Background/Aims: Esophageal transit scintigraphy is a non-invasive nuclear medicine imaging modality for people with esophageal transit problems. In particular, changes in esophageal motor function can be evaluated non-invasively before and after the treatment in patients undergoing peroral endoscopic myotomy (POEM) for achalasia. This study compared the changes in several parameters of esophageal transit and manometry in patients with achalasia who underwent POEM. Methods: This study retrospectively analyzed prospectively collected data from POEM participants. We included 38 patients with achalasia who underwent high-resolution manometry and esophageal transit scintigraphy before POEM and after POEM from 2016 to 2023. Results: All patients had clinical treatment successfully (Eckardt score < 3). Lower esophageal sphincter (LES) pressures were significantly reduced after POEM, including basal resting LES pressure and integrated relaxation pressure (P < 0.001).Esophageal emptying, as assessed by the residual fraction of retained radioactivity at 10 seconds after isotope ingestion, improved from 54.3% to 27.3% (P < 0.001). Analysis of the change in time-to-peak on the time-radioactivity curve showed that it shortened significantly in the upper and middle portions of the esophagus (P < 0.05) but not in the lower portion.The Eckardt symptom score significantly correlated with pre-POEM integrated relaxation pressure (P < 0.05). Post-POEM, the symptom score significantly correlated with time-to-peak of the upper portion of the esophagus (P < 0.05). Conclusions Patients with achalasia who received POEM showed improved not only manometric LES parameters but also esophageal transit. Analysis of the radiation curve’s time-to-peak showed that improved retention in the upper portion is an indicator of symptoms improvement in patients who underwent POEM.

The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.

The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

South Korea’s current healthcare system stands at a critical crossroads that will determine whether it can progress in a better direction over the next decade. Behind the relatively stable level of population health that has been maintained until now, it has become clear that the deterioration of patient experiences, the risk of collapse in critical emergency medical services, the burnout of healthcare providers, and the crisis in the sustainability of healthcare finances have all accumulated simultaneously. This crisis can no longer be overcome by partial fixes or short-term measures alone. The answer to what needs to change first must begin with a reaffirmation of what the healthcare system should aim for. Ultimately, what needs to be changed now is not an individual policy, but the criteria and priorities through which we view healthcare. The focus must shift from what to provide more of, to questioning what holds greater social value. If such a shift does not begin now, in ten years we won’t face a better healthcare system, but care enmeshed in a deeper crisis. Now is precisely the time to fundamentally define the direction of the healthcare system.

Myopia, particularly high myopia, is a significant risk factor for several ocular pathologies including cataract, glaucoma, and retinal detachment. Excessive axial elongation associated with high myopia can induce biomechanical stretching, increasing the risk of serious complications like posterior staphyloma and myopic maculopathy. Global meta-analyses estimate that approximately 10 million people were visually impaired due to myopic maculopathy in 2015, with 3 million being blind. Recent nationwide surveys in South Korea revealed a prevalence of 65.4% for myopia and 6.9% for high myopia in children and adolescents, highlighting the urgent need for effective management. Delaying the onset and slowing the progression of myopia during childhood and adolescence is crucial for reducing the potential lifetime risk of these complications. This consensus statement, prepared by the Korean Myopia Society for the Korean Association for Pediatric Ophthalmology and Strabismus (KAPOS), reviews the current evidence for myopia control interventions and provides management strategies applicable to the South Korean clinical setting. Key interventions covered include lifestyle modifications (outdoor time, near work adjustment), optical methods (myopia-control spectacle lenses, dual-focus soft contact lenses, orthokeratology), and pharmacologic treatment (low-concentration atropine), as well as combination therapies. The statement also addresses patient selection, treatment outcome evaluation using spherical equivalent and axial length changes, and the crucial aspects related to treatment cessation and the rebound effect.

Background: Epidermal growth factor (EGF) is widely applied in dermatology for its regenerative effects; however, its clinical utility is limited by low stability and high production costs.To overcome these limitations, we developed a novel probiotic-derived epidermal growth factor (pEGF) by engineering Pediococcus pentosaceus CBT SL4 to express and secrete EGF. Objective: To investigate the anti-photoaging effects of topical pEGF in a ultraviolet B (UVB)-irradiated mice by assessing histological and molecular changes related to collagen synthesis, extracellular matrix (ECM) remodeling, oxidative stress, and inflammation. Methods: SKH1 hairless mice were exposed to UVB for twelve weeks to induce photoaging and treated with topical 10% pEGF cream from week 9 to 12. Skin samples were analyzed using dermoscopy, histology, immunohistochemistry, quantitative real-time polymerase chain reaction, western blotting, and proteomics to evaluate morphological and molecular alterations in ECM components and inflammatory markers. Results: Topical pEGF treatment improved skin texture and reduced wrinkles. Histological evaluation revealed that EGF significantly attenuated UVB-induced epidermal thickening and restored collagen density, with the strongest effects observed in the pEGF group. Molecular analysis showed downregulation of matrix metalloproteinases (MMPs; MMP-1, MMP-3), upregulation of collagen (type I collagen, type III collagen) and tissue inhibitors of metalloproteinases (TIMPs; TIMP-1, TIMP-2). Additionally, pEGF reduced pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β) and oxidative stress markers. Conclusion pEGF demonstrated potent anti-photoaging effects through ECM restoration, inflammation modulation, and barrier reinforcement. These findings support the therapeutic potential of pEGF as a stable, cost-effective alternative to conventional EGF in dermatological applications.

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Microglia are the resident immune cells of the brain; they respond rapidly to inflammatory stimuli and contribute to the progression of neurodegenerative diseases. Receptor-interacting protein kinase 3 (RIPK3) is known to mediate pro-inflammatory signaling and necroptosis, a form of regulated necrotic cell death. However, the role of RIPK3 in microglial activation remains unclear. This study aimed to investigate the role of RIPK3 in both in vitro and in vivo models of neuroinflammation and necroptosis using a selective RIPK3 inhibitor, GSK872. In lipopolysaccharide (LPS)-injected mice, GSK872 attenuated microglial activation, decreased the expression of pro-inflammatory mediators, and reduced the phosphorylation of RIPK3 and mixed lineage kinase domain-like protein (MLKL). In BV2 microglial cells, GSK872 suppressed the production of inflammatory mediators under both inflammatory and necroptotic conditions induced by LPS or LPS/Z-VAD. In particular, GSK872 reduced necroptosis-associated cell death and the release of HMGB1 and IL-1 in LPS/Z-VAD-treated cells. Detailed mechanistic studies revealed that GSK872 inhibits the c-Jun N-terminal kinase (JNK) pathway, while pharmacological inhibition of JNK using SP600125 recapitulates the effects of GSK872 on inflammatory and necroptotic markers. These results indicate that JNK plays a critical role in mediating the effects of GSK872. Notably, IL-1 released during necroptosis appears to contribute modestly to the phosphorylation of JNK and MLKL, indicating a potential feedback mechanism that reinforces necroptotic signaling. Our findings provide compelling evidence that the inhibition of RIPK3 by GSK872 alleviates neuroinflammatory responses and necroptotic cell death by modulating JNK signaling in activated microglia, offering a promising therapeutic strategy for neurodegenerative diseases.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.