Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Composite gangliocytomaeuroma and neuroendocrine tumors (CoGNETs) are extremely rare periampullary neoplasms composed of neuroendocrine epithelial, Schwannian spindle, and ganglion cells. Although endoscopic papillectomy or surgery have been used to treat ampullary CoGNETs, underwater endoscopic mucosal resection (UEMR) for periampullary lesions has not been previously described. In this study, we present a case of a 53-year-old man referred to our hospital with an incidentally detected subepithelial tumor in the second portion of the duodenum. Endoscopic ultrasound revealed a 13×10-mm homogeneous, hypoechoic, and well-demarcated submucosal mass. UEMR was performed under conscious sedation without submucosal injection, achieving safe en bloc resection within 12 min. Histopathology revealed a 2.0×1.5×1.2-cm lesion composed of mixed neuroendocrine epithelial, Schwannian spindle, and ganglion cells. Immunohistochemical staining was positive for chromogranin A, synaptophysin, CD56, neuron-specific enolase, and S-100, confirming CoGNET with a Ki-67 index of <1% and no lymphovascular or perineural invasion. Follow-up endoscopy 3 months later revealed only a post-resection scar without residual or recurrent tumors. This appears to be the first reported case of periampullary CoGNET successfully treated with UEMR. Therefore, UEMR might represent a safe and effective therapeutic option for selected periampullary subepithelial tumors.

This review examines the challenges associated with occupational disease surveillance in Korea, particularly emphasizing the limitations of current data sources such as the Industrial Accident Compensation Insurance (IACI) statistics and special health examinations. The IACI system undercounts cases due to its emphasis on severe diseases and restrictions on approvals. Special health examinations, although they cover a broad workforce, are constrained by their annual scheduling, which leads to missed acute illnesses and subclinical conditions. The paper also explores the history of occupational disease surveillance in Korea, highlighting the fragmented and disease-specific approach of earlier systems. The authors introduce the newly established Korea Occupational Disease Surveillance Center (KODSC), a comprehensive nationwide system designed to gather, analyze, and interpret data on occupational diseases through a network of regional centers. By incorporating hospital-based surveillance and focusing on acute poisonings and other sentinel events, the KODSC aims to overcome the limitations of previous systems and promote collaboration with various agencies. Although it is still in the early stages of implementation, the KODSC demonstrates potential for improving data accuracy and contributing valuable insights for public health policy.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Background and Objectives: The Korean Organ Transplant Registry (KOTRY) provided data for this third official report on adult heart transplantation (HT), including information from 709 recipients. Methods: Data from HTs performed at seven major centers in Korea between March 2014 and December 2020 were analyzed, focusing on immunosuppression, acute rejection, cardiac allograft vasculopathy (CAV), post-transplant survival, and mechanical circulatory support (MCS) usage. Results: The median ages of the recipients and donors were 56.0 and 43.0 years, respectively.Cardiomyopathy and ischemic heart disease were the most common preceding conditions for HT. A significant portion of patients underwent HT at waiting list status 1 and 0. In the multivariate analysis, a predicted heart mass mismatch was associated with a higher risk of 1-year mortality. Patients over 70 years old had a significantly increased risk of 6-year mortality. The risk of CAV was higher for male donors and donors older than 45 years. Acute rejection was more likely in patients with panel reactive antibody levels above 80%, while statin use was associated with a reduced risk. The employment of left ventricular assist device as a bridge to transplantation increased from 2.17% to 22.4%. Pre-transplant extra-corporeal membrane oxygenation was associated with worse post-transplant survival. Conclusions In this third KOTRY report, we analyzed changes in the characteristics of adult HT recipients and donors and their impact on post-transplant outcomes. The most notable discovery was the increased use of MCS before HT and their impact on post-transplant outcomes.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

This review examines the challenges associated with occupational disease surveillance in Korea, particularly emphasizing the limitations of current data sources such as the Industrial Accident Compensation Insurance (IACI) statistics and special health examinations. The IACI system undercounts cases due to its emphasis on severe diseases and restrictions on approvals. Special health examinations, although they cover a broad workforce, are constrained by their annual scheduling, which leads to missed acute illnesses and subclinical conditions. The paper also explores the history of occupational disease surveillance in Korea, highlighting the fragmented and disease-specific approach of earlier systems. The authors introduce the newly established Korea Occupational Disease Surveillance Center (KODSC), a comprehensive nationwide system designed to gather, analyze, and interpret data on occupational diseases through a network of regional centers. By incorporating hospital-based surveillance and focusing on acute poisonings and other sentinel events, the KODSC aims to overcome the limitations of previous systems and promote collaboration with various agencies. Although it is still in the early stages of implementation, the KODSC demonstrates potential for improving data accuracy and contributing valuable insights for public health policy.

Background/Aims: The clinical outcomes and optimal treatment of esophageal squamous cell carcinoma (ESCC) in elderly patients are unclear. This study aimed to assess the clinical outcomes of ESCC in patients aged ≥ 80 years. Methods: Medical records of patients diagnosed with ESCC between December 2008 and February 2024 were retrospectively reviewed. In total, 479 patients with ESCC were included and divided into the elderly (n = 52) and younger (n = 427) groups based on age. The clinical outcomes and survival rates, according to treatment, were compared between the two groups. Results: The median ages of the two groups were 82 years (range, 80–95 yr) and 66 years (41–79 yr). The overall survival was slightly lower in the elderly group; however, no statistical significance (hazard ratio [HR] 1.27, 95% confidence interval [CI] 0.85−1.91; p = 0.238) was observed. No differences were observed in the outcomes or survival between the two groups according to the treatment method (surgery, chemoradiotherapy or radiotherapy alone, and endoscopic resection). The elderly group was more likely to receive no treatment for cancer (30.8% vs. 13.6%, p = 0.002) than the younger group. However, when there was no treatment for cancer in the elderly group, survival was significantly lower than when treatment was administered (HR 0.08, 95% CI 0.03−020; p < 0.001). Conclusions In patients with ESCC aged ≥ 80 years, active cancer treatment was beneficial, and the results did not differ from those of younger patients.

Purpose: Smoking may have a protective role in developing ulcerative colitis (UC) but have the opposite effect on Crohn’s disease (CD). This study aimed to determine the risk of developing inflammatory bowel disease (IBD) according to smoking status and onset age of smoking. Materials and Methods: We collected data on the smoking experiences of participants aged 20–39 years who underwent biannual examinations provided by the Korean National Health Screening Program from 2009 to 2012. IBD diagnosis was identified using the National Health Insurance Service. The risk of IBD according to smoking status and onset age of smoking was analyzed after adjusting for major clinical variables. Results: During a median 10.59-year follow-up, the risk of UC in ex-smokers was significantly higher than that in non-smokers, and the earlier ex-smokers started smoking, the higher risk of UC [ex-smokers whose onset age of smoking was <20 years, adjusted hazard ratio (aHR) 1.928, 95% confidence interval (CI)=1.649–2.255; 20–24 years, aHR 1.728, 95% CI=1.541–1.939; 25–29 years, aHR 1.676, 95% CI=1.489–1.887; ≥30 years, aHR 1.226, 95% CI=1.010–1.486]. The risk of UC was significantly lower in current smokers whose onset age of smoking was 25–29 years than in non-smokers (aHR 0.825, 95% CI=0.709–0.959). The risk of CD did not differ according to smoking status and onset age of smoking. Conclusion Ex-smokers who started smoking at a young age have a high risk of UC, even after adjusting for the smoking amount.