SCI 발표논문

1. 1222013

   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
2. 1212013

   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
3. 1202013

   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
4. 1192013

   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
5. 1182013

   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
6. 1172013

   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
7. 1162013

   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
8. 1152013

   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
9. 1142013

   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
10. 1132013

    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
11. 1122013

    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
12. 1112013

    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
13. 1102013

    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
14. 1092013

    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
15. 1082013

    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
16. 1072013

    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
17. 1062013

    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
18. 1052013

    제1저자 강민정 · 교신저자 김태유

    Kang MJ, Kim HP, Lee KS, Yoo YD, Kwon YT, Kim KM, Kim TY, Yi EC

    Proteomic analysis reveals that CD147/EMMPRIN confers chemoresistance in cancer stem cell-like cells.

    Proteomics. 2013;13(10-11):1714-25.

    Abstract

    Cancer stem cells (CSCs) are a subpopulation of tumor cells that can self-renew, metastasize, and promote cancer recurrence. A comprehensive characterization of the CSC proteome has been hampered due to their scarcity and rapid differentiation. Here, we present a systematic analysis of the cell-surface proteome using a CSC-like cell line derived from MDA-MB453 breast cancer cells, which exhibited a CD44(+) /CD24(-) (where CD is cluster of differentiation) phenotype and chemoresistance. We identified differentially expressed proteins in CSC-like cells, including upregulated plasma membrane proteins such as CD44, CD133, epidermal growth factor receptor (EGFR), CD147, cadherin 1, integrins, and catenin (cadherin-associated protein), beta 1 (CTNNB1), using an in-situ biotinylation approach followed by MS analysis. We examined the role of CD147 in the promotion of CSC growth and survival, and demonstrated that inhibition of CD147 with a monoclonal antibody induced significant inhibition of cell growth. siRNA-mediated silencing of CD147 gene expression restored the sensitivity of CSC-like cells to 5-fluorouracil (5-FU), along with decreasing the expression of thymidylate synthase, p-AKT, and β-catenin, while increasing the expression of p-glycogen synthase kinase (GSK)3β. Increased CD147 expression in the CSC-like cells, as seen by proteomic analysis, and the functional consequences of CD147 overexpression in CSC-like cells suggest that CD147 may be one of the critical cell-surface proteins involved in promoting chemoresistance and survival in CSCs.

    PubMed IF 4.1 혈액종양내과
19. 1042013

    제1저자 한세원 · 교신저자 김태유

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

    Methylation and microsatellite status and recurrence following adjuvant FOLFOX in colorectal cancer.

    Int J Cancer. 2013;132(9):2209-16.

    Abstract

    The prognostic impact of CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the treatment outcome of colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. We investigated CIMP and MSI status in colorectal cancer patients treated with adjuvant FOLFOX. Stages II and III sporadic colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Eight CpG island loci (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, CDKN2A (p16), RUNX3 and SOCS1) and five microsatellite markers were examined. Disease-free survival (DFS) was analyzed according to CIMP and MSI status. A total of 322 patients were included: male/female 192/130, median age 61 years (range 30-78), proximal/distal location 118/204 and Stages II/III 43/279. CIMP status was high in 25 patients (7.8%) and 21 patients (6.5%) had MSI-high tumor. CIMP/MSI status was not significantly associated with DFS: 3-year DFS 100% in CIMP(-)/MSI(+), 84% in CIMP(-)/MSI(-), 82% in CIMP(+)/MSI(-) and 75% in CIMP(+)/MSI(+) (p = 0.33). Results of exploratory analysis showed that concurrent methylation at NEUROG1 and CDKN2A (p16) was associated with shorter DFS: 3-year DFS 69% in NEUROG1(+)/CDKN2A (p16)(+) versus 87% in NEUROG1(-)/CDKN2A (p16)(-) (p = 0.006). In conclusion, concurrent methylation of NEUROG1 and CDKN2A (p16) is associated with recurrence following adjuvant FOLFOX in Stages II/III colorectal cancer.

    PubMed IF 4.9 혈액종양내과
20. 1032013

    제1저자 이윤규 · 교신저자 김인호

    Lee YG, Kim I, Yoon SS, Park S, Cheong JW, Min YH, Lee JO, Bang SM, Yi HG, Kim CS, Park Y, Kim BS, Mun YC, Seong CM, Park J, Lee JH, Kim SY, Lee HG, Kim YK, Kim HJ, Korean Society of Haematology AML/MDS working party

    Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes.

    Br J Haematol. 2013;161(3):339-47.

