Choon-Taek Lee

Seoul National University Bundang Hospital, Sŏul, Seoul, South Korea

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Publications (153)459.87 Total impact

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    ABSTRACT: Background: Sodium-potassium-chloride cotransporter isoform 1 (NKCC1) is an active ions cotransporter and modulates cellular volume and migration. NKCC1 blockers can inhibit cancer cell growth. Aim: We aimed to elucidate the expression and prognostic significance of NKCC1 in non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed 788 NSCLC patients with either adenocarcinoma (n = 503) or squamous cell carcinoma (n = 285) by immunohistochemistry to correlate NKCC1 expression with clinicopathologic and survival outcomes. Results: In adenocarcimoma, high NKCC1 expression was associated with larger tumor size (p = 0.013), vascular invasion (p < 0.001), lymphatic invasion (p < 0.001), perineural invasion (p = 0.019) and advanced pathologic stage (p < 0.001), but there are no significant correlations between NKCC1 expression and clinicopathological parameters in squamous cell carcinoma. Patients with high NKCC1 expression had significantly shorter disease-free survival (DFS; p < 0.001) and shorter overall survival (OS; p < 0.001) than those with low NKCC1 expression in adenocarcinoma. In squamous cell carcinoma, NKCC1 expression was not associated with prognosis. Multivariate analysis revealed that high NKCC1 expression was an independent prognostic factor for DFS in lung adenocarcinomas (HR, 1.709; 95% CI, 1.029 to 2.130; p = 0.033) and for OS in EGFR-mutated adenocarcinoma patients (HR, 3.165; 95% CI, 1.424 to 7.035; p = 0.005). Conclusion: NKCC1 high expression predicted a bad clinical outcome for lung adenocarcinoma patients and EGFR-mutated subgroup. Therefore, NKCC1 may play a role in lung adenocarcinoma and novel therapeutic tactics could be developed by targeting NKCC1 protein.
    QJM: monthly journal of the Association of Physicians 11/2015; DOI:10.1093/qjmed/hcv207 · 2.50 Impact Factor
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    ABSTRACT: Background and objective: Development of CPE in CAP is associated with prolonged hospital stay and it may increase the morbidity and mortality. We aimed to identify microbiological and clinical factors that predicate a prolonged hospital admission in patients treated with a tube thoracostomy to control CPE. Methods: This retrospective cohort included patients with CPE requiring chest tube drainage in a tertiary referral Korean hospital from 1 January 2004 to 30 July 2012. After dichotomous grouping according to the mean duration of hospital stay, clinical, laboratory and microbiological parameters were compared. Results: The final analysis included 158 patients with CPE. The majority were male (130, 85.0%), and the mean age was 62.8 years. The mean duration of hospital stay was 17.7 (±10.2) days. The mean duration of chest tube drainage was 9.6 (±6.7) days. Streptococcus viridans (48.4%) was the most common pathogen. Intrapleural fibrinolysis was performed in 85 (53.8%); additional tube insertion was needed in 40 (25.3%) patients. In the multivariate analysis after adjusting for covariates, a prolonged hospital stay was associated with fever (aOR: 3.42, P = 0.02), lower PaO2 (aOR: 4.89, P = 0.007) and haemoglobin (aOR: 4.90, P = 0.003) levels, and an increased blood neutrophil fraction (aOR: 3.83, P = 0.01) on admission as well as the identification of microbes in CPE (aOR: 4.14, P = 0.03), and ineffective pleural drainage (aOR: 3.28, P = 0.03). Conclusions: This study suggests that physicians should note the clinical symptoms and laboratory findings of severe infection and effectiveness of pleural drainage to predicate which patients with a CAP needing thoracostomy for CPE will have a prolonged hospital stay.
    Respirology 10/2015; DOI:10.1111/resp.12658 · 3.35 Impact Factor
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    ABSTRACT: Excessive dynamic airway collapse (EDAC) is a disease entity of excessive reduction of the central airway diameter during exhalation, without cartilage collapse. An 80-year-old female presented with generalized edema and dyspnea at our hospital. The patient was in a state of acute decompensated heart failure due to pneumonia with respiratory failure. We accordingly managed the patient with renal replacement therapy, mechanical ventilation and antibiotics. Bronchoscopy confirmed the diagnosis of EDAC. We scheduled extubation after the improvement of pneumonia and heart condition. However, extubation failure occurred due to hypercapnic respiratory failure with poor expectoration. Her EDAC was improved in response to high flow nasal oxygen therapy (HFNOT). Subsequently, the patient was stabilized and transferred to the general ward. HFNOT, which generates physiologic positive end expiratory pressure (PEEP) effects, could be an alternative and effective management of EDAC. Further research and clinical trials are needed to demonstrate the therapeutic effect of HFNOT on EDAC.
