Purpose: Patient-derived cells (PDCs) and patient-derived organoids (PDOs) are complementary preclinical models widely used in translational cancer research. However, their molecular and functional differences have not been systematically characterized. This study established and analyzed paired PDC and PDO models derived from the same gastric cancer ascites to delineate platform-dependent molecular and functional profiles. Materials and Methods: Malignant ascites or pleural fluid obtained from 6 patients with advanced gastric cancer were used to establish paired PDC and PDO models. All pairs underwent comprehensive multi-omics profiling, integrating genomic, transcriptomic, and proteomic data. Phenotypic characterization included morphological, histological, proliferative, and cell cycle analyses. Drug sensitivity assays were performed using 4 chemotherapeutic agents commonly used to treat gastric cancer. Results: The 6 paired PDC and PDO models exhibited distinct morphological characteristics.Whole-genome analyses demonstrated high concordance among primary tumors, PDCs, and PDOs, confirming tumor representation across platforms. Multi-omics profiling identified platform-dependent molecular signatures; PDOs were enriched for extracellular matrix remodeling and stemness, whereas PDCs displayed proliferation- and immune-related signatures. Clinically relevant biomarkers, including HER2 and MET alterations, were concordant with primary tumors. Notably, drug responses differed between platforms and patients, indicating platform-dependent and patient-specific chemosensitivity. Conclusions Paired PDC and PDO models derived from the same patients preserved core patient-specific tumor characteristics while exhibiting distinct molecular and functional profiles. These findings underscore the culture platform as a critical determinant of experimental outcomes and therapeutic responses. Therefore, careful selection of an appropriate preclinical model is essential to accurately address biological questions and optimize precision oncology strategies.

Purpose: Stress radiographs have long been used to evaluate chronic lateral ankle instability. Several measurement methods exist, but their diagnostic value remains controversial. This paper introduces a new measurement method for stress radiographs, the fibular tip to talar neck (FTN) method, and compares it with established methods to assess its diagnostic accuracy and reliability. Materials and Methods: Forty-one patients who underwent a modified Broström procedure for chronic lateral ankle instability were included. Lateral standing and anterior drawer radiographs were analyzed using two conventional methods (methods I and II) and the novel FTN method. The contralateral unaffected side served as an internal control. The diagnostic accuracy was evaluated using receiver operating characteristic curve analysis. The intra-observer and inter-observer reliability were assessed using intraclass correlation coefficients (ICCs). Results: Using the FTN method, the mean gap on the affected side (14.39±4.79 mm) was significantly greater than on the contralateral side (10.24±4.19 mm, p<0.001). The side-to-side difference (SSD) was significantly higher in the FTN method (4.14±2.94 mm) compared to methods I (0.89±1.94 mm) and II (0.91±1.78 mm, p<0.001). The FTN method showed a balanced diagnostic performance with an area under the curve of 0.743 and an optimal cut-off of 13.5 mm. The intra-observer and inter-observer reliability were good for all methods. The intra-observer and inter-observer ICCs for the FTN method were 0.858 and 0.783, respectively. Conclusion The FTN method provides a reliable and reproducible measure of chronic lateral ankle instability. The method facilitates a more intuitive diagnosis compared to conventional techniques by providing a larger numerical differentiation (SSD) and a statistically balanced threshold.

Background/Aims: Endoscopic anti-reflux therapy is a therapeutic option for gastroesophageal reflux disease (GERD), providing durable effects. However, clinical data from Korea remain limited. This study evaluates the clinical outcomes of endoscopic radiofrequency Stretta therapy in Korean patients. Methods: A retrospective analysis was conducted on 71 patients with GERD who underwent Stretta therapy at 2 tertiary hospitals in Korea between November 2015 and July 2021. Clinical outcomes, including patient satisfaction, medication cessation or reduction, and complications, were evaluated. Pre- and post-procedural esophageal manometry and 24-hour pH monitoring test results were also analyzed. Results: Patient satisfaction rates at 1, 6, and 12 months post-procedure were 54.7% (35/64), 70.0% (28/40), and 75.0% (21/28), respectively. Medication cessation or reduction was achieved in 31.2% (20/64) at 1 month, 70.0% (28/40) at 6 months, and 67.9% (19/28) at 12 months. Esophageal manometry (n = 21) showed no significant changes in mean lower esophageal sphincter pressure (18.7 mmHg [2.5-52.9] vs 17.4 mmHg [0.0-43.0], P = 0.702) or mean integrated relaxation pressure (8.2 mmHg [0.0-28.0] vs 10.1 mmHg [0.0-31.0], P = 0.840). The 24-hour pH monitoring (n = 18) demonstrated a nonsignificant decrease in acid exposure time (pH < 4) from 2.3% (0.0-8.4) to 1.6% (0.0-7.3) (P = 0.182). Similarly, the DeMeester score decreased non-significantly from 8.4 (0.8-27.7) to 6.6 (0.8-21.8) (P = 0.352). No procedure-related complications occurred. Conclusion Endoscopic radiofrequency Stretta therapy appears to be a safe treatment option for GERD and may provide favorable patient satisfaction and medication reduction.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

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: Esophagojejunostomy leakage (EJL) continues to be a serious and potentially fatal complication following total gastrectomy for gastric cancer. This study aimed to evaluate the clinical outcomes of endoscopic Histoacryl (B. Braun) injection in comparison to alternative treatment strategies for EJL. Methods: Out of 885 patients who underwent total gastrectomy at a single institution between January 2003 and August 2023, 26 (2.9%) developed EJL. Patients were categorized into four groups according to the management received:conservative treatment (n = 5), endoscopic Histoacryl injection (n = 10), reoperation (n = 8), and combined therapy (n = 3).Outcomes assessed included postoperative hospital stay, duration to oral intake, treatment success rate, and mortality. Results: Of the 26 patients with EJL, 3 (11.5%) succumbed to sepsis: two in the reoperation group and 1 in the Histoacryl group. In the 23 successfully managed cases, the Histoacryl group achieved the shortest median postoperative hospital stay, the shortest time to resuming of oral intake, and a 90% success rate without any procedure-related complications.The reoperation group experienced increased morbidity and mortality. Stent migration was reported in one patient from the combined treatment group. Differences in recovery between the four groups reached statistical significance (P < 0.05). Conclusion Endoscopic Histoacryl injection represents a safe, effective, and minimally invasive modality for managing EJL, providing improved recovery times and reduced complication rates. It is beneficial both as a primary intervention and as part of combination therapy.

