Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

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: We developed a simplified variant of the ADV score, the AFP-PIVKAII (AP) score for post-transplant hepatocellular carcinoma (HCC) prognosis, which considers only AFP and PIVKA-II levels excluding morphometric tumor size information from the ADV score. This study investigated the prognostic performance of the AP score in predicting HCC recurrence and overall survival (OS) after living donor liver transplantation (LDLT). Methods: We analyzed 843 patients with HCC who underwent LDLT between 2006 and 2015, assessing HCC recurrence and OS in relation to AP score. Results: The median pretransplant AFP and PIVKA-II levels were 12.8 ng/mL and 27 mAU/mL, respectively. The median and mean AP scores were 2.6 log (range: 0.6–9.2 log) and 2.9±1.1 log, respectively. The 5-year time-dependent area under the receiver operating characteristic curve for the AP score in predicting post-transplant HCC recurrence was 0.672 (p<0.001). HCC recurrence and OS curves along AP score intervals of 1.0 log showed statistical differences in accordance with the AP scores (both p<0.001). Using a Youden index J-derived AP score cutoff of 4.0 log, two-tiered groups (ADV <4.0 log vs. ADV ≥4.0 log) showed statistically significant differences in HCC recurrence and OS (both p<0.001). Harrell’s c-indices for AP score with cutoff of 4.0 log and ADV scores with cutoff of 5.0 log regarding HCC recurrence and OS were similar. Conclusion The AP score functions as an integrated surrogate marker for predicting post-transplant outcomes in patients with HCC undergoing LDLT. It may serve as a simplified alternative to the ADV score, particularly in patients with small HCCs.

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.

Purpose: Older cancer patients face unique challenges due to age-related physiological changes, increasing their vulnerability to treatment-related toxicities. Geriatric assessment (GA) is a validated tool for optimizing care, yet there is no consensus on integrating geriatric interventions into oncology. This study evaluates the feasibility of a tailored onco-geriatric intervention model incorporating the KG-7 screening tool. Materials and Methods: This prospective study included 30 patients aged ≥ 70 years with solid tumors undergoing adjuvant or palliative chemotherapy. Patients scoring ≤ 5 of KG-7 were eligible. Tailored interventions incorporating KG-7 included polypharmacy, functional status, mobility, nutrition, cognition, emotional well-being, insomnia, social support, and medical problem. KG-7, GA, and quality of life (QoL) were followed at 12 weeks. Results: Participants (median age, 79.5 years) had colon (43.3%), pancreatic (23.3%), or gastric cancer (23.3%). At baseline, most patients showed independent activities of daily living (100%)/instrumental activities of daily living (90%). However, 93.3% had abnormal GA. Particularly, 86.7% were either malnourished or at risk of malnutrition. The most frequently identified intervention needs included polypharmacy (70.0%), nutritional support (60.0%), and emotional well-being (50.0%) with high adherence (100.0%, 88.9%, and 46.7%, respectively). At 12 weeks, KG-7 scores improved in 43.8% of patients, and 69.2% of GA domains were improved. QoL analysis revealed modest improvement in Global Health Status (mean difference, 6.3; p=0.176). One-year survival rates were 92.3% and 79.4% for adjuvant and palliative groups, respectively. Conclusion The onco-geriatric intervention model incorporating KG-7 demonstrated high feasibility and potential to enhance clinical outcomes. Future studies should validate this approach in randomized trials to optimize care for older cancer patients.

Purpose: To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers. Methods: A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals. Results: The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence. Conclusion The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.

