Publications by authors named "Yul Hwangbo"

39 Publications

Metabolic Effects of Gastrectomy and Duodenal Bypass in Early Gastric Cancer Patients with T2DM: A Prospective Single-Center Cohort Study.

J Clin Med 2021 Sep 4;10(17). Epub 2021 Sep 4.

Center for Gastric Cancer, National Cancer Center, Goyang 10408, Korea.

We evaluated the metabolic effects of gastrectomies and endoscopic submucosal dissections (ESDs) in early gastric cancer (EGC) patients with type 2 diabetes mellitus (T2DM). Forty-one EGC patients with T2DM undergoing gastrectomy or ESD were prospectively evaluated. Metabolic parameters in the patients who underwent gastrectomy with and without a duodenal bypass (groups 1 and 2, = 24 and = 5, respectively) were compared with those in patients who underwent ESD (control, = 12). After 1 year, the proportions of improved/equivocal/worsened glycemic control were 62.5%/29.2%/8.3% in group 1, 40.0%/60.0%/0.0% in group 2, and 16.7%/50.0%/33.3% in the controls, respectively ( = 0.046). The multivariable ordered logistic regression analysis results showed that both groups had better 1-year glycemic control. Groups 1 and 2 showed a significant reduction in postprandial glucose (-97.9 and -67.8 mg/dL), body mass index (-2.1 and -2.3 kg/m), and glycosylated hemoglobin (group 1 only, -0.5% point) (all < 0.05). Furthermore, improvements in group 1 were more prominent when preoperative leptin levels were high ( for interaction < 0.05). Metabolic improvements in both groups were also observed for insulin resistance, leptin, plasminogen activator inhibitor-1, and resistin. Gastrectomy improved glycemic control and various metabolic parameters in EGC patients with T2DM. Patients with high leptin levels may experience greater metabolic benefits from gastrectomy with duodenal bypass.
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http://dx.doi.org/10.3390/jcm10174008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432535PMC
September 2021

Global Trends of Regional Health Information Systems and Suggested Strategic Utilization of their Medical Information.

Healthc Inform Res 2021 Jul 31;27(3):175-181. Epub 2021 Jul 31.

Department of Family Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea.

Objective: Along with the exponentially-growing data produced and accumulated every day through mobile platforms, social networking services, the Internet, and other media, information is becoming increasingly important as a strategic resource. This report presents specific and clear directions and suggests empirical project plans regarding innovations in regional health information systems to promote the utilization of medical information.

Methods: We reviewed and examined documents about global trends and examples of regional health information systems. The problems and solutions of health information utilization and regional health information systems in Korea were analyzed.

Results: This study presented examples of the establishment of health information systems, problems in the use of local healthcare information, and an empirical project for improvement.

Conclusions: The results of this study imply the need for long-term and systematic approaches for the use of medical information and the establishment of a local healthcare information system, along with implementation plans. As a first step, it is imperative to clarify the goal of building a medical information system, the information that must be provided to build the system, and the data that should be collected to provide such information, while moving away from the mentality of focusing on technology-oriented medical information services. In addition, it is necessary to consider information governance, data-based service development, and the medical innovation framework, which are ways to efficiently manage, utilize, and systemize the data to be collected.
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http://dx.doi.org/10.4258/hir.2021.27.3.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369055PMC
July 2021

Can computed tomography scanning in adults lead to an increased risk of thyroid cancer? A nationwide nested case-control study.

Eur Radiol 2021 Jul 10. Epub 2021 Jul 10.

Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea.

Objective: To evaluate the association between computed tomography (CT) scanning and newly diagnosed thyroid cancer cases in relation to the confounding effect of the healthcare utilization rate.

Methods: This nested case-control study used the Korean National Health Insurance Service-National Sample Cohort 2002-2015: 3557 adult thyroid cancer cases were matched to 17,785 controls by age, sex, and diagnosis date. Odds ratios (ORs) were estimated for thyroid cancer associated with cumulative exposure to CT scanning > 3 years before cancer diagnosis. Changes in estimated ORs with and without adjustment for outpatient visit frequency were investigated.

Results: ORs for newly diagnosed thyroid cancer increased according to the higher number of total CT scans and thyroid-exposing CT scans (CT scans of the head, neck, or chest compartment; OR and 95% confidence interval [CI], 1.09 [1.03-1.16] and 1.28 [1.05-1.57], respectively). ORs for thyroid cancer increased according to higher outpatient visit frequency. The association between thyroid cancer incidence and CT scans became insignificant when outpatient visit frequency was adjusted in the models (OR [95% CI], 1.03 [0.97-1.10]: total CT scans, 1.14 [0.93-1.41]: thyroid-exposing CT scans). Subgroup analyses stratified by age, sex, and history of other malignancies did not reveal independent associations between CT scanning and thyroid cancer.

Conclusions: The high incidence of thyroid cancer in adults exposed to ionizing radiation during CT scanning can be largely explained by the confounding effect of the healthcare utilization rate. These effects should be considered to avoid overestimation of the CT scanning-associated risk of thyroid cancer.

Key Points: • Studies indicate that diagnostic imaging using low-ionizing radiation may increase risks for thyroid cancer in adults. • Our findings suggest that the risk for radiation-induced thyroid cancer following CT scanning in adults may have been overestimated in observational studies due to medical surveillance-related biases.
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http://dx.doi.org/10.1007/s00330-021-08186-0DOI Listing
July 2021

Application of Machine Learning to Identify Clinically Meaningful Risk Group for Osteoporosis in Individuals Under the Recommended Age for Dual-Energy X-Ray Absorptiometry.