    Abstract

    The present study aimed to directly compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndromes (MDS). We compared the overall response rate (ORR) (complete responses, partial responses, marrow complete responses, and haematological improvements), overall survival (OS), event-free survival (EFS), time to leukaemic transformation, and adverse outcomes between azacitidine and decitabine. To minimize the effects of treatment selection bias in this observational study, adjustments were made using the propensity-score matching method. Among 300 patients, 203 were treated with azacitidine and 97 with decitabine. Propensity-score matching yielded 97 patient pairs. In the propensity-matched cohort, there were no significant differences between the azacitidine and decitabine groups regarding ORR (44% vs. 52%), OS (26 vs. 22.9 months), EFS (7.7 vs. 7.0 months), and rate of leukaemic transformation (16% vs. 22% at 1 year). In patients ≥ 65 years of age, survival was significantly better in the azacitidine group (P = 0.017). Patients who received decitabine experienced more frequent episodes of grade 3 or 4 cytopenia and infectious episodes. We found that azacitidine and decitabine showed comparable efficacy. Among patients ≥ 65 years of age, survival was significantly better in the azacitidine group (ClinicalTrials.gov Identifier: NCT01409070).

    PubMed IF 3.6 혈액종양내과
21. 1022013

    제1저자 진광남 · 교신저자 이창훈

    Jin KN, Kim DK, Kim JS, Heo EY, Lee CH

    Bubble-like air opacities in the mediastinum.

    Am J Respir Crit Care Med. 2013;187(9):e16-7.

    PubMed IF 21.7 호흡기내과
22. 1012013

    제1저자 유수종 · 교신저자 김윤준

    Yu SJ, Lee JH, Jang ES, Cho EJ, Kwak MS, Yoon JH, Lee HS, Kim CY, Kim YJ

    Hepatocellular carcinoma: high hepatitis B viral load and mortality in patients treated with transarterial chemoembolization.

    Radiology. 2013;267(2):638-47.

    Abstract

    PURPOSE To determine the relationship between hepatitis B virus (HBV) DNA level and the survival of patients with hepatocellular carcinoma treated by means of transarterial chemoembolization (TACE).

    MATERIALS AND METHODS This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. From January 2005 to March 2007, 183 patients with HBV-related hepatocellular carcinoma who underwent TACE but never received antiviral therapy were consecutively enrolled in our cohort. All patients were tested for pre-TACE serum level of HBV DNA, and overall survival was measured from date of enrollment until death from any cause. Radiologic progression was evaluated by using the modified response evaluation criteria in solid tumors by means of independent radiologic assessment.

    RESULTS The median overall survival was 19 months (95% confidence interval: 13.7, 24.3) and median time to progression was 4 months (95% confidence interval: 3.03, 4.97). Multivariate analysis revealed that a high pre-TACE serum level of HBV DNA (> 2000 IU/L) was an independent risk factor for reduced overall survival (P = .021; hazard ratio [HR], 1.725), high cancer progression-related mortality (P = .014; HR, 1.936), and hepatic failure-related mortality associated with cancer progression (P = .005, HR, 3.908). Pre-TACE level of HBV DNA did not significantly affect hepatic failure-related mortality that was not caused by cancer progression.

    CONCLUSION A high pre-TACE serum level of HBV DNA was associated with poor overall survival and rapid progression of hepatocellular carcinoma after TACE, and the cause of mortality was not hepatitis exacerbation but cancer progression.

    PubMed IF 17.6 소화기내과
23. 1002013

    제1저자 윤혁 · 교신저자 김상균

    Yoon H, Kim SG, Choi J, Im JP, Kim JS, Kim WH, Jung HC

    Risk factors of residual or recurrent tumor in patients with a tumor-positive resection margin after endoscopic resection of early gastric cancer.

    Surg Endosc. 2013;27(5):1561-8.

    Abstract

    BACKGROUND In cases with a tumor-positive resection margin after endoscopic resection of early gastric cancer (EGC), not all patients are found to have residual or recurrent tumor. The aim of this study was to identify risk factors associated with residual/recurrent tumor in patients with incomplete endoscopic resection of EGC.

    METHODS A retrospective analysis was performed on consecutive patients who underwent endoscopic resection of EGC at a single institution in South Korea. Patients with a tumor-positive resection margin in the specimen were divided into two groups, with and without residual/recurrent tumor, and the clinicopathologic characteristics were compared.

