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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Prevalence of and Risk Factors for Colorectal Neoplasia in Asymptomatic Young Adults (20-39 Years Old).

BACKGROUND & AIMS: The incidence of colorectal cancer is increasing among persons 50 years old or younger. However, data on the epidemiology of young-onset colorectal neoplasia (CRN) are limited. Although some studies have investigated the epidemiology of CRN in persons younger than 50 years, most have focused on persons 40 years or older. We evaluated the prevalence of and risk factors for CRN in adults younger than 40 years. METHODS: We performed a cross-sectional analysis of 72,356 asymptomatic individuals, 20-39 years old, who underwent colonoscopies as participants in the Kangbuk Samsung Health Study in South Korea, from August 2004 through December 2015. Data on medical history and health-related behavior were collected from self-administered questionnaires. Patients were divided into groups based on age (20-29 years, n = 7340 or 30-39 years, n = 65,016), and χ2 tests were used to compare categorical variables between groups. A multivariate logistic regression model was used to assess the risk factors for overall and advanced CRN. RESULTS: The prevalence of overall CRN in group of 20-29 years was 5.9% and in the group of 30-39 years was 9.5% (P < .001); prevalence values for advanced CRN were 0.6% and 0.9%, respectively (P = .005). In the group of 30-39 years, age, smoking, alcohol intake, obesity, and abdominal obesity were independent risk factors for overall and advanced CRN. Additionally, male sex and metabolic syndrome were independent risk factors for overall CRN, whereas regular exercise reduced risk of overall CRN. Even in the 20-29 years group, obesity, abdominal obesity, and increased levels of triglycerides were independent risk factors for overall and advanced CRN, whereas age, increased blood pressure, and increased fasting blood glucose level were independent risk factors for overall CRN. CONCLUSION: In a retrospective analysis of 72,356 asymptomatic persons under 40 years of age evaluated by colonoscopy in Korea, we found modifiable factors, such as smoking, alcohol intake, obesity, and metabolic syndrome, to be significant risk factors for CRN-even in persons of 20-39 years old. Colorectal cancer screening strategies should consider these risk factors.

Risk of Developing Metachronous Advanced Colorectal Neoplasia After Polypectomy in Patients With Multiple Diminutive or Small Adenomas.

INTRODUCTION: Current post-polypectomy guidelines recommend a 3-year surveillance interval for ≥3 nonadvanced adenomas (NAAs) without discrimination between diminutive (1-5 mm) and small (6-9 mm) adenomas. We compared the risk of metachronous advanced colorectal neoplasia (ACRN) among these groups. METHODS: We studied 9,733 patients who underwent ≥1 adenoma removal and follow-up colonoscopic surveillance. Patients were classified based on baseline adenoma characteristics: group 1, 1-2 NAAs (n = 8,051); group 2, ≥3 diminutive NAAs (n = 293); group 3, ≥3 small NAAs (n = 258); and group 4, advanced adenomas (AAs) (n = 1,131). RESULTS: The mean age of the study population was 45.8 ± 8.2 years. In group 4, most patients (94.5%) had 1 AA. The 3- and 5-year cumulative incidence rates of metachronous ACRN in groups 1, 2, 3, and 4 were 0.9%, 2.8%, 3.5%, and 4.0% and 3.1%, 10.7%, 15.1%, and 8.5%, respectively. Groups 2, 3, and 4 had a higher risk of metachronous ACRN than group 1. Compared with those for group 1, adjusted hazard ratios (95% confidence interval) for metachronous ACRN were 2.07 (1.16-3.68), 3.29 (1.94-5.56), and 2.73 (2.00-3.72) for groups 2, 3, and 4, respectively. However, this relationship was statistically insignificant between groups 2, 3, and 4. Compared with those for group 2, adjusted hazard ratios (95% confidence intervals) for groups 3 and 4 were 1.59 (0.76-3.30) and 1.32 (0.72-2.42), respectively, and 0.83 (0.47-1.46) for group 4 compared with group 3. The results of patients aged ≥50 years were identical to those of all patients. DISCUSSION: Risk of metachronous ACRN was not different between patients aged ≥50 years who underwent polypectomy of ≥3 diminutive NAAs, ≥3 small NAAs, and AA, thus supporting current guidelines that recommend a uniform surveillance interval for these lesions.