Calcif Tissue Int 2021 Jun 30. Epub 2021 Jun 30.

Healthcare AI Team, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, 10408, South Korea.

Dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis; it is generally recommended in men ≥ 70 and women ≥ 65 years old. Therefore, assessment of clinical risk factors for osteoporosis is very important in individuals under the recommended age for DXA. Here, we examine the diagnostic performance of machine learning-based prediction models for osteoporosis in individuals under the recommended age for DXA examination. Data of 2210 men aged 50-69 and 1099 women aged 50-64 obtained from the Korea National Health and Nutrition Examination Survey IV-V were analyzed. Extreme gradient boosting (XGBoost) was used to find relevant clinical features and applied to three machine learning models: XGBoost, logistic regression, and a multilayer perceptron. For the prediction of osteoporosis, the XGBoost model using the top 20 features extracted from XGBoost showed the most reliable performance with area under the receiver operating characteristic curve (AUROC) of 0.73 and 0.79 in men and women, respectively. We compared the diagnostic accuracy of the Shapley additive explanation values based on a risk-score model obtained from XGBoost and conventional osteoporosis risk assessment tools for prediction of osteoporosis using optimal cut-off values for each model. We observed that a cut-off risk score of ≥ 28 in men and ≥ 47 in women was optimal to classify a positive screening for osteoporosis (an AUROC of 0.86 in men and 0.91 in women). The XGBoost-based osteoporosis-prediction model outperformed conventional risk assessment tools. Therefore, machine learning-based prediction models are a more suitable option than conventional risk assessment methods for screening osteoporosis in individuals under the recommended age for DXA examination.
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http://dx.doi.org/10.1007/s00223-021-00880-xDOI Listing
June 2021

Evaluation of modifiable factors and polygenic risk score in thyroid cancer.

Endocr Relat Cancer 2021 Jun 17;28(7):481-494. Epub 2021 Jun 17.

Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Gyeonggi-do, Republic of Korea.

The cumulative effect of single-nucleotide polymorphisms (SNPs) on thyroid cancer has been adequately defined in individuals of European ancestry; however, similar evidence in the Korean population is limited. This study aimed to investigate the influence of modifiable factors and the polygenic risk score (PRS) and their interactive and combined effects on thyroid cancer. Using data from the cancer screenee cohort, this study included 759 thyroid cancer cases and 759 age- and sex-matched controls. We examined the effects of tobacco smoking, alcohol consumption, and regular exercise habits, BMI, and the PRS of six SNPs on thyroid cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations were obtained using a conditional logistic regression model. The results indicated that family history, obesity, and the unweighted and weighted PRS were independently associated with susceptibility to thyroid cancer, with ORs (95% CIs) of 2.96 (1.63-5.36), 1.72 (1.20-2.48), 1.46 (1.10-1.93), and 1.56 (1.19-2.03), respectively, whereas the effect of smoking, drinking, and regular exercise was not significant. The contribution of the PRS remained after stratifying participants with healthy behaviors, such as nonsmokers/nondrinkers, and regular exercise. Although the PRS did not significantly contribute to the risk for thyroid cancer when participants were stratified according to BMI, BMI and the PRS had a cumulative effect on thyroid cancer risk. The combined effect of genetic polymorphisms on predisposition to thyroid cancer may differ based on tobacco smoking, alcohol consumption, regular exercise behaviors and cumulative BMI. Larger population-based studies are needed to validate these findings.
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http://dx.doi.org/10.1530/ERC-21-0078DOI Listing
June 2021

Impact of image compression on deep learning-based mammogram classification.

Sci Rep 2021 Apr 12;11(1):7924. Epub 2021 Apr 12.

Healthcare AI Team, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.

Image compression is used in several clinical organizations to help address the overhead associated with medical imaging. These methods reduce file size by using a compact representation of the original image. This study aimed to analyze the impact of image compression on the performance of deep learning-based models in classifying mammograms as "malignant"-cases that lead to a cancer diagnosis and treatment-or "normal" and "benign," non-malignant cases that do not require immediate medical intervention. In this retrospective study, 9111 unique mammograms-5672 normal, 1686 benign, and 1754 malignant cases were collected from the National Cancer Center in the Republic of Korea. Image compression was applied to mammograms with compression ratios (CRs) ranging from 15 to 11 K. Convolutional neural networks (CNNs) with three convolutional layers and three fully-connected layers were trained using these images to classify a mammogram as malignant or not malignant across a range of CRs using five-fold cross-validation. Models trained on images with maximum CRs of 5 K had an average area under the receiver operating characteristic curve (AUROC) of 0.87 and area under the precision-recall curve (AUPRC) of 0.75 across the five folds and compression ratios. For images compressed with CRs of 10 K and 11 K, model performance decreased (average 0.79 in AUROC and 0.49 in AUPRC). Upon generating saliency maps that visualize the areas each model views as significant for prediction, models trained on less compressed (CR <  = 5 K) images had maps encapsulating a radiologist's label, while models trained on images with higher amounts of compression had maps that missed the ground truth completely. In addition, base ResNet18 models pre-trained on ImageNet and trained using compressed mammograms did not show performance improvements over our CNN model, with AUROC and AUPRC values ranging from 0.77 to 0.87 and 0.52 to 0.71 respectively when trained and tested on images with maximum CRs of 5 K. This paper finds that while training models on images with increased the robustness of the models when tested on compressed data, moderate image compression did not substantially impact the classification performance of DL-based models.
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http://dx.doi.org/10.1038/s41598-021-86726-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042042PMC
April 2021

Incidence and disease course of new-onset diabetes mellitus in breast and colorectal cancer patients undergoing chemotherapy: A prospective multicenter cohort study.

