Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.

Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.

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.

Purpose: The conventional method for evaluating inferior oblique overaction (IOOA) relies on subjective, qualitative grading. This study aimed to introduce and perform a pilot evaluation of a novel, objective, and quantitative measurement method for IOOA using a newly designed device, the interocular level difference gauge (IOLDG). Methods: Sixty-two consecutive patients (124 eyes) with intermittent exotropia, IOOA or superior oblique palsy were recruited. The degree of IOOA was measured using two methods: (1) the conventional subjective grading scale (+0 to +4) by two examiners (A and B); and (2) the objective IOLDG method by two examiners (C and D). The IOLDG utilizes a spectacle-like frame with a 1 mm-spaced horizontal grid to measure the interocular height difference of the inferior corneal margin in millimeters. Interobserver repeatability was assessed using the paired t-test and the intraclass correlation coefficient (ICC). Results: The conventional method showed a statistically significant difference between examiners (paired t-test, p = 0.002) and moderate repeatability (ICC, 0.749). In contrast, the IOLDG method showed no significant difference between examiners (paired t-test, p = 0.064) and demonstrated excellent repeatability (ICC, 0.903; p < 0.001). The correlation analysis established quantitative equivalents for the conventional grades: grade +1 corresponded to 1.04 ± 0.75 mm, grade +2 to 1.75 ± 0.60 mm, and grade +3 to 2.81 ± 0.75 mm. Conclusions The IOLDG provides a highly repeatable, objective, and quantitative measurement for IOOA, largely independent of the examiner’s subjective judgment. This simple, chair-side method offers superior reliability compared to the conventional grading scale.

Peripheral nerve injury and oxidative stress can severely impair Schwann cell function by disrupting the expression of key myelin proteins, promoting intracellular lipid accumulation, and damaging mitochondrial integrity. These pathological changes are central to various neurodegenerative disorders and chemotherapy-induced peripheral neuropathy, yet effective therapeutic approaches remain limited. Clemastine, an FDA-approved antihistamine with known remyelination-enhancing effects in the central nervous system, has not been thoroughly explored for its protective role in peripheral myelinating cells under oxidative stress. In this study, we investigated the time-dependent protective effects of Clemastine in S16 Schwann cells exposed to hydrogen peroxide (H2O2) as a model of oxidative injury. Treatment with Clemastine significantly increased the expression of myelin-related proteins such as myelin protein zero (MPZ), alongside in increase in AMPK phosphorylation at Thr172. However, co-treatment with H2O2 ensued oxidative damage, leading to reduced pAMPK(T172) and MPZ expression, elevated ROS levels, and increased lipid accumulation. These results suggest that oxidative stress can attenuate Clemastine’s effects in association with disrupted redox balance and energy metabolism. Subsequent treatment with Metformin (Met), a pharmacological activator of AMPK, was associated with partial recovery from H2O2-induced oxidative damage. Overall, our findings support the potential of a combinatorial approach using Clemastine and Met to promote myelin-related protein expression and lipid metabolic balance in Schwann cells under oxidative stress, rather than establishing a definitive synergistic or causal mechanism.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.