Publications by authors named "Kang Hyeon Choe"

42 Publications

Increased Incidence and Associated Risk Factors of Aspergillosis in Patients with Bronchiectasis.

J Pers Med 2021 May 17;11(5). Epub 2021 May 17.

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07441, Korea.

There are insufficient data regarding the relationship between non-cystic fibrosis bronchiectasis and incident aspergillosis. We performed a population-based, matched cohort study using data from the Korean National Health Insurance database between 2003 and 2013. The incidence of aspergillosis was 50/100,000 person-years in the bronchiectasis cohort and 11/100,000 person-years in the matched cohort (subdistribution hazard ratio, 4.53; 95% confidence interval (CI), 3.25-6.32). Among the bronchiectasis cohort, chronic obstructive pulmonary disease (adjusted HR, 1.95; 95% CI, 1.07-3.57), previous pulmonary tuberculosis (adjusted HR, 3.67; 95% CI, 2.03-6.64), and non-tuberculous mycobacterial pulmonary disease (adjusted HR, 11.25; 95% CI, 1.49-85.18) increased the risk of incident aspergillosis. The incidence of aspergillosis in patients with bronchiectasis was approximately 4.5-fold that in those without bronchiectasis. Comorbid pulmonary diseases-chronic obstructive pulmonary disease, previous pulmonary tuberculosis, and non-tuberculous mycobacterial pulmonary disease-significantly increased the risk of aspergillosis in patients with bronchiectasis. Our study indicates that close monitoring is warranted for aspergillosis in patients with bronchiectasis.
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http://dx.doi.org/10.3390/jpm11050422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155934PMC
May 2021

Clinical profiles and outcomes of pulmonary tuberculosis patients with delayed treatment at a tertiary hospital in South Korea.

Ann Palliat Med 2021 Mar 23;10(3):2948-2957. Epub 2021 Feb 23.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.

Background: Data on the clinical characteristics of delayed treatment initiation among pulmonary tuberculosis (TB) patients are lacking. Thus, this study aimed to identify the factors associated with delayed treatment in culture-confirmed pulmonary TB and to assess outcomes of delayed treatment.

Methods: We retrospectively evaluated 151 patients with culture-confirmed pulmonary TB between 2015 and 2017. Delayed and timely treatment was defined as initiation of anti-TB treatment after and before the identification of Mycobacterium tuberculosis complex isolate, respectively. Factors related to delayed treatment, such as comorbidities, clinical presentation, and patterns of initial healthcare use, were collected. We analyzed whether delayed treatment was associated with all-cause mortality using a multivariate binary logistic regression model adjusted for age, sex, cardiovascular disease, and malignancy.

Results: In total, 55 (36.4%) patients had delayed treatment. The median length between the first medical visit and treatment initiation was 9 days. Compared with timely treatment, delayed treatment was associated with no initial visit to a non-pulmonary department [adjusted odds ratio (aOR) =10.49, 95% confidence interval (CI), 2.56-42.93] and absence of nucleic acid amplification test (aOR =7.54, 95% CI, 2.75-20.67). After adjusting for age, sex, cardiovascular disease, and solid malignancies, delayed treatment was significantly associated with all-cause mortality (aOR =3.79, 95% CI, 1.36-10.58). The most frequent possible cause of delayed treatment was the doctor's low suspicion of active TB disease.

Conclusions: Given that delayed treatment is associated with worse outcomes in South Korea, targeted interventions to increase awareness on TB in the healthcare community are necessary for additional mycobacterial tests and consults of suspicious patients to TB specialists.
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http://dx.doi.org/10.21037/apm-20-1521DOI Listing
March 2021

The Role of Granzyme B Containing Cells in the Progression of Chronic Obstructive Pulmonary Disease.

Tuberc Respir Dis (Seoul) 2020 Dec 20;83(Supple 1):S25-S33. Epub 2020 Oct 20.

The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Lung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remain unclear. There is growing interest in the role of granzyme B (GzmB) because CD8+ T cells can induce apoptosis of target cells by releasing GzmB, which in turn may cause tissue injury and remodeling. However, GzmB is also expressed by regulatory cells, which are able to suppress CD8+ T cell. The role of GzmB+ cells needs to be defined in COPD.

Methods: GzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 nonsmoking control, 12 panlobular emphysema (PLE) and 30 centrilobular emphysema (CLE) subjects were localized by immunohistochemical method. Positively stained cells on alveolar wall were counted and length of corresponding alveolar wall was measured. The results were expressed as mean number of positively stained cells per mm of alveolar wall in each subject.

Results: The number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05 and p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and forced expiratory volume in 1 second (FEV1) (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1.

Conclusion: Our finding that number of alveolar GzmB+ cells was associated with FEV1 suggests that GzmB+ cells might have protective role in the progression of lung destruction and airflow limitation in CLE, which is the predominant emphysema subtype of COPD.
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http://dx.doi.org/10.4046/trd.2020.0089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837379PMC
December 2020

Comparison of Postextubation Outcomes Associated with High-Flow Nasal Cannula vs. Conventional Oxygen Therapy in Patients at High Risk of Reintubation: a Randomized Clinical Trial.

J Korean Med Sci 2020 Jun 29;35(25):e194. Epub 2020 Jun 29.

Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.