Diabetes Res Clin Pract 2021 Apr 17;174:108751. Epub 2021 Mar 17.

Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Aims: To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM.

Methods: This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy.

Results: Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007).

Conclusions: DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG.

Trial Registration: ClinicalTrials.gov (NCT03062072).
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http://dx.doi.org/10.1016/j.diabres.2021.108751DOI Listing
April 2021

Prediction of Prolonged Length of Hospital Stay After Cancer Surgery Using Machine Learning on Electronic Health Records: Retrospective Cross-sectional Study.

JMIR Med Inform 2021 Feb 22;9(2):e23147. Epub 2021 Feb 22.

Healthcare AI Team, National Cancer Center, Goyang, Republic of Korea.

Background: Postoperative length of stay is a key indicator in the management of medical resources and an indirect predictor of the incidence of surgical complications and the degree of recovery of the patient after cancer surgery. Recently, machine learning has been used to predict complex medical outcomes, such as prolonged length of hospital stay, using extensive medical information.

Objective: The objective of this study was to develop a prediction model for prolonged length of stay after cancer surgery using a machine learning approach.

Methods: In our retrospective study, electronic health records (EHRs) from 42,751 patients who underwent primary surgery for 17 types of cancer between January 1, 2000, and December 31, 2017, were sourced from a single cancer center. The EHRs included numerous variables such as surgical factors, cancer factors, underlying diseases, functional laboratory assessments, general assessments, medications, and social factors. To predict prolonged length of stay after cancer surgery, we employed extreme gradient boosting classifier, multilayer perceptron, and logistic regression models. Prolonged postoperative length of stay for cancer was defined as bed-days of the group of patients who accounted for the top 50% of the distribution of bed-days by cancer type.

Results: In the prediction of prolonged length of stay after cancer surgery, extreme gradient boosting classifier models demonstrated excellent performance for kidney and bladder cancer surgeries (area under the receiver operating characteristic curve [AUC] >0.85). A moderate performance (AUC 0.70-0.85) was observed for stomach, breast, colon, thyroid, prostate, cervix uteri, corpus uteri, and oral cancers. For stomach, breast, colon, thyroid, and lung cancers, with more than 4000 cases each, the extreme gradient boosting classifier model showed slightly better performance than the logistic regression model, although the logistic regression model also performed adequately. We identified risk variables for the prediction of prolonged postoperative length of stay for each type of cancer, and the importance of the variables differed depending on the cancer type. After we added operative time to the models trained on preoperative factors, the models generally outperformed the corresponding models using only preoperative variables.

Conclusions: A machine learning approach using EHRs may improve the prediction of prolonged length of hospital stay after primary cancer surgery. This algorithm may help to provide a more effective allocation of medical resources in cancer surgery.
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http://dx.doi.org/10.2196/23147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939945PMC
February 2021

Risk Factors of Undiagnosed Diabetes Mellitus among Korean Adults: A National Cross-Sectional Study Using the KNHANES Data.

Int J Environ Res Public Health 2021 01 29;18(3). Epub 2021 Jan 29.

Cancer Data Center, National Cancer Control Institute, National Cancer Center, Gyeonggi-do, Goyang-si 10408, Korea.

In this cross-sectional study, we investigated the baseline risk factors of diabetes mellitus (DM) in patients with undiagnosed DM (UDM). We utilized the Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2017 data. Data regarding the participants' demographic characteristics, health status, health determinants, healthcare accessibility, and laboratory tests were gathered to explore the differences between the DM, UDM, and without-DM groups. Among the 64,759 individuals who participated in the KNHANES 2010-2017, 32,611 individuals aged ≥20 years with fasting plasma glucose levels of <100 or ≥126 mg/dL were selected. The odds ratios (ORs) regarding family history of diabetes and the performance of national health and cancer screening tests were lower in the UDM group than in the DM group (adjusted OR: 0.54; 95% confidence interval (CI): 0.43, 0.66; adjusted OR: 0.74; 95% CI: 0.62, 0.89; adjusted OR: 0.71; 95% CI: 0.60, 0.85). The ORs of hypertension and obesity were higher in the UDM group than in the DM group (adjusted OR: 1.32; 95% CI: 1.06, 1.64; adjusted OR: 1.80; 95% CI: 1.37, 2.36, respectively). Patients with UDM were more likely to be exposed to DM-related risk factors than those with and without DM. Public health interventions to prevent UDM development are necessary.
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http://dx.doi.org/10.3390/ijerph18031195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908078PMC
January 2021

Factors Affecting Central Node Metastasis and Metastatic Lymph Node Ratio in Papillary Thyroid Cancer.

Otolaryngol Head Neck Surg 2021 Feb 9:194599821991465. Epub 2021 Feb 9.

Department of Otorhinolaryngology-Head and Neck Surgery, National Cancer Center, Goyang, Republic of Korea.

Objective: Despite the growing evidence that metastatic lymph node ratio (MLNR) is a valuable predictor for the prognosis of papillary thyroid carcinoma, it has not yet been fully determined which factors give the ratio predictive value independent of the number of metastatic lymph nodes (MLNs).

Study Design: Retrospective cohort study.