    Tuberculosis and Respiratory Diseases 10/2015; 78(4):455-8. DOI:10.4046/trd.2015.78.4.455
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    ABSTRACT: Therapeutic drug monitoring in tuberculosis remains controversial. We evaluated the relationship between anti-tuberculosis drug levels in blood and clinical outcome.Serum concentrations of first-line anti-tuberculosis drugs were measured in tuberculosis patients between March 2006 and April 2013. Venous blood was drawn 2 h after drug ingestion and analyzed using high-performance liquid chromatography/tandem mass spectrometry. We retrospectively reviewed the data and determined the association of serum drug levels with clinical outcome.Among 413 patients, the prevalence of low serum concentrations of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA) was 59.3%, 27.8%, 12.8%, and 8.0%, respectively. The low INH group had a greater percentage of patients with a history of tuberculosis treatment (19.2% vs. 11.0%; P = .026) and was more likely to present with drug-resistant strains (17.6% vs. 8.8%; P = .049) than the normal INH group; however, low levels of INH, RMP, EMB, and PZA were not related to treatment outcome. Low INH level had a tendency to be associated with 2-month culture positivity, but it was not statistically significant (P = .072) in multivariate analysis. Seventeen (4.1%) patients experienced a recurrence. However, the recurrence rate was not statistically different between the low and normal INH groups.Low-serum INH may play a role both in recurrence and in acquired drug resistance. However, the serum level of INH was not directly related to either treatment response or recurrence rate. The role and usefulness of therapeutic drug monitoring should be evaluated in further prospective studies.
    Antimicrobial Agents and Chemotherapy 10/2015; DOI:10.1128/AAC.00693-15 · 4.48 Impact Factor
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    ABSTRACT: Background: Radiogenomic features are predictive of anaplastic lymphoma kinase (ALK) rearrangement in surgically resected non-small cell lung cancer (NSCLC). Methods: ALK rearrangement was screened by fluorescent in situ hybridization in 497 patients with resected NSCLC. Of these, 198 patients screened for both ALK and epidermal growth factor receptor (EGFR) mutation were enrolled. Clinicopathologic findings, survival after surgical procedure, computed tomographic (CT) features, and maximum standardized uptake value according to different genotypes were investigated with univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. Results: The prevalence of ALK positivity in resected NSCLC was 5.0% (25 of 497). Patients with ALK rearrangement showed significant differences in terms of patient's age (p = 0.006 for ALK versus EGFR, and 0.04 for ALK versus wild type [WT]/WT, respectively), solid lesion (p = 0.0074 for ALK versus EGFR), degree of contrast enhancement (p = 0.0006 for ALK versus EGFR), and lesion margin (p = 0.0011 for ALK versus EGFR, and 0.0314 for ALK versus WT/WT, respectively) compared with EGFR mutant and WT/WT cohorts. Multivariate analysis revealed that young age, solid lesion, lobulated margin, and hypoattenuation at contrast-enhanced CT scan were independent predictors of ALK positivity (p = 0.027, 0.046, 0.001, 0.021, respectively). The area under the ROC curve of the predictive model was 0.832, which suggests good discrimination. Conclusions: ALK-rearranged lung cancer has characteristic clinical and imaging features compared with EGFR mutant or WT/WT cohorts. Our findings suggest that young age, lobulated margin, solid lesion, and hypoattenuation at contrast-enhanced CT scan are important predictors of ALK-rearranged lung cancer.
