Background: DNA methylation is under investigation as an early diagnostic biomarker for cancers such as hepatocellular carcinoma (HCC). p21-activated protein kinase 1 (PAK1) demonstrates a high methylation tendency in HCC. We assessed the diagnostic and prognostic performance of PAK1 methylation in liver transplantation (LT) recipients with and without HCC. Methods: To assess PAK1 methylation, stored pretransplant blood samples from LT recipients were analyzed by droplet digital polymerase chain reaction. Results: This study included 274 patients with HCC and 100 control patients without the disease. Ten-year survival rates in the HCC and control groups were 60.5% and 80.6%, respectively (P=0.001). The 10-year HCC recurrence rate was 39.0%. Ten-year survival rates in the HCC recurrence and nonrecurrence groups were 13.3% and 91.2%, respectively (P<0.001); median PAK1 methylation levels in the control and HCC groups were 50.0 and 108.0 copies (P=0.102). The area under the receiver operating characteristic curve was 0.599, and the Youden J index was 0.199, indicating 57.9% sensitivity and 62.0% specificity at a cutoff of 78 copies. With a cutoff of 5 copies, sensitivity was 94.1% and specificity was 14.0%. The positive likelihood ratio was 1.09 and the negative likelihood ratio was 0.42, indicating diagnostic accuracy below α-fetoprotein and protein induced by vitamin K absence or antagonist-II. PAK1 cutoffs of 5 and 10 copies did not affect HCC recurrence, but a cutoff of 2 copies appeared associated with lower recurrence. Conclusions These data suggest that PAK1 methylation is not a clinically useful biomarker for HCC in LT recipients. New DNA methylation biomarkers are required for early diagnosis.

Purpose: Surveillance guidelines following breast cancer surgery recommend mammography as the sole imaging modality. However, the accuracy of mammography is low in younger women and in those with dense breast tissue. Additional imaging modalities, such as ultrasonography and magnetic resonance imaging (MRI), may offer diagnostic benefits.This prospective, multicenter study (KBCSG-27) aims to compare the diagnostic performances of mammography, ultrasonography, and MRI for detecting second breast cancer (SBC) in women with a personal history of breast cancer (PHBC) and dense breasts. Methods This study will recruit approximately 1,756 women, aged 20–75 years, who were treated for stage 0–III breast cancer and have dense breast tissue on mammography.Participants will undergo two annual breast screenings, each consisting of mammography, ultrasonography, and MRI. MRI will be performed using either abbreviated magnetic resonance imaging (AB-MRI) or full-protocol magnetic resonance imaging (FP-MRI), which will be randomly assigned such that each participant receives both protocols alternately.Radiologists will independently interpret all images. A combination of pathology results and 12-month follow-up will serve as the reference standard. A patient-reported outcome (PRO) tool will be used to assess patients’ experiences and preferences between AB-MRI and FPMRI. The primary objective is to compare the cancer detection rates of ultrasonography versus AB-MRI and ultrasonography versus FP-MRI. Secondary outcomes include comparisons of the invasive cancer detection rates, abnormal interpretation rates, sensitivity, specificity, positive and negative predictive values, accuracy, and interval cancer rates. Subgroup analyses will be conducted based on age, menopausal status, mammographic breast density, and molecular subtype. Additionally, PRO results of AB-MRI and FP-MRI will be compared.Discussion: This ongoing, prospective, multicenter study aims to evaluate the performance of ultrasonography, AB-MRI, and FP-MRI in SBC surveillance in women with PHBC and dense breasts. Enrollment is expected to be completed by 2025, with results anticipated after 2028.

Background and Objectives: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a life-threatening inherited arrhythmogenic disorder. Recently, RYR2, the major CPVTcausative gene, was associated with neuropsychiatric manifestations. We aimed to analyze the clinical presentations, neuropsychiatric manifestations, and treatment outcomes of children with CPVT. Methods: We retrospectively reviewed 23 patients diagnosed with CPVT before 19 years of age. Genetic analysis, history of neuropsychiatric manifestations, changes in ventricular arrhythmia burden before and after treatment, occurrence of cardiac events, and overall survival (OS) were investigated. Results: RYR2 variants were identified in 17 patients, and 14 were classified as pathogenic or likely pathogenic. Neuropsychiatric manifestations, including intellectual disability and attention deficit hyperactivity disorder, were identified in 10 patients (43.5%). The 5-year cardiac event-free survival rate was 31.2%, and the 10-year OS rate was 73.1%. Patients diagnosed since 2009 had a higher cardiac event-free survival rate than those diagnosed before 2009 (p=0.0028).Combined beta-blocker and flecainide therapy demonstrated a lower risk of cardiac events than beta-blocker monotherapy (hazard ratio [HR], 0.08; 95% confidence interval [CI], 0.02–0.38;p=0.002). Left cardiac sympathetic denervation (LCSD) reduced the ventricular arrhythmia burden in Holter monitoring. Occurrence of near-fatal cardiac events after diagnosis was an independent predictor of death (HR, 33.40; 95% CI, 6.23–179.95; p<0.001). Conclusions Neuropsychiatric manifestations are common in children with CPVT. Flecainide and/or LCSD, when added to beta-blocker therapy, reduce the ventricular arrhythmia burden and cardiac events, thereby improving treatment outcomes in recent years.