Background: Liberation and extubation are important for patients supported by mechanical ventilation. Extubation success is related to the duration of an intensive care unit (ICU) stay and mortality rate. High-flow nasal cannula (HFNC) oxygen therapy has physiological and clinical benefits in respiratory care. The present study compared clinical outcomes associated with HFNC and conventional oxygen therapy (COT) among patients at high risk for reintubation.

Methods: A single-center randomized clinical trial was conducted between March 2018 and June 2019. Sixty adults admitted to the ICU and who were at high-risk of reintubation and met the inclusion criteria were enrolled in this study. "High risk" for reintubation was defined as having at least one of the following risk factors: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 points on extubation day, obesity, poor expectoration, airway patency problems, difficult or prolonged weaning, and more than one comorbidity. The primary outcome of interest was reintubation within 72 hours. Secondary outcomes included duration of ICU and hospital stay, mortality rate, and time to reintubation.

Results: Of 60 patients, 31 received HFNC and 29 received COT (mean age, 78 ± 7.8 vs. 76 ± 6.5 years, respectively). Reintubation rate within 72 hours did not differ between the groups (3 patients [9.7%] vs. 1 patient [3.4%], respectively). Reintubation time was shorter among patients who received COT than among patients who received HFNC (0.5 hour vs. 25 hours), but this difference was not statistically significant. Duration of ICU did not differ between the groups (14.7 ± 9.6 days vs. 13.8 ± 15.7 days, for HFNC and COT, respectively).

Conclusion: Among patients at high risk for reintubation, compared with COT, HFNC did not reduce the risk of reintubation within 72 hours.
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http://dx.doi.org/10.3346/jkms.2020.35.e194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324267PMC
June 2020

Clinical Role of the Chronic Obstructive Pulmonary Disease Assessment Test in Prediction of the Response to Treatment for Exacerbations.

J Korean Med Sci 2020 Jan 13;35:e10. Epub 2020 Jan 13.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.

Background: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a validated, eight-item questionnaire used to quantify the health status of patients. The aim of this study was to evaluate the usefulness of the CAT questionnaire as a tool to assess the response to treatment in acute exacerbations of COPD in an outpatient setting.

Methods: A multicenter, phase 3 randomized controlled trial was conducted previously to examine the efficacy and safety of oral zabofloxacin for the treatment of COPD exacerbations. In the present post hoc analysis of the original study, patients with COPD exacerbation were categorized as responders or non-responders according to the respiratory symptoms persisting on day 10 (visit 3) of treatment. The CAT questionnaire was completed daily by patients at home from the initial visit to the second visit on day 5. Subsequently, the questionnaire was completed in the presence of a physician on days 10 (visit 3) and 36 (visit 4). Multivariate regression analysis was performed to determine the association between CAT scores and the therapeutic response.

Results: The CAT scores decreased more rapidly in responders compared to non-responders during the first 5 days (23.3-20.4 vs. 23.5-22). Among responders, patients with higher severity of illness also revealed higher CAT scores on the first day of an exacerbation (mild, 19.8; moderate, 21.4; severe, 23.8; very severe, 28.6). Multivariate analysis revealed that a change in the CAT score during the first 3 days influenced the therapeutic response. A significant decrease in scores in the domains of sputum production, chest tightness, and activities of daily living was seen among responders.

Conclusion: Early improvement in CAT scores may be associated with a more favorable response to the treatment of COPD exacerbations.

Trial Registration: ClinicalTrials.gov Identifier: NCT01658020.

Trial Registration: Clinical Research Information Service Identifier: KCT0000532.
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http://dx.doi.org/10.3346/jkms.2020.35.e10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955431PMC
January 2020

Exacerbations of Chronic Obstructive Pulmonary Disease Tool to assess the efficacy of acute treatment.

Int J Chron Obstruct Pulmon Dis 2019;14:471-478. Epub 2019 Feb 25.

Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea,

Background And Objective: The Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Patient-Reported Outcomes (EXACT-PRO) has been suggested as a reliable and valid measure for early assessment of COPD exacerbations and perceived recovery. However, there has been no evidence for EXACT-PRO efficacy in assessing recovery from treatment in a randomized controlled trial. The study evaluated the reliability, validity, and responsiveness of EXACT-PRO for the evaluation of the efficacy of acute treatment in patients with COPD exacerbation.

Methods: In a Phase III randomized controlled study for assessing the efficacy of antibiotic treatment on COPD exacerbation, EXACT-PRO was evaluated in the responders and non-responders.

Results: A total of 295 patients were analyzed (259 responders and 37 non-responders). Cronbach's α was 0.96 for EXACT total, 0.96 for the breathlessness domain, 0.89 for the cough and sputum domain, and 0.93 for the chest symptoms domain. The EXACT score correlated with the COPD assessment test (CAT) score (=0.8, <0.01). A stronger decrease in the EXACT score was found in the responder group than in the non-responder group from the fifth day after treatment. The difference in the EXACT score from exacerbation onset to recovery was -6.3 in responders and -1.9 in non-responders (=0.01).

Conclusion: EXACT-PRO is a comprehensive and sensitive method for assessing symptomatic resolution of COPD exacerbations during treatment.
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http://dx.doi.org/10.2147/COPD.S189300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394236PMC
July 2019

Investigation of false-positive culture tests using whole genome sequencing.

Ann Thorac Med 2019 Jan-Mar;14(1):90-93

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.