Purpose: Neoadjuvant chemotherapy (NAC) significantly revolutionized the management of locally advanced breast cancer, especially in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes. However, its effectiveness is limited in estrogen receptor (ER)-positive, HER2-negative breast cancer. This study investigates the clinical response and prognosis of ER-positive, HER2-negative breast cancer after NAC. Methods: The clinicopathological characteristics and treatment responses of 149 patients with ER-positive, HER2-negative breast cancer treated with NAC and surgery at The Catholic University of Korea, Seoul St. Mary’s Hospital between 2018 and 2023 were retrospectively analyzed. Pathologic complete response (pCR) was defined as the absence of invasive tumors (ypT0/is, ypN0). Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier methods, stratified by age (≤50 years vs. >50 years). Results: Among 149 patients, 13 (8.7%) achieved pCR, 87 (58.4%) attained partial responses, 40 (26.8%) had stable disease, and 9 (6.0%) experienced progressive disease. RECIST responses differed significantly by age (P = 0.003). DFS (P = 0.011) and OS (P = 0.005) were significantly associated with clinical response in patients aged ≤50 years. Post-NAC Ki-67 was associated with DFS (P = 0.013) but not OS (P = 0.083) in patients aged ≤50 years. Clinical responses and post-NAC Ki-67 were not associated with DFS (P = 0.544) or OS (P = 0.569) in patients aged >50 years. Conclusion In ER-positive, HER2-negative breast cancer, clinical responses and post-NAC Ki-67 were significant prognostic factors in patients aged ≤50 years but not in older patients. These findings highlight the need for tailored therapeutic approaches that consider age-specific prognostic differences.

Genetic variation in the leptin receptor (LEPR) gene has been implicated in metabolic regulation, while the gut microbiome and circulating metabolites are increasingly recognized as mediators of host metabolic phenotype. However, the systems-level interactions among LEPR genotypes, gut microbial composition, and serum metabolomic profiles remain poorly understood, particularly in healthy individuals. We conducted a cross-sectional study involving 37 healthy Korean adults. Three LEPR single nucleotide polymorphisms (rs1137101, rs1173100, rs790419) were genotyped. Untargeted metabolomics of fasting serum was performed using gas chromatography–time-of-flight mass spectrometry, and gut microbiome composition was profiled by 16S rRNA gene sequencing. Statistical analysis included principal component analysis, Mann–Whitney U tests, and Spearman correlations. Network analysis integrating microbiome, metabolomic, and clinical phenotype data was conducted using Cytoscape. A total of 54 serum metabolites were identified. LEPR genotypes, particularly rs1137101 and rs1173100, were associated with differences in metabolites such as pimelic acid, malonic acid, and 2,4-dihydroxybutyric acid. Firmicutes negatively correlated with saturated fatty acids and organic acids, whereas Actinobacteria positively correlated with cholesterol and amino acids. Network analysis revealed indole-3-acetate and cholesterol as central nodes linking microbial taxa with body mass index and leptin levels. However, no direct molecular pathways connecting leptin or its receptor were identified. LEPR genetic variation is associated with distinct serum metabolomic patterns and microbiome–host networks in healthy adults. Although no direct leptin signaling links were found, network-level associations suggest indirect genetic influences on metabolic states through microbiome–metabolome interactions.These findings advance understanding of personalized metabolic regulation and gene–microbiome interplay.

The comprehensive in vitro proarrhythmia assay (CiPA) initiative, led by the U.S. Food and Drug Administration (FDA), provides a framework for predicting drug-induced arrhythmia risk. To support domestic CiPA implementation, we evaluated the proarrhythmic risk of sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor. Sildenafil has been misused recreationally, with reports of highdose non-medical intake. To simulate misuse, in vitro assays were conducted using concentrations up to 100× the maximum therapeutic plasma concentration (Cmax). The assessment followed the three core components of the CiPA paradigm. Patch clamp assays were conducted in Human Embryonic Kidney 293 (HEK293) and Chinese hamster ovary (CHO) cells transiently expressing Nav1.5, Cav1.2, and hERG ion channels. In silico modeling was performed using the CiPAORdv1.0 model based on IC₅₀ and Hill coefficient values. Functional evaluation included multi-electrode array (MEA) recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and in vivo electrocardiography (ECG) analysis in rats was performed to observe QT interval prolongation. Sildenafil significantly inhibited hERG currents by 40.5% at 100× Cmax. In silico modeling predicted a low Torsades de Pointes (TdP) risk based on qNet biomarkers. In contrast, MEA recordings showed a concentration-dependent prolongation of corrected field potential duration (FPDc), with a significant 13.3% increase at 100× Cmax. The TdP risk estimated from MEA modeling was 64%. In vivo ECG analysis revealed significant QT prolongation at 50× Cmax. Despite low in silico TdP predictions, functional assays suggest that high concentrations of sildenafil as in misuse may pose a clinically relevant risk of QT prolongation and arrhythmia.