Seonwoo Kim

MEDIPOST Biomedical Research Institute, Sŏul, Seoul, South Korea

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Publications (83)300.21 Total impact

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    ABSTRACT: Growth factor receptors, often carrying tyrosine kinase activities in their cytoplasmic domains, are overexpressed in many cancers. Coactivation of receptor tyrosine kinases (RTKs) plays a critical role in tumor response to targeted therapeutics. We examined concomitant overexpression of EGFR and MET in patients with HER2+ and HER2- gastric cancers (GCs). Tissue microarray samples obtained from 1,589 GC patients who received R0 gastrectomy with extensive node dissection and adjuvant chemoradiationtherapy were analyzed by immunohistochemistry and fluorescence in situ hybridization. HER2+ was observed in 169 patients (11%). Out of 169 HER2+ patients, 15 (9%) were EGFR+ and MET+, 29 (17%) were EGFR+, 37 (22%) were MET+, and the remaining 88 patients (52%) were HER2+ only, without concomitant EGFR or MET overexpression. Greater number of overexpressed RTKs correlated with younger age (p<0.001), larger tumor size (p=0.027), intestinal histology (p<0.001), and shorter overall survival (p=0.002). The mean overall survival was 113 months for HER2-/EGFR-/MET- and 63 months for HER2+/EGFR+/MET+ subgroups. Patients with HER2+/EGFR+/MET+ GCs had a substantial risk of death with a hazard ratio of 3.01 (95% CI, 1.54–5.90), compared to HER2-/EGFR-/MET- GC patients. Using patient-derived tumor cell models isolated from pericardial effusion of HER2+ and MET+ GC cases, we demonstrated that the combination of HER2-inhibitor (lapatinib) and MET-inhibitor offered a more profound inhibition in the ERK/AKT pathway and cell proliferation than lapatinib alone. Co-overexpression of RTKs was demonstrated in small subsets of GC associated with aggressive behavior, and in these cases, combination therapy may be considered as potential treatment options. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2014; · 6.20 Impact Factor
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    ABSTRACT: The aim of this study was to both develop and validate a nomogram based on the Ki-67 index to predict recurrence. We constructed a nomogram using the Cox proportional hazards model with 953 N0 and N1 postoperative hormone receptor (HR)-positive breast cancer patients and validated it in an external cohort of 895 patients. A prognostic model that used classical variables, Adjuvant! Online, St. Gallen risk stratification, and the four immunohistochemistry (IHC) markers (IHC4 score) was created and assessed by the likelihood ratio χ(2) (LR-χ(2)) test using the bootstrapping method. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.75 (95% CI 0.72-0.77) in the training set. The validation set showed good discrimination with an AUC of 0.63 (95% CI 0.60-0.66). In the LR-χ(2) test, the nomogram score was found to be more informative than the IHC4 with clinical score (CS) [LR-χ(2) 13.365 (1 d.f.); 95% CI 2.50-24.23 for CS-IHC4 + nomogram score vs. CS-IHC4] on distant recurrence-free survival. This study implies that the amount of prognostic information contained in the nomogram is superior to that in the CS-IHC4 score in HR-positive N0 and N1 breast cancer patients (NCT1273415). © 2014 S. Karger AG, Basel.
    Oncology 06/2014; 86(5-6):279-288. · 2.17 Impact Factor
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    ABSTRACT: Caregivers for patients with Alzheimer's disease (AD) suffer from psychological and financial burdens. However, the results of the relationship between burden and cognitive function, performance of activities of daily living, and depressive symptoms have remained inconsistent. Therefore, the aim of this study was to examine which factors are more significant predictors of heightened burden, cognitive impairment or functional decline, besides neuropsychiatric symptoms.
