Impact of metabolic unhealthiness and its changes on the risk of erosive esophagitis: a cohort study.

BACKGROUND AND AIM: We aimed to compare the risk of erosive esophagitis (EE) among individuals with different phenotypes based on metabolic health status and obesity and investigate the role of changes in metabolic health in EE risk. METHODS: A cohort of 258 892 asymptomatic adults without EE at baseline who underwent ollow-up esophagogastroduodenoscopy (EGD) were categorized into the following four groups according to metabolic health and obesity status: (i) metabolically healthy (MH) non-obese; (ii) metabolically unhealthy (MU) non-obese; (iii) MH obese; and (iv) MU obese. EE was defined as the presence of grade A or higher mucosal breaks on EGD. RESULTS: During a median follow-up of 4.5 years, the incidence rates of EE were 0.6/103 person-years (PY), 1.7/103 PY, 1.7/103 PY, and 3.1/103 PY in the MH non-obese, MU non-obese, MH obese, and MU obese groups, respectively. The multivariable-adjusted hazard ratio (HR) (95% confidence intervals [CI]) for developing EE comparing the MH obese, MU non-obese, and MU obese groups with the MH non-obese group were 1.49 (1.29-1.71), 1.56 (1.25-1.94), and 2.18 (1.90-2.49), respectively. The multivariable-adjusted HR (95% CI) comparing the progression of MH to MU, regression of MU to MH, and persistent MU with the persistent MH group were 1.39 (1.10-1.76), 1.39 (1.09-1.77), and 1.86 (1.56-2.21), respectively. The increased risk of EE among the persistent MU group was consistently observed in individuals without obesity or abdominal obesity. CONCLUSION: Metabolic unhealthiness and obesity were independent risk factors for the development of EE, suggesting that maintaining both normal weight and metabolic health may help reduce the risk of EE.

Efficacy and Safety of Fexuprazan in Patients with Acute or Chronic Gastritis.

Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups. No significant difference was noted in the incidence of adverse drug reactions. Conclusions: Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

Efficacy and Tolerability of 14-Day Tegoprazan- versus Rabeprazole-Based Triple Therapy for Eradication of Helicobacter pylori: A Real-World Evidence Study.

Background/Aims: Tegoprazan, a new, fast, and strong potassium-competitive acid blocker, has been approved for the treatment of gastric acid-related diseases in Korea. However, real-world clinical data regarding this drug are scarce. We aimed to compare the Helicobacter pylori eradication rates of tegoprazan- and rabeprazole-based triple therapy. Methods: We retrospectively reviewed data from patients who received first-line treatment for H. pylori infection using tegoprazan- or rabeprazole-based triple therapy for 2 weeks (50 mg tegoprazan or 20 mg rabeprazole+1,000 mg amoxicillin+500 mg clarithromycin twice daily). The primary endpoint was the eradication rate as determined by intention-to-treat analysis. Results: Of the 677 patients included in our study, 344 and 333 received tegoprazan-based and rabeprazole-based triple therapy, respectively. The eradication rate from intention-to-treat analysis was 76.7% (95% confidence interval [CI], 72.1% to 81.0%) for tegoprazan-based triple therapy and 75.4% (95% CI, 70.5% to 79.8%) for rabeprazole-based triple therapy. There was no significant difference in the eradication rates between the two groups (p>0.999). Per-protocol analysis also revealed no significant difference between the eradication rates of the two groups (tegoprazan 83.4% [95% CI, 79.0% to 87.2%] vs rabeprazole 83.5% [79.0% to 87.4%], p>0.999). Furthermore, there was no significant difference in adverse event rates between the two groups (tegoprazan, 27.6%; rabeprazole, 25.8%; p=0.604). Conclusions: The eradication rate of tegoprazan-based triple therapy was similar to that of rabeprazole-based triple therapy. Further studies on the dose-escalation effect of tegoprazan for H. pylori eradication and the efficacy of tegoprazan in regimens other than conventional triple therapy are needed.

Risk of post-polypectomy bleeding after endoscopic mucosal resection in patients receiving antiplatelet medication: comparison between the continue and hold groups.

