Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Objective: This study aimed to evaluate the accuracy of predicting final adult height (FAH) in Korean girls with central precocious puberty (CPP) using artificial intelligence (AI)-derived bone age assessments integrated into the Bayley–Pinneau (BP) or Korean National Growth Chart (KGC) prediction models. Materials and Methods: This single-center, retrospective study included 122 Korean girls with CPP who received gonadotropinreleasing hormone agonist (GnRHa) treatment for at least two years between January 2000 and November 2022. We assessed bone age and predicted adult height at the initiation and completion of GnRHa treatment. We used three bone age assessment methods: human expert assessment based on the Greulich-Pyle (GP) atlas (Human-GP), AI-derived GP (AI-GP), and AI-weighted GP scoring (AI-GPw). We calculated predicted adult heights (PAHs) using both the BP and KGC models, generating 12 PAH estimates per patient (2 time points x 3 bone-age methods x 2 height-prediction models). We assessed prediction accuracy and agreement with FAH using linear regression analysis and Bland–Altman plots and performed multivariable analysis to identify significant predictors of FAH. Results: Human-GP, AI-GP, and AI-GPw demonstrated comparable overall performance in predicting FAH (R 2 : 0.470–0.646 and 0.691–0.822 for treatment initiation and completion, respectively). AI-GPw combined with BP yielded slightly better point estimates but showed no statistically significant differences. At both time points, the BP model demonstrated consistently narrower 95% limits of agreement (LoA) than the KGC model. Multivariable analysis identified AI-GPw-BP and height percentile score as significant predictors of FAH at both time points; mid-parental height was significant only at treatment initiation. Conclusion Human-GP, AI-GP, and AI-GPw demonstrated comparable accuracy in predicting FAH. The BP model demonstrated consistently narrower 95% LoA than did the KGC model. AI-GPw-BP was an independent predictor of FAH. These findings support the clinical utility of AI-derived bone age assessments for individualized FAH prediction in patients with CPP.

Purpose: Due to its rarity, treatment guidelines for appendiceal cancer have traditionally followed those established for colorectal cancer, despite showing distinct histologic and clinical features. This study aimed to compare the clinicopathologic characteristics and long-term oncologic outcomes of appendiceal cancer with those of right-sided colon cancers. Methods: We retrospectively reviewed the records of patients with stage I–III appendiceal, cecal, or ascending colon cancer who underwent curative resection between 2010 and 2020 at our center. A 1:3:3 exact matching for age, sex, TNM stage, and adjuvant chemotherapy was performed. Survival outcomes were analyzed using the Kaplan-Meier and Cox regression methods. Results: Overall, 245 patients with appendiceal cancer (n = 35), ascending colon cancer (n = 105), and cecal cancer (n = 105) were analyzed. Appendiceal cancer exhibited a higher proportion of T4 tumors and fewer harvested lymph nodes compared with ascending or cecal cancers. The mean follow-up duration was 9.5 years. The 5- and 10-year overall survival rates were lower in appendiceal cancer (66.2% and 52.9%) than in ascending (91.2% and 78.4%) or cecal cancer (88.5% and 78.3%). Similarly, the 10-year disease-free survival rate was lower in appendiceal cancer (59.2%) compared with ascending (83.1%) and cecal cancers (78.4%). Cox regression analysis identified age (≥65 years), perforation, nodal metastasis, and lymphovascular invasion as independent predictors of poor prognosis. Conclusion Appendiceal cancer exhibited significantly worse long-term survival compared to cecal or ascending colon cancer. Tumor perforation, nodal metastasis, and lymphovascular invasion were adverse prognostic factors for overall and disease-free survival.

Purpose: Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs. Materials and Methods: This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor. Results: Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively. Conclusion Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

Purpose: Emergency room bouncing has become a critical social issue in South Korea. While the government seeks to address this problem by imposing stricter penalties, healthcare providers remain reluctant to accept high-risk patients. This study aimed to analyze the structural causes of emergency patient refusal using a game-theoretic framework, with a focus on the asymmetry between emergency care regulations and medical malpractice risks. Methods: A non-cooperative game model was developed to analyze strategic interactions between the government and healthcare providers. A minimax approach was used to evaluate the impact of maximum liability (approximately 1 billion Korean won [KRW]) and administrative fines for delays in emergency patient transfer. Specifically, a break-even analysis was conducted to estimate the surgical volume required to offset this liability under a realistic fee schedule. Results: The expected loss from accepting a high-risk emergency patient substantially exceeded the penalty for refusal. Simulations indicated that, even under optimistic revenue assumptions, it would take more than 66 years of accident-free operations for a specialist to offset a single liability of 1 billion KRW. Consequently, refusal remains the rational dominant strategy for providers seeking to avoid professional bankruptcy. Conclusion The primary cause of transfer delays is a structural imbalance characterized by high risk and low returns, in which medical fees do not cover the substantial liabilities imposed by recent judicial rulings. Without state indemnification for accidents caused by force majeure and exemptions from criminal liability, legislative efforts that merely mandate acceptance will accelerate the collapse of the emergency medical infrastructure.