    Psychiatry investigation 04/2014; 11(2):152-9. · 1.06 Impact Factor
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    ABSTRACT: Endoscopic resection has become standard therapy for selected patients with early gastric carcinoma (EGC). However, the preoperative diagnostic accuracy for excluding submucosal (SM) invasion is not precise. Moreover, histologic features predicting SM invasion in gastric carcinomas (SMiGC) have not been studied extensively. Pre-treatment gastric biopsies from 60 patients with SM invasion who underwent endoscopic resection were reviewed and compared to 58 biopsies of lesions confirmed to be intramucosal carcinomas (IMC). For validation of the results, an independent cohort consisting of 616 gastric biopsies confirmed as EGC were analyzed. For statistical analyses, chi-square test, Fisher's exact test and multiple logistic progression tests were used. In the biopsy specimens of patients with SMiGCs, differentiated histology, poorly differentiated component, wisps of muscularis mucosa, tumor cribriforming, papillary architecture, desmoplasia and intraglandular eosinophilic necrotic debris (IEND) were observed in 96.7%, 36.7%, 16.7%, 16.7%, 23.3%, 40%, and 46.7% of cases, respectively, while the same features were observed in 100%, 5.2%, 0%, 1.7%, 5.2%, 19%, and 22.4% of biopsies with IMC. In multivariate analyses, poorly differentiated component [odds ratio (OR), 9.59, p = 0.002], IEND [OR, 6.23, p = 0.012], tumor cribriforming [OR, 4.66, p = 0.03] and papillary architecture [OR, 5.52, p = 0.018] were significantly associated with the detection of SM invasion. In the validation cohort, poorly differentiated component (p = 0.003) and papillary architecture (p = 0.008) remained significant. Poorly differentiated component and papillary architecture are significant histopathologic predictors of SM invasion in pretreatment gastric biopsies of lesions considered for endoscopic therapy. Additional prospective studies are warranted to confirm our findings.Virtual slide: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1588557731103084.
    Diagnostic Pathology 02/2014; 9(1):34. · 2.41 Impact Factor
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    ABSTRACT: The impact of pretreatment nutritional status on the treatment outcome of non-Hodgkin lymphoma has never been explored. Among the 953 patients who were registered in a prospective cohort at Samsung Medical Center., we analyzed 262 patients who had been treated with Ruximab-cyclophosphamide, doxorubicin, vincristine, and prednisone for newly diagnosed diffuse large B-cell lymphoma (DLBCL) and for whom data were available regarding pretreatment nutritional status. Nutritional status at diagnosis was assessed by triceps skin fold (TSF), mid-arm muscle circumference (MAMC), body mass index (BMI), serum albumin, prealbumin, and transferrin. For patients aged 60 yr and older, poor performance and higher tumor burden were associated with malnourishment represented by albumin <3.5 g/dL, prealbumin < 17 g/dL, and transferrin <170 mg/L. Lower BMI (<20), serum albumin, prealbumin, and transferrin were identified as risk factors for febrile neutropenia in univariate analysis, but not in multivariate analysis. In the univariate analysis for OS, all nutritional parameters except MAMC showed a significant association with survival. However, BMI was the only parameter that was independently prognostic for OS in the multivariate analysis (P = 0.031; hazards ratio = 3.32). Nutritional insufficiency encountered in DLBCL patients might influence the occurrence of treatment-related toxicity and poor survival outcome of patients.
    Nutrition and Cancer 01/2014; · 2.70 Impact Factor
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    ABSTRACT: Background The incidence, risk factors and management strategy of paradoxical reaction to midazolam during endoscopy are yet to be clarified. Methods This single center prospective study included 4140 adult patients (2263 males, mean age of 57.7 ± 12.6) undergoing endoscopy under sedation with midazolam and pethidine between September 2011 and December 2011. The characteristics of patients with and without paradoxical reaction were compared. For patients who experienced paradoxical reaction and received flumazenil, their endoscopic images were reviewed to assess whether European Society of Gastrointestinal Endoscopy guidelines were met as quality indicator of endoscopy. Results The incidence of paradoxical reaction was 1.4%. In multivariate analyses, male gender, unsuccessful sedation in previous endoscopy, upper endoscopy, higher dose of midazolam, and lower dose of pethidine were identified as independent risk factors for paradoxical reaction. Despite paradoxical reaction, endoscopic procedures were successfully completed in 93.3% of cases when flumazenil was administered. The rates of meeting quality indicator of endoscopy were 92.3% in patients receiving flumazenil for paradoxical reaction and 97.6% in patients without paradoxical reaction. Conclusions For patients with risk factors for paradoxical reaction, active use of pethidine with a dose reduction of midazolam might be helpful to prevent the occurrence of paradoxical reaction. Administration of flumazenil might be positively considered in cases of paradoxical reaction.