BACKGROUND: Current guidelines recommend continuing aspirin and discontinuing clopidogrel for colon polypectomy, but evidence for endoscopic mucosal resection (EMR) is insufficient. We aimed to assess post-polypectomy bleeding (PPB) in patients receiving antiplatelet agents and underwent EMR for various polyp sizes. METHODS: A single-center, prospective observational study was performed. Patients who underwent at least one EMR for polypectomy and those who received aspirin or clopidogrel were included. We compared PPB between the antiplatelet hold group (stopped antiplatelet therapy at least 5 days before the procedure) and continue group (antiplatelet therapy was maintained or stopped within 5 days before the procedure). RESULTS: Among patients who underwent EMR, 305 took aspirin (hold group 257, continue group 48) and 77 took clopidogrel (hold group 66, continue group 11). The mean number of polyps was four, and the mean size was 8.6 mm. There was no difference in the major PPB rate between the hold and continue groups among aspirin users (2.0% vs. 4.2%, P = 0.30), but it was significantly higher in the continue group than in the hold group among clopidogrel users (18.2% vs. 0%, P = 0.02). In patient- and polyp-based logistic regression analysis of clopidogrel users, the number of EMRs (OR 2.12, 95% CI 1.16-3.88), polyp size (OR 1.26, 95% CI 1.06-1.49), and continuing clopidogrel (OR 9.75, 95% CI 1.99-47.64) were independent risk factors for PPB. CONCLUSION: Continuous administration of antiplatelet agents was significantly associated with higher PPB in clopidogrel users, but not in aspirin users. Endoscopists should consider holding clopidogrel if the EMR includes polypectomy.

Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults.

Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011-2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P < 0.001). Compared to men, the prevalence of hemorrhoidal disease was higher in parous women (adjusted odds ratio [OR] 1.06; 95% confidence interval [CI] 1.02-1.10), and lower in nulliparous women (adjusted OR 0.92; 95% CI 0.86-0.98). In the adjusted analyses, older age, female sex, smoking, overweight, and being hypertensive were independently associated with the presence of hemorrhoidal disease. The prevalence of hemorrhoidal disease was positively associated with body mass index and waist circumference in parous women. The prevalence of hemorrhoidal disease was higher in older age, females, ever-smokers, and hypertensive participants. The association of excess adiposity with the prevalence of hemorrhoidal disease differed by sex and parity.

Comparative Analysis of Relaxation Time Interval and Integrated Relaxation Pressure as Risk Factors for Aspiration in Patients With Oropharyngeal Dysphagia.

BACKGROUND/AIMS: Integrated relaxation pressure (IRP) is an important metric for functional evaluation of the lower esophageal sphincter. However, the effectiveness of IRP for evaluation of upper esophageal sphincter (UES) function has not yet been clarified. METHODS: High-resolution manometry (HRM) was performed in 180 patients with dysphagia. For comparison, 26 asymptomatic subjects were also recruited. IRP of the UES was defined as means of 0.2, 0.25, or 0.3 seconds (sIRPs) of maximal deglutitive relaxation in a 0.4-second window (a new equation for IRP calculation was developed using MATLAB). Also, the relaxation time interval of the UES, and mesopharyngeal and hypopharyngeal contractility (as a contractile integral) were evaluated using HRM. RESULTS: In normal subjects, mean values of 0.2, 0.25, and 0.3 sIRPs differed significantly from each other (P < 0.05). They were not associated with the relaxation time interval of the UES. In contrast, in patients with dysphagia, mean values of 0.2, 0.25, and 0.3 sIRPs were strongly related to relaxation time intervals of the UES (P < 0.05), and mean values of 0.2, 0.25, and 0.3 sIRPs in patients with aspiration were significantly higher than those of patients without aspiration (P < 0.01). However, in multivariate regression analyses, the main risk factor for aspiration was only a shorter relaxation time interval. CONCLUSIONS: IRP values were significantly higher in patients with dysphagia and aspiration. However, its usefulness as a predictive factor for aspiration was less than the relaxation time interval of the UES.

Optimization of the surveillance strategy in patients with colorectal adenomas: A combination of clinical parameters and index colonoscopy findings.

