1.Surgical outcome and risk scoring to predict survival after hepatic resection for hepatocellular carcinoma with portal vein tumor thrombosis
Tae-Seok KIM ; Kwangho YANG ; Gi Hong CHOI ; Hye Yeon YANG ; Dong-Sik KIM ; Hye-Sung JO ; Gyu-Seong CHOI ; Kwan Woo KIM ; Young Chul YOON ; Jaryung HAN ; Doo Jin KIM ; Shin HWANG ; Koo Jeong KANG
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(2):134-143
Background:
s/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT.
Methods:
We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea.
Results:
The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA−II, neutrophil-to-lymphocyte ratio, and albumin–bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors–tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001).
Conclusions
HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.
2.Development and Testing of a Machine Learning Model Using 18 F-Fluorodeoxyglucose PET/CT-Derived Metabolic Parameters to Classify Human Papillomavirus Status in Oropharyngeal Squamous Carcinoma
Changsoo WOO ; Kwan Hyeong JO ; Beomseok SOHN ; Kisung PARK ; Hojin CHO ; Won Jun KANG ; Jinna KIM ; Seung-Koo LEE
Korean Journal of Radiology 2023;24(1):51-61
Objective:
To develop and test a machine learning model for classifying human papillomavirus (HPV) status of patients with oropharyngeal squamous cell carcinoma (OPSCC) using 18 F-fluorodeoxyglucose ( 18 F-FDG) PET-derived parameters in derived parameters and an appropriate combination of machine learning methods in patients with OPSCC.
Materials and Methods:
This retrospective study enrolled 126 patients (118 male; mean age, 60 years) with newly diagnosed, pathologically confirmed OPSCC, that underwent 18 F-FDG PET-computed tomography (CT) between January 2012 and February 2020. Patients were randomly assigned to training and internal validation sets in a 7:3 ratio. An external test set of 19 patients (16 male; mean age, 65.3 years) was recruited sequentially from two other tertiary hospitals. Model 1 used only PET parameters, Model 2 used only clinical features, and Model 3 used both PET and clinical parameters. Multiple feature transforms, feature selection, oversampling, and training models are all investigated. The external test set was used to test the three models that performed best in the internal validation set. The values for area under the receiver operating characteristic curve (AUC) were compared between models.
Results:
In the external test set, ExtraTrees-based Model 3, which uses two PET-derived parameters and three clinical features, with a combination of MinMaxScaler, mutual information selection, and adaptive synthetic sampling approach, showed the best performance (AUC = 0.78; 95% confidence interval, 0.46–1). Model 3 outperformed Model 1 using PET parameters alone (AUC = 0.48, p = 0.047) and Model 2 using clinical parameters alone (AUC = 0.52, p = 0.142) in predicting HPV status.
Conclusion
Using oversampling and mutual information selection, an ExtraTree-based HPV status classifier was developed by combining metabolic parameters derived from 18 F-FDG PET/CT and clinical parameters in OPSCC, which exhibited higher performance than the models using either PET or clinical parameters alone.
3.Inhibition of DNMT3B and PI3K/AKT/mTOR and ERK Pathways as a Novel Mechanism of Volasertib on Hypomethylating Agent-Resistant Cells
Eun-Ji CHOI ; Bon-Kwan KOO ; Eun-Hye HUR ; Ju Hyun MOON ; Ji Yun KIM ; Han-Seung PARK ; Yunsuk CHOI ; Kyoo-Hyung LEE ; Jung-Hee LEE ; Eun Kyung CHOI ; Je-Hwan LEE
Biomolecules & Therapeutics 2023;31(3):319-329
Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/ AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.
4.18F-FDG PET/CT Parameters Enhance MRI Radiomicsfor Predicting Human Papilloma Virus Status in Oropharyngeal Squamous Cell Carcinoma
Kwan Hyeong JO ; Jinna KIM ; Hojin CHO ; Won Jun KANG ; Seung-Koo LEE ; Beomseok SOHN
Yonsei Medical Journal 2023;64(12):738-744
Purpose:
Predicting human papillomavirus (HPV) status is critical in oropharyngeal squamous cell carcinoma (OPSCC) radiomics. In this study, we developed a model for HPV status prediction using magnetic resonance imaging (MRI) radiomics and18F-fluorodeoxyglucose ( 18F-FDG) positron emission tomography (PET)/computed tomography (CT) parameters in patients withOPSCC.
Materials and Methods:
Patients with OPSCC who underwent 18F-FDG PET/CT and contrast-enhanced MRI before treatment between January 2012 and February 2020 were enrolled. Training and test sets (3:2) were randomly selected. 18F-FDG PET/CT parameters and MRI radiomics feature were extracted. We developed three light-gradient boosting machine prediction models using the training set: Model 1, MRI radiomics features; Model 2, 18F-FDG PET/CT parameters; and Model 3, combination of MRI radiomics features and 18F-FDG PET/CT parameters. Area under the receiver operating characteristic curve (AUROC) values were used to analyze the performance of the models in predicting HPV status in the test set.