Setting: A comprehensive cancer center.

Methods: Recurrence and clinicopathologic factors were analyzed in 2409 patients with papillary thyroid carcinoma who underwent total thyroidectomy and central node dissection.

Results: Cutoff values of MLNs ≥2 and MLNR ≥28.2% increased the recurrence risk (hazard ratio [95% CI], 9.97 [4.73-21.0] and 11.4 [5.53-23.3], respectively). Younger age, male sex, multifocality, tumor size, lymphatic and vascular invasion, and gross extrathyroidal extension positively correlated with MLN and MLNR (all < .05). Meanwhile, lymphocytic thyroiditis negatively correlated with MLNR in female patients ( < .001), by increasing total lymph node yields as compared with papillary thyroid carcinoma without lymphocytic thyroiditis. In multivariate analysis, younger age, tumor size, and lymphatic invasion remained significant in male and female patients for MLN and MLNR; lymphocytic thyroiditis was also significantly correlated with MLNR in female patients.

Conclusion: Our study demonstrates that MLN and MLNR are independently observed prognostic markers for tumor recurrence. However, lymphocytic thyroiditis in female patients seems to have lower MLNR by increasing total lymph node yields. In light of their association, a different cutoff for MLNR needs to be applied according to the presence or absence of underlying lymphocytic thyroiditis in the use of MLNR for predicting the recurrence.

Level Of Evidence: 4.
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http://dx.doi.org/10.1177/0194599821991465DOI Listing
February 2021

Limitations of Deep Learning Attention Mechanisms in Clinical Research: Empirical Case Study Based on the Korean Diabetic Disease Setting.

J Med Internet Res 2020 12 16;22(12):e18418. Epub 2020 Dec 16.

Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.

Background: Despite excellent prediction performance, noninterpretability has undermined the value of applying deep-learning algorithms in clinical practice. To overcome this limitation, attention mechanism has been introduced to clinical research as an explanatory modeling method. However, potential limitations of using this attractive method have not been clarified to clinical researchers. Furthermore, there has been a lack of introductory information explaining attention mechanisms to clinical researchers.

Objective: The aim of this study was to introduce the basic concepts and design approaches of attention mechanisms. In addition, we aimed to empirically assess the potential limitations of current attention mechanisms in terms of prediction and interpretability performance.

Methods: First, the basic concepts and several key considerations regarding attention mechanisms were identified. Second, four approaches to attention mechanisms were suggested according to a two-dimensional framework based on the degrees of freedom and uncertainty awareness. Third, the prediction performance, probability reliability, concentration of variable importance, consistency of attention results, and generalizability of attention results to conventional statistics were assessed in the diabetic classification modeling setting. Fourth, the potential limitations of attention mechanisms were considered.

Results: Prediction performance was very high for all models. Probability reliability was high in models with uncertainty awareness. Variable importance was concentrated in several variables when uncertainty awareness was not considered. The consistency of attention results was high when uncertainty awareness was considered. The generalizability of attention results to conventional statistics was poor regardless of the modeling approach.

Conclusions: The attention mechanism is an attractive technique with potential to be very promising in the future. However, it may not yet be desirable to rely on this method to assess variable importance in clinical settings. Therefore, along with theoretical studies enhancing attention mechanisms, more empirical studies investigating potential limitations should be encouraged.
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http://dx.doi.org/10.2196/18418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773508PMC
December 2020

Association among Body Mass Index, Genetic Variants of FTO, and Thyroid Cancer Risk: A Hospital-Based Case-Control Study of the Cancer Screenee Cohort in Korea.

Cancer Res Treat 2021 Jul 7;53(3):857-873. Epub 2020 Dec 7.

Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.

Purpose: Obesity has been determined to be associated with fat mass and obesity-associated (FTO) gene and thyroid cancer risk. However, the effect of combined interactions between obesity and the FTO gene on thyroid cancer needs further investigation. This study aimed to examine whether interactions between body mass index (BMI) and the FTO gene are associated with an increased risk of thyroid cancer.

Materials And Methods: A total of 705 thyroid cancer cases and 705 sex- and age-matched normal controls were selected from the Cancer Screenee Cohort in National Cancer Center, Korea. A conditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the measure of associations and the combined effect of BMI and FTO gene on thyroid cancer.

Results: BMI was associated with an increased risk of thyroid cancer in subclasses of overweight (23-24.9 kg/m2; adjusted OR, 1.50; 95% CI, 1.12 to 2.00) and obese (≥ 25 kg/m2) (adjusted OR, 1.62; 95% CI, 1.23 to 2.14). There were positive associations between the FTO genetic variants rs8047395 and rs8044769 and an increased risk of thyroid cancer. Additionally, the combination of BMI subclasses and FTO gene variants was significantly associated with thyroid cancer risk in the codominant (rs17817288), dominant (rs9937053, rs12149832, rs1861867, and rs7195539), and recessive (rs17817288 and rs8044769) models.

Conclusion: Findings from this study identified the effects of BMI on thyroid cancer risk among individuals carrying rs17817288, rs9937053, rs12149832, rs1861867, rs7195539, and rs8044769, whereas the effects of BMI may be modified according to individual characteristics of other FTO variants.
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http://dx.doi.org/10.4143/crt.2020.720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291195PMC
July 2021

Screening Model for Estimating Undiagnosed Diabetes among People with a Family History of Diabetes Mellitus: A KNHANES-Based Study.

Int J Environ Res Public Health 2020 11 30;17(23). Epub 2020 Nov 30.

