PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

BACKGROUND AND OBJECTIVES: Although current guidelines recommend early initiation of statin in patients with acute myocardial infarction (AMI), there is no consensus for optimal timing of statin initiation. METHODS: A total of 3,921 statin-naïve patients undergoing percutaneous coronary intervention were analyzed, and divided into 3 groups according to statin initiation time: group 1 (statin initiation <24 hours after admission), group 2 (24–48 hours) and group 3 (≥48 hours). We also made 3 stratified models to reduce bias: model 1 (<24 hours vs. ≥24 hours), model 2 (<48 hours vs. ≥48 hours) and model 3 (<24 hours vs. 24–48 hours). The endpoint was major adverse cardiac events (MACE; composite of cardiac death, myocardial infarction and target-vessel revascularization) during median 3.8 years. RESULTS: During follow-up, incidence of MACE was lower in early statin group in both model 1 (14.3% vs. 18.4%, hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66–0.91; p=0.002) and model 2 (14.6% vs. 19.7%, HR, 0.81; 95% CI, 0.67–0.97; p=0.022). After propensity-score matching, results remained unaltered. Statin initiation <24 hours reduced MACE compared to statin initiation ≥24 hours in model 1. Statin initiation <48 hours also reduced MACE compared to statin initiation later in model 2. However, there was no difference in incidence of MACE between statin initiation <24 hours and 24–48 hours) in model 3. CONCLUSIONS: Early statin therapy within 48 hours after admission in statin-naïve patients with AMI reduced long-term clinical outcomes compared with statin initiation later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02385682
Bias (Epidemiology) ; Consensus ; Death ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention

BACKGROUND/AIMS: Previous studies from Korea have described chronic intestinal pseudo-obstruction (CIPO) patients with transition zone (TZ) in the colon. In this study, we evaluated the pathological characteristics and their association with long-term outcomes in Korean colonic pseudo-obstruction (CPO) patients with TZ. METHODS: We enrolled 39 CPO patients who were refractory to medical treatment and underwent colectomy between November 1989 and April 2016 (median age at symptoms onset: 45 [interquartile range, 29–57] years, males 46.2%). The TZ was defined as a colonic segment connecting a proximally dilated and distally non-dilated segment. Detailed pathologic analysis was performed. RESULTS: Among the 39 patients, 37 (94.9%) presented with TZ and 2 (5.1%) showed no definitive TZ. Median ganglion cell density in the TZ adjusted for the colonic circumference was significantly decreased compared to that in proximal dilated and distal non-dilated segments in TZ (+) patients (9.2 vs 254.3 and 150.5, P < 0.001). Among the TZ (+) patients, 6 showed additional pathologic findings including eosinophilic ganglionitis (n = 2), ulcers with combined cytomegalovirus infection (n = 2), diffuse ischemic changes (n = 1), and heterotropic myenteric plexus (n = 1). During follow-up (median, 61 months), 32 (82.1%) TZ (+) patients recovered without symptom recurrence after surgery. The presence of pathological features other than hypoganglionosis was an independent predictor of symptom recurrence after surgery (P = 0.046). CONCLUSIONS: Hypoganglionosis can be identified in the TZ of most Korean CPO patients. Detection of other pathological features in addition to TZ-associated hypoganglionosis was associated with poor post-operative outcomes.
Cell Count ; Colectomy ; Colon ; Colonic Pseudo-Obstruction ; Cytomegalovirus Infections ; Eosinophils ; Follow-Up Studies ; Ganglion Cysts ; Humans ; Intestinal Pseudo-Obstruction ; Korea ; Male ; Myenteric Plexus ; Pathology ; Recurrence ; Ulcer

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

BACKGROUND/AIMS: Recent studies have demonstrated that etomidate is a safe sedative drug with noninferior sedative effects. In our recent study, we revealed that etomidate/midazolam was more hemodynamically stable than propofol/midazolam in elderly patients undergoing colonoscopies. We aimed to investigate whether compared with propofol/midazolam, etomidate/midazolam causes fewer cardiopulmonary adverse events with noninferior efficacy for screening colonoscopies in patients of all ages. METHODS: In this single-center, randomized, double-blind study, we prospectively enrolled 200 patients. The patients were divided into etomidate and propofol groups. The primary outcome was the occurrence of cardiopulmonary adverse events. The secondary outcomes were the proportion of patients with fluctuations in vital signs (oxygen desaturation and transient hypotension), adverse events interrupting the procedure, and sedation-related outcomes. RESULTS: Adverse cardiopulmonary events were more common in the propofol group than the etomidate group (65.0% vs 51.0%, respectively; p=0.045). Forty-six patients (46.0%) in the propofol group and 29 (29.0%) in the etomidate group experienced fluctuations in their vital signs (p=0.013). The proportions of patients experiencing adverse events that interrupted the procedure, including myoclonus, were not significantly different between the two groups (etomidate: 20.0% vs propofol: 11.0%; p=0.079). Both groups had similar sedation-related outcomes. Multivariate analysis revealed that compared with the propofol groups, the etomidate group had a significantly lower risk of fluctuations in vital signs (odds ratio, 0.427; 95% confidence interval, 0.230 to 0.792; p=0.007). CONCLUSIONS: Compared with using propofol/midazolam, using etomidate/midazolam for screening colonoscopies results in more stable hemodynamic responses in patients of all ages; therefore, we recommend using etomidate/midazolam for colonoscopies in patients with cardiovascular risk factors.
Aged ; Colonoscopy ; Double-Blind Method ; Etomidate ; Hemodynamics ; Humans ; Hypnotics and Sedatives ; Mass Screening ; Midazolam ; Multivariate Analysis ; Myoclonus ; Propofol ; Prospective Studies ; Risk Factors ; Vital Signs