Alcoholic and Nonalcoholic Fatty Liver Disease and Liver-Related Mortality: A Cohort Study.

OBJECTIVES: We compared liver-related mortality by fibrosis severity between 2 types of fatty liver disease (FLD), nonalcoholic FLD (NAFLD) and alcoholic FLD (AFLD), in a large cohort of nonobese and obese individuals. METHODS: A cohort study was performed with 437,828 Korean adults who were followed up for up to 14 years. Steatosis was diagnosed based on ultrasonography; fibrosis severity was determined by the fibrosis 4 (FIB-4) score. Vital status and liver-related deaths were ascertained through linkage to national death records. RESULTS: The prevalence of NAFLD and AFLD was 20.9% and 4.0%, respectively. During 3,145,541.1 person-years of follow-up, 109 liver-related deaths were identified (incidence rate of 3.5 per 10 person-years). When changes in fatty liver status, FIB-4 scores, and confounders during follow-up were updated as time-varying covariates, compared with the reference (absence of both excessive alcohol use and FLD), the multivariable-adjusted hazard ratios with 95% confidence intervals for liver-related mortality among those with low, intermediate, and high FIB-4 scores were 0.43 (0.19-0.94), 2.74 (1.23-6.06), and 84.66 (39.05-183.54), respectively, among patients with NAFLD, whereas among patients with AFLD, the corresponding hazard ratios (95% confidence intervals) were 0.67 (0.20-2.25), 5.44 (2.19-13.49), and 59.73 (27.99-127.46), respectively. The associations were more evident in nonobese individuals than in obese individuals (P for interaction = 0.004). DISCUSSION: In this large cohort of young and middle-aged individuals, NAFLD and AFLD with intermediate to high fibrosis scores were associated with an increased risk of liver-related mortality in a dose-dependent manner, especially among nonobese individuals.

Usefulness of risk stratification models for colorectal cancer based on fecal hemoglobin concentration and clinical risk factors.

BACKGROUND AND AIMS: We aimed to develop risk stratification models for advanced colorectal neoplasia (ACRN) and colorectal cancer (CRC) based on fecal hemoglobin (f-Hb) concentration and clinical risk factors. METHODS: We reviewed screenees aged ≥50 years who underwent fecal immunochemical test (FIT) and colonoscopy and developed risk-scoring models for ACRN and CRC using logistic regression analysis. Participants were classified into low- (risk lower than that in FIT-negative individuals), intermediate- (risk higher than that in FIT-negative but lower than that in FIT-positive individuals), high- (risk similar to that in FIT-positive individuals), and very-high- (risk higher than that in FIT-positive individuals) risk groups. RESULTS: Of 3733 participants, 367 (9.8%) and 70 (1.9%) had ACRN and CRC, respectively. On multivariable analysis, age (ß = .043/y), former smoker (ß = .401), current smoker (ß = .841), diabetes (ß = .097), and square root of f-Hb concentration (ß = .071) were significantly associated with ACRN. In terms of CRC, age (ß = .035/y) and square root of f-Hb concentration (ß = .004) were associated factors. After point assignments based on the regression coefficient, we could classify screenees as low-, intermediate-, high-, and very-high-risk groups. ACRN was identified in 2.9%, 5.3%, 16.2%, and 35.7% of screenees in the low-, intermediate-, high-, and very-high-risk groups, respectively. CRC was identified in .1%, .5%, 3.9%, and 11.1% of screenees in the low-, intermediate-, high-, and very-high-risk groups, respectively. CONCLUSIONS: The proposed models can effectively stratify the risk for ACRN and CRC and provide accurate information on this risk in individuals who undergo FIT.

Yield of repeat colonoscopy in asymptomatic individuals with a positive fecal immunochemical test and recent colonoscopy.

