Purpose: This study investigated epidemiologic features of patients with pancreatic cancer in Korea, according to the histologic subtypes. Methods: The Korea Central Cancer Registry data on patients with pancreatic cancer from 1999 to 2019 were reviewed. The 101,446 patients with pancreatic cancer (C25 based on the International Classification of Diseases, 10th revision) were allocated according to the following morphological codes: A, endocrine; B, carcinoma excluding cystic and mucinous; C, cystic or mucinous; D, acinar cell; and E, sarcoma and soft tissue tumor. Results: The distribution of each pancreatic cancer subtype group in Korea from 1999 to 2019 was as follows: A, n = 3,101 (3.1%); B, n = 95,051 (93.7%); C, n = 2,856 (2.8%); D, n = 299 (0.3%); and E, n = 139 (0.1%). In group B, 49.2% of patients were aged >70 years, and half of them did not receive treatment within 4 months of diagnosis. In addition, only 30.9% of the patients were in the localized and regional stage in which surgical treatment was possible. Pancreatic cancer occurred more frequently in females than in males only in group C. Between 1999 and 2019, the average annual percentage changes in the age-specific incidence rates were positive in groups A (13.9%, P < 0.001), B (1.0%, P < 0.001), and C (6.5%, P = 0.025). Significant improvements in 5-year survival rates over time were observed in subtypes A, B, and C. Conclusion The subgroups of pancreatic cancer show different epidemiologic features, including incidences, treatment rates, and prognoses.

Purpose: Common bile duct (CBD) stone recurrence after laparoscopic CBD exploration (LCBDE) is relatively common. No studies have been conducted evaluating the safety and feasibility of re-do LCBDE in the treatment of recurrent CBD stones. Methods: This single-center retrospective study reviewed 340 consecutive patients who underwent LCBDE for CBD stones between January 2004 and December 2020. Patients with pancreatobiliary malignancies and those who underwent other surgical procedures were excluded. Results: Of the 340 included patients, 45 experienced a recurrence after a mean follow-up period of 24.2 months. Of them, 18 underwent re-do LCBDE, 20 underwent endoscopic intervention, 2 underwent radiologic intervention, and 5 underwent observation. Re-do LCBDE and initial LCBDE showed similar surgical outcomes in terms of operative time (113.1 minutes vs. 107.5 minutes, P = 0.515), estimated blood loss (42.5 mL vs. 49.1 mL, P = 0.661), open conversion rate (2.9% vs. 0%, P = 0.461), postoperative complication (15.3% vs. 22.2%, P = 0.430), and postoperative hospital stay (6.5 days vs. 6.4 days, P = 0.921). Comparing re-do LCBDE and nonsurgical treatment (endoscopic or radiologic), no statistically significant differences were noted in posttreatment complication (22.2% vs. 13.6%, P = 0.477), hospital stay (6.4 days vs.7.3 days, P = 0.607), and recurrence (50.0% vs. 36.4%, P = 0.385). The clearance rate was higher in the re-do LCBDE group than in the nonsurgical group (100% vs. 81.8%, P = 0.057). Conclusion Compared to initial LCBDE and endoscopic or radiological treatments, re-do LCBDE for recurrent CBD stones is a treatment option worth considering in selected patients.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

Purpose: This study investigated epidemiologic features of patients with pancreatic cancer in Korea, according to the histologic subtypes. Methods: The Korea Central Cancer Registry data on patients with pancreatic cancer from 1999 to 2019 were reviewed. The 101,446 patients with pancreatic cancer (C25 based on the International Classification of Diseases, 10th revision) were allocated according to the following morphological codes: A, endocrine; B, carcinoma excluding cystic and mucinous; C, cystic or mucinous; D, acinar cell; and E, sarcoma and soft tissue tumor. Results: The distribution of each pancreatic cancer subtype group in Korea from 1999 to 2019 was as follows: A, n = 3,101 (3.1%); B, n = 95,051 (93.7%); C, n = 2,856 (2.8%); D, n = 299 (0.3%); and E, n = 139 (0.1%). In group B, 49.2% of patients were aged >70 years, and half of them did not receive treatment within 4 months of diagnosis. In addition, only 30.9% of the patients were in the localized and regional stage in which surgical treatment was possible. Pancreatic cancer occurred more frequently in females than in males only in group C. Between 1999 and 2019, the average annual percentage changes in the age-specific incidence rates were positive in groups A (13.9%, P < 0.001), B (1.0%, P < 0.001), and C (6.5%, P = 0.025). Significant improvements in 5-year survival rates over time were observed in subtypes A, B, and C. Conclusion The subgroups of pancreatic cancer show different epidemiologic features, including incidences, treatment rates, and prognoses.

