Background: The 5th edition of WHO classification (WHO5) renamed pituitary adenoma as pituitary neuroendocrine tumor (PitNET), aligning with NET nomenclature from other sites.This study investigated the clinicopathological characteristics of surgically resected PitNET based on the WHO5 classification. Methods: A retrospective analysis was conducted on 210 cases of surgically resected and pathologically confirmed PitNET treated at Seoul National University Hospital from 2021 to 2023. The tumors were graded using the French five-tiered grading system proposed by Trouillas et al. Detailed information on grade 3 metastatic PitNET cases is provided. Results: The cohort’s median age was 53 years (age range: 8–84 years), with a male-to-female ratio of 1:1.1. Mean tumor size was 2.5 cm (range: 0.1–6.5 cm). Macroadenomas predominated (91.9%), followed by microadenoma (6.7%), and giant tumors (1.4%), with 56.2% extending suprasellarly. SF1-lineage PitNET was most prevalent (49.5%), followed by PIT1-lineage (23.3%) and TPIT-lineage (17.1%). Null cell tumors (5.7%) and unclassified plurihormonal PitNET (4.3%) were rare. PIT1-lineage PitNET comprised somatotrophs (47.0%), mature plurihormonal PIT1 lineage tumors (18.4%), thyrotrophs (16.3%), immature PIT1-lineage tumors (16.3%), and acidophilic stem cell tumors (n=1), however, there was no lactotroph PitNET. Among SF1-lineage tumors, serologically non-functional tumors predominated (79%), while, immunohistochemically, 71.2% were gonadotrophin (FSH/LH)-positive.Tumor grades by the French five-tiered classification system were distributed as follows:grade 1a (58.1%), 1b (17.6%), 2a (16.2%), 2b (7.1%), and 3 (1.0%). Two cases of metastatic corticotroph PitNET were observed: The first case, a 50-year-old female had liver metastasis and experienced tumor recurrence 7 years after his initial diagnosis of PitNET, ultimately dying 9.5 years later. The primary tumor appeared bland, but the metastatic tumor exhibited a high mitotic rate and a Ki-67 index was 48%. The second case involved a 44-year-old man with metastases to the paranasal sinus, liver, and bone. Despite showing initial bland histopathology and a low proliferation index, this tumor displayed aggressive behavior.The patient had a recurrence 1.5 years after diagnosis, with additional metastases emerging 3 years later. He survived for 8.0 years and is currently disease-free following surgery, chemotherapy, and radiotherapy. Conclusion This comprehensive analysis of surgically resected PitNETs using the new WHO5 classification provides valuable insights into the distribution of the subtypes in the surgical cohort. Key findings were the predominant gonadotroph PitNET, the absence of lactotroph PitNET, and the rarity of null cell tumors in surgical cases. The lack of lactotrophs was mainly due to medical treatment. This study highlights the discrepancy between serological and immunohistochemical findings of SF1-lineage PitNETs. While metastatic PitNET cases showed poor prognosis, the predictive value of the French grading system for PitNET requires further validation through extended follow-up.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Objectives: This study examined the potential of a new analytical framework for the Korea Community Health Survey (KCHS) with classification criteria for the sub-national governmental level, the degree of urbanization including an urban-rural multimodal category, and population size as a more effective tool to address local health problems and deduce practical implications. Methods: Retrospective survey data from 2023 KCHS were obtained. Frequency analyses were performed for self-rated good health status, current smoking status, and unmet medical needs as proxies for health status, as well as health behavior and healthcare utilization, utilizing individual weights to represent national community residents. Results: We established a new classification of local governments into 7 types to facilitate regional comparisons. These local government types are presumably composed of populations showing statistically significant differences in demographic characteristics. There were evident differences in health status, health behavior, and healthcare utilization in comparisons of groups categorized by local government types. Conclusions This study suggests that regional disparities can be analyzed using a new typology of local governments. This practically effective approach could be used in decision-making for community-centered health projects in terms of community health planning. Future research should conduct analyses of KCHS data that use these 7 local government types to comprehensively reflect regional characteristics.