BACKGROUND AND AIM: In addition to index colonoscopy findings, demographic parameters including age are associated with the risk of metachronous advanced colorectal neoplasia. Here, we aimed to develop a risk scoring model for predicting advanced colorectal neoplasia (ACRN) during surveillance using a combination of clinical factors and index colonoscopy findings. METHODS: Patients who underwent the removal of one or more adenomas and surveillance colonoscopy were included. A risk scoring model for ACRN was developed using the Cox proportional hazard model. Surveillance interval was determined as a time point exceeding 4% of the cumulative ACRN incidence in each risk group. RESULTS: Of 9591 participants, 4725 and 4866 were randomly allocated to the derivation and validation cohorts, respectively. Age, abdominal obesity, advanced adenoma, and ≥ 3 adenomas at index colonoscopy were identified as risk factors for metachronous ACRN. Based on the regression coefficients, point scores were assigned as follows: age, 1 point (per 1 year); abdominal obesity, 10 points; advanced adenoma, 10 points; and ≥ 3 adenomas, 15 points. Patients were classified into high-risk (≥ 80 points), moderate-risk (50-79 points), and low-risk (30-49 points) groups. In the validation cohort, the high-risk and moderate-risk groups showed a higher risk of ACRN than the low-risk group (hazard ratio [95% confidence interval]: 7.11 [4.10-12.32] and 1.58 [1.09-2.30], respectively). Two-, 4-, and 5-year surveillance intervals were recommended for the high-risk, moderate-risk, and low-risk groups, respectively. CONCLUSIONS: Our proposed model may facilitate effective risk stratification of ACRN during surveillance and the determination of appropriate surveillance intervals.

Impact of nonalcoholic fatty liver disease on the risk of metachronous colorectal neoplasia after polypectomy.

BACKGROUND/AIMS: Metabolic syndrome has been reported to be a risk factor for metachronous colorectal neoplasia (CRN). However, the impact of nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, on the development of metachronous CRN after polypectomy has been rarely examined. We evaluated the association between NAFLD and the development of metachronous CRN after polypectomy. METHODS: Asymptomatic subjects who underwent abdominal ultrasonography and endoscopic removal of ≥ 1 adenomas at the index colonoscopy between 2010 and 2014, and had a follow-up surveillance colonoscopy until 2017 were analyzed. RESULTS: Of 6,182 participants, 2,642 (42.7%) had NAFLD at the time of the index colonoscopy. Patients with NAFLD had significantly higher cumulative incidence rates of metachronous overall CRN than those without NAFLD in both men (19.4% vs. 18.2% at 3 years and 49.2% vs. 44.0% at 5 years; p = 0.001) and women (18.7% vs. 10.5% at 3 years and 56.1% vs. 29.8% at 5 years; p < 0.001). Even after adjusting for confounders, NAFLD remained independently associated with an increased risk of metachronous overall CRN in both men (adjusted hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.06 to 1.29) and women (adjusted HR, 1.63; 95% CI, 1.27 to 2.07). Additionally, NAFLD was an independent risk factor for metachronous advanced CRN (ACRN) in women (adjusted HR, 2.61; 95% CI, 1.27 to 5.37). CONCLUSION: NAFLD is related to an increased risk of metachronous CRN after polypectomy. Especially, women with NAFLD are at an increased risk of developing metachronous ACRN. Our results indicate a possible effect of NAFLD on the pathogenesis of CRN.

Efficacy and Safety of DWJ1252 Compared With Gasmotin in the Treatment of Functional Dyspepsia: A Multicenter, Randomized, Double-blind, Active-controlled Study.

