Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Purpose: We compared short-term clinical outcomes after cataract surgery with implantation of a novel refractive extended depth-of-focus TECNIS PureSee intraocular lens (IOL) between patients with stage 1 epiretinal membrane (ERM)—characterized by a thin membrane over the macula with preserved foveal depression―and those with a normal retina. Methods: This retrospective study included 60 eyes of 60 patients who underwent cataract surgery with implantation of the TECNIS PureSee IOL between January 2024 and January 2025: 30 eyes with stage 1 ERM and 30 eyes with a normal retina. Preoperative characteristics, including age, sex distribution, cataract severity, corrected distance visual acuity (CDVA), and higher-order aberrations, were compared between groups, as were IOL power and target refraction. Postoperative outcomes at 1 month―including CDVA, uncorrected distance, intermediate, and near visual acuity, ocular aberrations, and contrast sensitivity―were evaluated. Results: There were no significant differences in preoperative characteristics, such as age, sex distribution, cataract grade, CDVA, higher-order aberrations, IOL power, or target refraction between the two groups. At 1 month postoperatively, CDVA, uncorrected distance, intermediate, and near visual acuity, higher-order aberrations, and contrast sensitivity exhibited no significant differences between groups. Conclusions In this short-term analysis, the PureSee IOL demonstrated comparable efficacy and safety in cataract patients with stage 1 ERM to those with a normal retina.

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.

Mutations in p53 have been implicated in poor prognosis and reduced sensitivity to 5-fluorouracil (5-FU) treatment in colon cancer.While p53-dependent mechanisms have been widely studies, less is known about how p53 deficiency reshapes cellular signaling and contributes to 5-FU resistance. In this study, we aimed to profile proteomic alterations associated with p53 loss by comparing colon cancer cells with and without p53 expression. Differentially expressed proteins (DEPs) related to cell cycle regulation were of particular interest, as 5-FU treatment induced G1 phase arrest in HCT116 p53 wild-type (WT) cells, whereas p53 knockout (KO) cells predominantly showed S phase arrest. We identified several DEPs in p53 deficient cells following 5-FU treatment. Notably, F3 expression was increased, while aldehyde dehydrogenase family 1 member A4 (ALDH1A3), histone deacetylase 2 (HDAC2), and protein S100-A4 (S100A4) were decreased. The expression levels of these genes were associated with overall survival in patients with colon cancer. These findings highlight proteomic alterations linked to p53 deficiency and support a proposed model in which differential regulation of specific proteins may be associated with reduced sensitivity to 5-FU, providing a basis for future mechanistic and functional studies.

Osteoarthritis (OA) is a prevalent, chronic joint disorder characterized by cartilage degradation, synovial inflammation, and extracellular matrix (ECM) remodeling, yet disease-modifying therapies remain elusive. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, and cellular senescence, characterized by growth arrest and a senescence-associated secretory phenotype (SASP), as central contributors to OA pathogenesis. Ferroptotic chondrocytes release reactive lipid species and damage-associated molecular patterns (DAMPs) that induce paracrine senescence in neighboring cells, while senescent cells amplify oxidative stress and ferroptotic susceptibility, forming a self-perpetuating feed-forward loop that accelerates tissue degeneration. Histological, molecular, and in vivo studies demonstrate iron accumulation, lipid peroxidation, glutathione peroxidase 4 (GPX4) depletion, and SASP factor secretion in human OA cartilage, synovium, and animal models, linking these processes to ECM breakdown and joint inflammation. Targeted interventions, alone or in combination, can disrupt this pathological loop, preserve chondrocyte viability, reduce SASP-mediated inflammation, and mitigate cartilage damage. Integration of biomarker-guided patient stratification, advanced imaging, and spatial transcriptomic profiling may enable precision-targeted, disease-modifying therapies. Therefore, elucidating the crosstalk between ferroptosis and senescence offers a conceptual and translational framework for shifting OA management from symptomatic relief toward preservation of joint integrity and long-term disease modification.

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.

Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.

Background: Liver transplantation (LT) is the standard treatment for end-stage liver disease; however, it can lead to biliary strictures in 25%–30% of cases. We aimed to develop a biodegradable stent loaded with paclitaxel that could be inserted during surgery without requiring removal. We evaluated the safety and efficacy of this stent using a porcine model. Methods: Fourteen pigs underwent simulated ischemic injury during LT, and a biodegradable paclitaxel-eluting stent was inserted after duct-to-duct anastomosis.Pigs were divided into four groups: no stent (n=3), bare stent (n=3), 300 µg paclitaxel stent (n=4), and 900 µg paclitaxel stent (n=4). After 3 months of follow-up, autopsies were conducted to obtain common bile duct tissue samples, and inflammation and fibrosis thicknesses were assessed under a microscope. Results: Most tissues had resolved the inflammatory reactions by the 3-month mark. The thinnest fibrosis thickness was observed in the 900 µg group (359.08±167.23 µm); however, no statistical significance was observed. Conclusion This study demonstrated the safety of paclitaxel-eluting biodegradable biliary stents and their positive effects on fibrosis in an ischemic bile duct porcine model. This biodegradable stent represents a potential approach for overcoming the complications associated with biliary strictures after LT.

Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.