Results:
A total of 126 patients (118 male and 8 female; mean age: 60 years) were included. Of these, 103 patients (81.7%) were HPV-positive, and 23 patients (18.3%) were HPV-negative. AUROC values in the test set were 0.762 [95% confidence interval (CI), 0.564–0.959], 0.638 (95% CI, 0.404–0.871), and 0.823 (95% CI, 0.668–0.978) for Models 1, 2, and 3, respectively. The net reclassification improvement of Model 3, compared with that of Model 1, in the test set was 0.119.
Conclusion
When combined with an MRI radiomics model, 18F-FDG PET/CT exhibits incremental value in predicting HPV status in patients with OPSCC.
5.Clinical Results of Drug-Coated Balloon Treatment in a Large-Scale Multicenter Korean Registry Study
Sang Yeub LEE ; Yun-Kyeong CHO ; Sang-Wook KIM ; Young-Joon HONG ; Bon-Kwon KOO ; Jang-Whan BAE ; Seung-Hwan LEE ; Tae Hyun YANG ; Hun Sik PARK ; Si Wan CHOI ; Do-Sun LIM ; Soo-Joong KIM ; Young Hoon JEONG ; Hyun-Jong LEE ; Kwan Yong LEE ; Eun-Seok SHIN ; Ung KIM ; Moo Hyun KIM ; Chang-Wook NAM ; Seung-Ho HUR ; Doo-Il KIM ;
Korean Circulation Journal 2022;52(6):444-454
Background and Objectives:
The aim of this study was to demonstrate the efficacy and safety of treatment with drug-coated balloon (DCB) in a large real-world population.
Methods:
Patients treated with DCBs were included in a multicenter observational registry that enrolled patients from 18 hospitals in Korea between January 2009 and December 2017. The primary outcome was target lesion failure (TLF) defined as a composite of cardiovascular death, target vessel myocardial infarction, and clinically indicated target lesion revascularization at 12 months.
Results:
The study included 2,509 patients with 2,666 DCB-treated coronary artery lesions (1,688 [63.3%] with in-stent restenosis [ISR] lesions vs. 978 [36.7%] with de novo lesions).The mean age with standard deviation was 65.7±11.3 years; 65.7% of the patients were men.At 12 months, the primary outcome, TLF, occurred in 179 (6.7%), 151 (8.9%), 28 (2.9%) patients among the total, ISR, and de novo lesion populations, respectively. A history of hypertension, diabetes, acute coronary syndrome, previous coronary artery bypass graft, reduced left ventricular ejection fraction, B2C lesion and ISR lesion were independent predictors of 12 months TLF in the overall study population.
Conclusions
This large multicenter DCB registry study revealed the favorable clinical outcome of DCB treatment in real-world practice in patient with ISR lesion as well as small de novo coronary lesion.
6.Cardiac Behçet's Disease Presenting with Right Ventricular Endomyocardial Fibrosis and Intracardiac Thrombosis: a Case Report
Eun Ji CHOI ; Min Sun KIM ; Hyun Jung KOO ; Jae-Kwan SONG ; Joo Seon SONG ; Joon-Won KANG ; Dong Hyun YANG
Investigative Magnetic Resonance Imaging 2021;25(4):332-337
Behçet’s disease is a chronic inflammatory disorder involving vessels of various sizes and organs, including the skin, joints, gastrointestinal tract, lungs, and cardiovascular system. The etiology of Behçet’s disease is unclear, and clinical diagnosis is important in the absence of definitive laboratory or pathological findings diagnostic of Behçet’s disease. Cardiac involvement is rare but might present as endocarditis, myocarditis, pericarditis, or intracardiac thrombosis. This report presents a case of Behçet’s disease involving the heart in a 22-year-old man with unusual manifestations of right ventricular fibrosis and intracardiac thrombosis. Cardiac magnetic resonance imaging revealed multiple intracardiac thrombi and delayed diffuse subendocardial enhancement involving the right ventricle. No peripheral eosinophilia was detected. Endomyocardial biopsy showed mixed inflammatory cell infiltrates. Based on the patient’s clinical history of oral ulcer and arthritis, a diagnosis of Behçet’s disease was made considering the clinical, radiological, and histological findings. Intracardiac thrombi and endomyocardial fibrosis are rare manifestations of Behçet’s disease, and the diagnosis is often a clinical challenge. Early diagnosis is important for appropriate management. Behçet’s disease should be considered in the differential diagnosis of patients with intracardiac thrombosis and endomyocardial fibrosis of the right chamber.
7.Prognostic Implication of Right Ventricle Parameters Measured on Preoperative Cardiac MRI in Patients with Functional Tricuspid Regurgitation
Yura AHN ; Hyun Jung KOO ; Joon-Won KANG ; Won Jin CHOI ; Dae-Hee KIM ; Jong-Min SONG ; Duk-Hyun KANG ; Jae-Kwan SONG ; Joon Bum KIM ; Sung-Ho JUNG ; Suk Jung CHOO ; Cheol Hyun CHUNG ; Jae Won LEE ; Dong Hyun YANG
Korean Journal of Radiology 2021;22(8):1253-1265
Objective:
To investigate the prognostic value of preoperative cardiac magnetic resonance imaging (MRI) for long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR).