Objectives: Lonely death is defined as “a person living in a state of social isolation, disconnected from family, relatives, and others, who dies from suicide, illness, or other causes”. This study investigated the characteristics of individuals who die alone in Korea. Methods: We constructed a database of lonely death cases by linking data from the Korea Crime Scene Investigation Unit of the Korea National Police Agency with National Health Insurance Service (NHIS) records. A descriptive analysis was performed to evaluate the demographics, underlying diseases, and healthcare utilization patterns among lonely death cases. Results: Among the 3122 individuals identified as lonely death cases, 2621 (84.0%) were male and 501 (16.0%) were female. The most common age group was 50-59 years (n=930, 29.8%). The NHIS covered 2161 individuals (69.2%), whereas 961 individuals (30.8%) were enrolled in Medical Aid (MA). The highest number of lonely deaths occurred in Seoul areas, with 1468 cases (47.0%). Mood disorders were diagnosed in 1020 individuals (32.7%), and various alcohol-related diseases, including alcoholic liver disease, were also observed. Outpatient visits increased leading up to death but declined in the final 3 months, while hospitalizations decreased and emergency room visits slightly increased. Conclusions Most lonely death cases involved male in their 50s, with a disproportionately high number of MA beneficiaries compared to the general population. Many of these individuals also experienced mental health issues or alcohol-related disorders. Preventing social isolation and strengthening social safety nets are critical to reducing the occurrence of lonely deaths.

Background and Objectives: Pediatric chronic rhinosinusitis (CRS) significantly affects children’s quality of life and learning abilities. This study aimed to evaluate the postoperative outcomes in pediatric patients who underwent functional endoscopic sinus surgery (FESS) for CRS. Methods: A retrospective review was conducted on pediatric patients who underwent FESS for CRS at 11 university hospitals. The inclusion criteria were patients under 20 years old with bilateral disease who were operated on between January 2005 and December 2021. The data collected included demographics, clinical history, blood tests, preoperative computed tomography, and preoperative and postoperative symptom control. The Kruskal-Wallis and Fisher exact tests were used to compare the quantitative and qualitative data, respectively. Results: In total, 213 patients were enrolled. The mean age was 13.4±3.0 years, and 145 (68.1%) were male. One hundred sixty-four patients (77.0%) had nasal polyps and 33 patients (15.5%) underwent revision FESS. The preoperative symptoms, in order of prevalence, included nasal obstruction (87.8%), rhinorrhea (71.8%), a sense of postnasal drip (58.2%), hyposmia (44.6%), cough (24.4%), and facial fullness (18.3%). These symptoms were significantly alleviated for up to 3 years after surgery (p<0.001). At the time of the last follow-up, 121 patients (56.8%) were controlled, 80 (37.6%) were partly controlled, and 12 (5.6%) were uncontrolled. Patients in the uncontrolled group had higher Lund-Mackay scores, longer follow-up durations, and more instances of revision surgery compared to those in the controlled and partly controlled groups. When age was categorized into three groups, those aged 16 years or older tended to have lower Lund-Mackay scores and better control. Conclusion FESS significantly improves both the postoperative symptoms and the long-term quality of life in pediatric CRS patients. Better symptom control is associated with older age and a lower disease burden.

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: This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules. Methods: This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images. Results: Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity. Conclusion CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

Background/Aims: The study investigated the incidence, risk factors, and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with ulcerative colitis (UC). Methods: This single-center retrospective study included patients with UC who underwent total proctocolectomy with ileal pouch-anal anastomosis at the Asan Medical Center in Korea between January 1987 and December 2022. The primary outcomes were endoscopic remission and pouch failure. The Cox’s proportional hazard model was used to identify the risk factors for CARP. Results: The clinical data of 232 patients were analyzed. The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). Among 74 patients (31.9%) with chronic pouchitis (CP), 31 (13.4%) had CARP, and 43 (18.5%) had chronic antibiotic-dependent pouchitis (CADP). The most frequent endoscopic phenotype was focal inflammation of the pouch (CP, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to use concomitant probiotics than patients with CADP (29.0% vs 72.1%, p<0.01). The endoscopic remission rate of CP, CARP, and CADP was 14.9%, 9.7%, and 18.6%, respectively.The pouch failure rate associated with CP, CARP, and CADP was 13.5%, 16.1%, and 11.6%, respectively. Current smoking status (adjusted hazard ratio [aHR], 2.96; 95% confidence interval [CI], 1.27 to 6.90; p=0.01) and previous use of biologics/small molecules (aHR, 2.40; 95% CI, 1.05 to 5.53; p=0.04) were significantly associated with CARP development. Conclusions UC patients who were current smokers and previously used biologics/small molecules had a higher risk of developing CARP. Concomitant use of probiotics was less likely to be associated with CARP development.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.