Cancer Big Data Center, National Cancer Center, Goyang-si 10408, Gyeonggi-do, Korea.

A screening model for estimating undiagnosed diabetes mellitus (UDM) is important for early medical care. There is minimal research and a serious lack of screening models for people with a family history of diabetes (FHD), especially one which incorporates gender characteristics. Therefore, the primary objective of our study was to develop a screening model for estimating UDM among people with FHD and enable its validation. We used data from the Korean National Health and Nutrition Examination Survey (KNHANES). KNAHNES (2010-2016) was used as a developmental cohort (n = 5939) and was then evaluated in a validation cohort (n = 1047) KNHANES (2017). We developed the screening model for UDM in male (SMM), female (SMF), and male and female combined (SMP) with FHD using backward stepwise logistic regression analysis. The SMM and SMF showed an appropriate performance (area under curve (AUC) = 76.2% and 77.9%) compared with SMP (AUC = 72.9%) in the validation cohort. Consequently, simple screening models were developed and validated, for the estimation of UDM among patients in the FHD group, which is expected to reduce the burden on the national health care system.
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http://dx.doi.org/10.3390/ijerph17238903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730533PMC
November 2020

Effect of Initial Treatment Choice on 2-year Quality of Life in Patients with Low-risk Papillary Thyroid Microcarcinoma.

J Clin Endocrinol Metab 2021 03;106(3):724-735

Department of Internal Medicine, Seoul National University Hospital and College of Medicine, Seoul, Republic of Korea.

Context: The long-term quality of life (QoL) in patients with low-risk papillary thyroid microcarcinoma (PTMC) underwent active surveillance (AS) and immediate surgery is unclear.

Objective: The aim of this study was to investigate the effect of initial treatment choice on 2-year QoL in patients with low-risk PTMC.

Design, Setting, And Participants: We analyzed 2652 QoL surveys from 1055 subjects enrolled in ongoing multicenter prospective cohort study on active surveillance of PTMC, in which the median follow-up duration was 24.4 months.

Major Outcome Measure: We evaluated QoL of patients with low-risk PTMC according to their treatment modality using generalized estimating equation.

Results: Six hundred and seventy-four subjects (male = 161; mean age = 48.8 ± 11.9 years) with low-risk PTMC chose AS while 381 subjects (male = 75; mean age = 45.7 ± 10.4 years) chose immediate surgery, including lobectomy/isthmusectomy (L/I) and total thyroidectomy (TT). Among the 817 subjects who completed baseline QoL surveys, 2-year QoL was good in order of AS (n = 500), L/I (n = 238), and TT (n = 79) groups after adjustment for age, sex, baseline tumor size, and baseline QoL scores. Among the 101 subjects who changed their treatment from AS to surgery during the follow-up period, 35 subjects who changed treatment due to disease progression had better QoL than 66 subjects who had no disease progression.

Conclusions: This study identified QoL as a major issue in choosing an initial treatment of low-risk PTMC and highlighted the possibility of using AS as the primary treatment.
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http://dx.doi.org/10.1210/clinem/dgaa889DOI Listing
March 2021

Effect of Helicobacter pylori treatment on the long-term mortality in patients with type 2 diabetes.

Korean J Intern Med 2021 05 25;36(3):584-595. Epub 2020 Nov 25.

Center for Gastric Cancer, National Cancer Center, Goyang, Korea.

Background/aims: Meta-analyses of randomized trials reported a non-significant increase in overall mortality risk after Helicobacter pylori eradication. In this study, we investigated whether H. pylori treatment is associated with increased risk of overall mortality in patients with type 2 diabetes.

Methods: In this retrospective population-based cohort study, we identified 66,706 patients treated for type 2 diabetes between 2002 and 2010 from the Korean National Health Insurance Service-National Sample Cohort. Patients who received H. pylori treatment (Hp-treatment cohort, 1,727 patients) were matched to those who did not (non-treatment cohort, 3,454 patients) at a 1:2 ratio. The primary outcome was overall mortality. The secondary outcomes were mortalities due to cardiovascular disease, cerebrovascular disease, or cancers. To estimate hazard ratio (HR) with confidential interval (CI), we used the Cox proportional-hazard model.

Results: During a median follow-up of 4.7 years, the overall mortality was 5.9% (101/1,727 patients) among patients in the Hp-treatment cohort and 7.6% (364/3,454 patients) among patients in the non-treatment cohort. Adjusted HR (aHR) for overall mortality in the Hp-treatment cohort was 0.74 (95% CI, 0.59 to 0.93; p = 0.011). The mortality risks due to cardiovascular disease (aHR, 1.34; 95% CI, 0.54 to 3.30; p = 0.529), cerebrovascular disease (aHR, 0.97; 95% CI, 0.37 to 2.55; p = 0.947), and cancer (aHR, 1.08; 95% CI, 0.68 to 1.72; p = 0.742) were not significantly different between the groups.

Conclusion: In type 2 diabetes patients, overall mortality did not increase after H. pylori treatment.
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http://dx.doi.org/10.3904/kjim.2019.428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137405PMC
May 2021

A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol.

Endocrinol Metab (Seoul) 2020 09 22;35(3):571-577. Epub 2020 Sep 22.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades.

Methods: This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio <0.4). Patients choose to undergo RAI ablation (131I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (131I or 123I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL.

