Purpose: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Materials and Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes.Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5,460 ESD cases from 5,250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Purpose: Atypical hyperplasia (AH) management remains controversial due to variable malignant disease progression rates. While Western studies report 10% to 25% upgrade rates, data from Asian populations, particularly from referral academic centers, are limited. We aimed to identify predictive factors for malignant upgrade in Korean women with AH at academic hospitals. Methods: This retrospective multi-institutional study analyzed 340 patients diagnosed with AH on initial biopsy who underwent subsequent excision at five Korean academic hospitals from 2000 to 2022. Malignant upgrade was defined as ductal carcinoma in situ or invasive cancer on the final pathology. Multivariate logistic regression was used to identify independent predictors of upgrades. Results: Among 340 patients (319 atypical ductal hyperplasia, 20 atypical lobular hyperplasia, and 1 mixed), 128 (37.6%) experienced a malignant upgrade, 98 (76.6%) to ductal carcinoma in situ, and 30 (23.4%) to invasive cancer. In multivariate analysis, multifocal atypia (odds ratio [OR], 25.61; 95% confidence interval [CI], 11.20–58.55; P<0.001) and Breast Imaging-Reporting and Data System 4c-5 lesions (OR, 11.02; 95% CI, 1.43–84.86; P=0.021) were significant predictors. Multifocal atypia showed an 84.4% upgrade rate. Core needle biopsy had higher upgrade rates than vacuum-assisted biopsy (45.2% vs. 20.0%; P<0.001). The upgrade rates decreased from 50% to 25% over the study period (P<0.05). Conclusion The 37.6% upgrade rate in this tertiary referral cohort exceeded that in Western reports, with multifocal atypia emerging as the strongest predictor. These findings support immediate excision for multifocal atypia while allowing individualized management for unifocal lesions with favorable imaging in Korean tertiary care settings.

Objectives: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes. Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5460 ESD cases from 5250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Purpose: The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy. Materials and Methods: Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m2 on days 1 and 8, cisplatin 70 mg/m2 on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety. Results: Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS. Conclusion Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.

Purpose: Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. Materials and Methods: The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. Results: Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). Conclusion The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Background: Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. Methods: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco’s modified Eagle’s medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. Results: SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. Conclusion These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Background: A healthcare system’s collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. Methods: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. Results: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. Conclusion In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Purpose: To assess the feasibility and short-term efficacy of maintenance enzalutamide following first-line docetaxel plus androgen deprivation therapy (ADT) in patients with high-volume, metastatic castration-naive prostate cancer (mCNPC). Materials and Methods: The present study included 38 consecutive patients with mCNPC who did not have disease progression with ADT plus docetaxel between October 2022 and October 2023. Patients received a switch maintenance therapy with enzalutamide until progression, unacceptable toxicity, or patient withdrawal. Endpoints included time to prostate-specific antigen (PSA) progression and safety. Results: Among the 38 patients, the median age was 68 years, and the most frequently observed metastatic site was bone (n=36), followed by lymph nodes (n=28), lung (n=8), and liver (n=1). The median duration of firstline docetaxel was 2.8 months (range, 2.7–5.0 months). At the time of commencing maintenance enzalutamide, the median PSA was 3.2 ng/mL (range, 0.01–258 ng/mL). Maintenance enzalutamide was generally welltolerated. A total of 11 patients (28%) discontinued enzalutamide, and the main reasons included adverse events (prolonged fatigue of grade 1 or 2, n=6), disease progression (n=3) and financial burdens (n=2). Median time to PSA progression was not reached, and 93% were PSA progression-free at 12 months. Conclusions Maintenance enzalutamide is a feasible treatment option with potential clinical benefit for patients with high-volume mCNPC who were progression-free after first-line ADT+docetaxel.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.