Purpose: To develop and validate an artificial intelligence (AI)-based personalized outcome prediction model for upper-urinary tract urothelial carcinoma patients undergoing radical nephroureterectomy. Materials and Methods: Data from patients who underwent radical nephroureterectomy between 2010 and 2020 across three hospitals were retrospectively analyzed. A model was developed using one tertiary center’s data and externally validated with data from two other hospitals. An AI model using XGBoost as risk estimator and bootstrapped Weibull Accelerated Failure Time model for 10-year survival probability was employed. Hyperparameter tuning used Optuna method. Model efficacy was assessed using concordance index, average Brier score, D-calibration, and six-month interval time-dependent area under the curve (AUC). Results: Of 1,039 patients, 627 qualified after excluding 50 with neoadjuvant chemotherapy. Model development used 564 patients (507 training, 57 test) with 9:1 stratified random split, plus 63 for internal validation and 362 for external validation. Significant parameters included preoperative glomerular filtration rate (p<0.001), hydroureteronephrosis (p=0.013), pathological N stage (p<0.001), concurrent carcinoma in situ (p<0.001), disease progression (p<0.001), and survival rate (p<0.001). Disease-free survival (DFS) model’s concordance index: internal validation 0.789, external validations 0.734 and 0.771. Overall survival (OS) model’s concordance index: internal validation 0.819, external validations 0.780 and 0.771. Mean time-dependent AUC was 0.66–0.77 for DFS and 0.67–0.80 for OS during 10-year periods. Conclusions AI-based model effectively predicts disease-free and OS outcomes for upper-urinary tract urothelial carcinoma patients with post-radical nephroureterectomy, showcasing robust performance across multicenter settings.

Background and Objectives: The clinical significance of incidental pulmonary nodules detected during thyroid cancer evaluation remains unclear. This study aimed to investigate how such findings affect surgical decisionmaking and whether management differs by physician characteristics. Materials and Methods: A web-based survey was distributed to 722 active members of the Korean Thyroid Association in March 2025. Eligible participants included board-certified endocrinologists, endocrine surgeons, and otolaryngologists actively treating thyroid cancer. The questionnaire included clinical scenarios featuring incidental lung nodules found during thyroid cancer work-up, with respondents asked to choose preferred surgical extent (thyroid lobectomy vs. total thyroidectomy) and management approaches. Results: Out of 72 physicians who completed the survey, half (n=36, 50.0%) of the respondents answered that the presence of incidental lung nodules could influence their decision on thyroidectomy extent. Among those influenced by lung nodules, 86.1% recommended total thyroidectomy in patients with high- or intermediate-risk thyroid cancer, while 11.1% would do so for all thyroid cancer patients.Endocrinologists, compared to surgeons, were more likely to choose total thyroidectomy in patients with preoperative incidental lung nodules (78.3% vs. 36.7%, p=0.001). Conclusion Incidental lung nodules may influence surgical planning in clinicians due to the risk of micrometastasis from thyroid cancer. Endocrinologists tend to favor a more extensive surgical approach compared to surgeons, reflecting greater concern for potential metastatic disease. These findings underscore the need for multidisciplinary consensus guidelines for the management of incidental pulmonary nodules in thyroid cancer patients.

Purpose: Adjuvant chemotherapy (AC) is recommended for muscle-invasive or lymph node-positive upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). However, disease recurrences are frequently observed in pT1 disease, and AC may increase the risk of overtreatment in pT2 UTUC patients. This study aimed to validate a risk-adapted scoring model for selecting UTUC patients with ≤pT2 disease who would benefit from AC. Materials and Methods: We retrospectively analyzed 443 ≤pT2 UTUC patients who underwent RNU. A risk-adapted scoring model was applied, categorizing patients into low- or high-risk groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were analyzed according to risk group. Results: Overall, 355 patients (80.1%) and 88 patients (19.9%) were categorized into the low- and high-risk groups, respectively, with the latter having higher pathological stages, concurrent carcinoma in situ, and synchronous bladder tumors. Disease recurrence occurred in 45 patients (10.2%), among whom 19 (5.4%) and 26 (29.5%) belonged to the low- and high-risk groups, respectively (p<0.001). High-risk patients had significantly shorter RFS (64.3% vs. 93.6% at 60 months; hazard ratio [HR] 13.66; p<0.001) and worse CSS (80.7% vs. 91.5% at 60 months; HR 4.25; p=0.002). Multivariate analysis confirmed that pT2 stage and the high-risk group were independent predictors of recurrence and cancer-specific death (p<0.001). Decision curve analysis for RFS showed larger net benefits with our model than with the T stage model. Conclusions The risk-adapted scoring model effectively predicts recurrence and identifies optimal candidates for AC post RNU in non-metastatic UTUC.

OBJECTIVES: This study aimed to compare maternal outcomes and the home environment between non‑vulnerable families with children under 2 receiving universal home visiting services and vulnerable families receiving sustained home visiting services. METHODS: This study was conducted in Seoul, Korea, where the country’s first nurse‑led early childhood home visiting program was introduced. A total of 551 mother‑child dyads participated in cross‑sectional surveys conducted at various child ages (6±2 weeks, 6±1 months, 12±1 months, and 24±1 months). Universal home visiting services were provided within six weeks postpartum to non‑vulnerable families, while vulnerable families received sustained services consisting of 25 visits over 24 months. Maternal knowledge of sudden infant death syndrome (SIDS) and childcare, maternal distress, and the Korean Infant‑Toddler Home Observation for Measurement of Environment (K‑IT‑HOME) were assessed. RESULTS: Overall, the universal home visitation group demonstrated higher levels of maternal knowledge regarding SIDS and childcare compared to the sustained home visitation group (all p-values <0.05), while the sustained home visitation group reported higher levels of maternal distress (p<0.001). The total K‑IT‑HOME score was 1.47 points higher in the universal home visitation group than in the sustained home visitation group (p<0.001). No significant differences were observed in the acceptance, organization, or involvement subscales of the K‑IT‑HOME (all p-values >0.05). CONCLUSIONS This study demonstrated that disparities in maternal outcomes and home environments persisted in early childhood between the sustained and universal home visitation groups.