Background: Human muscle satellite (stem) cells (MuSCs) are essential for investigating muscle physiology, regeneration, and disease mechanisms. Primary cultures derived directly from human tissues offer a more physiologically relevant model than immortalized cell lines. However, the isolation and characterization of MuSCs from human upper limb tissues are limited. Therefore, this study aimed to establish and characterize a primary culture system for MuSCs obtained from human upper limb muscle tissue. Methods: Human muscle tissues were obtained from upper limb surgical specimens. Muscle samples were mechanically and enzymatically dissociated to isolate muscle-derived cells, which were cultured under standard growth conditions. Cell morphology and proliferation were monitored during the culture period. Myogenic characteristics were assessed by examining the expression of muscle-specific markers including myogenic regulatory factors and structural proteins. Additionally, myogenic differentiation capacity was evaluated by inducing differentiation and analyzing the formation of multinucleated myotubes. Results: Primary MuSCs were isolated from human upper limb tissues and expanded in vitro. The cultured cells exhibited a typical spindle-shaped morphology and demonstrated significant proliferative capacity. Characterization confirmed the expression of myogenic markers, indicating the presence of muscle-derived precursor cells. Following induction of differentiation, the cells formed multinucleated myotube-like structures and expressed muscle proteins associated with differentiation, highlighting their potential for myogenic differentiation. Conclusion This study established a reliable protocol for isolating and culturing MuSCs from human upper limb tissues. Cultured cells displayed typical myogenic characteristics and differentiation capacity, indicating that this model could be a valuable platform for studying human muscle biology and potential therapeutic applications.

Background: One-lung ventilation (OLV) during thoracic surgery frequently requires approximately 100% oxygen, imposing the risk of hyperoxemia. This study aimed to assess whether oxygen reserve index (ORI)-guided fraction of inspired oxygen (FiO2) adjustment can reduce the incidence of hyperoxemia in children undergoing lung resection. Methods: This prospective, randomized controlled trial enrolled children aged < 7 years scheduled for thoracoscopic lung resection. The participants were randomly assigned to either a conventional group (FiO2 adjusted based on arterial blood gas analysis [ABGA]) or an ORI group (FiO2 titrated to maintain an ORI target of 0.15). ABGA was performed 10 and 30 min after the start of OLV (T1 and T2). The primary outcome was the incidence of hyperoxemia 30 min after OLV (T2). Results: Data from 64 children (31 conventional, 33 ORI groups) were analyzed. The incidence rate of hyperoxemia at T2 was similar between the conventional and ORI groups (54.8% vs. 60.6%, P = 0.801). However, partial pressure of arterial oxygen at T1 was significantly lower in the ORI group than in the conventional group (214.6 ± 65.5 mmHg vs. 268.8 ± 92.7 mmHg, P = 0.014). The ORI group demonstrated a lower time-weighted average FiO2 during OLV (0.79 ± 0.12 vs. 0.87 ± 0.09, P = 0.004). The ORI group required more rescue interventions than the conventional group and experienced fewer episodes of hypoxia. Conclusions ORI-guided FiO2 adjustment does not significantly reduce the incidence of hyperoxemia in children undergoing OLV but reduces time-weighted FiO2 and hypoxic events.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Background: Studies on whether donor-to-recipient sex match status affects long-term survival after liver transplantation (LT) have yielded contradictory results. This study evaluated whether donor-to-recipient sex match status influenced long-term survival after living donor liver transplantation (LDLT) or deceased donor liver transplantation (DDLT) at a high-volume center. Methods: The study included 6,664 patients who underwent primary LT between January 2000 and December 2022 at our institution. Patients were divided into four groups according to donor-to-recipient sex match status: male-to-male (n=3,427 [51.4%]), male-to-female (n=1,152 [17.3%]), female-to-male (n=1,385 [20.8%]), and female-to-female (n=700 [10.5%]). Results: Regarding clinical characteristics, the four groups differed significantly regarding background liver disease (P<0.001), model for end-stage liver disease score (P<0.001), serum protein induced by vitamin K absence or antagonist II level (P=0.003), presence of concurrent hepatocellular carcinoma (HCC; P<0.001), and type of LT (P=0.003). Overall survival (OS) of all LT recipients did not differ significantly among the groups (P=0.377). Donor-to-recipient sex match status did not affect long-term OS in either LDLT (P=0.176) or DDLT (P=0.220) groups. In addition, sex match status did not significantly influence posttransplant OS among patients who underwent LDLT without HCC (P=0.464), LDLT with HCC (P=0.236), DDLT without HCC (P=0.338), or DDLT with HCC (P=0.818). Conclusions Donor-to-recipient sex match status does not significantly affect posttransplant patient survival or HCC prognosis after LDLT or DDLT.