    The Annals of thoracic surgery 10/2015; DOI:10.1016/j.athoracsur.2015.07.062 · 3.85 Impact Factor
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    ABSTRACT: Objectives: Some non-small-cell lung cancer patients have preserved pulmonary function after surgery. Compared with open thoracotomy, video-assisted thoracic surgery (VATS) is widely performed and preserves pulmonary function. Patients with non-small-cell lung cancer have an extremely poor prognosis without surgery. Clinicians should therefore decide which patients can safely tolerate lung resection. This study aimed to identify factors associated with preserving pulmonary function after VATS in non-small-cell lung cancer patients. Methods: Three hundred and fifty-one patients with non-small-cell lung cancer underwent VATS and preoperative and 12-month postoperative pulmonary function tests. Patients with and patients without preserved forced expiratory volume in 1 s (FEV1) and diffusing capacity of carbon monoxide were compared. Results: The FEV1 was preserved after VATS in 142 (40.5%) patients. In multivariable analysis, this group was significantly associated with VATS sublobar resection (P < 0.001) and resection at the right upper lobe or right middle lobe (vs right lower lobe, P = 0.048; vs left upper lobe, P = 0.003; vs left lower lobe, P = 0.015). Diffusing capacity of carbon monoxide was preserved in 129 (36.8%) patients. Multivariable analysis showed that VATS sublobar resection (P < .001), lower baseline diffusing capacity of carbon monoxide (P < 0.001) and right upper lobe or right middle lobe resection (vs right lower lobe, P = 0.0014; vs left upper lobe, P = 0.029, vs left lower lobe, P = 0.014) were significantly associated with preserved diffusing capacity of carbon monoxide. Conclusions: For preserving pulmonary function after non-small-cell lung cancer surgery, VATS sublobar resection was superior to VATS lobectomy, and surgery on the right upper lobe or right middle lobe was superior to that at other sites.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 09/2015; DOI:10.1093/ejcts/ezv325 · 3.30 Impact Factor
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    08/2015; 7(2):54-61. DOI:10.15747/jcn.2015.7.2.54
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    ABSTRACT: : Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC. : IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance. : Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p= .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor ( EGFR )-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p= .009). : Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR -mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.
    08/2015; DOI:10.4132/jptm.2015.07.10
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    ABSTRACT: A handful of studies have reported that bronchoscopies influence the clinical outcome of mechanically ventilated patients with aspiration pneumonia. The purpose of the present study is to elucidate the therapeutic role of early bronchoscopy in patients with aspiration who are mechanically ventilated. A retrospective cohort study was conducted via medical record review from 2003 through 2013 in a tertiary hospital. All the diagnoses of pneumonia were supported by the probability of aspiration and consolidation of dependent areas confirmed by computed tomography. Patients who underwent bronchoscopy within 24 h after intubation were categorized as the early bronchoscopy group and the others as the late bronchoscopy group. We compared the demographics, clinical parameters and outcomes between the two groups. Of the 154 patients who were included, the early bronchoscopy group (n = 93) showed significantly lower in-intensive care unit (ICU) mortality and 90-day mortality (in-ICU: 4.9% vs 24.6%; 90-day: 11.8 vs 32.8%) regardless of the initial empirical antibiotics. In addition, their sequential organ failure assessment score on day 7 tended to decrease more rapidly. Among the survivors, patients in the early bronchoscopy group were extubated earlier with a higher success rate, had a shorter length of mechanical ventilation and had a shorter ICU stay. The early bronchoscopy was associated with lower 90-day mortality in multivariate analysis (odds ratio: 0.412; 95% confidence interval: 0.192-0.883). Early bronchoscopy could benefit the clinical outcomes of mechanically ventilated patients with aspiration pneumonia. © 2015 Asian Pacific Society of Respirology.