Although accurate identification of is the gold standard for tuberculosis (TB) diagnosis, there have been several reports of false-positive results. After identifying a sudden increase in extensively drug-resistant TB, false-positive mycobacterial culture tests were suspected, and we contacted the supranational reference center for molecular typing. genotyping tests showed that isolates from all five patients had an identical genotype pattern, and all harbored the same Beijing strain based on sequence-based phylogenic analysis and drug-resistant single nucleotide polymorphisms (SNPs) analysis. We also used whole genome sequencing (WGS) to compare the SNPs of all isolates with a reference genome, and all were identical. We adapted WGS to efficiently detect false-positive MTB culture tests.
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http://dx.doi.org/10.4103/atm.ATM_184_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341868PMC
February 2019

Clinical features of octogenarian patients with tuberculosis at a tertiary hospital in South Korea.

J Int Med Res 2019 Jan 21;47(1):271-280. Epub 2018 Oct 21.

2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.

Objective: The growth of the older population is a great challenge for tuberculosis (TB) control in South Korea. This study was performed to investigate the clinical characteristics of and treatment outcomes among octogenarian patients with TB.

Methods: We retrospectively analyzed the medical records of 109 patients with TB (age of ≥80 years) from January 2014 to March 2017. Clinical, microbiologic, and radiologic findings were obtained.

Results: Fifty-five patients (50.5%) were male, the mean age of the patients was 83.8 years, and 75 patients (68.8%) had pulmonary TB. All patients with pulmonary TB underwent either chest X-ray or chest computed tomography examination, and the results showed that only one-third (n = 33, 39.3%) had active lesions suggestive of TB. Twenty-nine patients (26.4%) had an unfavorable outcome (21 died and 8 were lost to follow-up). Only two TB-related deaths occurred, and both were caused by respiratory failure. Among the 15 non-TB-related deaths, the progression of malignancy and sepsis were the most frequent causes of death.

Conclusions: A high mortality rate was observed in octogenarian patients with TB, and most of these deaths were non-TB-related. Among all causes of mortality, solid malignancy was a significant risk factor for death.
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http://dx.doi.org/10.1177/0300060518800597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384473PMC
January 2019

Bronchopleural phrenic fistula caused by methicillin-resistant staphylococcus aureus pneumonia.

J Thorac Dis 2018 Aug;10(8):E620-E624

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.

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http://dx.doi.org/10.21037/jtd.2018.07.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129881PMC
August 2018

Diagnostic benefits of the combined use of liquid-based cytology, cell block, and carcinoembryonic antigen immunocytochemistry in malignant pleural effusion.

J Thorac Dis 2018 Aug;10(8):4931-4939

Department of Pathology, Chungbuk National University Hospital, Cheongju, Korea.

Background: Malignant pleural effusion (MPE) is a common complication of cancer cell metastasis to the pleura. Discrimination between MPE and benign pleural effusion is necessary to design treatment strategies. Cytology is important for the diagnosis of MPE. Carcinoembryonic antigen (CEA) is an epithelial biomarker with a strong staining pattern in adenocarcinomas. Here, the diagnostic performances of liquid-based cytology (LBC), cell block (CB) preparation, and CEA immunostaining for the detection of malignancy in effusion cytology were compared in a large case series.

Methods: In a single institution, 1,014 cytology samples from 862 patients were retrospectively collected and reviewed between January 2013 and November 2015. Ethanol-fixed, paraffin embedded CB of pleural effusions was analyzed by CEA immunostaining. Diagnostic values were compared among LBC, CB, CEA immunostaining, and the combination of two methods.

Results: The sensitivity and specificity of the CB preparation were 94.3% and 98.7%, respectively, compared with 81.3% and 99.4% for LBC preparations, respectively. Combination of LBC and CB increased sensitivity by 98.3%. Although the accuracy of CEA staining itself was moderate (sensitivity, 89.8%), the combined use of CB and CEA tumor marker increased the detection rate of malignancy (sensitivity, 100%; specificity, 100%), compared with that of cytology (LBC or CB) alone.

Conclusions: The sensitivity and specificity for the diagnosis of MPE could be improved by integrating the CB and CEA staining into LBC in routine clinical practice to improve diagnostic accuracy.
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http://dx.doi.org/10.21037/jtd.2018.07.139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129876PMC
August 2018

Transcultural Adaptation and Validation of the Korean Version of the Brief Illness Perception Questionnaire for Patients with Pulmonary Tuberculosis.

J Glob Infect Dis 2017 Jul-Sep;9(3):113-116

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Republic of Korea.

Background And Aim: The brief illness perception questionnaire (BIPQ) has been used in many populations for both adults and children, and it provides a rapid assessment of illness perception. This study was performed to create a translated version of the BIPQ to fit the Korean society and to test its validity through pulmonary tuberculosis (TB) patients.

Methods: Translation and transcultural adaptation of BIPQ, applicable to the Korean society, was performed in accordance with the international guidelines. Internal consistency, test-retest reliability, concurrent validity, and discrimination validity were evaluated. To assess the discrimination validity, the BIPQ scores were compared between pulmonary TB and chronic obstructive pulmonary disease (COPD).