BACKGROUND AND AIMS: A fecal immunochemical test (FIT) is often repeated annually, even after a recent colonoscopy. However, there are no published data on the proper approach to FIT-positive patients after a recent colonoscopy. We compared colorectal cancer (CRC) and advanced colorectal neoplasia (ACRN) prevalence based on the interval since the last colonoscopy. METHODS: We reviewed asymptomatic screenees aged ≥50 years who underwent FIT and colonoscopy. RESULTS: Of 2228 FIT-positive participants, 514 had a colonoscopy less than 3 years before (group 1), 427 had a colonoscopy had a colonoscopy 3 to 10 years before (group 2), and 1287 had a colonoscopy >10 years before or no colonoscopy (group 3). The prevalence of CRC in groups 1, 2, and 3 was 2.1%, 1.6%, and 7.2%, respectively, and that for ACRN was 10.9%, 12.6%, and 26.0%, respectively. Even after adjusting for confounders, CRC and ACRN detection rates in group 1 were lower than those in group 3 but not lower than those in group 2. Among 6135 FIT-negative participants, the prevalence of CRC in the 3 groups was .7%, .4%, and 3.4%, respectively, and that for ACRN was 6.0%, 6.1%, and 14.7%, respectively. CRC and ACRN detection rates were significantly higher in FIT-positive participants than in FIT-negative participants in all 3 groups. CONCLUSIONS: In FIT-positive patients who underwent colonoscopy within the prior 3 years, CRC and ACRN prevalence was not low. Our findings support the U.S. Multi-Society Task Force on the CRC screening recommendation that repeat colonoscopy be offered to patients with positive FIT results and recent colonoscopy.

Abdominal Obesity is More Predictive of Advanced Colorectal Neoplasia Risk Than Overall Obesity in Men: A Cross-sectional Study.

GOALS: We aimed to ascertain whether waist circumference (WC) is associated with risk of colorectal neoplasia (CRN), independent of body mass index (BMI). BACKGROUND: Although several studies have reported the association between abdominal obesity, measured by WC, and CRN, it remains unclear whether their association is biased by BMI. STUDY: A cross-sectional study was performed on 154,552 asymptomatic examinees who underwent colonoscopy for a health check-up. RESULTS: The mean age was 42.6 years, and the proportion of males was 65.2%. The prevalence rate of CRN in subjects in WC quartiles 1, 2, 3, and 4 was 15.6%, 18.1%, 20.4%, and 22.0% among men and 7.8%, 9.4%, 12.2%, and 15.8% among women, respectively. WC and BMI were independent risk factors for overall CRN and nonadvanced CRN in both men and women. In men, the association of BMI with advanced CRN was attenuated to null after adjusting for WC [Q2, Q3, and Q4 vs. Q1; odds ratios (95% confidence intervals), 0.93 (0.79-1.10), 0.85 (0.71-1.03), and 0.99 (0.80-1.22), respectively; Ptrend=0.822], whereas the association of WC with advanced CRN significantly persisted even after adjusting for BMI [Q2, Q3, and Q4 vs. Q1; 1.20 (1.02-1.42), 1.45 (1.20-1.75), and 1.64 (1.32-2.04), respectively; Ptrend<0.001]. In women, neither WC nor BMI was associated with the risk of advanced CRN. CONCLUSIONS: Abdominal obesity is associated with an increased risk of advanced CRN, independent of overall obesity (BMI) in men. Our findings suggest that abdominal obesity is more strongly predictive of advanced CRN than overall obesity in men.

Association Between Cotinine-verified Smoking Status and Risk of Colorectal Neoplasia.