    Respirology 07/2015; 20(7). DOI:10.1111/resp.12590 · 3.35 Impact Factor

  • 06/2015; 6(1):42-44. DOI:10.17241/smr.2015.6.1.42
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    ABSTRACT: ROS1 rearrangement has been found in a subset of lung cancer and ROS1-rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications and histomorphological characteristics of ROS1-rearranged tumors, especially micropapillary and aerogenous spread growth and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement. ROS1 rearrangement characterizations by fluorescence in situ hybridization and ROS1 protein and E-cadherin expression by immunohistochemistry were performed using 754 non-small cell lung cancer surgical specimens. ROS1 rearrangement was identified in 10 samples. Histologically, all 10 ROS1-rearranged tumors harbored an adenocarcinoma component. Significantly, we noted a high association between ROS1 rearrangement with a micropapillary component (p<0.001), aerogenous spread (p=0.002), and E-cadherin loss (p=0.049). Survival analysis showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence (p=0.024). The best criterion to detect ROS1-rearrangement by immunohistochemistry was an H-score of ≥100, with a sensitivity and specificity of 90% and 93.5%, respectively. ROS1-rearranged adenocarcinoma exhibited distinct morphological and clinicopathological features. Decreased membranous E-cadherin expression and aerogenous spread may be associated with worse disease-free survival. ROS1 immunohistochemistry correlated well with ROS1 gene rearrangement. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Lung cancer (Amsterdam, Netherlands) 06/2015; 89(3). DOI:10.1016/j.lungcan.2015.06.012 · 3.96 Impact Factor
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    ABSTRACT: In carcinogenesis of peripheral pulmonary carcinomas, multiple genetic and epigenetic alterations are involved. In this study, we quantified methylation levels of repetitive DNA elements (L1 and Alu) and six CpG island methylator phenotype (CIMP)-panel markers in various lesions representing steps in the development of lung adenocarcinoma (ADC), including atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive ADC. We then assessed methylation levels in an independent set of stage I ADCs (n = 100) and correlated methylation status with clinicopathological findings and clinical outcome. The pattern of changes in the methylation levels of L1 and Alu was different during progression of the lesion along the process of multistep carcinogenesis. A methylation level of >52.4 % of L1 and of >19.7 % of Alu in stage I ADC was associated with shorter cancer-specific survival in univariate but not in multivariate analysis. A tumor to normal lung tissue methylation ratio of >0.693 of L1 was an independent parameter heralding poor prognosis for stage I ADC patients. Methylation of CIMP-related genes was found in ADC. Stage I ADC cases without methylation of any of the six markers had a significantly shorter cancer-specific survival than ADC with methylation of one or more markers. The combination of tumor to normal L1 methylation ratio > 0.693 and absence of methylation of CIMP markers correlated independently with shorter cancer-specific survival. In conclusion, our findings suggest that Alu hypomethylation is an early and L1 hypomethylation a later event during multistep pulmonary carcinogenesis. The prognostic significance of the combination of methylation status of L1 and CIMP markers must be validated in large-scale studies of pulmonary ADC.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 03/2015; 466(6). DOI:10.1007/s00428-015-1749-0 · 2.65 Impact Factor
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    ABSTRACT: The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs. Graphical Abstract
    Chest 02/2015; 30(2):167-72. DOI:10.3346/jkms.2015.30.2.167 · 7.48 Impact Factor
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    ABSTRACT: Video-assisted thoracoscopic surgery (VATS) is widely performed in patients with resectable non-small cell lung cancer. However, it is unknown whether VATS sublobar resection has advantages compared with VATS lobectomy in preserving pulmonary function. Three hundred patients with non-small cell lung cancer who underwent VATS were enrolled. Pulmonary function tests were performed three times: preoperatively, and at 3 and 12 months postoperatively. Pulmonary function was compared between the VATS lobectomy group (n = 227) and the VATS sublobar resection group (n = 73). The VATS sublobar resection group had greater preserved pulmonary function than the VATS lobectomy group at 3 and 12 months postoperatively (p < 0.001). However, a VATS lobectomy of the right upper or right middle lobe revealed no difference in forced vital capacity (-1.21% versus -1.45%; p = 0.88) or the diffusion capacity of carbon monoxide (-3.99% versus -2.45%; p = 0.61) compared with VATS sublobar resection after 12 months. In those who underwent VATS of the right lower lobe, forced expiratory volume in 1 second (-8.60% versus -3.69%; p = 0.12) was not different between the two groups after 12 months. Video-assisted thoracoscopic surgery lobectomy of the left upper or left lower lobe resulted in lower pulmonary function than VATS sublobar resection (p < 0.05). Patients with non-small cell lung cancer who underwent VATS sublobar resection demonstrated greater pulmonary function than those who underwent VATS lobectomy. However, in right-side VATS lobectomy, some differences dissipated at 1 year. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 01/2015; 99(1):210-7. DOI:10.1016/j.athoracsur.2014.07.066 · 3.85 Impact Factor