Results: Sixty-eight patients with pulmonary TB participated in this study. Cronbach's α coefficient was 0.753, which indicated satisfactory internal consistency. The concurrent validity showed significant correlations (Pearson's correlation of 0.753). The test-retest reliability was confirmed with an intraclass correlation coefficient of 0.892. The total score of BIPQ in patients with COPD was significantly higher than that in those with pulmonary TB (37.67 vs. 30.85; = 0.005), which supported the discrimination validity.

Conclusions: The Korean version of BIPQ was found to be a reliable and valid questionnaire for patients with pulmonary TB.
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http://dx.doi.org/10.4103/0974-777X.212583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572195PMC
September 2017

The Need for a Well-Organized, Video-Assisted Asthma Education Program at Korean Primary Care Clinics.

Tuberc Respir Dis (Seoul) 2017 Apr 31;80(2):169-178. Epub 2017 Mar 31.

Department of Internal Medicine, Inje University Seoul Paik Hospital, Seoul, Korea.

Background: The purpose of this study was to assess the effect of our new video-assisted asthma education program on patients' knowledge regarding asthma and asthma control.

Methods: Adult asthmatics who were diagnosed by primary care physicians and followed for at least 1 year were educated via smart devices and pamphlets. The education sessions were carried out three times at 2-week intervals. Each education period lasted at most 5 minutes. The effectiveness was then evaluated using questionnaires and an asthma control test (ACT).

Results: The study enrolled 144 patients (mean age, 56.7±16.7 years). Half of the patients had not been taught how to use their inhalers. After participating in the education program, the participants' understanding of asthma improved significantly across all six items of a questionnaire assessing their general knowledge of asthma. The proportion of patients who made errors while manipulating their inhalers was reduced to less than 10%. The ACT score increased from 16.6±4.6 to 20.0±3.9 (p<0.001). The number of asthmatics whose ACT score was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude of improvement in the ACT score did not differ between patients who received an education session at least three times within 1 year and those who had not. The majority of patients agreed to the need for an education program (95.8%) and showed a willingness to pay an additional cost for the education (81.9%).

Conclusion: This study indicated that our newly developed education program would become an effective component of asthma management in primary care clinics.
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http://dx.doi.org/10.4046/trd.2017.80.2.169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392488PMC
April 2017

The Prognostic Value of Residual Volume/Total Lung Capacity in Patients with Chronic Obstructive Pulmonary Disease.

J Korean Med Sci 2015 Oct 12;30(10):1459-65. Epub 2015 Sep 12.

Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

The prognostic role of resting pulmonary hyperinflation as measured by residual volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease (COPD) remains poorly understood. Therefore, this study aimed to identify the factors related to resting pulmonary hyperinflation in COPD and to determine whether resting pulmonary hyperinflation is a prognostic factor in COPD. In total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort recruited from 16 hospitals were enrolled. Resting pulmonary hyperinflation was defined as RV/TLC ≥ 40%. Multivariate logistic regression analysis demonstrated that older age (P = 0.001), lower forced expiratory volume in 1 second (FEV1) (P < 0.001), higher St. George Respiratory Questionnaire (SGRQ) score (P = 0.019), and higher emphysema index (P = 0.010) were associated independently with resting hyperinflation. Multivariate Cox regression model that included age, gender, dyspnea scale, SGRQ, RV/TLC, and 6-min walking distance revealed that an older age (HR = 1.07, P = 0.027), a higher RV/TLC (HR = 1.04, P = 0.025), and a shorter 6-min walking distance (HR = 0.99, P < 0.001) were independent predictors of all-cause mortality. Our data showed that older age, higher emphysema index, higher SGRQ score, and lower FEV1 were associated independently with resting pulmonary hyperinflation in COPD. RV/TLC is an independent risk factor for all-cause mortality in COPD.
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http://dx.doi.org/10.3346/jkms.2015.30.10.1459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575935PMC
October 2015

Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity.

Biomaterials 2015 Oct 14;67:32-41. Epub 2015 Jul 14.

Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea. Electronic address:

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays a crucial role in tumorigenesis of lung cancer. However, the therapeutic potential for anti CEACAM6 monoclonal antibody (mAb) has only been limitedly explored. Here, we evaluate the therapeutic potential of naked anti CEACAM6 mAb against lung adenocarcinoma. Clone 8F5, recognizing B domain of CEACAM6, is established by immunizing A549 cells and screening for clones double positive for A549 and CEACAM6-Fc recombinant protein. We found that 85.7% of 70 resected lung adenocarcinoma tissue sections were positive for CEACAM6, whereas all squamous cell carcinoma examined were negative. A549 cells with high levels of CEACAM6 demonstrated more aggressive growth nature and showed increased paclitaxel chemosensitivity upon 8F5 binding. Treatment with 8F5 to A549 decreased cellular CEACAM6 expression and reversed anoikis resistance. 8F5 also decreased cellular status of Akt phosphorylation and increased apoptosis via caspase activation. In a mouse model of lung adenocarcinoma with xenotransplanted A549 cells, 8F5 treatment alone demonstrated 40% tumor growth inhibition. When combined with paclitaxel treatment, 8F5 markedly enhanced tumor growth inhibition, up to 80%. In summary, we demonstrate that anti CEACAM6 mAb is an effective therapeutic treatment for lung adenocarcinoma whose effect is further enhanced by combined treatment with paclitaxel.
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http://dx.doi.org/10.1016/j.biomaterials.2015.07.012DOI Listing
October 2015

Interactions between paraoxonase 1 genetic polymorphisms and smoking and their effects on oxidative stress and lung cancer risk in a Korean population.