    RESULTS A total of 102 patients with a tumor-positive lateral or vertical resection margin after endoscopic mucosal resection (n = 10) or submucosal dissection (n = 92) were enrolled. Overall, the rate of residual/recurrent tumor was 33.3 % (34/102): 17 residual tumors in 46 patients who immediately underwent additional endoscopic or surgical resection, and 17 recurrent tumors in 56 patients who were initially followed up with regular endoscopy during a median period of 17 (range = 2-70) months. Univariate analysis showed that the presence of ulcer, the direction of the tumor-positive resection margin, and length of lateral resection margin involvement by the tumor were associated with the incidence of residual/recurrent tumor. In multivariate analysis, total length (cm) of lateral resection margin involvement was the only independent risk factor for residual/recurrent tumor (OR 2.05; 95 % CI 1.22-3.44, p = 0.006).

    CONCLUSIONS Patients with extensive tumor involvement of a lateral resection margin after endoscopic resection of EGC should consider additional endoscopic or surgical resection due to a high risk of residual/recurrent tumor.

    PubMed IF 3.3 소화기내과
24. 992013

    제1저자 서정원 · 교신저자 최동주

    Suh JW, Yoon YE, Oh IY, Yoon CH, Cho YS, Youn TJ, Chae IH, Choi DJ

    A single-center prospective randomized controlled trial evaluating the safety and efficacy of IntraCoronary Erythropoietin delivery BEfore Reperfusion: gauging infarct size in patients with acute ST-segment elevation myocardial infarction. Study design and rationale of the 'ICEBERG Trial'.

    Contemp Clin Trials. 2013;35(1):145-50.

    Abstract

    BACKGROUND Erythropoietin (EPO) protected the myocardium from ischemia and reperfusion injury in preclinical studies. However, whether EPO can reduce myocardial injury in patients with acute myocardial infarction (MI) is controversial. The inconsistent results of previous studies have been attributed to differences in the doses, timing, and routes of administration of EPO. In this study, we will evaluate intracoronary treatment with a long-acting EPO analog, darbepoetin-α, administered immediately before reperfusion in patients with acute anterior ST-segment elevation MI.

    METHODS This trial will be a single-center, prospective, randomized, two-arm, controlled trial with blind evaluation of the endpoints. At the time of the primary percutaneous coronary intervention, 80 patients will randomly receive one of the following treatments immediately before the first ballooning: intracoronary darbepoetin-α (ARANESP®; Jeil-Kirin Pharm., Korea) 300μg (n=40) or saline (n=40), administered via the over-the-wire balloon system. The objectives of this study are to evaluate the safety and efficacy of intracoronary darbepoetin-α therapy.

    DISCUSSION This is the first study to evaluate the safety and efficacy of intracoronary darbepoetin-α treatment in patients with acute MI.

    PubMed IF 1.9 순환기내과
25. 982013

    제1저자 김상균, 송호준 · 교신저자 정현채

    Kim SG, Song HJ, Choi IJ, Cho WY, Lee JH, Keum B, Lee YC, Kim JG, Park SK, Park BJ, Jung HC, Korean College of Helicobacter, Upper Gastrointestinal Research

    Helicobacter pylori eradication on iatrogenic ulcer by endoscopic resection of gastric tumour: a prospective, randomized, placebo-controlled multi-centre trial.

    Dig Liver Dis. 2013;45(5):385-9.

    Abstract

    INTRODUCTION The role of Helicobacter pylori (H. pylori) eradication has not been clarified in the healing of iatrogenic ulcer after endoscopic resection of gastric neoplasm. The aim of this study was to evaluate whether H. pylori eradication could facilitate the healing of iatrogenic ulcer after endoscopic resection of gastric neoplasm.

    METHODS A total of 232 patients with H. pylori-positive early gastric cancer or gastric adenoma underwent endoscopic resection and were randomly allocated to eradication or placebo group in a prospective, double-blinded, and placebo-controlled manner. The primary outcome was measured by healing rate of ulcer, and the secondary outcomes by reduction rate of ulcer size, relief rate from ulcer-related symptoms, and adverse event rates.

    RESULTS The healing rate of ulcer was 53% in eradication group and 51.6% in placebo group, respectively (p value=0.95). The reduction rate of ulcer size, relief rate from ulcer-related symptoms and adverse event rates were also not different between two groups. In multivariate analysis, initial ulcer size more than 3 cm and histology of cancer were significant factors affecting iatrogenic ulcer healing.

    CONCLUSIONS H. pylori eradication did not facilitate iatrogenic ulcer healing at early and late phase after endoscopic resection of gastric neoplasm.