Conclusion: This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.
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http://dx.doi.org/10.3803/EnM.2020.681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520583PMC
September 2020

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Endocrinol Metab (Seoul) 2020 06 24;35(2):272-287. Epub 2020 Jun 24.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.
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http://dx.doi.org/10.3803/EnM.2020.35.2.272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386113PMC
June 2020

Long Work Hours Are Associated with Hypothyroidism: A Cross-Sectional Study with Population-Representative Data.

Thyroid 2020 10 5;30(10):1432-1439. Epub 2020 May 5.

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea.

Studies have highlighted the adverse effects of long work hours on workers' health; however, the association of long work hours with thyroid function has not been studied. This study aimed at assessing long work hours as a risk factor for thyroid dysfunction. This cross-sectional study was based on data obtained from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. A total of 2160 adults who worked 36-83 hours per week were included. Thyroid function was defined based on the population thyroid-stimulating hormone reference ranges, after excluding individuals with positive results for thyroid peroxidase antibody. The association between work hours and thyroid function was confirmed via multinomial logistic regression. Hypothyroidism was more prevalent among those with longer work hours (3.5% vs. 1.4% for 53-83 and 36-42 work hours per week, respectively). Individuals who worked longer hours had an increased odds for hypothyroidism (odds ratio 1.46, confidence interval 1.12 - 1.90, per 10-hour increase in work hours per week), after adjustment for age, sex, body mass index, urine iodine concentration, smoking status, work schedule, and socioeconomic status. The association between work hours and hypothyroidism was consistent in various subgroups stratified by sex or socioeconomic status. To our knowledge, this study is the first to show that long work hours are associated with hypothyroidism. Further large longitudinal studies are needed to clarify causality.
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http://dx.doi.org/10.1089/thy.2019.0709DOI Listing
October 2020

Aspirin Use Is Not Associated with Lower Thyroid Cancer Risk: A Nationwide Nested Case-Control Study.

Thyroid 2020 06 14;30(6):829-837. Epub 2020 Feb 14.

Department of Laboratory Medicine, National Cancer Center, Goyang, Republic of Korea.

While aspirin use is known to be associated with reduced incidence of various cancer types, it is unclear whether this benefit extends to thyroid cancer. We aimed to evaluate the association between aspirin use and thyroid cancer development. This nested case-control study used nationwide data from the Korean National Health Insurance Service-National Sample Cohort 2002-2015. In total, 4547 individuals with newly developed thyroid cancer were matched with 13,641 controls based on age, sex, and follow-up period. Odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid cancer development according to aspirin use were analyzed using a multivariable conditional logistic regression model. The number of days for which patients with thyroid cancer used aspirin (the proportions of no use, <30 days/year, 30-90 days/year, and ≥90 days/year were 93.03%, 6.51%, 0.31%, and 0.15%, respectively) was comparable with that of the controls ( = 0.371, chi-squared test). The risk of thyroid cancer development was not associated with the duration of aspirin use (ORs [CI] for aspirin use <30 days/year, 30-90 days/year, and ≥90 days/year were 1.11 [0.96-1.28], 1.01 [0.54-1.88], and 1.23 [0.50-3.06], respectively, compared with no use) after adjusting for body mass index, smoking status, hypertension, Charlson comorbidity index, and number of outpatient visits per year. In addition, subgroup analyses stratified by age, sex, and follow-up duration did not reveal any significant association between aspirin use and thyroid cancer. Our findings suggest that even extended aspirin use may not impact the prevention or onset of thyroid cancer.
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http://dx.doi.org/10.1089/thy.2019.0641DOI Listing
June 2020

Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro).

Thyroid 2019 08 12;29(8):1089-1096. Epub 2019 Jul 12.

1Department of Internal Medicine, Seoul National University Hospital and College of Medicine, Seoul, Republic of Korea.

In this ongoing multicenter prospective cohort study on active surveillance (AS) in low-risk papillary thyroid microcarcinoma (PTMC), we aimed to compare the quality of life (QoL) of participants based on their choice of treatment, that is, AS or immediate surgery (OP). QoL of 203 participants who chose AS and 192 participants who underwent OP was evaluated using a thyroid-specific QoL questionnaire at diagnosis and during follow-up (median 8 months). The mean ages of the participants in the AS and OP groups were 47.3 ± 11.7 and 45.6 ± 10.5 years ( = 0.138), respectively, and the mean tumor sizes were 5.7 ± 1.6 and 6.5 ± 2.1 mm ( = 0.065), respectively. At baseline, significantly better psychological health (7.1 ± 1.3 vs. 6.8 ± 1.6,  = 0.023) and overall health (6.8 ± 1.2 vs. 6.5 ± 1.3,  = 0.018) were observed in the AS group than in the OP group. During follow-up, significantly better physical (7.9 ± 1.1 vs. 7.4 ± 1.2,  < 0.001), psychological (7.4 ± 1.3 vs. 6.9 ± 1.6,  = 0.004), and overall health (6.9 ± 1.0 vs. 6.5 ± 1.1,  = 0.002) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups. Compared with the AS group, the OP group experienced more fatigue, changes in voice and appearance, less satisfaction, and low fear of recurrence. The self-assessed financial burden was similar at baseline and follow-up in both groups. The QoL of PTMC patients is different according to the type of treatment. Better psychological health at baseline and physical and psychological health at follow-up were observed in the AS group than in the OP group. However, studies with longer follow-up periods are needed.
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http://dx.doi.org/10.1089/thy.2018.0624DOI Listing
August 2019

Tumor doubling time predicts response to sorafenib in radioactive iodine-refractory differentiated thyroid cancer.