PLoS One 2015 5;10(3):e0119100. Epub 2015 Mar 5.

Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea; Center for Farmers Safety & Health, Chungbuk National University Hospital, Cheongju, Korea.

Background: Few studies in epidemiology have evaluated the effects of gene-environment interaction on oxidative stress, even though this interaction is an important etiologic factor in lung carcinogenesis. We investigated the effects of the genetic polymorphisms of paraoxonase 1 (PON1), smoking, and the interaction between the two on lung cancer risk and oxidative stress.

Methods: This study's subjects consisted of 416 newly diagnosed lung cancer patients and an equal number of matched controls. The GoldenGate assay was used for genotypic analyses of the PON1 gene. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid reactive substances levels were measured as indicators of oxidative stress.

Results: The PON1 rs662 AA genotype showed a significantly lower risk of lung cancer than the GG genotype (OR = 0.60, 95% CI: 0.36-0.99). The protective effect of the PON1 rs662 AA genotype on lung cancer risk was limited to non-smokers. Lung cancer patients who had the rs662 A allele showed a dose-dependent association between smoking status and oxidative stress markers. Among non-smoking lung cancer patients, urinary 8-OHdG levels were significantly lower in individuals with the rs662 GA and AA genotypes than in those with the GG genotype. Furthermore, we found a significant interaction effect between PON1 rs662 and smoking status on urinary 8-OHdG levels in lung cancer patients.

Conclusions: Our results suggest that the protective effect of PON1 rs662 SNP against lung carcinogenesis and the induction of oxidative stress might be modulated by the interaction between PON1 genetic polymorphisms and tobacco smoking.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119100PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350985PMC
January 2016

Diagnostic performance of CD66c in lung adenocarcinoma-associated malignant pleural effusion: comparison with CEA, CA 19-9, and CYFRA 21-1.

Pathology 2015 Feb;47(2):123-9

1Departments of Pathology 2Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

Various tumour markers have been evaluated in malignant pleural effusions, but not CD66c. This study evaluated the diagnostic ability of CD66c in lung adenocarcinoma-associated malignant pleural effusions (LA-MPEs) and compared it with other known tumour markers. Forty-seven cases of LA-MPE and 52 cases of benign pleural effusions were collected. The levels of CD66c, CEA, CA 19-9, and CYFRA 21-1 were measured by enzyme immunoassay. The expression of CD66c, CEA, and CA 19-9 in cell blocks was measured by immunocytochemistry. CEA had the best diagnostic values, with a sensitivity of 87.2% and specificity of 92.3%. Both CD66c and CA 19-9 showed the highest specificity of 98.1%, with sensitivities of 63.8% and 55.3%, respectively. CYFRA 21-1 had a sensitivity of 83.0% and specificity of 76.9%. CEA combined with CA 19-9 reached a sensitivity of 91.5% and a specificity of 98.1%. The sensitivities of immunocytochemical staining for CD66c, CEA, and CA 19-9 were 72.5%, 75%, and 40%, respectively. CD66c showed a diagnostic performance comparable to CYFRA 21-1 and CA 19-9 by enzyme immunoassay. Immunocytochemical study showed that CD66c and CEA were more sensitive than CA19-9. Both studies support CD66c as a potential tumour marker to differentiate LA-MPE from benign effusions.
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http://dx.doi.org/10.1097/PAT.0000000000000215DOI Listing
February 2015

Aspergillus tracheobronchitis in a mild immunocompromised host.

Tuberc Respir Dis (Seoul) 2014 Nov 28;77(5):223-6. Epub 2014 Nov 28.

Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

Aspergillus tracheobronchitis is a form of invasive pulmonary aspergillosis in which the Aspergillus infection is limited predominantly to the tracheobronchial tree. It occurs primarily in severely immunocompromised patients such as lung transplant recipients. Here, we report a case of Aspergillus tracheobronchitis in a 42-year-old man with diabetes mellitus, who presented with intractable cough, lack of expectoration of sputum, and chest discomfort. The patient did not respond to conventional treatment with antibiotics and antitussive agents, and he underwent bronchoscopy that showed multiple, discrete, gelatinous whitish plaques mainly involving the trachea and the left bronchus. On the basis of the bronchoscopic and microbiologic findings, we made the diagnosis of Aspergillus tracheobronchitis and initiated antifungal therapy. He showed gradual improvement in his symptoms and continued taking oral itraconazole for 6 months. Physicians should consider Aspergillus tracheobronchitis as a probable diagnosis in immunocompromised patients presenting with atypical respiratory symptoms and should try to establish a prompt diagnosis.
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http://dx.doi.org/10.4046/trd.2014.77.5.223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250923PMC
November 2014

Massive hemoptysis after a bronchoscopic biopsy in patients with endobronchial tuberculosis.

Chin Med J (Engl) 2014 ;127(21):3837-8

Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea. Email:

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February 2017

Eosinophilic pleuritis due to sparganum: a case report.

Korean J Parasitol 2014 Oct 22;52(5):541-3. Epub 2014 Oct 22.

Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju 361-711, Korea.