GOALS: We evaluated the association of urinary cotinine-verified smoking status with the risk of colorectal neoplasia (CRN). BACKGROUND: Many studies have reported the association between the risk of CRN and smoking status, based on self-reported questionnaires. Although self-reported smoking status may be inaccurate, to our knowledge, no study has yet assessed the association between objective biomarkers of tobacco exposure and the risk of CRN. STUDY: A cross-sectional study was conducted on 96,806 asymptomatic examinees who underwent colonoscopy and urinary cotinine measurements as part of a health check-up. Cotinine-verified current smokers were participants having a urinary cotinine level ≥50 ng/mL. RESULTS: The mean participant age was 38.4 years, and the proportion of cotinine-verified current smokers was 23.0%. Cotinine-verified current smoking was an independent risk factor for CRN [adjusted odds ratio (AOR), 1.49; 95% confidence interval (CI), 1.42-1.56] and advanced CRN (ACRN) (AOR, 1.79; 95% CI, 1.57-2.05). Moreover, the risk of CRN and ACRN increased with increasing cotinine levels. Among self-reported never smokers, cotinine-verified current smokers had a higher risk of CRN (AOR, 1.77; 95% CI, 1.57-2.00) and ACRN (AOR, 1.94; 95% CI, 1.37-2.74) than cotinine-verified never smokers did, whereas among self-reported current smokers, cotinine-verified never smokers had a lower risk of CRN (AOR, 0.78; 95% CI, 0.70-0.87) and ACRN (AOR, 0.71; 95% CI, 0.52-0.98) than cotinine-verified current smokers did. CONCLUSIONS: Cotinine-captured smoking status and metabolic variation exhibit associations with CRN more accurately and objectively than self-reporting does, providing clearer evidence for the role of tobacco in the development of CRN.

Impact of obesity and metabolic abnormalities on the risk of metachronous colorectal neoplasia after polypectomy in men.

BACKGROUND AND AIM: Obesity and metabolic syndrome are well-known risk factors for the development of metachronous colorectal neoplasia (CRN). However, data on the risks of metachronous CRN among subgroups according to obesity and metabolic status are scarce. Therefore, we aimed to compare the risk of metachronous CRN among men with different obesity and metabolic status. METHODS: In total, 8059 asymptomatic men who underwent ≥ 1 adenoma removal between 2010 and 2014 and follow-up colonoscopic surveillance until 2017 were categorized into four groups according to obesity and metabolic status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). RESULTS: Of the 8059 men, 2389 (29.6%), 351 (4.4%), 1986 (24.6%), and 3333 (41.4%) subjects were assigned to the MHNO, MHO, MUNO, and MUO groups, respectively. The mean surveillance interval was 3.5 ± 1.4 years. Compared to the MHNO group, the risk of metachronous advanced CRN was significantly increased in the MUO group (adjusted hazard ratio [HR] = 1.50; 95% confidence interval [CI]: 1.02-2.19), but not in the MHO and MUNO groups, while the risk of metachronous overall CRN significantly increased in the MUNO (adjusted HR = 1.12; 95% CI: 1.01-1.24) and MUO groups (adjusted HR = 1.17; 95% CI: 1.07-1.29), but not in the MHO group. CONCLUSIONS: Men who had both obesity and poor metabolic health were found to be at an increased risk of metachronous advanced CRN, suggesting that MUO men may need to undergo more intensive surveillance colonoscopy after polypectomy.

Association between family history of colorectal cancer and the risk of metachronous colorectal neoplasia following polypectomy in patients aged < 50 years.

BACKGROUND AND AIM: The relationship between a family history of colorectal cancer (CRC) and the risk of metachronous colorectal neoplasia (CRN) following polypectomy remains unknown. We aimed to compare the risk of metachronous CRN according to CRC family history in groups of patients aged < 50 and ≥ 50 years. METHODS: We studied patients who underwent ≥ 1 adenoma removal between 2010 and 2014 and follow-up surveillance colonoscopic examinations until 2017. RESULTS: Among the 9866 patients studied, 544 (5.5%) had ≥ 1 first-degree relatives (FDRs) affected by CRC. In patients aged < 50 years (n = 7787), as compared with having no family history of CRC, a positive family history in any FDR (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.16-1.62), a father (HR 1.35, 95% CI 1.09-1.68), or a mother (HR 1.32, 95% CI 1.005-1.74) was associated with an increased risk of metachronous CRN after adjusting for confounding factors. However, in patients aged ≥ 50 years (n = 2079), there was no significant association between having an FDR with CRC and the risk of metachronous CRN. For metachronous advanced CRN, the association between its risk and family history of CRC was not observed in either the < 50 years or ≥ 50 years of age group. CONCLUSIONS: Having an FDR with CRC at a young age (< 50 years) appears to be closely related to the risk of metachronous CRN. However, considering that the risk of metachronous advanced CRN did not depend on CRC family history, the interval of post-polypectomy surveillance colonoscopy may not need to be adjusted depending on CRC family history.