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.

Purpose: This study evaluated long-term trends in gastric cancer epidemiology and survival with a focus on conditional relative survival (CRS). Materials and Methods: Using the Korea Central Cancer Registry, we analyzed 665,184 patients who were newly diagnosed with gastric cancer between 1999 and 2022.The study period was divided into four intervals: Period I (1999–2005), Period II (2006–2011), Period III (2012–2017), and Period IV (2018–2022). Temporal trends in the incidence and mortality were assessed using crude and age-standardized rates. Relative survival was estimated using the Ederer II method, and the 5-year CRS was calculated according to the survival duration after diagnosis. Results: The incidence of gastric cancer increased until 2011 and subsequently declined, with a marked decrease observed in 2020. Individuals aged ≥70 years consistently had the highest incidence rates. Mortality rates showed a sustained decline throughout the study period. The overall 5-year relative survival improved from 69.8% in Period II to 78.4% in Period IV. The 5-year CRS increased from 86.1% at 1 year after diagnosis to 96.3% at 5 years.Patients with localized stage maintained a 5-year CRS above 95% at 1 year after diagnosis, whereas those with regional and distant stages showed 5-year CRS that consistently remained below 95%. Conclusions The incidence and mortality rates of gastric cancer in Korea have declined over the past two decades, accompanied by improved survival outcomes. The CRS analysis suggests that long-term follow-up is warranted, with the optimal duration varying according to patient characteristics.

Genetic variation in the leptin receptor (LEPR) gene has been implicated in metabolic regulation, while the gut microbiome and circulating metabolites are increasingly recognized as mediators of host metabolic phenotype. However, the systems-level interactions among LEPR genotypes, gut microbial composition, and serum metabolomic profiles remain poorly understood, particularly in healthy individuals. We conducted a cross-sectional study involving 37 healthy Korean adults. Three LEPR single nucleotide polymorphisms (rs1137101, rs1173100, rs790419) were genotyped. Untargeted metabolomics of fasting serum was performed using gas chromatography–time-of-flight mass spectrometry, and gut microbiome composition was profiled by 16S rRNA gene sequencing. Statistical analysis included principal component analysis, Mann–Whitney U tests, and Spearman correlations. Network analysis integrating microbiome, metabolomic, and clinical phenotype data was conducted using Cytoscape. A total of 54 serum metabolites were identified. LEPR genotypes, particularly rs1137101 and rs1173100, were associated with differences in metabolites such as pimelic acid, malonic acid, and 2,4-dihydroxybutyric acid. Firmicutes negatively correlated with saturated fatty acids and organic acids, whereas Actinobacteria positively correlated with cholesterol and amino acids. Network analysis revealed indole-3-acetate and cholesterol as central nodes linking microbial taxa with body mass index and leptin levels. However, no direct molecular pathways connecting leptin or its receptor were identified. LEPR genetic variation is associated with distinct serum metabolomic patterns and microbiome–host networks in healthy adults. Although no direct leptin signaling links were found, network-level associations suggest indirect genetic influences on metabolic states through microbiome–metabolome interactions.These findings advance understanding of personalized metabolic regulation and gene–microbiome interplay.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

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.

Background: Shortage of organ donors in the Republic of Korea has become a major problem. To address this, it has been questioned whether heart transplant (HTx) allocation should be modified to reduce priority of older patients. We aimed to evaluate post-HTx outcomes according to recipient age and specific pre-HTx conditions using a nationwide prospective cohort. Methods: We analyzed clinical characteristics of 628 patients from the Korean Organ Transplant Registry who received HTx from January 2015 to December 2020. Enrolled recipients were divided into three groups according to age. We also included comorbidities including ambulatory status. Non-ambulatory status was defined as pre-HTx support with either extracorporeal membrane oxygenation, continuous renal replacement therapy, or mechanical ventilation. Results: Of the 628 patients, 195 were < 50 years, 322 were 50–64 years and 111 were ≥ 65years at transplant. Four hundred nine (65.1%) were ambulatory and 219 (34.9%) were nonambulatory. Older recipients tended to have more comorbidities, ischemic cardiomyopathy, and received older donors. Post-HTx survival was significantly lower in older recipients (P = 0.025) and recipients with non-ambulatory status (P < 0.001). However, in contrast to non-ambulatory recipients who showed significant survival differences according to the recipient’s age (P = 0.004), ambulatory recipients showed comparable outcomes (P = 0.465). Conclusion Our results do not support use of age alone as an allocation criterion. Transplant candidate age in combination with some comorbidities such as non-ambulatory status may identify patients at a sufficiently elevated risk at which suitability of HTx should be reconsidered.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.