Background and Objectives: This study aimed to analyze the outcomes of Fontan surgery in the Republic of Korea, as there were only a few studies from Asian countries. Methods: The medical records of 1,732 patients who underwent Fontan surgery in 10 cardiac centers were reviewed. Results: Among them, 1,040 (58.8%) were men. The mean age at Fontan surgery was 4.3±4.2 years, and 395 (22.8%) patients presented with heterotaxy syndrome. According to the types of Fontan surgery, 157 patients underwent atriopulmonary (AP) type; 303, lateral tunnel (LT) type; and 1,266, extracardiac conduit (ECC) type. The overall survival rates were 91.7%, 87.1%, and 74.4% at 10, 20, and 30 years, respectively. The risk factors of early mortality were male, heterotaxy syndrome, AP-type Fontan surgery, high mean pulmonary artery pressure (mPAP) in pre-Fontan cardiac catheterization, and early Fontan surgery year. The risk factors of late mortality were heterotaxy syndrome, genetic disorder, significant atrioventricular valve regurgitation (AVVR) before Fontan surgery, high mPAP in pre-Fontan cardiac catheterization, and no fenestration. Conclusions In Asian population with a high incidence of heterotaxy syndrome, the heterotaxy syndrome was identified as the poor prognostic factors for Fontan surgery. The preoperative low mPAP and less AVVR are associated with better early and long-term outcomes of Fontan surgery.

Purpose: To analyze the degree of psychological distress experienced pre- and postoperatively in patients who underwent radical prostatectomy after being diagnosed with prostate cancer. Materials and Methods: Patients diagnosed with prostate cancer who underwent radical prostatectomy without history of psychiatric disorders were included in this study. The degree of psychological distress was evaluated using hospital anxiety and depression scale (HADS) and distress thermometer (DT) questionnaires preoperatively and at 1, 3, 6, and 12 months postoperatively. Results: Distress was high preoperatively and decreased over the entire period. In addition, HADS-anxiety and HADS-depression scores showed an improved severity, shifting from an abnormal state to a borderline state in some patients. However, the DT score, including emotional problems, spiritual concerns, physical problems, family problems, and practical problems, was slightly higher at 1 month postoperatively compared to preoperatively. Furthermore, even at 12 months postoperatively, about one fifth of patients surveyed had a DT score of 4 or higher, requiring psychiatric intervention. Conclusions Before and after radical prostatectomy, a significant number of patients complained of distress such as anxiety, depression, and insomnia, and they needed help from a specialist because of psychological distress even 12 months postoperatively.Therefore, a close evaluation of the patient’s psychological distress and supportive treatment are needed during the entire pre- and postoperative period.

Background and Objectives: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a life-threatening inherited arrhythmogenic disorder. Recently, RYR2, the major CPVTcausative gene, was associated with neuropsychiatric manifestations. We aimed to analyze the clinical presentations, neuropsychiatric manifestations, and treatment outcomes of children with CPVT. Methods: We retrospectively reviewed 23 patients diagnosed with CPVT before 19 years of age. Genetic analysis, history of neuropsychiatric manifestations, changes in ventricular arrhythmia burden before and after treatment, occurrence of cardiac events, and overall survival (OS) were investigated. Results: RYR2 variants were identified in 17 patients, and 14 were classified as pathogenic or likely pathogenic. Neuropsychiatric manifestations, including intellectual disability and attention deficit hyperactivity disorder, were identified in 10 patients (43.5%). The 5-year cardiac event-free survival rate was 31.2%, and the 10-year OS rate was 73.1%. Patients diagnosed since 2009 had a higher cardiac event-free survival rate than those diagnosed before 2009 (p=0.0028).Combined beta-blocker and flecainide therapy demonstrated a lower risk of cardiac events than beta-blocker monotherapy (hazard ratio [HR], 0.08; 95% confidence interval [CI], 0.02–0.38;p=0.002). Left cardiac sympathetic denervation (LCSD) reduced the ventricular arrhythmia burden in Holter monitoring. Occurrence of near-fatal cardiac events after diagnosis was an independent predictor of death (HR, 33.40; 95% CI, 6.23–179.95; p<0.001). Conclusions Neuropsychiatric manifestations are common in children with CPVT. Flecainide and/or LCSD, when added to beta-blocker therapy, reduce the ventricular arrhythmia burden and cardiac events, thereby improving treatment outcomes in recent years.