BACKGROUND: Snoring is the cardinal symptom of obstructive sleep apnea (OSA). Snoring and upper airway obstruction associated with major oxygen desaturation may occur in populations undergoing flexible bronchoscopy. METHODS: To evaluate the prevalence of patients at a high risk of having OSA among patients undergoing bronchoscopy with sedation and to investigate whether snoring during the procedure predicts patients who are at risk of OSA, we prospectively enrolled 517 consecutive patients who underwent the procedure with moderate sedation. Patients exhibiting audible snoring for any duration during the procedure were considered snorers. The STOP-Bang (Snoring, Tiredness, Observed apnea, high blood Pressure-Body mass index, Age, Neck circumference and Gender) questionnaire was used to identify patients at high (score ≥3 out of 8) or low risk (score <3) of OSA. RESULTS: Of the 517 patients, 165 (31.9%) snored during bronchoscopy under sedation. The prevalence of a STOP-Bang score ≥3 was 61.9% (320/517), whereas 200 of the 352 nonsnorers (56.8%) and 120 of the 165 snorers (72.7%) had a STOP-Bang score ≥3 (p=0.001). In multivariable analysis, snoring during bronchoscopy was significantly associated with a STOP-Bang score ≥3 after adjustment for the presence of diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, and stroke (adjusted odds ratio, 1.91; 95% confidence interval, 1.26–2.89; p=0.002). CONCLUSION: Two-thirds of patients undergoing bronchoscopy with moderate sedation were at risk of OSA based on the screening questionnaire. Snoring during bronchoscopy was highly predictive of patients at high risk of OSA.
Airway Obstruction ; Apnea ; Bronchoscopy ; Conscious Sedation ; Diabetes Mellitus ; Humans ; Mass Screening ; Neck ; Odds Ratio ; Oxygen ; Prevalence ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; Renal Insufficiency, Chronic ; Sleep Apnea, Obstructive ; Snoring ; Stroke

PURPOSE: Current neoadjuvant chemotherapy (NAC) may enable therapies such as surgical resection and local ablation of metastases in patients with colorectal liver metastasis (CLM). We evaluated outcomes in CLM patients who underwent resection and/or local treatment after NAC and identified prognostic factors for oncologic outcomes. METHODS: Patients who received NAC followed by resection and/or local treatment of hepatic metastasis from 2013 to 2015 were included. Treatment and tumor-related variables were tabulated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox regression analysis was used to identify factors associated with RFS and OS. RESULTS: Sixty-eight patients received NAC followed by resection and/or local treatment of hepatic metastases. Targeted therapy was administered in 50% of the patients. RFS was 35.8% at 1 year and 19.4% at 2 years postoperatively. OS was 95.6% at 1 year and 88.2% at 2 years postoperatively. In the multivariable analysis, R1 resection margin (hazard ratio [HR], 3.95; P = 0.008) of the liver metastases and ypN1/ypN2 (HR, 2.356 and 1.983, respectively; P = 0.041) were associated with poor RFS. Both factors were also significantly related to OS. CONCLUSION: Resection margin of the metastatic tumor and ypN status are the only relevant factors for RFS and OS in CLM patients treated with NAC. Despite early and high rates of recurrence, CLM patients treated with NAC who undergo resection and/or local treatment have acceptable OS. Multidisciplinary review of candidates for surgery and cautious planning are crucial for achieving optimal outcomes.
Colorectal Neoplasms ; Drug Therapy ; Humans ; Liver ; Methods ; Neoplasm Metastasis ; Recurrence

BACKGROUND/AIMS: Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB. METHODS: The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding. RESULTS: In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations. CONCLUSIONS: The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.
Hemorrhage* ; Humans ; Incidence ; Korea ; Mortality ; Multivariate Analysis ; Peptic Ulcer Hemorrhage ; Peptic Ulcer* ; Prospective Studies ; Proton Pump Inhibitors ; Risk Factors

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is useful for obtaining pancreatic mass samples. The combination of modified techniques (i.e., slow-pull technique and fanning technique) may improve the quality of the sample obtained by EUS-FNA. We investigated the effectiveness of a combined slow-pull fanning technique in EUS-FNA for pancreatic mass. METHODS: This prospective comparative study investigated EUS-FNA performed for pancreatic solid masses between August 2015 and July 2016. Pairwise specimens were alternately obtained using the following two techniques for targeted pancreatic lesions: standard suction or slow-pull with fanning. We compared the specimen quality, blood contamination, and diagnostic accuracy of these techniques. RESULTS: Forty-eight consecutive patients were included (29 men; mean age, 68.1±11.9 years), and 96 pancreatic mass specimens were obtained. The slow-pull with fanning technique had a significantly superior diagnostic accuracy than the suction technique (88% vs 71%, p=0.044). Furthermore, blood contamination was significantly reduced using the slow-pull with fanning technique (ratio of no or slight contamination, 77% vs 56%, p=0.041). No difference was observed in the acquisition of adequate cellularity between the groups. In the subgroup analysis, the tumor size and sampling technique were related to the EUS-FNA diagnostic accuracy. CONCLUSIONS: The slow-pull with needle fanning technique showed a good diagnostic yield for EUS-FNA for pancreatic mass. This technique can be useful for performing EUS-guided sampling for diagnosing pancreatic disease.
Biopsy, Fine-Needle* ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Endosonography ; Humans ; Male ; Needles ; Pancreas ; Pancreatic Diseases ; Prospective Studies ; Suction*

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.
Cohort Studies ; Coronavirus ; Coronavirus Infections* ; Follow-Up Studies ; Humans ; Korea ; Middle East* ; Pneumonia* ; Prospective Studies ; Survivors