  • 01/2015; 30(3):151. DOI:10.4266/kjccm.2015.30.3.151
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    ABSTRACT: Elevated cardiac troponin (cTn) has been associated with worse outcomes in critically ill patients, but few studies have focused on whether these markers are related to outcomes in patients with severe pneumonia. We investigated the levels of cTnI in critically ill patients hospitalized for severe pneumonia and whether elevated levels of cTnI correlated with the clinical outcome of this patient group. We conducted a retrospective study of patients admitted to the medical intensive care unit (ICU) with severe pneumonia with levels of cTnI obtained within 24 hours of admittance. Patients with evidence of acute coronary syndrome were excluded. A cTnI level greater than 0.034 ng/mL was considered positive. P value < .05 was considered significant. A total of 152 patients (community-acquired pneumonia [39.5%], health care-associated pneumonia [40.8%], and hospital-acquired pneumonia [19.7%]) were included in the study. Eighty-eight (58%) patients had detectable cTnI levels (median, 0.049 ng/mL). Patients with increased cTnI levels showed higher in-ICU mortality (38.6% vs 21.9%, P = .028). The association between elevated cTnI levels and mortality remained significant after adjustment using a multivariate model (adjusted hazard ratio = 1.398; 95% confidence interval, 1.005-1.945; P = .047). Increased levels of cTnI are an independent predictor of ICU mortality in patients hospitalized with severe pneumonia without evidence of acute coronary syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.
    Journal of Critical Care 12/2014; 30(2). DOI:10.1016/j.jcrc.2014.12.001 · 2.00 Impact Factor
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    ABSTRACT: Acute respiratory distress syndrome (ARDS) remains an unsolved problem in the intensive care unit (ICU) that can be treated with venovenos extracorporeal membrane oxygenation (VV-ECMO). We summarized retrospectively collected data from an institutional experience with VV-ECMO in patients with severe acute respiratory failure and identified the clinical parameters associated with successful ECMO weaning. Among the 45 cases who received ECMO for pneumonia(n=19), exacerbation of interstitial lung disease (n=11), ARDS secondary to sepsis(n=8), aspiration pneumonitis(n=2), postoperative ARDS (n=3), and others(n=2), 21(46.7%) were successfully weaned from ECMO. In a univariate analysis median platelet (PLT) count at ICU admission(162 vs. 97 × 10/L, p=0.046) and pre-day 1(118.5 vs. 62.5 × 10/L, p = 0.046) were higher in the ECMO-weaned group than those in the weaning failure group. Using a PLT level of 70 × 10/L, the odds ratio for successful ECMO weaning was 11.0(95% CI 1.34-87.16, p=0.023) in the multivariate analysis. Bleeding complication rates were similar between the two groups. High PLT counts at ICU admission and the day immediately prior to initiating ECMO might play a key role in successful weaning of VV-ECMO for severe acute respiratory failure. Further studies should evaluate the proper target PLT level to enhance ECMO outcomes.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 11/2014; 61(2). DOI:10.1097/MAT.0000000000000174 · 1.52 Impact Factor
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    ABSTRACT: Percutaneous needle aspiration or biopsy (PCNA or PCNB) is an established diagnostic technique that has a high diagnostic yield. However, its role in the diagnosis of nodular ground-glass opacities (nGGOs) is controversial, and the necessity of preoperative histologic confirmation by PCNA or PCNB in nGGOs has not been well addressed. We here evaluated the rates of malignancy and surgery-related complications, and the cost benefits of resecting nGGOs without prior tissue diagnosis when those nGGOs were highly suspected for malignancy based on their size, radiologic characteristics, and clinical courses. Patients who underwent surgical resection of nGGOs without preoperative tissue diagnosis from January 2009 to October 2013 were retrospectively analyzed. Among 356 nGGOs of 324 patients, 330 (92.7%) nGGOs were resected without prior histologic confirmation. The rate of malignancy was 95.2% (314/330). In the multivariate analysis, larger size was found to be an independent predictor of malignancy (odds ratio, 1.086; 95% confidence interval, 1.001-1.178, p =0.047). A total of 324 (98.2%) nGGOs were resected by video-assisted thoracoscopic surgery (VATS), and the rate of surgery-related complications was 6.7% (22/330). All 16 nGGOs diagnosed as benign nodules were resected by VATS, and only one patient experienced postoperative complications (prolonged air leak). Direct surgical resection without tissue diagnosis significantly reduced the total costs, hospital stay, and waiting time to surgery. With careful selection of nGGOs that are highly suspicious for malignancy, surgical resection of nGGOs without tissue diagnosis is recommended as it reduces costs and hospital stay.
