Purpose: Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. Materials and Methods: We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. Results: In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. Conclusion Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

BACKGROUND/AIM: We aimed to evaluate the efficacy of sending educational video clips via smartphone mobile messenger (SMM) on enhancing bowel preparation before colonoscopy. METHODS: This was a prospective, endoscopist-blinded, randomized controlled study. Patients in the SMM group received two video clips sent via SMM that explained the diet and regimen for bowel preparation, whereas those in the control group did not receive any video clips. We compared the quality of bowel preparation between the two groups, which was assessed by an endoscopist using the Ottawa scale. RESULTS: Between August and November 2014, 140 patients in the SMM group and 141 patients in the control group underwent colonoscopic examination. The total Ottawa score of the SMM group was significantly lower than that of the control group (5.47±1.74 vs. 5.97±1.78, p=0.018). These results were particularly prominent in the younger age group; the total Ottawa score of patents in the SMM group aged <40 years was significantly lower than that of patients in the control group aged <40 years (5.10±1.55 vs. 6.22±2.33, p=0.034). CONCLUSIONS: We demonstrated that sending educational video clips via SMM could result in better bowel preparation, especially in the younger age group.
Colonoscopy ; Diet ; Education ; Humans ; Prospective Studies ; Smartphone

Chronic cough is common in the community and causes significant morbidity. Several factors may underlie this problem, but comorbid conditions located at sensory nerve endings that regulate the cough reflex, including rhinitis, rhinosinusitis, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease, are considered important. However, chronic cough is frequently non-specific and accompanied by not easily identifiable causes during the initial evaluation. Therefore, there are unmet needs for developing empirical treatment and practical diagnostic approaches that can be applied in primary clinics. Meanwhile, in referral clinics, a considerable proportion of adult patients with chronic cough are unexplained or refractory to conventional treatment. The present clinical practice guidelines aim to address major clinical questions regarding empirical treatment, practical diagnostic tools for non-specific chronic cough, and available therapeutic options for chronic wet cough in children and unexplained chronic cough in adults in Korea.
Adult* ; Asthma ; Bronchitis ; Child* ; Cough* ; Eosinophils ; Evidence-Based Medicine ; Gastroesophageal Reflux ; Humans ; Korea* ; Referral and Consultation ; Reflex ; Rhinitis ; Sensory Receptor Cells

BACKGROUND/AIMS: Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model. METHODS: Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed. RESULTS: In the training cohort, four factors were independent negative predictors of survival (p<0.05). Based on the β regression coefficient of each factor, we established the NEXT score (Survival after Stopping Nexavar Treatment), allocating 1 point each for an Eastern Cooperative Oncology Group score ≥2, Child-Pugh class B or C, serum sodium ≤135 mEq/L, and α-fetoprotein >400 ng/mL. Area under the receiver operating characteristic curve values to predict 1-, 3-, and 6-month survival rates were 0.805, 0.809, and 0.774, respectively, in the training cohort and 0.783, 0.728, and 0.673, respectively, in the validation cohort (n=137). When the training and validation cohorts were stratified into three risk groups (NEXT score 0 [low-risk] vs 1 to 2 [intermediate-risk] vs 3 to 4 [high-risk]), survival differed significantly between the groups (p<0.05, log-rank test). CONCLUSIONS: In patients with HCC, survival after stopping sorafenib is poor. However, risk estimates based on a new “NEXT score” may help predict survival and prognosis even in patients who discontinue sorafenib treatment.
Carcinoma, Hepatocellular* ; Cohort Studies ; Humans ; Prognosis ; ROC Curve ; Sodium ; Survival Rate

PURPOSE: To evaluate the diagnostic accuracy of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) in predicting pelvic lymph node (LN) metastases in patients with cervical cancer. MATERIALS AND METHODS: From January 2009 to March 2015, 114 patients with FIGO stage IA1-IIB uterine cervical cancer who underwent hysterectomy with pelvic lymphadenectomy and took CT, MRI, and PET/CT before surgery were enrolled in this study. The criteria for LN metastases were a LN diameter ≥1.0 cm and/or the presence of central necrosis on CT, a LN diameter ≥1.0 cm on MRI, and a focally increased FDG uptake on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for pelvic LN metastases were estimated. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy for detection of pelvic LN metastases were 51.4%, 85.9%, 41.3%, 90.1%, and 80.3% for CT; 24.3%, 96.3%, 56.3%, 86.8%, and 84.6% for MRI; and 48.6%, 89.5%, 47.4%, 90.0%, and 82.9% for PET/CT, respectively. The sensitivity of PET/CT and CT was higher than that of MRI (p=0.004 and p= 0.013, respectively). The specificity of MRI was higher than those of PET/CT and CT (p=0.002 and p=0.001, respectively). The difference of specificity between PET/CT and CT was not statistically significant (p=0.167). CONCLUSION: These results indicate that preoperative CT, MRI, and PET/CT showed low to moderate sensitivity and PPV, and moderate to high specificity, NPV, and accuracy. More efforts are necessary to improve sensitivity of imaging modalities in order to predict pelvic LN metastases.
Electrons ; Humans ; Hysterectomy ; Lymph Node Excision ; Lymph Nodes* ; Magnetic Resonance Imaging ; Necrosis ; Neoplasm Metastasis* ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Sensitivity and Specificity ; Uterine Cervical Neoplasms*

We used a survey about the need for an educational training of infectious disease response staff in Korea Centers for Disease Control and Prevention (KCDC) and officer in metropolitan cities and provincial government to conduct field epidemiological investigation. The survey was conducted from January 25 to March 15, 2016. A total of 173 participants were selected from four different groups as follows: 27 clinical specialists, 22 Epidemic Intelligence Service (EIS) officers, 82 KCDC staff, and 42 local health department officials. Results revealed that 83% of KCDC staff and 95% of local health department officials agreed on the need for educational training to strengthen capability of personnel to conduct epidemic research and investigation. The level of their need for training was relatively high, while self-confidence levels of individuals to conduct epidemic research and investigation was low. It was concluded that there was a need to develop training programs to enhance the ability of public health officials, EIS officers, KCDC staff, and local health department personnel to conduct epidemic research and investigation.
Centers for Disease Control and Prevention (U.S.) ; Communicable Diseases* ; Education* ; Epidemiology* ; Intelligence ; Korea* ; Public Health ; Specialization ; State Government ; Surveys and Questionnaires

We used a survey about the need for an educational training of infectious disease response staff in Korea Centers for Disease Control and Prevention (KCDC) and officer in metropolitan cities and provincial government to conduct field epidemiological investigation. The survey was conducted from January 25 to March 15, 2016. A total of 173 participants were selected from four different groups as follows: 27 clinical specialists, 22 Epidemic Intelligence Service (EIS) officers, 82 KCDC staff, and 42 local health department officials. Results revealed that 83% of KCDC staff and 95% of local health department officials agreed on the need for educational training to strengthen capability of personnel to conduct epidemic research and investigation. The level of their need for training was relatively high, while self-confidence levels of individuals to conduct epidemic research and investigation was low. It was concluded that there was a need to develop training programs to enhance the ability of public health officials, EIS officers, KCDC staff, and local health department personnel to conduct epidemic research and investigation.
Centers for Disease Control and Prevention (U.S.) ; Communicable Diseases ; Education ; Epidemiology ; Intelligence ; Korea ; Public Health ; Specialization ; State Government ; Surveys and Questionnaires