    Digestive and Liver Disease. 01/2014;
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    ABSTRACT: Genetic polymorphism contributes to variation in response to drug treatment of depression. We conducted three independent 6-week treatment studies in outpatients with major depressive disorder (MDD) to develop a pharmacogenomic model predicting response and nonresponse. We screened candidate genomic markers for association with response to selective serotonin reuptake inhibitors (SSRIs). No patients had received any antidepressant drug treatment in the current episode of depression. Outcome evaluation was blinded to drug and genotype data. The prediction model derived from a development sample of 239 completer cases treated with SSRIs comprised haplotypes and polymorphisms related to serotonin synthesis, serotonin transport, glutamate receptors, and GABA synthesis. The model was evaluated prospectively for prediction of outcome in a validation sample of 176 new SSRI-treated completer cases. The model gave a prediction in 60% of these cases. Predictive values were 85% for predicted responders and 86% for predicted nonresponders, compared to prior probabilities of 66% for observed response and 34% for observed nonresponse in those cases (both P<0.001). Convergent cross-validation was obtained through failure of the model to predict outcomes in a third independent sample of 189 completer cases who received non-SSRI antidepressants. We suggest proof of principle for genetic guidance to use or avoid SSRIs in a majority of Korean depressed patients.
    PLoS ONE 01/2014; 9(9):e107098. · 3.53 Impact Factor
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    ABSTRACT: Paclitaxel and gemcitabine (PG) combination chemotherapy is effective as a maintenance chemotherapeutic regimen in metastatic breast cancer (MBC) patients because it increases progression-free survival (PFS), which increases overall survival (OS). The primary purpose of our study was to investigate the association between genetic polymorphisms in the genes involved in PG pathways and clinical outcomes in MBC patients treated with PG chemotherapy. A total of 324 MBC patients were enrolled in this prospective multicenter trial of PG as the first-line chemotherapy. Eighty-five of the 324 patients from two institutes were available for analysis of single nucleotide polymorphisms (SNPs). Germline DNA was extracted from peripheral blood mononuclear cells. Thirty-eight SNPs in 15 candidate genes selected from pathways that may influence the metabolism and transport of, or sensitivity, to PG were analysed. The median PFS and OS of all 324 patients were 8.7months (95% confidence interval [CI]: 7.5-9.6months) and 26.9months (95% CI: 23.6-30.1months), respectively. An SNP in SLC28A3 (rs7867504, C/T) was associated with OS (CC or CT versus TT: 37 versus 21months, p=0.027, hazard ratio [HR] 2.6, 95% CI: 1.1-6.3). SLC29A1 GA haplotype had a significantly shorter OS (p=0.030, HR 3.391, 95% CI: 1.13-10.19). RRM1 (ribonucleotide reductase large subunit M1) SNP (rs9937), and haplotypes ATAA and ATGA were significantly associated with neurotoxicity. Genetic polymorphisms in SLC28A3, SLC29A1 and RRM1 can influence the clinical outcome of MBC patients treated with PG chemotherapy. Further studies on the functional mechanisms relating to these germline polymorphisms in these genes are warranted.
    European journal of cancer (Oxford, England: 1990) 12/2013; · 4.12 Impact Factor
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    ABSTRACT: PURPOSE We compared the diagnostic accuracy of co-registered whole body (WB) MRI-PET with that of WB PET-CT in determining the preoperative stage of non-small cell lung cancer (NSCLC). METHOD AND MATERIALS From January 2010 through November 2011, we prospectively enrolled 141 NSCLC patients (86 men, 55 women; mean age, 62 years) who had resectable disease on conventional staging using chest CT. They underwent whole body MRI including diffusion weighted MR imaging of the thorax and PET-CT, which were postprocessed for co-registration of MRI and PET. Two independent, blinded readers determined preoperative stage in the review of WB MRI-PET or PET-CT. Reference standards were obtained for T (n = 106) and N (n = 126) stages based on pathologic results, while M stage (n = 141) were obtained based on pathologic or follow-up imaging findings. The accurate staging, over staging, and under staging were compared by using the McNemar test. RESULTS The accuracy of TNM stage grouping were higher with WB MR-PET (95/141, 67%) than with PET-CT (82/141, 58%) (P =.009) and WB MR-PET significantly decreased the number of under stage (27% in PET-CT vs. 16% MR-PET, P <.001), not increasing the number of over stage (15% in PET-CT vs. 17% in MR-PET, P =.439). T stage was more accurate with MR-PET (81%) than PET-CT (72%) (P =.025) and MR-PET significantly decreased the number of under stage (12% in PET-CT vs. 5% in MR-PET, P =.020). The accuracy of N staging was not different between two modalities (71% in PET-CT vs. 70% in MR-PET, P =.782). The number of under stage was decreased with borderline significance (18% in PET-CT vs. 14% in MR-PET, P =.059). M staging was not different in number of accurate staging (87% in PET-CT vs. 90%, in MR-PET, P =.132) and over staging (1% in PET-CT vs. 3% in MR-PET, P =.317), but MR-PET significantly decreased the number of under stage (12% in PET-CT vs. 7% in MR-PET, P =.008). CONCLUSION WB MRI-PET can be a superior diagnostic modality to PET/CT for T and M staging of NSCLC. For N staging, both MRI-PET and PET-CT show comparable results. CLINICAL RELEVANCE/APPLICATION The development and application of simultaneous WB MRI-PET would be advantageous for the tumor evaluation and the detection of metastasis in cancer imaging and staging.