Purpose: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. Materials and Methods: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. Results: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. Conclusion Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

Background: Cardiac arrest during or after office-based cosmetic surgery is rare, and little is known about its prognosis. We assessed the clinical outcomes of patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics. Methods: Between May 2009 and May 2016, 32 patients who developed cardiac arrest during or after treatment at cosmetic surgery clinics were consecutively enrolled. We compared clinical outcomes, including complications, between survivors (n=19) and non-survivors (n=13) and attempted to determine the prognostic factors of mortality. Results: All 32 of the patients were female, with a mean age of 30.40±11.87 years. Of the 32 patients, 13 (41%) died. Extracorporeal life support (ECLS) was applied in a greater percentage of non-survivors than survivors (92.3% vs. 47.4%, respectively; p=0.009). The mean duration of in-hospital cardiopulmonary resuscitation (CPR) was longer for the non-survivors than the survivors (31.55±33 minutes vs. 7.59±9.07 minutes, respectively; p=0.01).The mean Acute Physiology and Chronic Health Evaluation score was also higher among non-survivors than survivors (23.85±6.68 vs. 16.79±7.44, respectively; p=0.01). No predictor of death was identified in the patients for whom ECLS was applied. Of the 19 survivors, 10 (52.6%) had hypoxic brain damage, and 1 (5.3%) had permanent lower leg ischemia.Logistic regression analyses revealed that the estimated glomerular filtration rate was a predictor of mortality. Conclusion Patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics experienced poor prognoses, even though ECLS was applied in most cases. The survivors suffered serious complications. Careful monitoring of subjects and active CPR (when necessary) in cosmetic surgery clinics may be essential.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

Keratinocytes are constantly exposed to extracellular insults, such as ultraviolet B, toxic chemicals and mechanical stress, all of which can facilitate the aging of keratinocytes via the generation of intracellular reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in protecting keratinocytes against oxidants and xenobiotics by binding to the antioxidant response element (ARE), a cis-acting element existing in the promoter of most phase II cytoprotective genes. In the present study, we have attempted to find novel ethanol extract(s) of indigenous plants of Jeju island, Korea that can activate the Nrf2/ARE-dependent gene expression in human keratinocyte HaCaT cells. As a result, we identified that ethanol extract of Cirsium japonicum var. ussuriense Kitamura (ECJUK) elicited strong stimulatory effect on the ARE-dependent gene expression. Supporting this observation, we found that ECJUK induced the expression of Nrf2, hemoxygenase-1, and NAD(P)H:quinone oxidoreductase-1 and this event was correlated with Akt1 phosphorylation. We also found that ECJUK increased the intracellular reduced glutathione level and suppressed 12-O-tetradecanoylphorbol acetate-induced 8-hydroxyguanosine formation without affecting the overall viability. Collectively, our results provide evidence that ECJUK can protect against oxidative stress-mediated damages through the activation of Nrf2/ARE-dependent phase II cytoprotective gene expression.
Aging ; Antioxidant Response Elements* ; Cirsium* ; DNA Damage* ; DNA* ; Ethanol* ; Gene Expression ; Glutathione ; Humans* ; Keratinocytes* ; Korea ; Oxidants ; Phosphorylation ; Reactive Oxygen Species ; Stress, Mechanical ; Transcription Factors ; Xenobiotics

Insulin-induced allergy is a rare adverse drug reaction since the introduction of recombinant human insulin. However, recombinant insulin-induced allergy is still being reported in 0.1% to 2% of all patients treated with insulin. This allergic reaction varies from mild localized skin reactions to life-threatening anaphylaxis. It has been shown that one-third of insulin allergy cases is related to insulin itself and the remaining occur due to preservatives contained in the insulin preparations, such as protamine, zinc, or metacresol. This case report describes a 75-year-old woman with poorly controlled diabetes who experienced insulin allergy. She complained of urticaria with itching after the injection of insulin. Allergic skin tests showed positive responses to all available human insulin preparations, and specific IgE to human insulin was also detected, which suggested that her urticaria was developed by insulin itself. This is the first case of insulin allergy that was sensitive to all available human insulin preparations and confirmed by the presence of specific IgE to human insulin. It is important to remember that allergic reactions to insulin may be directly associated with adherence and can be the reason of poor glucose control.
Aged ; Anaphylaxis ; Drug-Related Side Effects and Adverse Reactions ; Female ; Glucose ; Humans* ; Hypersensitivity* ; Immunoglobulin E ; Insulin Antibodies ; Insulin* ; Pruritus ; Skin ; Skin Tests ; Urticaria ; Zinc