    PubMed IF 4.9 소화기내과
26. 972013

    제1저자 조유리 · 교신저자 김윤준

    Cho Y, Lee DH, Chung KH, Jin E, Lee JH, Cho EJ, Yu SJ, Kim JW, Jeong SH, Yoon JH, Lee HS, Kim CY, Kim YJ

    The efficacy of adefovir plus entecavir combination therapy in patients with chronic hepatitis B refractory to both lamivudine and adefovir.

    Dig Dis Sci. 2013;58(5):1363-70.

    Abstract

    BACKGROUND The efficacy of adefovir (ADV) plus entecavir (ETV) combination in patients with chronic hepatitis B (CHB) who developed multidrug refractoriness had not been fully evaluated. We aimed to evaluate the efficacy of ADV plus ETV as compared to that of lamivudine (LAM) plus ADV in the patients with antiviral refractoriness to sequential LAM monotherapy and then ADV monotherapy.

    METHODS Twenty-seven patients were treated with a combination of ADV plus ETV and 63 patients were treated with a combination of LAM plus ADV. The virological and biochemical parameters were compared between the two groups, retrospectively.

    RESULTS Treatment with a combination of ADV plus ETV produced significantly superior virological response than that of a combination of LAM plus ADV. At 12 months, the HBV DNA declined more in the ADV plus ETV group than in the LAM plus ADV (-4.52 ± 1.956 vs. -2.65 ± 1.723 log 10 IU/mL; p = 0.001). The rate of a complete response at 12 months was greater in the ADV plus ETV group than that in the LAM plus ADV group (63.16 vs. 14.81 %, p < 0.001).

    CONCLUSION In the patients with CHB refractory to both LAM and ADV, the response to ADV plus ETV was significantly superior compared to that of the LAM plus ADV in suppressing HBV DNA. The result indicates that ADV plus ETV can be used as a bridging therapy in the patients with refractoriness to both LAM and ADV, especially in the areas where tenofovir is not yet available.

    PubMed IF 2.8 소화기내과
27. 962013

    제1저자 주권욱, 김세중 · 교신저자 나기영

    Joo KW, Kim S, Ahn SY, Chin HJ, Chae DW, Lee J, Han JS, Na KY

    Dipeptidyl peptidase IV inhibitor attenuates kidney injury in rat remnant kidney.

    BMC Nephrol. 2013;14:98.

    Abstract

    BACKGROUND The inhibition of dipeptidyl peptidase (DPP) IV shows protective effects on tissue injury of the heart, lung, and kidney. Forkhead box O (FoxO) transcriptional factors regulate cellular differentiation, growth, survival, the cell cycle, metabolism, and oxidative stress. The aims of this study were to investigate whether the DPP IV inhibitor sitagliptin could attenuate kidney injury and to evaluate the status of FoxO3a signaling in the rat remnant kidney model.

    METHODS Rats were received two-step surgery of 5/6 renal mass reduction and fed on an oral dose of 200 mg/kg/day sitagliptin for 8 weeks. Before and after the administration of sitagliptin, physiologic parameters were measured. After 8 weeks of treatment, the kidneys were harvested.

    RESULTS The sitagliptin treatment attenuated renal dysfunction. A histological evaluation revealed that glomerulosclerosis and tubulointerstitial injury were significantly decreased by sitagliptin. Sitagliptin decreased DPP IV activity and increased the renal expression of glucagon-like peptide-1 receptor (GLP-1R). The subtotal nephrectomy led to the activation of phosphatidylinositol 3-kinase (PI3K)-Akt and FoxO3a phosphorylation, whereas sitagliptin treatment reversed these changes, resulting in PI3K-Akt pathway inactivation and FoxO3a dephosphorylation. The renal expression of catalase was increased and the phosphorylation of c-Jun N-terminal kinase (JNK) was decreased by sitagliptin. Sitagliptin treatment reduced apoptosis by decreasing cleaved caspase-3 and -9 and Bax levels and decreased macrophage infiltration.

    CONCLUSIONS In rat remnant kidneys, DPP IV inhibitor attenuated renal dysfunction and structural damage. A reduction of apoptosis, inflammation and an increase of antioxidant could be suggested as a renoprotective mechanism together with the activation of FoxO3a signaling. Therefore, DPP IV inhibitors might provide a promising approach for treating CKD, but their application in clinical practice remains to be investigated.

    PubMed IF 2.9 신장내과
28. 952013

    제1저자 김진원, 전은주 · 교신저자 이근욱

    Kim JW, Chun EJ, Choi SI, Park DJ, Kim HH, Bang SM, Kim MJ, Lee JH, Lee MS, Lee JO, Kim YJ, Kim JH, Lee JS, Lee KW

    A prospective study on the incidence of postoperative venous thromboembolism in Korean gastric cancer patients: an inquiry into the application of Western guidelines to Asian cancer patients.

