 patients did not (non-chemoTx group). Cumulative SEMS patency in the 49 patients who achieved clinical success were 84, 54 and 41% at 2, 3 and 6 months, respectively. By univariate and multivariate analysis, there was no statistical difference in the SEMS patency between the two groups (cumulative SEMS patency rate: 95 vs 73% at 2 months, 15 vs 63% at 3 months, 40 vs 42% at 6 months, respectively, P < 0.793).

    CONCLUSION Chemotherapy does not improve SEMS patency in patients with malignant gastroduodenal obstruction caused by unresectable gastric or pancreatic cancer.

    PubMed IF 2.1 소화기내과
20. 12392013

    제1저자 이대원 · 교신저자 한세원

    Lee DW, Han SW, Lee HJ, Rhee YY, Bae JM, Cho NY, Lee KH, Kim TY, Oh DY, Im SA, Bang YJ, Jeong SY, Park KJ, Park JG, Kang GH, Kim TY

    Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy.

    Br J Cancer. 2013;108(10):1978-84.

    Abstract

    BACKGROUND There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear.

    METHODS Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared.

    RESULTS Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76-16.8).

    CONCLUSION Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.

    PubMed IF 7.8 혈액종양내과
21. 12382013

    제1저자 최인아 · 교신저자 이은봉

    Choi IA, Park JK, Lee EY, Song YW, Lee EB

    Random spot urine protein to creatinine ratio is a reliable measure of proteinuria in lupus nephritis in Koreans.

    Clin Exp Rheumatol. 2013;31(4):584-8.

    Abstract

    OBJECTIVES The accurate assessment of proteinuria is critical for the management of lupus nephritis. Measuring the protein to creatinine (P/C) ratio in random spot urine (RSU) samples has been introduced as an alternative to the 24-hour (24h) urine collection method. However, it remains unclear as to whether the RSU P/C ratio is reliable for assessing lupus nephritis (LN) in routine clinical practice.

    METHODS In total, 275 pairs of 24h urine and RSU samples from 102 patients with biopsy-proven LN were analysed. The correlation and concordance between the P/C ratios in the two sample types were assessed by Pearson or Spearman correlation and intra-class correlation coefficient (ICC) using mixed models for repeated measurements, respectively.

    RESULTS The mean 24h urine P/C ratio was 3.2 ± 4.9. Overall, RSU P/C ratio correlated strongly with the 24h urine P/C ratio (r=0.944, p<0.001) with an excellent agreement (ICC=0.949, 95% confidence interval [CI]: 0.69-1.00). Subgroup analyses revealed that the correlation remained high in class II, III, IV, and V LN (rho=0.868, p<0.001; rho=0.649, p=0.007; r=0.945, p<0.001; and rho=0.900, p=0.001, respectively). The correlation between the 24h urine and RSU P/C ratio in the range of 0.5 to 3 was good (r=0.720, p<0.001) with ICC of 0.659 (95%CI 0.554-0.812). RSU P/C ratio ≥0.5 could predict 24h PCR ≥0.5 with 91.7% sensitivity and 70.2% specificity, whereas RSU P/C ratio ≥1.0 increased specificity up to 94.7%.

    CONCLUSIONS The RSU P/C ratio is an excellent alternative to the 24 hour P/C ratio for assessing the presence of clinically significant proteinuria in LN. RSU P/C ratio >1.0 may prompt directly to a renal biopsy, whereas RSU P/C ratio between 0.5-1.0 should be followed by a confirmatory 24h urine collection.

    PubMed IF 3.2 류마티스내과
22. 12372013

    제1저자 김효진 · 교신저자 오국환

    Kim HJ, Kim H, Shin N, Na KY, Kim YL, Kim D, Chang JH, Song YR, Hwang YH, Kim YS, Ahn C, Lee J, Oh KH, Representing the Cinacalcet stUdy for Peritoneal Dialysis Patients In Double Arm on the Lowing Effect Of iPTH Level (CUPID) Study Group

    Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study.

    BMC Nephrol. 2013;14:112.

    Abstract

    BACKGROUND Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.

    OBJECTIVES The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.

    DESIGN Multicenter, open-labeled, randomized controlled study.

    SETTING Seven university-affiliated hospitals in Korea.

    PARTICIPANTS Overall, 66 peritoneal dialysis patients were enrolled.

    INTERVENTION Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.

    MAIN OUTCOME MEASURES Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary).

    RESULTS 72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (- 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction.

