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/Aims: To improve the eradication rate of a first-line therapy for Helicobacter pylori infection, alternate regimens such as sequential, concomitant, and hybrid therapies have been tried. The aim of this study was to evaluate the eradication rate of the 10-day hybrid therapy as a first-line therapy. Materials and Methods: This retrospective study enrolled 124 patients from the Korea University Ansan Hospital between April 2016 and December 2019. The 10-day hybrid therapy comprised 5 days of dual therapy (proton pump inhibitor [PPI] standard dose and amoxicillin 1 g, twice daily) followed by 5 days of quadruple therapy (PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily). We compared the 10-day hybrid therapy with the 10-day concomitant therapy comprising PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily. Eradication was assessed by a 13C-urea breath test or gastroscopic biopsy at least 4 weeks after treatment completion. Results: The eradication rates of the 10-day hybrid and concomitant therapies were 74.2% (46/62) and 67.7% (42/62), respectively, in the intention-to-treat (ITT) analysis and 88.5% (46/52) and 82.4% (42/51), respectively, in the per-protocol (PP) analysis. There was no significant difference in the eradication rates between the two groups in the ITT (P=0.429) and PP analysis (P=0.380). Adverse events developed in 75.0% and 70.6% of patients in the hybrid and concomitant groups, respectively, but there was no significant difference (P=0.615). Conclusions The 10-day hybrid therapy can be an option for a first-line therapy of Helicobacter pylori infection.

Background/Aims: To improve the eradication rate of a first-line therapy for Helicobacter pylori infection, alternate regimens such as sequential, concomitant, and hybrid therapies have been tried. The aim of this study was to evaluate the eradication rate of the 10-day hybrid therapy as a first-line therapy. Materials and Methods: This retrospective study enrolled 124 patients from the Korea University Ansan Hospital between April 2016 and December 2019. The 10-day hybrid therapy comprised 5 days of dual therapy (proton pump inhibitor [PPI] standard dose and amoxicillin 1 g, twice daily) followed by 5 days of quadruple therapy (PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily). We compared the 10-day hybrid therapy with the 10-day concomitant therapy comprising PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily. Eradication was assessed by a 13C-urea breath test or gastroscopic biopsy at least 4 weeks after treatment completion. Results: The eradication rates of the 10-day hybrid and concomitant therapies were 74.2% (46/62) and 67.7% (42/62), respectively, in the intention-to-treat (ITT) analysis and 88.5% (46/52) and 82.4% (42/51), respectively, in the per-protocol (PP) analysis. There was no significant difference in the eradication rates between the two groups in the ITT (P=0.429) and PP analysis (P=0.380). Adverse events developed in 75.0% and 70.6% of patients in the hybrid and concomitant groups, respectively, but there was no significant difference (P=0.615). Conclusions The 10-day hybrid therapy can be an option for a first-line therapy of Helicobacter pylori infection.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been regarded as a curative treatment for early gastric cancer (EGC) in indicated cases. The aim of this study was to evaluate the nationwide long-term clinical outcomes of ESD for EGC in Korea. METHODS: A prospective multicenter cohort study was performed to evaluate the long-term efficacy of ESD for EGC within pre-defined indications at 12 institutes in Korea. The cases that met the expanded criteria upon pathological review after ESD were followed for 5 years. The primary outcome was 5-year disease specific free survival. RESULTS: Six hundred ninety-seven patients with 722 EGCs treated with ESD were prospectively enrolled and followed for 5 years. Complete resection was achieved in 81.3% of the cases, and curative resection was achieved in 86.1%. During the 5-year follow-up, the overall survival rate was 96.6%, and the disease specific free survival rate was 90.6%. Local recurrence developed in 0.9%, and metachronous tumor development occurred in 7.8%; both conditions were treated by endoscopic or surgical treatment. Distant metastasis developed in 0.5% during follow-up. CONCLUSIONS: ESD showed excellent long-term clinical outcomes and can be accepted as a curative treatment for patients with EGC who meet the expanded criteria in final pathology studies.
Academies and Institutes ; Cohort Studies* ; Follow-Up Studies ; Humans ; Korea ; Neoplasm Metastasis ; Pathology ; Prospective Studies* ; Recurrence ; Stomach Neoplasms* ; Survival Rate