BACKGROUND/AIMS: Prokinetics such as mosapride citrate CR (conventional-release; Gasmotin) are commonly used in functional dyspepsia (FD). This study aims to evaluate the efficacy and safety of once-a-day mosapride citrate SR (DWJ1252), a sustained-release formulation of mosapride citrate, compared with mosapride citrate CR 3 times a day, in patients with FD. METHODS: In this multicenter, randomized, double-blind, active-controlled, non-inferiority study, 119 patients with FD (by the Rome III criteria, 60 for mosapride citrate SR and 59 for mosapride citrate CR) were randomly allocated to mosapride citrate SR once daily or mosapride citrate CR thrice daily for 4 weeks in 16 medical institutions. Primary end point was the change in gastrointestinal symptom (GIS) score from baseline, assessed by GIS questionnaires on 5-point Likert scale after 4-week treatment. Secondary end points and safety profiles were also analyzed. RESULTS: The study included 51 and 49 subjects in the mosapride citrate SR and mosapride citrate CR groups, respectively. GIS scores at week 4 were significantly reduced in both groups (mean ± SD: -10.04 ± 4.45 and -10.86 ± 5.53 in the mosapride citrate SR and mosapride citrate CR groups, respectively; P < 0.001), and the GIS changes from baseline did not differ between the 2 groups (difference, 0.82 point; 95% CI, -1.17, 2.81; P = 0.643). Changes in GIS at weeks 2 and 4 and quality of life at week 4, and the improvement rates of global assessments at weeks 2 and 4, did not differ between the groups. Adverse events were similar in the 2 groups, and there were no serious adverse events. CONCLUSION: In patients with FD, mosapride citrate SR once daily is as effective as mosapride citrate CR thrice daily, with a similar safety profile.

Metabolically Healthy Obesity Is Associated with an Increased Risk of Colorectal Adenoma Occurrence Diagnosed by Surveillance Colonoscopy.

Background/Aims: The risk of recurrence of colorectal adenoma among obese individuals without metabolic abnormalities or in those with metabolically healthy obesity is largely unexplored. Therefore, we longitudinally investigated the risk of adenoma occurrence in individuals undergoing surveillance colonoscopy according to metabolic status and obesity. Methods: This retrospective cohort study included 16,872 Korean adults who underwent their first screening colonoscopy between 2003 and 2012 and who then underwent follow-up colonoscopy until 2017. Participants were categorized into a metabolically healthy nonobese group (reference group), a metabolically healthy obese group, a metabolically abnormal nonobese group, and a metabolically abnormal obese group. Hazard ratios (HRs) for adenoma recurrence compared to the reference group were calculated in each group. Results: During a median follow-up duration of 47.3 months (interquartile range, 35.6 to 58.9 months), 3,673 (21.8%) and 292 (1.73%) participants developed adenoma and advanced adenoma, respectively. When age, sex, smoking, alcohol consumption, family history of colorectal cancer, and baseline adenoma risk were adjusted, the risk of adenoma recurrence was increased in metabolically healthy obese individuals (HR, 1.33; 95% confidence interval [CI], 1.12 to 1.57) and metabolically abnormal obese individuals (HR, 1.18; 95% CI, 1.08 to 1.30) but not in metabolically abnormal nonobese individuals (HR, 1.03; 95% CI, 0.94 to 1.13). Conclusions: In this study, metabolically healthy obese individuals and metabolically abnormal obese individuals exhibited increased risks of occurrence of colorectal adenoma diagnosed by surveillance colonoscopy. This finding implies that obesity itself, even without metabolic abnormalities, is associated with an increased risk of adenoma recurrence.

Changes in Abdominal Obesity Affect the Risk of Metachronous Advanced Colorectal Neoplasia Development after Polypectomy.

PURPOSE: The impact of changes in body mass index and waist circumference on the development of metachronous colorectal neoplasia (CRN) after polypectomy has rarely been examined. We evaluated the association between changes in overall/abdominal obesity and metachronous CRN risk. MATERIALS AND METHODS: We studied patients who underwent ≥1 adenoma removal and surveillance colonoscopy. Patients were classified into the following four groups based on the changes in overall obesity from index to follow-up colonoscopy: non-obesity persisted (group 1), obesity to non-obesity (group 2), non-obesity to obesity (group 3), and obesity persisted (group 4). Patients were also divided into another four groups based on similar changes in abdominal obesity (groups 5-8). RESULTS: The number of patients in groups 1, 2, 3, and 4 was 5074, 457, 643, and 3538, respectively, and that in groups 5, 6, 7, and 8 was 4229, 538, 656, and 2189, respectively. Group 4 had a significantly higher risk of metachronous CRN compared to groups 1 and 2. However, metachronous advanced CRN (ACRN) risk was not different among groups 1, 2, 3, and 4. Metachronous CRN risk in group 8 (abdominal obesity persisted) was higher than that in groups 5 (non-abdominal obesity persisted) and 7 (non-abdominal obesity to abdominal obesity), and tended to be higher than that in group 6 (abdominal obesity to non-abdominal obesity). Additionally, group 8 had a significantly higher risk of metachronous ACRN compared to groups 5, 6, and 7. CONCLUSION: Changes in obesity affected the metachronous CRN risk. In particular, changes in abdominal obesity affected the metachronous ACRN risk.

