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Background and Aim: The global inflammatory bowel disease (IBD) escalation has precipitated an increased disease burden and economic impact, particularly in Asia. This study primarily aimed to predict the future prevalence of IBD in Korea and elucidate its evolution pattern. Methods: Using a validated diagnostic algorithm, we analyzed data from the Korean National Health Insurance Service between 2004 and 2017 to identify patients with IBD. We predicted the number and prevalence of patients with IBD from 2018 to 2048 with the autoregressive integrated moving average method. A generalized linear model (GLM) was also employed to identify factors contributing to the observed trend in IBD prevalence. Results: Our prediction model validation demonstrated an acceptable error range for IBD prevalence, with a 2.45% error rate and a mean absolute difference of 2.61. We foresee a sustained average annual increase of 4.51 IBD cases per 100 000, culminating in a prevalence of 239.73 per 100 000 by 2048. The forecasted average annual percent change was 6.17% for males and 2.75% for females over the next 30 years. The GLM analysis revealed that age, gender and time significantly impact the prevalence of IBD, with notable disparities observed between genders in specific age groups for both Crohn's disease and ulcerative colitis (all interaction P < 0.05). Conclusions: Our study forecasts a notable increase in Korean IBD prevalence by 2048, particularly among males and the 20–39 age group, highlighting the need to focus on these high‐risk groups to mitigate the future disease burden. [ABSTRACT FROM AUTHOR]

Background/Aims: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. Methods: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. Results: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas = 10 mm, tubulovillous or villous adenomas, = 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs = 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps (> 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. Conclusions: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines. [ABSTRACT FROM AUTHOR]

Background & Aims: Although non‐alcoholic fatty liver disease (NAFLD) is becoming a leading cause of hepatocellular carcinoma (HCC), HCC risk in non‐cirrhotic NAFLD received little attention. We aimed to develop and validate an HCC risk prediction model for non‐cirrhotic NAFLD. Methods: A nationwide cohort of non‐cirrhotic NAFLD patients in Korea was recruited to develop a risk prediction model and validate it internally (n = 409 088). A model using a simplified point system was developed by Cox proportional hazard model. K‐fold cross‐validation assessed the accuracy, discrimination and calibration. The model was validated externally using a hospital cohort from Asan Medical Center (n = 8721). Results: An 11‐point HCC risk prediction model for non‐cirrhotic NAFLD was developed using six independent factors of age, sex, diabetes, obesity, serum alanine aminotransferase level and gamma‐glutamyl transferase level (c‐index 0.75). The average area under receiver operating curves (AUROCs) of the model was 0.72 at 5 years and 0.75 at 10 years. In the external validation cohort, the AUROCs were 0.79 [95% confidence interval [CI], 0.59–0.95] at 5 years and 0.84 (95% CI, 0.73–0.94) at 10 years. The calibration plots showed the expected risks corresponded well with the observed risks. Risk stratification categorized patients into the low (score 0–6), moderate (7, 8) and high (9–11; estimated incidence rate >0.2%/year) risk groups. Conclusions: A novel HCC risk prediction model for non‐cirrhotic NAFLD patients was developed and validated with fair performance. The model is expected to serve as a simple and reliable tool to assess HCC risk and assist precision screening of HCC. [ABSTRACT FROM AUTHOR]

Background and Aims Crohn's disease [CD] has a complex polygenic aetiology with high heritability. There is ongoing effort to identify novel variants associated with susceptibility to CD through a genome-wide association study [GWAS] in large Korean populations. Methods Genome-wide variant data from 902 Korean patients with CD and 72 179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1621 patients with CD and 4419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term. Results We identified two novel genetic associations with the risk of CD near ZBTB38 and within the leukocyte immunoglobulin-like receptor [LILR] gene cluster [ p  < 5 × 10−8], with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci [QTL] for multiple LILR genes, of which LILRB2 directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants for TAP2 involved in the antigen presentation of MHC class I molecules [ p  = 4.11 × 10−4], showing higher CD-risk effects of the TAP2 variant in individuals carrying more risk alleles of the LILR lead variant (odds ratio [OR] = 0.941, p  = 0.686 in non-carriers; OR = 1.45, p  = 2.51 × 10−4 in single-copy carriers; OR = 2.38, p  = 2.76 × 10−6 in two-copy carriers). Conclusions This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR and TAP2 loci confer a risk of CD. [ABSTRACT FROM AUTHOR]