    BMC Cancer 11/2014; 14(1):838. DOI:10.1186/1471-2407-14-838 · 3.36 Impact Factor
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    ABSTRACT: Diabetes mellitus (DM) is a well-known risk factor to develop tuberculosis (TB). Some reports indicate the serum concentrations of anti-TB drugs are lower in patients with TB and DM than those with TB only. Therefore, we developed a nonlinear mixed-effects model (NONMEM) to determine the population PK parameters of rifampin and assessed the effects of DM status in patients with TB. One-compartment linear modeling with first-order absorption was evaluated using the 206 plasma samples of rifampin from 54 patients with DM. Based on the final model, DM affected the absorption rate constant (ka) and the volume of distribution (Vd) of rifampin. The body mass index (BMI) of the patients affected rifampin clearance (CL). The ka of rifampin in patients with TB and DM was greater than that in patients with TB only. Further, the predicted Vd in patients with DM was greater than that in patients without DM. As Vd is inversely correlated with plasma concentrations, the rifampin concentrations were predicted to be lower in the patients with DM. The authors recommend administering the greater doses of rifampin for the treatment of TB in patients with DM compared with the doses for the patients without DM to prevent treatment failure. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Tuberculosis 11/2014; 95(1). DOI:10.1016/ · 2.71 Impact Factor
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    ABSTRACT: ROS1 has attracted much attention as a possible oncogenic driver and ROS1-rearranged tumors show sensitivity to most ALK inhibitors. We aimed to clarify the prevalence of ROS1 gene rearrangement and investigate the clinical implications of ROS1 gene copy number gain (CNG) in non-small cell lung cancer (NSCLC) patients. We carried out fluorescent in situ hybridization with ROS1 and centromere enumeration 6 probes and immunohistochemistry for ROS1 protein expression. ROS1 rearrangement was detected in 3 of 375 samples (0.8 %); all of whom were female, never-smokers, and harbored an adenocarcinoma component. ROS1 gene CNG was found in 18 cases (4.8 %). ROS1 gene CNG was significantly associated with shorter disease-free survival (DFS, 12 vs. 58 months; p = 0.003) and shorter overall survival (OS, 40 vs. 67 months; p <0.001) than the group without CNG. Multivariate analysis confirmed that ROS1 gene CNG was significantly associated with poorer DFS (hazard ratio [HR]=2.16, 95 % confidence interval [CI] = 1.22-3.81, p = 0.008), and OS ([HR] = 2.53, 95 % [CI] = 1.31-4.89, p = 0.006). ROS1 protein overexpression was observed in 5.0 % (18 out of 357), of which 2 cases harbored ROS1 gene rearrangement. There was no statistically significant correlation between ROS1 gene CNG and protein overexpression. This study demonstrated ROS1 gene rearrangement was detected in 0.8 % of surgically resected NSCLC; and ROS1 gene CNG is an independent poor prognostic factor. This survival analyses may contribute to future studies on the utility of ROS1-targeted therapy for patients.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2014; 466(1). DOI:10.1007/s00428-014-1679-2 · 2.65 Impact Factor

Publication Stats

2k Citations
459.87 Total Impact Points


  • 2004-2015
    • Seoul National University Bundang Hospital
      • • Department of Thoracic and Cardiovascular Surgery
      • • Department of Pathology
      • • Department of Radiology
      Sŏul, Seoul, South Korea
  • 2014
    • Kyungpook National University Hospital
      • Department of Pathology
      Sŏul, Seoul, South Korea
  • 2001-2014
    • Seoul National University
      • • Department of Internal Medicine
      • • Medical Research Center
      • • College of Medicine
      Sŏul, Seoul, South Korea
  • 2010
    • Korea Medical Research Institute
      Sŏul, Seoul, South Korea
  • 2000-2010
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2002-2007
    • Vanderbilt University
      • Vanderbilt-Ingram Cancer Center (VICC)
      Nashville, Michigan, United States