Purpose: Common bile duct (CBD) stone recurrence after laparoscopic CBD exploration (LCBDE) is relatively common. No studies have been conducted evaluating the safety and feasibility of re-do LCBDE in the treatment of recurrent CBD stones. Methods: This single-center retrospective study reviewed 340 consecutive patients who underwent LCBDE for CBD stones between January 2004 and December 2020. Patients with pancreatobiliary malignancies and those who underwent other surgical procedures were excluded. Results: Of the 340 included patients, 45 experienced a recurrence after a mean follow-up period of 24.2 months. Of them, 18 underwent re-do LCBDE, 20 underwent endoscopic intervention, 2 underwent radiologic intervention, and 5 underwent observation. Re-do LCBDE and initial LCBDE showed similar surgical outcomes in terms of operative time (113.1 minutes vs. 107.5 minutes, P = 0.515), estimated blood loss (42.5 mL vs. 49.1 mL, P = 0.661), open conversion rate (2.9% vs. 0%, P = 0.461), postoperative complication (15.3% vs. 22.2%, P = 0.430), and postoperative hospital stay (6.5 days vs. 6.4 days, P = 0.921). Comparing re-do LCBDE and nonsurgical treatment (endoscopic or radiologic), no statistically significant differences were noted in posttreatment complication (22.2% vs. 13.6%, P = 0.477), hospital stay (6.4 days vs.7.3 days, P = 0.607), and recurrence (50.0% vs. 36.4%, P = 0.385). The clearance rate was higher in the re-do LCBDE group than in the nonsurgical group (100% vs. 81.8%, P = 0.057). Conclusion Compared to initial LCBDE and endoscopic or radiological treatments, re-do LCBDE for recurrent CBD stones is a treatment option worth considering in selected patients.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: Tinnitus is a multifactorial condition with no universally accepted assessment guidelines. The Korean Tinnitus Study Group previously established consensus statements on the definition, classification, and diagnostic tests for tinnitus. As a continuation of this effort, this study aims to establish expert consensus on tinnitus assessment and treatment outcome evaluation, specifically tailored to the Korean clinical context. Methods: A modified Delphi method involving 26 otology experts from across Korea was used. A two-round Delphi survey was conducted to evaluate statements related to tinnitus assessment before and after treatment. Statements were rated on a scale of 1 to 9 for the level of agreement. Consensus was defined as ≥ 70% agreement (score of 7–9) and ≤ 15% disagreement (score of 1–3). Statistical measures such as content validity ratio and Kendall’s coefficient of concordance (W) were calculated to assess agreement levels. Results: Of the 46 assessment-related statements, 17 (37%) reached consensus, though overall pre-treatment assessments showed weak agreement (Kendall’s W = 0.319). Key areas of agreement included the use of the visual analogue scale, numeric rating scale, and validated questionnaires for pre-treatment evaluation. Five statements, such as the use of computed tomography, magnetic resonance imaging, and angiography for diagnosing pulsatile tinnitus, achieved over 90% agreement. For treatment outcome measurements, 8 of 12 statements (67%) reached a consensus, with moderate agreement (Kendall’s W = 0.513). Validated questionnaires and psychoacoustic tests were recommended for evaluating treatment effects within 12 weeks. While standardized imaging for pulsatile tinnitus and additional clinical tests were strongly recommended, full consensus was not achieved across all imaging modalities. Conclusion This study provides actionable recommendations for tinnitus assessment and treatment evaluation, emphasizing the use of standardized tools and individualized approaches based on patient needs. These findings offer a practical framework to enhance consistency and effectiveness in tinnitus management within Korean clinical settings.