BACKGROUND/AIMS: The aim of this study was to investigate the mortality, bleeding control rate, and their associated predictors in patients treated with Sengstaken-Blakemore (SB) tube for uncontrolled variceal hemorrhage associated with hemodynamic instability or failure of endoscopic treatment. METHODS: The clinical data of 66 consecutive patients with uncontrolled variceal hemorrhage treated with SB tube at Gyeongsang National University Hospital from October 2010 to October 2015 were retrospectively analyzed. RESULTS: The overall success rate of initial hemostasis with SB tube was 75.8%, and the independent factors associated with hemostasis were non-intubated state before SB tube (odds ratio, 8.50; p = 0.007) and Child-Pugh score < 11 (odds ratio, 15.65; p = 0.022). Rebleeding rate after successful initial hemostasis with SB tube was 22.0%, and esophageal rupture occurred in 6.1%. Mortality within 30 days was 42.4%, and the related independent factors with mortality were failure of initial hemostasis with SB tube (hazard ratio, 6.24; p < 0.001) and endotracheal intubation before SB tube (hazard ratio, 2.81; p = 0.018). CONCLUSIONS: Since the era of endoscopic band ligation, SB tube might be a beneficial option as a temporary salvage treatment for uncontrolled variceal hemorrhage. However, rescue therapy had a high incidence of fatal complication and rebleeding.
Hemodynamics ; Hemorrhage* ; Hemostasis ; Humans ; Incidence ; Intubation, Intratracheal ; Ligation ; Mortality ; Retrospective Studies ; Rupture ; Salvage Therapy

BACKGROUND/AIMS: Sleep impairment is a common complaint among patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD). This study aimed to evaluate the prevalence of sleep impairment in FD or IBS patients, and to determine whether IBS-FD overlap induced more sleep disturbance than FD or IBS alone. METHODS: A population-based cohort in South Korea including 2251 subjects was asked about gastrointestinal symptoms including IBS and dyspepsia-related symptoms. In addition, sleep disturbance was measured using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale questionnaires. One-way ANOVA and logistic regression were used to assess differences among the 4 groups (healthy subjects, IBS alone, FD alone, and IBS-FD overlap). RESULTS: Of 2251 subjects who were surveyed by questionnaire, 2031 responded (92.5% response rate) and were analyzed. The prevalence of IBS, FD, and IBS-FD overlap was 8.0% (95% confidence interval [CI], 6.8–9.2%), 4.8% (95% CI, 3.9–5.8%), and 1.8% (95% CI, 1.2–2.4%), respectively. FD alone, but not IBS alone, was significantly associated with a poorer sleep quality index (OR, 2.68; 95% CI, 1.43–5.01) and more daytime sleepiness (OR, 2.21; 95% CI, 1.14–4.30), compared to healthy subjects. IBS-FD overlap had the greatest likelihood of a poorer sleep quality index (OR, 3.88; 95% CI, 1.83–8.19), daytime sleepiness (OR, 2.47; 95% CI, 1.01–5.67), and insomnia (OR, 2.84; 95% CI, 1.39–5.82), compared to healthy subjects. CONCLUSION: A correlation between functional gastrointestinal disorders and sleep disturbance was demonstrated, which was significantly pronounced in the context of IBS-FD overlap.
Cohort Studies ; Dyspepsia ; Gastrointestinal Diseases ; Healthy Volunteers ; Humans ; Irritable Bowel Syndrome ; Korea ; Logistic Models ; Prevalence ; Sleep Initiation and Maintenance Disorders

BACKGROUND/AIMS: Various clinical scoring systems, including the Glasgow-Blatchford score (GBS), Rockall risk score (RS), and AIMS65 score (AIMS65), have been validated to predict the clinical outcomes in patients with upper gastrointestinal bleeding (UGIB). We compared the performance of these three scoring systems in predicting clinical outcomes in patients with UGIB in Korea. METHODS: We retrospectively evaluated 286 patients with UGIB who visited emergency department. The primary outcome was the need for clinical intervention (endoscopic, radiologic, or surgical) and blood transfusion. RESULTS: The causes of UGIB were esophageal/gastric varices in 64 patients, peptic ulcer in 168, Mallory-Weiss tear in 32, malignancy of UGI tract in eight, and unknown in 14. One hundred seventy-four (61%) patients required blood transfusion, 166 (58%) required endoscopic intervention, and 10 (3.5%) required surgical intervention. The GBS outperformed the RS and AIMS65 in predicting the need for endoscopic intervention. CONCLUSIONS: The GBS and RS were more accurate than AIMS65 in predicting the need for clinical interventions and transfusion patients with UGIB, regardless of variceal or nonvariceal bleeding. The AIMS65 may not be optimal for predicting clinical outcomes of UGIB in Korea.
Blood Transfusion ; Emergency Service, Hospital ; Gastrointestinal Hemorrhage ; Hemorrhage* ; Humans ; Korea ; Mallory-Weiss Syndrome ; Mortality ; Peptic Ulcer ; Retrospective Studies ; Risk Assessment ; Varicose Veins