Endocr J 2019 Jul 19;66(7):597-604. Epub 2019 Apr 19.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Sorafenib has emerged as an effective therapeutic option for radioactive iodine (RAI)-refractory, locally advanced or metastatic differentiated thyroid cancer (DTC). We investigated the efficacy and safety of sorafenib treatment in a real-world setting and unveil predictive markers of responsiveness to sorafenib. The treatment response, progression-free survival (PFS), overall survival, and adverse events (AEs) of sorafenib-treated RAI-refractory, locally advanced or metastatic DTC patients at three institutes were retrospectively reviewed, and their tumor doubling time was calculated by three investigators. Total eighty-five patients were treated with sorafenib, and seven patients discontinued sorafenib due to AEs before the first tumor assessment. The median PFS was 14.4 months, and the objective response rate was 10.3% in 78 patients who were able to evaluate the tumor response. Age, sex, histologic type, tumor location, RAI avidity, or the presence of FDG-PET uptake did not affect PFS. However, smaller tumor size (≤1.5 cm) of the target lesions in lung showed better PFS (hazard ratio [HR] 0.39, p = 0.01), and tumors with the shortest doubling time (≤6 months) had worse outcome (HR 2.70, p < 0.01). Because of AEs, dose reductions or drug interruptions were required in 64% of patients, and eventually, 23% of patients discontinued sorafenib permanently. The most common AE was hand-foot skin reaction (HFSR). Patients with severe HFSR showed better PFS, but there were no statistical significance (HR 0.65, p = 0.05). In conclusion, small tumor size and long doubling time of each target lesion can be a prognostic marker to predict the responsiveness to sorafenib in RAI-refractory DTC patients.
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http://dx.doi.org/10.1507/endocrj.EJ18-0488DOI Listing
July 2019

Effect of Antihypertensive Medications on Sepsis-Related Outcomes: A Population-Based Cohort Study.

Crit Care Med 2019 05;47(5):e386-e393

Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.

Objectives: Although the effect of antihypertensive agents on sepsis has been studied, evidence for survival benefit was limited in the literature. We investigated differences in sepsis-related outcomes depending on the antihypertensive drugs given prior to sepsis in patients with hypertension.

Design: Population-based cohort study.

Setting: Sample cohort Database of the National Health Insurance Service from 2003 to 2013 in South Korea.

Patients: Patients over 30 years old who were diagnosed with sepsis after receiving hypertension treatment.

Interventions: None.

Measurements And Main Results: Primary outcomes, 30-day and 90-day mortality rates, were analyzed for differences among three representative antihypertensive medications: angiotensin- converting enzyme inhibitors or angiotensin II receptor blockers, calcium channel blockers, and thiazides. In total, 4,549 patients diagnosed with hypertension prior to hospitalization for sepsis were identified. The 30-day mortality was significantly higher among patients who did not receive any medications within 1 month before sepsis (36.8%) than among patients who did (32.0%; p < 0.001). The risk for 90-days mortality was significantly lower in prior angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker users (reference) than in other drug users (odds ratio, 1.27; 95% CI, 1.07-1.52). There was no difference in the risk for 30-day and 90-day mortality depending on whether calcium channel blockers or thiazides were used. Use of calcium channel blockers was associated with a decreased risk for inotropic agent administration, compared with those of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (odds ratio, 1.23; 95% CI, 1.05-1.44) and thiazides (odds ratio, 1.33; 95% CI, 1.12-1.58).

Conclusions: In patients with sepsis, lower mortality rate was associated with prior use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers not with use of calcium channel blockers or thiazides. The requirement of inotropic agents was significantly lower in prior use of calcium channel blockers, although the survival benefits were not prominent.
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http://dx.doi.org/10.1097/CCM.0000000000003654DOI Listing
May 2019

Risk of Diabetes Associated With Cancer Development-In Reply.

JAMA Oncol 2019 03;5(3):429-430

Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.

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http://dx.doi.org/10.1001/jamaoncol.2018.6647DOI Listing
March 2019

Genetic variations in TAS2R3 and TAS2R4 bitterness receptors modify papillary carcinoma risk and thyroid function in Korean females.

Sci Rep 2018 10 9;8(1):15004. Epub 2018 Oct 9.

Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Korea.

Type 2 taste receptors (T2Rs, TAS2Rs) mediate bitterness perception and are involved in diverse defence mechanisms in extraoral tissues. The thyrocyte-expressed T2Rs control thyroid hormone production, and this regulatory role may be associated with susceptibility to thyroid diseases. This study examined whether the variations in TAS2Rs modify the risk of papillary thyroid carcinoma (PTC) and whether such T2R-related PTC risk is associated with genetically modified thyroid function. We conducted a case-control study with 763 Korean females, including 250 PTC cases. Seventy-three single-nucleotide polymorphisms in 13 TAS2R genes and the pre-diagnosis levels of 4 thyroid-related functional markers [total triiodothyronine (TT3), free thyroxine, thyroid-stimulating hormone and thyroglobulin] were analysed. Individuals with TAS2R3/4 CC haplotype (rs2270009 and rs2234001) were at a lower risk for PTC than those with the remaining haplotypes (odds ratio = 0.59, 95% confidence interval: 0.36-0.97). Furthermore, TT3 levels were significantly reduced for TAS2R3/4 CC haplotype carriers compared with other haplotype carriers (p = 0.005). No other genetic variants exhibited critical associations with the PTC phenotype and biomarkers. In summary, genetic variations in T2R3/4 bitterness receptors may modify the PTC risk, and the genetically modified thyroid hormone level by those variations may be linked with the PTC-T2Rs association.
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http://dx.doi.org/10.1038/s41598-018-33338-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177438PMC
October 2018

Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer.