Materials and Methods:
The preoperative cardiac MR images, New York Heart Association functional class, comorbidities, and clinical events of 78 patients (median [interquartile range], 59 [51–66.3] years, 28.2% male) who underwent TV surgery for functional TR were comprehensively reviewed. Cox proportional hazards analyses were performed to assess the associations of clinical and imaging parameters with MACCEs and all-cause mortality.
Results:
For the median follow-up duration of 5.4 years (interquartile range, 1.2–6.6), MACCEs and all-cause mortality were 51.3% and 23.1%, respectively. The right ventricular (RV) end-systolic volume index (ESVI) and the systolic RV mass index (RVMI) were higher in patients with MACCEs than those without them (77 vs. 68 mL/m2 , p = 0.048; 23.5 vs. 18.0%, p = 0.011, respectively). A high RV ESVI was associated with all-cause mortality (hazard ratio [HR] per value of 10 higher ESVI = 1.10, p = 0.03). A high RVMI was also associated with all-cause mortality (HR per increase of 5 mL/m2 RVMI = 1.75, p < 0.001).After adjusting for age and sex, only RVMI remained a significant predictor of MACCEs and all-cause mortality (p < 0.05 for both). After adjusting for multiple clinical variables, RVMI remained significantly associated with all-cause mortality (p = 0.005).
Conclusion
RVMI measured on preoperative cardiac MRI was an independent predictor of long-term outcomes in patients who underwent TV surgery for functional TR.
8.Establishment of the Korea National Health and Nutrition Examination Survey air pollution study dataset for the researchers on the health impact of ambient air pollution
Myung-Jae HWANG ; Jisun SUNG ; Miryoung YOON ; Jong-Hun KIM ; Hui-Young YUN ; Dae-Ryun CHOI ; Youn-Seo KOO ; Kyungwon OH ; Sungha YUN ; Hae-Kwan CHEONG
Epidemiology and Health 2021;43(1):e2021015-
To provide a nationwide representative dataset for the study on health impact of air pollution, we combined the data from the Korea National Health and Nutrition Examination Survey with the daily air quality and weather data by matching the date of examination and the residential address of the participants. The database of meteorological factors and air quality as sources of exposure data were estimated using the Community Multiscale Air Quality model. The linkage dataset was merged by three ways; administrative district, si-gun-gu (city, county, and district), and geocode (in latitude and longitude coordinate units) based on the participants’ residential address, respectively. During the study period, the exposure dataset of 85,018 individuals (38,306 men and 46,712 women) whose examination dates were recorded were obtained. According to the definition of exposure period, the dataset was combined with the data on short-term, mid-term, and long-term exposure to air pollutants and the meteorological indices. Calculation of the daily merged dataset’s average air pollution linked by si-gun-gu and geocode units showed similar results. This study generated a daily average of meteorological indices and air pollution exposure dataset for all regions including rural and remote areas in Korea for 11 years. It is expected to provide a platform for the researchers studying the health impact of air pollution and climate change on the representative population and area, which may facilitate the establishment of local health care plans by understanding the residents’ health status at the local as well as national level.
9.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
10.Establishment of the Korea National Health and Nutrition Examination Survey air pollution study dataset for the researchers on the health impact of ambient air pollution
Myung-Jae HWANG ; Jisun SUNG ; Miryoung YOON ; Jong-Hun KIM ; Hui-Young YUN ; Dae-Ryun CHOI ; Youn-Seo KOO ; Kyungwon OH ; Sungha YUN ; Hae-Kwan CHEONG
Epidemiology and Health 2021;43(1):e2021015-
To provide a nationwide representative dataset for the study on health impact of air pollution, we combined the data from the Korea National Health and Nutrition Examination Survey with the daily air quality and weather data by matching the date of examination and the residential address of the participants. The database of meteorological factors and air quality as sources of exposure data were estimated using the Community Multiscale Air Quality model. The linkage dataset was merged by three ways; administrative district, si-gun-gu (city, county, and district), and geocode (in latitude and longitude coordinate units) based on the participants’ residential address, respectively. During the study period, the exposure dataset of 85,018 individuals (38,306 men and 46,712 women) whose examination dates were recorded were obtained. According to the definition of exposure period, the dataset was combined with the data on short-term, mid-term, and long-term exposure to air pollutants and the meteorological indices. Calculation of the daily merged dataset’s average air pollution linked by si-gun-gu and geocode units showed similar results. This study generated a daily average of meteorological indices and air pollution exposure dataset for all regions including rural and remote areas in Korea for 11 years. It is expected to provide a platform for the researchers studying the health impact of air pollution and climate change on the representative population and area, which may facilitate the establishment of local health care plans by understanding the residents’ health status at the local as well as national level.

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