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been an established treatment for indicated early gastric cancer (EGC) without deterioration of quality of life (QOL) compared with surgical resection. The aim of this study was to evaluate long-term QOL in patients undergoing ESD for EGC. METHODS: Patients scheduled to undergo curative ESD for EGC were prospectively enrolled from 12 institutions between May 2010 and December 2011. Assessments of QOL with Korean versions of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and a gastric cancer-specific questionnaire (STO22) were performed at baseline and at 7 days, 3 months, and 6 months after ESD. RESULTS: A total of 666 subjects were assessed for QLQ-C30 and QLQ-STO22. The mean QLQ-C30 score was 69.5 at baseline, 68.8 at 7 days, 73.1 at 3 months, and 73.2 at 6 months. The global health status on the EORTC QLQ-C30 was significantly improved after 3 and 6 months (p=0.0003 and p<0.0001, respectively). The QLQ-C30 and STO22 scores were not significantly different, or they only slightly deteriorated between before and immediately after ESD, but they were significantly improved after 3 and 6 months (p<0.05). CONCLUSIONS: QOL did not deteriorate immediately after ESD, and it improved more significantly at up to 6 months in patients who underwent curative ESD for EGC without significant complications.
Cohort Studies* ; Global Health ; Humans ; Prospective Studies* ; Quality of Life* ; Stomach Neoplasms*

The objective of this study was to investigate national surgical trends for distal radius fractures (DRFs) in Korea and analyze healthcare institution type-specific surgical trends. We analyzed a nationwide database acquired from the Korean Health Insurance Review and Assessment Service (HIRA) from 2011 to 2015. International Classification of Diseases, 10th revision (ICD-10) codes and procedure codes were used to identify patients aged ≥ 20 years with newly diagnosed DRFs. A total of 459,388 DRFs occurred from 2011 to 2015. The proportion of DRF cases treated by surgery tended to increase over time, from 32.6% in 2011 to 38.3% in 2015 (P < 0.001). Open reduction with internal fixation (ORIF) using a plate steadily gained in popularity each year, increasing from 39.2% of overall surgeries in 2011 to 60.9% in 2015. The type of surgery for DRFs differed depending on the type of healthcare institution. ORIF (91%) was the most popular procedure in tertiary hospitals, whereas percutaneous pinning (58%) was most popular in clinics. In addition, general hospitals and hospitals with 30–100 beds used external fixation more frequently than tertiary hospitals and clinics did. Overall, our findings indicate that surgical treatment of DRF, particularly ORIF, continues to increase, and that the component ratio of operation codes differed according to the healthcare institution type.
Delivery of Health Care ; Epidemiology ; Hospitals, General ; Humans ; Insurance, Health ; International Classification of Diseases ; Korea* ; Radius Fractures* ; Radius* ; Tertiary Care Centers

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized the reporting of thyroid cytology specimens. The objective of the current study was to evaluate the nationwide usage of TBSRTC and assess the malignancy rates in each category of TBSRTC in Korea. METHODS: Questionnaire surveys were used for data collection on the fine needle aspiration (FNA) of thyroid nodules at 74 institutes in 2012. The incidences and follow-up malignancy rates of each category diagnosed from January to December, 2011, in each institute were also collected and analyzed. RESULTS: Sixty out of 74 institutes answering the surveys reported the results of thyroid FNA in accordance with TBSRTC. The average malignancy rates for resected cases in 15 institutes were as follows: nondiagnostic, 45.6%; benign, 16.5%; atypical of undetermined significance, 68.8%; suspicious for follicular neoplasm (SFN), 30.2%; suspicious for malignancy, 97.5%; malignancy, 99.7%. CONCLUSIONS: More than 80% of Korean institutes were using TBSRTC as of 2012. All malignancy rates other than the SFN and malignancy categories were higher than those reported by other countries. Therefore, the guidelines for treating patients with thyroid nodules in Korea should be revisited based on the malignancy rates reported in this study.
Academies and Institutes ; Biopsy, Fine-Needle ; Data Collection ; Follow-Up Studies ; Humans ; Incidence ; Korea* ; Thyroid Gland* ; Thyroid Nodule