Sparganosis is a rare parasitic disease caused by migrating plerocercoid tapeworm larva of the genus Spirometra. Infection in humans is mainly caused by the ingestion of raw or inadequately cooked flesh of infected frogs, snakes, and chickens. Here, we report a rare case of a 45-year-old man who was admitted to our hospital with left lower chest pain. The chest radiograph and computed tomography (CT) scan revealed localized pleural effusion in the left lower lobe; further, peripheral blood eosinophilia and eosinophilic pleural effusion were present. Percutaneous catheter drainage was performed, which revealed long worm-shaped material that was identified as a sparganum by DNA sequencing. The patient showed clinical improvement after drainage of the sparganum. This study demonstrates the importance of considering parasitic diseases in the differential diagnosis of eosinophilic pleural effusion.
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http://dx.doi.org/10.3347/kjp.2014.52.5.541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210739PMC
October 2014

Crazy paving radiography finding in asymptomatic pulmonary alveolar proteinosis.

Asian Cardiovasc Thorac Ann 2015 Jun 2;23(5):588-90. Epub 2014 Sep 2.

Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea

Pulmonary alveolar proteinosis is a rare disorder characterized by alveolar accumulation of surfactant phospholipids and protein components. The symptoms and prognosis are extremely variable. Bronchoalveolar lavage fluid and/or transbronchial lung biopsy are useful for diagnosis; surgical lung biopsy is often unnecessary but useful in the focal involvement. We report a case of pulmonary alveolar proteinosis in a 50-year-old woman, confirmed by a video-assisted thoracoscopic surgery biopsy from the initial focal involvement, with normal bronchoalveolar lavage and transbronchial lung biopsy findings.
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http://dx.doi.org/10.1177/0218492314548232DOI Listing
June 2015

Single pleural relapse of a nasal-type extranodal natural killer/t-cell lymphoma: a case report.

Tuberc Respir Dis (Seoul) 2014 Apr 25;76(4):184-7. Epub 2014 Apr 25.

Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

A nasal-type extranodal natural killer/T-cell lymphoma is considered an aggressive form of non-Hodgkin's lymphoma, with approximately half of all patients relapsing during the follow-up period, and most relapses occurring within the first 2 years of remission. Here we report an unusual case of a 42-year-old man who experienced recurrence in single pleura after 8 years of remission.
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http://dx.doi.org/10.4046/trd.2014.76.4.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021267PMC
April 2014

Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion.

Cancer Res Treat 2014 Apr 22;46(2):178-85. Epub 2014 Apr 22.

Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

Purpose: The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE).

Materials And Methods: Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA).

Results: The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%.

Conclusion: The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.
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http://dx.doi.org/10.4143/crt.2014.46.2.178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022827PMC
April 2014

The diagnostic efficacy and safety of endobronchial ultrasound-guided transbronchial needle aspiration as an initial diagnostic tool.

Korean J Intern Med 2013 Nov 29;28(6):660-7. Epub 2013 Oct 29.

Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

Background/aims: Real-time, convex probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used for the staging of malignant mediastinal lymph nodes. We evaluated the diagnostic efficacy and safety of EBUS-TBNA when used as an initial diagnostic tool.

Methods: We retrospectively studied 56 patients who underwent EBUS-TBNA as an initial diagnostic tool between August 2010 and December 2011. Procedure purpose were classified into four categories: 1) intrathoracic masses adjacent to the central airway; 2) enlarged lymph nodes for concurrent diagnosis and staging in suspected malignancy; 3) enlarged lymph nodes in suspected malignancy cases with inability to perform percutaneous core needle biopsy (PCNB); and 4) solely mediastinal masses/lymph nodes in lieu of mediastinoscopy.

Results: The diagnostic accuracy of EBUS-TBNA regardless of procedure purpose was calculated to be 83.9%. Furthermore, the diagnostic accuracy of malignant disease was significantly higher than benign disease (93.9% vs. 70.6%, p < 0.001). The diagnostic accuracy of EBUS-TBNA for each disease is as follows: tuberculosis, 50%; sarcoidosis, 60%; aspergillosis, 100%; lung abscess, 100%; lung cancer, 93%; and lymphoma, 100%. There were minor complications in seven patients during the EBUS-TBNA procedure. The complications included mild hypoxia and bleeding.

Conclusions: In conclusion, EBUS-TBNA is a useful initial diagnostic tool for both benign and malignant diseases. EBUS-TBAN is also a very safe procedure and less invasive compared to mediastinoscopy or PCNB.
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http://dx.doi.org/10.3904/kjim.2013.28.6.660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846991PMC
November 2013

Characterization of mutations in multi- and extensive drug resistance among strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea.

Diagn Microbiol Infect Dis 2013 Jun 2;76(2):187-96. Epub 2013 Apr 2.

Korean Institute of Tuberculosis, Osong Saengmyeong 4-ro 168-5, Cheongwon-gun, Chungcheongbuk-do, 363-954, Republic of Korea.