Skeletal muscle mass and risk of advanced adenoma in surveillance colonoscopy.

BACKGROUND AND AIM: Sarcopenia has been suggested to be associated with chronic inflammation and insulin resistance. This study aimed to evaluate whether low muscle mass is associated with the incidence and recurrence of advanced colorectal adenoma. METHODS: We conducted a cohort study including 14 701 participants who underwent first-time screening colonoscopy between 2003 and 2012 and follow-up colonoscopy until 2017. Skeletal muscle mass was measured using a bioelectrical impedance analyzer and divided by body weight to calculate the skeletal muscle mass index (SMI). RESULTS: During a median 47 (interquartile range, 35-58) months of follow-up, overall and advanced adenoma developed in 2988 (20.3%) and 207 (1.41%) participants, respectively. In multivariate analysis using models adjusted for baseline adenoma risk, lifestyle factors, markers for insulin resistance and chronic inflammation, and metabolic syndrome, decreasing SMI quartiles were associated with increased risk of occurrence of advanced adenoma and overall adenoma. The adjusted hazard ratios (95% confidence intervals) comparing SMI quartiles 3, 2, and 1 to quartile 4 were 1.57 (1.03-2.41), 1.22 (0.78-1.92), and 1.77 (1.13-2.76), respectively, for advanced adenoma (P for trend = 0.049) and 1.05 (0.95-1.17), 1.09 (0.98-1.21), and 1.26 (1.13-1.41), respectively, for overall adenoma (P for trend < 0.001). CONCLUSIONS: In this large cohort with long-term colonoscopy follow-up, low relative muscle mass was associated with increased risk of occurrence of advanced adenoma and overall adenoma at follow-up colonoscopy, independent of metabolic and inflammatory markers. Timely and thorough surveillance colonoscopy may be emphasized in such populations.

Impact of Smoking on Human Natural Killer Cell Activity: A Large Cohort Study.

Some studies have reported a decrease in the natural killer (NK) cell activity in smokers. However, large-scale data on the relationship between NK cell activity and smoking are unavailable. A cross-sectional study was performed on 12,249 asymptomatic examinees who underwent an NK cell activity test, between January 2016 and May 2017. The test quantitated the amount of interferon-γ secreted into the plasma by NK cells, using a patented stimulatory cytokine. The mean age of the study population was 39.1 years, and the proportions of "never", "former", and "current" smokers were 65.5%, 20.9%, and 13.6%, respectively. Current smokers (1,422 pg/mL) had a lower median level of NK cell activity than never smokers (1,504 pg/mL, P = 0.039) and former smokers (1,791 pg/mL, P < 0.001). Among current smokers, NK cell activity decreased with increase in the number of cigarettes smoked among current smokers (median, 1,537, 1,429, and 1,175 pg/mL at <10, 10-19, and ≥ 20 pack-years, respectively; P < 0.001). Additionally, it decreased linearly with increasing quartiles of cotinine levels (median, 1,707, 1,636, 1,348, and 1,292 pg/mL at cotinine levels < 292, 292-879, 880-1,509, and ≥ 1,510 ng/mL, respectively; r = -0.122, P < 0.001). NK cell activity was lower in current smokers. It also decreased with an increase in the number of cigarettes smoked, and it was negatively correlated with cotinine levels among current smokers. Our findings indicate a clear relationship between smoking and decreased NK cell activity.

Simple proxies for detection of clinically significant serrated polyps and data for their benchmarks.

