Replicative senescence in endothelial cells is characterized by an irreversible cell cycle arrest and impaired endothelial function, contributing to vascular aging and cardiovascular disease. Natural compounds are being actively studied for their potential to delay cellular senescence and protect vascular health. Among them, rice bran has demonstrated several vascular benefits that are mainly attributed to gamma-oryzanol (γ-Orz), a major bioactive component in rice bran. However, its role in regulating endothelial replicative senescence and the underlying molecular mechanisms remain unclear. This study aimed to explore the protective effects of rice bran extract (RBE) and γ-Orz on replicative senescence in porcine coronary artery endothelial cells (PCAECs). Replicative senescence was modeled in PCAECs by serial passaging from P1 to P3 with varying concentrations of RBE and γ-Orz.Senescence was evaluated by measuring senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, oxidative stress, and the expression of cell cycle regulatory proteins. RBE and γ-Orz significantly reduced SA-β-gal activity, improved proliferation, and decreased oxidative stress in P3 cells, along with downregulation of senescence-related proteins p53, p21, and p16. Additionally, γ-Orz suppressed sodium-glucose co-transporter 2 expression, reduced NADPH oxidase overexpression, and restored eNOS levels. These findings indicate that RBE and γ-Orz delay endothelial senescence by alleviating oxidative stress, highlighting their potential to reduce cardiovascular disease risk associated with endothelial senescence.

Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

Purpose: Non-operative management (NOM) has emerged as a promising organ-preserving strategy for patients with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (CRT). However, no standardized treatment protocol has been established for watch-and-wait strategies. Materials and Methods: This prospective study evaluated oncological outcomes of NOM combined with 4 months of adjuvant capecitabine. Patients with resectable rectal cancer (≤ 8 cm from the anal verge, cT2-4 or N+) underwent CRT (50-54 Gy in 25-27 fractions with capecitabine). Eight weeks post-CRT, a multidisciplinary team assessed cCR. Patients achieving cCR received six cycles of capecitabine (2 weeks on/1 week off) and were actively monitored. Results: Among 89 patients receiving CRT (2018-2023), 17 (19.1%) achieved cCR and were included. The median age was 65 years, and 64.7% were male. Eleven (64.7%) completed all six cycles of adjuvant therapy. After a median follow-up of 31.4 months, 11 patients (64.7%) remained disease-free. Local regrowth occurred in six patients (35.3%) with 2- and 4-year rates of 34.5% and 47.6%, respectively. Five underwent radical surgery, and one received transanal excision with systemic chemotherapy. At the time of assessment, 15 patients (88.2%) showed no evidence of disease, while two (11.8%) received palliative chemotherapy. All patients were alive. Conclusion NOM with adjuvant capecitabine showed promising oncological outcomes, offering an alternative to passive watch-and-wait approaches. Further refinement through multidisciplinary strategies is warranted.

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.

Purpose: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets. Materials and Methods: Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM. Results: Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D. Conclusion This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

Purpose: Although human epidermal growth factor receptor 2 (HER2) positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy. Materials and Methods: The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed. Results: The analysis included 799 female patients. The median age was 51 years (range, 23 to 79 years), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n=238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% confidence interval [CI], 114.0 to 127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1 to 93.3), 97.5% (95% CI, 96.4 to 98.7), and 98.8% (95% CI, 98.0 to 99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease. Conclusion A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

Purpose: This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool’s effectiveness in elderly multiple myeloma (MM) patients to prevent under and overtreatment. Materials and Methods: This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022. Results: The median age was 77 years, and 73.0% of patients were classified at International Staging System stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.09 to 5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03 to 5.86; p=0.043) had a significantly higher risk of grade 3-4 non-hematologic toxicity, whereas the International Myeloma Working Group definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated. Conclusion The pilot study, which had a limited number of participants, did not demonstrate KG-7’s effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

Purpose: This study aimed to explore the practices, perceptions, and barriers related to specialty palliative care (SPC) referrals among oncologists in Korea, highlighting the clinical implications of early integration. Materials and Methods: A cross-sectional online survey targeting board-certified hemato-oncology specialists was conducted between August 1-25, 2024. The survey assessed referral practices, attitudes toward early SPC integration, referral criteria, barriers, and institutional characteristics. Results: A total of 227 oncologists participated (response rate, 36.7%). Among them, 68.7% reported frequent SPC referrals, with higher referral rates observed among younger physicians, those in tertiary hospitals, and institutions with in-house SPC teams (p < 0.001). Although 74.9% supported early SPC integration, referrals were often inconsistently timed, frequently occurring after disease progression or at the discontinuation of chemotherapy. For time-based referrals, the most commonly endorsed triggers were disease progression despite palliative second-line treatment and a prognosis of expected mortality within 6-12 months. Need-based referral triggers such as patient or family requests (96.5%), psychological distress (89.9%), or uncontrolled symptoms (83.3%), were also widely endorsed. The major barriers to early SPC integration included patient and family resistance (70.0%) and limited availability of SPC teams (34.4%). Conclusion This study emphasizes the importance of systematic efforts to promote timely SPC integration in Korea, including education to raise patient awareness, improved referral systems, and enhanced infrastructure. The positive attitudes toward early SPC among oncologists reflect a growing recognition of its value, highlighting the need for strategies that align with international standards.

Subglottic stenosis (SGS) and tracheal stenosis (TS) are rare conditions that can cause significant breathing difficulties and, if not properly managed, may lead to life-threatening complications. Despite their clinical importance, debate continues regarding the optimal management of adult SGS and TS, and no comprehensive guidelines have been established to date. The Korean Bronchoesophagological Society appointed a task force to develop clinical practice guidelines with the goal of providing evidence-based recommendations for managing SGS and TS in adults. The task force conducted a systematic review of the relevant literature by searching PubMed, Embase, and the Cochrane Library using predefined search terms aligned with key clinical questions. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which also informed the formulation and reporting of the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for eligible patients. After drafting the guidelines, feedback was obtained through Delphi questionnaires completed by members of the Korean Bronchoesophagological Society. Ultimately, the committee developed 17 evidence-based recommendations across four categories: initial evaluation, medical management, surgical treatment, and postoperative management and rehabilitation. These guidelines aim to support clinicians in delivering optimal care to adult patients with SGS and TS.

Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.