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: Although peripherally-inserted central catheter (PICC) insertion is commonly performed under fluoroscopic guidance, few reports have addressed performance and dosimetry when PICC is inserted under C-arm fluoroscopy. To evaluate the risk factors of radiation dose in performing PICC insertion using flat panel detector-based mobile C-arm fluoroscopy and a conventional angiography machine. Ninety-eight patients underwent the PICC procedure using conventional angiography equipment (n=49) or flat panel detector-based mobile C-arm fluoroscopy (n=49). Data were prospectively analyzed from July to November 2012. Dose-area product (DAP), tube voltage, tube current, fluoroscopy time, and image quality measured on a 5-point scale were estimated and compared using appropriate statistical tests. There were no significant differences in tube voltage, fluoroscopy time, and image quality between conventional angiography and mobile C-arm fluoroscopy. DAP, mean arm tube current, and tube current in chest fluoroscopy were significantly lower in mobile C-arm fluoroscopy than using the conventional angiography machine (P <0.05). Multivariate analysis identified tube current in chest fluoroscopy, arm tube current, and fluoroscopy equipment as significant risk factors for elevated radiation dose in PICC insertion. PICC insertion can be performed using flat panel detector-based mobile C-arm fluoroscopy instead of a conventional angiography machine. Image quality and fluoroscopy time were not different between the two systems and the use of C-arm fluoroscopy significantly reduced radiation dose.
    Acta Radiologica 11/2013; · 1.33 Impact Factor
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    ABSTRACT: Single nucleotide polymorphisms (SNP) are inter-individual genetic variations that could explain inter-individual differences of response/survival to chemotherapy. The present study was performed to build up a risk model for survival in 247 patients with acute myeloid leukaemia (AML) with normal karyotype (AML-NK). Genome-wide Affymetrix SNP array 6.0 was used for genotyping in discovery set (n = 118). After identifying significant SNPs for overall survival (OS) in single SNP analysis, a risk model was constructed. Out of 632 957 autosomal SNPs analysed, finally four SNPs (rs2826063, rs12791420, rs11623492 and rs2575369) were introduced into the risk model. The model could stratify the patients according to their OS in discovery set (P = 1·053656 × 10−4). Replication was performed using Sequenom platform for genotyping in the validation cohort (n = 129). The model incorporated with clinical and four SNP risk score was successfully replicated in a validation set (P = 5·38206 × 10−3). The integration of four SNPs and clinical factors into the risk model showed higher area under the curve (AUC) reults than in the model incorporating only clinical or only four SNPs, suggesting improved prognostic stratification power by combination of four SNPs and clinical factors. In conclusion, a genome-wide SNP-based risk model in 247 patients with AML-NK can identify a group of high risk patients with poor survival.
    British Journal of Haematology 10/2013; 163(1):62-71. · 4.94 Impact Factor
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    ABSTRACT: The establishment of better selection criteria for identifying sub-populations that may benefit from treatment is a key aspect of the development and success of targeted therapy. To investigate methods for assessing MET overexpression in gastric cancer, we conducted immunohistochemistry using a new anti-Total MET monoclonal antibody in a single-institution cohort of 495 patients. As antibody is directed against a membranous and/or cytoplasmic epitope, two interpretation methods were used: (1) membranous and cytoplasmic and (2) membranous alone. In selected 120 cases, copy number gain and mRNA expression levels were measured using quantitative real-time PCR. Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in 108 cases (21.8%) and membranous alone overexpression was observed in 40 cases (8.1%). The highest correlation was observed in membranous and cytoplasmic staining of MET: MET expression scores correlated significantly with high MET mRNA levels (r=0.465, P<0.0001), increased copy number gain (r=0.393, P=0.000002) and amplification of MET gene. Moreover, patients with MET overexpression showed shorter overall survival (HR, 1.781; 95% CI, 1.324-2.395; P<0.001) and disease-free survival (HR, 1.765; 95% CI, 1.227-2.541; P=0.002) compared with patients without MET overexpression. However, membranous overexpression of MET did not highly correlate with mRNA level (r=0.274, P=0.002), copy number gain or survival (P>0.05). We developed highly correlating interpretation methods of MET immunohistochemistry in gastric carcinomas. MET overexpression is an independent prognostic factor and could be a potential target and predictor of benefit for targeted therapy with MET inhibitors.Modern Pathology advance online publication, 28 June 2013; doi:10.1038/modpathol.2013.108.