BACKGROUND AND AIMS: Serrated polyp detection rate (SDR) is a potential quality indicator for preventing colorectal cancer associated with the serrated pathway. Using clinically significant SDR (CSSDR) has been suggested based on clinically significant serrated polyp's ability to be colorectal cancer precursors. Correlations between CSSDR and simpler SDRs, other than proximal SDR, have not yet been studied. We aimed to investigate which simpler SDR indicator is most relevant to CSSDR or adenoma detection rate (ADR) and provide benchmark data. METHODS: We analyzed 26 627 colonoscopies performed by 30 endoscopists. Clinically significant serrated polyps were defined as any sessile serrated adenoma/polyp or traditional serrated adenoma, hyperplastic polyps ≥ 5 mm in the proximal colon, or hyperplastic polyps ≥ 10 mm anywhere in the colon. Correlation of CSSDR and ADR with other simple SDRs, SDR-pathology (sessile serrated adenoma/polyp or traditional serrated adenoma), SDR-size (≥ 10 mm), and SDR-location (proximal location) was analyzed using Pearson's correlation test and Steiger's z-test. RESULTS: The CSSDR was 1.7% to 13.2% (mean = 6.1%). The correlation coefficient of CSSDR/SDR-size was 0.91 (P < 0.01), which was higher than that of CSSDR/SDR-location (0.64, P < 0.01) (0.91 vs 0.61, P < 0.01). The correlation coefficient of ADR/CSSDR and ADR/SDR-location was 0.41 (P < 0.01) and 0.81 (P < 0.01), respectively. For ADR ≥ 25%, endoscopists' median screening CSSDR was 5.4%, while SDR-location and SDR-size were 10.9% and 2.2%, respectively. CONCLUSION: Large SDR could be a simple proxy for CSSDR, in addition to proximal SDR. Large SDR and proximal SDR benchmarks of 2.2% and 10.9% may guide adequate serrated polyp detection with uniform definitions and simpler calculations.

Association between waist circumference and risk of colorectal neoplasia in normal-weight adults.

BACKGROUND AND AIM: Abdominal obesity, measured using waist circumference (WC), is associated with the colorectal neoplasia (CRN) risk. We examined whether WC is associated with the CRN risk even in normal-weight individuals. METHODS: A cross-sectional study was performed on asymptomatic normal-weight (body mass index 18.5-23 kg/m2 ) individuals who underwent colonoscopy as health checkups. RESULTS: Of 63 057 examinees, 30 498 were men (mean age, 41.1 years) and 32 559 were women (mean age, 41.7 years). The prevalence of overall CRN in WC quartiles 1, 2, 3, and 4 was 14.2%, 15.5%, 15.5%, and 18.7%, respectively, in men and 7.4%, 8.9%, 9.4%, and 11.5%, respectively, in women. The prevalence of advanced CRN (ACRN) in WC quartiles 1, 2, 3, and 4 was 1.5%, 1.3%, 1.6%, and 2.1%, respectively, in men and 1.0%, 1.3%, 1.2%, and 1.3%, respectively, in women. Among men, the overall CRN risk in quartile 4 (> 82 cm) was higher than that in quartiles 1, 2, and 3 (adjusted odds ratio, OR [95% confidence interval, CI], 1.22 [1.11-1.34], 1.12 [1.05-1.23], and 1.18 [1.07-1.29], respectively); the ACRN risk in quartile 4 was also higher than that in quartiles 1, 2, and 3 (adjusted OR [95% CI], 1.41 [1.09-1.81], 1.56 [1.19-2.03], and 1.50 [1.16-1.94], respectively). Among women, the overall CRN risk in quartile 4 (> 77 cm) was higher than that in quartiles 1 and 3; the ACRN risk was not different among all groups. CONCLUSIONS: Even with a normal weight, a large WC was associated with the CRN risk, especially with the ACRN risk in men.

Low Levels of Alcohol Consumption, Obesity, and Development of Fatty Liver With and Without Evidence of Advanced Fibrosis.