    CONCLUSION Cinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.

    TRIAL REGISTRATION Controlled trials NCT01101113.

    PubMed IF 2.9 신장내과
23. 12362013

    제1저자 김현수, 김경곤 · 교신저자 윤정환

    Kim H, Kim K, Yu SJ, Jang ES, Yu J, Cho G, Yoon JH, Kim Y

    Development of biomarkers for screening hepatocellular carcinoma using global data mining and multiple reaction monitoring.

    PLoS One. 2013;8(5):e63468.

    Abstract

    Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers and is associated with a poor survival rate. Clinically, the level of alpha-fetoprotein (AFP) has been used as a biomarker for the diagnosis of HCC. The discovery of useful biomarkers for HCC, focused solely on the proteome, has been difficult; thus, wide-ranging global data mining of genomic and proteomic databases from previous reports would be valuable in screening biomarker candidates. Further, multiple reaction monitoring (MRM), based on triple quadrupole mass spectrometry, has been effective with regard to high-throughput verification, complementing antibody-based verification pipelines. In this study, global data mining was performed using 5 types of HCC data to screen for candidate biomarker proteins: cDNA microarray, copy number variation, somatic mutation, epigenetic, and quantitative proteomics data. Next, we applied MRM to verify HCC candidate biomarkers in individual serum samples from 3 groups: a healthy control group, patients who have been diagnosed with HCC (Before HCC treatment group), and HCC patients who underwent locoregional therapy (After HCC treatment group). After determining the relative quantities of the candidate proteins by MRM, we compared their expression levels between the 3 groups, identifying 4 potential biomarkers: the actin-binding protein anillin (ANLN), filamin-B (FLNB), complementary C4-A (C4A), and AFP. The combination of 2 markers (ANLN, FLNB) improved the discrimination of the before HCC treatment group from the healthy control group compared with AFP. We conclude that the combination of global data mining and MRM verification enhances the screening and verification of potential HCC biomarkers. This efficacious integrative strategy is applicable to the development of markers for cancer and other diseases.

    PubMed IF 2.8 윤정환
24. 12352013

    제1저자 이주희 · 교신저자 연태진

    Lee JH, Youn TJ, Yoon YE, Park JJ, Hong SJ, Chun EJ, Choi SI, Cho YS, Cho GY, Chae IH, Choi DJ

    Coronary artery stenosis in moyamoya disease: tissue characterization by 256-slice multi-detector CT and virtual histology.

    Circulation. 2013;127(20):2063-5.

    PubMed IF 41.3 순환기내과
25. 12342013

    제1저자 한세원 · 교신저자 김태유

    Han SW, Kim HP, Shin JY, Jeong EG, Lee WC, Lee KH, Won JK, Kim TY, Oh DY, Im SA, Bang YJ, Jeong SY, Park KJ, Park JG, Kang GH, Seo JS, Kim JI, Kim TY

    Targeted sequencing of cancer-related genes in colorectal cancer using next-generation sequencing.

    PLoS One. 2013;8(5):e64271.

    Abstract

    Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in cancer. We have established a targeted sequencing platform using next-generation sequencing (NGS) technology for clinical use, which can provide mutation and copy number variation data. NGS was performed with paired-end library enriched with exons of 183 cancer-related genes. Normal and tumor tissue pairs of 60 colorectal adenocarcinomas were used to test feasibility. Somatic mutation and copy number alteration were analyzed. A total of 526 somatic non-synonymous sequence variations were found in 113 genes. Among these, 278 single nucleotide variations were 232 different somatic point mutations. 216 SNV were 79 known single nucleotide polymorphisms in the dbSNP. 32 indels were 28 different indel mutations. Median number of mutated gene per tumor was 4 (range 0-23). Copy number gain (>X2 fold) was found in 65 genes in 40 patients, whereas copy number loss (<X0.5 fold) was found in 103 genes in 39 patients. The most frequently altered genes (mutation and/or copy number alteration) were APC in 35 patients (58%), TP53 in 34 (57%), and KRAS in 24 (40%). Altered gene list revealed ErbB signaling pathway as the most commonly involved pathway (25 patients, 42%). Targeted sequencing platform using NGS technology is feasible for clinical use and provides comprehensive genetic alteration data.

    PubMed IF 2.8 혈액종양내과
26. 12332013

    제1저자 오세원 · 교신저자 진호준

    Oh SW, Lee ES, Kim S, Na KY, Chae DW, Kim S, Chin HJ

    Bilirubin attenuates the renal tubular injury by inhibition of oxidative stress and apoptosis.