Summary: Background: The association between antibiotic use and risk of inflammatory bowel disease (IBD), particularly among adults, remains unclear. Furthermore, there is a scarcity of data among non‐Western countries. Aims: To investigate the association and dose–response relationships between antibiotic use and subsequent IBD risk across all ages Methods: This population‐based case–control analysis used data from the Korean National Health Insurance Service database (2004–2018). We compared 68,633 patients with new‐onset IBD to matched controls (n = 343,165) using multivariable conditional logistic regression analysis. We also examined the dose–response relationship using non‐linear regression analysis, and separately analysed childhood‐onset IBD (aged ≤14 years) risk following early‐life antibiotic exposure. Results: The mean age at diagnosis was 45.2 ± 16.8 years. Antibiotic prescriptions between 2 and 5 years before diagnosis significantly increased the odds of developing IBD (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.21–1.27). Additionally, sensitivity analysis revealed an elevated risk up to 9 years before diagnosis. Broad‐spectrum antibiotics increased IBD risk, independent of gastroenteritis. A distinct dose–response relationship was observed irrespective of the IBD subtype and study population (all p < 0.001). Furthermore, antibiotic exposure within the first year of life was linked with the risk of childhood‐onset IBD (OR, 1.51; 95% CI: 1.25–1.82). Conclusions: Broad‐spectrum antibiotics dose‐dependently increased the risk for IBD in the Korean population. Our findings provide a fundamental epidemiological basis for identifying antibiotic use as a significant risk factor for IBD across different environmental backgrounds. [ABSTRACT FROM AUTHOR]

Background and Aim: We conducted a nationwide validation study of diagnostic algorithms to identify cases of inflammatory bowel disease (IBD) within the Korea National Health Insurance System (NHIS) database. Method: Using the NHIS dataset, we developed 44 algorithms combining the International Classification of Diseases (ICD)‐10 codes, codes for Rare and Intractable Diseases (RID) registration and claims data for health care encounters, and pharmaceutical prescriptions for IBD‐specific drugs. For each algorithm, we compared the case identification results from electronic medical records data with the gold standard (chart‐based diagnosis). A multiple sampling test verified the validation results from the entire study population. Results: A random nationwide sample of 1697 patients (848 potential cases and 849 negative control cases) from 17 hospitals were included for validation. A combination of the ICD‐10 code, ≥ 1 claims for health care encounters, and ≥ 1 prescription claims (reference algorithm) achieved excellent performance (sensitivity, 93.1% [95% confidence interval 91–94.7]; specificity, 98.1% [96.9–98.8]; positive predictive value, 97.5% [96.1–98.5]; negative predictive value, 94.5% [92.8–95.8]) with the lowest error rate (4.2% [3.3–5.3]). The multiple sampling test confirmed that the reference algorithm achieves the best performance regarding IBD diagnosis. Algorithms including the RID registration codes exhibited poorer performance compared with that of the reference algorithm, particularly for the diagnosis of patients affiliated with secondary hospitals. The performance of the reference algorithm showed no statistical difference depending on the hospital volume or IBD type, with P‐value < 0.05. Conclusions: We strongly recommend the reference algorithm as a uniform standard operational definition for future studies using the NHIS database. [ABSTRACT FROM AUTHOR]