BACKGROUND AND AIMS: The effects of low-level alcohol consumption on fatty liver disease and the potential for effect modification by obesity is uncertain. We investigated associations among low-level alcohol consumption, obesity status, and the development of incident hepatic steatosis (HS), either with or without an increase in noninvasive liver fibrosis score category (from low to intermediate or high category). APPROACH AND RESULTS: A total of 190,048 adults without HS and a low probability of fibrosis with alcohol consumption less than 30 g/day (men) and less than 20 g/day (women) were followed for up to 15.7 years. Alcohol categories of no, light, and moderate consumption were defined as 0, 1-9.9, and 10-29.9 g/day (10-19.9 g/day for women), respectively. HS was diagnosed by ultrasonography, and the probability of fibrosis was estimated using the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 43,466 participants developed HS, 2,983 of whom developed HS with an increase in FIB-4 index (to intermediate or high scores). Comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for incident HS were 0.93 (0.90-0.95) and 0.90 (0.87-0.92), respectively. In contrast, comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for developing HS plus intermediate/high FIB-4 were 1.15 (1.04-1.27) and 1.49 (1.33-1.66), respectively. The association between alcohol consumption categories and incident HS plus intermediate/high FIB-4 was observed in both nonobese and obese individuals, although the association was stronger in nonobese individuals (P for interaction by obesity = 0.017). CONCLUSIONS: Light/moderate alcohol consumption has differential effects on the development of different stages of fatty liver disease, which is modified by the presence of obesity.

Alcoholic and Nonalcoholic Fatty Liver Disease and Incident Hospitalization for Liver and Cardiovascular Diseases.

BACKGROUND & AIMS: We compared the associations of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (AFLD) with risk of incident hospitalization for liver and cardiovascular diseases. METHODS: We collected data from the Kangbuk Samsung Health Study on 218,030 men and women in Korea who underwent a health examination from 2011 through 2016. Fatty liver disease (FLD) was detected by ultrasound during the initial examination. The Fibrosis-4 index was used to identify individuals with liver fibrosis. Participants were followed up for as long as 5.9 years and data on hospitalizations for liver and cardiovascular diseases were collected. RESULTS: The prevalence of NAFLD was 22.0% and the prevalence of AFLD was 6.4%. Over a median follow-up period of 4.2 years, we observed 51 and 1097 incident cases of liver disease- or cardiovascular disease-related hospitalizations, respectively. After adjustment for potential confounders, the multivariable-adjusted hazard ratios for liver disease-related hospitalization, comparing NAFLD and AFLD with the reference category (no excessive alcohol intake and no FLD), were 1.73 (95% CI, 0.76-3.96) and 5.00 (95% CI, 2.12-11.83), respectively. The corresponding hazard ratios for cardiovascular disease hospitalization were 1.20 (95% CI, 1.02-1.40) and 1.08 (95% CI, 0.86-1.34), respectively. Among participants with FLD, the risk of liver disease-related hospitalization increased with high Fibrosis-4 index scores, whereas the risk of incident cardiovascular disease did not. CONCLUSIONS: In a large cohort study, we found an increased risk of liver disease-related hospitalizations for patients with NAFLD or AFLD, especially among those with Fibrosis-4 index scores. An increased risk of cardiovascular disease-associated hospitalization was observed in patients with NAFLD but not AFLD.

Effect of Cotinine-Verified Change in Smoking Status on Risk of Metachronous Colorectal Neoplasia After Polypectomy.

BACKGROUND & AIMS: Previous assessments of colorectal neoplasia (CRN) recurrence after polypectomy used self-report to determine smoking status. We evaluated the association between change in smoking status and metachronous CRN risk after polypectomy using cotinine level in urine to determine tobacco exposure. METHODS: We performed a retrospective study of participants in the Kangbuk Samsung Health Study in Korea who underwent a screening colonoscopy examination and measurement of cotinine in urine samples. Our analysis included 4762 patients who had 1 or more adenomas detected in an index colonoscopy performed between January 2010 and December 2014, and underwent a surveillance colonoscopy, 6 or more months later, until December 2017. RESULTS: Patients were classified into 4 groups based on the change in cotinine-verified smoking status from index to follow-up colonoscopy (mean interval, 3.2 ± 1.3 y), as follows: remained nonsmokers (n = 2962; group 1), smokers changed to nonsmokers (n = 600; group 2), nonsmokers changed to smokers (n = 138; group 3), and remained smokers (n = 1062; group 4). After adjustment for confounding factors, group 4 had a significantly higher risk of metachronous CRN than group 1 (hazard ratio [HR], 1.54; 95% CI, 1.36-1.73) and group 2 (HR, 1.63; 95% CI, 1.39-1.99). Group 4 also had a higher risk of metachronous advanced CRN than group 1 (HR, 2.84; 95% CI, 1.79-4.53) and group 2 (HR, 2.10; 95% CI, 1.13-3.89). Group 3 had a higher risk of metachronous CRN than group 1 (HR, 1.50; 95% CI, 1.14-1.97) and group 2 (HR, 1.62; 95% CI, 1.20-2.20). CONCLUSIONS: In a retrospective study of individuals with at least 1 adenoma, we found that cotinine-verified changes in smoking status between index and follow-up colonoscopy are associated with a risk of metachronous CRN. Helping patients quit smoking is important for effective prevention of colorectal cancer.