J Clin Endocrinol Metab 2018 12;103(12):4384-4394

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Context: Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown.

Objective: To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer.

Design And Setting: We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data.

Results: The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues.

Conclusions: To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.
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http://dx.doi.org/10.1210/jc.2017-02439DOI Listing
December 2018

Relation of Subclinical Hypothyroidism is Associated With Cardiovascular Events and All-Cause Mortality in Adults With High Cardiovascular Risk.

Am J Cardiol 2018 08 16;122(4):571-577. Epub 2018 May 16.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

The aim of this study was to determine the association between subclinical hypothyroidism and cardiovascular (CVD) events, and mortality using the atherosclerotic CVD risk score. We carried out an observational study in a prospective cohort that was followed up for 12 years. The study included 3,021 participants aged ≥ 40 years at baseline from the Ansung cohort, part of the Korean Genome and Epidemiology Study. Cox regression models were constructed to evaluate the hazards ratio (HR) and 95% confidence interval (CI) for all-cause mortality and CVD events in groups classified according to thyroid status. Subgroup analysis was performed with a cut-off age of 65 years or 7.5% of the 10-year atherosclerotic CVD risk score. The subclinical hypothyroidism group in the highest quartile of thyroid-stimulating hormone (>6.57 mIU/L) had a significantly increased risk of all-cause mortality (HR 2.12, 95% CI 1.27 to 3.56) and CVD events (HR 1.92, 95% CI 1.21 to 3.04) compared with euthyroid participants. Subgroup analysis by CVD risk revealed that participants with high CVD risk only had a high risk of all-cause mortality (HR 2.18, 95% CI 1.22 to 3.87) and CVD events (HR 2.42, 95% CI 1.35 to 4.33). Further analysis showed that participants aged <65 years with high CVD risk had the highest risk of all-cause mortality (HR 3.50, 95% CI 1.50 to 8.16) and CVD events (HR 3.37, 95% CI 1.46 to 9.57). Our results demonstrated that high thyroid-stimulating hormone levels were associated with a greater risk of mortality and new CVD risks, particularly among subjects with high CVD risk.
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http://dx.doi.org/10.1016/j.amjcard.2018.03.371DOI Listing
August 2018

Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro).

Endocrinol Metab (Seoul) 2018 Jun;33(2):278-286

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups.

Methods: This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis.

Results: Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014).

Conclusion: The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.
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http://dx.doi.org/10.3803/EnM.2018.33.2.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021306PMC
June 2018

Genome-Wide Association Studies of Autoimmune Thyroid Diseases, Thyroid Function, and Thyroid Cancer.

Endocrinol Metab (Seoul) 2018 Jun;33(2):175-184

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Thyroid diseases, including autoimmune thyroid diseases and thyroid cancer, are known to have high heritability. Family and twin studies have indicated that genetics plays a major role in the development of thyroid diseases. Thyroid function, represented by thyroid stimulating hormone (TSH) and free thyroxine (T4), is also known to be partly genetically determined. Before the era of genome-wide association studies (GWAS), the ability to identify genes responsible for susceptibility to thyroid disease was limited. Over the past decade, GWAS have been used to identify genes involved in many complex diseases, including various phenotypes of the thyroid gland. In GWAS of autoimmune thyroid diseases, many susceptibility loci associated with autoimmunity (human leukocyte antigen [HLA], protein tyrosine phosphatase, non-receptor type 22 [PTPN22], cytotoxic T-lymphocyte associated protein 4 [CTLA4], and interleukin 2 receptor subunit alpha [IL2RA]) or thyroid-specific genes (thyroid stimulating hormone receptor [TSHR] and forkhead box E1 [FOXE1]) have been identified. Regarding thyroid function, many susceptibility loci for levels of TSH and free T4 have been identified through genome-wide analyses. In GWAS of differentiated thyroid cancer, associations at FOXE1, MAP3K12 binding inhibitory protein 1 (MBIP)-NK2 homeobox 1 (NKX2-1), disrupted in renal carcinoma 3 (DIRC3), neuregulin 1 (NRG1), and pecanex-like 2 (PCNXL2) have been commonly identified in people of European and Korean ancestry, and many other susceptibility loci have been found in specific populations. Through GWAS of various thyroid-related phenotypes, many susceptibility loci have been found, providing insights into the pathogenesis of thyroid diseases and disease co-clustering within families and individuals.
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http://dx.doi.org/10.3803/EnM.2018.33.2.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021314PMC
June 2018

Incidence of Diabetes After Cancer Development: A Korean National Cohort Study.

JAMA Oncol 2018 08;4(8):1099-1105

Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.

Importance: Diabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive.

Objective: To evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes.

Design, Setting, And Participants: This cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524 089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included.

Exposures: Incident cancer (time-varying exposure).

Main Outcomes And Measures: Incident type 2 diabetes using insurance claim codes.

Results: During 3 492 935.6 person-years of follow-up (median follow-up, 7.0 years) in 494 189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15 130 participants developed cancer and 26 610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P < .001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes.

Conclusions And Relevance: In this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.
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http://dx.doi.org/10.1001/jamaoncol.2018.1684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143049PMC
August 2018
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