    Modern Pathology 06/2013; · 5.25 Impact Factor
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    ABSTRACT: Background:Extrapyramidal signs (EPSs) are commonly observed in patients with Alzheimer disease (AD). We report here the base rate of EPS in a large cohort of patients with AD who were not receiving neuroleptic drugs, and the associations of EPS with functional outcomes and depressive symptoms.Methods:In a consortium involving 56 clinics, we recruited 2614 patients with AD. We estimated basic activities of daily living (ADL) and instrumental ADL by the Barthel index and the Seoul-Instrumental Activities of Daily Living (S-IADL) scales, respectively. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). The EPS group was defined by the presence of at least 1 EPS based on a focused neurologic examination.Results:The prevalence of EPS-positive patients was 12%. These had lower Korean version of the Mini-Mental State Examination (K-MMSE) scores than the EPS-negative cases (P < .001). After controlling for demographic, medical, radiological, genetic, and cognitive (K-MMSE) factors, the proportion of patients with impaired ADL was significantly higher in the EPS group than in the non-EPS group (P < .001, odds ratio = 1.90, 95% confidence interval, 1.45-2.48, and logistic regression). The S-IADL scores were significantly higher in the EPS group than this in the non-EPS group (P < .001, regression coefficient = 3.19, and median regression). The GDS-15 scores were higher in the EPS group (P = .04, regression coefficient = 0.89, and median regression).Conclusion:The presence of EPS in patients with AD who were not receiving neuroleptic drugs was associated with more impaired basic and instrumental ADL functioning and with greater depression symptoms.
    Journal of Geriatric Psychiatry and Neurology 06/2013; · 3.53 Impact Factor
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    ABSTRACT: We were not aware of a well-validated patellofemoral joint-specific scoring system. We performed this study to develop and validate a scoring system (Samsung Medical Center [SMC] patellofemoral scoring system) suitable for the evaluation of patellofemoral joint status. We recruited 179 individuals consisting of a study group of 123 patients with anterior knee pain but without pain in another part of the knee, twenty-eight patients with knee pain other than anterior knee pain (group A), and twenty-eight healthy volunteers without knee pain (group B). Items in the development of the scoring system that showed a significant difference between the study group and group A and between the study group and the group B were selected. Test-retest reliability was measured by intraclass correlation coefficient, internal consistency was measured by the Cronbach alpha, content validity was assessed by ceiling and floor effects, and construct validity was determined by the association of the Feller scores and the SMC patellofemoral scores. After the item verification process, seventeen items (eight items for patellofemoral pain and nine items for patellofemoral function) were selected. Test-retest reliability for overall SMC patellofemoral scores showed excellent reliability (intraclass correlation coefficient, 0.85), and internal consistency was excellent (Cronbach alpha, 0.97). Floor and ceiling effects were acceptable (<30%) for all the items of the SMC patellofemoral scoring system, except one: sitting down on a chair, in the patellofemoral function score. The SMC patellofemoral scores showed moderate correlation with the Feller scores (ρ = -0.45). The SMC patellofemoral score is a novel scoring system that distinguishes patients with anterior knee pain or patellofemoral dysfunction from patients with knee pain or dysfunction arising from other knee problems, and from those without knee pain. The reliability and validity of the SMC patellofemoral scoring system were verified in the present study.
    The Journal of Bone and Joint Surgery 04/2013; 95(7):620-6. · 3.23 Impact Factor
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    ABSTRACT: Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD). Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences. Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives. BDNF genotyping may be informative for anticipating chronicity in major depression.
    Psychiatry investigation 03/2013; 10(1):56-61. · 1.06 Impact Factor
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    ABSTRACT: BACKGROUND: The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging-positron emission tomography (MRI-PET) would increase the number of correctly upstaged patients compared with WB PET-computed tomography (PET-CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC). METHODS: From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI-PET or WB PET-CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging. RESULTS: Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI-PET group and in 26 of 120 patients (21.7%) in the PET-CT plus brain MRI group (4.2% difference; 95% confidence interval, -6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI-PET group and in 7 of 120 patients (5.8%) in the PET-CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%-20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (-10.7% difference; 95% confidence interval, -20.1% to -1.4%; P = .022). CONCLUSIONS: Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI-PET did not appear to help identify significantly more correctly upstaged patients than PET-CT plus brain MRI in patients with NSCLC. Cancer 2013;. © 2013 American Cancer Society.