In order to characterize molecular mechanisms of first- and second-line drug resistance in Mycobacterium tuberculosis and to evaluate the use of molecular markers of resistance, we analyzed 62 multidrug-resistant, 100 extensively drug-resistant, and 30 pan-susceptible isolates from Korean tuberculosis patients. Twelve genome regions associated with drug resistance, including katG, ahpC, and inhA promoter for isoniazid (INH); embB for ethambutol (EMB), rpoB for rifampin (RIF), pncA for pyrazinamide (PZA), gyrA for fluoroquinolones; rpsL, gidB, and rrs for streptomycin; rrs and eis for kanamycin (KM); rrs and tylA for capreomycin (CAP); and rrs for amikacin (AMK) were amplified simultaneously by polymerase chain reaction, and the DNA sequences were determined. We found mutations in 140 of 160 INH-resistant isolates (87.5%), 159 of 162 RIF-resistant isolates (98.15%), 127 of 143 EMB-resistant isolates (88.8%), 108 of 123 ofloxacin-resistant isolates (87.8%), and 107 of 122 PZA-resistant isolates (87.7%); 43 of 51 STM-resistant isolates (84.3%), 15 of 17 KM-resistant isolates (88.2%), and 14 of 15 (AMK and CAP)-resistant isolates (93.3%) had mutations related to specific drug resistance. In addition, the sequence analyses of the study revealed many novel mutations involving these loci. This result suggests that mutations in the rpoB531, katGSer315Thr, and C-15T in the inhA promoter region, and gyrA94, embB306, pncA159, rpsL43, and A1401G in the rrs gene could serve as useful markers for rapid detection of resistance profile in the clinical isolates of M. tuberculosis in Korea, with potentials for the new therapeutic benefits in actual clinical practice.
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http://dx.doi.org/10.1016/j.diagmicrobio.2013.02.035DOI Listing
June 2013

A possible role for CD8+ and non-CD8+ cell granzyme B in early small airway wall remodelling in centrilobular emphysema.

Respirology 2013 May;18(4):688-96

Division of Pulmonary Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.

Background And Objective: CD8(+) cell infiltration and apoptosis of airway epithelial cells are increased in chronic obstructive pulmonary disease (COPD). CD8(+) T cells induce apoptosis by releasing granzymes, which can also cause extracellular matrix degradation and remodelling. Granzyme B levels and T cells expressing granzyme B are increased in bronchoalveolar lavage fluid of COPD patients, which suggests that granzyme B may contribute to the pathogenesis of COPD. This study provides quantitation of granzyme B-positive cells in relation to CD8(+) cells in the small airway walls of emphysema.

Methods: Antibodies against CD8 and granzyme B were used to identify CD8(+) and granzyme B(+) cells. Volume fraction (Vv) of CD8(+) and granzyme B(+) cells were quantitated by the point counting method in the small airways of 13 non-smoker control subjects and 46 emphysema patients (14 panlobular emphysema (PLE) and 32 centrilobular emphysema (CLE) lungs). Immunohistochemical detection of macrophage scavenger receptor was also performed in randomly selected cases.

Results: The Vv of CD8(+) and granzyme B(+) cells in CLE was greater than those in control and PLE (both P < 0.001) subjects. The Vv of granzyme B(+) cells was greater than that of CD8(+) cells (P = 0.006), and not all CD8(+) cells were positive for granzyme B in CLE subjects. Monocytes expressing both granzyme B and macrophage scavenger receptor and granulocytes expressing granzyme B were identified.

Conclusions: Upregulation of granzyme B in CD8(+) and non-CD8(+) cells is an early phenomenon of small airway wall remodelling in centrilobular emphysema and suggests its possible role in the pathogenesis of COPD.
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http://dx.doi.org/10.1111/resp.12069DOI Listing
May 2013

Goodness-of-Fits of the Spirometric Reference Values for Koreans and USA Caucasians to Spirometry Data from Residents of a Region within Chungbuk Province.

Tuberc Respir Dis (Seoul) 2012 Mar 31;72(3):302-9. Epub 2012 Mar 31.

Department of Preventive Medicine and Medical Research Institute, Chungbuk National University College of Medicine, Cheongju, Korea.

Background: Korean regression models for spirometric reference values are different from those of Americans. Using spirometry results of Korean adults, goodness-of-fits of the Korean and the USA Caucasian regression models for forced vital capacity (FVC) and forced expiratory volume in one second (FEV(1)) were compared.

Methods: The number of study participants was 2,360 (1,124 males and 1,236 females). Spirometry was performed under the guidelines of the American Thoracic Society and the European Respiratory Society. After excluding unsuitable participants, spirometric data for 729 individuals (105 males and 624 females) was included in the statistical analysis. The estimated FVC and FEV(1) values were compared with those measured. Goodness-of-fits for Korean and USA Caucasian models were compared using an F-test.

Results: In males, the expected values of FVC and FEV(1) using the Korean model were 12.5% and 5.7% greater than those measured, respectively. The corresponding values for the USA Caucasian model were 3.5% and 0.6%. In females, the difference in FVC and FEV(1) were 13.5% and 7.7% for the Korean model, and 6.3% and 0.4% for the USA model, respectively. Goodness-of-fit for the Korean model regarding FVC was not good to the study population, but the Korean regression model for FEV(1), and the USA Caucasian models for FVC and FEV(1) showed good fits to the measured data.

Conclusion: These results suggest that the USA Caucasian model correlates better to the measured data than the Korean model. Using reference values derived from the Korean model can lead to an overestimation regarding the prevalence of abnormal lung function.
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http://dx.doi.org/10.4046/trd.2012.72.3.302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510280PMC
March 2012

Bowel infarction due to intestinal mucormycosis in an immunocompetent patient.

J Korean Surg Soc 2012 Nov 29;83(5):325-9. Epub 2012 Oct 29.

Department of Surgery, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Korea.