Background and Aim: PBK‐1701TC is a novel sulfate tablet‐based that contains 320 mg of simethicone and delivers 90% of the salt and water delivered by oral sulfate solution (OSS) preparation. This study evaluated the efficacy, safety, and tolerability of PBK‐1701TC compared with OSS in bowel preparation for colonoscopy. Methods: This randomized, multicenter, phase 3 non‐inferiority trial included adults aged 19 years or older with a body mass index of 19–30 kg/m2 undergoing colonoscopy at five university hospitals in Korea. The primary efficacy endpoint was successful bowel‐cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded central readers. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Tolerability was assessed via participant interview. Results: Overall, 235 participants were randomized, and 224 were included in the per‐protocol analysis (PBK, 112; OSS, 112). Successful bowel cleansing was achieved for 95.5% (107/112) in the PBK group, which was non‐inferior to the OSS group (98.2%, 110/112) with a difference of −2.7% (one sided 97.5% confidence limit, −8.1%). The participants in the PBK group had fewer intraluminal bubbles (0.9% vs 81.3%, P < 0.001) and reported a lower incidence of nausea and vomiting, with better acceptance, taste, and willingness to repeat the regimen than those in the OSS group (all P < 0.05). Conclusion: The novel sulfate tablet, PBK‐1701TC, was non‐inferior to OSS with respect to bowel‐cleansing efficacy and exhibited better safety and tolerability in adults undergoing colonoscopy. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Oh et al papers. To view these articles, visit https://doi.org/10.1111/apt.17542 and https://doi.org/10.1111/apt.17563 [ABSTRACT FROM AUTHOR]

Background and Aim: Despite the frequent loss of Ras association domain family 1 isoform A (RASSF1A) expression in various cancers, the precise mechanism underlying its tumor‐suppressive effect is not fully understood. To elucidate the growth‐inhibitory role for RASSF1A in colorectal tumorigenesis, this study investigated the RASSF1A regulation of the p53‐p21WAF1 pathway. Methods: Ras association domain family 1 isoform A effect on cellular growth was tested in three human colon cancer cell lines by flow cytometry, cell counting, and [3H]‐thymidine incorporation assay. HCT116 p53+/+ and p53−/− isogenic sublines were utilized to determine the p53 dependence of RASSF1A effect on p21WAF1. Cycloheximide chase experiment and immunoprecipitation assay were carried out to define RASSF1A effect on p53 stability and mouse double minute 2 (MDM2) homolog ubiquitination. Results: Ras association domain family 1 isoform A expression inhibits colonic cell proliferation by preventing the G1 to S phase transition of the cell cycle. The RASSF1A‐induced G1 cell cycle arrest is accompanied by the increase in the level of p21WAF1 mRNA expression. The p21WAF‐inducing activity of RASSF1A was substantially higher in HCT116 p53+/+ cell compared with isogenic p53−/− cells. The cycloheximide chase assay revealed that RASSF1A expression leads to p53 stabilization and MDM2 homolog degradation. Using p53−/− and p21WAF1−/− subline cells, this study finally validated a crucial role of the p53‐p21WAF1 axis in RASSF1A‐mediated growth inhibition. Conclusions: RASSF1A suppresses colonic tumor growth through the activation of the p53‐p21WAF1 pathway. This finding supports that RASSF1A could be a valuable marker for the assessment of colorectal cancer development and progression. [ABSTRACT FROM AUTHOR]

Background: Expression of caveolin-1 (Cav-1) is frequently altered in many human cancers and both tumor suppression and promotion functions of Cav-1 have been suggested based on its expression status. However, it remains unanswered how Cav-1 provokes opposite effects in different cancers or different phases of tumor progression.Methods: To explore the implication of Cav-1 alteration in gastric tumorigenesis, the expression and mutational status of Cav-1 and its effects on tumor cell growth were characterized.Results: A substantial fraction of primary tumors and cell lines displayed abnormally low or high Cav-1 mRNA expression, indicating the bidirectional alteration of Cav-1 in gastric cancers. While allelic imbalance and mutational alterations of the Cav-1 gene were rarely detected, aberrant promoter hyper- or hypo-methylation showed a tight correlation with bidirectional alteration of its expression. Abnormally low and high Cav-1 expression was more frequently observed in early and advanced cancers, respectively, suggesting the oncogenic switch of its function in tumor progression. Cell cycle progression, DNA synthesis, and colony forming ability were markedly decreased by Cav-1 transfection in low-expressing tumor cells but by its depletion in high-expressing cells. Interestingly, Cav-1 exerted opposite effects on MEK-ERK signaling in these two cell types through the reciprocal regulation of the RAF-ERK negative feedback loop. A feedback inhibition of RAF by ERK was stimulated by restoration of Cav-1 expression in low-expressing cells but by it depletion in high-expressing cells. As predicted, the opposite effects of Cav-1 on both tumor cell growth and inhibitory RAF phosphorylation were abolished if ERK is depleted.Conclusion: Bidirectional alteration of Cav-1 is linked to its opposite effects on gastric tumor cell growth, which stem from the reciprocal control on the RAF-ERK negative feedback loop. [ABSTRACT FROM AUTHOR]