    BMC Nephrol. 2013;14:105.

    Abstract

    BACKGROUND Bilirubin (BIL) has been recognized as an endogenous antioxidant that shows a protective effect for cardiorenal diseases. We investigated whether administration of BIL had a protective effect on cyclosporine (CsA)-induced nephropathy (CIN), and examined the effects of BIL on the oxidative stress and apoptosis.

    METHODS BIL was pretreated intraperitoneally three times for a week (60 mg/kg), and CsA was injected for 4 weeks (15 mg/kg/day, subcutaneous). Proximal tubular epithelial (HK2) cells were pretreated with 0.1mg/ml of BIL for 24 hours, and then treated with 20 μM of CsA for another 24 hours.

    RESULTS CsA induced marked increases in urine kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (P < 0.05). BIL reduced urine Kim-1 in CIN (P < 0.05), while urine NGAL exhibited a decreasing tendency. In CsA-treated rat kidneys, the protein expression of NOX4 and p22phox was reduced by BIL (P < 0.05). BIL ameliorated CsA-induced arteriolopathy, tubulointerstitial fibrosis, tubular injury, and the apoptosis examined by TUNEL assay (P < 0.01). In HK2 cells, BIL reduced intracellular reactive oxygen species in CsA-treated cells. CsA increased the protein expression of bax, cleaved caspase-9, caspase-3 and the activity of caspase-3; however, the anti-apoptotic bcl-2 protein was reduced. These changes were recovered by BIL (P < 0.05).

    CONCLUSIONS The direct administration of BIL protected against CsA-induced tubular injury via inhibition of oxidative stress and apoptosis.

    PubMed IF 2.9 신장내과
27. 12322013

    제1저자 임주현 · 교신저자 류지곤

    Lim JH, Ryu JK, Choi YJ, Kwon J, Kim JY, Lee YB, Kim JH, Yoon WJ, Kim YT, Yoon YB

    A Case of Common Bile Duct Cancer That Completely Responded to Combination Chemotherapy of Gemcitabine and TS-1.

    Gut Liver. 2013;7(3):371-6.

    Abstract

    Common bile duct (CBD) cancer is a relatively rare malignancy that arises from the biliary epithelium and is associated with a poor prognosis. Here, we report a case of advanced metastatic CBD cancer successfully treated by chemotherapy with gemcitabine combined with S-1 (tegafur+gimeracil+oteracil). A 65-year-old male presented with pyogenic liver abscess. After antibiotic therapy and percutaneous drainage, follow-up computed tomography (CT) showed an enhanced nodule in the CBD. Biopsy was performed at the CBD via endoscopic retrograde cholangiopancreatography, which showed adenocarcinoma. Additional CT and magnetic resonance imaging showed multiple small nodules in the right hepatic lobe, which were confirmed as metastatic adenocarcinoma by sono-guided liver biopsy. The patient underwent combination chemotherapy with gemcitabine and S-1. After nine courses of chemotherapy, the hepatic lesion disappeared radiologically. Pylorus-preserving pancreaticoduodenectomy was performed, and no residual tumor was found in the resected specimen. Three weeks after the operation, the patient was discharged with no complications. Through 3 months of follow-up, no sign of recurrence was observed on CT scan. Gemcitabine combined with S-1 may be a highly effective treatment for advanced cholangiocarcinoma.

    PubMed IF 4.1 소화기내과
28. 12312013

    제1저자 이병환 · 교신저자 김나영

    Joo YE, Park HK, Myung DS, Baik GH, Shin JE, Seo GS, Kim GH, Kim HU, Kim HY, Cho SI, Kim N

    Prevalence and risk factors of atrophic gastritis and intestinal metaplasia: a nationwide multicenter prospective study in Korea.

    Gut Liver. 2013;7(3):303-10.

    Abstract

    BACKGROUND/AIMS Atrophic gastritis (AG) and intestinal metaplasia (IM) are premalignant gastric lesions. The aims of this study were to evaluate the prevalence of endoscopic AG and IM and to document the risk factors for these lesions.

    METHODS In total, 4,023 subjects were enrolled at eight hospitals in Korea. AG and IM were diagnosed by endoscopy. Helicobacter pylori immunoglobulin G antibodies were measured.