Mucormycosis is a fatal opportunistic fungal infection that typically occurs in immunocompromised patients. The classical manifestation of mucormycosis is a rhinocerebral infection, and although primary gastrointestinal infection is uncommon, it has an extremely high mortality rate in immunocompromised patients. Furthermore, cases of gastrointestinal mucormycosis in an immunocompetent host are rarely reported. Here, we describe our experience of a male patient, with no underlying disease, who succumbed to a bowel infarction caused by intestinal mucormycosis during mechanical ventilatory care for severe pneumonia and septic shock.
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http://dx.doi.org/10.4174/jkss.2012.83.5.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491236PMC
November 2012

Invasive aspergillosis involving the lungs and brain after short period of steroid injection: a case report.

Tuberc Respir Dis (Seoul) 2012 May 29;72(5):448-51. Epub 2012 May 29.

Department of Internal Medicine, Chungbuk University College of Medicine, Cheongju, Korea.

Invasive pulmonary aspergillosis (IPA) has emerged as a severe infection in patients with immunocompromised hosts. However, recently, several IPA cases, without an apparent predisposition to immunodeficiency, has been reported. A 72-year-old woman was admitted for evaluation of general weakness and poor oral intake. She reported no medical history, except for intraarticular injection of a corticosteroid for joint pain for the duration of two months. A chest radiography revealed multiple cavitary nodules in both lungs. Examination of specimens, obtained by percutaneous needle biopsy, led to a diagnosis of invasive aspergillosis. Brain magnetic resonance imagining revealed numerous peripheral thin enhancing cystic nodules in both cerebral hemispheres. We initiated intravenous administration of amphotercin B. However, the patient died after nine days. Here, we report an invasive aspergillosis case, which involves the lungs and brain after a short period of steroid injection.
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http://dx.doi.org/10.4046/trd.2012.72.5.448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475467PMC
May 2012

Detection of EGFR mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods of differential sensitivity.

J Thorac Oncol 2012 Feb;7(2):355-64

Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, South Korea.

Introduction: To evaluate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods with different sensitivities.

Methods: EGFR mutation status was determined by peptide nucleic acid (PNA) clamping and direct sequencing. The samples consisted of 41 cell blocks of malignant pleural effusions with various proportions of tumor cells, as well as 23 lung biopsy specimens containing more than 20% tumor cells and the corresponding surgically resected tumors.

Results: In the analysis of malignant pleural effusions, EGFR mutations were detected only by PNA clamping in four of nine patients who exhibited partial response to EGFR tyrosine kinase inhibitors; all the cell blocks of these four patients contained less than 20% tumor cells. Direct sequencing revealed wild-type EGFR, whereas PNA clamping revealed mutant EGFR, in one of five patients who exhibited progressive disease in response to EGFR tyrosine kinase inhibitor; the cell block of this patient contained a high proportion of tumor cells. A comparison of biopsy specimens containing sufficient tumor cells and the corresponding surgically resected tumors revealed discordance in the EGFR mutation status in four patients based on PNA clamping, whereas no discrepancies were observed by direct sequencing.

Conclusions: Highly sensitive methods, such as PNA clamping, may be superior to direct sequencing for the detection of EGFR mutations in diagnostic specimens with a low proportion of tumor cells. Direct sequencing may be more representative when diagnostic specimens with a high proportion of tumor cells are available.
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http://dx.doi.org/10.1097/JTO.0b013e31823c4c1bDOI Listing
February 2012

EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases.

Clin Lung Cancer 2011 Nov 20;12(6):380-6. Epub 2011 May 20.

Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

Unlabelled: We evaluated EGFR and KRAS mutations between 37 paired primary tumors and corresponding metastases in lung adenocarcinoma. A substantial discordance was found in EGFR mutation status between primary tumors and corresponding metastases including pleural metastases. Moreover, the responsiveness to EGFR tyrosine kinase inhibitors tend to be correlated with EGFR mutation status in metastatic lesions than in primary tumors.

Introduction: The aim of this study was to compare epidermal growth factor receptor (EGFR) and KRAS mutations between primary tumors and corresponding metastases including pleural metastases in lung adenocarcinoma.

Methods: Thirty-seven paired primary lung adenocarcinomas and corresponding metastatic tumors were analyzed for EGFR and KRAS mutations. In addition, 21 pleural metastases including malignant pleural effusion or pleural biopsy were used in performing these mutation analyses.

Results: EGFR mutations were detected in 18 primary lung adenocarcinomas (48.6%) and in 16 corresponding metastases (43.2%). EGFR mutations showed a discordance rate of 16.2% (6 of 37 patients) between primary lung adenocarcinomas and corresponding metastases. Among 21 pleural metastases, 3 patients (14.3%) showed that the EGFR mutation was discordant. KRAS mutations were detected in one primary tumor and in two metastatic tumors. Eighteen patients were treated with EGFR tyrosine kinase inhibitors. One of seven patients who experienced partial response had EGFR mutations only in the metastasis, and two of seven patients who experienced progressive disease carried wild-type EGFR only in the metastasis.

Conclusions: EGFR mutations were discordant between primary tumors and corresponding metastases in a significant portion of lung adenocarcinomas. Furthermore, these discordance was also observed in metastases to the pleura, the nearest metastatic site.
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http://dx.doi.org/10.1016/j.cllc.2011.02.006DOI Listing
November 2011
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