Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

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.

Background/Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) represent the updated nomenclature and diagnostic criteria for nonalcoholic fatty liver disease, studies comparing the prognostic implications of these conditions remain limited. This meta-analysis aimed to quantify the associations among MAFLD, MASLD, and long-term clinical outcomes. Methods: A comprehensive literature search was performed to identify cohort studies that assessed the association of MASLD and MAFLD with all-cause mortality, cause-specific (cardiovascular and cancer-related) mortality, and the incidence of cardiovascular disease in the PubMed, Embase, Web of Science, CINAHL, and CENTRAL databases from inception through October 31, 2024. Pooled hazard ratios (HRs) were calculated for relevant outcomes. Results: We identified 18 cohort studies, comprising 10,653,666 patients with MAFLD from 13 studies and 3,202,447 patients with MASLD from nine studies. MAFLD was significantly associated with an increased risk of overall mortality (pooled HR [95% confidence interval], 1.30 [1.16 to 1.47]) and cardiovascular mortality (1.31 [1.08 to 1.60]; both p<0.01), but not with cancer-related mortality (1.10 [0.97 to 1.24]; p=0.130). Conversely, MASLD was associated with a higher risk for all mortality outcomes: overall mortality (1.34 [1.12 to 1.61]), cardiovascular mortality (1.17 [1.07 to 1.27]), and cancer-related mortality (1.24 [1.19 to 1.29]; all p<0.01). The risk of cardiovascular disease was increased in patients with both MAFLD (1.48 [1.31 to 1.66]) and MASLD (1.33 [1.21 to 1.46]; both p<0.001). Conclusions MAFLD and MASLD were both associated with increased risks of mortality and cardiovascular outcomes. Notably, a significant association with cancer-related mortality was observed for MASLD, but not for MAFLD.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Background: The impact of weight or weight changes on kidney function remains a matter of debate. This study aimed to investigate the association between weight fluctuation and the incidence of end-stage renal disease (ESRD) using data from the Korean National Health Insurance Corporation health checkups (2009–2015). Methods: The study included 2,310,667 participants (1,546,749 men and 763,918 women), aged ≥40 years. Weight fluctuation was assessed using the average real variability (ARV) of weight and categorized into quartiles (Q1–Q4). Hazard ratios (HRs) and 95% confidence intervals for ESRD incidence were calculated using multivariable Cox proportional hazards models. Results: After adjustment for comorbidities, increased body mass index was associated with a decreased HR for ESRD. The highest quartile of weight variability (ARV Q4) demonstrated a higher probability and HR for ESRD compared to the lower variability quartiles (Q1–Q3). Among men, individuals with sustained weight, and those with weight gain, the ARV Q4 group showed significantly increased HRs for ESRD (HR of 1.372, 1.222, and 1.49, respectively). Furthermore, irrespective of changes in creatinine levels, all ARV Q4 groups exhibited increased HRs for ESRD (HR of 1.342, 1.472, and 1.299, respectively). Conclusions High weight fluctuation (ARV Q4) was associated with an increased incidence of ESRD in the general Korean population, with notable significance in men and in groups with sustained or increased weight. Clinically, individuals in the ARV Q4 category should be considered at risk for ESRD, and early interventions should be pursued for this population.

Statins are effective in improving outcomes in the general population. However, in patients with chronic kidney disease (CKD), clinical outcomes and therapeutic approaches require careful interpretation from multiple perspectives. Managing dyslipidemia in CKD presents unique challenges requiring a comprehensive understanding of alterations in lipid metabolism in renal dysfunction. This review explored the key factors influencing statin efficacy, safety, and guideline recommendations in the CKD population, with a focus on lipid-lowering strategies tailored to renal function.

Hypertension is one of the leading chronic diseases globally and a major contributor to cardiovascular morbidity and mortality. Despite advances in pharmacological therapy, medication alone remains limited in achieving optimal control. This review synthesizes recent hypertension management guidelines, including those from the European Society of Cardiology (ESC, 2024), American Heart Association/American College of Cardiology (AHA/ACC, 2025), Taiwan Society of Cardiology/Hypertension Society (2022), and Korean Society of Hypertension (KSH, 2018). All guidelines consistently emphasize sodium restriction, weight reduction, regular exercise, moderation of alcohol intake, smoking cessation, and adoption of healthy dietary patterns such as the Dietary Approaches to Stop Hypertension, Mediterranean, or culturally adapted diets. The ESC 2024 guideline elevates lifestyle modification to Class I, Level A, specifying targets for sodium (<2 g/day) and potassium (≥3.5 g/day). The AHA/ACC 2025 guideline provides quantitative estimates, reporting approximately 1/1 mm Hg blood pressure reduction per kilogram of weight loss, and incorporates newer strategies such as glucagon-like peptide-1 receptor agonists and bariatric surgery when lifestyle measures alone are insufficient. Taiwan’s 2022 guideline frames recommendations under the S-ABCDE (sodium restriction, alcohol limitation, body weight reduction, cigarette cessation, diet adaptation, exercise adoption) mnemonic and uniquely includes genetic factors such as ALDH2 polymorphisms. The KSH 2018 guideline emphasizes salt restriction (<6 g/day), maintaining a body mass index <25 kg/m2, and adherence to traditional Korean diets. Lifestyle modification remains the cornerstone of hypertension prevention and management, particularly in primary care. Future directions should focus on integrating these approaches with pharmacotherapy, digital health strategies, and personalized prescriptions.

Smoking and sodium intake (SI) have been evaluated as risk factors for kidney disease; however, the data are inconsistent. We assessed the association between SI and cotinine-verified smoking status and the risk of albuminuria. Methods: An observational study using the Korea National Health and Nutrition Examination Survey (2008–2011 and 2014– 2018) was performed. We included 37,410 adults with an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2. The smoking status was assumed based on the urine cotinine/creatinine ratio (Ucot/Ucrea). SI was estimated from spot urine sodium using the Kawasaki formula. Results: Ucot/Ucrea levels were significantly higher in current smokers (920.22 ± 9.00 ng/mg) than in ex-smokers and nonsmokers (48.31 ± 2.47 and 23.84 ± 1.30 ng/mg) (p < 0.001). Ucot/Ucrea levels were significantly higher in second-hand smokers than in participants without a history of smoking (p < 0.001). Ucot/Ucrea levels were positively associated with SI (p for trend < 0.001). Smoking status was not associated with albuminuria. SI had a linear relationship with albuminuria (p < 0.001). In groups with the highest Ucot/Ucrea levels, the highest SI quartile indicated a significantly higher risk of albuminuria than that in the lowest quartile (risk ratio, 2.22; 95% confidence interval, 1.26–3.92; p = 0.006). The risk of albuminuria was not significant in groups with the lowest and middle tertile adjusted for multiple risk factors. Conclusion: Smokers consume higher dietary sodium and dietary SI was positively related to the risk of albuminuria. Smoking is not associated with albuminuria as a single factor. The risk of albuminuria is the higher in participants with smoking and high SI.