    RESULTS The prevalences of endoscopic AG and IM were 40.7% and 12.5%. In a multivariate analysis, the risk factors for AG were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, IM, and education below the college level (odds ratio [OR], 2.55, 5.00, 1.38, 1.41, 4.29, and 1.35, respectively). The risk factors for IM were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, AG, having relatives with gastric cancer, education below the college level and consumption of dairy products (OR, 3.16, 3.25, 1.88, 2.17, 3.68, 1.48, 1.47, and 1.40, respectively).

    CONCLUSIONS A nationwide survey regarding the prevalence of endoscopic AG and IM and their risk factors in Korea supports the hypothesis that endoscopic diagnosis of these premalignant lesions could be helpful to describe a group at high risk for gastric cancer.

    PubMed IF 4.1 소화기내과
29. 12302013

    제1저자 손성욱 · 교신저자 조상헌

    Sohn SW, Jung JW, Lee SY, Kang HR, Park HW, Min KU, Cho SH

    Expression pattern of GSTP1 and GSTA1 in the pathogenesis of asthma.

    Exp Lung Res. 2013;39(4-5):173-81.

    Abstract

    Reactive oxygen species (ROS) are known aggravating factors for airway inflammation in asthma. Glutathione S-transferases (GSTs) detoxify ROS and toxic compounds in environmental exposures. However, little is known about the regulation of GST and expression of GST subtypes in asthma. The aim of this study was to evaluate how GSTs are regulated in asthma. We observed total GST activity and expression of GST subtypes in murine asthma models and GST expressions in induced sputum cells of asthmatics. Total GST activity was increased in BAL fluids of OVA-treated murine asthma model. GSTP and GSTA are highly expressed in peribronchiolar mononuclear inflammatory cells and epithelial cells in OVA-treated mice. GSTM are expressed in epithelial cells in both OVA and PBS-treated groups. GSTP1 mRNA expression was increased in the lung of OVA-treated mice compared with PBS-treated mice. GSTA1, GSTM1, and GSTT1 mRNA expressions were not different between both groups. GSTA1 mRNA expression was increased in induced sputum cells of asthmatics compared with healthy controls. GSTP1, GSTM1, and GSTT1 mRNA expressions were not different between asthmatics and healthy controls. In asthmatics, GSTP1 and GSTA1 mRNA expressions were higher in induced sputum cells of asthmatics with PC20 ≤ 4 mg/ml than those with PC20 > 4 mg/ml. GSTM1 and GSTT1 mRNA expressions were not different between two groups. These findings suggest that GSTs are upregulated in the airways of asthmatics in response to increased oxidative stress. GSTP and GSTA are thought to play an important role in protecting the airways of asthmatics compared with GSTM and GSTT.

    PubMed IF 1.9 알레르기내과
30. 12292013

    제1저자 백우현 · 교신저자 류지곤

    Paik WH, Ryu JK, Song BJ, Kim J, Park JK, Kim YT, Yoon YB

    Clinical usefulness of plasma chromogranin a in pancreatic neuroendocrine neoplasm.

    J Korean Med Sci. 2013;28(5):750-4.

    Abstract

    Chromogranin A (CgA) is widely used as an immunohistochemical marker of neuroendocrine neoplasms and has been measurable in plasma of patients. We assessed the clinical role of plasma CgA in diagnosing pancreatic neuroendocrine neoplasm (PNEN). CgA was checked in 44 patients with pancreatic mass who underwent surgical resection from 2009 through 2011. The cutoff value for diagnosing PNEN and the relationships between CgA and clinicopathologic variables were analyzed. Twenty-six patients were PNENs and 18 patients were other pancreatic disorders. ROC analysis showed a cutoff of 60.7 ng/mL with 77% sensitivity and 56% specificity, and the area under the curve (AUC) was 0.679. Among PNEN group, the sensitivity and specificity of diagnosing metastasis were 100% and 90% respectively when CgA cutoff was 156.5 ng/mL. The AUC was 0.958. High Ki-67 index (160.8 vs 62.1 ng/mL, P = 0.001) and mitotic count (173.5 vs 74.6 ng/mL, P = 0.044) were significantly correlated with plasma CgA, but the tumor size was not. In conclusion, CgA has a little value in diagnosing PNEN. However, the high level of CgA (more than 156.5 ng/mL) can predict the metastasis. Also, plasma CgA level correlates with Ki-67 index and mitotic count which represents prognosis of PNENs.

    PubMed IF 3.2 소화기내과

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