Diabetes mellitus is associated with an increased risk of gastric cancer: a cohort study.

BACKGROUND: Diabetes mellitus (DM) has been considered a potential risk factor for gastric cancer, but the evidence is conflicting. We evaluated the association of DM with incident gastric cancer in a large cohort of men and women with endoscopic assessment at baseline and during follow-up. METHODS: We performed a retrospective cohort study of 195,312 adult men and women who underwent upper endoscopy at baseline and during follow-up between 2003 and 2014. DM was defined as fasting serum glucose ≥ 126 mg/dL, self-reported history of DM or current use of antidiabetic medications. Gastric cancer was confirmed histologically. RESULTS: The prevalence of DM at baseline was 3.0% (n = 5774). Over 865,511 person-years of follow-up, 198 participants developed gastric cancer. The fully adjusted hazard ratio (HR) for incident gastric cancer comparing participants with and without DM at baseline was 1.76 [95% confidence interval (CI) 1.04-2.97; P = 0.033). When we evaluated DM as a time-varying covariate, the fully adjusted HR was 1.66 (95% CI 1.04-2.68; P = 0.036). The association between DM and incident gastric cancer did not differ by the presence of intestinal metaplasia (P for interaction = 0.61). CONCLUSIONS: In this large cohort with endoscopic follow-up, DM was independently associated with increased gastric cancer incidence. The increased risk was independent of mucosal atrophy and intestinal metaplasia and was consistent in participants with newly developed DM during follow-up. Patients with DM may require more intensive endoscopic follow-up for gastric cancer screening.

Risk of developing metachronous advanced colorectal neoplasia after resection of low-risk diminutive versus small adenomas.

BACKGROUND AND AIMS: Current postpolypectomy guidelines classify 1 to 2 diminutive (1-5 mm) nonadvanced adenomas (NAAs) and 1 to 2 small (6-9 mm) NAAs as low-risk adenomas and recommend the same surveillance interval for both lesions. We compared the risk of metachronous advanced colorectal neoplasia (ACRN) for both groups. METHODS: We studied 8602 patients who underwent removal of ≥1 NAA and follow-up colonoscopic surveillance. Patients were categorized into 4 groups based on size and number of baseline NAAs: group 1, ≤2 diminutive NAAs (n = 6379); group 2, ≤2 small NAAs (n = 1672); group 3, ≥3 diminutive NAAs (n = 293); and group 4, ≥3 small NAAs (n = 258). Size was classified based on the largest NAA. RESULTS: The 5-year cumulative incidence rates of metachronous ACRN in groups 1, 2, 3, and 4 were 2.7%, 5.1%, 10.7%, and 15.1%, respectively. Groups 2, 3, and 4 had a higher risk of metachronous ACRN than group 1. Compared with group 1, the adjusted hazard ratios for metachronous ACRN were 2.06 (95% confidence interval [CI], 1.46-2.91) for group 2, 2.75 (95% CI, 1.53-4.96) for group 3, and 4.49 (95% CI, 2.62-7.70) for group 4. However, the risk of metachronous ACRN was not significantly different between groups 3 and 4 (adjusted hazard ratio, 1.62; 95% CI, .76-3.44). CONCLUSIONS: Among patients with ≤2 NAAs, patients with 1- to 5-mm NAAs had a lower risk of metachronous ACRN than those with 6- to 9-mm NAAs. The guidelines should consider extending surveillance intervals in patients with ≤2 diminutive NAAs.