    Cancer 02/2013; · 5.20 Impact Factor
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    ABSTRACT: Acute hepatic failure (AHF) is one of the most serious complications of transcatheter arterial chemoembolization (TACE). The aims of this study were to investigate risk factors of AHF after TACE and to establish a predictive model for AHF. In the evaluation set, a total of 820 patients who underwent TACE as a first treatment for hepatocellular carcinoma were included. The demographic, laboratory, radiological and treatment-related factors were analysed to identify risk factors for AHF after TACE and a predictive model was established using the identified risk factors. In the validation set, a different cohort of 438 patients was included to validate the predictive model. The incidence of post-TACE AHF was 15.1% (124/820). Multivariate analysis revealed that presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and log alpha-foetoprotein levels, and low albumin and sodium levels were independent risk factors. A mathematical model was established using these independent risk factors, and the area under the receiver operating characteristic curve of the model was 0.773 (95% confidence interval, 0.726-0.820). The cut-off value of 9 had a sensitivity of 78.2%, a specificity of 72.3%, a positive likelihood ratio of 2.82, a negative likelihood ratio of 0.30, a positive predictive value of 28.9% and a negative predictive value of 95.8%. The risk factors of post-TACE AHF were presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and alpha-foetoprotein levels, and low serum albumin and sodium levels. A mathematical model to predict post-TACE AHF was established.
    Liver international: official journal of the International Association for the Study of the Liver 02/2013; 33(2):197-202. · 3.87 Impact Factor
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    ABSTRACT: Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.
    PLoS ONE 01/2013; 8(12):e82770. · 3.53 Impact Factor
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    ABSTRACT: Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be performed in both primary and distant metastatic sites.Modern Pathology advance online publication, 14 December 2012; doi:10.1038/modpathol.2012.205.
    Modern Pathology 12/2012; · 5.25 Impact Factor
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    ABSTRACT: BACKGROUND: In the past few years, the number of clinical trials has increased rapidly in East Asia, especially for gastric and hepatobiliary cancer that are prevalent in Asian populations. However, the actual degree of understanding or perceptions of clinical trials by cancer patients in East Asian countries have seldom been studied. METHODS: Between July 1st and November 30th of 2011, we conducted a prospective study to survey cancer patients regarding their awareness of, and willingness to participate in, a clinical trial. Patients with gastrointestinal/hepatobiliary cancer who visited the Hematology-Oncology outpatient clinic at Samsung Medical Center (SMC) were enrolled. A total of 21 questions were asked including four questions which used the Visual analogue scale (VAS) score. RESULTS: In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%). The awareness of clinical trials was substantially higher in patients who had a higher level of education (p<0.001), were married (p=0.004), and had a higher economic status (p=0.001). However, the willingness to participate in a clinical trial was not affected by the level of education or economic status of patients. The most influential factors for patient willingness to participate were a physician recommendation (n=181, 26.8%), limited treatment options (n=178, 26.4%), and expectations of effectiveness of new anti-cancer drugs (n=142, 21.0%). Patients with previous experience in clinical trials had a greater willingness to participate in clinical trials compared to patients without previous experience (p<0.001). CONCLUSIONS: This large patient cohort survey study showed that Korean cancer patients are more aware of clinical trials, but awareness did not translate into willingness to participate.
    BMC Cancer 12/2012; 12(1):594. · 3.33 Impact Factor

Publication Stats

1k Citations
300.21 Total Impact Points

Institutions

  • 2009–2014
    • MEDIPOST Biomedical Research Institute
      Sŏul, Seoul, South Korea
  • 2013
    • Korea Electrotechnology Research Institute-KERI
      • Advanced Medical Device Research Center
      Tsau-liang-hai, Busan, South Korea
  • 2006–2012
    • Samsung Medical Center
      • Department of Hematology and Oncology
      Sŏul, Seoul, South Korea
  • 2002–2012
    • Sungkyunkwan University
      • • Department of Psychiatry
      • • Samsung Medical Center
      • • School of Medicine
      • • Department of Radiology
      Sŏul, Seoul, South Korea
  • 2011
    • Dongguk University
      • Department of Internal Medicine
      Seoul, Seoul, South Korea