PURPOSE: This study evaluated the relationship of living near to main roads to allergic diseases, airway hyperresponsiveness (AHR), allergic sensitization, and lung function in Korean children. METHODS: A total of 5,443 children aged 6-14 years from 33 elementary schools in 10 cities during 2005-2006 were included in a baseline survey of the Children's Health and Environmental Research. We assessed association of traffic-related air pollution (TAP) exposure with the distance to the nearest main road, total road length of main roads and the proportion of the main road area within the 200-m home area. RESULTS: Positive exposure-response relationships were found between the length of the main road within the 200-m home area and lifetime wheeze (adjusted prevalence ratio [PR] for comparison of the longest to the shortest length categories=1.24; 95% CIs, 1.04-1.47; P for trend=0.022) and diagnosed asthma (PR=1.42; 95% CIs, 1.08-1.86; P for trend=0.011). Living less than 75 m from the main road was significantly associated with lifetime allergic rhinitis (AR), past-year AR symptoms, diagnosed AR, and treated AR. The distance to the main road (P for trend=0.001), the length of the main road (P for trend=0.041), and the proportion of the main road area (P for trend=0.006) had an exposure-response relationship with allergic sensitization. A strong inverse association was observed between residential proximity to the main load and lung function, especially FEV1, FEV1/FVC, and FEF25-75. The length of the main road and the proportion of the main road area were associated with reduced FEV1 in schoolchildren. CONCLUSIONS: The results of this study suggest that exposure to traffic-related air pollution may be associated with increased risk of asthma, AR, and allergic sensitization, and with reduced lung function in schoolchildren.
Air Pollution* ; Asthma ; Bronchial Hyperreactivity ; Child ; Surveys and Questionnaires ; Humans ; Lung ; Prevalence ; Respiratory Function Tests ; Rhinitis

PURPOSE: Pulmonary function tests are useful and important methods for evaluating patients with respiratory diseases. To assess lung function, we need to establish normal values of lung function, which vary according to population, age, gender and growth, particularly in children. This study was undertaken to establish normal predicted values of pulmonary function tests and to predict renewed reference values by spirometry in Korean school children. METHODS: Spirometric forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25% to 75% of FVC (FEF25%-75%), and peak expiratory flow rate (PEFR) were measured in 406 healthy elementary school children (age, 6-12 years old) in May, 2012. Multiple linear regression analysis was performed for each spirometric parameter against age, height, weight and body surface area (BSA) separately for boys and girls, and derived reference equations and coefficients for all the spirometric parameters. RESULTS: All the measured spirometric parameters were significantly correlated with age, height, weight, and BSA. FVC was higher in boys aged 6-10 years than girls at ages matched. Height showed the highest correlation coefficient for all the spirometric parameters followed by BSA, weight and age in both genders. The normal predicted values of FVC and FEV1 at 130 cm in this study using renewed reference equations were approximately in the middle compared to previous studies. CONCLUSION: We reported here the renewed reference equations for normal predicted values of pulmonary function tests with high coefficients of determination based on updated data in healthy Korean children.
Body Surface Area ; Child* ; Female ; Forced Expiratory Volume ; Humans ; Linear Models ; Lung ; Peak Expiratory Flow Rate ; Reference Values* ; Respiratory Function Tests* ; Spirometry ; Vital Capacity

BACKGROUND/AIMS: Laparoscopic Heller myotomy with antireflux procedure is considered to be a standard treatment for achalasia. Recently, peroral endoscopic myotomy (POEM) was developed and performed on patients with achalasia. However, there is no report on POEM use in South Korea. The aim of this study was to evaluate the technical feasibility of POEM in a porcine model. METHODS: POEM was performed on two mini pigs. We performed upper endoscopy under general anesthesia. A submucosal tunnel was created and the circular muscle layer was incised using several knives. The mucosal entry was closed using resolution clips. We performed a follow-up endoscopy and sacrificed the pigs 2 weeks after the POEM. The myotomy site was evaluated grossly and histologically. RESULTS: POEM was successfully performed on the two mini pigs. No injuries to any abdominal or mediastinal structures occurred. Two weeks after the POEM, the esophageal mucosa healed without any endoscopic evidence of complications. Necropsy revealed that the circular muscle layer was completely lost and replaced with fibrotic tissue. CONCLUSIONS: We found that POEM is a technically feasible method which can be performed on an animal model. However, to ensure safe use on patients with achalasia, further studies on technical methods and long-term follow-up examinations are required.
Anesthesia, General ; Animals ; Dietary Sucrose ; Endoscopy ; Esophageal Achalasia ; Esophagus ; Feasibility Studies ; Follow-Up Studies ; Humans ; Models, Animal ; Mucous Membrane ; Muscles ; Republic of Korea ; Swine

Flexible bronchoscopy is a safe medical procedure, but the incidence rate of major complications is 0.08-0.3%. Here, we report 2 cases of stress induced cardiomyopathy, which developed immediately after flexible bronchoscopy. Stress related cardiomyopathy was confirmed by EKG, echocardiography, and coronary angiogram. The cardiac functions of these patients were fully recovered with conservative treatment. Although, the pathogenesis of stress related cardiomyopathy is not well understood, post-bronchoscopy tachycardia or arrhythmia is thought to be associated with hypoxemia or catecholamine excess. Because the clinical presentation is quite similar to acute myocardial infarction, discrete evaluations are required for appropriate treatment.
Anoxia ; Arrhythmias, Cardiac ; Bronchoscopy ; Cardiomyopathies ; Echocardiography ; Electrocardiography ; Humans ; Incidence ; Myocardial Infarction ; Tachycardia ; Takotsubo Cardiomyopathy

Ileal Dieulafoy lesion is an unusual vascular abnormality that can cause gastrointestinal bleeding. It can be associated with massive, life-threatening hemorrhage and requires urgent angiographic intervention or surgery. Ileal Dieulafoy lesion is hard to recognize due to inaccessibility and normal-appearing mucosa. With advances in endoscopy, aggressive diagnostic and therapeutic approaches including enteroscopy have recently been performed for small bowel bleeding. We report two cases of massive ileal Dieulafoy lesion bleeding diagnosed and treated successfully by single balloon enteroscopy with a review of the literature.
Endoscopy ; Gastrointestinal Hemorrhage ; Hemorrhage ; Ileum ; Mucous Membrane