Background/aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL)., Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis., Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05)., Conclusions: While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.

The risk factors for immediate post-polypectomy bleeding (IPPB) after cold snare polypectomy (CSP) are not well-known. We sought to define such risk factors and develop a predictive risk-scoring model. This prospective observational study included 161 polyps (4-9 mm in diameter) that were removed via CSP from 118 patients during the period from June to September 2019 in 2 tertiary hospitals. IPPB was defined as post-polypectomy bleeding within 24 hours or grade 3 or 4 intraprocedural bleeding requiring endoscopic hemostasis. IPPB incidences according to grade were 13.0% (21/161) (grade 3) and 0% (grade 4). Univariate analysis showed that the polyp size and morphology, as well as iatrogenic ulcer size and shape, were significantly associated with IPPB. Multivariate analysis showed that polyp size [6-9 mm vs 4-5 mm, odds ratio (OR) 3.72, 95% confidence interval (CI) 1.28-10.79], polyp morphology (polypoid vs non-polypoid, OR: 3.93, 95% CI: 1.22-12.64), and iatrogenic ulcer size (≥10 vs ≤ 9 mm, OR: 3.12, 95% CI: 1.04-9.38) were significantly associated with IPPB. We created a four-marker risk-scoring model to predict IPPB after CSP; we summed the points assigned for the 4 factors. At a cutoff of 2, the sensitivity was 85.7% and the specificity was 65.0%; at a cutoff of 3, the sensitivity was 65% and the specificity was 90.0%. Polyp size and morphology, as well as iatrogenic ulcer size and shape, were associated with IPPB after CSP. The four-marker risk-scoring model appears to effectively predict IPPB after CSP (Clinical Research Information Service: KCT0004375)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aim: Despite the frequent loss of Ras association domain family 1 isoform A (RASSF1A) expression in various cancers, the precise mechanism underlying its tumor-suppressive effect is not fully understood. To elucidate the growth-inhibitory role for RASSF1A in colorectal tumorigenesis, this study investigated the RASSF1A regulation of the p53-p21 WAF1 pathway., Methods: Ras association domain family 1 isoform A effect on cellular growth was tested in three human colon cancer cell lines by flow cytometry, cell counting, and [ 3 H]-thymidine incorporation assay. HCT116 p53 +/+ and p53 -/- isogenic sublines were utilized to determine the p53 dependence of RASSF1A effect on p21 WAF1 . Cycloheximide chase experiment and immunoprecipitation assay were carried out to define RASSF1A effect on p53 stability and mouse double minute 2 (MDM2) homolog ubiquitination., Results: Ras association domain family 1 isoform A expression inhibits colonic cell proliferation by preventing the G1 to S phase transition of the cell cycle. The RASSF1A-induced G1 cell cycle arrest is accompanied by the increase in the level of p21 WAF1 mRNA expression. The p21 WAF -inducing activity of RASSF1A was substantially higher in HCT116 p53 +/+ cell compared with isogenic p53 -/- cells. The cycloheximide chase assay revealed that RASSF1A expression leads to p53 stabilization and MDM2 homolog degradation. Using p53 -/- and p21 WAF1-/- subline cells, this study finally validated a crucial role of the p53-p21 WAF1 axis in RASSF1A-mediated growth inhibition., Conclusions: RASSF1A suppresses colonic tumor growth through the activation of the p53-p21 WAF1 pathway. This finding supports that RASSF1A could be a valuable marker for the assessment of colorectal cancer development and progression., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)