    PLoS One. 2013;8(4):e61968.

    Abstract

    Several Western guidelines recommend the routine use of pharmacologic thromboprophylaxis for cancer surgery patients to prevent venous thromboembolism (VTE). However, the necessity of routine pharmacologic perioperative thromboprophylaxis in Asian gastric cancer (GC) patients has not been clearly determined. To determine the necessity of routine perioperative pharmacologic thromboprophylaxis in Korean gastric cancer patients, the incidence of postoperative VTE was prospectively evaluated in gastric cancer patients receiving surgery. Among 610 GC patients who had received surgery, 375 patents underwent routine duplex Doppler ultrasonography (DUS) on days 5-12 following surgery to detect VTE and then VTE-related symptoms and signs were checked at 4 weeks after surgery (cohort A). The 235 patients that declined DUS were registered to cohort B and the occurrence of postoperative VTE was retrospectively analyzed. In cohort A, symptomatic or asymptomatic VTE until 4 weeks after surgery was detected in 9 patients [2.4%; 95% confidence interval (CI); 0.9-3.9]. Tumor stage was a significant factor related to VTE development [stage I, 1.4%; stage II/III, 2.4%; stage IV, 9.7% (P = 0.008)]. In multivariate analysis, patients with stage IV had a higher postoperative VTE development [odds ratio, 8.18 (95% CI, 1.54-43.42)] than those with stage I. In cohort B, a low incidence of postoperative VTE was reaffirmed; only one postoperative VTE case (0.4%) was observed. In conclusion, the incidence of postoperative VTE in Korean GC patients was only 2.4%. Risk-stratified applications of perioperative pharmacologic thromboprophylaxis are thought to be more appropriate than the routine pharmacologic thromboprophylaxis in Korean GC patients receiving surgery.

    PubMed IF 2.8 혈액종양내과
29. 942013

    제1저자 박진현 · 교신저자 김태유

    Park JH, Kim TY, Lee KH, Han SW, Oh DY, Im SA, Kang GH, Chie EK, Ha SW, Jeong SY, Park KJ, Park JG, Kim TY

    The beneficial effect of palliative resection in metastatic colorectal cancer.

    Br J Cancer. 2013;108(7):1425-31.

    Abstract

    BACKGROUND We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment.

    METHODS A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied.

    RESULTS Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003).

    CONCLUSION Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.

    PubMed IF 7.8 혈액종양내과
30. 932013

    제1저자 조현진 · 교신저자 김나영

    Jo HJ, Lee HS, Kim N, Nam RH, Chang H, Kim MS, Kim SE, Oh JC, Lee DH, Jung HC

    Predictable Marker for Regression of Barrett's Esophagus by Proton Pump Inhibitor Treatment in Korea.

    J Neurogastroenterol Motil. 2013;19(2):210-8.

    Abstract

    BACKGROUND/AIMS There has been no report regarding the regression of Barrett's esophagus (BE) by continuous treatment of proton pump inhibitor (PPI). The aim of this study was to determine the regression rate of BE by PPI and predictable markers related to regression.

    METHODS Thirty-five patients diagnosed as BE were consecutively enrolled and most of them took continuous PPI. The 25 patients underwent endoscopic surveillance and received biopsy. If the specialized intestinal metaplasia (SIM) was lost at any point of surveillance and did not recur, the case was regarded as the regression group. The proportion of SIM was graded and the mucin phenotype was decided using immunohistochemistry for MUC2, MUC5AC and MUC6. To assess the cell proliferation indexes and the degree of intestinal maturation, immunohistochemistry for Ki67 and CDX2 were performed.

    RESULTS The regression of BE occurred in the 11 (44%) patients. The clinical and demographic factors showed no difference between the regression (n = 11) and persistence group (n = 14). The lower grade of SIM (P < 0.001) and gastric predominant mucin phenotype (P = 0.018) were more frequent, and the number of Ki67 positive cell per gland (P = 0.008) and the mean extent of CDX2 (P = 0.022) were lower in the regression group than in the persistence group.

    CONCLUSIONS The regression of BE by PPI treatment was frequent in Korea. The immunohistochemical detection of mucin phenotype, grade of SIM, Ki67 and CDX2 expression in Barrett's mucosa could be useful as a predictable marker for regression of SIM in BE.

    PubMed IF 3.7 소화기내과

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